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Sample records for compartmental vascularized bone

  1. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung.

    Science.gov (United States)

    Kaner, R J; Crystal, R G

    2001-04-01

    Based on assessment of mRNA expression, the lung is a major site of expression of the vascular endothelial growth factor (VEGF) gene, largely from type II alveolar epithelial cells. With the knowledge that VEGF can function to induce vascular leak, we hypothesized that to protect the lung from pulmonary edema, the VEGF produced in the lung must be compartmentalized from the pulmonary endothelium, and thus must be compartmentalized to the surface of the respiratory epithelium. To assess this hypothesis, we quantified the levels of VEGF in human respiratory epithelial lining fluid recovered by bronchoalveolar lavage from normal individuals. Strikingly, human respiratory epithelial lining fluid contains 11 +/- 5 ng/mL as quantified by ELISA, a 500-fold greater concentration than plasma (22 +/- 10 pg/mL, p Damocles sword" poised to induce lung endothelial permeability in conditions of acute lung injury when the integrity of the alveolar epithelial barrier is breached.

  2. Vascular tumors of bone : Imaging findings

    NARCIS (Netherlands)

    Vermaat, Marieke; Vanel, Daniel; Kroon, Herman M.; Verbeke, Sofie L. J.; Alberghini, Marco; Bovee, Judith V. M. G.; Bloem, Johan L.

    Purpose: To identify radiological features of malignant vascular tumors of bone, which can be used to avoid erroneously diagnosing metastases based on radiological multifocality, and histological epitheloid phenotype. Materials and methods: From the databases of the Bologna & Netherlands Committee

  3. Vascularized fibular graft in infected tibial bone loss

    OpenAIRE

    C Cheriyan Kovoor; R Jayakumar; V V George; Vinod Padmanabhan; A J Guild; Sabin Viswanath

    2011-01-01

    Background : The treatment options of bone loss with infections include bone transport with external fixators, vascularized bone grafts, non-vascularized autogenous grafts and vascularized allografts. The research hypothesis was that the graft length and intact ipsilateral fibula influenced hypertrophy and stress fracture. We retrospectively studied the graft hypertrophy in 15 patients, in whom vascularized fibular graft was done for post-traumatic tibial defects with infection. Materials...

  4. Compartmental syndromes in children.

    Science.gov (United States)

    Matsen, F A; Veith, R G

    1981-01-01

    Compartmental syndromes are reported in 24 children after injuries and surgery. In these cases, increased tissue pressure compromised local perfusion and neuromuscular function. Compartmental syndromes occurred in the interosseous compartments of the hand, the volar and dorsal compartments of the forearm, and the four compartments of the leg. The most common etiologies were fracture, vascular injury, and tibial osteotomy. In many instances, clinical data were sufficient to establish the diagnosis. However, in young patients or in patients with neurologic or vascular injuries, tissue pressure measurement helped to resolve otherwise ambiguous findings. The most significant determinant of the quality of the end result was the duration of the compartmental syndrome prior to surgical decompression. We conclude that prompt diagnosis and decompression of compartmental syndromes can minimize the sequela from these conditions.

  5. New Options for Vascularized Bone Reconstruction in the Upper Extremity

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    Houdek, Matthew T.; Wagner, Eric R.; Wyles, Cody C.; Nanos, George P.; Moran, Steven L.

    2015-01-01

    Originally described in the 1970s, vascularized bone grafting has become a critical component in the treatment of bony defects and non-unions. Although well established in the lower extremity, recent years have seen many novel techniques described to treat a variety of challenging upper extremity pathologies. Here the authors review the use of different techniques of vascularized bone grafts for the upper extremity bone pathologies. The vascularized fibula remains the gold standard for the treatment of large bone defects of the humerus and forearm, while also playing a role in carpal reconstruction; however, two other important options for larger defects include the vascularized scapula graft and the Capanna technique. Smaller upper extremity bone defects and non-unions can be treated with the medial femoral condyle (MFC) free flap or a vascularized rib transfer. In carpal non-unions, both pedicled distal radius flaps and free MFC flaps are viable options. Finally, in skeletally immature patients, vascularized fibular head epiphyseal transfer can provide growth potential in addition to skeletal reconstruction. PMID:25685100

  6. Compartmentalization of immune responses during Staphylococcus aureus cranial bone flap infection.

    Science.gov (United States)

    Cheatle, Joseph; Aldrich, Amy; Thorell, William E; Boska, Michael D; Kielian, Tammy

    2013-08-01

    Decompressive craniectomy is often required after head trauma, stroke, or cranial bleeding to control subsequent brain swelling and prevent death. The infection rate after cranial bone flap replacement ranges from 0.8% to 15%, with an alarming frequency caused by methicillin-resistant Staphylococcus aureus, which is problematic because of recalcitrance to antibiotic therapy. Herein we report the establishment of a novel mouse model of S. aureus cranial bone flap infection that mimics several aspects of human disease. Bacteria colonized bone flaps for up to 4 months after infection, as revealed by scanning electron microscopy and quantitative culture, demonstrating the chronicity of the model. Analysis of a human cranial bone flap with confirmed S. aureus infection by scanning electron microscopy revealed similar structural attributes as the mouse model, demonstrating that it closely parallels structural facets of human disease. Inflammatory indices were most pronounced within the subcutaneous galeal compartment compared with the underlying brain parenchyma. Specifically, neutrophil influx and chemokine expression (CXCL2 and CCL5) were markedly elevated in the galea, which demonstrated substantial edema on magnetic resonance images, whereas the underlying brain parenchyma exhibited minimal involvement. Evaluation of immune mechanisms required for bacterial containment and inflammation revealed critical roles for MyD88-dependent signaling and neutrophils. This novel mouse model of cranial bone flap infection can be used to identify key immunologic and therapeutic mechanisms relevant to persistent bone flap infection in humans. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Vascularized bone grafts for congenital pseudarthrosis of the tibia.

    Science.gov (United States)

    Kanaya, F; Tsai, T M; Harkess, J

    1996-01-01

    Eight vascularized fibula grafts and two vascularized rib grafts were used for the treatment of 10 Boyd's Type II congenital pseudarthrosis of the tibia. All but one vascularized fibula graft united within 4 months. The two vascularized rib grafts did not unite until receiving a conventional bone graft. Nine spontaneous fractures were seen in four patients; all were subsequently treated successfully with cast or conventional bone graft. Corrective osteotomies were done in two patients. Follow-up averaged 8 years and 5 months (range, 5 years and 1 month to 14 years and 4 months). Average age at end of follow-up was 13 years and 6 months (range, 7 years and 10 months to 20 years and 4 months). After bony union was achieved, shortening of the affected leg averaged 3.8 centimeters, flexion deformity averaged 20 degrees, and valgus deformity averaged 24 degrees. In three patients, whose leg discrepancy averaged 4.9 centimeters, the leg was lengthened at an average patient age of 13 years and 9 months (age range, 11 years and 7 months to 15 years and 2 months). The resulting limb length discrepancy averaged 2.2 centimeters. Vascularized bone grafting is a reliable technique for achieving bony union in congenital pseudarthrosis of the tibia. Residual shortening may be corrected later by limb lengthening.

  8. BMP signaling in vascular and heterotopic bone diseases

    NARCIS (Netherlands)

    Cai, Jie

    2016-01-01

    Bone morphogenetic proteins (BMPs) are multifunctional regulators in embryonic development and tissue homeostasis. Disruptions in BMP signaling lead to various diseases, such as skeletal diseases, vascular diseases and cancer. Studies in this thesis mainly focused on the role of BMP signaling in

  9. Vascularized fibula grafts for reconstruction of bone defects after resection of bone sarcomas

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hovgaard, Dorrit; Elberg, Jens Jørgen

    2010-01-01

    We evaluated the results of limb-sparing surgery and reconstruction of bone defects with vascularized fibula grafts in 8 consecutive patients (mean age at operation 13.6 years (range 4.1-24.2 years), female/male = 6/2) with bone sarcomas (BS) (osteosarcoma/Ewing's sarcoma/chondrosarcoma= 4...

  10. Vascularized fibula grafts for reconstruction of bone defects after resection of bone sarcomas

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hovgaard, Dorrit; Elberg, Jens Jørgen

    2010-01-01

    We evaluated the results of limb-sparing surgery and reconstruction of bone defects with vascularized fibula grafts in 8 consecutive patients (mean age at operation 13.6 years (range 4.1-24.2 years), female/male = 6/2) with bone sarcomas (BS) (osteosarcoma/Ewing's sarcoma/chondrosarcoma= 4/3/1) o...... (n = 2), and hip dislocation (n = 1). Limb-sparing surgery with reconstruction of bone defects using vascularized fibular grafts in BS cases is feasible with acceptable clinical results, but fractures should be expected in many patients....

  11. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

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    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  12. Effects of the placement of endosseous implants in vascularized bone grafts on bone union in beagle dogs.

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    Kobayashi, E; Ishihara, O; Mataga, I

    2005-09-01

    Recently, reconstructive surgery with revascularized osteocutaneous flaps has been used to restore function in patients with bone defects caused by surgery for oral cancer. However, few basic studies have addressed problems such as the union of bone segments after osteotomy, the effects of dental implant placement on blood flow, and bone formation at the bone:implant interface in grafted bone. Nine adult beagle dogs were divided into three groups of three dogs each. Each group received osteotomized vascularized tibial grafts, osteotomized tibial grafts with implants (implants placed in contralateral limbs as control), or simple (non-vascularized) tibial grafts. The development of bone around the implants was studied by histological examination, contact micro-radiography (CMR), and fluorescent bone labeling. In the dogs receiving osteotomized vascularized tibial grafts, bone bridging was confirmed at both the medial and distal junctions of the bone segments after 4 weeks. Additional newly formed bone was observed after 8 weeks, and bone union at the surface of the segments was completed after 12 weeks. In contrast, bone formation was clearly delayed in dogs receiving simple (non-vascularized) tibial grafts. Histologically, no difference in bone union was evident between limbs with dental implants in tibial bone and control limbs without implants, suggesting that implant placement does not negatively affect revascularization. Fluorescent bone labeling technique confirmed high vascularity of the vascularized tibial bone grafts but not of the simple (non-vascularized) tibial bone grafts early after the procedure. Our results suggest that osseointegration occurred around dental implants placed at the same time as reconstruction with osteotomized vascularized bone grafts in this animal model.

  13. Bone matrix microdamage and vascular changes characterize bone marrow lesions in the subchondral bone of knee osteoarthritis.

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    Muratovic, Dzenita; Findlay, David M; Cicuttini, Flavia M; Wluka, Anita E; Lee, Yea-Rin; Kuliwaba, Julia S

    2018-01-10

    Bone marrow lesions (BMLs) in the subchondral bone in osteoarthritis (OA) are suggested to be multifactorial, although the pathogenic mechanisms are unknown. Bone metabolism and cardiovascular risk factors associate with BML in epidemiologic studies. However, there are no studies at the tissue level investigating the relationship between these processes and BML. The aim of this study was to investigate the relationship between BMLs in the tibial plateau (TP) of knee OA and bone matrix microdamage, osteocyte density and vascular changes. TP were obtained from 73 patients at total knee replacement surgery and BMLs were identified ex vivo in TP tissue using MRI. Comparator 'No BML' tissue was from matched anatomical sites to the BMLs. Quantitative assessment was made of subchondral bone microdamage, bone resorption indices, osteocyte cellularity, and vascular features. Several key parameters were different between BML and No BML tissue. These included increased microcrack burden (p = .01, p = .0001), which associated positively with bone resorption and negatively with cartilage volume, and greater osteocyte numerical density (p = .02, p = .01), in the subchondral bone plate and subchondral trabeculae, respectively. The marrow tissue within BML zones contained increased arteriolar density (p = .04, p = .0006), and altered vascular characteristics, in particular increased wall thickness (p = .007) and wall:lumen ratio (wall thickness over internal lumen area) (p = .001), compared with No BML bone. Increased bone matrix microdamage and altered vasculature in the subchondral bone of BMLs is consistent with overloading and vascular contributions to the formation of these lesions. Given the important role of BMLs in knee OA, these contributing factors offer potential targets for the treatment and prevention of knee OA. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  14. Metabolic acidosis and vascular calcification: using blueprints from bone to map a new venue for vascular research.

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    Al-Aly, Z

    2008-02-01

    Vascular calcification is an important problem in patients with chronic kidney disease. The pathobiology of vascular calcification is complex and is intricately related to bone remodeling. Mendoza et al. report that experimental metabolic acidosis prevents calcitriol-induced vascular calcification in uremic animals. To fully understand the effect of acidosis on the vasculature, a comprehensive and integrated approach that simultaneously examines the effect of metabolic acidosis on bone and vasculature is needed.

  15. Vascularized fibular graft in infected tibial bone loss

    Directory of Open Access Journals (Sweden)

    C Cheriyan Kovoor

    2011-01-01

    Full Text Available Background : The treatment options of bone loss with infections include bone transport with external fixators, vascularized bone grafts, non-vascularized autogenous grafts and vascularized allografts. The research hypothesis was that the graft length and intact ipsilateral fibula influenced hypertrophy and stress fracture. We retrospectively studied the graft hypertrophy in 15 patients, in whom vascularized fibular graft was done for post-traumatic tibial defects with infection. Materials and Methods : 15 male patients with mean age 33.7 years (range 18 - 56 years of post traumatic tibial bone loss were analysed. The mean bony defect was 14.5 cm (range 6.5 - 20 cm. The mean length of the graft was 16.7 cm (range 11.5 - 21 cm. The osteoseptocutaneous flap (bone flap with attached overlying skin flap from the contralateral side was used in all patients except one. The graft was fixed to the recipient bone at both ends by one or two AO cortical screws, supplemented by a monolateral external fixator. A standard postoperative protocol was followed in all patients. The hypertrophy percentage of the vascularized fibular graft was calculated by a modification of the formula described by El-Gammal. The followup period averaged 46.5 months (range 24 - 164 months. The Pearson correlation coefficient (r was worked out, to find the relationship between graft length and hypertrophy. The t-test was performed to find out if there was any significant difference in the graft length of those who had a stress fracture and those who did not and to find out whether there was any significant difference in hypertrophy with and without ipsilateral fibula union. The Chi square test was performed to identify whether there was any association between the stress fracture and the fibula union. Given the small sample size we have not used any statistical analysis to determine the relation between the percentage of the graft hypertrophy and stress fracture. Results : Graft

  16. Role of Galectin-3 in Bone Cell Differentiation, Bone Pathophysiology and Vascular Osteogenesis

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    Carla Iacobini

    2017-11-01

    Full Text Available Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and cartilage matrix mineralization. It was also shown to be highly expressed in differentiating osteoblasts and osteoclasts, in concomitance with expression of osteogenic markers and Runt-related transcription factor 2 and with the appearance of a mature phenotype. Galectin-3 is expressed also by osteocytes, though its function in these cells has not been fully elucidated. The effects of galectin-3 on bone cells were also investigated in galectin-3 null mice, further supporting its role in all stages of bone biology, from development to remodeling. Galectin-3 was also shown to act as a receptor for advanced glycation endproducts, which have been implicated in age-dependent and diabetes-associated bone fragility. Moreover, its regulatory role in inflammatory bone and joint disorders entitles galectin-3 as a possible therapeutic target. Finally, galectin-3 capacity to commit mesenchymal stem cells to the osteoblastic lineage and to favor transdifferentiation of vascular smooth muscle cells into an osteoblast-like phenotype open a new area of interest in bone and vascular pathologies.

  17. Vascularized bone graft for oncological reconstruction of the extremities: review of the biological advantages.

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    Muramatsu, Keiichi; Hashimoto, Takahiro; Tominaga, Yasuhiro; Taguchi, Toshihiko

    2014-06-01

    Vascularized bone graft (VBG) is a form of vascularized bone marrow transplant in which the bone marrow is surgically grafted with its microenvironment intact. Due to the preservation of cellular viability, VBG have significant advantages over non-vascularized bone grafts. Free vascularized fibula grafts have superior material properties and tolerate infection. Bone healing can be accomplished in a shorter period, even in an irradiated bed. In addition to these properties, VBG has other biological advantages that are not always familiar to oncological surgeons. Hypertrophic change can be divided into reactive and adaptive hypertrophy. Early hypertrophy is associated with donor-derived cells, whereas later remodeling is associated with recipient-derived cells. VBG has significant advantages in enhancing neo-revascularization of necrotic bone. We reviewed VBG from a novel viewpoint that stems from our basic research. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Characterization of vascular endothelial progenitor cells from chicken bone marrow

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    Bai Chunyu

    2012-05-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC are a type of stem cell used in the treatment of atherosclerosis, vascular injury and regeneration. At present, most of the EPCs studied are from human and mouse, whereas the study of poultry-derived EPCs has rarely been reported. In the present study, chicken bone marrow-derived EPCs were isolated and studied at the cellular level using immunofluorescence and RT-PCR. Results We found that the majority of chicken EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P 1, -5 and -9 were typically “S”-shaped. The viability of chicken EPCs, before and after cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1 uptake assays and immunofluorescent detection of the cell surface markers CD34, CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation of endothelial-specific Weibel-Palade bodies using transmission electron microscopy further confirmed that the cells were of endothelial lineage. In addition, chicken EPCs differentiated into endothelial cells and smooth muscle cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the chicken EPCs retained multipotency in vitro. Conclusions These results suggest that chicken EPCs not only have strong self-renewal capacity, but also the potential to differentiate into endothelial and smooth muscle cells. This research provides theoretical basis and experimental evidence for potential therapeutic application of endothelial progenitor cells in the treatment of atherosclerosis, vascular injury and diabetic complications.

  19. Fibrocartilage Stem Cells Engraft and Self-Organize into Vascularized Bone.

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    Nathan, J; Ruscitto, A; Pylawka, S; Sohraby, A; Shawber, C J; Embree, M C

    2017-10-01

    Angiogenesis is a complex, multicellular process that is critical for bone development and generation. Endochondral ossification depends on an avascular cartilage template that completely remodels into vascularized bone and involves a dynamic interplay among chondrocytes, osteoblasts, and endothelial cells. We have discovered fibrocartilage stem cells (FCSCs) derived from the temporomandibular joint (TMJ) mandibular condyle that generates cartilage anlagen, which is subsequently remodeled into vascularized bone using an ectopic transplantation model. Here we explore FCSC and endothelial cell interactions during vascularized bone formation. We found that a single FCSC colony formed transient cartilage and host endothelial cells may participate in bone angiogenesis upon subcutaneous transplantation in a nude mouse. FCSCs produced an abundance of the proangiogenic growth factor vascular endothelial growth factor A and promoted the proliferation of human umbilical vein endothelial cells (HUVECs). Using a fibrinogen gel bead angiogenesis assay experiment, FCSC cell feeder layer induced HUVECs to form significantly shorter and less sprouts than D551 fibroblast controls, suggesting that FCSCs may initially inhibit angiogenesis to allow for avascular cartilage formation. Conversely, direct FCSC-HUVEC contact significantly enhanced the osteogenic differentiation of FCSCs. To corroborate this idea, upon transplantation of FCSCs into a bone defect microenvironment, FCSCs engrafted and regenerated intramembranous bone. Taken together, we demonstrate that the interactions between FCSCs and endothelial cells are essential for FCSC-derived vascularized bone formation. A comprehensive understanding of the environmental cues that regulate FCSC fate decisions may contribute to deciphering the mechanisms underlying the role of FCSCs in regulating bone formation.

  20. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

    Science.gov (United States)

    García, José R.; Clark, Amy Y.; García, Andrés J.

    2016-01-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded polyethylene glycol (PEG) hydrogels functionalized with either a triple-helical, α2β1 integrin-specific peptide (GFOGER) or an αvβ3 integrin-targeting peptide (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  1. Vascular bone tumors: a proposal of a classification based on clinicopathological, radiographic and genetic features

    Energy Technology Data Exchange (ETDEWEB)

    Errani, Costantino [Istituto Ortopedico Rizzoli, Ortopedia Generale, Orthopaedic Service, Bagheria (Italy); Struttura Complessa Ortopedia Generale, Dipartimento Rizzoli-Sicilia, Bagheria, PA (Italy); Vanel, Daniel; Gambarotti, Marco; Alberghini, Marco [Istituto Ortopedico Rizzoli, Pathology Service, Bologna (Italy); Picci, Piero [Istituto Ortopedico Rizzoli, Laboratory for Cancer Research, Bologna (Italy); Faldini, Cesare [Istituto Ortopedico Rizzoli, Ortopedia Generale, Orthopaedic Service, Bagheria (Italy)

    2012-12-15

    The classification of vascular bone tumors remains challenging, with considerable morphological overlap spanning across benign to malignant categories. The vast majority of both benign and malignant vascular tumors are readily diagnosed based on their characteristic histological features, such as the formation of vascular spaces and the expression of endothelial markers. However, some vascular tumors have atypical histological features, such as a solid growth pattern, epithelioid change, or spindle cell morphology, which complicates their diagnosis. Pathologically, these tumors are remarkably similar, which makes differentiating them from each other very difficult. For this rare subset of vascular bone tumors, there remains considerable controversy with regard to the terminology and the classification that should be used. Moreover, one of the most confusing issues related to vascular bone tumors is the myriad of names that are used to describe them. Because the clinical behavior and, consequently, treatment and prognosis of vascular bone tumors can vary significantly, it is important to effectively and accurately distinguish them from each other. Upon review of the nomenclature and the characteristic clinicopathological, radiographic and genetic features of vascular bone tumors, we propose a classification scheme that includes hemangioma, hemangioendothelioma, angiosarcoma, and their epithelioid variants. (orig.)

  2. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: A better model

    Energy Technology Data Exchange (ETDEWEB)

    Dong Qingshan [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Shang Hongtao; Wu Wei [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Chen Fulin [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, Xi' an 710069 (China); Zhang Junrui [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Guo Jiaping [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Mao Tianqiu, E-mail: tianqiumao@126.com [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China)

    2012-08-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. - Highlights: Black-Right-Pointing-Pointer A modified arteriovenous loop (AVL) model in rabbit was developed in this study. Black-Right-Pointing-Pointer Axial prevascularization was induced in a larger coral block by using the AVL. Black-Right-Pointing-Pointer The prefabrication of axial vascularized coral bone is superior as vascular carrier.

  3. Assessment of vascularity in irradiated and nonirradiated maxillary and mandibular minipig alveolar bone using laser doppler flowmetry.

    NARCIS (Netherlands)

    Verdonck, H.W.; Meijer, G.J.; Laurin, T.; Nieman, F.H.; Stoll, C.; Riediger, D.; Stoelinga, P.J.W.; Baat, C. de

    2007-01-01

    PURPOSE: The purpose of this animal study was to confirm that laser Doppler flowmetry (LDF) is a reproducible method for the assessment of maxillary and mandibular alveolar bone vascularity and that there is less vascularity in irradiated mandibular and maxillary bone compared to nonirradiated bone.

  4. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

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    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  5. Rabbit tibial periosteum and saphenous arteriovenous vascular bundle as an in vivo bioreactor to construct vascularized tissue-engineered bone: a feasibility study.

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    Han, Dong; Guan, Xiaoyi; Wang, Jian; Wei, Jiao; Li, Qingfeng

    2014-02-01

    The aim of this project was to construct vascularized tissue-engineered living bone with an autologous vascular network by means of a rabbit bioreactor in vivo. The key components of the in vivo bioreactor for bone formation were the vascularized tibial periosteum and the saphenous vascular bundle. Beta-tricalcium phosphate (β-TCP) scaffolds were implanted into the in vivo bioreactor (vascular pedicle implantation and vascularized periosteum encapsulation). At 4 weeks postsurgery, new bone formation was mainly "cartilage-bone inducing" in the inner periosteum, and was primarily seen in the outer aspects of the scaffold with some amount in the middle part as well. Microvascular infusion showed that direct revascularization of β-TCP was obtained by means of vascular implantation. Triple staining results showed a large amount of blue collagen fibers. Vascular endothelial growth factor immunohistochemical staining displayed endothelial cells of new blood vessels in bone tissue. The bioreactor established in this study can be used to prepare tissue-engineered bone with a vascular network. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  6. Structure and Functions of Blood Vessels and Vascular Niches in Bone

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    Saravana K. Ramasamy

    2017-01-01

    Full Text Available Bone provides nurturing microenvironments for an array of cell types that coordinate important physiological functions of the skeleton, such as energy metabolism, mineral homeostasis, osteogenesis, and haematopoiesis. Endothelial cells form an intricate network of blood vessels that organises and sustains various microenvironments in bone. The recent identification of heterogeneity in the bone vasculature supports the existence of multiple vascular niches within the bone marrow compartment. A unique combination of cells and factors defining a particular microenvironment, supply regulatory signals to mediate a specific function. This review discusses recent developments in our understanding of vascular niches in bone that play a critical role in regulating the behaviour of multipotent haematopoietic and mesenchymal stem cells during development and homeostasis.

  7. Non-Vascularized Autogenous Bone Grafts for Reconstruction of Maxillofacial Osseous Defects.

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    Ahmed, Waseem; Asim, Muhammad Adil; Ehsan, Afeefa; Abbas, Qalab

    2018-01-01

    To determine the outcomes of non-vascularized bone grafts for reconstruction of maxillofacial defects. Case series. Department of Oral and Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi, from January 2013 to December 2015. Descriptive analyses of 30 patients, who underwent maxillofacial reconstruction with non-vascularized bone grafts, were conducted. The demographic information, diagnosis, and type of graft harvested to reconstruct the defect were statistically analyzed. Outcomes of reconstruction with non-vascularized bone grafts were analyzed in terms of mouth opening, success of dental rehabilitation, and postoperative complications, i.e. surgical site infection and hardware loosening. A total of 30 patients ranging from 8 to 60 years (33.57 ±14.74 years) had maxillofacial defects reconstructed mostly due to gunshot injuries, followed by post-resection defects. Overall 15 cases (50%) were reconstructed with iliac crest cortico-cancellous bone graft, 11 cases (36.7%) with rib; while in four cases (13.3%), costochondral graft was used for reconstruction. In 26 cases (86.7%), graft was found to be successful. In three cases, re-operation for onlay bone graft was required to provide optimal dental rehabilitation; while in just one case, postoperative surgical site infection was observed. Non-vascularized bone grafts provide a reasonable and effective modality for reconstruction of maxillofacial defects.

  8. The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats.

    Science.gov (United States)

    Henley, Charles; Davis, James; Miller, Gerald; Shatzen, Edward; Cattley, Russ; Li, Xiaodong; Martin, David; Yao, Wei; Lane, Nancy; Shalhoub, Victoria

    2009-08-15

    Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism receiving dialysis, a disease state associated with parathyroid hyperplasia, vascular calcification, bone disease, and increased mortality. The aim of this study was to determine the effects of the research calcimimetic AMG 641 (Amgen, Inc., Thousand Oaks, CA) or calcitriol (Sigma Aldrich Corporation, St. Louis, MO) on vascular calcification in a rodent model of progressive uremia with accompanying secondary hyperparathyroidism induced by dietary adenine. Treatment effects on parathyroid gland hyperplasia and bone loss were also investigated. Rats were treated daily with vehicle, calcitriol (10 ng), AMG 641 (3 mg/kg), or no treatment during the 4 week period the animals were fed adenine. The uremia-induced increases in serum PTH levels were significantly attenuated by both AMG 641 (>90%) and calcitriol (approximately 50%). AMG 641 significantly reduced calcium-phosphorus product (CaxP) and significantly attenuated the development of both parathyroid hyperplasia and vascular calcification. In addition, AMG 641 prevented the defects in trabecular bone volume, trabecular number, and bone mineralization, as well as increases in trabecular spacing in this rodent model of secondary hyperparathyroidism. Calcitriol (10 ng/rat) decreased osteoid surface/bone surface, but had no effects on other bone parameters, or parathyroid hyperplasia (likely due to the lower PTH suppressive effect of calcitriol at the dose used in this study). However, this dose of calcitriol significantly exacerbated vascular calcification. These results suggest that calcimimetics can reduce the development of vascular calcification, parathyroid hyperplasia and bone abnormalities associated with secondary hyperparathyroidism.

  9. Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Knudsen, Kirsten Quyen Nguyen; Olesen, Ping; Ledet, Thomas

    2007-01-01

    The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved in the transformat......The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved...

  10. Vascularization of the facial bones by the facial artery: implications for full face allotransplantation.

    Science.gov (United States)

    Gharb, Bahar Bassiri; Rampazzo, Antonio; Kutz, Joseph E; Bright, Linda; Doumit, Gaby; Harter, Thomas B

    2014-05-01

    The maxillary artery is recognized as the main vascular supply of the facial bones; nonetheless, clinical evidence supports a codominant role for the facial artery. This study explores the extent of the facial skeleton within a facial allograft that can be harvested based on the facial artery. Twenty-three cadaver heads were used in this study. In 12 heads, the facial, superficial temporal, and maxillary arteries were injected. In one head, facial artery angiography was performed. Ten facial allografts were raised. The soft tissues were dissected to show the arterial anastomotic connections. Radiographs and computed tomographic scans were obtained. Constant anastomosis between the facial, inferior alveolar, and infraorbital arteries at the mental and infraorbital foramina were found. The facial artery vascularized the homolateral mandibular symphysis, body, and ramus. The condylar and coronoid processes were vascularized in 67 percent of the allografts. The homolateral maxilla was contrasted in all allografts. The alveolar and palatine processes contained the contrast in 83 percent of specimens. The maxillary process of the zygomatic bone was perfused in all allografts, followed by the body, frontal (83 percent), and temporal processes (67 percent). The nasal lateral wall and septum were vascularized in 83 percent of the allografts. The medial and lateral orbital walls and the orbital floor were stained in all specimens. The zygomatic process of the temporal bone was the least perfused bone. A composite allograft containing 90 to 95 percent of the facial bones can be based on bilateral facial arteries.

  11. Novel Bone-Anchored Vascular Access on the Mastoid for Hemodialysis: Concept and Preclinical Trials.

    Science.gov (United States)

    Stieger, Christof; Arnold, Andreas; Kruse, Anja; Wiedmer, Simona; Widmer, Matthias; Guignard, Jeremie; Schutz, Daniel; Guenat, Jean-Marc; Bachtler, Matthias; Caversaccio, Marco; Uehlinger, Dominik E; Frey, Felix J; Hausler, Rudolf

    2016-05-01

    We present the development of a bone-anchored port for the painless long-term hemodialytic treatment of patients with renal failure. This port is implanted behind the ear. The port was developed based on knowledge obtained from long-term experience with implantable hearing devices, which are firmly anchored to the bone behind the ear. This concept of bone anchoring was adapted to the requirements for a vascular access during hemodialysis. The investigational device is comprised of a base plate that is firmly fixed with bone screws to the bone behind the ear (temporal bone). A catheter leads from the base plate valve block through the internal jugular vein and into the right atrium. The valves are opened using a special disposable adapter, without any need to puncture the blood vessels. Between hemodialysis sessions, the port is protected with a disposable cover. Flow rate, leak tightness, and purification were tested on mockups. Preoperative planning and the surgical procedure were verified in 15 anatomical human whole head specimens. Preclinical evaluations demonstrated the technical feasibility and safety of the investigational device. Approximately 1.5 million people are treated with hemodialysis worldwide, and 25% of the overall cost of dialysis therapy results from vascular access problems. New approaches toward enhancing vascular access could potentially reduce the costs and complications of hemodialytic therapy.

  12. Sost deficiency does not alter bone's lacunar or vascular porosity in mice

    Science.gov (United States)

    Mosey, Henry; Núñez, Juan A.; Goring, Alice; Clarkin, Claire E.; Staines, Katherine A.; Lee, Peter D.; Pitsillides, Andrew A.; Javaheri, Behzad

    2017-09-01

    SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation and activity. Recent in vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the mechanisms responsible for SCLEROSTIN action, no previous studies have examined whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT) counterparts with high resolution CT to examine whether lack of SCLEROSTIN influences the morphometric properties of lacunae and vascular canal porosity relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice (n = 6 /group) were sacrificed at 12 weeks of age. Fixed tibiae were analysed using microCT to examine cortical bone mass and architecture. Then, samples were imaged by using benchtop and synchrotron nanoCT at the tibiofibular junction. Our data, consistent with previous studies show that, Sost deficiency leads to significant enhancement of bone mass by cortical thickening and bigger cross-sectional area and we find that this occurs without modifications of tibial ellipticity, a measure of bone shape. In addition, our data show that there are no significant differences in any lacunar or vascular morphometric or geometric parameters between Sost KO mouse tibia and WT counterparts. We therefore conclude that the significant increases in bone

  13. Vascularized connective tissue flap for bone graft coverage.

    Science.gov (United States)

    Herford, Alan S; Cooper, Todd C; Maiorana, Carlo; Cicciù, Marco

    2011-04-01

    Alveolar defects are characterized by missing soft and hard tissues. It is often necessary to combine secondary procedures to address the soft-tissue component. The authors describe a technique that uses a split-thickness flap design that is placed over the crest of the remaining ridge and extends in a palatal direction. This allows advancement of the flap with its exposed connective tissue over the bone graft and provides restoration of both bone and keratinized tissue. Seventeen patients with defects involving the anterior maxilla who required grafting procedures were including in this study. All patients had an autogenous bone graft (n  =  17) combined with osseointegrated implants (n  =  41). A split-thickness flap design was used at the time of bone graft placement (primary) in 9 patients and at the time of implant uncovering (secondary) in 8 patients. There were no cases of flap necrosis or dehiscence with exposure of the bone graft. All patients demonstrated an increase in keratinized tissue involving the peri-implant area. An apical repositioned split-thickness flap provides an increased zone of keratinized tissue with improved esthetics and implant maintenance. This technique can be performed simultaneously with the grafting procedure, thus avoiding extensive undermining of the adjacent soft tissue.

  14. Engineering vascularized bone grafts by integrating a biomimetic periosteum and β-TCP scaffold.

    Science.gov (United States)

    Kang, Yunqing; Ren, Liling; Yang, Yunzhi

    2014-06-25

    Treatment of large bone defects using synthetic scaffolds remain a challenge mainly due to insufficient vascularization. This study is to engineer a vascularized bone graft by integrating a vascularized biomimetic cell-sheet-engineered periosteum (CSEP) and a biodegradable macroporous beta-tricalcium phosphate (β-TCP) scaffold. We first cultured human mesenchymal stem cells (hMSCs) to form cell sheet and human umbilical vascular endothelial cells (HUVECs) were then seeded on the undifferentiated hMSCs sheet to form vascularized cell sheet for mimicking the fibrous layer of native periosteum. A mineralized hMSCs sheet was cultured to mimic the cambium layer of native periosteum. This mineralized hMSCs sheet was first wrapped onto a cylindrical β-TCP scaffold followed by wrapping the vascularized HUVEC/hMSC sheet, thus generating a biomimetic CSEP on the β-TCP scaffold. A nonperiosteum structural cell sheets-covered β-TCP and plain β-TCP were used as controls. In vitro studies indicate that the undifferentiated hMSCs sheet facilitated HUVECs to form rich capillary-like networks. In vivo studies indicate that the biomimetic CSEP enhanced angiogenesis and functional anastomosis between the in vitro preformed human capillary networks and the mouse host vasculature. MicroCT analysis and osteocalcin staining show that the biomimetic CSEP/β-TCP graft formed more bone matrix compared to the other groups. These results suggest that the CSEP that mimics the cellular components and spatial configuration of periosteum plays a critical role in vascularization and osteogenesis. Our studies suggest that a biomimetic periosteum-covered β-TCP graft is a promising approach for bone regeneration.

  15. Use of non-vascularized autologous fibula strut graft in the treatment of segmental bone loss.

    Science.gov (United States)

    Lawal, Y Z; Garba, E S; Ogirima, M O; Dahiru, I L; Maitama, M I; Abubakar, K; Ejagwulu, F S

    2011-01-01

    Fractures resulting in segmental bone loss challenge the orthopedic surgeon. Orthopedic surgeons in developed countries have the option of choosing vascularized bone transfers, bone transport, allogenic bone grafts, bone graft substitutes and several other means to treat such conditions. In developing countries where such facilities or expertise may not be readily available, the surgeon has to rely on other techniques of treatment. Non-vascularized fibula strut graft and cancellous bone grafting provides a reliable means of treating such conditions in developing countries. Over a period of six years all patients with segmental bone loss either from trauma or oncologic resection were included in the study. Data concerning the type of wound, size of gap and skin loss at tumor or fracture were obtained from clinical examination and radiographs. Ten patients satisfied the inclusion criteria for the study. The average length of the fibula strut is 7 cm, the longest being 15 cm and the shortest 3 cm long. The average defect length was 6.5 cm. Five patients had Gustillo III B open tibial fractures. One patient had recurrent giant cell tumor of the distal radius and another had a polyostotic bone cyst of the femur, which was later confirmed to be osteosarcoma. Another had non-union of distal tibial fracture with shortening. One other patient had gunshot injury to the femur and was initially managed by skeletal traction. The tenth patient had a comminuted femoral fracture. All trauma patients had measurement of missing segment, tissue envelope assessment, neurological examination, and debridement under general anesthesia with fracture stabilization with external fixators or casts. Graft incorporation was 80% in all treated patients. Autologous free, non-vascularized fibula and cancellous graft is a useful addition to the armamentarium of orthopedic surgeon in developing countries attempting to manage segmental bone loss, whether created by trauma or excision of tumors.

  16. [ITI dental implants immediately placed into vascularized iliac bone grafts for reconstruction of mandibular defect: analysis of 12 consecutive cases].

    Science.gov (United States)

    Wu, Yi-qun; Zhang, Zhi-yong; Zhang, Zhi-yuan; Huang, Wei; Lai, Hong-chang; Hu, Yong-jie; Zhang, Chen-ping

    2005-04-01

    Vascularized iliac bone graft combined implantation has become a routine procedure in the functional reconstruction of mandibular defects. The aim of this study was to assess the clinical outcomes of the implants immediately placed into the vascularized iliac bone grafts. In this study, 12 consecutive patients with 36 ITI dental implants who had reconstruction of mandibular defect between 2000 and 2004 were presented. All implants were inserted immediately after bone grafting and loaded after 3 to 5 months of submerged healing. In general, a primary stability for implants placed in vascularized iliac bone grafts were achieved. After 1 year of observation the mean vertical bone loss was less than 1mm. There was no implant failure in the observation period. The vascularized iliac bone grafts are safe implant-bearing areas and allows a reliable and predictable restoration with dental implants. Implant-supported bridges and overdentures can be used in this procedure.

  17. Bone ingrowth and vascular supply in experimental spinal fusion with platelet-rich plasma.

    Science.gov (United States)

    Cinotti, Gianluca; Corsi, Alessandro; Sacchetti, Benedetto; Riminucci, Mara; Bianco, Paolo; Giannicola, Giuseppe

    2013-03-01

    Prospective investigation using a posterolateral spinal fusion (PLSF) model in rabbits. To assess the effects of platelet-rich plasma (PRP) alone, or with uncultured bone marrow, on bone ingrowth and angiogenesis in experimental PLSF. PRP is an autologous substance potentially beneficial to spinal fusion, because it includes several growth factors that may stimulate bone ingrowth and angiogenesis. However, the results of experimental and clinical investigations on the effectiveness of PRP in spinal fusion are controversial. This study was aimed at analyzing the influence of PRP on bone ingrowth and angiogenesis in experimental PLSF. Twenty White New Zealand rabbits underwent PLSF at L4-L5 level. The graft material included a ceramic carrier (Pro-Osteon 500R) loaded, in 7 rabbits, with PRP alone on the right side (group 1A) and with uncultured bone marrow in the left side (group 1B). In 7 rabbits, the ceramic carrier was used alone in the right side (group 2A), and with uncultured bone marrow in the left side (group 2B). Six rabbits (group 3) were sham operated on both right and left sides. Six months after surgery, the lumbar spine was harvested en bloc and evaluated by high-resolution radiographs (Faxitron, Wheeling, IL) and histology. The radiographical outcome showed a fusion rate of 86% in groups 1A, 1B, and 2B and a fusion rate of 71% in group 2A. No specimen showed a solid fusion in the sham group. Histological analysis revealed new bone formation in the periapophyseal area in groups 1 and 2, but a complete bony bridge between the transverse processes was not observed in any specimen. In all groups, vascular density was significantly greater in the peri- compared with the interapophyseal region. In the PRP group, there was no evidence of increased vascular density in the grafted material compared with the other groups. In experimental PLSF model in rabbits, PRP was not effective in promoting new bone formation and vascularization.

  18. Bioactive Nano-fibrous Scaffold for Vascularized Craniofacial Bone Regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda

    2017-01-01

    and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; (human bone marrow skeletal (mesenchymal) stem cells (hMSC) and dental pulp stem cells (DPSC)). In addition, the scaffold supported in vitro osteogenic...... the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA) - poly (ε) caprolactone (PCL) - Bioceramic (HAB), namely, PVA-PCL-HAB. The scaffold prepared by dual...... electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic poly (ε) caprolactone (PCL) by combination with a hydrophilic polyvinyl alcohol (PVA) and the bioceramic (HAB) can contribute to enhance osteo-conductivity. We characterized the physicochemical...

  19. Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization.

    Science.gov (United States)

    Barbeck, Mike; Najman, Stevo; Stojanović, Sanja; Mitić, Žarko; Živković, Jelena M; Choukroun, Joseph; Kovačević, Predrag; Sader, Robert; Kirkpatrick, C James; Ghanaati, Shahram

    2015-09-11

    The present study aimed to analyze the effects of the addition of blood to the phycogenic bone substitute Algipore(®) on the severity of in vivo tissue reaction. Initially, Fourier-transform infrared spectroscopy (FTIR) of the bone substitute was conducted to analyze its chemical composition. The subcutaneous implantation model in Balb/c mice was then applied for up to 30 d to analyze the tissue reactions on the basis of specialized histochemical, immunohistochemical, and histomorphometrical methods. The data of the FTIR analysis showed that the phycogenic bone substitute material is mainly composed of hydroxyapatite with some carbonate content. The in vivo analyses revealed that the addition of blood to Algipore(®) had a major impact on both angiogenesis and vessel maturation. The higher vascularization seemed to be based on significantly higher numbers of multinucleated TRAP-positive cells. However, mostly macrophages and a relatively low number of multinucleated giant cells were involved in the tissue reaction to Algipore(®). The presented data show that the addition of blood to a bone substitute impacts the tissue reaction to it. In particular, the immune response and the vascularization were influenced, and these are believed to have a major impact on the regenerative potential of the process of bone tissue regeneration.

  20. Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

    Science.gov (United States)

    Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

    2013-01-01

    Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

  1. Guided bone regeneration (GBR) utilizing injectable Vascular Endothelial Growth Factor (VEGF) delivery gel

    Science.gov (United States)

    Kaigler, Darnell; Silva, Eduardo A.; Mooney, David J.

    2013-01-01

    Background Vascularization underlies the success of guided bone regeneration (GBR) procedures. This study evaluated the regenerative potential of GBR in combination with Vascular Endothelial Growth Factor (VEGF) delivery, via an injectable hydrogel system. Methods Critical-sized defects were created in rat calvariae and GBR procedures were performed with a collagen membrane either alone (control), plus bolus delivery of VEGF, or plus application of VEGF releasing hydrogels (VEGF - Alg). Four and eight weeks following treatment, defect sites were evaluated with microcomputed tomographic and histomorphometric analyses for blood vessel and bone formation. Results At four weeks, relative to the control condition, the bolus addition of VEGF did not affect blood vessel density within the defect site; yet, the application of the VEGF+ Alg significantly (pGBR may be a promising strategy for enhancing outcomes of GBR. PMID:22668339

  2. Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

    Science.gov (United States)

    Alwood, J. S.; Limoli, C. L.; Delp, M. D.; Castillo, A. B.; Globus, R. K.

    2012-01-01

    Weightlessness causes a cephalad fluid shift and reduction in mechanical stimulation, adversely affecting both cortical and trabecular bone tissue in astronauts. In rodent models of weightlessness, the onset of bone loss correlates with reduced skeletal perfusion, reduced and rarified vasculature and lessened vasodilation, which resembles blood-bone symbiotic events that can occur with fracture repair and aging. These are especially serious risks for long term, exploration class missions when astronauts will face the challenge of increased exposure to space radiation and abrupt transitions between different gravity environments upon arrival and return. Previously, we found using the mouse hindlimb unloading model and exposure to heavy ion radiation, both disuse and irradiation cause an acute bone loss that was associated with a reduced capacity to produce bone-forming osteoblasts from the bone marrow. Together, these findings led us to hypothesize that exposure to space radiation exacerbates weightlessness-induced bone loss and impairs recovery upon return, and that treatment with anti-oxidants may mitigate these effects. The specific aims of this recently awarded grant are to: AIM 1 Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress. AIM 2 Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction. AIM 3 Determine how space radiation influences later skeletal and vasculature recovery from prolonged weightlessness and the potential of anti-oxidants to preserve adaptive remodeling.

  3. [Resection of an aneurysmal bone cyst in the proximal humerus with a non-vascularized fibular graft. Case report].

    Science.gov (United States)

    Lima-Ramírez, P G; Chavarría-Jacinto, J; Martínez-Asención, P; Montiel-Jarquín, A J; Barragán-Hervella, R G; Salvatori-Rubí, J J; Domínguez-Cid, M I

    2015-01-01

    An aneurysmal bone cyst is a benign lesion involving the marrow of long bones; it accounts for 6% of primary bone lesions and may occur as a secondary lesion with other benign or malignant bone tumors. We describe herein the case of a seven year-old female with an aneurysmal bone cyst which was diagnosed clinically, radiographically and with a CAT scan, and confirmed with histopathology. Resection was performed using the eggshell technique and a non-vascularized left fibular bone graft. The patient did well up to the fourth postoperative year, which is consistent with what has been reported in world literature.

  4. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.

    Science.gov (United States)

    Maes, Christa; Carmeliet, Peter; Moermans, Karen; Stockmans, Ingrid; Smets, Nico; Collen, Désiré; Bouillon, Roger; Carmeliet, Geert

    2002-02-01

    Vascular endothelial growth factor (VEGF)-mediated angiogenesis is an important part of bone formation. To clarify the role of VEGF isoforms in endochondral bone formation, we examined long bone development in mice expressing exclusively the VEGF120 isoform (VEGF120/120 mice). Neonatal VEGF120/120 long bones showed a completely disturbed vascular pattern, concomitant with a 35% decrease in trabecular bone volume, reduced bone growth and a 34% enlargement of the hypertrophic chondrocyte zone of the growth plate. Surprisingly, embryonic hindlimbs at a stage preceding capillary invasion exhibited a delay in bone collar formation and hypertrophic cartilage calcification. Expression levels of marker genes of osteoblast and hypertrophic chondrocyte differentiation were significantly decreased in VEGF120/120 bones. Furthermore, inhibition of all VEGF isoforms in cultures of embryonic cartilaginous metatarsals, through the administration of a soluble receptor chimeric protein (mFlt-1/Fc), retarded the onset and progression of ossification, suggesting that osteoblast and/or hypertrophic chondrocyte development were impaired. The initial invasion by osteoclasts and endothelial cells into VEGF120/120 bones was retarded, associated with decreased expression of matrix metalloproteinase-9. Our findings indicate that expression of VEGF164 and/or VEGF188 is important for normal endochondral bone development, not only to mediate bone vascularization but also to allow normal differentiation of hypertrophic chondrocytes, osteoblasts, endothelial cells and osteoclasts.

  5. Vascularization mediated by mesenchymal stem cells from bone marrow and adipose tissue: a comparison

    Directory of Open Access Journals (Sweden)

    Karoline Pill

    2015-01-01

    Full Text Available Tissue-engineered constructs are promising to overcome shortage of organ donors and to reconstruct at least parts of injured or diseased tissues or organs. However, oxygen and nutrient supply are limiting factors in many tissues, especially after implantation into the host. Therefore, the development of a vascular system prior to implantation appears crucial. To develop a functional vascular system, different cell types that interact with each other need to be co-cultured to simulate a physiological environment in vitro. This review provides an overview and a comparison of the current knowledge of co-cultures of human endothelial cells (ECs with human adipose tissue-derived stem/stromal cells (ASCs or bone marrow-mesenchymal stem cells (BMSCs in three dimensional (3D hydrogel matrices. Mesenchymal stem cells (MSCs, BMSCs or ASCs, have been shown to enhance vascular tube formation of ECs and to provide a stabilizing function in addition to growth factor delivery and permeability control for ECs. Although phenotypically similar, MSCs from different tissues promote tubulogenesis through distinct mechanisms. In this report, we describe differences and similarities regarding molecular interactions in order to investigate which of these two cell types displays more favorable characteristics to be used in clinical applications. Our comparative study shows that ASCs as well as BMSCs are both promising cell types to induce vascularization with ECs in vitro and consequently are promising candidates to support in vivo vascularization.

  6. Vascular lesions of bone in children, adolescents, and young adults. A clinicopathologic reappraisal and application of the ISSVA classification.

    Science.gov (United States)

    Bruder, Elisabeth; Perez-Atayde, Antonio R; Jundt, Gernot; Alomari, Ahmad I; Rischewski, Johannes; Fishman, Steven J; Mulliken, John B; Kozakewich, Harry P W

    2009-02-01

    Vascular lesions of bone are rare and their terminology is not standardized. Herein, we report 77 patients with such lesions in order to characterize their morphologic spectrum and the applicability of the International Society for the Study of Vascular Anomalies (ISSVA) classification. In this system, malformations are structural anomalies distinguishable from tumors, which are proliferative. The radiologic images/reports and pathologic materials from all patients were reviewed. All lesions were either restricted to bone or had minimal contiguous soft tissue involvement with the exception of some multifocal lymphatic lesions that extensively affected soft tissue and/or viscera. We found that certain lesions of bone often regarded as tumors should be classified as malformations. Malformations (n = 46) were more common than tumors (n = 31); lymphatic and venous malformations were equally frequent. In the tumor category, hemangioendothelioma and epithelioid hemangioma were the most common. We also describe new vascular entities that arise in or involve bone. Utilizing the ISSVA approach, the diverse and often contradictory terminology of vascular lesions of bone can be largely eliminated. Standardized nomenclature is critical for scientific communication and patient management, and we hereby recommend the ISSVA classification be applied to vascular lesions of bone, just as for skin, soft tissue, and viscera.

  7. Aging and estrogen status: a possible endothelium-dependent vascular coupling mechanism in bone remodeling.

    Directory of Open Access Journals (Sweden)

    Rhonda D Prisby

    Full Text Available Bone loss with aging and menopause may be linked to vascular endothelial dysfunction. The purpose of the study was to determine whether putative modifications in endothelium-dependent vasodilation of the principal nutrient artery (PNA of the femur are associated with changes in trabecular bone volume (BV/TV with altered estrogen status in young (6 mon and old (24 mon female Fischer-344 rats. Animals were divided into 6 groups: 1 young intact, 2 old intact, 3 young ovariectomized (OVX, 4 old OVX, 5 young OVX plus estrogen replacement (OVX+E2, and 6 old OVX+E2. PNA endothelium-dependent vasodilation was assessed in vitro using acetylcholine. Trabecular bone volume of the distal femoral metaphysis was determined by microCT. In young rats, vasodilation was diminished by OVX and restored with estrogen replacement (intact, 82±7; OVX, 61±9; OVX+E2, 90±4%, which corresponded with similar modifications in BV/TV (intact, 28.7±1.6; OVX, 16.3±0.9; OVX+E2, 25.7±1.4%. In old animals, vasodilation was unaffected by OVX but enhanced with estrogen replacement (intact, 55±8; OVX, 59±7; OVX+E2, 92±4%. Likewise, modifications in BV/TV followed the same pattern (intact, 33.1±1.6; OVX, 34.4±3.7; OVX+E2, 42.4±2.1%. Furthermore, in old animals with low endogenous estrogen (i.e., intact and old OVX, vasodilation was correlated with BV/TV (R(2 = 0.630; P<0.001. These data demonstrate parallel effects of estrogen on vascular endothelial function and BV/TV, and provide for a possible coupling mechanism linking endothelium-dependent vasodilation to bone remodeling.

  8. RNA catalysis through compartmentalization

    Science.gov (United States)

    Strulson, Christopher A.; Molden, Rosalynn C.; Keating, Christine D.; Bevilacqua, Philip C.

    2012-11-01

    RNA performs important cellular functions in contemporary life forms. Its ability to act both as a catalyst and a storage mechanism for genetic information is also an important part of the RNA world hypothesis. Compartmentalization within modern cells allows the local concentration of RNA to be controlled and it has been suggested that this was also important in early life forms. Here, we mimic intracellular compartmentalization and macromolecular crowding by partitioning RNA in an aqueous two-phase system (ATPS). We show that the concentration of RNA is enriched by up to 3,000-fold in the dextran-rich phase of a polyethylene glycol/dextran ATPS and demonstrate that this can lead to approximately 70-fold increase in the rate of ribozyme cleavage. This rate enhancement can be tuned by the relative volumes of the two phases in the ATPS. Our observations support the importance of compartmentalization in the attainment of function in an RNA World as well as in modern biology.

  9. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

    Science.gov (United States)

    Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

    2014-09-01

    Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (Posteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    Science.gov (United States)

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  11. Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct from osteoid osteoma and osteoblastoma, radiologically simulating a vascular tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kyriakos, Michael [Washington University School of Medicine, Division of Surgical Pathology, Campus Box 8118, St. Louis, MO (United States); El-Khoury, Georges Y. [University of Iowa, Department of Radiology, Roy J. and Lucille A. Carver School of Medicine, Iowa City, IA (United States); McDonald, Douglas J. [Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO (United States); Buckwalter, Joseph A. [University of Iowa, Department of Orthopaedics, Roy J. and Lucille A. Carver School of Medicine, Iowa City, IA (United States); Sundaram, Murali [Cleveland Clinic Foundation, Department of Radiology, Cleveland, OH (United States); DeYoung, Barry [University of Iowa, Department of Pathology, School of Medicine, Iowa City, IA (United States); O' Brien, Michael P. [University of Wisconsin Hospital, Department of Radiology, Madison, WI (United States)

    2007-03-15

    Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors. (orig.)

  12. Methods for histochemical demonstration of vascular structures at the muscle-bone interface from cryostate sections of demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S

    1981-01-01

    In tissue decalcified with MgNa2EDTA at a neutral pH activity for ATPase can used be for demonstration of the vascular structures at the muscle-bone interface. The GOMORI method for alkaline phosphatase is only of value, when fresh unfixed tissue is to be examined. The azo-dye method for alkaline...

  13. High Acute Myeloid Leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow

    NARCIS (Netherlands)

    Weidenaar, Alida C.; ter Elst, Arja; Koopmans-Klein, Gineke; Rosati, Stefano; den Dunnen, Wilfred F. A.; Meeuwsen-de Boer, Tiny; Kamps, Willem A.; Vellenga, Edo; de Bont, Eveline S. J. M.

    Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the

  14. Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences.

    Science.gov (United States)

    Villa, Julia Khéde Dourado; Diaz, Marisa Alves Nogueira; Pizziolo, Virgínia Ramos; Martino, Hércia Stampini Duarte

    2017-12-12

    Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K1) and menaquinone (vitamin K2). In this study, it was especially investigated the action of vitamin K2 in bones and vessels. Vitamin K2 has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K2 reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K2 reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K2 in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women.

  15. Bone Morphogenetic Protein 9 Enhances Lipopolysaccharide-Induced Leukocyte Recruitment to the Vascular Endothelium.

    Science.gov (United States)

    Appleby, Sarah L; Mitrofan, Claudia-Gabriela; Crosby, Alexi; Hoenderdos, Kim; Lodge, Katharine; Upton, Paul D; Yates, Clara M; Nash, Gerard B; Chilvers, Edwin R; Morrell, Nicholas W

    2016-10-15

    Bone morphogenetic protein (BMP)9 is a circulating growth factor that is part of the TGF-β superfamily and is an essential regulator of vascular endothelial homeostasis. Previous studies have suggested a role for BMP9 signaling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying mechanisms have not been elucidated. In this study, we report that BMP9 upregulates TLR4 expression in human endothelial cells and that BMP9 pretreatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay. BMP9 alone did not induce neutrophil recruitment to the endothelium. We also show that E-selectin and VCAM-1, but not ICAM-1, are upregulated in response to BMP9 in LPS-stimulated human endothelial cells. Small interfering RNA knockdown of activin receptor-like kinase 1 inhibited the BMP9-induced expression of TLR4 and VCAM-1 and inhibited BMP9-induced human neutrophil recruitment to LPS-stimulated human endothelial cells. BMP9 treatment also increased leukocyte recruitment within the pulmonary circulation in a mouse acute endotoxemia model. These results demonstrate that although BMP9 alone does not influence leukocyte recruitment, it primes the vascular endothelium to mount a more intense response when challenged with LPS through an increase in TLR4, E-selectin, and VCAM-1 and ultimately through enhanced leukocyte recruitment. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. High Calcium Bioglass Enhances Differentiation and Survival of Endothelial Progenitor Cells, Inducing Early Vascularization in Critical Size Bone Defects

    Science.gov (United States)

    Nguyen Ngoc, Christina; Meier, Simon; Nau, Christoph; Schaible, Alexander; Marzi, Ingo; Henrich, Dirk

    2013-01-01

    Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12). Controls (n = 6) received BG40 and the treatment group (n = 6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects. PMID:24244419

  17. A 3D vascularized bone remodeling model combining osteoblasts and osteoclasts in a CaP nanoparticle-enriched matrix.

    Science.gov (United States)

    Bongio, Matilde; Lopa, Silvia; Gilardi, Mara; Bersini, Simone; Moretti, Matteo

    2016-05-01

    We aimed to establish a 3D vascularized in vitro bone remodeling model. Human umbilical endothelial cells (HUVECs), bone marrow mesenchymal stem cells (BMSCs), and osteoblast (OBs) and osteoclast (OCs) precursors were embedded in collagen/fibrin hydrogels enriched with calcium phosphate nanoparticles (CaPn). We assessed vasculogenesis in HUVEC-BMSC coculture, osteogenesis with OBs, osteoclastogenesis with OCs, and, ultimately, cell interplay in tetraculture. HUVECs developed a robust microvascular network and BMSCs differentiated into mural cells. Noteworthy, OB and OC differentiation was increased by their reciprocal coculture and by CaPn, and even more by the combination of the tetraculture and CaPn. We successfully developed a vascularized 3D bone remodeling model, whereby cells interacted and exerted their specific function.

  18. Alendronate as an Effective Treatment for Bone Loss and Vascular Calcification in Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Masanori Okamoto

    2014-01-01

    Full Text Available Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects and a control group (group C: 7 subjects. Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1 the time-dependent change in bone mineral density (BMD estimated with DEXA and (2 progression of abdominal AC, calculated twice as an index (ACI using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% (P=0.015 versus baseline, and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%, but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%, P=0.061. In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR.

  19. Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT.

    Directory of Open Access Journals (Sweden)

    Hervé Nyangoga

    Full Text Available BACKGROUND: Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography. They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. CONCLUSION: This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular

  20. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis.

    Science.gov (United States)

    Frisbie, David D; Kisiday, John D; Kawcak, Chris E; Werpy, Natasha M; McIlwraith, C Wayne

    2009-12-01

    The purpose of this study was the assessment of clinical, biochemical, and histologic effects of intraarticular administered adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. Osteoarthritis was induced arthroscopically in the middle carpal joint of all horses, the contralateral joint being sham-operated. All horses received treatment on Day 14. Eight horses received placebo treatment and eight horses received adipose-derived stromal vascular fraction in their osteoarthritis-affected joint. The final eight horses were treated the in osteoarthritis-affected joint with bone marrow-derived mesenchymal stem cells. Evaluations included clinical, radiographic, synovial fluid analysis, gross, histologic, histochemical, and biochemical evaluations. No adverse treatment-related events were observed. The model induced a significant change in all but two parameters, no significant treatment effects were demonstrated, with the exception of improvement in synovial fluid effusion PGE2 levels with bone marrow-derived mesenchymal stem cells when compared to placebo. A greater improvement was seen with bone marrow-derived mesenchymal stem cells when compared to adipose-derived stromal vascular fraction and placebo treatment. Overall, the findings of this study were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in this model.

  1. Adipose Tissue-Derived Stromal Vascular Fraction Increases Osteogenesis in an Experimental Design Zygomatic Bone Defect Model.

    Science.gov (United States)

    Toplu, Gaye; Ozcelik, Derya; Serin, Merdan; Erdem, Havva; Topacoglu, Arzu Turkseven

    2017-11-01

    Facial bone defects are frequently encountered problems in clinical practice. Bone grafts, flaps, and alloplastic materials are often used in their treatment. This leads to donor site morbidity and prolongation of the operation. The authors have planned this study to examine whether adipose tissue derived stromal vascular fraction (SVF) has an osteogenic effect in the critical sized membranous bone defect of the zygomatic bone. Twenty male Wistar Albino rats were used. Bilateral zygomatic arches were opened with lateral incisions. A standard 3-mm bone defect was created bilaterally on the zygomatic arches of the rats. In the experiment side, the stem cell-rich SVF that was obtained by applying centrifugal process to the adipose tissue derived from the inguinal fat pad was injected into the site of the right zygomatic arch bone defect. In the control side, left zygomatic arch was left for secondary bone healing without any treatment after a 3-mm critical bone defect was created. In the postoperative 10th (n:5) and 20th weeks (n:13), the healing areas of bone defects were assessed by a 3-dimensional tomography, and then, the rats were sacrificed and bone healing was examined histologically. There were no statistically significant differences on the 10th week results. At the 20th week new bone formation amount calculated from the 3-dimensional computed tomography results was significantly higher in the experiment side (P = 0.033). In the histological examination at the 20th week, there was significantly more callus formation in the experiment side (P = 0.0112). Stem cells can increase the rate of bone healing by differentiating into certain tissues. It is predicted that adipose tissue-derived SVF rich with mesenchymal stem cells can increase bone healing in facial bone defects and this application could replace the use of bone grafts and flaps in clinical practice. As a result, it is concluded that adipose tissue-derived stem cells can potentiate osteogenesis

  2. Bone marrow concentrated cells and stromal vascular fraction cells injections for osteoarthritis treatment: a systematic review.

    Science.gov (United States)

    Vadalà, G; Papalia, R; La Verde, L; Russo, F; Denaro, V; Rosa, M A

    2016-01-01

    The aim of this systematic review is to examine current clinical evidences supporting the intraarticular injection of bone marrow concentrate cells (BMC) and adipose-derived stromal vascular fraction cells (SVF) for the treatment of osteoarthritis (OA). The research was performed on PubMed (Medline), EMBASE and Cochrane Library considering the English literature. Only clinical trials have been included. The systematic research identified twelve clinical trials. Articles included in the study, were one of level II, four of level III, six of level IV and one level V. Among clinical trials, none were randomized, four were comparative, seven were case series, and one was a case report. Seven studies were focused on the use of SVF (1332 patients) and five on the use of BMC (963 patients), with preliminary interesting findings in the OA treatment. Despite the growing interest in this biological approach for OA, knowledge on this topic is still preliminary. Randomized controlled trials are needed to support the potential of BMC and SVF injections and to evaluate advantages and disadvantages with respect to the available treatments.

  3. High calcium bioglass enhances differentiation and survival of endothelial progenitor cells, inducing early vascularization in critical size bone defects.

    Directory of Open Access Journals (Sweden)

    Karam Eldesoqi

    Full Text Available Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC, seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12. Controls (n = 6 received BG40 and the treatment group (n = 6 received BG40 seeded with 5×10(5 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca(2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects.

  4. Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells: A Translational Biologic Alternative for Healing Critical Bone Defects.

    Science.gov (United States)

    Lough, Denver; Swanson, Edward; Sopko, Nikolai A; Madsen, Christopher; Miller, Devin; Wang, Howard; Guo, Qiongyu; Sursala, Srinivas M; Kumar, Anand R

    2017-04-01

    Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis. Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two- and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model. Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell- and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two- and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation. Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.

  5. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  6. The accuracy of computer-assisted primary mandibular reconstruction with vascularized bone flaps: iliac crest bone flap versus osteomyocutaneous fibula flap.

    Science.gov (United States)

    Modabber, Ali; Ayoub, Nassim; Möhlhenrich, Stephan Christian; Goloborodko, Evgeny; Sönmez, Tolga Taha; Ghassemi, Mehrangiz; Loberg, Christina; Lethaus, Bernd; Ghassemi, Alireza; Hölzle, Frank

    2014-01-01

    The intention of mandibular reconstruction is to restore the complex anatomy with maximum possible functionality and high accuracy. The aim of this study was to evaluate the accuracy of computer-assisted surgery in primary mandibular reconstruction with an iliac crest bone flap compared with an osteomyocutaneous fibula flap. Preoperative computed tomography data of the mandible and the iliac crest or fibula donor site were imported into a specific surgical planning software program. Surgical guides were manufactured using a rapid prototyping technique for translating the virtual plan, including information on the transplant dimensions and shape, into real-time surgery. Using postoperative computed tomography scans and an automatic surface-comparison algorithm, the actual postoperative situation was compared with the preoperative virtual simulation. The actual flap position showed a mean difference from the virtual plan of 2.43 mm (standard deviation [SD] ±1.26) and a surface deviation of 39% virtual plan of 1.25 mm (SD ±1.31) and a surface deviation of 82% Virtual surgical planning is an effective method for mandibular reconstruction with vascularized bone flaps, and can help to restore the anatomy of the mandible with high accuracy in position and shape. It seems that primary mandibular reconstruction with the osteomyocutaneous fibula flap is more accurate compared with the vascularized iliac crest bone flap.

  7. The accuracy of computer-assisted primary mandibular reconstruction with vascularized bone flaps: iliac crest bone flap versus osteomyocutaneous fibula flap

    Directory of Open Access Journals (Sweden)

    Modabber A

    2014-06-01

    reconstruction with an iliac crest bone flap. For shape analysis, a similarly high accuracy could be calculated for both flaps. Conclusion: Virtual surgical planning is an effective method for mandibular reconstruction with vascularized bone flaps, and can help to restore the anatomy of the mandible with high accuracy in position and shape. It seems that primary mandibular reconstruction with the osteomyocutaneous fibula flap is more accurate compared with the vascularized iliac crest bone flap. Keywords: computer-assisted surgery, virtual planning, vascularized bone flaps, surgical guide, primary mandibular reconstruction

  8. Nonnegative and Compartmental Dynamical Systems

    CERN Document Server

    Haddad, Wassim M; Hui, Qing

    2010-01-01

    This comprehensive book provides the first unified framework for stability and dissipativity analysis and control design for nonnegative and compartmental dynamical systems, which play a key role in a wide range of fields, including engineering, thermal sciences, biology, ecology, economics, genetics, chemistry, medicine, and sociology. Using the highest standards of exposition and rigor, the authors explain these systems and advance the state of the art in their analysis and active control design. Nonnegative and Compartmental Dynamical Systems presents the most complete treatment available o

  9. Culture of equine bone marrow mononuclear fraction and adipose tissue-derived stromal vascular fraction cells in different media

    Directory of Open Access Journals (Sweden)

    Gesiane Ribeiro

    2013-12-01

    Full Text Available The objective of this study was to evaluate the culture of equine bone marrow mononuclear fraction and adipose tissue - derived stromal vascular fraction cells in two different cell culture media. Five adult horses were submitted to bone marrow aspiration from the sternum, and then from the adipose tissue of the gluteal region near the base of the tail. Mononuclear fraction and stromal vascular fraction were isolated from the samples and cultivated in DMEM medium supplemented with 10% fetal bovine serum or in AIM-V medium. The cultures were observed once a week with an inverted microscope, to perform a qualitative analysis of the morphology of the cells as well as the general appearance of the cell culture. Colony-forming units (CFU were counted on days 5, 15 and 25 of cell culture. During the first week of culture, differences were observed between the samples from the same source maintained in different culture media. The number of colonies was significantly higher in samples of bone marrow in relation to samples of adipose tissue.

  10. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.

    Science.gov (United States)

    Javaheri, B; Carriero, A; Staines, K A; Chang, Y-M; Houston, D A; Oldknow, K J; Millan, J L; Kazeruni, Bassir N; Salmon, P; Shefelbine, S; Farquharson, C; Pitsillides, A A

    2015-12-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay

  11. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

    Directory of Open Access Journals (Sweden)

    Heather A. Himburg

    2012-10-01

    Full Text Available The mechanisms through which the bone marrow (BM microenvironment regulates hematopoietic stem cell (HSC fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN in regulating HSC function in the niche. PTN−/− mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

  12. Effects of vascular formation during alveolar bone process morphogenesis in mice.

    Science.gov (United States)

    An, Seo-Young; Lee, Ye-Ji; Neupane, Sanjiv; Jun, Jong-Hwa; Kim, Ji-Youn; Lee, Youngkyun; Choi, Karp-Shik; An, Chang-Hyeon; Suh, Jo-Young; Shin, Hong-In; Sohn, Wern-Joo; Kim, Jae-Young

    2017-10-01

    The alveolar bone process is the thickened ridge of bone that bears the teeth and is known to have dynamic functional interactions with surrounding tissues. However, the detailed morphological changes that occur during alveolar bone process development and the underlying molecular mechanisms behind this morphogenesis have not been elucidated. In this study, we examined the detailed morphological changes of the alveolar bone process during mouse development using HE and MTC staining. In addition, we evaluated the precise localization pattern of various signaling molecules involved in blood vessel formation including CD31, α-SMA, VEGF, periostin, and TGF-β. Innervation of the alveolar bone process was examined following injection of the nerve terminal dye AM1-43. The morphological and immunohistochemical data suggested that there is an intimate relationship between alveolar bone process development and blood vessel formation. To more closely examine the role of blood vessels in alveolar bone process formation, we microinjected mice with a clinically available anti-VEGF antibody, bevacizumab, at PN5 and analyzed the effects 5 days later. Compared to the control animals, anti-VEGF treated animals showed a disruption of the integration of bony tissues to form the alveolar bone process structures, which should contain the periodontal ligaments. Based on these data, we conclude that specific morphogenesis of the alveolar bone process is closely associated with blood vessel formation.

  13. A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

    Science.gov (United States)

    Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

    2016-02-01

    3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

  14. A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair.

    Science.gov (United States)

    Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

    2016-02-12

    3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

  15. Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis

    NARCIS (Netherlands)

    Kollar, A.; Jones, R.L.; Stacchiotti, S.; Gelderblom, H.; Guida, M.; Grignani, G.; Steeghs, N.; Safwat, A.; Katz, D.; Duffaud, F.; Sleijfer, S.; Graaf, W.T. van der; Touati, N.; Litiere, S.; Marreaud, S.; Gronchi, A.; Kasper, B.

    2017-01-01

    BACKGROUND: Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited.

  16. 3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

    Science.gov (United States)

    Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

    2017-07-17

    Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

  17. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

    Directory of Open Access Journals (Sweden)

    Ryan E. Tomlinson

    2016-09-01

    Full Text Available Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

  18. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone.

    Science.gov (United States)

    Tomlinson, Ryan E; Li, Zhi; Zhang, Qian; Goh, Brian C; Li, Zhu; Thorek, Daniel L J; Rajbhandari, Labchan; Brushart, Thomas M; Minichiello, Liliana; Zhou, Fengquan; Venkatesan, Arun; Clemens, Thomas L

    2016-09-06

    Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkA(F592A) mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification. Published by Elsevier Inc.

  19. Repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells in a rat model

    National Research Council Canada - National Science Library

    Jiang, Xiao-Rui; Yang, Hui-Ying; Zhang, Xin-Xin; Lin, Guo-Dong; Meng, Yong-Chun; Zhang, Pei-Xun; Jiang, Shan; Zhang, Chun-Lei; Huang, Fei; Xu, Lin

    2017-01-01

    ...) and osteoblasts (OBs). Rats were divided into five groups: Group A: in vitro prefabrication with EPCs-RFP + in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Grou...

  20. Engineering Photocrosslinkable Bicomponent Hydrogel Constructs for Creating 3D Vascularized Bone

    NARCIS (Netherlands)

    Kazemzadeh-Narbat, Mehdi; Rouwkema, Jeroen; Annabi, Nasim; Cheng, Hao; Ghaderi, Masoumeh; Cha, Byung-Hyun; Aparnathi, Mansi; Khalilpour, Akbar; Byambaa, Batzaya; Jabbari, Esmaiel; Tamayol, Ali; Khademhosseini, Ali

    2017-01-01

    Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of

  1. Man as a Living Bioreactor: Prefabrication of a Custom Vascularized Bone Graft in the Gastrocolic Omentum.

    Science.gov (United States)

    Wiltfang, Jörg; Rohnen, Michael; Egberts, Jan-Hendrik; Lützen, Ulf; Wieker, Henning; Açil, Yahya; Naujokat, Hendrik

    2016-08-01

    Reconstruction of critical-size jaw defects still remains challenging. The standard treatment today is transplantation of autologous bone grafts, which is associated with high donor-site morbidity and unsatisfactory outcomes. We aimed to reconstruct a mandibular discontinuity defect after ablative surgery using the gastrocolic omentum as a bioreactor for heterotopic ossification. Three-dimensional computed tomography data were used to produce an ideal virtual replacement for the mandibular defect. A titanium mesh cage was filled with bone mineral blocks, infiltrated with 12 mg of recombinant human bone morphogenetic protein 2, and enriched with bone marrow aspirate. The scaffold was implanted into the gastrocolic omentum, and 3 months later, a free flap was harvested to reconstruct the mandibular defect. In vivo single photon emission computed tomography/computed tomography revealed bone remodeling and mineralization inside the mandibular transplant during prefabrication and after transplantation. Reconstruction was possible without any further modifications of the graft. A histological evaluation revealed that large sections of the Bio-Oss material were covered with osteoid matrix 3 months after transplantation. The quality of life of the patient significantly increased with acquisition of the ability to masticate and the improvement in pronunciation and aesthetics. Heterotopic bone induction to form a mandibular replacement inside the gastrocolic omentum is possible in human subjects. Heterotopic prefabrication is associated with many advantages, like allowing a reduced operative burden compared with conventional techniques and good three-dimensional outcomes.

  2. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing.

    Science.gov (United States)

    Kazmers, Nikolas H; McKenzie, Jennifer A; Shen, Tony S; Long, Fanxin; Silva, Matthew J

    2015-12-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3 days (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1 day and 3 days in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1 day, but decreased Shh expression by 37% at 3 days. GDC-0449 decreased woven bone volume (-37%) and mineral density (-17%) at 7 days. Dynamic histomorphometry revealed that the 7 day callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3 days), osteoblastic differentiation (Osx expression at 1 day and 3 days), chondrogenic gene expression (Acan, Sox9, and Col2α1 expression at 1 day and 3 days), or bone resorption metrics (callus TRAP staining at 3 days, Rankl and Opg expression at 1 day and 3 days). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3 days, which was associated with increased Hif1α gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent

  3. Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

    Science.gov (United States)

    Globus, R. K.; Alwood, J.; Tahimic, C.; Schreurs, A.-S.; Shirazi-Fard, Y.; Terada, M.; Zaragoza, J.; Truong, T.; Bruns, K.; Castillo, A.; hide

    2018-01-01

    We examined experimentally the effects of radiation and/or simulated weightlessness by hindlimb unloading on bone and blood vessel function either after a short period or at a later time after transient exposures in adult male, C57Bl6J mice. In sum, recent findings from our studies show that in the short term, ionizing radiation and simulate weightlessness cause greater deficits in blood vessels when combined compared to either challenge alone. In the long term, heavy ion radiation, but not unloading, can lead to persistent, adverse consequences for bone and vessel function, possibly due to oxidative stress-related pathways.

  4. Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering.

    Science.gov (United States)

    Wang, Martha O; Vorwald, Charlotte E; Dreher, Maureen L; Mott, Eric J; Cheng, Ming-Huei; Cinar, Ali; Mehdizadeh, Hamidreza; Somo, Sami; Dean, David; Brey, Eric M; Fisher, John P

    2015-01-07

    There is an unmet need for a consistent set of tools for the evaluation of 3D-printed constructs. A toolbox developed to design, characterize, and evaluate 3D-printed poly(propylene fumarate) scaffolds is proposed for vascularized engineered tissues. This toolbox combines modular design and non-destructive fabricated design evaluation, evaluates biocompatibility and mechanical properties, and models angiogenesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease

    Directory of Open Access Journals (Sweden)

    Lightfoot Stan A

    2007-09-01

    Full Text Available Abstract Background Evidence from epidemiological, clinical and animal studies suggests a link may exist between low bone density and cardiovascular disease, with inflammatory mediators implicated in the pathophysiology of both conditions. This project examined whether supplementation with soy isoflavones (IF, shown to have anti-inflammatory properties, could prevent tissue expression of TNF-α and the development of skeletal pathology in an animal model of chronic inflammation. Methods Eight-week old, intact, female C57BL/6J mice were used. In Phase 1, a lipopolysaccharide (LPS-dose response study (0, 0.133, 1.33 and 13.3 μg/d was conducted to determine the LPS dose to use in Phase 2. The results indicated the 1.33 μg LPS/d dose produced the greatest decrease in lymphocytes and increase in neutrophils. Subsequently, in Phase 2, mice were randomly assigned to one of six groups (n = 12–13 per group: 0 or 1.33 μg LPS/d (placebo or LPS in combination with 0, 126 or 504 mg aglycone equivalents of soy IF/kg diet (Control, Low or High dose IF. Mice were fed IF beginning 2 wks prior to the 30-d LPS study period. Results At the end of the study, no differences were detected in final body weights or uterine weights. In terms of trabecular bone microarchitecture, μCT analyses of the distal femur metaphysis indicated that LPS significantly decreased trabecular bone volume (BV/TV and number (TbN, and increased separation (TbSp. Trabecular bone strength (i.e. total force and stiffness were also compromised in response to LPS. The High IF dose provided protection against these detrimental effects on microarchitecture, but not biomechanical properties. No alterations in trabecular thickness (TbTh, or cortical bone parameters were observed in response to the LPS or IF. Immunohistomchemical staining showed that tumor necrosis factor (TNF-α was up-regulated by LPS in the endothelium of small myocardial arteries and arterioles as well as the tibial

  6. Different effects of implanting vascular bundles and sensory nerve tracts on the expression of neuropeptide receptors in tissue-engineered bone in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chen Siyuan; Qin Junjun; Wang Le; Mu Tianwang; Jin Dan; Jiang Shan; Zhao Peiran [Department of Orthopaedic and Trauma, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Pei Guoxian, E-mail: easonfaye_2001@qq.co [Department of Orthopaedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China)

    2010-10-01

    We investigated whether implantation of vascular bundles or sensory nerves affected the expression of calcitonin gene-related peptide type I receptor (CGRP1R) and neuropeptide Y1 receptor (NPY1R) in tissue-engineered bone. We implanted osteogenically induced bone marrow mesenchymal stem cells (BMSCs) with {beta}-tricalcium phosphate ({beta}-TCP) as the scaffold material either with sensory nerve tracts (group I, n = 18), vascular bundles (group II, n = 18) or alone (group III, n = 18) to repair a 1.2 cm femur defect in the rabbit. Better osteogenesis was observed by x-ray and histology in groups I and II than in group III at 4, 8 and 12 weeks. Within the new bone, the mRNA levels of the two neuropeptide receptors determined by real-time PCR increased through week 8, and then gradually decreased (P < 0.05). Expression of the neuropeptide receptors determined by immunohistochemistry was lowest at 4 weeks (P < 0.05) and was higher in group II than in group I (P < 0.05). Expression was significantly higher in groups I and II than in group III at all time points. We conclude that implanting vascular bundles into tissue-engineered bone can significantly improve the early expression of CGRP1R and NPY1R. In contrast, implantation of sensory nerves did not show the same dramatic effect as implantation of vascular bundles.

  7. Compartmental modeling and tracer kinetics

    CERN Document Server

    Anderson, David H

    1983-01-01

    This monograph is concerned with mathematical aspects of compartmental an­ alysis. In particular, linear models are closely analyzed since they are fully justifiable as an investigative tool in tracer experiments. The objective of the monograph is to bring the reader up to date on some of the current mathematical prob­ lems of interest in compartmental analysis. This is accomplished by reviewing mathematical developments in the literature, especially over the last 10-15 years, and by presenting some new thoughts and directions for future mathematical research. These notes started as a series of lectures that I gave while visiting with the Division of Applied ~1athematics, Brown University, 1979, and have developed in­ to this collection of articles aimed at the reader with a beginning graduate level background in mathematics. The text can be used as a self-paced reading course. With this in mind, exercises have been appropriately placed throughout the notes. As an aid in reading the material, the e~d of a ...

  8. The New Role of CD163 in the Differentiation of Bone Marrow Stromal Cells into Vascular Endothelial-Like Cells

    Directory of Open Access Journals (Sweden)

    Wei Lu

    2016-01-01

    Full Text Available Bone marrow stromal cells (BMSCs can differentiate into vascular endothelial cells (VECs. It is regarded as an important solution to cure many diseases, such as ischemic diseases and diabetes. However, the mechanisms underlying BMSC differentiation into VECs are not well understood. Recent reports showed that CD163 expression was associated with angiogenesis. In this study, overexpression of CD163 in BMSCs elevated the protein level of the endothelial-associated markers CD31, Flk-1, eNOS, and VE-cadherin, significantly increased the proportion of Alexa Fluor 488-acetylated-LDL-positive VECs, and promoted angiogenesis on Matrigel. Furthermore, we demonstrated that CD163 acted downstream homeobox containing 1 (Hmbox1 and upstream fibroblast growth factor 2 (FGF-2. These data suggested that CD163 was involved in Hmbox1/CD163/FGF-2 signal pathway in BMSC differentiation into vascular endothelial-like cells. We found a new signal pathway and a novel target for further investigating the gene control of BMSC differentiation into a VEC lineage.

  9. VEGFR2-mediated vascular dilation as a mechanism of VEGF-induced anemia and bone marrow cell mobilization.

    Science.gov (United States)

    Lim, Sharon; Zhang, Yin; Zhang, Danfang; Chen, Fang; Hosaka, Kayoko; Feng, Ninghan; Seki, Takahiro; Andersson, Patrik; Li, Jingrong; Zang, Jingwu; Sun, Baocun; Cao, Yihai

    2014-10-23

    Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1(TK-/-)) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1(+)/VEGFR2(+) populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Protocell design through modular compartmentalization.

    Science.gov (United States)

    Miller, David; Booth, Paula J; Seddon, John M; Templer, Richard H; Law, Robert V; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M C

    2013-10-06

    De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound 'proto-organelles', which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction.

  11. Vascular perfusion of the dorsal and palmar condyles of the equine third metacarpal bone.

    Science.gov (United States)

    Alber, M T; Brown, M P; Merritt, K A; Trumble, T N

    2014-05-01

    Palmar osteochondral disease (POD) is an overload arthrosis that commonly affects fetlock joints of racing Thoroughbreds (TB) but the aetiopathogenesis of the disease has not been well defined. The aim of this study was to compare India ink perfusion in the dorsal and palmar condyles of the third metacarpal bone (McIII) in both passively flexed and maximally extended fetlock joints from paired equine cadaver limbs. Descriptive cadaver study comparing perfusion of condyles of McIII in paired cadaver limbs in flexion (control group) and maximal extension (intervention group). Pairs of forelimbs were acquired from 5 TB horses subjected to euthanasia for reasons unrelated to lameness. Limb pairs were perfused intra-arterially with India ink and then randomly assigned to passive flexion or maximal extension of the fetlock joint. Limbs were sectioned sagittally in 3 mm sections through the fetlock and 12 sections per limb processed using a modified tissue-clearing technique. Sections were subsequently digitally imaged and bone perfusion evaluated with image analysis software. Greater perfusion of the dorsal condyle than of palmar condyle was observed in 78% of sections from limbs in passive flexion and 92% of maximally extended sections. Perfusion to the palmar aspect of the condyle was significantly decreased (P fetlock joint was in passive flexion and this difference was exacerbated by maximal extension. Based on the anatomical location of POD lesions, perfusion differences between the dorsal and palmar condyles of McIII may be associated with development of these lesions. © 2013 EVJ Ltd.

  12. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    Directory of Open Access Journals (Sweden)

    Harshini Chakravarthy

    Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  13. Application of high-tech three-dimensional imaging and computer-generated models in complex facial reconstructions with vascularized bone grafts.

    Science.gov (United States)

    Rose, E H; Norris, M S; Rosen, J M

    1993-02-01

    We present a series of six patients with eight flaps in whom computer-generated models were used for fabrication of vascularized bone grafts in complex facial restorations. Preoperative CT data, digitalized on tape, were converted by the CEMAX (Santa Clara, Calif.) 1500 Integrated Hardware and Software System to a three-dimensional visualization of the bone and soft-tissue deficiencies. These data were transmitted by direct computer link to a CNC milling machine that produced full-size slices "stacked" into a three-dimensional template. The acrylic replica aided selection of appropriate donor sites and intraoperative "carving" of bone transfers. Reconstructions included three zygomas, two maxillae, two mandibles, and one frontal bone. Donor sites were iliac crest, scapula, and outer calvarium. Four were free flaps and four island pedicle flaps. All healed without infection. Bone resorption was less than 10 percent. One flap was lost to thrombosis. Other complications included a transient facial palsy in one patient and temporary radial palsy from shoulder traction in another. Computer-generated templates for vascularized grafts are expensive and thus are not indicated or necessary in every patient. The advantages, however, are several. Custom models facilitate preoperative planning, with less guesswork of size, contour, and orientation of the graft, which is especially desirable with vascularized grafts, since the position of the pedicle is critical. Anesthesia time is decreased. Grafts can be fitted exactly, without reshaping and "nibbling." Nuances of depth and tapering are directly carved into the bone. By merging high-tech imaging and microsurgery, the best chance of optimal results can be achieved.

  14. Restoration of bone mineralization by cinacalcet is associated with a significant reduction in calcitriol-induced vascular calcification in uremic rats.

    Science.gov (United States)

    De Schutter, Tineke M; Behets, Geert J; Jung, Susanne; Neven, Ellen; D'Haese, Patrick C; Querfeld, Uwe

    2012-11-01

    The present study investigated to what extent normalization of bone turnover goes along with a reduction of high-dose calcitriol-induced vascular calcifications in uremic rats. Five groups of male Sprague-Dawley rats were studied: sham-operated controls (n = 7), subtotally nephrectomized (SNX) uremic (CRF) animals (n = 12), CRF + calcitriol (vitD) (0.25 μg/kg/day) (n = 12), CRF + vitD + cinacalcet (CIN) (10 mg/kg/day) (n = 12), and CRF + vitD + parathyroidectomy (PTX) (n = 12). Treatment started 2 weeks after SNX and continued for the next 14 weeks. High-dose calcitriol treatment in hyperparathyroid rats went along with the development of distinct vascular calcification, which was significantly reduced by >50 %, in both CIN-treated and PTX animals. Compared to control animals and those of the CRF group, calcitriol treatment either in combination with CIN or PTX or not was associated with a significant increase in bone area comprising ±50 % of the total tissue area. However, whereas excessive woven bone accompanied by a dramatically increased osteoid width/area was seen in the CRF + vitD group, CIN treatment and PTX resulted in significantly reduced serum PTH level, which was accompanied by a distinct reduction of both the bone formation rate and the amount of osteoid. These data indicate that less efficient calcium and phosphorus incorporation in bone inherent to the severe hyperparathyroidism in vitamin D-treated uremic rats goes along with excessive vascular calcification, a process which is partially reversed by CIN treatment in combination with a more efficacious bone mineralization, thus restricting the availability of calcium and phosphate for being deposited in the vessel wall.

  15. Blood Vessel Formation and Bone Regeneration Potential of the Stromal Vascular Fraction Seeded on a Calcium Phosphate Scaffold in the Human Maxillary Sinus Floor Elevation Model

    Directory of Open Access Journals (Sweden)

    Elisabet Farré-Guasch

    2018-01-01

    Full Text Available Bone substitutes are used as alternatives for autologous bone grafts in patients undergoing maxillary sinus floor elevation (MSFE for dental implant placement. However, bone substitutes lack osteoinductive and angiogenic potential. Addition of adipose stem cells (ASCs may stimulate osteogenesis and osteoinduction, as well as angiogenesis. We aimed to evaluate the vascularization in relation to bone formation potential of the ASC-containing stromal vascular fraction (SVF of adipose tissue, seeded on two types of calcium phosphate carriers, within the human MSFE model, in a phase I study. Autologous SVF was obtained from ten patients and seeded on β-tricalcium phosphate (n = 5 or biphasic calcium phosphate carriers (n = 5, and used for MSFE in a one-step surgical procedure. After six months, biopsies were obtained during dental implant placement, and the quantification of the number of blood vessels was performed using histomorphometric analysis and immunohistochemical stainings for blood vessel markers, i.e., CD34 and alpha-smooth muscle actin. Bone percentages seemed to correlate with blood vessel formation and were higher in study versus control biopsies in the cranial area, in particular in β-tricalcium phosphate-treated patients. This study shows the safety, feasibility, and efficiency of the use of ASCs in the human MSFE, and indicates a pro-angiogenic effect of SVF.

  16. Investigating the Vascularization of Tissue-Engineered Bone Constructs Using Dental Pulp Cells and 45S5 Bioglass(®) Scaffolds.

    OpenAIRE

    El-Gendy, R; J Kirkham; Newby, PJ; Mohanram, Y; Boccaccini, AR; Yang, XB

    2015-01-01

    Identification of a suitable cell source combined with an appropriate 3D scaffold is an essential prerequisite for successful engineering of skeletal tissues. Both osteogenesis and angiogenesis are key processes for bone regeneration. This study investigated the vascularization potential of a novel combination of human dental pulp stromal cells (HDPSCs) with 45S5 Bioglass(®) scaffolds for tissue-engineered mineral constructs in vivo and in vitro. 45S5 Bioglass scaffolds were produced by the f...

  17. [Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor].

    Science.gov (United States)

    Zhang, Minglei; Wang, Dapeng; Yin, Ruofeng

    2015-10-06

    To explorec Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor transinfected. Rat bone marrow mesenchymal stem cells (BMSCs) was separated, using BMSCs as target cells, and then vascular endothelial growth factor (VEGF) gene was transfected. Composite bone marrow mesenchymal stem cells and cells transfected with nano-hydroxyapatite (HA)/polylactic-co-glycolic acid (PLGA). The composition of cell and scaffold was observed. The blank plasmid transfection was 39.1%, 40.1% in VEGF group. The cell adhesion and growth was found on the scaffold pore wall after 5 days, and the number of adherent cells in the nano-HA/PLGA composite scaffold material basically had no significant difference in both. Although the nano-HA/PLGA scaffold material is still not fully meet the requirements of the matrix material for bone tissue engineering, but good biocompatibility, structure is its rich microporous satisfaction in material mechanics, toughening, enhanced obviously. Composition scaffold with BMSCs transfected by VEGF plasmid, the ability of angiogenesis is promoted.

  18. Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.

    Science.gov (United States)

    Zhang, Wenjie; Chang, Qing; Xu, Ling; Li, Guanglong; Yang, Guangzheng; Ding, Xun; Wang, Xiansong; Cui, Daxiang; Jiang, Xinquan

    2016-06-01

    Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

    Science.gov (United States)

    Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

    2016-01-01

    The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection.

    Directory of Open Access Journals (Sweden)

    Chuang Ma

    Full Text Available The main limitation of tissue engineering lies in the inability to stimulate osteogenesis, angiogenesis of stem cells and broad-spectrum antimicrobial activity. However, the development of multifunctional bioactive materials with these capabilities remains a great challenge. In this study, we prepared mesoporous silica nanoparticles encapsulated with silver nanocrystals (AG-MSN with uniform sphere size and mesopores. Platelet-derived growth factor BB (PDGF-BB was effectively loaded in the AG-MSN mesopores (P-AG-MSN. The silicon ions (Si released by P-AG-MSN stimulate osteogenic differentiation of bone marrow stromal cells (BMSC by activating the alkaline phosphatase (ALP activity of bone-related genes and increasing protein (OCN, RUNX2 and OPN expression. Ag+ ions could be slowly released from the interior of the shell, highlighting their durable antibacterial activity. The sustained release of PDGF-BB from P-AG-MSN stimulated the angiogenic differentiation of BMSC, as indicated by the enhanced secretion of vascular endothelial growth factor (VEGF, HIF-1α, HGF and ANG-1 and protein expression. Our results show that P-AG-MSN can clearly promote BMSC osteostimulation and vascularization. This research serves as a preliminary study of the utilization of this multifunctional mixture to fabricate a new active biological scaffold that integrates BMSC osteostimulation, vascularization and bactericidal effects by 3D printing technology.

  1. Compartmentalized nitric oxide signaling in the resistance vasculature.

    Science.gov (United States)

    Mutchler, Stephanie M; Straub, Adam C

    2015-09-15

    Nitric oxide (NO) was first described as a bioactive molecule through its ability to stimulate soluble guanylate cyclase, but the revelation that NO was the endothelium derived relaxation factor drove the field to its modern state. The wealth of research conducted over the past 30 years has provided us with a picture of how diverse NO signaling can be within the vascular wall, going beyond simple vasodilation to include such roles as signaling through protein S-nitrosation. This expanded view of NO's actions requires highly regulated and compartmentalized production. Importantly, resistance arteries house multiple proteins involved in the production and transduction of NO allowing for efficient movement of the molecule to regulate vascular tone and reactivity. In this review, we focus on the many mechanisms regulating NO production and signaling action in the vascular wall, with a focus on the control of endothelial nitric oxide synthase (eNOS), the enzyme responsible for synthesizing most of the NO within these confines. We also explore how cross talk between the endothelium and smooth muscle in the microcirculation can modulate NO signaling, illustrating that this one small molecule has the capability to produce a plethora of responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Diagnosis and management of compartmental syndromes.

    Science.gov (United States)

    Matsen, F A; Winquist, R A; Krugmire, R B

    1980-03-01

    Patients at risk for compartmental syndromes challenge both the diagnostic and the therapeutic abilities of the physician. Suboptimum results may be due to delays in diagnosis and treatment, to incomplete surgical decompression, and to difficulties in the management of the limb after decompression. Although careful clinical assessment permits the diagnosis of a compartmental syndrome in most patients, we have found measurement of tissue pressure and direct nerve stimulation to be helpful for resolving ambiguous or equivocal cases. In our experience, the four-compartment parafibular approach to the leg and the ulnar approach to the volar compartments of the forearm provide efficient and complete decompression of potentially involved compartments. The skeletal stabilization of fractures associated with compartmental syndromes may facilitate management of the limb after surgical decompression.

  3. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P. R.

    2016-01-01

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin−Sca-1+cKit+ (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10–12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy. PMID:27188595

  4. Collagen-embedded hydroxylapatite-beta-tricalcium phosphate-silicon dioxide bone substitute granules assist rapid vascularization and promote cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Ghanaati, Shahram M; Thimm, Benjamin W; Unger, Ronald E; Orth, Carina; Barbeck, Mike; Kirkpatrick, C James [Institute of Pathology, Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55101 Mainz (Germany); Kohler, Thomas; Mueller, Ralph, E-mail: ghanaati@uni-mainz.d [Institute for Biomechanics, ETH Zuerich, Wolfgang-Pauli-Str.10, 8093 Zuerich (Switzerland)

    2010-04-15

    In the present study we assessed the biocompatibility in vitro and in vivo of a low-temperature sol-gel-manufactured SiO{sub 2}-based bone graft substitute. Human primary osteoblasts and the osteoblastic cell line, MG63, cultured on the SiO{sub 2} biomatrix in monoculture retained their osteoblastic morphology and cellular functionality in vitro. The effect of the biomaterial in vivo and its vascularization potential was tested subcutaneously in Wistar rats and demonstrated both rapid vascularization and good integration within the peri-implant tissue. Scaffold degradation was progressive during the first month after implantation, with tartrate-resistant acid phosphatase-positive macrophages being present and promoting scaffold degradation from an early stage. This manuscript describes successful osteoblastic growth promotion in vitro and a promising biomaterial integration and vasculogenesis in vivo for a possible therapeutic application of this biomatrix in future clinical studies.

  5. Compartmental endoscopic surgical anatomy of the medial intraconal orbital space.

    Science.gov (United States)

    Bleier, Benjamin S; Healy, David Y; Chhabra, Nipun; Freitag, Suzanne

    2014-07-01

    Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face. © 2014 ARS-AAOA, LLC.

  6. Effects of lanthanum carbonate versus calcium carbonate on vascular stiffness and bone mineral metabolism in hemodialysis patients with type 2 diabetes mellitus: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Wada K

    2015-08-01

    Full Text Available Kentaro Wada,1 Yuko Wada,2 Haruhito Adam Uchida,3 Shuichi Tsuruoka4 1Division of Nephrology and Dialysis, Department of Internal Medicine, Nippon Kokan Fukuyama Hospital, Hiroshima, 2Department of Internal Medicine, Central Hospital, Hiroshima, 3Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 4Division of Nephrology, Department of Internal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Background: Vascular calcification contributes to cardiovascular disease in hemodialysis (HD patients with diabetes. The randomized controlled trial reported here compared the effects of lanthanum carbonate (LC and calcium carbonate (CC on vascular stiffness assessed using brachial-ankle pulse wave velocity (ba-PWV, intima-media thickness (IMT, bone mineral density (BMD, and serum markers of chronic kidney disease – mineral and bone disorder in such patients. Methods: Ba-PWV, IMT, BMD, and the biomarkers osteocalcin (OC and bone alkaline phosphatase (BAP were examined in 43 type 2 diabetes HD patients treated with LC (n=21 or CC (n=22 for 2 years. Results: Forty-one patients completed the study (19, LC; 22, CC. The mean ba-PWV significantly increased only in the CC group (median: 2,280.5 to 2,402.5 cm/s, P<0.05, after 24-month treatment; it remained unchanged in the LC group (median: 1,830.5 to 2,018.3 cm/s. However, the difference between the groups did not reach statistical significance. Changes in IMT and BMD were not different between the two groups. Changes in serum phosphorus, corrected calcium, and intact parathyroid hormone levels were similar between the groups. The incidence of fracture was 0% (0/19 in the LC group, and 13.6% (3/22 in the CC group (P=0.2478. The OC/BAP ratio increased significantly in the LC group (median: 0.83 to 2.47, compared with in the CC group (median: 0.77 to 1.40 (P=0.036. Conclusion: From

  7. Investigating the Vascularization of Tissue-Engineered Bone Constructs Using Dental Pulp Cells and 45S5 Bioglass® Scaffolds.

    Science.gov (United States)

    El-Gendy, Reem; Kirkham, Jennifer; Newby, Phillipa J; Mohanram, Yamuna; Boccaccini, Aldo Roberto; Yang, Xuebin B

    2015-07-01

    Identification of a suitable cell source combined with an appropriate 3D scaffold is an essential prerequisite for successful engineering of skeletal tissues. Both osteogenesis and angiogenesis are key processes for bone regeneration. This study investigated the vascularization potential of a novel combination of human dental pulp stromal cells (HDPSCs) with 45S5 Bioglass® scaffolds for tissue-engineered mineral constructs in vivo and in vitro. 45S5 Bioglass scaffolds were produced by the foam replication technique with the standard composition of 45 wt% SiO2, 24.5 wt% Na2O, 24.5 wt% CaO, and 6 wt% P2O5. HDPSCs were cultured in monolayers and on porous 45S5 Bioglass scaffolds under angiogenic and osteogenic conditions for 2-4 weeks. HDPSCs expressed endothelial gene markers (CD34, CD31/PECAM1, and VEGFR2) under both conditions in the monolayer. A combination of HDPSCs with 45S5 Bioglass enhanced the expression of these gene markers. Positive immunostaining for CD31/PECAM1 and VEGFR2 and negative staining for CD34 supported the gene expression data, while histology revealed evidence of endothelial cell-like morphology within the constructs. More organized tubular structures, resembling microvessels, were seen in the constructs after 8 weeks of implantation in vivo. In conclusion, this study suggests that the combination of HDPSCs with 45S5 Bioglass scaffolds offers a promising strategy for regenerating vascularized bone grafts.

  8. Optimising combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice

    DEFF Research Database (Denmark)

    Dreyer, Chris Halling; Kjærgaard, Kristian; Ditzel, Nicholas

    2017-01-01

    combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. METHODS: Twenty-eight SCID (NOD.CB17-Prkdcscid /J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1...

  9. Autologous Bone Marrow Mesenchymal Stem Cells Associated with Tantalum Rod Implantation and Vascularized Iliac Grafting for the Treatment of End-Stage Osteonecrosis of the Femoral Head

    Directory of Open Access Journals (Sweden)

    Dewei Zhao

    2015-01-01

    Full Text Available Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH to avert the need for total hip arthroplasty (THA. However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26–78. Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22–50 to 77.23 ± 14.75 points (range 33–95. This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH.

  10. Autologous Bone Marrow Mesenchymal Stem Cells Associated with Tantalum Rod Implantation and Vascularized Iliac Grafting for the Treatment of End-Stage Osteonecrosis of the Femoral Head

    Science.gov (United States)

    Zhao, Dewei; Liu, Baoyi; Wang, Benjie; Yang, Lei; Xie, Hui; Huang, Shibo; Zhang, Yao; Wei, Xiaowei

    2015-01-01

    Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26–78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22–50) to 77.23 ± 14.75 points (range 33–95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH. PMID:25802840

  11. Advanced compositional gradient and compartmentalization analysis

    Energy Technology Data Exchange (ETDEWEB)

    Canas, Jesus A.; Petti, Daniela; Mullins, Oliver [Schlumberger Servicos de Petroleo Ltda., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Acquisition of hydrocarbons samples from the reservoir prior to oil or gas production is essential in order to design production strategies and production facilities. In addition, reservoir compartmentalization and hydrocarbon compositional grading magnify the necessity to map fluid properties vertically and laterally in the reservoir prior to production. Formation testers supply a wealth of information to observe and predict the state of fluids in hydrocarbon reservoirs, through detailed pressure and fluid analysis measurements. With the correct understanding of the state of fluids in the reservoirs, reserve calculations and adequate development plans can be prepared. Additionally, flow barriers may then be revealed. This paper describes a new Downhole Fluid Analysis technology (DFA) for improved reservoir management. DFA is a unique process that combines new fluid identification sensors, which allow real time monitoring of a wide range of parameters as GOR, fluid density, viscosity, fluorescence and composition (CH{sub 4}, C2- C5, C6 +, CO{sub 2}), free gas and liquid phases detection, saturation pressure, as well WBM and OBM filtrate differentiation and pH. This process is not limited to light fluid evaluation and we extended to heavy oil (HO) reservoirs analysis successfully. The combination of DFA Fluid Profiling with pressure measurements has shown to be very effective for compartmentalization characterization. The ability of thin barriers to hold off large depletion pressures has been established, as the gradual variation of hydrocarbon quality in biodegraded oils. In addition, heavy oils can show large compositional variation due to variations in source rock charging but without fluid mixing. Our findings indicates that steep gradients are common in gas condensates or volatile oils, and that biodegradation is more common in HO than in other hydrocarbons, which generate fluid gradients and heavy ends tars near the OWC, limiting the aquifer activity and

  12. Evaluation of computer-assisted mandibular reconstruction with vascularized iliac crest bone graft compared to conventional surgery: a randomized prospective clinical trial

    Science.gov (United States)

    2014-01-01

    Background Computer-assisted surgery plays an increasingly important role in mandibular reconstruction, ensuring the best possible masticatory function and aesthetic outcome. Methods Twenty patients were randomly assigned to computer-assisted or conventional mandibular reconstruction with vascularized iliac crest bone graft in a prospective study design. Virtual surgical planning was based on preoperative CT-data using specific surgical planning software. A rapid prototyping guide transferred the virtual surgery plan to the operation site. During surgery the transplant ischemic time, reconstruction time, time for shaping the transplant and amount of bone removed were measured. Additionally, the difference in the intercondylar distance before and after surgery was calculated. Results Computer-assisted surgery shortened the time of transplant ischemia (P < 0.005) and defect reconstruction (P < 0.001) compared to conventional surgery. The time to saw and shape the transplant at the donor site was shorter using conventional surgery (P < 0.005); therefore, the overall time for surgery didn’t change (P = 0.527). In the computer-assisted group, the amount of bone harvested equaled the defect size, whereas the transplant size in the conventional group exceeded the defect site by 16.8 ± 5.6 mm (P < 0.001) on average. The intercondylar distance before compared to after surgery was less affected in the computer-assisted than in the conventional group (P < 0.001). Conclusions The presented study shows that computer-assisted surgery can help reduce the time for mandibular defect reconstruction and consequently the transplant ischemic time. In the computer-assisted group, the iliac crest donor site defect was downsized and the postoperative condyle position was less altered, reducing possible risks of postoperative complications and donor site morbidity. Trial Registration DRKS00005181. PMID:24716651

  13. Reactive oxygen species and redox compartmentalization

    Directory of Open Access Journals (Sweden)

    Nina eKaludercic

    2014-08-01

    Full Text Available Reactive oxygen species (ROS formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatiotemporal manner. This makes ROS signaling similar to that of Ca2+ or other second messengers. Some subcellular compartments are more oxidizing (such as lysosomes or peroxisomes whereas others are more reducing (mitochondria, nuclei. Moreover, although more reducing, mitochondria are especially susceptible to oxidation, most likely due to the high number of exposed thiols present in that compartment. Recent advances in the development of redox probes allow specific measurement of defined ROS in different cellular compartments in intact living cells or organisms. The availability of these tools now allows simultaneous spatiotemporal measurements and correlation between ROS generation and organelle and/or cellular function. The study of ROS compartmentalization and microdomains will help elucidate their role in physiology and disease. Here we will examine redox probes currently available and how ROS generation may vary between subcellular compartments. Furthermore, we will discuss ROS compartmentalization in physiological and pathological conditions focusing our attention on mitochondria, since their vulnerability to oxidative stress is likely at the basis of several diseases.

  14. Compartmental model of 18F-choline

    Science.gov (United States)

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  15. Acute compartmental syndrome from hematogenous osteomyelitis of the ulna.

    Science.gov (United States)

    Lundy, D W; Lourie, G M; Morrissy, R T

    1998-08-01

    Compartmental syndrome of the forearm in children is usually caused by fractures, soft-tissue damage, burns, or arterial injury. This report presents the case of a child who had compartmental syndrome of the forearm resulting from acute hematogenous osteomyelitis of the ulna.

  16. Enzyme compartmentalization during biphasic enamel matrix processing.

    Science.gov (United States)

    Brookes, S J; Kirkham, J; Shore, R C; Bonass, W A; Robinson, C

    1998-01-01

    Processing of enamel matrix proteins is essentially biphasic. Secretory stage metalloprotease activity generates a discrete, presumably functional, spectrum of molecules which may also undergo dephosphorylation. Maturation stage serine proteases almost completely destroy the matrix. The present aim was to examine the tissue compartmentalization of these enzyme activities in relation to their possible function. A sequential extraction using synthetic enamel fluid, phosphate buffer and SDS was used to identify enzymes free in the enamel fluid, crystal bound or aggregated with the bulk matrix respectively. Results indicated that the metallo-proteases and alkaline phosphatase were free in the secretory stage enamel fluid while the serine proteases appeared to be largely bound to the maturation stage crystals. The mobility of the metallo-proteases and alkaline phosphatase would ensure efficient initial processing of secretory matrix, while the largely mineral bound serine proteases would ensure retention of protease activity despite massive destruction and protein removal.

  17. VASCULAR DEMENTIA

    Directory of Open Access Journals (Sweden)

    Maria Alekseyevna Cherdak

    2010-01-01

    vascular cognitive disorders and vascular dementia (VD. The heterogeneity of vascular cognitive disorders, concurrence of vascular and neurodegenerative diseases are discussed. Data from studies of specific therapy for VD are given.

  18. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. W. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 International Energy Conservation Code (IECC) has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure (3 ACH50) for single-family and multifamily construction (in climate zones 3–8). The Leadership in Energy & Environmental Design certification program and ASHRAE Standard 189 have comparable compartmentalization requirements. ASHRAE Standard 62.2 will soon be responsible for all multifamily ventilation requirements (low rise and high rise); it has an exceptionally stringent compartmentalization requirement. These code and program requirements are driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  19. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa.

    Directory of Open Access Journals (Sweden)

    Theodora Kanni

    Full Text Available Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS.Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured.CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8.Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

  20. Compartmentalization and Transport in Synthetic Vesicles

    Directory of Open Access Journals (Sweden)

    Christine eSchmitt

    2016-02-01

    Full Text Available Nano-scale vesicles have become a popular tool in life sciences. Besides liposomes that are generated from phospholipids of natural origin, polymersomes fabricated of synthetic block copolymers enjoy increasing popularity, as they represent more versatile membrane building blocks that can be selected based on their specific physicochemical properties, like permeability, stability or chemical reactivity.In this review, we focus on the application of simple and nested artificial vesicles in synthetic biology. First, we provide an introduction into the utilization of multi-compartmented vesosomes as compartmentalized nano-scale bioreactors. In the bottom-up development of protocells from vesicular nano-reactors, the specific exchange of pathway intermediates across compartment boundaries represents a bottleneck for future studies. To date, most compartmented bioreactors rely on unspecific exchange of substrates and products. This is either based on changes in permeability of the coblock polymer shell by physicochemical triggers or by the incorporation of unspecific porin proteins into the vesicle membrane. Since the incorporation of membrane transport proteins into simple and nested artificial vesicles offers the potential for specific exchange of substances between subcompartments, it opens new vistas in the design of protocells. Therefore we devote the main part of the review to summarize the technical advances in the use of phospholipids and block copolymers for the reconstitution of membrane proteins.

  1. Compartmental analysis of dynamic nuclear medicine data: models and identifiability

    Science.gov (United States)

    Delbary, Fabrice; Garbarino, Sara; Vivaldi, Valentina

    2016-12-01

    Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how nonlinear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology.

  2. Compartmental analysis approach to fluorescence anisotropy: Perylene in viscous solvents

    OpenAIRE

    Piston, DW; Bilash, T; Gratton, E

    1989-01-01

    The fluorescence and polarization anisotropy decays of perylene in viscous solvents are investigated at several temperatures between -20 and 35 °C by using the technique of multifrequency phase and modulation fluorometry. The anisotropy decay data are globally analyzed over all temperatures studied and fit directly to physical quantities by using a compartmental model. We present a generalized compartmental model that can be used to calculate anisotropy decay arising from any type of intercon...

  3. Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response

    Directory of Open Access Journals (Sweden)

    Caroline Regina de Jesus

    2011-06-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22, resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM, which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR and bone marrow biopsies (BMB were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.A Leucemia Mielóide Crônica (LMC é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22, que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI, o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC e as biópsias de medula óssea (BMO antes e após o

  4. Aneurysmal bone cyst of the zygomatic bone.

    Science.gov (United States)

    Lee, Jun Yong; Ko, Young-Il; Kwon, Ho; Jung, Sung-No

    2014-01-01

    Aneurysmal bone cyst is a rare, non-neoplastic lesion that mostly involves the long bone and the spine, and is characterized by its expansile, vascular, and multi-cystic features. Reports of facial bone lesions are rare, and when it occurs, is usually located in the mandible. Herein, this report is aimed to describe a very rare case of an aneurysmal bone cyst in the zygoma with a brief review of the literature.

  5. Differential inflammatory networks distinguish responses to bone marrow-derived versus adipose-derived mesenchymal stem cell therapies in vascularized composite allotransplantation.

    Science.gov (United States)

    Zamora, Ruben; Ravuri, Sudheer K; Plock, Jan A; Vodovotz, Yoram; Gorantla, Vijay S

    2017-07-01

    Vascularized composite allotransplantation (VCA) is aimed at enabling injured individuals to return to their previous lifestyles. Unfortunately, VCA induces an immune/inflammatory response, which mandates lifelong, systemic immunosuppression, with attendant detrimental effects. Mesenchymal stem cells (MSC)-both adipose-derived (AD-MSC) and bone marrow-derived (BM-MSC)-can reprogram inflammation and have been suggested as an alternative to immunosuppression, but their mechanism of action is as yet not fully elucidated. We sought to gain insights into these mechanisms using a systems biology approach. PKH26 (red) dye-labeled AD-MSC or BM-MSC were administered intravenously to Lewis rat recipients of mismatched Brown-Norway hindlimb transplants. Short course tacrolimus (FK-506) monotherapy was withdrawn at postoperative day 21. Sera were collected at 4 weeks, 6 weeks, and 18 weeks; assayed for 29 inflammatory/immune mediators; and the resultant data were analyzed using Dynamic Network Analysis (DyNA), Dynamic Bayesian Network (DyBN) inference, and Principal Component Analysis. DyNA network complexity decreased with time in AD-MSC rats, but increased in BM-MSC rats. DyBN and Principal Component Analysis suggested mostly different central nodes and principal characteristics, respectively, in AD-MSC versus BM-MSC rats. AD-MSC and BM-MSC are associated with both overlapping and distinct dynamic networks and principal characteristics of inflammatory/immune mediators in VCA grafts with short-course tacrolimus induction therapy. The decreasing inflammatory complexity of dynamic networks in the presence of AD-MSC supports the previously suggested role for T regulatory cells induced by AD-MSC. The finding of some overlapping and some distinct central nodes and principal characteristics suggests the role of key mediators in the response to VCA in general, as well as potentially differential roles for other mediators ascribed to the actions of the different MSC populations. Thus

  6. Drivers of compartmentalization in a Mediterranean pollination network

    DEFF Research Database (Denmark)

    Gonzalez, Ana M. Martin; Allesina, Stefano; Rodrigo, Anselm

    2012-01-01

    of several species attributes related to pollination syndromes, species phenology, abundance and connectivity in structuring compartmentalization. BM could not identify compartments in our network. By contrast, UM revealed four modules composed of plants and pollinators, and GM four groups of plants and five...... syndrome-related features in compartmentalization mostly emerged with UM. Only UM compartments differed in corolla length and pollen production. Both UM and GM compartments differed in their pollinator spectra. We found inconsistent reciprocity between plant attributes and pollinator spectra, thus......We study compartmentalization in a Mediterranean pollination network using three different analytical approaches: unipartite modularity (UM), bipartite modularity (BM) and the group model (GM). Our objectives are to compare compartments obtained with these three approaches and to explore the role...

  7. Upper extremity compartmental anatomy: clinical relevance to radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Toomayan, Glen A.; Robertson, Fabienne; Major, Nancy M. [Duke University Medical Center, Department of Radiology, P.O. Box 3808, Durham, NC (United States); Duke University Medical Center, Division of Orthopaedic Surgery, Department of Surgery, P.O. Box 3808, Durham, NC (United States); Brigman, Brian E. [Duke University Medical Center, Division of Orthopaedic Surgery, Department of Surgery, P.O. Box 3808, Durham, NC (United States)

    2006-04-15

    Malignant tumors of the upper extremity are uncommon, and their care should be referred to specialized facilities with experience treating these lesions. The Musculoskeletal Tumor Society (MSTS) staging system is used by the surgeon to determine appropriate surgical management, assess prognosis, and communicate with other healthcare providers. Magnetic resonance imaging (MRI) is employed pre-operatively to identify a lesion's compartment of origin, determine extent of spread, and plan biopsy and resection approaches. Involvement of neurovascular structures may result in devastating loss of upper extremity function, requiring amputation. Violation of high-resistance compartmental barriers necessitates more extensive surgical resection. Biopsy may be performed by the radiologist using imaging guidance. Knowledge of compartmental anatomy allows the radiologist or surgeon to use an easily excisable biopsy approach and prevent iatrogenic spread to unaffected compartments. Case examples are presented to illustrate the importance of compartmental anatomy in the management of benign and malignant upper extremity tumors. (orig.)

  8. Association between CYP4F2 genotype and circulating plasma vitamin K concentration in children on chronic warfarin therapy: Possible long-term implications for bone development and vascular health.

    Science.gov (United States)

    Kampouraki, Emmanouela; Avery, Peter J; Biss, Tina; Kamali, Farhad

    2017-12-01

    Vitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix-Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability. We show that children on chronic warfarin therapy have low levels of vitamin K and vitamin K levels are linked to CYP4F2 genotype. Long-term low levels of vitamin K, influenced by CYP4F2 genotype, might affect bone development and vascular health in children on chronic warfarin therapy. © 2017 Wiley Periodicals, Inc.

  9. Macroanatomy of compartmentalization in fire scars of three western conifers

    Science.gov (United States)

    Kevin T. Smith; Elaine Sutherland; Estelle Arbellay; Markus Stoffel; Donald. Falk

    2013-01-01

    Fire scars are visible evidence of compartmentalization and closure processes that contribute to tree survival after fire injury. Preliminary observations of dissected fire scars from trees injured within the last decade showed centripetal development of wound-initiated discoloration (WID) through 2-3 decades of former sapwood in Larix occidentalis and Pseudotsuga...

  10. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  11. Vascularized epiphyseal transplant.

    Science.gov (United States)

    Innocenti, Marco; Delcroix, Luca; Romano, G Federico; Capanna, Rodolfo

    2007-01-01

    In skeletally immature patients, the transfer of vascularized epiphysis along with a variable amount of adjoining diaphysis may provide the potential for growth of such a graft, preventing future limb length discrepancy. This article describes the authors' experience with the vascularized transfer of the proximal fibular epiphysis in the reconstruction of large bone defects including the epiphysis in a series of 27 patients ranging in age from 2 to 11 years. The follow-up, ranging from 2 to 14 years, has been long enough to allow some evaluation of the validity, indications, and limits of this reconstructive option.

  12. Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice.

    Science.gov (United States)

    Kizuka-Shibuya, Fumie; Tokuda, Nobuko; Takagi, Kiyoshi; Adachi, Yasuhiro; Lee, Lifa; Tamura, Isao; Maekawa, Ryo; Tamura, Hiroshi; Suzuki, Takashi; Owada, Yuji; Sugino, Norihiro

    2014-01-21

    Neovascularization is necessary for follicular growth. Vascularization is first observed in preantral follicles, and thereafter the vasculature markedly increases in follicles undergoing development. Neovascularization includes angiogenesis and vasculogenesis. Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. It is unclear whether vasculogenesis occurs during follicular growth. Blood vessels must be mature to be functional blood vessels. Mature blood vessels are characterized by the recruitment of pericytes. However, it is unclear where pericytes come from and whether they contribute to neovascularization in the follicle during follicular growth. In this study, we investigated whether bone marrow-derived progenitor cells that differentiate into vascular endothelial cells or pericytes contribute to neovascularization during follicular growth. A parabiosis model was used in this study. Six-week-old wild-type and transgenic female mice expressing green fluorescent protein (GFP) were conjoined between the lateral abdominal regions to create a shared circulatory system. After 6 weeks, the ovaries were obtained and immunostained for CD31/CD34 (a vascular endothelial cell marker), platelet-derived growth factor receptor-β (PDGFR-β) (a pericyte marker), and GFP (a bone marrow-derived cell marker). Cells that were positive for CD34 and PDGFR-β were observed in the stroma adjacent to the primary or early preantral follicles and in the theca cell layer of the follicles from the late preantral stage to the preovulatory stage. CD31/CD34 and GFP double-positive cells were observed in the theca cell layer of the follicle from the antral stage to the preovulatory stage while the number of double-positive cells in the preovulatory follicles did not increase. PDGFR-β and GFP double-positive cells were observed in the theca cell layer of the preovulatory follicle but not in the smaller follicle. Locally existing endothelial

  13. Vascular Cures

    Science.gov (United States)

    ... is the first national program to bring the power of the patient to vascular research and care. ... Our recent national Vascular Research Summit brought together leaders from 31 institutions to generate collaborative projects for ...

  14. Subcellular compartmentation of glutathione in dicotyledonous plants

    Science.gov (United States)

    Müller, Maria

    2010-01-01

    This study describes the subcellular distribution of glutathione in roots and leaves of different plant species (Arabidopsis, Cucurbita, and Nicotiana). Glutathione is an important antioxidant and redox buffer which is involved in many metabolic processes including plant defense. Thus information on the subcellular distribution in these model plants especially during stress situations provides a deeper insight into compartment specific defense reactions and reflects the occurrence of compartment specific oxidative stress. With immunogold cytochemistry and computer-supported transmission electron microscopy glutathione could be localized in highest contents in mitochondria, followed by nuclei, peroxisomes, the cytosol, and plastids. Within chloroplasts and mitochondria, glutathione was restricted to the stroma and matrix, respectively, and did not occur in the lumen of cristae and thylakoids. Glutathione was also found at the membrane and in the lumen of the endoplasmic reticulum. It was also associated with the trans and cis side of dictyosomes. None or only very little glutathione was detected in vacuoles and the apoplast of mesophyll and root cells. Additionally, glutathione was found in all cell compartments of phloem vessels, vascular parenchyma cells (including vacuoles) but was absent in xylem vessels. The specificity of this method was supported by the reduction of glutathione labeling in all cell compartments (up to 98%) of the glutathione-deficient Arabidopsis thaliana rml1 mutant. Additionally, we found a similar distribution of glutathione in samples after conventional fixation and rapid microwave-supported fixation. Thus, indicating that a redistribution of glutathione does not occur during sample preparation. Summing up, this study gives a detailed insight into the subcellular distribution of glutathione in plants and presents solid evidence for the accuracy and specificity of the applied method. PMID:20186447

  15. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaffolds with defined architecture

    NARCIS (Netherlands)

    Poldervaart, Michelle T; Gremmels, Hendrik; van Deventer, Kelly; Fledderus, Joost O; Oner, F Cumhur; Verhaar, Marianne C; Dhert, Wouter J A; Alblas, Jacqueline

    2014-01-01

    Timely vascularization is essential for optimal performance of bone regenerative constructs. Vascularization is efficiently stimulated by vascular endothelial growth factor (VEGF), a substance with a short half-life time. This study investigates the controlled release of VEGF from gelatin

  16. The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation and proteolysis.

    Science.gov (United States)

    Kato, Shin; Chen, Jingsi; Cornog, Katherine H; Zhang, Huili; Roberts, Jesse D

    2015-06-01

    cGMP-dependent protein kinase I (PKGI) is an important effector of cGMP signaling that regulates vascular smooth muscle cell (SMC) phenotype and proliferation. PKGI has been detected in the perinuclear region of cells, and recent data indicate that proprotein convertases (PCs) typically resident in the Golgi apparatus (GA) can stimulate PKGI proteolysis and generate a kinase fragment that localizes to the nucleus and regulates gene expression. However, the role of the endomembrane system in PKGI compartmentation and processing is unknown. Here, we demonstrate that PKGI colocalizes with endoplasmic reticulum (ER), ER-Golgi intermediate compartment, GA cisterna, and trans-Golgi network proteins in pulmonary artery SMC and cell lines. Moreover, PKGI localizes with furin, a trans-Golgi network-resident PC known to cleave PKGI. ER protein transport influences PKGI localization because overexpression of a constitutively inactive Sar1 transgene caused PKGI retention in the ER. Additionally, PKGI appears to reside within the GA because PKGI immunoreactivity was determined to be resistant to cytosolic proteinase K treatment in live cells. The GA appears to play a role in PKGI proteolysis because overexpression of inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate, not only tethered heterologous PKGI-β to the ER and decreased its localization to the GA, but also diminished PKGI proteolysis and nuclear translocation. Also, inhibiting intra-GA protein transport with monensin was observed to decrease PKGI cleavage. These studies detail a role for the endomembrane system in regulating PKGI compartmentation and proteolysis. Moreover, they support the investigation of mechanisms regulating PKGI-dependent nuclear cGMP signaling in the pulmonary vasculature with Golgi dysfunction. Copyright © 2015 the American Physiological Society.

  17. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  18. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

    Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

  19. Rewiring and regulation of cross-compartmentalized metabolism in protists

    OpenAIRE

    Ginger, Michael L.; McFadden, Geoffrey I.; Michels, Paulus

    2010-01-01

    Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled dur...

  20. A Novel Method for Performance Analysis of Compartmentalized Reservoirs

    Directory of Open Access Journals (Sweden)

    Shahamat Mohammad Sadeq

    2016-05-01

    Full Text Available This paper presents a simple analytical model for performance analysis of compartmentalized reservoirs producing under Constant Terminal Rate (CTR and Constant Terminal Pressure (CTP. The model is based on the well-known material balance and boundary dominated flow equations and is written in terms of capacitance and resistance of a production and a support compartment. These capacitance and resistance terms account for a combination of reservoir parameters which enable the developed model to be used for characterizing such systems. In addition to considering the properties contrast between the two reservoir compartments, the model takes into account existence of transmissibility barriers with the use of resistance terms. The model is used to analyze production performance of unconventional reservoirs, where the multistage fracturing of horizontal wells effectively creates a Stimulated Reservoir Volume (SRV with an enhanced permeability surrounded by a non-stimulated region. It can also be used for analysis of compartmentalized conventional reservoirs. The analytical solutions provide type curves through which the controlling reservoirs parameters of a compartmentalized system can be estimated. The contribution of the supporting compartment is modeled based on a boundary dominated flow assumption. The transient behaviour of the support compartment is captured by application of “distance of investigation” concept. The model shows that depletion of the production and support compartments exhibit two unit slopes on a log-log plot of pressure versus time for CTR. For CTP, however, the depletions display two exponential declines. The depletion signatures are separated by transition periods, which depend on the contribution of the support compartment (i.e. transient or boundary dominated flow. The developed equations can be implemented easily in a spreadsheet application, and are corroborated with the use of a numerical simulation. The study

  1. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions.

    Science.gov (United States)

    de Mas, Igor Marin; Selivanov, Vitaly A; Marin, Silvia; Roca, Josep; Orešič, Matej; Agius, Loranne; Cascante, Marta

    2011-10-28

    Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate). The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose phosphates in cytosol. In contrast, the observed distribution

  2. Compartmental syndrome of the forearm: report of an unusual case.

    Science.gov (United States)

    Pollock, M S; Morris, S B; Sadeghpour, E

    1984-02-01

    Compartmental syndrome of the forearm is a well-recognized complication of upper extremity injuries. An unusual case of the syndrome is presented, which developed after a "sprained" wrist. The etiology of the syndrome in this case was possibly tearing of anterior compartment muscle fibers when the wrist was forcibly extended in the fall, or a reflex sympathetic arc set up by the wrist trauma. Copyright 2013, SLACK Incorporated.

  3. Fractional two-compartmental model for articaine serum levels

    Science.gov (United States)

    Petronijevic, Branislava; Sarcev, Ivan; Zorica, Dusan; Janev, Marko; Atanackovic, Teodor M.

    2016-06-01

    Two fractional two-compartmental models are applied to the pharmacokinetics of articaine. Integer order derivatives are replaced by fractional derivatives, either of different, or of same orders. Models are formulated so that the mass balance is preserved. Explicit forms of the solutions are obtained in terms of the Mittag-Leffler functions. Pharmacokinetic parameters are determined by the use of the evolutionary algorithm and trust regions optimization to recover the experimental data.

  4. Rewiring and regulation of cross-compartmentalized metabolism in protists.

    Science.gov (United States)

    Ginger, Michael L; McFadden, Geoffrey I; Michels, Paul A M

    2010-03-12

    Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.

  5. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single-family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, driving the need for easier and more effective methods of compartmentalization in multifamily buildings. Builders and practitioners have found that fire-resistance rated wall assemblies are a major source of difficulty in air sealing/compartmentalization, particularly in townhouse construction. This problem is exacerbated when garages are “tucked in” to the units and living space is located over the garages. In this project, Building Science Corporation examined the taping of exterior sheathing details to improve air sealing results in townhouse and multifamily construction, when coupled with a better understanding of air leakage pathways. Current approaches are cumbersome, expensive, time consuming, and ineffective; these details were proposed as a more effective and efficient method. The effectiveness of these air sealing methods was tested with blower door testing, including “nulled” or “guarded” testing (adjacent units run at equal test pressure to null out inter-unit air leakage, or “pressure neutralization”). Pressure diagnostics were used to evaluate unit-to-unit connections and series leakage pathways (i.e., air leakage from exterior, into the fire-resistance rated wall assembly, and to the interior).

  6. [Imaging diagnostics of bone sarcomas].

    Science.gov (United States)

    Krämer, J A; Gübitz, R; Beck, L; Heindel, W; Vieth, V

    2014-06-01

    Bone tumors and especially bone sarcomas are rare lesions of the skeletal system in comparison to the much more frequently occurring bone metastases. Despite the relative rarity they are important differential diagnoses of bone lesions. The aim of this article is to give the reader an insight into the fundamentals of the primary imaging of bone sarcomas and to illustrate this with the help of two examples (e.g. osteosarcoma and chondrosarcoma). The foundation of the imaging of bone sarcomas is the radiograph in two planes. This method delivers important information on bone tumors. This information should be analyzed with the help of the Lodwick classification, the configuration of periosteal reactions and a possible reaction of the cortex. A possible tumor matrix and the localization within the skeleton or within long bones also provide important information for differential diagnostic delimitation. Magnetic resonance imaging (MRI) with specific adapted bone tumor sequences allows an exact local staging of a bone sarcoma. In addition to local imaging a compartmental MRI which illustrates the entire extent of tumor-bearing bone and the adjacent joints should be performed to rule out possible skip lesions. The most common distant metastases of osteosarcoma and chondrosarcoma occur in the lungs; therefore, a computed tomography (CT) of the chest is part of staging. Other imaging methods, such as CT of the tumor, positron emission tomography CT (PET-CT), bone scan and whole body MRI supplement the imaging depending on tumor type.

  7. A new reconstructive technique for intercalary defects of long bones: the association of massive allograft with vascularized fibular autograft. Long-term results and comparison with alternative techniques.

    Science.gov (United States)

    Capanna, Rodolfo; Campanacci, Domenico A; Belot, Nicolas; Beltrami, Giovanni; Manfrini, Marco; Innocenti, Marco; Ceruso, Massimo

    2007-01-01

    In 1988, the excellent results obtained with the use of vascularized fibular autograft as a salvage procedure in massive allograft failures caused by non-union or massive resorption prompted a trial of an original reconstructive technique for intercalary defects based on the primary combination of the two types of graft. The authors believe the excellent final results and the ability to avoid further salvage surgical procedures justify the primary application of this more complicated technique despite longer surgical times.

  8. Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins.

    Science.gov (United States)

    Kang, Hara; Davis-Dusenbery, Brandi N; Nguyen, Peter H; Lal, Ashish; Lieberman, Judy; Van Aelst, Linda; Lagna, Giorgio; Hata, Akiko

    2012-02-03

    The bone morphogenetic protein 4 (BMP4) signaling pathway plays a critical role in the promotion and maintenance of the contractile phenotype in vascular smooth muscle cell (vSMC). Misexpression or inactivating mutations of the BMP receptor gene can lead to dedifferentiation of vSMC characterized by increased migration and proliferation that is linked to vascular proliferative disorders. Previously we demonstrated that vSMCs increase microRNA-21 (miR-21) biogenesis upon BMP4 treatment, which induces contractile gene expression by targeting programmed cell death 4 (PDCD4). To identify novel targets of miR-21 that are critical for induction of the contractile phenotype by BMP4, biotinylated miR-21 was expressed in vSMCs followed by an affinity purification of mRNAs associated with miR-21. Nearly all members of the dedicator of cytokinesis (DOCK) 180-related protein superfamily were identified as targets of miR-21. Down-regulation of DOCK4, -5, and -7 by miR-21 inhibited cell migration and promoted cytoskeletal organization by modulating an activity of small GTPase. Thus, this study uncovers a regulatory mechanism of the vSMC phenotype by the BMP4-miR-21 axis through DOCK family proteins.

  9. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  10. The iDuo Bi-compartmental Knee Replacement: Our Early Experience.

    Directory of Open Access Journals (Sweden)

    Peter Jemmett

    2016-12-01

    Our early results suggest that the iDuo knee is a good option for those with isolated bi-compartmental disease and outcome scores are comparable with those reported for the BKA. This bi-compartmental design may bridge the gap between the uni-compartmental and total knee replacement. The choice between monolithic or modular designs remains in debate. We will continue to use this prosthesis for a carefully selected group of patients.

  11. Septins and the lateral compartmentalization of eukaryotic membranes.

    Science.gov (United States)

    Caudron, Fabrice; Barral, Yves

    2009-04-01

    Eukaryotic cells from neurons and epithelial cells to unicellular fungi frequently rely on cellular appendages such as axons, dendritic spines, cilia, and buds for their biology. The emergence and differentiation of these appendages depend on the formation of lateral diffusion barriers at their bases to insulate their membranes from the rest of the cell. Here, we review recent progress regarding the molecular mechanisms and functions of such barriers. This overview underlines the importance and conservation of septin-dependent diffusion barriers, which coordinately compartmentalize both plasmatic and internal membranes. We discuss their role in memory establishment and the control of cellular aging.

  12. Human memory T cells: generation, compartmentalization and homeostasis.

    Science.gov (United States)

    Farber, Donna L; Yudanin, Naomi A; Restifo, Nicholas P

    2014-01-01

    Memory T cells constitute the most abundant lymphocyte population in the body for the majority of a person's lifetime; however, our understanding of memory T cell generation, function and maintenance mainly derives from mouse studies, which cannot recapitulate the exposure to multiple pathogens that occurs over many decades in humans. In this Review, we discuss studies focused on human memory T cells that reveal key properties of these cells, including subset heterogeneity and diverse tissue residence in multiple mucosal and lymphoid tissue sites. We also review how the function and the adaptability of human memory T cells depend on spatial and temporal compartmentalization.

  13. Analytical properties of a three-compartmental dynamical demographic model

    Science.gov (United States)

    Postnikov, E. B.

    2015-07-01

    The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace.

  14. Transit times and mean ages for nonautonomous and autonomous compartmental systems

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Martin; Hastings, Alan; Smith, Matthew J.; Agusto, Folashade B.; Chen-Charpentier, Benito M.; Hoffman, Forrest M.; Jiang, Jiang; Todd-Brown, Katherine E. O.; Wang, Ying; Wang, Ying-Ping; Luo, Yiqi

    2016-04-01

    We develop a theory for residence times and mean ages for nonautonomous compartmental systems. Using the McKendrick–von Forster equation, we show that the mean ages of mass in a compartmental system satisfy a linear nonautonomous ordinary differential equation that is exponentially stable. We then define a nonautonomous version of residence time as the mean age of mass leaving the compartmental system at a particular time and show that our nonautonomous theory is consistent with the autonomous case. We apply these results to study a nine-dimensional nonautonomous compartmental system modeling the carbon cycle, which is a simplified version of the Carnegie–Ames–Stanford approach (CASA) model.

  15. Vascular ring

    DEFF Research Database (Denmark)

    Schmidt, Anne Mette S; Larsen, Signe H; Hjortdal, Vibeke E

    2018-01-01

    BACKGROUND: Vascular ring is a rare cause of recurrent respiratory infections, dysphagia and stridor. Surgical repair is considered safe but the long-term outcomes are unclear. The purpose of this study was to investigate the mortality and morbidity following vascular ring surgery in a single...... age of 1.4 years (range 0.008-64 years) were operated for vascular ring. Median follow-up was 6.8 years (range 2.4-34 years). Presenting symptoms were stridor (52%), dysphagia or vomiting (52%) and recurrent respiratory infections (48%). There were no early or late deaths. Three months postoperatively...

  16. Vascular anomalies

    Directory of Open Access Journals (Sweden)

    Murthy Jyotsna

    2005-01-01

    Full Text Available Management of vascular anomalies is an emerging multidisciplinary, super-specialisation field involving several surgical, medical and radiological specialties. Over the years, development in this field has been limited because of complex nomenclature and lack of consensus on the best practice for treatment of some of the more complex vascular anomalies. It was only in 1996 that the International Society of the Study of Vascular Anomalies defined nomenclature for the anomalies and gave clear guidelines on management, allowing for improved clinical practices. As in all fields of clinical medicine, the correct diagnosis of the vascular anomalies is essential to choose the appropriate treatment. This paper gives clear guidelines for diagnosis, understanding of the anomalies and discusses their management.

  17. Vascular Dementia

    OpenAIRE

    Maria Alekseyevna Cherdak; O V Uspenskaya

    2015-01-01

    This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)00463-8 Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the e...

  18. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar

    2017-02-01

    Full Text Available Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

  19. MDCT of hand and wrist infections: emphasis on compartmental anatomy.

    Science.gov (United States)

    Ahlawat, S; Corl, F M; LaPorte, D M; Fishman, E K; Fayad, L M

    2017-04-01

    Hand and wrist infections can present with a spectrum of manifestations ranging from cellulitis to deep-space collections. The various infectious processes can be categorised as superficial or deep infections based on their respective locations relative to the tendons. Superficial hand infections are located superficial to the tendons and are comprised of cellulitis, lymphangitis, paronychia, pulp-space infections, herpetic whitlow, and include volar as well as dorsal subcutaneous abscesses. Deep hand infections are located deep to the tendon sheaths and include synovial space infections, such as infectious tenosynovitis, deep fascial space infections, septic arthritis, necrotising fasciitis, and osteomyelitis. Knowledge of hand and wrist compartmental anatomy is essential for the accurate diagnosis and management of hand infections. Although early and superficial infections of the hand may respond to non-surgical management, most hand infections are surgical emergencies. Multidetector computed tomography (MDCT), with its muliplanar reformation (MPR) and three-dimensional (3D) capabilities, is a powerful tool in the emergency setting for the evaluation of acute hand and wrist pathology. The clinical and imaging features of hand and wrist infections as evident on MDCT will be reviewed with emphasis on contiguous and closed synovial and deep fascial spaces. Knowledge of hand compartmental anatomy enables accurate characterisation of the infectious process and localise the extent of disease in the acute setting. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  20. Lower extremity compartmental anatomy: clinical relevance to radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Toomayan, Glen A.; Robertson, Fabienne; Major, Nancy M. [Duke University Medical Center, Department of Radiology, Durham (United States)

    2005-06-01

    A thorough understanding of compartmental anatomy is necessary for the radiologist participating in the care of a patient with a lower extremity musculoskeletal malignancy. Localization of tumor to compartment of origin and identification of extracompartmental spread preoperatively are needed to correctly stage a tumor and determine the appropriate surgical management. An understanding of the locations of fascial boundaries, extracompartmental tissues, and neurovascular structures of the thigh and lower leg facilitates this diagnostic process. For the radiologist planning to biopsy a suspicious musculoskeletal lesion, consultation with the referring orthopaedic surgeon is recommended in order to jointly select an appropriate percutaneous biopsy approach. Adequate preprocedural planning ensures selection of an approach which prevents iatrogenic tumor spread beyond the compartment of origin, protects neurovascular structures, and allows complete resection of the biopsy tract and scar at the time of surgical resection without jeopardizing a potential limb-sparing procedure. Cross-sectional anatomic review and case examples demonstrate the importance of a detailed understanding of compartmental anatomy when approaching the patient with a lower extremity musculoskeletal tumor. (orig.)

  1. Ipsilateral Femoral Fracture Non-Union and Delayed Union Treated By Hybrid Plate Nail Fixation and Vascularized Fibula Bone Grafting: A Case Report

    Directory of Open Access Journals (Sweden)

    CK Chan

    2013-07-01

    Full Text Available Non-union is a well recognized complication of femoral neck fractures. The decision whether to attempt fracture fixation or to resort to hip replacement is particularly difficult in patients in the borderline age group in whom complex attempts at gaining union may fail and later present a difficult revision. On the other hand the patient may be young enough that arthroplasty best be avoided . Besides, presence of ipsilateral femoral shaft fracture with delayed union in addition to the femoral neck non-union will pose major problems at operation. We share our experience in treating a femoral neck fracture non-union with ipsilateral femoral shaft delayed union in the shaft and in the distal femur in a fifty years old patient. The fracture was treated with an angle blade plate and supracondylar nail supplemented with a free vascularised fibular bone grafting and autologous cancellous graft. There was radiological union at fourth month. At sixth months, the patient was free of pain and able to walk without support. Thus, we would like to suggest that vascularised fibula bone grafting with supracondylar nailing is a viable option for this pattern of fracture.

  2. Bone tumor

    Science.gov (United States)

    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 passed down ...

  3. Vascular Access Procedures

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Vascular Access Procedures A vascular access procedure inserts a flexible, ... the limitations of Vascular Access Procedures? What are Vascular Access Procedures? A vascular access procedure involves the insertion ...

  4. Vascular Access for Hemodialysis

    Science.gov (United States)

    ... Adequacy Eating & Nutrition for Hemodialysis Vascular Access for Hemodialysis What is a vascular access? A vascular access ... Set Up the Vascular Access Well before Starting Hemodialysis Patients should set up a vascular access well ...

  5. What Is Vascular Disease?

    Science.gov (United States)

    ... Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of the blood ... Privacy Policy × Your ticket for the: What Is Vascular Disease? Title What Is Vascular Disease? USD Close Print

  6. Bone scintiscanning updated.

    Science.gov (United States)

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

    1976-03-01

    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  7. Biological reconstruction after resection of bone tumors of the proximal tibia using allograft shell and intramedullary free vascularized fibular graft: long-term results.

    Science.gov (United States)

    Innocenti, Marco; Abed, Yasser Y; Beltrami, Giovanni; Delcroix, Luca; Manfrini, Marco; Capanna, Rodolfo

    2009-01-01

    Reconstruction after excision of bone tumor of the proximal tibia is a challenging issue for the reconstructive surgeon. The combined use of a free fibular flap and allograft can provide a reliable reconstructive option in this location. This article describes the authors' long-term follow-up using this technique. Twenty-seven patients that had resection of proximal tibia bone tumors underwent reconstruction using this technique. Only 21 patients that had primary reconstruction were included in this study. All patients had their surgeries performed at least 24 months before the end of the study. The average age at time of operation was 18.1 years. The average follow-up time was 139.3 months. Limb salvage was 82.7%. The average length of the resected tibial segment was 15.3 cm and that of the residual proximal tibia remaining after resection was 2.7 cm. The average time of union of fibula was 5.4 months and for union of allograft was 19.1 months. Primary union of the allograft was achieved in 90.5% of cases. Full weight-bearing was achieved at an average of 21.6 months. Ten patients (47.6%) had 14 local complications. The (MTSRS) average score at final follow-up was 27.3. Local recurrences occurred in two patients (9.5%). Distant metastasis to the lung occurred in three patients (14.3%). One patient died of disease. This technique provides good long-term results in reconstruction of proximal tibia. The viability of the fibula is a cornerstone in both success of reconstruction as well as successful management of complications.

  8. Building America Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2015-01-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, thus driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  9. Modelling compartmentalization towards elucidation and engineering of spatial organization in biochemical pathways.

    Science.gov (United States)

    Menon, Govind; Okeke, Chinedu; Krishnan, J

    2017-09-21

    Compartmentalization is a fundamental ingredient, central to the functioning of biological systems at multiple levels. At the cellular level, compartmentalization is a key aspect of the functioning of biochemical pathways and an important element used in evolution. It is also being exploited in multiple contexts in synthetic biology. Accurate understanding of the role of compartments and designing compartmentalized systems needs reliable modelling/systems frameworks. We examine a series of building blocks of signalling and metabolic pathways with compartmental organization. We systematically analyze when compartmental ODE models can be used in these contexts, by comparing these models with detailed reaction-transport models, and establishing a correspondence between the two. We build on this to examine additional complexities associated with these pathways, and also examine sample problems in the engineering of these pathways. Our results indicate under which conditions compartmental models can and cannot be used, why this is the case, and what augmentations are needed to make them reliable and predictive. We also uncover other hidden consequences of employing compartmental models in these contexts. Or results contribute a number of insights relevant to the modelling, elucidation, and engineering of biochemical pathways with compartmentalization, at the core of systems and synthetic biology.

  10. TNF-α enhances vascular cell adhesion molecule-1 expression in human bone marrow mesenchymal stem cells via the NF-κB, ERK and JNK signaling pathways.

    Science.gov (United States)

    Lu, Zi-Yuan; Chen, Wan-Cheng; Li, Yong-Hua; Li, Li; Zhang, Hang; Pang, Yan; Xiao, Zhi-Fang; Xiao, Hao-Wen; Xiao, Yang

    2016-07-01

    The migration of circulating mesenchymal stem cells (MSCs) to injured tissue is an important step in tissue regeneration and requires adhesion to the microvascular endothelium. The current study investigated the underlying mechanism of MSC adhesion to endothelial cells during inflammation. In in vitro MSC culture, tumor necrosis factor‑α (TNF‑α) increased the level of vascular cell adhesion molecule‑1 (VCAM‑1) expression in a dose‑dependent manner. The nuclear factor-κB (NF-κB), extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK) signaling pathway inhibitors, pyrrolidine dithiocarbamate (PDTC), U0126 and SP600125, respectively, suppressed VCAM‑1 expression induced by TNF‑α at the mRNA and protein levels (Padhesion to human umbilical vein endothelial cells; however, the inhibitors of NF‑κB, ERK and JNK did not affect this process in these cells. The results of the current study indicate that adhesion of circulating MSCs to the endothelium is regulated by TNF-α-induced VCAM-1 expression, which is potentially mediated by the NF‑κB, ERK and JNK signaling pathways.

  11. Vascular dementia.

    Science.gov (United States)

    O'Brien, John T; Thomas, Alan

    2015-10-24

    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment targets. Although there is an established relation between vascular and degenerative Alzheimer's pathology, the mechanistic link between the two has not yet been identified. This Series paper critiques some of the key areas and controversies, summarises treatment trials so far, and makes suggestions for what progress is needed to advance our understanding of pathogenesis and thus maximise opportunities for the search for new and effective management approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. [Vascular trauma].

    Science.gov (United States)

    Furuya, T; Nobori, M; Tanaka, N

    1999-07-01

    Vascular trauma is essentially acute arterial obstruction, often combined with hemorrhage, fracture, and infection. It can be both life-threatening and limb-threatening and needs an emergency operation. In vascular trauma patient, multiple fracture and organ injury, such as brain, lung, liver, spleen, kidney, or gastrointestinal tract should be evaluated to decide treatment priority. When the pulse distal from the injured site is absent or diminished, vascular trauma is most likely and reconstruction should be accomplished within "the golden time (6-8 hours)". Intimal damage followed by platelet aggregation and thrombus formation will necessitate resection and repair of the site instead of simple thrombectomy. Although autogenous vein is the first choice, artificial graft can be implanted for short segment in non-infected field.

  13. Use of non-vascularized autologous fibula strut graft in the treatment ...

    African Journals Online (AJOL)

    Background: Fractures resulting in segmental bone loss challenge the orthopedic surgeon. Orthopedic surgeons in developed countries have the option of choosing vascularized bone transfers, bone transport, allogenic bone grafts, bone graft substitutes and several other means to treat such conditions. In developing ...

  14. Compartmentalization of GPCR signalling controls unique cellular responses.

    Science.gov (United States)

    Ellisdon, Andrew M; Halls, Michelle L

    2016-04-15

    With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs. © 2016 Authors; published by Portland Press Limited.

  15. Apartment Compartmentalization With an Aerosol-Based Sealing Process

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, S. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States); Berger, D. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States); Harrington, C. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States)

    2015-03-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis. CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing.

  16. Partitioning Variability of a Compartmentalized In Vitro Transcriptional Thresholding Circuit.

    Science.gov (United States)

    Kapsner, Korbinian; Simmel, Friedrich C

    2015-10-16

    Encapsulation of in vitro biochemical reaction circuits into small, cell-sized compartments can result in considerable variations in the dynamical properties of the circuits. As a model system, we here investigate a simple in vitro transcriptional reaction circuit, which generates an ultrasensitive fluorescence response when the concentration of an RNA transcript reaches a preset threshold. The reaction circuit is compartmentalized into spherical water-in-oil microemulsion droplets, and the reaction progress is monitored by fluorescence microscopy. A quantitative statistical analysis of thousands of individual droplets ranging in size from a few up to 20 μm reveals a strong variability in effective RNA production rates, which by computational modeling is traced back to a larger-than-Poisson variability in RNAP activities in the droplets. The noise level in terms of the noise strength (the Fano factor) is strongly dependent on the ratio between transcription templates and polymerases, and increases for higher template concentrations.

  17. A topological map of the compartmentalized Arabidopsis thaliana leaf metabolome.

    Directory of Open Access Journals (Sweden)

    Stephan Krueger

    Full Text Available BACKGROUND: The extensive subcellular compartmentalization of metabolites and metabolism in eukaryotic cells is widely acknowledged and represents a key factor of metabolic activity and functionality. In striking contrast, the knowledge of actual compartmental distribution of metabolites from experimental studies is surprisingly low. However, a precise knowledge of, possibly all, metabolites and their subcellular distributions remains a key prerequisite for the understanding of any cellular function. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe results for the subcellular distribution of 1,117 polar and 2,804 lipophilic mass spectrometric features associated to known and unknown compounds from leaves of the model plant Arabidopsis thaliana. Using an optimized non-aqueous fractionation protocol in conjunction with GC/MS- and LC/MS-based metabolite profiling, 81.5% of the metabolic data could be associated to one of three subcellular compartments: the cytosol (including the mitochondria, vacuole, or plastids. Statistical analysis using a marker-'free' approach revealed that 18.5% of these metabolites show intermediate distributions, which can either be explained by transport processes or by additional subcellular compartments. CONCLUSION/SIGNIFICANCE: Next to a functional and conceptual workflow for the efficient, highly resolved metabolite analysis of the fractionated Arabidopsis thaliana leaf metabolome, a detailed survey of the subcellular distribution of several compounds, in the graphical format of a topological map, is provided. This complex data set therefore does not only contain a rich repository of metabolic information, but due to thorough validation and testing by statistical methods, represents an initial step in the analysis of metabolite dynamics and fluxes within and between subcellular compartments.

  18. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer porous-coated...

  19. VASCULAR SURGERY

    African Journals Online (AJOL)

    Venous thromboembolism (VTE) is a complex and serious condition encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), usually in the lower extremities.1,2. Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are ...

  20. Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG).

    Science.gov (United States)

    Kimmig, Rainer; Aktas, Bahriye; Buderath, Paul; Rusch, Peter; Heubner, Martin

    2016-04-01

    To evaluate feasibility of intraoperative visualization of embryologically defined organ compartments and their drainage by ICG in uterine cancer. Total of 2.5 mg of ICG have been injected into cervix or corpus in uterine cancer patients immediately prior to surgery. Green fluorescence was intermittently detected during robotically assisted laparoscopic surgery (Firefly System®, Intuitve Surgical Inc.). Total of 36 patients with uterine cancer without macroscopically suspicious nodes were evaluated with respect to their compartmental lymphatic network, collecting lymphatic vessels, and the connection to the postponed lymph basins. Müllerian (sub) compartment and transport of lymph fluid along the lymphatic collectors and connecting vessels to the postponed lymph basins could be visualized invariably in all patients. Cervix drained along the ligamentous and caudal part of vascular mesometria, whereas midcorporal and fundal drainage occurred along the upper part of vascular mesometria and along the mesonephric pathway along the ovarian vessels. Visualization of lymphatic network and downstream flow of lymphatic fluid to the postponed lymph basins by ICG is feasible; it can be used to navigate along compartment boarders for education, intraoperative orientation, and quality control. It seems to confirm the compartmental order of pelvic organ systems and postponed lymph basins. J. Surg. Oncol. 2016;113:554-559. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Compartmentation of sucrose during radial transfer in mature sorghum culm

    Directory of Open Access Journals (Sweden)

    Vietor Donald M

    2007-06-01

    Full Text Available Abstract Background The sucrose that accumulates in the culm of sorghum (Sorghum bicolor (L. Moench and other large tropical andropogonoid grasses can be of commercial value, and can buffer assimilate supply during development. Previous study conducted with intact plants showed that sucrose can be radially transferred to the intracellular compartment of mature ripening sorghum internode without being hydrolysed. In this study, culm-infused radiolabelled sucrose was traced between cellular compartments and among related metabolites to determine if the compartmental path of sucrose during radial transfer in culm tissue was symplasmic or included an apoplasmic step. This transfer path was evaluated for elongating and ripening culm tissue of intact plants of two semidwarf grain sorghums. The metabolic path in elongating internode tissue was also evaluated. Results On the day after culm infusion of the tracer sucrose, the specific radioactivity of sucrose recovered from the intracellular compartment of growing axillary-branch tissue was greater (nearly twice than that in the free space, indicating that sucrose was preferentially transferred through symplasmic routes. In contrast, the sucrose specific radioactivity in the intracellular compartment of the mature (ripening culm tissue was probably less (about 3/4's than that in free space indicating that sucrose was preferentially transferred through routes that included an apoplasmic step. In growing internodes of the axillary branch of sorghum, the tritium label initially provided in the fructose moiety of sucrose molecules was largely (81% recovered in the fructose moiety, indicating that a large portion of sucrose molecules is not hydrolysed and resynthesized during radial transfer. Conclusion During radial transfer of sucrose in ripening internodes of intact sorghum plants, much of the sucrose is transferred intact (without hydrolysis and resynthesis and primarily through a path that includes an

  2. Metabolic flux and compartmentation analysis in the brain in vivo

    Directory of Open Access Journals (Sweden)

    Bernard eLanz

    2013-10-01

    Full Text Available Through significant developments and progresses in the last two decades, in vivo localized nuclear magnetic resonance spectroscopy (MRS became a method of choice to probe brain metabolic pathways in a non-invasive way. Beside the measurement of the total concentration of more than 20 metabolites, 1H MRS can be used to quantify the dynamics of substrate transport across the blood brain barrier (BBB by varying the plasma substrate level. On the other hand, 13C MRS with the infusion of 13C enriched substrates enables the characterization of brain oxidative metabolism and neurotransmission by incorporation of 13C in the different carbon positions of amino acid neurotransmitters. The quantitative determination of the biochemical reactions involved in these processes requires the use of appropriate metabolic models, whose level of details is strongly related to the amount of data accessible with in vivo MRS. In the present work, we present the different steps involved in the elaboration of a mathematical model of a given brain metabolic process and its application to the experimental data in order to extract quantitative brain metabolic rates. We review the recent advances in the localized measurement of brain glucose transport and compartmentalized brain energy metabolism, and how these reveal mechanistic details on glial support to glutamatergic and GABAergic neurons.

  3. Metabolic Flux and Compartmentation Analysis in the Brain In vivo

    Science.gov (United States)

    Lanz, Bernard; Gruetter, Rolf; Duarte, João M. N.

    2013-01-01

    Through significant developments and progresses in the last two decades, in vivo localized nuclear magnetic resonance spectroscopy (MRS) became a method of choice to probe brain metabolic pathways in a non-invasive way. Beside the measurement of the total concentration of more than 20 metabolites, 1H MRS can be used to quantify the dynamics of substrate transport across the blood-brain barrier by varying the plasma substrate level. On the other hand, 13C MRS with the infusion of 13C-enriched substrates enables the characterization of brain oxidative metabolism and neurotransmission by incorporation of 13C in the different carbon positions of amino acid neurotransmitters. The quantitative determination of the biochemical reactions involved in these processes requires the use of appropriate metabolic models, whose level of details is strongly related to the amount of data accessible with in vivo MRS. In the present work, we present the different steps involved in the elaboration of a mathematical model of a given brain metabolic process and its application to the experimental data in order to extract quantitative brain metabolic rates. We review the recent advances in the localized measurement of brain glucose transport and compartmentalized brain energy metabolism, and how these reveal mechanistic details on glial support to glutamatergic and GABAergic neurons. PMID:24194729

  4. Adaptive and neuroadaptive control for nonnegative and compartmental dynamical systems

    Science.gov (United States)

    Volyanskyy, Kostyantyn Y.

    Neural networks have been extensively used for adaptive system identification as well as adaptive and neuroadaptive control of highly uncertain systems. The goal of adaptive and neuroadaptive control is to achieve system performance without excessive reliance on system models. To improve robustness and the speed of adaptation of adaptive and neuroadaptive controllers several controller architectures have been proposed in the literature. In this dissertation, we develop a new neuroadaptive control architecture for nonlinear uncertain dynamical systems. The proposed framework involves a novel controller architecture with additional terms in the update laws that are constructed using a moving window of the integrated system uncertainty. These terms can be used to identify the ideal system weights of the neural network as well as effectively suppress system uncertainty. Linear and nonlinear parameterizations of the system uncertainty are considered and state and output feedback neuroadaptive controllers are developed. Furthermore, we extend the developed framework to discrete-time dynamical systems. To illustrate the efficacy of the proposed approach we apply our results to an aircraft model with wing rock dynamics, a spacecraft model with unknown moment of inertia, and an unmanned combat aerial vehicle undergoing actuator failures, and compare our results with standard neuroadaptive control methods. Nonnegative systems are essential in capturing the behavior of a wide range of dynamical systems involving dynamic states whose values are nonnegative. A sub-class of nonnegative dynamical systems are compartmental systems. These systems are derived from mass and energy balance considerations and are comprised of homogeneous interconnected microscopic subsystems or compartments which exchange variable quantities of material via intercompartmental flow laws. In this dissertation, we develop direct adaptive and neuroadaptive control framework for stabilization, disturbance

  5. Lingual vascular canals of the interforaminal region of the mandible: evaluation with conventional tomography

    National Research Council Canada - National Science Library

    Liang, H; Frederiksen, N L; Benson, B W

    2004-01-01

    The presence of lingual vascular foramina and canals in the interforaminal region may increase the risk of surgical complications during implant placement, bone grafting procedures and osteodistraction...

  6. Compartmental models for assessing the fishery production in the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Dalal, S.G.; Parulekar, A.H.

    Compartmental models for assessing the fishery production in the Indian Ocean is discussed. The article examines the theoretical basis on which modern fishery sciences is built. The model shows that, large changes in energy flux from one pathway...

  7. In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei

    NARCIS (Netherlands)

    Haanstra, Jurgen R.; Bakker, Barbara M.; Michels, Paul A. M.

    2014-01-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucel. The recent finding of pore-forming

  8. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan

    OpenAIRE

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-01-01

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution...

  9. Na+ compartmentalization related to salinity stress tolerance in upland cotton (Gossypium hirsutum) seedlings

    OpenAIRE

    Zhen Peng; Shoupu He; Junling Sun; Zhaoe Pan; Wenfang Gong; Yanli Lu; Xiongming Du

    2016-01-01

    The capacity for ion compartmentalization among different tissues and cells is the key mechanism regulating salt tolerance in plants. In this study, we investigated the ion compartmentalization capacity of two upland cotton genotypes with different salt tolerances under salt shock at the tissue, cell and molecular levels. We found that the leaf glandular trichome could secrete more salt ions in the salt-tolerant genotype than in the sensitive genotype, demonstrating the excretion of ions from...

  10. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  11. Combined Massive Allograft and Intramedullary Vascularized Fibula Transfer: The Capanna Technique for Lower-Limb Reconstruction

    National Research Council Canada - National Science Library

    Bakri, Karim; Stans, Anthony; Mardini, Samir; Moran, Steven

    2008-01-01

    .... Recently, a novel approach to limb salvage has been described by Capanna and colleagues whereby a massive bone allograft and intramedullary vascularized fibula are combined to reconstruct large, segmental bone defects...

  12. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: dhlee@cau.ac.kr [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)

    2011-09-15

    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  13. Differential gating of dendritic spikes by compartmentalized inhibition

    Directory of Open Access Journals (Sweden)

    Katharina Anna Wilmes

    2014-03-01

    Full Text Available Different types of local inhibitory interneurons innervate different dendritic sites of pyramidal neurons in cortex and hippocampus (Klausberger 2009. What could be the functional role of compartmentalized inhibition? Pyramidal cell dendrites support different forms of active signal propagation, which are important not only for dendritic and neuronal signal processing (Smith et al. 2013, but also for synaptic plasticity. While back-propagating action potentials signal post-synaptic activity to synapses in apical oblique and basal dendrites (Markram et al. 1997, Cho et al. 2006, calcium spikes cause plasticity of distal apical tuft synapses (Golding et al. 2002. Suspiciously, the associated regions of the dendrite are targeted by different interneuron populations. Parvalbumin-positive interneurons typically target the proximal dendritic and somatic parts of the neuron, while somatostatin-positive interneurons target the apical dendrite. The matching compartmentalization in terms of dendritic spikes and inhibitory control suggests that inhibition could differentially regulate different dendritic spikes and thereby introduce a compartment-specific modulation of synaptic plasticity. We evaluate this hypothesis in a biophysical multi-compartment model of a pyramidal neuron, receiving shunting inhibition at different locations on the dendrite. The model shows that, first, inhibition can gate dendritic spikes in an all-or-none manner. Second, spatially selective inhibition can individually suppress back-propagating action potentials and calcium spikes, thereby allowing a compartment-specific switch for synaptic plasticity. In our model, proximal inhibition on the apical dendrite eliminated both the back-propagating action potential and the calcium spike, thus influencing plasticity in the whole apical dendrite. Distal apical inhibition could selectively affect calcium spikes and thus distal plasticity, without suppressing back­propagation of action

  14. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

    Directory of Open Access Journals (Sweden)

    Zhiwen Yu

    Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics.

  15. Deciphering neuron-glia compartmentalization in cortical energy metabolism

    Directory of Open Access Journals (Sweden)

    Renaud Jolivet

    2009-07-01

    Full Text Available Energy demand is an important constraint on neural signaling. Several methods have been proposed to assess the energy budget of the brain based on a bottom-up approach in which the energy demand of individual biophysical processes are first estimated independently and then summed up to compute the brain's total energy budget. Here, we address this question using a novel approach that makes use of published datasets that reported average cerebral glucose and oxygen utilization in humans and rodents during different activation states. Our approach allows us (1 to decipher neuron-glia compartmentalization in energy metabolism and (2 to compute a precise state-dependent energy budget for the brain. Under the assumption that the fraction of energy used for signaling is proportional to the cycling of neurotransmitters, we find that in the activated state, most of the energy (~80% is oxidatively produced and consumed by neurons to support neuron-to-neuron signaling. Glial cells, while only contributing for a small fraction to energy production (~6%, actually take up a significant fraction of glucose (50% or more from the blood and provide neurons with glucose-derived energy substrates. Our results suggest that glycolysis occurs for a significant part in astrocytes whereas most of the oxygen is utilized in neurons. As a consequence, a transfer of glucose-derived metabolites from glial cells to neurons has to take place. Furthermore, we find that the amplitude of this transfer is correlated to (1 the activity level of the brain; the larger the activity, the more metabolites are shuttled from glia to neurons and (2 the oxidative activity in astrocytes; with higher glial pyruvate metabolism, less metabolites are shuttled from glia to neurons. While some of the details of a bottom-up biophysical approach have to be simplified, our method allows for a straightforward assessment of the brain's energy budget from macroscopic measurements with minimal

  16. Compartmentation and complexation of metals in hyperaccumulator plants

    Directory of Open Access Journals (Sweden)

    Barbara eLeitenmaier

    2013-09-01

    Full Text Available Hyperaccumulators are being intensely investigated. They are not only interesting in scientific context due to their strange behaviour in terms of dealing with high concentrations of metals, but also because of their use in phytoremediation and phytomining, for which understanding the mechanisms of hyperaccumulation is crucial. Hyperaccumulators naturally use metal accumulation as a defence against herbivores and pathogens, and therefore deal with accumulated metals in very specific ways of complexation and compartmentation, different from non-hyperaccumulator plants and also non-hyperaccumulated metals. For example, in contrast to non-hyperaccumulators, in hyperaccumulators even the classical phytochelatin-inducing metal, cadmium, is predominantly not bound by such sulfur ligands, but only by weak oxygen ligands. This applies to all hyperaccumulated metals investigated so far, as well as hyperaccumulation of the metalloid arsenic. Stronger ligands, as they have been shown to complex metals in non-hyperaccumulators, are in hyperaccumulators used for transient binding during transport to the storage sites. This confirmed that enhanced active metal transport, and not metal complexation, is the key mechanism of hyperaccumulation. Hyperaccumulators tolerate the high amount of accumulated heavy metals by sequestering them into vacuoles, usually in large storage cells of the epidermis. This is mediated by strongly elevated expression of specific transport proteins in various tissues from metal uptake in the shoots up to the storage sites in the leaf epidermis. However, this mechanism seems to be very metal specific. Non-hyperaccumulated metals in hyperaccumulators seem to be dealt with like in non-hyperaccumulator plants, i.e. detoxified by binding to strong ligands such as metallothioneins.

  17. The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis

    National Research Council Canada - National Science Library

    Menini, Stefano; Iacobini, Carla; Ricci, Carlo; Blasetti Fantauzzi, Claudia; Salvi, Laura; Pesce, Carlo M; Relucenti, Michela; Familiari, Giuseppe; Taurino, Maurizio; Pugliese, Giuseppe

    2013-01-01

    ...). This study compared the roles of galectin-3 and receptor for AGEs (RAGE), two ALEs/AGEs-receptors with diverging effects on inflammation and bone metabolism, in the process of vascular calcification...

  18. Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2017-12-01

    Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O 2 , nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to influencing bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered. © 2017 Society for Endocrinology.

  19. Osteoporosis and adynamic bone in chronic kidney disease

    OpenAIRE

    Cannata, J.B. (Jorge); Rodríguez, Minerva; Gómez, Carlos

    2013-01-01

    Among the chronic kidney disease–mineral bone disease (CKD-MBD) disorders, osteoporosis and adynamic bone are highly prevalent, and they have been consistently associated with low bone mass, bone fractures, vascular calcifications and greater mortality in general and CKD populations. Despite the fact that osteoporosis and adynamic bone have similar clinical outcomes, they have different pathogeneses and clinical management. In osteoporosis, there is a lack of balance between bone format...

  20. Neuro-vascular injuries associated with limb fractures | Mirdad | East ...

    African Journals Online (AJOL)

    Neuro-vascular injuries associated with limb fractures. ... PROMOTING ACCESS TO AFRICAN RESEARCH. AFRICAN JOURNALS ... Subjects: Forty three patients with bone fractures associated with vascular and peripheral nerve injury seen at the Emergency Room of Assir Central Hospital from 1990 to 1999. There were ...

  1. Circulating Progenitor Cells in Diabetic Vascular Disease

    NARCIS (Netherlands)

    van Oostrom, O.

    2009-01-01

    Patients with diabetes have altered levels and function of (bone marrow-derived) vascular progenitor cells (endothelial progenitor cells-EPC, smooth muscle progenitor cells-SPC) which may contribute to their accelerated atherosclerosis. The results from clinical and experimental studies in this

  2. Na+ compartmentalization related to salinity stress tolerance in upland cotton (Gossypium hirsutum) seedlings.

    Science.gov (United States)

    Peng, Zhen; He, Shoupu; Sun, Junling; Pan, Zhaoe; Gong, Wenfang; Lu, Yanli; Du, Xiongming

    2016-10-04

    The capacity for ion compartmentalization among different tissues and cells is the key mechanism regulating salt tolerance in plants. In this study, we investigated the ion compartmentalization capacity of two upland cotton genotypes with different salt tolerances under salt shock at the tissue, cell and molecular levels. We found that the leaf glandular trichome could secrete more salt ions in the salt-tolerant genotype than in the sensitive genotype, demonstrating the excretion of ions from tissue may be a new mechanism to respond to short-term salt shock. Furthermore, an investigation of the ion distribution demonstrated that the ion content was significantly lower in critical tissues and cells of the salt-tolerant genotype, indicating the salt-tolerant genotype had a greater capacity for ion compartmentalization in the shoot. By comparing the membrane H+-ATPase activity and the expression of ion transportation-related genes, we found that the H+-ATPase activity and Na+/H+ antiporter are the key factors determining the capacity for ion compartmentalization in leaves, which might further determine the salt tolerance of cotton. The novel function of the glandular trichome and the comparison of Na+ compartmentalization between two cotton genotypes with contrasting salt tolerances provide a new understanding of the salt tolerance mechanism in cotton.

  3. Silk Biomaterials with Vascularization Capacity.

    Science.gov (United States)

    Han, Hongyan; Ning, Hongyan; Liu, Shanshan; Lu, Qiang; Fan, Zhihai; Lu, Haijun; Lu, Guozhong; Kaplan, David L

    2016-01-20

    Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver or bone. The immobilization or delivery of growth factors has been explored to improve vascularization capacity of tissue engineered constructs, however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications such as immunological responses and cancer. Here, a new method of preparing water-insoluble silk protein scaffolds with vascularization capacity using an all aqueous process is reported. Acid was added temporally to tune the self-assembly of silk in lyophilization process, resulting in water insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk-based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.

  4. Compartmental analysis of dynamic nuclear medicine data: regularization procedure and application to physiology

    CERN Document Server

    Fabrice, Delbary

    2016-01-01

    Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the second of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. While the previous work was devoted to the discussion of identifiability issues for 2, 3 and n-dimension compartmental systems, here we discuss the problem of numerically determining the tracer coefficients by means of a general regularized Multivariate Gauss Newton scheme. In this paper, applications concerning cerebral, hepatic and renal functions are considered, involving experimental measurements on FDG-PET data on different set of murine models.

  5. Global identifiability of linear compartmental models--a computer algebra algorithm.

    Science.gov (United States)

    Audoly, S; D'Angiò, L; Saccomani, M P; Cobelli, C

    1998-01-01

    A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

  6. Concomitant pleural and disseminated tuberculosis in AIDS: immune response or HIV infection compartmentalization?

    Science.gov (United States)

    Tuon, Felipe Francisco; Tonacio, Adriana Coracini; Gryschek, Ronaldo César

    2007-01-01

    Although, pleural (PT) and disseminated tuberculosis (DT) have been considered as extreme endpoints of the Th1-Th2 immunological spectrum of the Mycobacterium tuberculosis infection, these conditions can occur together. The presence of PT and DT could be explained by (1) PT as primary condition, with progression of HIV infection possibly leading to dissemination of bacilli located in the pleura; (2) preexisting PT, with reinfection at lower LTCD4+ count explaining the DT form; (3) simultaneous acute PT and DT, considering immune compartmentalization phenomena in pleura. There are several important aspects of the immune response and its compartmentalization in co-infected patients with tuberculosis and HIV. PT and DT should not be always considered as extremes of the immunological response against M. tuberculosis, both diseases together may be explained after the understanding of compartmentalization of immune response. Associations between these entities are not so rare, while they remain incompletely explained. This brief review discusses several points of this contradictory association.

  7. The architecture of antagonistic networks: Node degree distribution, compartmentalization and nestedness

    Directory of Open Access Journals (Sweden)

    Savannah Nuwagaba

    2015-12-01

    Full Text Available Describing complex ecosystems as networks of interacting components has proved fruitful - revealing many distinctive patterns and dynamics of ecological systems. Of these patterns, three have often been brought up in literature, including species degree distribution, compartmentalization and nestedness, due largely to their implications for the functionality and stability of communities. Here, using 61 empirical antagonistic networks, we aim to settle the inconsistency in literature by (i fitting their node degree distributions to five different parametric models and identifying the one fits the best, (ii measuring the levels of nestedness and compartmentalization of these 61 networks and testing their significance using different null models, and (iii exploring how network connectance affects these three network architecture metrics. This research showed that most antagonistic networks do not display power law degree distributions and that resource species are generally uniformly distributed. We also clearly showed that the conclusion of whether a network is significantly compartmentalized or nested depends largely on the null model used.

  8. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    Directory of Open Access Journals (Sweden)

    Pei-Chi Yang

    2016-07-01

    Full Text Available Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and

  9. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

    Science.gov (United States)

    Daba, Alina; Gkouvatsos, Konstantinos; Sebastiani, Giada; Pantopoulos, Kostas

    2013-01-01

    The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

  10. Increased presence of capillaries next to remodeling sites in adult human cancellous bone

    DEFF Research Database (Denmark)

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels

    2013-01-01

    Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remode...

  11. Plant Vascular Biology 2013: vascular trafficking.

    Science.gov (United States)

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  12. Combined Massive Allograft and Intramedullary Vascularized Fibula Transfer: The Capanna Technique for Lower-Limb Reconstruction

    OpenAIRE

    Bakri, Karim; Stans, Anthony A.; Mardini, Samir; Moran, Steven L.

    2008-01-01

    Limb salvage has now replaced amputation as the standard treatment for primary bone tumors and can usually be offered to more than 85% of patients. Recently, a novel approach to limb salvage has been described by Capanna and colleagues whereby a massive bone allograft and intramedullary vascularized fibula are combined to reconstruct large, segmental bone defects. This produces a structurally competent reconstruction with enhanced vascular and osteogenic capabilities and the potential to achi...

  13. Bioprinting for vascular and vascularized tissue biofabrication.

    Science.gov (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  14. Improved method for examination of microvascular structures in bone tissue.

    Science.gov (United States)

    Møller, J F; Robertsen, K; Bünger, C; Hansen, E S

    1997-01-01

    Scanning electron microscopy of methylmethacrylate vascular corrosion casts was used for the morphologic examination of the microvascular system in bone. The methylmethacrylate used for vascular casting was prepared by prepolymerization with ultraviolet light. To approximate the viscosity of blood in the microcirculation, where the hematocrit of blood is lower than in the rest of the circulation, a viscosity between that of plasma and full blood was chosen for the casting material. Neither the ultraviolet prepolymerization of methylmethacrylate nor the choice of a viscosity this low has been used in microcorrosion casting in bone before. Further preparation of the tissue followed 2 directions: (1) complete maceration and decalcification of the specimens, thereby exposing all the vascular structures for detailed examination. By this procedure, it was possible to show detailed and sharp impressions of the vascular bed, and to show, for the first time, the vascular loop from a cutting cone; and (2) maceration without decalcification of the specimens, which is suitable for examination of relations between the microvascular system and the bone tissue. This technique enables studies of the role of the vascular system in bone remodeling and of the involvement of vascular structures in bone disorders. This improved technique for examination of microvascular structures in bone enables detailed studies of the vascular system and its relation to active remodeling sites in bone.

  15. Bone Diseases

    Science.gov (United States)

    ... need to get enough calcium, vitamin D, and exercise. You should also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds of bone problems include Low bone density and osteoporosis, which make your bones weak and ...

  16. Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles

    Directory of Open Access Journals (Sweden)

    Taro Furubayashi

    2018-01-01

    Full Text Available The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host–parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.

  17. Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

    Science.gov (United States)

    Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

    2015-01-25

    Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

  18. Meningoencephalitis and Compartmentalization of the Cerebral Ventricles Caused by Enterobacter sakazakii

    Science.gov (United States)

    Kleiman, Martin B.; Allen, Stephen D.; Neal, Patricia; Reynolds, Janet

    1981-01-01

    A necrotizing meningoencephalitis complicated by ventricular compartmentalization and abscess formation caused by Enterobacter sakazakii in a previously healthy 5-week-old female is described. A detailed description of the isolate is presented. This communication firmly establishes the pathogenicity of E. sakazakii. PMID:7287892

  19. Size control and compartmentalization in self-assembled nano-structures of a multisegment amphiphilew

    NARCIS (Netherlands)

    Boekhoven, J.; Van Rijn, P.; Brizard, A.M.; Stuart, M.C.A.; Van Esch, J.H.

    2010-01-01

    A ‘‘multisegment amphiphile’’ has been synthesized by covalently connecting two well known building blocks, a gelator and a micelle forming surfactant. Self-assembly results in the formation of compartmentalized nano-object displaying properties inherited from both parents.

  20. Beyond Compartmentalization: A Relational Approach towards Agency and Vulnerability of Young Migrants

    Science.gov (United States)

    Huijsmans, Roy

    2012-01-01

    Based on fieldwork material from Lao People's Democratic Republic, this paper introduces an analytical framework that transcends compartmentalized approaches towards migration involving young people. The notions of fluid and institutionalized forms of migration illuminate key differences and commonalities in the relational fabric underpinning…

  1. Macroanatomy and compartmentalization of recent fire scars in three North American conifers

    Science.gov (United States)

    Kevin T. Smith; Estelle Arbellay; Donald A. Falk; Elaine Kennedy Sutherland

    2016-01-01

    Fire scars are initiated by cambial necrosis caused by localized lethal heating of the tree stem. Scars develop as part of the linked survival processes of compartmentalization and wound closure. The position of scars within dated tree ring series is the basis for dendrochronological reconstruction of fire history. Macroanatomical features were described for western...

  2. Technology Solutions Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-01-01

    Fire-resistance rated (or area separation) wall assemblies present a great difficulty in air sealing/compartmentalization, particularly in townhouse construction. To address this challenge, Building Science Corporation partnered with builder K. Hovnanian Homes to determine whether taping exterior sheathing details improves air sealing in townhouse and multifamily construction, and to better understand air leakage pathways.

  3. Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes

    NARCIS (Netherlands)

    J.R. Haanstra (Jurgen); A. van Tuijl (Arjen); P. Kessler (Peter); W. Reijnders (Willem); P.A.M. Michels (Paul); H.V. Westerhoff (Hans); M. Parsons (Marilyn); B.M. Bakker (Barbara)

    2008-01-01

    textabstractATP generation by both glycolysis and glycerol catabolism is autocatalytic, because the first kinases of these pathways are fuelled by ATP produced downstream. Previous modeling studies predicted that either feedback inhibition or compartmentation of glycolysis can protect cells from

  4. Compartmental Model For Uptake Of 137cs By Pine In Forest Soil ...

    African Journals Online (AJOL)

    A compartmental model of soil to pine tree transfer of 137Cs following the Chernobyl nuclear accident is presented. The model was validated using data collected in 1996 at five sites in Northern Ukraine. The transfer constants of 137Cs between model compartments are estimated using a semi-empirical method.

  5. Linear regressive model structures for estimation and prediction of compartmental diffusive systems

    NARCIS (Netherlands)

    Vries, D.; Keesman, K.J.; Zwart, H.

    2006-01-01

    Abstract In input-output relations of (compartmental) diffusive systems, physical parameters appear non-linearly, resulting in the use of (constrained) non-linear parameter estimation techniques with its short-comings regarding global optimality and computational effort. Given a LTI system in state

  6. Linear regressive model structures for estimation and prediction of compartmental diffusive systems

    NARCIS (Netherlands)

    Vries, D; Keesman, K.J.; Zwart, Heiko J.

    In input-output relations of (compartmental) diffusive systems, physical parameters appear non-linearly, resulting in the use of (constrained) non-linear parameter estimation techniques with its short-comings regarding global optimality and computational effort. Given a LTI system in state space

  7. The Contradictions and Compartmentalizing the Interactions between Integrated Business Structures: Aspect of Branding

    Directory of Open Access Journals (Sweden)

    Nifatova Olena M.

    2017-04-01

    Full Text Available The article is aimed at identifying contradictions and developing a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management. The main specific features and contradictions that arise in the process of integration in the domestic market of mergers and acquisitions have been allocated. The contradictions identified were systematized and substantiated at three economic levels: macro-, meso-, and microeconomic. A compartmentalizing of the business units interaction in a merge or an acquisition process has been proposed. This compartmentalizing takes account of the branding aspect through the introduction of «brands interaction» – cluster interaction, circular interaction, holding interaction, linear interaction, which enhances the scientific view of exploring the problem of business units interaction in the process of the formations becoming integrated. The development of a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management, would provide a more effective use of the fundamental nature of branding as synergistic force in terms of the system of integration of business structures at the current stage of development of the national economy. Further development of branding issues in this sphere will have a significant impact on the functioning of the integrated business structures with the participation of Ukrainian companies.

  8. Compartmental resection of peripheral nerve tumours with limb preservation in 16 dogs (1995–2011)

    NARCIS (Netherlands)

    van Stee, L.|info:eu-repo/dai/nl/413490645; Boston, Sarah E; Teske, E.|info:eu-repo/dai/nl/114300240; Meij, B.|info:eu-repo/dai/nl/164045805

    2017-01-01

    Peripheral nerve tumours (PNTs) affecting the limbs may lead to chronic pain, lameness and/or monoparesis that is refractory to medical treatment. The most common radical therapy for PNTs has been surgical excision with limb amputation. However, compartmental resection with preservation of the limb

  9. Optical compartmentation of vegetating algae species as a basis for their growth-specific characterization.

    Science.gov (United States)

    Gerashchenko, Bogdan I; Kosaka, Toshikazu; Hosoya, Hiroshi

    2002-07-01

    The number of microalgal strains known to date is enormous and continuously growing, and their characterization accordingly requires quick and reliable methodologies. Asynchronously growing logarithmic (3- and 6-day cultures) and stationary (9-day cultures) phase cell populations of two algae species that are difficult to distinguish microscopically (one Chlorella sp., C. vulgaris [c-27], and another that might belong to the same genus, SA-3 algae exsymbiotic from Paramecium bursaria) were characterized by means of flow cytometry (FCM). Forward light scatter (FSC) of algae was monitored in association with their 90 degrees side light scatter (SSC) and fluorescence of endogenous chlorophyll (FL3-height). Two-parameter FSC versus SSC and FSC versus FL3-height plots distinctly showed growth-specific compartmentation of algae into discrete cell subpopulations staying at a particular stage of the life cycle, and numbers of cells constituting these subpopulations could be quantitated. The growth pattern of C. vulgaris (c-27) differed substantially from that of SA-3 algae, particularly in the late-logarithmic (6-day) cultures. At this phase of growth, C. vulgaris (c-27) cells compartmentalized into three subpopulations, whereas SA-3 cells compartmentalized into two subpopulations. Different compartmentations of optical signals from late-logarithmic phase SA-3 algae and C. vulgaris (c-27) likely were caused by the differences in timing of the life cycle stages of these types of cells. Growth-specific compartmentation of vegetating microalgae by FCM provides a good basis for characterization of morphologically similar algae species. Because algae are also present in symbiotic relationships with other organisms, this tool might be of potential interest for the study of symbiosis mechanisms. Copyright 2002 Wiley-Liss, Inc.

  10. Bone Metastasis

    Science.gov (United States)

    ... help reduce pain and other symptoms of bone metastases. Symptoms Sometimes, bone metastasis causes no signs and ... cancers most likely to cause bone metastasis include: Breast cancer Kidney cancer Lung cancer Lymphoma Multiple myeloma Prostate ...

  11. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  12. An Aneurysmal Bone Cyst in the Skull Base.

    Science.gov (United States)

    Kim, Sangjun; Jung, Dong Won; Pak, Min Gyoung; Song, Young Jin; Bae, Woo Yong

    2017-10-01

    An aneurysmal bone cyst (ABC) is believed to be attributable to intraosseous circulatory disturbance. An ABC is a vascular tumor of the bone caused by bony expansion after partial vascular occlusion and congestion. Most ABCs are found in adolescents (approximately 75% of ABCs are observed in patients under 20 years of age). The most common ABC sites are the long bones of the limbs, the vertebrae, and the cranial bone. Aneurysmal bone cysts in the skull base or ethmoid sinus have been but rarely reported worldwide. The authors report on a patient with a very large ABC in the skull base and the ethmoid sinus; this was successfully managed by a neurosurgeon.

  13. Collagen vascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific conditions ...

  14. A comparative evaluation of two decompression procedures for technical diving using inflammatory responses: compartmental versus ratio deco.

    Science.gov (United States)

    Spisni, Enzo; Marabotti, Claudio; De Fazio, Luigia; Valerii, Maria Chiara; Cavazza, Elena; Brambilla, Stefano; Hoxha, Klarida; L'Abbate, Antonio; Longobardi, Pasquale

    2017-03-01

    The aim of this study was to compare two decompression procedures commonly adopted by technical divers: the ZH-L16 algorithm modified by 30/85 gradient factors (compartmental decompression model, CDM) versus the 'ratio decompression strategy' (RDS). The comparison was based on an analysis of changes in diver circulating inflammatory profiles caused by decompression from a single dive. Fifty-one technical divers performed a single trimix dive to 50 metres' sea water (msw) for 25 minutes followed by enriched air (EAN50) and oxygen decompression. Twenty-three divers decompressed according to a CDM schedule and 28 divers decompressed according to a RDS schedule. Peripheral blood for detection of inflammatory markers was collected before and 90 min after diving. Venous gas emboli were measured 30 min after diving using 2D echocardiography. Matched groups of 23 recreational divers (dive to 30 msw; 25 min) and 25 swimmers were also enrolled as control groups to assess the effects of decompression from a standard air dive or of exercise alone on the inflammatory profile. Echocardiography at the single 30 min observation post dive showed no significant differences between the two decompression procedures. Divers adopting the RDS showed a worsening of post-dive inflammatory profile compared to the CDM group, with significant increases in circulating chemokines CCL2 (P = 0.001) and CCL5 (P = 0.006) levels. There was no increase in chemokines following the CDM decompression. The air scuba group also showed a statistically significant increase in CCL2 (P < 0.001) and CCL5 (P = 0.003) levels post dive. No cases of decompression sickness occurred. The ratio deco strategy did not confer any benefit in terms of bubbles but showed the disadvantage of increased decompression-associated secretion of inflammatory chemokines involved in the development of vascular damage.

  15. Primitive retroperitoneal tumors. Vascular involvement--a major prognostic factor.

    Science.gov (United States)

    Lazar, A M; Brătucu, E; Straja, N D; Daha, C; Marincaş, M; Cirimbei, C; Prunoiu, V

    2012-01-01

    Primitive retroperitoneal tumors, although very rare, arouse an increased interest, because of the poor prognosis, unsatisfactory surgical and complementary therapy results. Up to now, the very low number of cases has impeded the acquisition of a unitary view of these tumors, a unanimously accepted algorithm of diagnostic and treatment being absent. Randomized trials regarding the effects of different therapies have not been possible. The main factor that can fundamentally increase the survival of these patients is radical resection, some authors even recommending compartmental surgery. We found no significant statistical difference between the survival rates of the patients with different types of non-radical interventions, that shoud be therefore, as much as possible, avoided. Our study evidences that vascular involvement is the main limiting factor in achieving radicality. The involvement of large retroperitoneal vessels makes often impossible a radical intervention, usually because of the lack of an adequate material and human endowment for ample vascular resections followed by laborious reconstructions. That is why, in our study, vascular involvement was associated with a decreased survival rate for operated patients. Therefore, we underline the necessity both of a solid material base and of establishing multidisciplinary surgical teams for adequate vascular interventions in oncologic general surgery.

  16. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille

    2009-01-01

    , C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise......, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated...... dephosphorylation at sites 2+2a, 3a, and 3a + 3b. Furthermore, we report the existence of several glycogen metabolism regulatory mechanisms based on GS intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to GS site 1b phosphorylation targeting...

  17. Organization of parent knowledge: compartmentalization and integration in adult child-parent relationships.

    Science.gov (United States)

    Limke, Alicia; Showers, Carolin J

    2010-09-01

    Previous research has demonstrated an association between structure of beliefs about romantic partners and feelings for that partner. Here, the structure of college students' beliefs about their parents was linked to distinct types of ongoing parent-child relationships identified by cluster analysis. An integrative structure of mother knowledge was associated with an evaluatively complex type of relationship ("dealing"), characterized by greater liking and closeness and less cooperation and contact. Positive compartmentalization of mother knowledge was associated with mother relationships that were consistently positive ("denying") across different dimensions. In contrast, the most positive father relationships were reported by daughters with evaluatively integrative father structures. Possible reasons for daughters' tendency to integrate father structures and to compartmentalize mother structures are discussed.

  18. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator.

    Science.gov (United States)

    Weitz, Maximilian; Kim, Jongmin; Kapsner, Korbinian; Winfree, Erik; Franco, Elisa; Simmel, Friedrich C

    2014-04-01

    In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function.

  19. [Gorham's disease and intra-osseous vascular abnormalities].

    Science.gov (United States)

    Héritier, Sébastien; Donadieu, Jean

    2012-05-01

    Gorham's disease is a rare condition of unknown etiology, which is characterized by intra-osseous vascular abnormalities leading to osteolysis and sometimes, extension to adjacent tissues. Although there is no histological evidence of malignancy, the lesions display an aggressive potential responsible of osteolysis with pathological fractures and respiratory failure. The extension of the disease varies from one location to multiple bone lesions throughout the skeleton and the clinical presentations depend on the sites of involvement. In the ISSVA (International Society for the Study of Vascular Abnormalities) classification, its affiliation to the group of vascular tumors or vascular malformations is still debated. To date, there is no standard treatment defined for this disease. The proposed treatments are inhibitors of bone resorption (bisphosphonates) and interferon alpha therapy or anti-angiogenic molecules. Radiation therapy and surgery may also have a place in the therapeutic strategy.

  20. Natural Isotopic Signatures of Variations in Body Nitrogen Fluxes: A Compartmental Model Analysis

    OpenAIRE

    Poupin, Nathalie; Mariotti, François; Huneau, Jean-François; Hermier, Dominique; Fouillet, Hélène

    2014-01-01

    Body tissues are generally N-15-enriched over the diet, with a discrimination factor (Delta N-15) that varies among tissues and individuals as a function of their nutritional and physiopathological condition. However, both N-15 bioaccumulation and intra-and inter-individual D N-15 variations are still poorly understood, so that theoretical models are required to understand their underlying mechanisms. Using experimental D N-15 measurements in rats, we developed a multi-compartmental model tha...

  1. Analysis of segmental phosphate absorption in intact rats. A compartmental analysis approach.

    OpenAIRE

    Kayne, L H; D'Argenio, D Z; Meyer, J H; Hu, M S; Jamgotchian, N; Lee, D B

    1993-01-01

    Available information supports the dominance of the proximal intestine in inorganic phosphate (Pi) absorption. However, there is no strategy for analyzing segmental Pi absorption from a spontaneously propelled meal in an intact animal. We propose a solution using compartmental analysis. After intragastric administration of a 32P-labeled Pi liquid meal containing a nonabsorbable marker, [14C]polyethylene glycol (PEG), rats were killed at 2, 10, 20, 30, 60, 120, and 240 min. The gastrointestina...

  2. A compartmentalized solute transport model for redox zones in contaminated aquifers--1, Theory and development

    Science.gov (United States)

    Abrams , Robert H.; Loague, Keith

    2000-01-01

    This paper, the first of two parts [see Abrams and Loague, this issue], takes the compartmentalized approach for the geochemical evolution of redox zones presented by Abrams et al. [1998] and embeds it within a solute transport framework. In this paper the compartmentalized approach is generalized to facilitate the description of its incorporation into a solute transport simulator. An equivalent formulation is developed which removes any discontinuities that may occur when switching compartments. Rate-limited redox reactions are modeled with a modified Monod relationship that allows either the organic substrate or the electron acceptor to be the rate-limiting reactant. Thermodynamic constraints are used to inhibit lower-energy redox reactions from occurring under infeasible geochemical conditions without imposing equilibrium on the lower-energy reactions. The procedure used allows any redox reaction to be simulated as being kinetically limited or thermodynamically limited, depending on local geochemical conditions. Empirical reaction inhibition methods are not needed. The sequential iteration approach (SIA), a technique which allows the number of solute transport equations to be reduced, is adopted to solve the coupled geochemical/solute transport problem. When the compartmentalized approach is embedded within the SIA, with the total analytical concentration of each component as the dependent variable in the transport equation, it is possible to reduce the number of transport equations even further than with the unmodified SIA. A one-dimensional, coupled geochemical/solute transport simulation is presented in which redox zones evolve dynamically in time and space. The compartmentalized solute transport (COMPTRAN) model described in this paper enables the development of redox zones to be simulated under both kinetic and thermodynamic constraints. The modular design of COMPTRAN facilitates the use of many different, preexisting solute transport and geochemical codes

  3. Guaranteed computation methods for compartmental in-series models under uncertainty

    OpenAIRE

    Pereda Sebastián, Diego de; Romero Vivó, Sergio; Ricarte Benedito, Beatriz; Bondía Company, Jorge

    2013-01-01

    The pattern of some real phenomenon can be described by compartmental in-series models. Nevertheless, most of these processes are characterized by their variability, which produces that the exact values of the model parameters are uncertain, although they can be bounded by intervals. The aim of this paper is to compute tight solution envelopes that guarantee the inclusion of all possible behaviors of such processes. Current methods, such as monotonicity analysis, enable us t...

  4. The construction of next-generation matrices for compartmental epidemic models

    OpenAIRE

    Diekmann, O.; Heesterbeek, J.A.P; Roberts, M G

    2009-01-01

    The basic reproduction number ℛ0 is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of ℛ0 where finitely many different categories of individuals are recognized. We clear up confusion that has been around in the literature concerning the construction of this matrix, specifically for the most frequently used so-called compartmental models. We present a detailed easy recipe for the ...

  5. Probing the compartmentalization of HIV-1 in the central nervous system through its neutralization properties.

    Science.gov (United States)

    Stefic, Karl; Chaillon, Antoine; Bouvin-Pley, Mélanie; Moreau, Alain; Braibant, Martine; Bastides, Frédéric; Gras, Guillaume; Bernard, Louis; Barin, Francis

    2017-01-01

    Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders. Dynamics of viral evolution were evaluated with a bayesian coalescent approach for individuals with longitudinal samples. Pseudotyped viruses expressing envelope glycoproteins variants representative of the quasi-species present in each compartment were generated, and their sensitivity to autologous neutralization, broadly neutralizing antibodies (bNAbs) and entry inhibitors was assessed. Significant compartmentalization of HIV populations between blood and CSF were detected in 5 out of 9 subjects. Some of the previously described genetic determinants for compartmentalization in the CNS were observed regardless of the HIV-1 clade. There was no difference of sensitivity to autologous neutralization between blood- and CSF-variants, even for subjects with compartmentalization, suggesting that selective pressure by autologous NAb is not the main driver of HIV evolution in the CNS. However, we observed major differences of sensitivity to sCD4 or to at least one bNAb targeting either the N160-V1V2 site, the N332-V3 site or the CD4bs, between blood- and CSF-variants in all cases. In particular, HIV-1 variants present in the CSF were more resistant to bNAbs than their blood counterpart in some cases. Considering the possible migration from CSF to blood, the CNS could be a reservoir of bNAb resistant viruses, an observation that should be considered for

  6. The effect of body position on compartmental intra-abdominal pressure following liver transplantation.

    Science.gov (United States)

    Cresswell, Adrian B; Jassem, Wayel; Srinivasan, Parthi; Prachalias, Andreas A; Sizer, Elizabeth; Burnal, William; Auzinger, Georg; Muiesan, Paolo; Rela, Mohammed; Heaton, Nigel D; Bowles, Matthew J; Wendon, Julia A

    2012-07-05

    Current assumptions rely on intra-abdominal pressure (IAP) being uniform across the abdominal cavity. The abdominal contents are, however, a heterogeneous mix of solid, liquid and gas, and pressure transmission may not be uniform. The current study examines the upper and lower IAP following liver transplantation. IAP was measured directly via intra-peritoneal catheters placed at the liver and outside the bladder. Compartmental pressure data were recorded at 10-min intervals for up to 72 h following surgery, and the effect of intermittent posture change on compartmental pressures was also studied. Pelvic intra-peritoneal pressure was compared to intra-bladder pressure measured via a FoleyManometer. A significant variation in upper and lower IAP of 18% was observed with a range of differences of 0 to 16 mmHg. A sustained difference in inter-compartmental pressure of 4 mmHg or more was present for 23% of the study time. Head-up positioning at 30° provided a protective effect on upper intra-abdominal pressure, resulting in a significant reduction in all patients. There was excellent agreement between intra-bladder and pelvic pressure. A clinically significant variation in inter-compartmental pressure exists following liver transplantation, which can be manipulated by changes to body position. The existence of regional pressure differences suggests that IAP monitoring at the bladder alone may under-diagnose intra-abdominal hypertension and abdominal compartment syndrome in these patients. The upper and lower abdomen may need to be considered as separate entities in certain conditions.

  7. The effect of body position on compartmental intra-abdominal pressure following liver transplantation

    OpenAIRE

    Cresswell, Adrian B; Jassem, Wayel; Srinivasan, Parthi; Andreas A Prachalias; Sizer, Elizabeth; Burnal, William; Auzinger, Georg; Muiesan, Paolo; Rela, Mohammed; Heaton, Nigel D; Bowles, Matthew J.; Wendon, Julia A

    2012-01-01

    Background Current assumptions rely on intra-abdominal pressure (IAP) being uniform across the abdominal cavity. The abdominal contents are, however, a heterogeneous mix of solid, liquid and gas, and pressure transmission may not be uniform. The current study examines the upper and lower IAP following liver transplantation. Methods IAP was measured directly via intra-peritoneal catheters placed at the liver and outside the bladder. Compartmental pressure data were recorded at 10-min intervals...

  8. A Residual Approach for Balanced Truncation Model Reduction (BTMR of Compartmental Systems

    Directory of Open Access Journals (Sweden)

    William La Cruz

    2014-05-01

    Full Text Available This paper presents a residual approach of the square root balanced truncation algorithm for model order reduction of continuous, linear and time-invariante compartmental systems. Specifically, the new approach uses a residual method to approximate the controllability and observability gramians, whose resolution is an essential step of the square root balanced truncation algorithm, that requires a great computational cost. Numerical experiences are included to highlight the efficacy of the proposed approach.

  9. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

    National Research Council Canada - National Science Library

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-01-01

    ...™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo...

  10. Verification of Compartmental Epidemiological Models using Metamorphic Testing, Model Checking and Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Ramanathan, Arvind [ORNL; Steed, Chad A [ORNL; Pullum, Laura L [ORNL

    2012-01-01

    Compartmental models in epidemiology are widely used as a means to model disease spread mechanisms and understand how one can best control the disease in case an outbreak of a widespread epidemic occurs. However, a significant challenge within the community is in the development of approaches that can be used to rigorously verify and validate these models. In this paper, we present an approach to rigorously examine and verify the behavioral properties of compartmen- tal epidemiological models under several common modeling scenarios including birth/death rates and multi-host/pathogen species. Using metamorphic testing, a novel visualization tool and model checking, we build a workflow that provides insights into the functionality of compartmental epidemiological models. Our initial results indicate that metamorphic testing can be used to verify the implementation of these models and provide insights into special conditions where these mathematical models may fail. The visualization front-end allows the end-user to scan through a variety of parameters commonly used in these models to elucidate the conditions under which an epidemic can occur. Further, specifying these models using a process algebra allows one to automatically construct behavioral properties that can be rigorously verified using model checking. Taken together, our approach allows for detecting implementation errors as well as handling conditions under which compartmental epidemiological models may fail to provide insights into disease spread dynamics.

  11. Self-concept structure and borderline personality disorder: evidence for negative compartmentalization.

    Science.gov (United States)

    Vater, Aline; Schröder-Abé, Michela; Weißgerber, Susan; Roepke, Stefan; Schütz, Astrid

    2015-03-01

    Borderline personality disorder (BPD) is characterized by an unstable and incongruent self-concept. However, there is a dearth of empirical studies investigating self-concept in BPD. In order to bridge this research gap, the purpose of this study was to apply an in-depth analysis of structural aspects of the self-concept in BPD. We examined the degree of compartmentalization, i.e., a tendency to organize knowledge about the self into discrete, extremely valenced (i.e., either positive or negative) categories (Showers, 1992). We hypothesized and found that BPD patients had the most compartmentalized self-concept structure and a higher proportion of negative self-attributes relative to both a non-clinical and a depressed control group. Moreover, BPD patients rated negative self-aspects as more important than positive ones relative to non-clinical controls. We cannot determine whether causal relationships exist between psychological symptoms and self-concept structure. Moreover, further comparisons to patients with other psychiatric disorders are necessary in order to further confirm the clinical specificity of our results. Our findings indicate that a negative compartmentalized self-concept is a specific feature of BPD. Implications for future research, psychological assessment, and psychotherapeutic treatment are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Lipid transfer proteins and the tuning of compartmental identity in the Golgi apparatus.

    Science.gov (United States)

    McDermott, Mark I; Mousley, Carl J

    2016-10-01

    The Golgi complex constitutes a central way station of the eukaryotic endomembrane system, an intricate network of organelles engaged in control of membrane trafficking and the processing of various cellular components. Previous ideas of compartmental stability within this network are gradually being reshaped by concepts describing a biochemical continuum of hybrid organelles whose constitution is regulated by compartmental maturation. Membrane lipid composition and lipid signaling processes make fundamental contributions to compartmentalization strategies that are themselves critical for organizing cellular architecture and biochemical activities. Phosphatidylinositol transfer proteins (PITPs) are increasingly recognized as key regulators of membrane trafficking through the secretory pathway. They do so by coordinating lipid metabolism with lipid signaling, translating this information to core protein components of the membrane trafficking machinery. In this capacity, PITPs can be viewed as regulators of an essential lipid-protein interface of cisternal maturation. It is also now becoming appreciated, for the first time, that such an interface plays important roles in larger systems processes that link secretory pathway function with cell proliferation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    Science.gov (United States)

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

    Energy Technology Data Exchange (ETDEWEB)

    DeLoache, William [Univ. of California, Berkeley, CA (United States); Russ, Zachary [Univ. of California, Berkeley, CA (United States); Samson, Jennifer [Univ. of California, Berkeley, CA (United States); Dueber, John [Univ. of California, Berkeley, CA (United States)

    2017-09-25

    The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.

  15. Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization

    Directory of Open Access Journals (Sweden)

    Scheffzek Klaus

    2005-10-01

    Full Text Available Abstract Background Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved. Results We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved. Conclusion We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.

  16. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

    2009-04-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  17. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2009-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  18. The lymphatic vascular system of the mouse head

    OpenAIRE

    Lohrberg, Melanie; Wilting, Jörg

    2016-01-01

    Histological studies of the lymphatic vascular system in adult mice are hampered because bones cannot be sectioned properly. Here, we decalcified the heads of 14-day-old mice, embedded them in paraffin and stained resultant serial sections with the lymphendothelial-specific antibodies Lyve-1 and Podoplanin. We show that the tissues with the highest lymphatic vascular density are the dermis and the oral mucous membranes. In contrast, the nasal mucous membrane is devoid of lymphatics, except fo...

  19. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  20. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  1. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...

  2. [Aneurysmal bone cyst of the mandible].

    Science.gov (United States)

    Onerci, M; Ergin, N T

    1996-05-01

    Aneurysmal bone cysts are benign lesions of bone consisting of a septated, cystic cavity filled with non-endothelium-lined, blood-filled spaces. Aneurysmal bone cysts mainly occur in children and adolescents. Only a few occur in the jaws. This is the report of a 9-year-old girl with an aneurysmal bone cyst in the condyle of the mandible who was admitted to the hospital with swelling in front of her right ear. Because of the location and to eliminate recurrence, complete surgical excision of the condyle was performed. Fifty-seven cases of aneurysmal bone cyst of the mandible have been reported to date. Aneurysmal bone cyst is treated by surgical excision, which ranges from enucleation and curettage to conservative resection. Simple curettage for aneurysmal bone cyst is reported to be associated with a high recurrence rate, a result of the difficulty of completely excising such a vascular lesion. We recommend complete surgical excision as the best treatment.

  3. Organ printing: the future of bone regeneration?

    Science.gov (United States)

    Fedorovich, Natalja E; Alblas, Jacqueline; Hennink, Wim E; Oner, F Cumhur; Dhert, Wouter J A

    2011-12-01

    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Uterine vascular lesions.

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.

  5. Vascular biology of preeclampsia.

    Science.gov (United States)

    Myatt, L; Webster, R P

    2009-03-01

    Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.

  6. Aneurysmal bone cyst of the frontal sinus.

    Science.gov (United States)

    Liu, J H; Newcomer, M T; Murray, A D; Myer, C M

    2001-01-01

    Aneurysmal bone cysts are benign, vascular, cystic osseous tumors. Approximately 2% of all aneurysmal bone cysts are found in the head and neck region, with the most common site being the mandible. We report a case of an aneurysmal bone cyst arising from the frontal sinus in a pediatric patient. The diagnosis was suggested through various radiographic studies, with the final pathologic diagnosis confirmed after tumor excision. Complete en-bloc excision was performed by using a bifrontal craniotomy approach, with immediate reconstruction of the defect by using a split calvarial bone graft.

  7. Inflammation, Fracture and Bone Repair

    Science.gov (United States)

    Loi, Florence; Córdova, Luis A.; Pajarinen, Jukka; Lin, Tzu-hua; Yao, Zhenyu; Goodman, Stuart B.

    2016-01-01

    The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair. PMID:26946132

  8. Bone Markers

    Science.gov (United States)

    ... Diabetes Diarrhea Disseminated Intravascular Coagulation (DIC) Down Syndrome Ebola Virus Infection Endocrine System and Syndromes Epilepsy Excessive ... to keep bones alive and sturdy. During early childhood and in the teenage years, new bone is ...

  9. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (possification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Clinical Application of Vascular Regenerative Therapy for Peripheral Artery Disease

    Directory of Open Access Journals (Sweden)

    Hiroshi Suzuki

    2013-01-01

    Full Text Available Prognosis of peripheral artery disease (PAD, especially critical limb ischemia, is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in leg amputation and, therefore, vascular regenerative therapy is expected in this field. Gene therapy using vascular endothelial growth factor is the first step of vascular regenerative therapy, but did not confirm effectiveness in a large-scale randomized comparative study. Based on animal experiments, bone marrow mononuclear cells (MNCs, peripheral blood MNCs were used as the cell source for regenerative therapy. Those cells were confirmed to be effective to decrease rest pain and ulcer size, but its effect was not fully satisfied. Mesenchymal stem cells (MSCs are expected as an effective cell source for vascular regeneration and clinical studies are ongoing, because the cells are able to differentiate into various cell types and produce a significant amount of vascular growth factors. Of vascular regeneration therapy, peripheral MNCs and bone marrow MNCs were recognized as advanced medical technology but do not attain to the standard therapy. However, clinical use of MSCs have already started, and induced pluripotent stem cells are surely promising tool for vascular regeneration therapy although further basic studies are required for clinical application.

  11. A Role for the Endothelium in Vascular Calcification

    Science.gov (United States)

    Yao, Yucheng; Jumabay, Medet; Ly, Albert; Radparvar, Melina; Cubberly, Mark R.; Boström, Kristina I.

    2013-01-01

    Rationale Vascular calcification is a regulated process that involves osteoprogenitor cells and frequently complicates common vascular disease such as atherosclerosis and diabetic vasculopathy. However, it is not clear if the vascular endothelium has a role in contributing osteoprogenitor cells to the calcific lesions. Objective To determine if the vascular endothelium contributes osteoprogenitor cells to vascular calcification. Methods and Results In this study, we use two mouse models of vascular calcification, mice with gene deletion of matrix Gla protein (MGP), a BMP-inhibitor, and Ins2Akita/+ mice, a diabetes model. We show that enhanced bone morphogenetic protein (BMP) signaling in both types of mice stimulates the vascular endothelium to contribute osteoprogenitor cells to the vascular calcification. The enhanced BMP signaling results in endothelial-mesenchymal transitions and the emergence of multipotent cells, followed by osteoinduction. Endothelial markers co-localize with multipotent and osteogenic markers in calcified arteries by immunostaining and fluorescence-activated cell sorting. Lineage tracing using Tie2-Gfp transgenic mice supports an endothelial origin of the osteogenic cells. Enhancement of MGP expression in Ins2Akita/+ mice, as mediated by an Mgp transgene limits the generation of multipotent cells. Moreover, MGP-depleted human aortic endothelial cells in vitro acquire multipotency rendering the cells susceptible to osteoinduction by BMP and high glucose. Conclusions Our data suggest that the endothelium is a source of osteoprogenitor cells in vascular calcification that occurs in disorders with high BMP activation such as deficiency of BMP inhibitors and diabetes. PMID:23852538

  12. Using biplanar fluoroscopy to guide radiopaque vascular injections: a new method for vascular imaging.

    Directory of Open Access Journals (Sweden)

    Haley D O'Brien

    Full Text Available Studying vascular anatomy, especially in the context of relationships with hard tissues, is of great interest to biologists. Vascular studies have provided significant insight into physiology, function, phylogenetic relationships, and evolutionary patterns. Injection of resin or latex into the vascular system has been a standard technique for decades. There has been a recent surge in popularity of more modern methods, especially radiopaque latex vascular injection followed by CT scanning and digital "dissection." This technique best displays both blood vessels and bone, and allows injections to be performed on cadaveric specimens. Vascular injection is risky, however, because it is not a standardizable technique, as each specimen is variable with regard to injection pressure and timing. Moreover, it is not possible to view the perfusion of injection medium throughout the vascular system of interest. Both data and rare specimens can therefore be lost due to poor or excessive perfusion. Here, we use biplanar video fluoroscopy as a technique to guide craniovascular radiopaque latex injection. Cadaveric domestic pigs (Sus scrofa domestica and white-tailed deer (Odocoileus virginianus were injected with radiopaque latex under guidance of fluoroscopy. This method was found to enable adjustments, in real-time, to the rate, location, and pressure at which latex is injected in order to avoid data and specimen loss. In addition to visualizing the injection process, this technique can be used to determine flow patterns, and has facilitated the development of consistent markers for complete perfusion.

  13. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...

  14. Bone pathology inpsoriatic arthritis

    Directory of Open Access Journals (Sweden)

    V. V. Badokin

    2007-01-01

    Full Text Available Objective. To study different variants of osteolysis in pts with psoriatic arthritis (PA and to reveal their relationship with other clinico-radiological features of joint damage. Material and methods. 370 pts with definite PA having different variants of joint damage were included. Radiological examination of bones and joints (in some cases large picture frame was performed. Morphological evaluation of synovial biopsies was done in 34 pts with PA and 10 pts with rheumatoid arthritis (RA. Results. Different types of osteolysis were revealed in 80 (21,6% pts. Osteolytic variant of joint damage was present in 29 pts. 33 pts had acral, 48 — intra-articular osteolysis and 16 - true bone atrophy. Frequency and intensity of bone resorption were associated with severity of PA. Acral osteolysis correlated with arthritis of distal interphalangeal joints and onychodystrophy. Intra-articular osteolysis was most often present in distal interphalangeal joints of hands and metacarpophalangeal joints (39,6% and 41,7% respectively. Characteristic feature of PA was combination of prominent resorption with formation of bone ankylosis and periosteal reaction. Ankylosis was present in 33,3% of pts with intra-articular osteolysis and in 60% of pts with combination of different osteolysis variants. Systemic reaction of microcirculation in synovial biopsies was most prominent in osteolytic variant: marked thickening of capillary and venule basal membrane with high level of acid phosphatase, increased capillary and precapillary blood flow with stasis features, vascular lymphocyte and macrophage infiltration, productive vasculitis with annular wall thickening, thrombovasculitis and villi deep layer sclerosis. Conclusion. Different variants of osteolysis show bone involvement in PA. Acral and intra- articular osteolysis association with bone ankylosis and periostitis proves their common pathogenetic entity.

  15. Vascular cognitive impairment and vascular dementia

    Directory of Open Access Journals (Sweden)

    Klavdija Ovčar

    2017-09-01

    Full Text Available In the developed world, five to ten percent of people older than 65 years have dementia. One fifth of dementia etiologies are due to vascular brain lesions (VaD – vascular dementia. A milder form is called vascular cognitive impairment (VCI. The main clinical criteria for VaD are: 1. cognitive decline verified with standardized cognitive test/scale, 2. evidence of the associated vascular brain lesion, 3. excluded reversible causes of cognitive decline. The main risk factors for VaD are age, atherosclerosis, diabetes and hypertension. They play a key role in pathogenesis of the cognitive impairment. Depending on the damaged brain region, different cognitive domains may be affected with or without other neurological signs. These diversities in the clinical picture challenge the correct diagnosis. Unique feature of VaD is its progression, which can be stopped, if patients receive an appropriate treatment.The treatment of VCI and VaD symptoms is similar to that in Alzheimer’s disease. More importantly, VCI may be slowed down or even stopped with proper secondary stroke prevention and good rehabilitation. The most efficient is primary stroke prevention with healthy lifestyle and treatment of acquired risk factors.

  16. Vascular disease burden in Indian subjects with vascular dementia.

    Science.gov (United States)

    Chandra, Mina; Anand, Kuljeet Singh

    2015-01-01

    Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia. To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia. In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis. Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001). People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.

  17. DISTING: A web application for fast algorithmic computation of alternative indistinguishable linear compartmental models.

    Science.gov (United States)

    Davidson, Natalie R; Godfrey, Keith R; Alquaddoomi, Faisal; Nola, David; DiStefano, Joseph J

    2017-05-01

    We describe and illustrate use of DISTING, a novel web application for computing alternative structurally identifiable linear compartmental models that are input-output indistinguishable from a postulated linear compartmental model. Several computer packages are available for analysing the structural identifiability of such models, but DISTING is the first to be made available for assessing indistinguishability. The computational algorithms embedded in DISTING are based on advanced versions of established geometric and algebraic properties of linear compartmental models, embedded in a user-friendly graphic model user interface. Novel computational tools greatly speed up the overall procedure. These include algorithms for Jacobian matrix reduction, submatrix rank reduction, and parallelization of candidate rank computations in symbolic matrix analysis. The application of DISTING to three postulated models with respectively two, three and four compartments is given. The 2-compartment example is used to illustrate the indistinguishability problem; the original (unidentifiable) model is found to have two structurally identifiable models that are indistinguishable from it. The 3-compartment example has three structurally identifiable indistinguishable models. It is found from DISTING that the four-compartment example has five structurally identifiable models indistinguishable from the original postulated model. This example shows that care is needed when dealing with models that have two or more compartments which are neither perturbed nor observed, because the numbering of these compartments may be arbitrary. DISTING is universally and freely available via the Internet. It is easy to use and circumvents tedious and complicated algebraic analysis previously done by hand. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Nuclear matrix and structural and functional compartmentalization of the eucaryotic cell nucleus.

    Science.gov (United States)

    Razin, S V; Borunova, V V; Iarovaia, O V; Vassetzky, Y S

    2014-07-01

    Becoming popular at the end of the 20th century, the concept of the nuclear matrix implies the existence of a nuclear skeleton that organizes functional elements in the cell nucleus. This review presents a critical analysis of the results obtained in the study of nuclear matrix in the light of current views on the organization of the cell nucleus. Numerous studies of nuclear matrix have failed to provide evidence of the existence of such a structure. Moreover, the existence of a filamentous structure that supports the nuclear compartmentalization appears to be unnecessary, since this function is performed by the folded genome itself.

  19. Reconstruction and modeling protein translocation and compartmentalization in Escherichia coli at the genome-scale

    DEFF Research Database (Denmark)

    Liu, Joanne K.; O’Brien, Edward J.; Lerman, Joshua A.

    2014-01-01

    cell morphology. Comparison of computations performed with this expanded ME-model, named iJL1678-ME, against available experimental data reveals that the model accurately describes translocation pathway expression and the functional proteome by compartmentalized mass. Conclusion: iJL1678-ME enables...... the functional content of membranes, cellular compartment-specific composition, and that it can be utilized to examine the effect of perturbing an expanded set of network components. iJL1678-ME takes a notable step towards the inclusion of cellular ultra-structure in genome-scale models....

  20. A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Vahidi, O; Kwok, K E; Gopaluni, R B

    2016-01-01

    We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main...... obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization...

  1. Connective tissue: Vascular and hematological (blood) support.

    Science.gov (United States)

    Calvino, Nick

    2003-01-01

    Connective Tissue (CT) is a ubiquitous component of all major tissues and structures of the body (50% of all body protein is CT), including that of the blood, vascular, muscle, tendon, ligament, fascia, bone, joint, IVD's (intervertebral discs) and skin. Because of its ubiquitous nature, CT is an often overlooked component of any essential nutritional program that may address the structure, and/or function of these tissues. The central role of CT in the health of a virtually all cells, tissues, organs, and organ systems, is discussed. General nutritional CT support strategies, as well as specific CT support strategies that focus on blood, vascular, structural system (eg, muscles, tendons, ligaments, fascia, bone, and joints), integument (skin) and inflammatory and immune mediation will be discussed here and will deal with connective tissue dynamics and dysfunction. An overview of the current scientific understanding and possible options for naturally enhancing the structure and function of CT through the application of these concepts will be discussed in this article, with specific attention on the vascular and hematological systems.

  2. The role of vascular endothelial growth factor in ossification

    Science.gov (United States)

    Yang, Yan-Qi; Tan, Ying-Ying; Wong, Ricky; Wenden, Alex; Zhang, Lin-Kun; Rabie, A Bakr M

    2012-01-01

    Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator during these processes. It not only functions in bone angiogenesis but also in various aspects of bone development. PMID:22722639

  3. Increased vascular endothelial growth factor (VEGF) expression in ...

    African Journals Online (AJOL)

    Vascular endothelial growth factor (VEGF), a well known angiogenic factor, has been shown to have direct and/or indirect influence on spinal cord injury (SCI). The purpose of this study is to observe VEGF expression changes in rats with SCI by bone marrow stromal cells (BMSCs) treatment. The mRNA expression of VEGF ...

  4. Vascular remodelling in asthma.

    Science.gov (United States)

    Walters, Eugene Haydn; Soltani, Amir; Reid, David William; Ward, Chris

    2008-02-01

    We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

  5. [Vascular injuries in joint replacement surgery].

    Science.gov (United States)

    Novotný, K; Pádr, R; Landor, I; Sosna, A

    2011-01-01

    Iatrogenic injuries to blood vessels in joint replacement surgery are rare events that occur as few per thousand. However, their sequelae are serious. The patient may either bleed to death, because vascular injury is not obvious and therefore difficult to diagnose, or lose the limb due to ischaemia. The highest risk of vascular injury is associated with repeat surgery and loosening of the acetabular component. We distinguish sharp and blunt force injuries. The former are caused by implants, sharp instruments, bone fragments or bone cement debris. The latter arise from stretching over a part of implanted material. Bleeding can be inapparent or apparent. Inapparent bleeding is difficult to diagnose and is recognized from the dynamics of blood losses. Haemodynamic instability or, in a worse case, even hypovolaemic shock may be the only signs of bleeding. Occlusion of an artery is manifested by limb ischaemia. The seriousness and progression of ischaemia depends on the rate of arterial occlusion, potential pathways for collateral circulation and the degree of atherosclerotic vascular disease. The patient with conduction anaesthesia does not feel pain and therefore the diagnosis must primarily be based on arterial pulsation in the limb and its skin colour. A pseudoaneurysm can develop due to a partially weakened vascular wall and its rupture is a life-threatening complication. Its presence is recognized as a pulsating mass in the groin. An arterio- venous fistula which arises from traumatic communication between the two vessels may lead to cardiac failure. The diagnosis is based on examination by sonography and digital subtraction angiography. The results of CT angiography and MR angiography are difficult to evaluate because of the presence of metal implants. In apparent bleeding it is sometimes difficult to locate the source. It is recommended to perform digital compression and gain access to the vessels from the extraperitoneal approach. When an expanding haematoma or

  6. Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants.

    Science.gov (United States)

    Hui, Cang; Richardson, David M; Pyšek, Petr; Le Roux, Johannes J; Kučera, Tomáš; Jarošík, Vojtěch

    2013-01-01

    Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities.

  7. Personalization of a compartmental physiological model for an artificial pancreas through integration of patient's state estimation.

    Science.gov (United States)

    Jallon, P; Lachal, S; Franco, C; Charpentier, G; Huneker, E; Doron, M; Franc, Sylvia; Benhamou, Pierre-Yves; Borot, Sophie; Guerci, Bruno; Hanaire, He le Ne; Jeandidier, Nathalie; Penfornis, Alfred; Renard, Eric; Reznik, Yves; Schaepelynck, Pauline; Simon, Chantal

    2017-07-01

    Artificial Pancreas (AP) are developed for patients with Type 1 diabetes. This medical device system consists in the association of a subcutaneous continuous glucose monitor (CGM) providing a proxy of the patient's glycaemia and a control algorithm offering the real-time modification of the insulin delivery with an automatic command of the subcutaneous insulin pump. The most complex algorithms are based on a compartmental model of the glucoregulatory system of the patient coupled to an approach of MPC (Model-Predictive-Control) for the command. The automatic and unsupervised control of insulin regulation constitutes a major challenge in AP projects. A given model with its parameterization on the shelf will not directly represent the patient's data behavior and the personalization of the model is a prerequisite before using it in a MPC. The present paper focuses on the personalization of a compartmental showing a method where taking into account the estimation of the patient's state in addition to the parameter estimation improves the results in terms of mean quadratic error.

  8. A compartmental model of the cAMP/PKA/MAPK pathway in Bio-PEPA

    Directory of Open Access Journals (Sweden)

    Federica Ciocchetta

    2009-11-01

    Full Text Available The vast majority of biochemical systems involve the exchange of information between different compartments, either in the form of transportation or via the intervention of membrane proteins which are able to transmit stimuli between bordering compartments. The correct quantitative handling of compartments is, therefore, extremely important when modelling real biochemical systems. The Bio-PEPA process algebra is equipped with the capability of explicitly defining quantitative information such as compartment volumes and membrane surface areas. Furthermore, the recent development of the Bio-PEPA Eclipse Plug-in allows us to perform a correct stochastic simulation of multi-compartmental models. Here we present a Bio-PEPA compartmental model of the cAMP/PKA/MAPK pathway. We analyse the system using the Bio-PEPA Eclipse Plug-in and we show the correctness of our model by comparison with an existing ODE model. Furthermore, we perform computational experiments in order to investigate certain properties of the pathway. Specifically, we focus on the system response to the inhibition and strengthening of feedback loops and to the variation in the activity of key pathway reactions and we observe how these modifications affect the behaviour of the pathway. These experiments are useful to understand the control and regulatory mechanisms of the system.

  9. Metabolism of monoterpenes: evidence for compartmentation of l-menthone metabolism in peppermint (Mentha piperita) leaves

    Energy Technology Data Exchange (ETDEWEB)

    Martinkus, C.; Croteau, R.

    1981-01-01

    Previous studies have shown that the monoterpene ketone l-(G-/sup 3/H)-menthone is reduced to the epimeric alcohols l-menthol and d-neomenthol in leaf discs of flowering peppermint (Mentha piperita L.), and that a portion of the menthol is converted to menthyl acetate while the bulk of the neomenthol is transformed to neomenthyl-..beta..-D-glucoside. When l-(3-/sup 3/H)menthol and d-(3-/sup 3/H)neomenthol are separately administered to leaf discs, both menthyl and neomenthyl acetates and menthyl and neomenthyl glucosides are formed with nearly equal facility, suggesting that the metabolic specificity observed with the ketone precursor was not a function of the specificity of the transglucosylase or transacetylase but rather a result of compartmentation of each stereospecific dehydrogenase with the appropriate transferase. Co-purification of the acceptor-mediated activities, and differential activation and inhibition studies, provided strong evidence that the same UDP-glucose-dependent enzyme could transfer glucose to either l-menthol or d-neometnthol. These results demonstrate that the specific in vivo conversion of l-menthone to l-menthyl acetate and d-neomenthyl-..beta..-D-glucoside cannot be attributed to the selectivity of the transferases, and they clearly indicate that the metabolic specificity observed is a result of compartmentation effects.

  10. Structure of the archaeal pab87 peptidase reveals a novel self-compartmentalizing protease family.

    Directory of Open Access Journals (Sweden)

    Vanessa Delfosse

    Full Text Available Self-compartmentalizing proteases orchestrate protein turnover through an original architecture characterized by a central catalytic chamber. Here we report the first structure of an archaeal member of a new self-compartmentalizing protease family forming a cubic-shaped octamer with D(4 symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 A resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 A wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 A wide central chamber holding the eight active sites. Surprisingly, activity assays revealed that Pab87 degrades specifically d-amino acid containing peptides, which have never been observed in archaea. Genomic context of the Pab87 gene showed that it is surrounded by genes involved in the amino acid/peptide transport or metabolism. We propose that CubicO proteases are involved in the processing of d-peptides from environmental origins.

  11. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    Directory of Open Access Journals (Sweden)

    María Camila Alvarez-Silva

    Full Text Available Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  12. Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs.

    Science.gov (United States)

    Rende, Francesca; Cavallari, Ilaria; Corradin, Alberto; Silic-Benussi, Micol; Toulza, Frederic; Toffolo, Gianna M; Tanaka, Yuetsu; Jacobson, Steven; Taylor, Graham P; D'Agostino, Donna M; Bangham, Charles R M; Ciminale, Vincenzo

    2011-05-05

    Human T-cell leukemia virus type 1 (HTLV-1) codes for 9 alternatively spliced transcripts and 2 major regulatory proteins named Tax and Rex that function at the transcriptional and posttranscriptional levels, respectively. We investigated the temporal sequence of HTLV-1 gene expression in primary cells from infected patients using splice site-specific quantitative RT-PCR. The results indicated a two-phase kinetics with the tax/rex mRNA preceding expression of other viral transcripts. Analysis of mRNA compartmentalization in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of the two-phase kinetics and revealed strong nuclear retention of HBZ mRNAs, supporting their function as noncoding transcripts. Mathematical modeling underscored the importance of a delay between the functions of Tax and Rex, which was supported by experimental evidence of the longer half-life of Rex. These data provide evidence for a temporal pattern of HTLV-1 expression and reveal major differences in the intracellular compartmentalization of HTLV-1 transcripts.

  13. Proline accumulation, ions dynamics and sodium root-shoot partition and compartmentation

    Directory of Open Access Journals (Sweden)

    Jesus Emanuel eBojorquez Quintal

    2014-11-01

    Full Text Available Despite its economic relevance, little is known about salt tolerance mechanisms in pepper plants. To address this question, we compared differences in responses to NaCl in two Capsicum chinense varieties: Rex (tolerant and Chichen-Itza (sensitive. Under salt stress (150 mM NaCl over 7 days roots of Rex variety accumulated 50 times more compatible solutes such as proline compared to Chichen-Itza. Mineral analysis indicated that Na+ is restricted to roots by preventing its transport to leaves. Fluorescence analysis suggested an efficient Na+ compartmentalization in vacuole-like structures and in small intracellular compartments in roots of Rex variety. At the same time, Na+ in Chichen-Itza plants was compartmentalized in the apoplast, suggesting substantial Na+ extrusion. Rex variety was found to retain more K+ in its roots under salt stress according to a mineral analysis and microelectrode ion flux estimation (MIFE. Vanadate-sensitive H+ efflux was higher in Chichen-Itza variety plants, suggesting a higher activity of the plasma membrane H+-ATPase, which fuels the extrusion of Na+, and, possibly, also the re-uptake of K+. Our results suggest a combination of stress tolerance mechanisms, in order to alleviate the salt-induced injury. Furthermore, Na+ extrusion to apoplast does not appear to be an efficient strategy for salt tolerance in pepper plants.

  14. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    Science.gov (United States)

    Alvarez-Silva, María Camila; Álvarez-Yela, Astrid Catalina; Gómez-Cano, Fabio; Zambrano, María Mercedes; Husserl, Johana; Danies, Giovanna; Restrepo, Silvia; González-Barrios, Andrés Fernando

    2017-01-01

    Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA) were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  15. Detecting compartmental non-Gaussian diffusion with symmetrized double-PFG MRI.

    Science.gov (United States)

    Paulsen, Jeffrey L; Özarslan, Evren; Komlosh, Michal E; Basser, Peter J; Song, Yi-Qiao

    2015-11-01

    Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth cumulant (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics, and act as a novel source of contrast to better resolve tissue micro-structure. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Neonatal Resuscitation Training: Implications of Course Construct and Discipline Compartmentalization on Role Confusion and Role Ambiguity.

    Science.gov (United States)

    Jnah, Amy J; Newberry, Desi M; Trembath, Andrea N; Robertson, Tracey; Downing, April; Greene, Miriam; Sewell, Kerry

    2016-06-01

    The Neonatal Resuscitation Program's (NRP's) Sixth Edition introduced simulation-based training (SBT) into neonatal life support training. SBT offers neonatal emergency response teams a safe, secure environment to rehearse coordinated neonatal resuscitations. Teamwork and communication training can reduce tension and anxiety during neonatal medical emergencies. To discuss the implications of variability in number and type of simulation scenario, number and type of learners who comprise a course, and their influence upon scope of practice, role confusion, and role ambiguity. Relevant articles from MEDLINE, CINAHL, EMBASE, Google Scholar, the World Health Organization, the American Heart Association, and NRP were included in this integrative review of the literature. Purposeful synergy of optimal SBT course construct with teamwork and communication can resist discipline compartmentalization, role confusion, and role ambiguity. Five key themes were identified and coined the "5 Rights" of NRP SBT. These "5 Rights" can guide healthcare institutions with planning, implementation, and evaluation of NRP SBT courses. NRP SBT can facilitate optimal team function and reduce errors when teams of learners and varied scenarios are woven into the course construct. The simulated environment must be realistic and fully equipped to encourage knowledge transfer and attainment of the NRP's key behavioral outcomes. Investigation of teamwork and communication training with NRP SBT, course construct, discipline compartmentalization, and behavioral and clinical outcomes is indicated. Investigation of outcomes of SBT using a team-teaching model, combining basic and advanced practice NRP instructors, is indicated.

  17. Multi-scale hierarchical approach for parametric mapping: assessment on multi-compartmental models.

    Science.gov (United States)

    Rizzo, G; Turkheimer, F E; Bertoldo, A

    2013-02-15

    This paper investigates a new hierarchical method to apply basis function to mono- and multi-compartmental models (Hierarchical-Basis Function Method, H-BFM) at a voxel level. This method identifies the parameters of the compartmental model in its nonlinearized version, integrating information derived at the region of interest (ROI) level by segmenting the cerebral volume based on anatomical definition or functional clustering. We present the results obtained by using a two tissue-four rate constant model with two different tracers ([(11)C]FLB457 and [carbonyl-(11)C]WAY100635), one of the most complex models used in receptor studies, especially at the voxel level. H-BFM is robust and its application on both [(11)C]FLB457 and [carbonyl-(11)C]WAY100635 allows accurate and precise parameter estimates, good quality parametric maps and a low percentage of voxels out of physiological bound (modeling at the voxel level. In particular, different from other proposed approaches, this method can also be used when the linearization of the model is not appropriate. We expect that applying it to clinical data will generate reliable parametric maps. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Modified Laminar Bone in Ampelosaurus atacis and Other Titanosaurs (Sauropoda): Implications for Life History and Physiology

    OpenAIRE

    Nicole Klein; Martin Sander, P.; Koen Stein; Jean Le Loeuff; Carballido, Jose L.; Eric Buffetaut

    2012-01-01

    BACKGROUND: Long bone histology of the most derived Sauropoda, the Titanosauria suggests that titanosaurian long bone histology differs from the uniform bone histology of basal Sauropoda. Here we describe the long bone histology of the titanosaur Ampelosaurus atacis and compare it to that of basal neosauropods and other titanosaurs to clarify if a special titanosaur bone histology exists. METHODOLOGY/PRINCIPAL FINDINGS: Ampelosaurus retains the laminar vascular organization of basal Sauropoda...

  19. Vascular patterning in human heterotopic ossification.

    Science.gov (United States)

    Cocks, Margaret; Mohan, Aditya; Meyers, Carolyn A; Ding, Catherine; Levi, Benjamin; McCarthy, Edward; James, Aaron W

    2017-05-01

    Heterotopic ossification (HO, also termed myositis ossificans) is the formation of extra-skeletal bone in muscle and soft tissues. HO is a tissue repair process gone awry, and is a common complication of surgery and traumatic injury. Medical strategies to prevent and treat HO fall well short of addressing the clinical need. Better characterization of the tissues supporting HO is critical to identifying therapies directed against this common and sometimes devastating condition. The physiologic processes of osteogenesis and angiogenesis are highly coupled and interdependent. However, few efforts have been made to document the vascular patterning within heterotopic ossification. Here, surgical pathology case files of 29 human HO specimens were examined by vascular histomorphometric analysis. Results demonstrate a temporospatial patterning of HO vascularity that depends on the "maturity" of the bony lesion. In sum, human HO demonstrates a time- and space-dependent pattern of vascularization suggesting a coupled pathophysiologic process involving the coordinate processes of osteogenesis and angiogenesis. Further imaging studies may be used to further characterize vasculogenesis within HO and whether anti-angiogenic therapies are a conceivable future therapy for this common condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Understanding Vascular Endothelium

    OpenAIRE

    Gimbrone, Michael A.

    2014-01-01

    Understanding Vascular Endothelium : Nature’s Container for Blood The entire cardiovascular system, from the chambers of the heart to the smallest capillaries of peripheral tissues, is lined by a single-cell-thick continuous layer—the vascular endothelium. For many years, this gossamer membrane was thought to function largely as an inert barrier, passively separating the reactive components of the circulating blood from the cells and connective tissue matrix of the various organs of the body....

  1. Hypercholesterolaemia and vascular dementia

    OpenAIRE

    Appleton, Jason P.; Scutt, Polly; Sprigg, Nikola; Bath, Philip M.

    2017-01-01

    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors–diabetes, hypercholesterolaemia, hypertension and smoking–are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet no...

  2. Central nervous system compartmentalization of HIV-1 subtype C variants early and late in infection in young children.

    Directory of Open Access Journals (Sweden)

    Christa Buckheit Sturdevant

    2012-12-01

    Full Text Available HIV-1 subtype B replication in the CNS can occur in CD4+ T cells or macrophages/microglia in adults. However, little is known about CNS infection in children or the ability of subtype C HIV-1 to evolve macrophage-tropic variants. In this study, we examined HIV-1 variants in ART-naïve children aged three years or younger to determine viral genotypes and phenotypes associated with HIV-1 subtype C pediatric CNS infection. We examined HIV-1 subtype C populations in blood and CSF of 43 Malawian children with neurodevelopmental delay or acute neurological symptoms. Using single genome amplification (SGA and phylogenetic analysis of the full-length env gene, we defined four states: equilibrated virus in blood and CSF (n = 20, 47%, intermediate compartmentalization (n = 11, 25%, and two distinct types of compartmentalized CSF virus (n = 12, 28%. Older age and a higher CSF/blood viral load ratio were associated with compartmentalization, consistent with independent replication in the CNS. Cell tropism was assessed using pseudotyped reporter viruses to enter a cell line on which CD4 and CCR5 receptor expression can be differentially induced. In a subset of compartmentalized cases (n = 2, 17%, the CNS virus was able to infect cells with low CD4 surface expression, a hallmark of macrophage-tropic viruses, and intermediate compartmentalization early was associated with an intermediate CD4 entry phenotype. Transmission of multiple variants was observed for 5 children; in several cases, one variant was sequestered within the CNS, consistent with early stochastic colonization of the CNS by virus. Thus we hypothesize two pathways to compartmentalization: early stochastic sequestration in the CNS of one of multiple variants transmitted from mother to child, and emergence of compartmentalized variants later in infection, on average at age 13.5 months, and becoming fully apparent in the CSF by age 18 months. Overall, compartmentalized viral

  3. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2008-02-01

    length from the tibial fusion site, and then stop which would be consistent with the resorption being associated with the lack of weight bearing load. In...Defect in the Rat Femur with Use of a Vascularized Periosteal Flap, a Biodegradable Matric, and Bone Morphogenetic Protein. J Bone Joint Surg 87-A(6

  4. Bone Gap Management Using Linear Rail System (LRS): Initial ...

    African Journals Online (AJOL)

    Background: Vascularized fibular grafting, free fibular graft, tibia profibula synostosis, amputation with a good prosthesis and Ilizarov technique are some of the suitable options for managing bone gaps that result from trauma or treatment of tumours, bone infection, congenital pseudoarthrosis and repeated failed ...

  5. Cortical and cancellous bone: age-related changes in morphologic features, fluid spaces, and calcium homeostasis in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Simonet, W.T.; Bronk, J.T.; Pinto, M.R.; Williams, E.A.; Meadows, T.H.; Kelly, P.J.

    1988-02-01

    The changes in cortical and cancellous bone that occur with aging were studied by measuring morphologic and physiologic variables for both types of bone in dogs. The percentage area of cortical and cancellous bone, rate of bone formation, vascular volume, bone water, and volume of distribution of calcium tracer all showed statistically significant changes at the time of bone maturity. Canine cortical bone cell volume progressively decreased with advancing age, and cancellous bone cell volume significantly decreased between adult and old dogs. The volume of distribution technique can be used to determine the relative contributions of cortical and cancellous bone to the total body exchangeable calcium ion pool.

  6. Bisphophonates in CKD Patients with Low Bone Mineral Density

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2013-01-01

    Full Text Available Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD have a high risk of bone fracture because of low bone mineral density and poor bone quality. Osteoporosis also features low bone mass, disarranged microarchitecture, and skeletal fragility, and differentiating between osteoporosis and CKD-MBD in low bone mineral density is a challenge and usually achieved by bone biopsy. Bisphosphonates can be safe and beneficial for patients with a glomerular filtration rate of 30 mL/min or higher, but prescribing bisphosphonates in advanced CKD requires caution because of the increased possibility of low bone turnover disorders such as osteomalacia, mixed uremic osteodystrophy, and adynamic bone, even aggravating hyperparathyroidism. Therefore, bone biopsy in advanced CKD is an important consideration before prescribing bisphosphonates. Treatment also may induce hypocalcemia in CKD patients with secondary hyperparathyroidism, but vitamin D supplementation may ameliorate this effect. Bisphosphonate treatment can improve both bone mineral density and vascular calcification, but the latter becomes more unlikely in patients with stage 3-4 CKD with vascular calcification but no decreased bone mineral density. Using bisphosphonates requires considerable caution in advanced CKD, and the lack of adequate clinical investigation necessitates more studies regarding its effects on these patients.

  7. A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone

    Directory of Open Access Journals (Sweden)

    Jérémie Guignard

    2013-11-01

    Full Text Available The bone-anchored port (BAP is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10 with conventional surgery without assistance (n = 5 in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone.

  8. Vascularized pedicle graft of ipsilateral fibula for recurrent congenital pseudoarthrosis of the tibia

    Directory of Open Access Journals (Sweden)

    Seyed Esmail Hassanpour

    2007-07-01

    Full Text Available

    We have performed the ipsilateral vascularized fibular transfer for the treatment of congenital pseudoarthrosis of the tibia (CPT. In the case under study, the conventional treatment by intramedullary rod and autogenous iliac bone grafting had failed. The follow up took place during the next 4 years and the patient can now walk without assistance. Combining a pedicle ipsilateral fibular transfer with an internal fixation and iliac bone graft may be a good option for the treatment of congenital pseudoarthrosis of tibia.
    KEY WORDS: Congenital pseudoarthrosis, tibia, vascularized fibular graft, bone graft.

  9. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  10. S100A4 and bone morphogenetic protein-2 codependently induce vascular smooth muscle cell migration via phospho-extracellular signal-regulated kinase and chloride intracellular channel 4.

    Science.gov (United States)

    Spiekerkoetter, Edda; Guignabert, Christophe; de Jesus Perez, Vinicio; Alastalo, Tero-Pekka; Powers, Janine M; Wang, Lingli; Lawrie, Allan; Ambartsumian, Noona; Schmidt, Ann-Marie; Berryman, Mark; Ashley, Richard H; Rabinovitch, Marlene

    2009-09-25

    S100A4/Mts1 is implicated in motility of human pulmonary artery smooth muscle cells (hPASMCs), through an interaction with the RAGE (receptor for advanced glycation end products). We hypothesized that S100A4/Mts1-mediated hPASMC motility might be enhanced by loss of function of bone morphogenetic protein (BMP) receptor (BMPR)II, observed in pulmonary arterial hypertension. Both S100A4/Mts1 (500 ng/mL) and BMP-2 (10 ng/mL) induce migration of hPASMCs in a novel codependent manner, in that the response to either ligand is lost with anti-RAGE or BMPRII short interference (si)RNA. Phosphorylation of extracellular signal-regulated kinase is induced by both ligands and is required for motility by inducing matrix metalloproteinase 2 activity, but phospho-extracellular signal-regulated kinase 1/2 is blocked by anti-RAGE and not by BMPRII short interference RNA. In contrast, BMPRII short interference RNA, but not anti-RAGE, reduces expression of intracellular chloride channel (CLIC)4, a scaffolding molecule necessary for motility in response to S100A4/Mts1 or BMP-2. Reduced CLIC4 expression does not interfere with S100A4/Mts1 internalization or its interaction with myosin heavy chain IIA, but does alter alignment of myosin heavy chain IIA and actin filaments creating the appearance of vacuoles. This abnormality is associated with reduced peripheral distribution and/or delayed activation of RhoA and Rac1, small GTPases required for retraction and extension of lamellipodia in motile cells. Our studies demonstrate how a single ligand (BMP-2 or S100A4/Mts1) can recruit multiple cell surface receptors to relay signals that coordinate events culminating in a functional response, ie, cell motility. We speculate that this carefully controlled process limits signals from multiple ligands, but could be subverted in disease.

  11. Aneurysmal bone cyst of the lumbar spine

    Science.gov (United States)

    Cugati, Goutham; Pande, Anil; Jain, Pradeep K.; Symss, Nigel Peter; Ramamurthi, Ravi; Vasudevan, Chakravarthy M.

    2015-01-01

    An aneurysmal bone cyst (ABC) is a benign, locally proliferative vascular disorder of non-neoplastic osseous lesions in children and young adults. Seventy-five percent of ABCs occur before the age of 20 years. They comprise 1.4% of all primary bone tumors, and commonly occur in the long bones. Spinal ABCs are much rarer. We present to you one such rare case of ABC involving the lumbar spine which was successfully treated with surgery. The clinical pathological and radiological features are described. The treatment options available are discussed. PMID:26396610

  12. Epithelioid and spindle cell haemangioma of bone

    Energy Technology Data Exchange (ETDEWEB)

    Maclean, Fiona M.; Bonar, S.F. [Douglass Hanly Moir Pathology, Macquarie Park (Australia); Schatz, Julie [Royal Prince Alfred Hospital, Department of Radiology, Camperdown (Australia); McCarthy, Stanley W.; Scolyer, Richard A. [Royal Prince Alfred Hospital, Anatomical Pathology, Camperdown (Australia); Stalley, Paul [Royal Prince Alfred Hospital, Department of Surgery, Camperdown (Australia)

    2007-06-15

    A case of epithelioid and spindle cell haemangioma of bone occurring in the proximal femur is presented. The tumour had typical microscopic features with a striking lobular pattern comprising spindled and epithelioid areas with admixed inflammatory cells. The case represents only the eighth reported example of this rare tumour, which appears to fit in the spectrum of epithelioid haemangioma. This is the first case to involve the proximal portion of a long bone. A review of the classification and features of similar vascular tumours of bone is presented. (orig.)

  13. Information Processing in Single Cells and Small Networks: Insights from Compartmental Models

    Science.gov (United States)

    Poirazi, Panayiota

    2009-03-01

    The goal of this paper is to present a set of predictions generated by detailed compartmental models regarding the ways in which information may be processed, encoded and propagated by single cells and neural assemblies. Towards this goal, I will review a number of modelling studies from our lab that investigate how single pyramidal neurons and small neural networks in different brain regions process incoming signals that are associated with learning and memory. I will first discuss the computational capabilities of individual pyramidal neurons in the hippocampus [1-3] and how these properties may allow a single cell to discriminate between different memories [4]. I will then present biophysical models of prefrontal layer V neurons and small networks that exhibit sustained activity under realistic synaptic stimulation and discuss their potential role in working memory [5].

  14. Recent advances in compartmentalized synthetic architectures as drug carriers, cell mimics and artificial organelles.

    Science.gov (United States)

    York-Duran, M J; Godoy-Gallardo, M; Labay, C; Urquhart, A J; Andresen, T L; Hosta-Rigau, L

    2017-04-01

    Compartmentalization is a key feature of biological cells which conduct their metabolic activity in individual steps isolated in distinct, separated compartments. The creation of architectures containing multiple compartments with a structure that resembles that of a biological cell has generated significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic metabolic activities, thus acting as artificial cells or organelles, are discussed. The developed technologies to assemble such complex architectures are outlined, the multicompartment carriers' properties which contribute to their performance in diverse applications are discussed, and their successful applications are highlighted. Finally, future directions and developments in the field are suggested. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Phagocytosis-inspired behaviour in synthetic protocell communities of compartmentalized colloidal objects

    Science.gov (United States)

    Rodríguez-Arco, Laura; Li, Mei; Mann, Stephen

    2017-08-01

    The spontaneous assembly of micro-compartmentalized colloidal objects capable of controlled interactions offers a step towards rudimentary forms of collective behaviour in communities of artificial cell-like entities (synthetic protocells). Here we report a primitive form of artificial phagocytosis in a binary community of synthetic protocells in which multiple silica colloidosomes are selectively ingested by self-propelled magnetic Pickering emulsion (MPE) droplets comprising particle-free fatty acid-stabilized apertures. Engulfment of the colloidosomes enables selective delivery and release of water-soluble payloads, and can be coupled to enzyme activity within the MPE droplets. Our results highlight opportunities for the development of new materials based on consortia of colloidal objects, and provide a novel microscale engineering approach to inducing higher-order behaviour in mixed populations of synthetic protocells.

  16. Fractional kinetics of compartmental systems: first approach with use digraph-based method

    Science.gov (United States)

    Markowski, Konrad Andrzej

    2017-08-01

    In the last two decades, integral and differential calculus of a fractional order has become a subject of great interest in different areas of physics, biology, economics and other sciences. The idea of such a generalization was mentioned in 1695 by Leibniz and L'Hospital. The first definition of the fractional derivative was introduced by Liouville and Riemann at the end of the 19th century. Fractional calculus was found to be a very useful tool for modelling the behaviour of many materials and systems. In this paper fractional calculus was applied to pharmacokinetic compartmental model. For introduced model determine all possible quasi-positive realisation based on one-dimensional digraph theory. The proposed method was discussed and illustrated in detail with some numerical examples.

  17. Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork

    Science.gov (United States)

    Sadegh, Sanaz; Higgins, Jenny L.; Mannion, Patrick C.; Tamkun, Michael M.; Krapf, Diego

    2017-01-01

    A broad range of membrane proteins display anomalous diffusion on the cell surface. Different methods provide evidence for obstructed subdiffusion and diffusion on a fractal space, but the underlying structure inducing anomalous diffusion has never been visualized because of experimental challenges. We addressed this problem by imaging the cortical actin at high resolution while simultaneously tracking individual membrane proteins in live mammalian cells. Our data confirm that actin introduces barriers leading to compartmentalization of the plasma membrane and that membrane proteins are transiently confined within actin fences. Furthermore, superresolution imaging shows that the cortical actin is organized into a self-similar meshwork. These results present a hierarchical nanoscale picture of the plasma membrane.

  18. Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

    Full Text Available The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

  19. Compositional compartmentalization of the nuclear genomes of Trypanosoma brucei and Trypanosoma equiperdum.

    Science.gov (United States)

    Isacchi, A; Bernardi, G; Bernardi, G

    1993-12-06

    High molecular weight DNA preparations from Trypanosoma brucei and Trypanosoma equiperdum were fractionated by preparative centrifugation in a Cs2SO4 density gradient in the presence of BAMD, bis(acetatomercurimethyl)dioxane, a sequence-specific DNA ligand. Analytical centrifugation in CsCl of the DNA fractions so obtained showed that both DNAs had a bimodal distribution with two major peaks banding at 1.702-1.703 and 1.708 g/cm3 and representing 1/3 and 2/3 of total DNA, respectively. Several minor components were also detected. These results indicate that a compositional compartmentalization is not only found in the genome of vertebrates and plants, as already described, but also in those of protozoa such as Trypanosomes.

  20. Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin

    Directory of Open Access Journals (Sweden)

    Srijana Upadhyay

    2016-03-01

    Full Text Available Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally derived melanosomes.

  1. NCAM2/OCAM/RNCAM: cell adhesion molecule with a role in neuronal compartmentalization.

    Science.gov (United States)

    Winther, Malene; Berezin, Vladimir; Walmod, Peter Schledermann

    2012-03-01

    Neural cell adhesion molecules 2 (NCAM2/OCAM/RNCAM), is a paralog of NCAM1. The protein exists in a transmembrane and a lipid-anchored isoform, and has an ectodomain consisting of five immunoglobulin modules and two fibronectin type 3 homology modules. Structural models of the NCAM2 ectodomain reveal that it facilitates cell adhesion through reciprocal interactions between the membrane-distal immunoglobulin modules. There are no known heterophilic NCAM2 binding partners, and NCAM2 is not glycosylated with polysialic acid, a posttranslational modification known to be a major modulator of NCAM1-mediated processes. This suggests that NCAM2 has a function or mode of action distinctly different from that of NCAM1. NCAM2 is primarily expressed in the brain, where it is believed to stimulate neurite outgrowth and to facilitate dendritic and axonal compartmentalization. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Lipid droplet-associated proteins (LDAPs) are required for the dynamic regulation of neutral lipid compartmentation in plant cells

    Science.gov (United States)

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols (TAGs) in seeds, their biogenesis and function in non-seed tissues is poorly understood. Recently, we identified a class of plant-sp...

  3. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  4. Nucleolar structure across evolution: the transition between bi- and tri-compartmentalized nucleoli lies within the class Reptilia.

    Science.gov (United States)

    Lamaye, Françoise; Galliot, Sonia; Alibardi, Lorenzo; Lafontaine, Denis L J; Thiry, Marc

    2011-05-01

    Two types of nucleolus can be distinguished among eukaryotic cells: a tri-compartmentalized nucleolus in amniotes and a bi-compartmentalized nucleolus in all the others. However, though the nucleolus' ultrastructure is well characterized in mammals and birds, it has been so far much less studied in reptiles. In this work, we examined the ultrastructural organization of the nucleolus in various tissues from different reptilian species (three turtles, three lizards, two crocodiles, and three snakes). Using cytochemical and immunocytological methods, we showed that in reptiles both types of nucleolus are present: a bi-compartmentalized nucleolus in turtles and a tri-compartmentalized nucleolus in the other species examined in this study. Furthermore, in a given species, the same type of nucleolus is present in all the tissues, however, the importance and the repartition of those nucleolar components could vary from one tissue to another. We also reveal that, contrary to the mammalian nucleolus, the reptilian fibrillar centers contain small clumps of condensed chromatin and that their surrounding dense fibrillar component is thicker. Finally, we also report that Cajal bodies are detected in reptiles. Altogether, we believe that these results have profound evolutionarily implications since they indicate that the point of transition between bipartite and tripartite nucleoli lies at the emergence of the amniotes within the class Reptilia. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Dynamics of the risk of smoking-induced lung cancer : A compartmental hidden markov model for longitudinal analysis

    NARCIS (Netherlands)

    Chadeau-Hyam, Marc; Tubert-Bitter, Pascale; Guihenneuc-Jouyaux, Chantal; Campanella, Gianluca; Richardson, Sylvia; Vermeulen, Roel; De Iorio, Maria; Galea, Sandro; Vineis, Paolo

    2014-01-01

    BACKGROUND:: To account for the dynamic aspects of carcinogenesis, we propose a compartmental hidden Markov model in which each person is healthy, asymptomatically affected, diagnosed, or deceased. Our model is illustrated using the example of smoking-induced lung cancer. METHODS:: The model was

  6. Assessment of spatial heterogeneity in continuous twin screw wet granulation process using three-compartmental population balance model.

    Science.gov (United States)

    Liu, Huolong; Galbraith, Shaun C; Park, Seo-Young; Cha, Bumjoon; Huang, Zhuangrong; Meyer, Robert Frederick; Flamm, Matthew H; O'Connor, Thomas; Lee, Sau; Yoon, Seongkyu

    2018-01-25

    In this study, a novel three-compartmental population balance model (PBM) for a continuous twin screw wet granulation process is developed, combining the techniques of PBM and regression process modeling. The developed model links screw configuration, screw speed, and blend throughput with granule properties to predict the granule size distribution (GSD) and volume-average granule diameter. The granulator screw barrel was divided into three compartments along barrel length: wetting compartment, mixing compartment, and steady growth compartment. Different granulation mechanisms are assumed in each compartment. The proposed model therefore considers spatial heterogeneity, improving model prediction accuracy. An industrial data set containing 14 experiments is applied for model development. Three validation experiments show that the three-compartmental PBM can accurately predict granule diameter and size distribution at randomly selected operating conditions. Sixteen combinations of aggregation and breakage kernels are investigated in predicting the experimental GSD to best judge the granulation mechanism. The three-compartmental model is compared with a one-compartmental model in predicting granule diameter at different experimental conditions to demonstrate its advantage. The influence of the screw configuration, screw speed and blend throughput on the volume-average granule diameter is analyzed based on the developed model.

  7. Metaphyseal bone formation induced by a new injectable β-TCP-based bone substitute: a controlled study in rabbits.

    Science.gov (United States)

    Krause, Matthias; Oheim, Ralf; Catala-Lehnen, Philip; Pestka, Jan M; Hoffmann, Christiane; Huebner, Wolf; Peters, Fabian; Barvencik, Florian; Amling, Michael

    2014-02-01

    Adequate filling of bone defects still poses a challenge in every day clinical work. As many bone defects are irregularly shaped the need for appropriate scaffolds reaching the complete defect surface are great. The purpose of this pre-clinical pilot study was to investigate the handling, biocompatibility, biodegradation and osteoconductivity of a new pasty bone substitute (pure phase β-TCP, hyaluronic acid, methylcellulose) in bone tissue. In an unilateral tibial defect model the peri-implant and bone tissue response to the new pasty bone substitute was tested in New Zealand white rabbits for up to 24 weeks compared to empty controls. Analysis included HR-pQCT scans, histomorphometric evaluation and quantification of vascularization of un-decalcified histological slices. After 1 week the experimental group presented significantly higher new bone volume fraction (p = 0.021) primarily consisting of immature bone matrix and higher vessel density compared to controls (p = 0.013). After 4 weeks bone formation was not significantly different to controls but was distributed more evenly throughout the defect. Bone matrix was now mineralized and trabeculae were thicker than in controls (p = 0.002) indicating faster intramedullary bone maturation. Controls presented extensive periosteal bone formation, major fibrous tissue influx and high vascularization. After 12 and 24 weeks there was no new bone detectable. There were no severe signs of inflammation at all time points. The substitute showed an early induction of bone formation. It promoted accelerated intramedullary bone repair and maturation and prevented periosteal bone formation indicating its potential use for reconstructive surgery of bone defects.

  8. Compartmentalized microfluidic perfusion system to culture human induced pluripotent stem cell aggregates.

    Science.gov (United States)

    Kondo, Yuki; Hattori, Koji; Tashiro, Shota; Nakatani, Eri; Yoshimitsu, Ryosuke; Satoh, Taku; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

    2017-08-01

    Microfluidic perfusion systems enable small-volume cell cultures under precisely controlled microenvironments, and are typically developed for cell-based high-throughput screening. However, most such systems are designed to manipulate dissociated single cells, not cell aggregates, and are thus unsuitable to induce differentiation in human induced pluripotent stem cells (hiPSCs), which is conventionally achieved by using cell aggregates to increase cell-cell interactions. We have now developed a compartmentalized microfluidic perfusion system with large flow channels to load, culture, and observe cell aggregates. Homogeneously sized cell aggregates to be loaded into the device were prepared by shredding flat hiPSC colonies into squares. These aggregates were then seeded into microchambers coated with fibronectin and bovine serum albumin (BSA) to establish adherent and floating cultures, respectively, both of which are frequently used to differentiate hiPSCs. However, the number of aggregates loaded in fibronectin-coated microchambers was much lower than in BSA-coated microchambers, suggesting that fibronectin traps cell aggregates before they reach the chambers. Accordingly, hiPSCs that reached the microchambers subsequently adhered. In contrast, BSA-coated microchambers did not allow cell aggregates to adhere, but were sufficiently deep to prevent cell aggregates from flowing out during perfusion of media. Immunostaining for markers of undifferentiated cells showed that cultures on both fibronectin- and BSA-coated microchambers were successfully established. Notably, we found that floating aggregates eventually adhered to surfaces coated with BSA upon differentiation, and that differentiation depends on the initial size of aggregates. Collectively, these results suggest that the microfluidic system is suitable for manipulating hiPSC aggregates in compartmentalized microchambers. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All

  9. Modulation in Wistar rats of blood corticosterone compartmentation by sex and a cafeteria diet.

    Directory of Open Access Journals (Sweden)

    María del Mar Romero

    Full Text Available In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG, which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression and higher physiological effectiveness for females. Good cross-reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG. The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms.

  10. The construction of next-generation matrices for compartmental epidemic models.

    Science.gov (United States)

    Diekmann, O; Heesterbeek, J A P; Roberts, M G

    2010-06-06

    The basic reproduction number (0) is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of (0) where finitely many different categories of individuals are recognized. We clear up confusion that has been around in the literature concerning the construction of this matrix, specifically for the most frequently used so-called compartmental models. We present a detailed easy recipe for the construction of the NGM from basic ingredients derived directly from the specifications of the model. We show that two related matrices exist which we define to be the NGM with large domain and the NGM with small domain. The three matrices together reflect the range of possibilities encountered in the literature for the characterization of (0). We show how they are connected and how their construction follows from the basic model ingredients, and establish that they have the same non-zero eigenvalues, the largest of which is the basic reproduction number (0). Although we present formal recipes based on linear algebra, we encourage the construction of the NGM by way of direct epidemiological reasoning, using the clear interpretation of the elements of the NGM and of the model ingredients. We present a selection of examples as a practical guide to our methods. In the appendix we present an elementary but complete proof that (0) defined as the dominant eigenvalue of the NGM for compartmental systems and the Malthusian parameter r, the real-time exponential growth rate in the early phase of an outbreak, are connected by the properties that (0) > 1 if and only if r > 0, and (0) = 1 if and only if r = 0.

  11. Consequences of plant invasions on compartmentalization and species' roles in plant-pollinator networks.

    Science.gov (United States)

    Albrecht, Matthias; Padrón, Benigno; Bartomeus, Ignasi; Traveset, Anna

    2014-08-07

    Compartmentalization-the organization of ecological interaction networks into subsets of species that do not interact with other subsets (true compartments) or interact more frequently among themselves than with other species (modules)-has been identified as a key property for the functioning, stability and evolution of ecological communities. Invasions by entomophilous invasive plants may profoundly alter the way interaction networks are compartmentalized. We analysed a comprehensive dataset of 40 paired plant-pollinator networks (invaded versus uninvaded) to test this hypothesis. We show that invasive plants have higher generalization levels with respect to their pollinators than natives. The consequences for network topology are that-rather than displacing native species from the network-plant invaders attracting pollinators into invaded modules tend to play new important topological roles (i.e. network hubs, module hubs and connectors) and cause role shifts in native species, creating larger modules that are more connected among each other. While the number of true compartments was lower in invaded compared with uninvaded networks, the effect of invasion on modularity was contingent on the study system. Interestingly, the generalization level of the invasive plants partially explains this pattern, with more generalized invaders contributing to a lower modularity. Our findings indicate that the altered interaction structure of invaded networks makes them more robust against simulated random secondary species extinctions, but more vulnerable when the typically highly connected invasive plants go extinct first. The consequences and pathways by which biological invasions alter the interaction structure of plant-pollinator communities highlighted in this study may have important dynamical and functional implications, for example, by influencing multi-species reciprocal selection regimes and coevolutionary processes. © 2014 The Author(s) Published by the Royal

  12. Bioaccessibility of selenium after human ingestion in relation to its chemical species and compartmentalization in maize.

    Science.gov (United States)

    Mombo, Stéphane; Schreck, Eva; Dumat, Camille; Laplanche, Christophe; Pierart, Antoine; Longchamp, Mélanie; Besson, Philippe; Castrec-Rouelle, Maryse

    2016-06-01

    Selenium is a micronutrient needed by all living organisms including humans, but often present in low concentration in food with possible deficiency. From another side, at higher concentrations in soils as observed in seleniferous regions of the world, and in function of its chemical species, Se can also induce (eco)toxicity. Root Se uptake was therefore studied in function of its initial form for maize (Zea mays L.), a plant widely cultivated for human and animal food over the world. Se phytotoxicity and compartmentalization were studied in different aerial plant tissues. For the first time, Se oral human bioaccessibility after ingestion was assessed for the main Se species (Se(IV) and Se(VI)) with the BARGE ex vivo test in maize seeds (consumed by humans), and in stems and leaves consumed by animals. Corn seedlings were cultivated in hydroponic conditions supplemented with 1 mg L(-1) of selenium (Se(IV), Se(VI), Control) for 4 months. Biomass, Se concentration, and bioaccessibility were measured on harvested plants. A reduction in plant biomass was observed under Se treatments compared to control, suggesting its phytotoxicity. This plant biomass reduction was higher for selenite species than selenate, and seed was the main affected compartment compared to control. Selenium compartmentalization study showed that for selenate species, a preferential accumulation was observed in leaves, whereas selenite translocation was very limited toward maize aerial parts, except in the seeds where selenite concentrations are generally high. Selenium oral bioaccessibility after ingestion fluctuated from 49 to 89 % according to the considered plant tissue and Se species. Whatever the tissue, selenate appeared as the most human bioaccessible form. A potential Se toxicity was highlighted for people living in seleniferous regions, this risk being enhanced by the high Se bioaccessibility.

  13. Compartmentalization of oxidative stress and antioxidant defense in the larval gut of Spodoptera littoralis.

    Science.gov (United States)

    Krishnan, Natraj; Sehnal, Frantisek

    2006-09-01

    Allelochemicals play important roles in the plant defense against herbivorous insects. They act as feeding deterrents, interfere with digestion and nutrient absorption, and cause production of potentially dangerous oxidative radicals. This study demonstrates that the distributions of oxidative radicals and of the antioxidant enzymes that eliminate them are compartmentalized in the digestive tract of Spodoptera littoralis larvae. Feeding on diets supplemented with the tannic acid (TA), alpha-solanine, and demissidine, respectively, did not affect the rate of food passage through the digestive tract of larvae but 1.25, 2.5, and 5% TA evoked a strong oxidative response. The amount of the superoxide anion in the foregut tissue and content increased up to 70-fold and the titer of total peroxides in the foregut content about 3-fold. This oxidative stress was associated with enhanced carbonyl content in the foregut tissue proteins, indicative of certain tissue deterioration. Extensive foregut damage was probably prevented by elevated activity of the glutathione S-transferase peroxidase. A complex antioxidant response was elicited in the midgut. The activities of superoxide dismutase and catalase increased significantly in the midgut tissue and content, and the activity of ascorbate peroxidase rose in the midgut tissue. The enzymes apparently eliminated oxidative radicals passing to midgut from the foregut with the food bolus and thereby prevented carbonylation of the midgut proteins. We postulate that the generation of oxidative radicals in the foregut and the induction of antioxidant defense in the midgut are controlled processes and that their compartmentalization is an important functional feature of the digestive tract. The glycoalkaloid alpha-solanine and the aglycone demissidine applied at 0.05 and 0.1% concentrations had no effect on any of the examined parameters.

  14. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols.

    Science.gov (United States)

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-05-27

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6-C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 &C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae.

  15. Effects of Air Stacking Maneuver on Cough Peak Flow and Chest Wall Compartmental Volumes of Subjects With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Sarmento, Antonio; Resqueti, Vanessa; Dourado-Júnior, Mario; Saturnino, Lailane; Aliverti, Andrea; Fregonezi, Guilherme; de Andrade, Armele Dornelas

    2017-11-01

    To assess the acute effects of air stacking on cough peak flow (CPF) and chest wall compartmental volumes of persons with amyotrophic lateral sclerosis (ALS) versus healthy subjects positioned at 45° body inclination. Cross-sectional study with a matched-pair design. University hospital. Persons (N=24) with ALS (n=12) and age-matched healthy subjects (n=12). CPF, chest wall compartmental inspiratory capacity, chest wall vital capacity, chest wall tidal volume and operational volumes, breathing pattern, and percentage of contribution of the compartments to the inspired volume were measured by optoelectronic plethysmography. Compared with healthy subjects, significantly lower CPF (P=.007), chest wall compartmental inspiratory capacity (P<.001), chest wall vital capacity (P<.001), and chest wall tidal volume (P<.001) were found in subjects with ALS. Immediately after air stacking, CPF (P<.001) and chest wall compartmental inspiratory capacity (P<.001) significantly increased in both groups, with values returning to basal only in healthy subjects. After air stacking, the abdominal compartment (P=.004) was determined to be responsible for the inspired volume in subjects with ALS. Significantly higher chest wall vital capacity (P=.05) was observed in subjects with ALS 5 minutes after air stacking, with the rib cage compartment (P=.049) being responsible for volume change. No differences were found in chest wall vital capacity and compartmental volumes of healthy subjects. Chest wall tidal volume (P<.001) significantly increased during the protocol in the healthy subjects, mainly because of end-inspiratory (P<.001) and abdominal volumes (P=.008). No significant differences were observed in percentage of contribution of the compartments to the inspired volume and end-expiratory volume of both groups. No significant differences were found in chest wall tidal volume, operational volume, and breathing pattern in persons with ALS. Air stacking is effective in increasing CPF

  16. Dental infection and vascular disease.

    Science.gov (United States)

    Zoellner, Hans

    2011-04-01

    Periodontitis is a chronic inflammatory response to bacterial plaque in which the anchoring bone and soft tissues supporting teeth are destroyed, resulting in tooth mobility and loss. Dental caries involves the spread of infection from the dentine to the vascular dental pulp and periapical bony tissues, before involvement of adjacent soft tissues and spreading sepsis. Several case-controlled, cross-sectional, and cohort studies report correlation between periodontitis and increased cardiovascular, cerebrovascular, and peripheral artery disease, as determined by clinical disease, angiography, ultrasonography, and reduced flow-mediated dilation. Some studies report a similar relationship of atherosclerosis with periapical infection and potentially also with coronal caries, and this review identifies the need to investigate these associations further. Smoking and cadmium exposure are epidemiologically confounding environmental risk factors shared by atherosclerosis and periodontitis. Further complicating epidemiological studies are the risk factors for both atherosclerosis and periodontitis, with which periodontitis appears to have separate positive feedback relationships. These include diabetes, increased plasma lipid levels, hypertension, and white blood cell count. Animal and human intervention studies provide some direct support of a causal role for periodontitis in atherosclerosis, and possible mechanisms include bacterial invasion of arteries, specific atherogenic properties of oral bacteria, the acute phase response, and cytokine polymorphisms. © Thieme Medical Publishers.

  17. HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure.

    Directory of Open Access Journals (Sweden)

    Martha J Lewis

    Full Text Available The gut is the largest lymphoid organ in the body and a site of active HIV-1 replication and immune surveillance. The gut is a reservoir of persistent infection in some individuals with fully suppressed plasma viremia on combination antiretroviral therapy (cART although the cause of this persistence is unknown. The HIV-1 accessory protein Nef contributes to persistence through multiple functions including immune evasion and increasing infectivity. Previous studies showed that Nef's function is shaped by cytotoxic T lymphocyte (CTL responses and that there are distinct populations of Nef within tissue compartments. We asked whether Nef's sequence and/or function are compartmentalized in the gut and how compartmentalization relates to local CTL immune responses. Primary nef quasispecies from paired plasma and sigmoid colon biopsies from chronically infected subjects not on therapy were sequenced and cloned into Env(- Vpu(- pseudotyped reporter viruses. CTL responses were mapped by IFN-γ ELISpot using expanded CD8+ cells from blood and gut with pools of overlapping peptides covering the entire HIV proteome. CD4 and MHC Class I Nef-mediated downregulation was measured by flow cytometry. Multiple tests indicated compartmentalization of nef sequences in 5 of 8 subjects. There was also compartmentalization of function with MHC Class I downregulation relatively well preserved, but significant loss of CD4 downregulation specifically by gut quasispecies in 5 of 7 subjects. There was no compartmentalization of CTL responses in 6 of 8 subjects, and the selective pressure on quasispecies correlated with the magnitude CTL response regardless of location. These results demonstrate that Nef adapts via diverse pathways to local selective pressures within gut mucosa, which may be predominated by factors other than CTL responses such as target cell availability. The finding of a functionally distinct population within gut mucosa offers some insight into how HIV-1

  18. Porcine Bone Scaffolds Adsorb Growth Factors Secreted by MSCs and Improve Bone Tissue Repair

    Directory of Open Access Journals (Sweden)

    Eitan Mijiritsky

    2017-09-01

    Full Text Available An ideal tissue-engineered bone graft should have both excellent pro-osteogenesis and pro-angiogenesis properties to rapidly realize the bone regeneration in vivo. To meet this goal, in this work a porcine bone scaffold was successfully used as a Trojan horse to store growth factors produced by mesenchymal stem cells (MSCs. This new scaffold showed a time-dependent release of bioactive growth factors, such as vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF, in vitro. The biological effect of the growth factors-adsorbed scaffold on the in vitro commitment of MSCs into osteogenic and endothelial cell phenotypes has been evaluated. In addition, we have investigated the activity of growth factor-impregnated granules in the repair of critical-size defects in rat calvaria by means of histological, immunohistochemical, and molecular biology analyses. Based on the results of our work bone tissue formation and markers for bone and vascularization were significantly increased by the growth factor-enriched bone granules after implantation. This suggests that the controlled release of active growth factors from porcine bone granules can enhance and promote bone regeneration.

  19. Ankle arthrodesis with bone graft after distal tibia resection for bone tumors.

    Science.gov (United States)

    Campanacci, Domenico Andrea; Scoccianti, Guido; Beltrami, Giovanni; Mugnaini, Marco; Capanna, Rodolfo

    2008-10-01

    Treatment of distal tibial tumors is challenging due to the scarce soft tissue coverage of this area. Ankle arthrodesis has proven to be an effective treatment in primary and post-traumatic joint arthritis, but few papers have addressed the feasibility and techniques of ankle arthrodesis in tumor surgery after long bone resections. Resection of the distal tibia and reconstruction by ankle fusion using non-vascularized structural bone grafts was performed in 8 patients affected by malignant (5 patients) or aggressive benign (3 patients) tumors. Resection length of the tibia ranged from 5 to 21 cm. Bone defects were reconstructed with cortical structural autografts (from contralateral tibia) or allografts or both, plus autologous bone chips. Fixation was accomplished by antegrade nailing (6 cases) or plating (2~cases). All the arthrodesis successfully healed. At followup ranging from 23 to 113 months (average 53.5), all patients were alive. One local recurrence was observed with concomitant deep infection (a below-knee amputation was performed). Mean functional MSTS score of the seven available patients was 80.4% (range, 53 to 93). Resection of the distal tibia and arthrodesis of the ankle with non-vascularized structural bone grafts, combined with autologous bone chips, can be an effective procedure in bone tumor surgery with durable and satisfactory functional results. In shorter resections, autologous cortical structural grafts can be used; in longer resections, allograft structural bone grafts are needed.

  20. Your Bones

    Science.gov (United States)

    ... the top are called the cervical (say: SIR-vih-kul) vertebrae. These bones are in the back ... purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  1. Bone Scan

    Science.gov (United States)

    ... posts Join Mayo Clinic Connect Bone scan About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  2. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  3. Vascularized Spare Parts Reconstruction of Hand Gunshot Injury.

    Science.gov (United States)

    Patrick, Nathan; Payatakes, Alexander

    2017-09-01

    Reconstruction of extensive traumatic bone and soft tissue deficits in the hand often presents a significant challenge. We present a case of a gunshot wound managed with a resourceful "vascularized spare parts" reconstruction in which a single compromised digit provided two separate vascularized tissue transfers. A rarely reported pedicled phalanx restored osseous stability, a digital fillet flap achieved soft tissue coverage, and the flexor tendons reanimated the hand. An excellent functional and cosmetic result was obtained and the patient was able to return to manual labor within six months of injury.

  4. Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2010-09-01

    Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well-established biomarkers of subclinical vascular inflammation such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been described.

  5. Hypercholesterolaemia and vascular dementia.

    Science.gov (United States)

    Appleton, Jason P; Scutt, Polly; Sprigg, Nikola; Bath, Philip M

    2017-07-15

    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors-diabetes, hypercholesterolaemia, hypertension and smoking-are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here. © 2017 The Author(s).

  6. Depression in vascular dementia.

    NARCIS (Netherlands)

    Naarding, P.; Koning, I. de; Kooten, F. van; Dippel, D.W.; Janzing, J.G.E.; Mast, R.C. van der; Koudstaal, P.J.

    2003-01-01

    OBJECTIVE: To study the presence of different dimensions of depression in subjects with vascular dementia. BACKGROUND: After a stroke, cognitive, affective and behavioural disturbances are common. It has been suggested that the nature of affective symptomatology can help to differentiate organic

  7. Vascular management in rotationplasty.

    Science.gov (United States)

    Mahoney, Craig R; Hartman, Curtis W; Simon, Pamela J; Baxter, B Timothy; Neff, James R

    2008-05-01

    The Van Nes rotationplasty is a useful limb-preserving procedure for skeletally immature patients with distal femoral or proximal tibial malignancy. The vascular supply to the lower limb either must be maintained and rotated or transected and reanastomosed. We asked whether there would be any difference in the ankle brachial index or complication rate for the two methods of vascular management. Vessels were resected with the tumor in seven patients and preserved and rotated in nine patients. One amputation occurred in the group in which the vessels were preserved. Four patients died secondary to metastatic disease diagnosed preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear similar using both methods of vascular management and one should not hesitate to perform an en bloc resection when there is a question of vascular involvement.

  8. Temperatures rising: brown fat and bone.

    Science.gov (United States)

    Motyl, Katherine J; Rosen, Clifford J

    2011-03-01

    Caloric restriction is associated with a reduction in body weight and temperature, as well as a reduction in trabecular bone volume and paradoxically an increase in adipocytes within the bone marrow. The nature of these adipocytes is uncertain, although there is emerging evidence of a direct relationship between bone remodeling and brown adipocytes. For example, in heterotrophic ossification, brown adipocytes set up a hypoxic gradient that leads to vascular invasion, chondrocyte differentiation, and subsequent bone formation. Additionally, deletion of retinoblastoma protein in an osteosarcoma model leads to increased hibernoma (brown fat tumor). Brown adipose tissue (BAT) becomes senescent with age at a time when thermoregulation is altered, bone loss becomes apparent, and sympathetic activity increases. Interestingly, heart rate is an unexpected but good predictor of fracture risk in elderly individuals, pointing to a key role for the sympathetic nervous system in senile osteoporosis. Hence the possibility exists that BAT could play an indirect role in age-related bone loss. However, evidence of an indirect effect from thermogenic dysfunction on bone loss is currently limited. Here, we present current evidence for a relationship between brown adipose tissue and bone as well as provide novel insights into the effects of thermoregulation on bone mineral density.

  9. Renal posttransplant's vascular complications

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    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  10. Scaffolds combined with stem cells and growth factors in healing of pseudotumoral lesions of bone.

    Science.gov (United States)

    De Biase, P; Campanacci, D A; Beltrami, G; Scoccianti, G; Ciampalini, L; Pecchioli, O; Capanna, R

    2011-01-01

    Reconstructions of large lesions or defects often require a bone graft or a bone substitute to promote healing. In common practice the reconstruction of a bone defect is dependent on the site and size of the lesion: in long bones intercalary defects may be managed with Ilizarov technique of bone transport and distraction osteogenesis or the use of a free or pedicled vascularized bone graft, or with Masquelet technique. For cavitary defects the available surgical options include autograft, allograft or xenograft or the use of synthetic scaffolds to promote bone regeneration. In order to promote a faster bone healing tissue engineering proposed the application of enriched graft to fill bone defects. The employment of enriched bone graft has been our choice in the last years to fill contained defects following curettage of a pseudotumoral lesion of bone. We report our clinical experience in terms of safety and success of these procedures at a long-term follow up.

  11. Medicines and Bone Loss

    Science.gov (United States)

    Fact Sheet Medici a ne n s d Bone Loss Some types of medicines can cause bone loss, making your bones weak, if used for a long time. Use over a short time ... old bone and replaces it with new bone. Bone loss occurs when old bone breaks down faster than ...

  12. Histochemical and morphological aspects of fresh frozen bone: a preliminary study.

    Science.gov (United States)

    De Ponte, F S; Cutroneo, G; Falzea, R; Rizzo, G; Catalfamo, L; Favaloro, A; Vermiglio, G; Runci, M; Centofanti, A; Anastasi, G

    2016-12-06

    Bone graft are used in dentistry for the reconstruction of severely atrophic jaws. Fresh frozen bone has no osteogenic property but it has osteoconductive and osteoinductive properties because its matrix contains growth factors such as vascular endothelial growth factor. The purpose of the present study was to evaluate morphological and protein expression characteristics of fresh frozen bone before graft and after six months of graft in patients who needed maxillary reconstruction. After 6 month of graft we observed the presence of viable bone as evidenced by full osteocyte lacunae and by the presence of RANKR, osteocalcin positive cells and vascular endothelial growth factor. In conclusion, our findings show that the fresh frozen bone after six month of graft is for the most part viable bone, encouraging its use as an alternative to autogenous bone for reconstructing maxillary bone defects prior to implant.

  13. Histochemical and morphological aspects of fresh frozen bone: a preliminary study

    Directory of Open Access Journals (Sweden)

    F.S. De Ponte

    2016-12-01

    Full Text Available Bone graft are used in dentistry for the reconstruction of severely atrophic jaws. Fresh frozen bone has no osteogenic property but it has osteoconductive and osteoinductive properties because its matrix contains growth factors such as vascular endothelial growth factor. The purpose of the present study was to evaluate morphological and protein expression characteristics of fresh frozen bone before graft and after six months of graft in patients who needed maxillary reconstruction. After 6 month of graft we observed the presence of viable bone as evidenced by full osteocyte lacunae and by the presence of RANKR, osteocalcin positive cells and vascular endothelial growth factor. In conclusion, our findings show that the fresh frozen bone after six month of graft is for the most part viable bone, encouraging its use as an alternative to autogenous bone for reconstructing maxillary bone defects prior to implant.

  14. Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro.

    Science.gov (United States)

    Blair, Harry C; Larrouture, Quitterie C; Li, Yanan; Lin, Hang; Beer-Stoltz, Donna; Liu, Li; Tuan, Rocky S; Robinson, Lisa J; Schlesinger, Paul H; Nelson, Deborah J

    2017-06-01

    We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and

  15. Vascular manifestations of Behcet's disease

    Directory of Open Access Journals (Sweden)

    Regina Georgiyeva Goloeva

    2010-01-01

    Conclusion. Vascular disorders in BD were diagnosed in one fourth of the patients, mainly in young male patients. Severe thromboses with the development of chronic venous insignificance, Budd-Chiari syndrome, pulmonary and iliac artery aneurysms, and arterial thromboses were observed in male patients only. Vascular events were associated with erythema nodosum and epididymitis; in these concomitances, the vascular risk was substantially increased. Vascular death rates were 2,2%.

  16. Engineering vascularized skeletal muscle tissue

    NARCIS (Netherlands)

    Levenberg, Shulamit; Rouwkema, Jeroen; Macdonald, Mara; Garfein, Evan S.; Kohane, Daniel S.; Darland, Diane C.; Marini, Robert; van Blitterswijk, Clemens; Mulligan, Richard C.; D'Amore, Patricia A.; Langer, Robert

    2005-01-01

    One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe

  17. Building better bone: The weaving of biologic and engineering strategies for managing bone loss.

    Science.gov (United States)

    Schwartz, Andrew M; Schenker, Mara L; Ahn, Jaimo; Willett, Nick J

    2017-09-01

    Segmental bone loss remains a challenging clinical problem for orthopaedic trauma surgeons. In addition to the missing bone itself, the local tissues (soft tissue, vascular) are often highly traumatized as well, resulting in a less than ideal environment for bone regeneration. As a result, attempts at limb salvage become a highly expensive endeavor, often requiring multiple operations and necessitating the use of every available strategy (autograft, allograft, bone graft substitution, Masquelet, bone transport, etc.) to achieve bony union. A cost-sensitive, functionally appropriate, and volumetrically adequate engineered substitute would be practice-changing for orthopaedic trauma surgeons and these patients with difficult clinical problems. In tissue engineering and bone regeneration fields, numerous research efforts continue to make progress toward new therapeutic interventions for segmental bone loss, including novel biomaterial development as well as cell-based strategies. Despite an ever-evolving literature base of these new therapeutic and engineered options, there remains a disconnect with the clinical practice, with very few translating into clinical use. A symposium entitled "Building better bone: The weaving of biologic and engineering strategies for managing bone loss," was presented at the 2016 Orthopaedic Research Society Conference to further explore this engineering-clinical disconnect, by surveying basic, translational, and clinical researchers along with orthopaedic surgeons and proposing ideas for pushing the bar forward in the field of segmental bone loss. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1855-1864, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    Science.gov (United States)

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  19. Evaluation of cancer stem cell migration using compartmentalizing microfluidic devices and live cell imaging.

    Science.gov (United States)

    Huang, Yu; Agrawal, Basheal; Clark, Paul A; Williams, Justin C; Kuo, John S

    2011-12-23

    In the last 40 years, the United States invested over 200 billion dollars on cancer research, resulting in only a 5% decrease in death rate. A major obstacle for improving patient outcomes is the poor understanding of mechanisms underlying cellular migration associated with aggressive cancer cell invasion, metastasis and therapeutic resistance. Glioblastoma Multiforme (GBM), the most prevalent primary malignant adult brain tumor, exemplifies this difficulty. Despite standard surgery, radiation and chemotherapies, patient median survival is only fifteen months, due to aggressive GBM infiltration into adjacent brain and rapid cancer recurrence. The interactions of aberrant cell migratory mechanisms and the tumor microenvironment likely differentiate cancer from normal cells. Therefore, improving therapeutic approaches for GBM require a better understanding of cancer cell migration mechanisms. Recent work suggests that a small subpopulation of cells within GBM, the brain tumor stem cell (BTSC), may be responsible for therapeutic resistance and recurrence. Mechanisms underlying BTSC migratory capacity are only starting to be characterized. Due to a limitation in visual inspection and geometrical manipulation, conventional migration assays are restricted to quantifying overall cell populations. In contrast, microfluidic devices permit single cell analysis because of compatibility with modern microscopy and control over micro-environment. We present a method for detailed characterization of BTSC migration using compartmentalizing microfluidic devices. These PDMS-made devices cast the tissue culture environment into three connected compartments: seeding chamber, receiving chamber and bridging microchannels. We tailored the device such that both chambers hold sufficient media to support viable BTSC for 4-5 days without media exchange. Highly mobile BTSCs initially introduced into the seeding chamber are isolated after migration though bridging microchannels to the parallel

  20. Compartmentalized cGMP Responses of Olfactory Sensory Neurons inCaenorhabditis elegans.

    Science.gov (United States)

    Shidara, Hisashi; Hotta, Kohji; Oka, Kotaro

    2017-04-05

    Cyclic guanosine monophosphate (cGMP) plays a crucial role as a second messenger in the regulation of sensory signal transduction in many organisms. In AWC olfactory sensory neurons of Caenorhabditis elegans , cGMP also has essential and distinctive functions in olfactory sensation and adaptation. According to molecular genetic studies, when nematodes are exposed to odorants, a decrease in cGMP regulates cGMP-gated channels for olfactory sensation. Conversely, for olfactory adaptation, an increase in cGMP activates protein kinase G to modulate cellular physiological functions. Although these opposing cGMP responses in single neurons may occur at the same time, it is unclear how cGMP actually behaves in AWC sensory neurons. A hypothetical explanation for opposing cGMP responses is region-specific behaviors in AWC: for odor sensation, cGMP levels in cilia could decrease, whereas odor adaptation is mediated by increased cGMP levels in soma. Therefore, we visualized intracellular cGMP in AWC with a genetically encoded cGMP indicator, cGi500, and examined spatiotemporal cGMP responses in AWC neurons. The cGMP imaging showed that, after odor exposure, cGMP levels in AWC cilia decreased transiently, whereas levels in dendrites and soma gradually increased. These region-specific responses indicated that the cGMP responses in AWC neurons are explicitly compartmentalized. In addition, we performed Ca 2+ imaging to examine the relationship between cGMP and Ca 2+ These results suggested that AWC sensory neurons are in fact analogous to vertebrate photoreceptor neurons. SIGNIFICANCE STATEMENT Cyclic guanosine monophosphate (cGMP) plays crucial roles in the regulation of sensory signal transduction in many animals. In AWC olfactory sensory neurons of Caenorhabditis elegans , cGMP also has essential and distinctive functions involving olfactory sensation and adaptation. Here, we visualized intracellular cGMP in AWC neurons with a genetically encoded cGMP indicator and examined

  1. A new compartmental method for the analysis of liver FDG kinetics in small animal models.

    Science.gov (United States)

    Garbarino, Sara; Vivaldi, Valentina; Delbary, Fabrice; Caviglia, Giacomo; Piana, Michele; Marini, Cecilia; Capitanio, Selene; Calamia, Iolanda; Buschiazzo, Ambra; Sambuceti, Gianmario

    2015-12-01

    Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreover, a tracer is supplied to the liver by both the hepatic artery and the portal vein, which is not visible in PET images. This study developed an innovative computational approach accounting for the reversible nature of FDG in the liver and directly computing the portal vein tracer concentration by means of gut radioactivity measurements. Twenty-one mice were subdivided into three groups: the control group 'CTR' (n = 7) received no treatment, the short-term starvation group 'STS' (n = 7) was submitted to food deprivation with free access to water within 48 h before imaging, and the metformin group 'MTF' (n = 7) was treated with metformin (750 mg/Kg per day) for 1 month. All mice underwent a dynamic micro-PET study for 50 min after an (18)F-FDG injection. The compartmental analysis considered two FDG pools (phosphorylated and free) in both the gut and liver. A tracer was carried into the liver by the hepatic artery and the portal vein, and tracer delivery from the gut was considered as the sole input for portal vein tracer concentration. Accordingly, both the liver and gut were characterized by two compartments and two exchange coefficients. Each one of the two two-compartment models was mathematically described by a system of differential equations, and data optimization was performed by applying a Newton algorithm to the inverse problems associated to these differential systems. All rate constants were stable in each group. The tracer coefficient from the free to the metabolized compartment in the liver was increased by STS, while it was unaltered by MTF. By contrast, the tracer coefficient from the metabolized to the free compartment was reduced by MTF and increased by STS. Data

  2. Surgical Treatment of an Aneurysmal Bone Cyst with Avascular Bone Graft.

    Science.gov (United States)

    Ulici, Alexandru; Nahoi, Catalin; Carp, Madalina; Fodor, Ioan; Dinu, Cristina

    2017-01-01

    Background: Aneurysmal bone cyst is a solitary bone tumor, expansile and lytic most often seen in the second decade of life, more frequently in men than in women (2: 1). They can occur in any bone, most common in the metaphysis of the long bones of the lower limbs. Although it is a benign tumor formation, aneurysmal cysts may have an aggressive local evolution and can cause a significant decrease in bone strength. The pacient may present local pain, the appearance of local deformation due to a tumor mass or occurrence of pathological fractures. Traditionally these lesions were treated surgically (curettage or resection and bone grafting) with a relapse rate of about 20%. Because bone resection may lead to bone defects, deformations or damage in the affected limb's function, lately the preferred treatement percutaneous sclerotherapy using fibrosing alcoholic agents. We present the case of a 14 year old pacient submitted for pain and deformity at the distal third of the right forearm with insidious onset and exacerbated lately. Following clinical investigations, laboratory and histopathology he was diagnosed with aneurysmal bone cyst of the right ulna. Since sclerotherapy is not available in our clinic, we initially performed an excisional biopsy with curettage of the lesion. Because the tumor still had an aggressive postoperative evolution, we decided for a bone resection and reconstruction using an avascular peroneal graft. Postoperative, the patient presents a favorable short and medium term evolution, the disappearance of pain and resumed function of the affected segment. Radiologically bone graft integration can be observed, with no evidence of local recurrence. Although modern tehniques for treating anurysmal bone cyst include either injecting fibrosing alcoholic agents or resection and grafting using vascular bone graft, the traditional tehnique described by Merle d'Aubigne which implies the usage of avascular bone graft is still heplful, leading to succesful

  3. Brain Vascular Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Bàrbara Laviña

    2016-12-01

    Full Text Available Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain during development and adulthood; as well as to observe the vascular responses in disease situations in vivo. This review offers a concise summary and brief historical reference of different imaging techniques and how these tools can be applied to study the brain vasculature and the blood-brain barrier integrity in both healthy and disease states. Moreover, it offers an overview on available transgenic animal models to study vascular biology and a description of useful online brain atlases.

  4. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  5. Pathophysiology of vascular dementia

    Directory of Open Access Journals (Sweden)

    Rizzo Claudia

    2009-11-01

    Full Text Available Abstract The concept of Vascular Dementia (VaD has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case. Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment.

  6. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  7. Strategies Developed to Induce, Direct, and Potentiate Bone Healing

    Directory of Open Access Journals (Sweden)

    Anne-Margaux Collignon

    2017-11-01

    Full Text Available Bone exhibits a great ability for endogenous self-healing. Nevertheless, impaired bone regeneration and healing is on the rise due to population aging, increasing incidence of bone trauma and the clinical need for the development of alternative options to autologous bone grafts. Current strategies, including several biomolecules, cellular therapies, biomaterials, and different permutations of these, are now developed to facilitate the vascularization and the engraftment of the constructs, to recreate ultimately a bone tissue with the same properties and characteristics of the native bone. In this review, we browse the existing strategies that are currently developed, using biomolecules, cells and biomaterials, to induce, direct and potentiate bone healing after injury and further discuss the biological processes associated with this repair.

  8. Pathophysiology of vascular dementia

    OpenAIRE

    Rizzo Claudia; Duro Giovanni; Iemolo Francesco; Castiglia Laura; Hachinski Vladimir; Caruso Calogero

    2009-01-01

    Abstract The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments th...

  9. Peripheral Vascular Disease

    Science.gov (United States)

    ... bones and very flexible joints. People with this syndrome often have aneurysms. What are the symptoms? Aortic aneurysms may cause shortness of breath, a croaky or raspy voice, backache, or pain in your left shoulder or between your shoulder blades. An aortic aneurysm ...

  10. Pulmonary vascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fedullo, P.F.; Shure, D.

    1987-03-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

  11. Update on Vascular Dementia.

    Science.gov (United States)

    Khan, Ayesha; Kalaria, Raj N; Corbett, Anne; Ballard, Clive

    2016-09-01

    Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment. © The Author(s) 2016.

  12. [The intra bone passage and nursing].

    Science.gov (United States)

    Durán Hoyos, Rafael; Ibarretxe Marcos, J R; Gil Martín, F J; Pérez Ordoñez, A

    2004-05-01

    The authors confirm the utility of the intra bone passage as a means of emergency vascular access when the installation of a peripheral and/or central venous passage is difficult or impossible when attending critically ill patients as another additional technique available to Nursing when caring for a critically ill patient. From the reference articles reviewed, the authors deduce that intra bone vascular access provides a passage to the vascular system which permits rapid, easy and efficient access, especially when attending children under the age of six. The use of the intra bone passage is justified whenever medical personnel take more than 90 seconds or have three failed tries to insert a peripheral venous tube in patients who are critically ill or unstable. The anatomical zones which are the most appropriate to puncture in children are the proximal and distal part of the tibia and the distal section of the femur. This intra bone passage permits the administering of liquids and drugs, just as a peripheral venous passage does. Both the complications and the countermeasures are minimal.

  13. Micro-compartmentalized cultivation of cyanobacteria for mutant screening using glass slides with highly water-repellent mark

    Directory of Open Access Journals (Sweden)

    Sayuri Arai

    2014-12-01

    Full Text Available Photosynthetic microorganisms such as cyanobacteria have attracted attention for their potential to produce biofuels and biochemicals directly from CO2. Cell isolation by colony has conventionally been used for selecting target cells. Colony isolation methods require a significant amount of time for cultivation, and the colony-forming ratio is potentially low for cyanobacteria. Here, we overcome such limitations by encapsulating and culturing cells in droplets with an overlay of dodecane using glass slides printed with highly water-repellent mark. In the compartmentalized culture, the oil phase protects the small volume of culture medium from drying and increases the CO2 supply. Since a difference in cell growth was observed with and without the addition of antibiotics, this compartmentalized culture method could be a powerful tool for mutant selection.

  14. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  15. Metabolic Compartmentation – A System Level Property of Muscle Cells

    Directory of Open Access Journals (Sweden)

    Theo Wallimann

    2008-05-01

    Full Text Available Problems of quantitative investigation of intracellular diffusion and compartmentation of metabolites are analyzed. Principal controversies in recently published analyses of these problems for the living cells are discussed. It is shown that the formal theoretical analysis of diffusion of metabolites based on Fick’s equation and using fixed diffusion coefficients for diluted homogenous aqueous solutions, but applied for biological systems in vivo without any comparison with experimental results, may lead to misleading conclusions, which are contradictory to most biological observations. However, if the same theoretical methods are used for analysis of actual experimental data, the apparent diffusion constants obtained are orders of magnitude lower than those in diluted aqueous solutions. Thus, it can be concluded that local restrictions of diffusion of metabolites in a cell are a system-level properties caused by complex structural organization of the cells, macromolecular crowding, cytoskeletal networks and organization of metabolic pathways into multienzyme complexes and metabolons. This results in microcompartmentation of metabolites, their channeling between enzymes and in modular organization of cellular metabolic networks. The perspectives of further studies of these complex intracellular interactions in the framework of Systems Biology are discussed.

  16. Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

    Directory of Open Access Journals (Sweden)

    Blanca eLizarbe

    2013-06-01

    Full Text Available We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI and Spectroscopy (MRS methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main Magnetic Resonance Imaging and Spectroscopy strategies that have been used to investigate appetite regulation. Manganese enhanced magnetic resonance imaging (MEMRI, Blood oxygenation level dependent contrast (BOLD and Diffusion weighted magnetic resonance imaging (DWI have revealed Mn2+accumulations, augmented oxygen consumptions and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks, becoming eventually MRI and MRS detectable.

  17. Dynamin regulates metaphase furrow formation and plasma membrane compartmentalization in the syncytial Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Richa Rikhy

    2015-02-01

    Full Text Available The successive nuclear division cycles in the syncytial Drosophila embryo are accompanied by ingression and regression of plasma membrane furrows, which surround individual nuclei at the embryo periphery, playing a central role in embryo compartmentalization prior to cellularization. Here, we demonstrate that cell cycle changes in dynamin localization and activity at the plasma membrane (PM regulate metaphase furrow formation and PM organization in the syncytial embryo. Dynamin was localized on short PM furrows during interphase, mediating endocytosis of PM components. Dynamin redistributed off ingressed PM furrows in metaphase, correlating with stabilized PM components and the associated actin regulatory machinery on long furrows. Acute inhibition of dynamin in the temperature sensitive shibire mutant embryo resulted in morphogenetic consequences in the syncytial division cycle. These included inhibition of metaphase furrow ingression, randomization of proteins normally polarized to intercap PM and disruption of the diffusion barrier separating PM domains above nuclei. Based on these findings, we propose that cell cycle changes in dynamin orchestrate recruitment of actin regulatory machinery for PM furrow dynamics during the early mitotic cycles in the Drosophila embryo.

  18. Hydraulic characteristics and their effects on working performance of compartmentalized anaerobic reactor.

    Science.gov (United States)

    Ji, Jun-yuan; Zheng, Kai; Xing, Ya-juan; Zheng, Ping

    2012-07-01

    The compartmentalized anaerobic reactor (CAR) is a patent novel high-rate reactor and shows a great potential for its application. The hydraulic characteristics and their effects on the working performance of CAR were investigated. The flow pattern tended to plug flow at normal organic loading rate (OLR) and completely mixed flow at high OLRs. The relation of hydraulic dead space (HDS or V(h)) with hydraulic loading rate (HLR or L) and biogas production rate (BPR or G) was V(h) = 3.75 L + 0.19 G-9.47. The hydraulic efficiency of CAR was good or near to good. Both HLR and BPR had significant effects on the hydraulic efficiency, but their effect became less at super-high OLR. They also had a slight influence on the effective volume ratios of CAR, but the influence of BPR almost disappeared at super-high OLR. The good working performance of CAR was ascribed to the improved reactor configuration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Reservoir compartmentalization and management strategies: Lessons learned in the Illinois basin

    Energy Technology Data Exchange (ETDEWEB)

    Grube, J.P.; Crockett, J.E.; Huff, B.G. [and others

    1997-08-01

    A research project jointly sponsored by the US Department of Energy and the Illinois State Geological Survey focused on the Cypress and Aux Vases Formations (Mississippian), major clastic reservoirs in the Illinois Basin. Results from the research showed that understanding the nature and distribution of reservoir compartments, and using effective reservoir management strategies, can significantly improve recovery efficiencies from oil fields in this mature basin. Compartments can be most effectively drained where they are geologically well defined and reservoir management practices are coordinated through unified, compartment-wide, development programs. Our studies showed that the Cypress and Aux Vases reservoirs contain lateral and vertical permeability barriers forming compartments that range in size from isolated, interlaminated sandstone and shale beds to sandstone bodies tens of feet in thickness and more than a mile in length. Stacked or shingled, genetically similar sandstone bodies are commonly separated by thin impermeable intervals that can be difficult to distinguish on logs and can, therefore, cause correlation problems, even between wells drilled on spacing of less than ten acres. Lateral separation of sandstone bodies causes similar problems. Reservoir compartmentalization reduces primary and particularly secondary recovery by trapping pockets of by-passed or banked oil. Compartments can be detected by comparing recovery factors of genetically similar sandstone bodies within a field; using packers to separate commingled intervals and analyzing fluid recoveries and pressures; making detailed core-to-log calibrations that identify compartment boundaries; and analyzing pressure data from waterflood programs.

  20. Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

    Science.gov (United States)

    Lizarbe, Blanca; Benitez, Ania; Peláez Brioso, Gerardo A.; Sánchez-Montañés, Manuel; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2013-01-01

    We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn2+ accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable. PMID:23781199

  1. Integrated compartmental model for describing the transport of solute in a fractured porous medium. [FRACPORT

    Energy Technology Data Exchange (ETDEWEB)

    DeAngelis, D.L.; Yeh, G.T.; Huff, D.D.

    1984-10-01

    This report documents a model, FRACPORT, that simulates the transport of a solute through a fractured porous matrix. The model should be useful in analyzing the possible transport of radionuclides from shallow-land burial sites in humid environments. The use of the model is restricted to transport through saturated zones. The report first discusses the general modeling approach used, which is based on the Integrated Compartmental Method. The basic equations of solute transport are then presented. The model, which assumes a known water velocity field, solves these equations on two different time scales; one related to rapid transport of solute along fractures and the other related to slower transport through the porous matrix. FRACPORT is validated by application to a simple example of fractured porous medium transport that has previously been analyzed by other methods. Then its utility is demonstrated in analyzing more complex cases of pulses of solute into a fractured matrix. The report serves as a user's guide to FRACPORT. A detailed description of data input, along with a listing of input for a sample problem, is provided. 16 references, 18 figures, 3 tables.

  2. Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil.

    Directory of Open Access Journals (Sweden)

    Rebecca Lee Smith

    2016-08-01

    Full Text Available Hansen's disease (HD, or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44-45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control.

  3. A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi

    Science.gov (United States)

    Dutheil, Julien Y.; Mannhaupt, Gertrud; Schweizer, Gabriel; M.K. Sieber, Christian; Münsterkötter, Martin; Güldener, Ulrich; Schirawski, Jan; Kahmann, Regine

    2016-01-01

    Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID:26872771

  4. Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Kai Kretzschmar

    2016-01-01

    Full Text Available Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6+ and LRIG1+ stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5+ cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5+ cells led to formation of pilomatricomas, while LRIG1+ cells formed trichoadenomas and LGR6+ cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity.

  5. Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells.

    Science.gov (United States)

    Jin, Ding Jun; Mata Martin, Carmen; Sun, Zhe; Cagliero, Cedric; Zhou, Yan Ning

    2017-02-01

    We have learned a great deal about RNA polymerase (RNA Pol), transcription factors, and the transcriptional regulation mechanisms in prokaryotes for specific genes, operons, or transcriptomes. However, we have only begun to understand how the transcription machinery is three-dimensionally (3D) organized into bacterial chromosome territories to orchestrate the transcription process and to maintain harmony with the replication machinery in the cell. Much progress has been made recently in our understanding of the spatial organization of the transcription machinery in fast-growing Escherichia coli cells using state-of-the-art superresolution imaging techniques. Co-imaging of RNA polymerase (RNA Pol) with DNA and transcription elongation factors involved in ribosomal RNA (rRNA) synthesis, and ribosome biogenesis has revealed similarities between bacteria and eukaryotes in the spatial organization of the transcription machinery for growth genes, most of which are rRNA genes. Evidence supports the notion that RNA Pol molecules are concentrated, forming foci at the clustering of rRNA operons resembling the eukaryotic nucleolus. RNA Pol foci are proposed to be active transcription factories for both rRNA genes expression and ribosome biogenesis to support maximal growth in optimal growing conditions. Thus, in fast-growing bacterial cells, RNA Pol foci mimic eukaryotic Pol I activity, and transcription factories resemble nucleolus-like compartmentation. In addition, the transcription and replication machineries are mostly segregated in space to avoid the conflict between the two major cellular functions in fast-growing cells.

  6. Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells

    Science.gov (United States)

    Jin, Ding Jun; Martin, Carmen Marta; Sun, Zhe; Cagliero, Cedric; Zhou, Yan Ning

    2017-01-01

    Overview. We have learned a great deal about RNA polymerase (RNA Pol), transcription factors, and the transcriptional regulation mechanisms in prokaryotes for specific genes, operons, or transcriptomes. However, we have only begun to understand how the transcription machinery is 3-dimensionally (3D) organized into bacterial chromosome territories to orchestrate the transcription process and to maintain harmony with the replication machinery in the cell. Much progress has been made recently in our understanding of the spatial organization of the transcription machinery in fast-growing Escherichia coli cells using state-of-the-art superresolution imaging techniques. Co-imaging of RNA polymerase (RNA Pol) with DNA and transcription elongation factors involved in ribosomal RNA (rRNA) synthesis and ribosome biogenesis has revealed similarities between bacteria and eukaryotes in the spatial organization of the transcription machinery for growth genes, most of which are rRNA genes. Evidence supports the notion that RNA Pol molecules are concentrated, forming foci at the clustering of rRNA operons resembling the eukaryotic nucleolus. RNA Pol foci are proposed to be active transcription factories for both rRNA genes expression and ribosome biogenesis to support maximal growth in optimal growing conditions. Thus, in fast-growing bacterial cells, RNA Pol foci mimic eukaryotic Pol I activity, and transcription factories resemble nucleolus-like compartmentation. In addition, the transcription and replication machineries are mostly segregated in space to avoid the conflict between the two major cellular functions in fast-growing cells. PMID:28006965

  7. Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Mike J; Yates, James T W; Jones, Kevin; Wood, Gemma; Coleman, Tanya

    2011-11-01

    A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. The Green's function formalism as a bridge between single- and multi-compartmental modeling.

    Science.gov (United States)

    Wybo, Willem A M; Stiefel, Klaus M; Torben-Nielsen, Benjamin

    2013-12-01

    Neurons are spatially extended structures that receive and process inputs on their dendrites. It is generally accepted that neuronal computations arise from the active integration of synaptic inputs along a dendrite between the input location and the location of spike generation in the axon initial segment. However, many application such as simulations of brain networks use point-neurons-neurons without a morphological component-as computational units to keep the conceptual complexity and computational costs low. Inevitably, these applications thus omit a fundamental property of neuronal computation. In this work, we present an approach to model an artificial synapse that mimics dendritic processing without the need to explicitly simulate dendritic dynamics. The model synapse employs an analytic solution for the cable equation to compute the neuron's membrane potential following dendritic inputs. Green's function formalism is used to derive the closed version of the cable equation. We show that by using this synapse model, point-neurons can achieve results that were previously limited to the realms of multi-compartmental models. Moreover, a computational advantage is achieved when only a small number of simulated synapses impinge on a morphologically elaborate neuron. Opportunities and limitations are discussed.

  9. Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model

    Directory of Open Access Journals (Sweden)

    Lingcai Kong

    2016-02-01

    Full Text Available Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R0, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period.

  10. Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil.

    Science.gov (United States)

    Smith, Rebecca Lee

    2016-08-01

    Hansen's disease (HD), or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44-45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control.

  11. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    Science.gov (United States)

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling.

  12. Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation.

    Science.gov (United States)

    McPhee, Joseph B; Schertzer, Jonathan D

    2015-12-01

    The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes. © 2015 Authors; published by Portland Press Limited.

  13. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

    OpenAIRE

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-01-01

    Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentr...

  14. Bone Loss in IBD

    Science.gov (United States)

    ... Home > Resources > Bone Loss in IBD Go Back Bone Loss in IBD Email Print + Share As many as ... halt bone loss are so important. CAUSES OF BONE LOSS IN IBD Experts point to several suspected causes ...

  15. Osteoprotegerin and Vascular Calcification: Clinical and Prognostic Relevance.

    Science.gov (United States)

    Makarović, Sandra; Makarović, Zorin; Steiner, Robert; Mihaljević, Ivan; Milas-Ahić, Jasminka

    2015-06-01

    Osteoprotegerin (OPG) is a key regulator in bone metabolism, that also has effect in vascular system. Studies suggest that osteoprotegerin is a critical arterial calcification inhibitor, and is released by endothelial cells as a protective mechanism for their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders. That has been shown in studies in vitro and in animal models. The discovery that OPG deficient mice (OPG -/- mice) develop severe osteoporosis and arterial calcification, has led to conclusion that osteoprotegerin might be mulecule linking vascular and bone system. Paradoxically however, clinical trials have shown recently that OPG serum levels is increased in coronary artery disease and correlates with its severity, ischemic cardial decompensation, and future cardiovascular events. Therefore it is possible that osteoprotegerin could have a new function as a potential biomarker in early identification and monitoring patients with cardiovascular disease. Amongst that osteoprotegerin is in association with well known atherosclerosis risc factors: undoubtedly it is proven its relationship with age, smoking and diabetes mellitus. There is evidence regarding presence of hyperlipoproteinemia and increased serum levels of osteoprotegerin. Also the researches have been directed in genetic level, linking certain single nucleotid genetic polymorphisms of osteoprotegerin and vascular calcification appearance. This review emphasises multifactorial role of OPG, presenting numerous clinical and experimental studies regarding its role in vascular pathology, suggesting a novel biomarker in cardiovascular diseases, showing latest conclusions about this interesting topic that needs to be further explored.

  16. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

  17. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  18. Histological analysis of femoral bones in rabbits administered by amygdalin

    Directory of Open Access Journals (Sweden)

    Veronika Kováčová

    2016-07-01

    Full Text Available Cyanogenic glycosides are present in several economically important plant foods. Amygdalin, one of the most common cyanoglucoside, can be found abundantly in the seeds of apples, bitter almonds, apricots, peaches, various beans, cereals, cassava and sorghum. Amygdalin has been used for the treatment of cancer, it shows killing effects on cancer cells by release of cyanide. However, its effect on bone structure has not been investigated to date. Therefore, the objective of this study was to determine a possible effect of amygdalin application on femoral bone microstructure in adult rabbits. Four month old rabbits were randomly divided into two groups of three animals each. Rabbits from E group received amygdalin intramuscularly at a dose 0.6 mg.kg-1 body weight (bw (group E, n = 3 one time per day during 28 days. The second group of rabbits without amygdalin supplementation served as a control (group C, n = 3. After 28 days, histological structure of femoral bones in both groups of rabbits was analysed and compared. Rabbits from E group displayed different microstructure in middle part of the compact bone and near endosteal bone surface. For endosteal border, an absence of the primary vascular longitudinal bone tissue was typical. This part of the bone was formed by irregular Haversian and/or by dense Haversian bone tissues. In the middle part of substantia compacta, primary vascular longitudinal bone tissue was observed. Cortical bone thickness did not change between rabbits from E and C groups. However, rabbits from E group had a significantly lower values of primary osteons' vascular canals and secondary osteons as compared to the C group. On the other hand, all measured parameters of Haversian canals did not differ between rabbits from both groups. Our results demonstrate that intramuscular application of amygdalin at the dose used in our study affects femoral bone microstructure in rabbits.

  19. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  20. [How Treatable is Vascular Dementia?].

    Science.gov (United States)

    Mori, Etsuro

    2016-04-01

    Vascular dementia is an umbrella term, encompassing the pathological changes in the brain due to cerebrovascular disease that result in dementia. Vascular dementia is the second most common form of dementia, after Alzheimer's disease. In this paper, I outline the concept of vascular dementia, the key aspects of the disease that are yet to be clarified, and the current status of clinical trials. Assessing these factors, I discuss how treatable vascular dementia presently is. Use of the term'vascular dementia'is riddled with uncertainties regarding disease classification, and non-standardized diagnostic criteria. There are difficulties in determining the exact relationship between cerebrovascular pathology and cognitive impairment. The comorbid effects of Alzheimer's pathology in some individuals also present an obstacle to reliable clinical diagnosis, and hinder research into effective management approaches. Vascular dementia is preventable and treatable, as there are established primary and secondary prevention measures for the causative cerebrovascular diseases, such as vascular risk factor intervention, antiplatelet therapy, and anticoagulation, amongst others. However, unlike Alzheimer's disease, there are no established symptomatic treatments for vascular dementia. Clinical trials of cholinesterase inhibitors and memantine indicate that they produce small cognitive benefits in patients with vascular dementia, though the exact clinical significance of these is uncertain. Data are insufficient to support the widespread use of these drugs in vascular dementia. Rehabilitation and physical and cognitive exercise may be beneficial, but evidence of cognitive benefit and relief of neuropsychiatric symptoms due to exercise is lacking.

  1. Shell bone histology indicates terrestrial palaeoecology of basal turtles.

    Science.gov (United States)

    Scheyer, Torsten M; Sander, P Martin

    2007-08-07

    The palaeoecology of basal turtles from the Late Triassic was classically viewed as being semi-aquatic, similar to the lifestyle of modern snapping turtles. Lately, this view was questioned based on limb bone proportions, and a terrestrial palaeoecology was suggested for the turtle stem. Here, we present independent shell bone microstructural evidence for a terrestrial habitat of the oldest and basal most well-known turtles, i.e. the Upper Triassic Proterochersis robusta and Proganochelys quenstedti. Comparison of their shell bone histology with that of extant turtles preferring either aquatic habitats or terrestrial habitats clearly reveals congruence with terrestrial turtle taxa. Similarities in the shell bones of these turtles are a diploe structure with well-developed external and internal cortices, weak vascularization of the compact bone layers and a dense nature of the interior cancellous bone with overall short trabeculae. On the other hand, 'aquatic' turtles tend to reduce cortical bone layers, while increasing overall vascularization of the bone tissue. In contrast to the study of limb bone proportions, the present study is independent from the uncommon preservation of appendicular skeletal elements in fossil turtles, enabling the palaeoecological study of a much broader range of incompletely known turtle taxa in the fossil record.

  2. Surgeon-Based 3D Printing for Microvascular Bone Flaps.

    Science.gov (United States)

    Taylor, Erin M; Iorio, Matthew L

    2017-07-01

    Background  Three-dimensional (3D) printing has developed as a revolutionary technology with the capacity to design accurate physical models in preoperative planning. We present our experience in surgeon-based design of 3D models, using home 3D software and printing technology for use as an adjunct in vascularized bone transfer. Methods  Home 3D printing techniques were used in the design and execution of vascularized bone flap transfers to the upper extremity. Open source imaging software was used to convert preoperative computed tomography scans and create 3D models. These were printed in the surgeon's office as 3D models for the planned reconstruction. Vascularized bone flaps were designed intraoperatively based on the 3D printed models. Results  Three-dimensional models were created for intraoperative use in vascularized bone flaps, including (1) medial femoral trochlea (MFT) flap for scaphoid avascular necrosis and nonunion, (2) MFT flap for lunate avascular necrosis and nonunion, (3) medial femoral condyle (MFC) flap for wrist arthrodesis, and (4) free fibula osteocutaneous flap for distal radius septic nonunion. Templates based on the 3D models allowed for the precise and rapid contouring of well-vascularized bone flaps in situ, prior to ligating the donor pedicle. Conclusions  Surgeon-based 3D printing is a feasible, innovative technology that allows for the precise and rapid contouring of models that can be created in various configurations for pre- and intraoperative planning. The technology is easy to use, convenient, and highly economical as compared with traditional send-out manufacturing. Surgeon-based 3D printing is a useful adjunct in vascularized bone transfer. Level of Evidence  Level IV. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. [Estrogens and vascular thrombosis].

    Science.gov (United States)

    Colmou, A

    1982-09-01

    The incidence of thromboses among young women has increased with widespread use of oral contraceptives (OCs) due to the significant thromboembolic risk of estrogen. Estrogens intervene at the vascular, platelet, and plasma levels as a function of hormonal variations in the menstrual cycle, increasing the aggregability of the platelets and thrombocytes, accelerating the formation of clots, and decreasing the amount of antithrombin III. Estrogens are used in medicine to treat breast and prostate cancers and in gynecology to treat dysmenorrhea, during the menopause, and in contraception. Smoking, cardiovascular disease and hypertension, hypercholesterolemia, and diabetes are contraindicators to estrogen use. Thrombosis refers to blockage of a blood vessel by a clot or thrombus. Before estrogens are prescribed, a history of phlebitis, obesity, hyperlipidemia, or significant varicosities should be ruled out. A history of venous thrombosis, hyperlipoproteinemia, breast nodules, serious liver condition, allergies to progesterone, and some ocular diseases of vascular origin definitively rule out treatment with estrogens. A family history of infarct, embolism, diabetes, cancer, or vascular accidents at a young age signals a need for greater patient surveillance. All patients receiving estrogens should be carefully observed for signs of hypertension, hypercholesterolemia, hypercoagulability, or diabetes. Nurses have a role to play in carefully eliciting the patient's history of smoking, personal and family medical problems, and previous and current laboratory results, as well as in informing the patients of the risks and possible side effects of OCs, especially for those who smoke. Nurses should educate patients receiving estrogens, especially those with histories of circulatory problems, to avoid standing in 1 position for prolonged periods, avoid heat which is a vasodilator, avoid obesity, excercise regularly, wear appropriate footgear, and follow other good health

  4. The pathobiology of vascular dementia.

    Science.gov (United States)

    Iadecola, Costantino

    2013-11-20

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Combined massive allograft and intramedullary vascularized fibula transfer: the capanna technique for lower-limb reconstruction.

    Science.gov (United States)

    Bakri, Karim; Stans, Anthony A; Mardini, Samir; Moran, Steven L

    2008-08-01

    Limb salvage has now replaced amputation as the standard treatment for primary bone tumors and can usually be offered to more than 85% of patients. Recently, a novel approach to limb salvage has been described by Capanna and colleagues whereby a massive bone allograft and intramedullary vascularized fibula are combined to reconstruct large, segmental bone defects. This produces a structurally competent reconstruction with enhanced vascular and osteogenic capabilities and the potential to achieve lower rates of infection, fracture, and nonunion. The Capanna technique has become a well-established means of long bone reconstruction and limb salvage in cases of large bony resection. The operative technique and reported outcomes of the Capanna technique are reviewed, and cases are presented.

  6. [Callus distraction and bone transport in the treatment of bone defects].

    Science.gov (United States)

    Baumgart, R; Schuster, B; Baumgart, T

    2017-08-01

    The method of "callus distraction" is the only technique which spontaneously produces vascularized bone within the surrounding soft tissues during lengthening reconstructive procedures. Remodeling of the regenerate bone to specific mechanical load can be influenced by the surgeon. In principle, there is no limit to the amount of new bone formation which can be created; this vascularized bone is both resistant to infection and can be created to replace resected infected bone. This is an important prerequisite for the successful treatment of large bone defects. The ring fixator is still a standard tool if no radiological control is available in the operating theater, or in other less sophisticated environments. Over the last 30 years, however, the development of motorized, external and fully implantable systems has made it possible to achieve a significant increase in device implementation, which goes far beyond the standard. High-performance, reliable, custom-made external and fully implantable systems are cost intensive and require special surgical skills, which can only be ensured at specialized centers. However, the complication-free treatment results justify the effort both for the patient and, ultimately, for the cost bearers.

  7. Dynamic dendritic compartmentalization underlies stimulus-specific adaptation in an insect neuron.

    Science.gov (United States)

    Prešern, Janez; Triblehorn, Jeffrey D; Schul, Johannes

    2015-06-01

    In many neural systems, repeated stimulation leads to stimulus-specific adaptation (SSA), with responses to repeated signals being reduced while responses to novel stimuli remain unaffected. The underlying mechanisms of SSA remain mostly hypothetical. One hypothesis is that dendritic processes generate SSA. Evidence for such a mechanism was recently described in an insect auditory interneuron (TN-1 in Neoconocephalus triops). Afferents, tuned to different frequencies, connect with different parts of the TN-1 dendrite. The specific adaptation of these inputs relies on calcium and sodium accumulation within the dendrite, with calcium having a transient and sodium a tonic effect. Using imaging techniques, we tested here whether the accumulation of these ions remained limited to the stimulated parts of the dendrite. Stimulation with a fast pulse rate, which results in strong adaptation, elicited a transient dendritic calcium signal. In contrast, the sodium signal was tonic, remaining high during the fast pulse rate stimulus. These time courses followed the predictions from the previous pharmacological experiments. The peak positions of the calcium and sodium signals differed with the carrier frequency of the stimulus; at 15 kHz, peak locations were significantly more rostral than at 40 kHz. This matched the predictions made from neuroanatomical data. Our findings confirm that excitatory postsynaptic potentials rather than spiking cause the increase of dendritic calcium and sodium concentrations and that these increases remain limited to the stimulated parts of the dendrite. This supports the hypothesis of "dynamic dendritic compartmentalization" underlying SSA in this auditory interneuron. Copyright © 2015 the American Physiological Society.

  8. Evaluation of the GastroPlus™ Advanced Compartmental and Transit (ACAT) Model in Early Discovery.

    Science.gov (United States)

    Gobeau, N; Stringer, R; De Buck, S; Tuntland, T; Faller, B

    2016-09-01

    The aim of this study was to evaluate the oral exposure predictions obtained early in drug discovery with a generic GastroPlus Advanced Compartmental And Transit (ACAT) model based on the in vivo intravenous blood concentration-time profile, in silico properties (lipophilicity, pKa) and in vitro high-throughput absorption-distribution-metabolism-excretion (ADME) data (as determined by PAMPA, solubility, liver microsomal stability assays). The model was applied to a total of 623 discovery molecules and their oral exposure was predicted in rats and/or dogs. The predictions of Cmax, AUClast and Tmax were compared against the observations. The generic model proved to make predictions of oral Cmax, AUClast and Tmax within 3-fold of the observations for rats in respectively 65%, 68% and 57% of the 537 cases. For dogs, it was respectively 77%, 79% and 85% of the 124 cases. Statistically, the model was most successful at predicting oral exposure of Biopharmaceutical Classification System (BCS) class 1 compounds compared to classes 2 and 3, and was worst at predicting class 4 compounds oral exposure. The generic GastroPlus ACAT model provided reasonable predictions especially for BCS class 1 compounds. For compounds of other classes, the model may be refined by obtaining more information on solubility and permeability in secondary assays. This increases confidence that such a model can be used in discovery projects to understand the parameters limiting absorption and extrapolate predictions across species. Also, when predictions disagree with the observations, the model can be updated to test hypotheses and understand oral absorption.

  9. Leveraging unsupervised training sets for multi-scale compartmentalization in renal pathology

    Science.gov (United States)

    Lutnick, Brendon; Tomaszewski, John E.; Sarder, Pinaki

    2017-03-01

    Clinical pathology relies on manual compartmentalization and quantification of biological structures, which is time consuming and often error-prone. Application of computer vision segmentation algorithms to histopathological image analysis, in contrast, can offer fast, reproducible, and accurate quantitative analysis to aid pathologists. Algorithms tunable to different biologically relevant structures can allow accurate, precise, and reproducible estimates of disease states. In this direction, we have developed a fast, unsupervised computational method for simultaneously separating all biologically relevant structures from histopathological images in multi-scale. Segmentation is achieved by solving an energy optimization problem. Representing the image as a graph, nodes (pixels) are grouped by minimizing a Potts model Hamiltonian, adopted from theoretical physics, modeling interacting electron spins. Pixel relationships (modeled as edges) are used to update the energy of the partitioned graph. By iteratively improving the clustering, the optimal number of segments is revealed. To reduce computational time, the graph is simplified using a Cantor pairing function to intelligently reduce the number of included nodes. The classified nodes are then used to train a multiclass support vector machine to apply the segmentation over the full image. Accurate segmentations of images with as many as 106 pixels can be completed only in 5 sec, allowing for attainable multi-scale visualization. To establish clinical potential, we employed our method in renal biopsies to quantitatively visualize for the first time scale variant compartments of heterogeneous intra- and extraglomerular structures simultaneously. Implications of the utility of our method extend to fields such as oncology, genomics, and non-biological problems.

  10. Application of oil gas-chromatography in reservoir compartmentalization in a mature Venezuelan oil field

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, N.G.; Mompart, L. [Maraven, Caracas (Venezuela); Talukdar, S.C.

    1996-08-01

    Gas chromatographic oil {open_quotes}fingerprinting{close_quotes} was successfully applied in a multidisciplinary production geology project by Maraven, S.A. to define the extent of vertical and lateral continuity of Eocene and Miocene sandstone reservoirs in the highly faulted Bloque I field, Maracaibo Basin, Venezuela. Seventy-five non-biodegraded oils (20{degrees}-37.4{degrees} API) were analyzed with gas chromatography. Fifty were produced from the Eocene Misoa C-4, C-5, C-6 or C-7 horizons, fifteen from the Miocene basal La Rosa and ten from multizone completions. Gas chromatographic and terpane and sterane biomarker data show that all of the oils are genetically related. They were expelled from a type II, Upper Cretaceous marine La Luna source rock at about 0.80-0.90% R{sub o} maturity. Alteration in the reservoir by gas stripping with or without subsequent light hydrocarbons mixing was observed in some oils. Detailed chromatographic comparisons among the oils shown by star plots and cluster analysis utilizing several naphthenic and aromatic peak height ratios, resulted in oil pool groupings. This led to finding previously unknown lateral and vertical reservoir communication and also helped in checking and updating the scaling character of faults. In the commingled oils, percentages of each contributing zone in the mixture were also determined giving Maraven engineers a proven, rapid and inexpensive tool for production allocation and reservoir management The oil pool compartmentalization defined by the geochemical fingerprinting is in very good agreement with the sequence stratigraphic interpretation of the reservoirs and helped evaluate the influence of structure in oil migration and trapping.

  11. Convex-Optimization-Based Compartmental Pharmacokinetic Analysis for Prostate Tumor Characterization Using DCE-MRI.

    Science.gov (United States)

    Ambikapathi, ArulMurugan; Chan, Tsung-Han; Lin, Chia-Hsiang; Yang, Fei-Shih; Chi, Chong-Yung; Wang, Yue

    2016-04-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful imaging modality to study the pharmacokinetics in a suspected cancer/tumor tissue. The pharmacokinetic (PK) analysis of prostate cancer includes the estimation of time activity curves (TACs), and thereby, the corresponding kinetic parameters (KPs), and plays a pivotal role in diagnosis and prognosis of prostate cancer. In this paper, we endeavor to develop a blind source separation algorithm, namely convex-optimization-based KPs estimation (COKE) algorithm for PK analysis based on compartmental modeling of DCE-MRI data, for effective prostate tumor detection and its quantification. The COKE algorithm first identifies the best three representative pixels in the DCE-MRI data, corresponding to the plasma, fast-flow, and slow-flow TACs, respectively. The estimation accuracy of the flux rate constants (FRCs) of the fast-flow and slow-flow TACs directly affects the estimation accuracy of the KPs that provide the cancer and normal tissue distribution maps in the prostate region. The COKE algorithm wisely exploits the matrix structure (Toeplitz, lower triangular, and exponential decay) of the original nonconvex FRCs estimation problem, and reformulates it into two convex optimization problems that can reliably estimate the FRCs. After estimation of the FRCs, the KPs can be effectively estimated by solving a pixel-wise constrained curve-fitting (convex) problem. Simulation results demonstrate the efficacy of the proposed COKE algorithm. The COKE algorithm is also evaluated with DCE-MRI data of four different patients with prostate cancer and the obtained results are consistent with clinical observations.

  12. Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit: compartmental analysis and PK-PD evaluation.

    Science.gov (United States)

    Pamulapati, Chandrasena R; Schoenwald, Ronald D

    2012-01-01

    The elimination kinetics of the pharmacologically active compound 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4) were characterized along with pharmacodynamic (PD) measurements. Four compartmental models based on ocular anatomy, physiology, and possible absorption and disposition pathways were proposed to model the pharmacokinetic (PK) data in WinNonlin and the best model was chosen based on statistical and goodness-of-fit criteria. A three-compartment physiologic-based PK model with a bidirectional transfer between cornea and aqueous humor and a unidirectional transfer between aqueous humor and iris-ciliary body best described the data. The ocular PD parameters, maximum effect attributed to drug (E(max)) and drug concentration which produces 50% of maximum effect (EC(50)), were estimated with change in intraocular pressure (ΔIOP) as the effect (PD response) in the effect compartment model (PK-PD link model) using aqueous humor concentration-time and ΔIOP-time profiles. The link model better described the effect compartment concentrations than a simple E(max) model that used iris-ciliary body concentration-time data, indicating that there is an apparent temporal displacement between aqueous humor concentration (plasma/central compartment equivalent) and pharmacological effect. A physiologically plausible value of 0.0159 min(-1) was obtained for the drug elimination rate constant (k(eo)) from the effect site to account for equilibration time in the biophase. Hysteresis was observed for the iris-ciliary body, aqueous humor drug concentrations, and effect data, further confirming the utility of the link model to describe the PD of MC4. Copyright © 2011 Wiley-Liss, Inc.

  13. Axial compartmentation of descending and ascending thin limbs of Henle's loops

    Science.gov (United States)

    Westrick, Kristen Y.; Serack, Bradley; Dantzler, William H.

    2013-01-01

    In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss. PMID:23195680

  14. Compartmentalization of ER-Bound Chaperone Confines Protein Deposit Formation to the Aging Yeast Cell.

    Science.gov (United States)

    Saarikangas, Juha; Caudron, Fabrice; Prasad, Rupali; Moreno, David F; Bolognesi, Alessio; Aldea, Martí; Barral, Yves

    2017-03-20

    In order to produce rejuvenated daughters, dividing budding yeast cells confine aging factors, including protein aggregates, to the aging mother cell. The asymmetric inheritance of these protein deposits is mediated by organelle and cytoskeletal attachment and by cell geometry. Yet it remains unclear how deposit formation is restricted to the aging lineage. Here, we show that selective membrane anchoring and the compartmentalization of the endoplasmic reticulum (ER) membrane confine protein deposit formation to aging cells during division. Supporting the idea that the age-dependent deposit forms through coalescence of smaller aggregates, two deposits rapidly merged when placed in the same cell by cell-cell fusion. The deposits localized to the ER membrane, primarily to the nuclear envelope (NE). Strikingly, weakening the diffusion barriers that separate the ER membrane into mother and bud compartments caused premature formation of deposits in the daughter cells. Detachment of the Hsp40 protein Ydj1 from the ER membrane elicited a similar phenotype, suggesting that the diffusion barriers and farnesylated Ydj1 functioned together to confine protein deposit formation to mother cells during division. Accordingly, fluorescence correlation spectroscopy measurements in dividing cells indicated that a slow-diffusing, possibly client-bound Ydj1 fraction was asymmetrically enriched in the mother compartment. This asymmetric distribution depended on Ydj1 farnesylation and intact diffusion barriers. Taking these findings together, we propose that ER-anchored Ydj1 binds deposit precursors and prevents them from spreading into daughter cells during division by subjecting them to the ER diffusion barriers. This ensures that the coalescence of precursors into a single deposit is restricted to the aging lineage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Nuclear antigens in Trichinella spiralis infected muscle cells: nuclear extraction, compartmentalization and complex formation.

    Science.gov (United States)

    Yao, C; Jasmer, D P

    1998-05-01

    Infection of mammalian skeletal muscle cells by Trichinella spiralis induces a series of changes that include: reentry of the terminally differentiated host cell into the cell cycle; suspension of infected cells in apparent G2/M; and transcriptional inactivation of the differentiated skeletal muscle gene program. Cell cycle repositioning and genetic reprogramming are chronic characteristics of host cells that can remain infected for years. Nuclear antigens (NA, 79, 86 and 97 kDa) that localize to host cell nuclei have been detected with antibodies against T. spiralis proteins. Since NA may play a role in regulating the infected cell phenotype, their origin, nuclear compartmentalization, and biochemical properties were investigated. We show that a monoclonal antibody to a defined epitope of T. spiralis glycans binds these NA, which indicates the parasite origin of these proteins. NA were not extracted under conditions that solubilized chromatin from infected cell nuclei. In contrast, NA were coextracted with B lamins (nuclear envelope) by 4 M urea. Urea extraction was pH dependent (8.0), suggesting ionic interaction of NA in protein complexes. Nevertheless, confocal microscopy demonstrated colocalization of NA with host chromatin, and not B lamins. Nuclear protein complexes containing NA were observed under non-reducing conditions, and NA were readily cross-linked in isolated nuclei by succinimidyl protein conjugating reagents. The results establish methods to extract NA from infected cell nuclei for further biochemical analysis, establish the existence of nuclear protein complexes containing NA and demonstrate colocalization of NA with host chromatin. Collectively, the results provide a foundation from which to investigate the role of NA in regulating the T. spiralis infected skeletal muscle cell phenotype.

  16. Single-cell nanobiopsy reveals compartmentalization of mRNA in neuronal cells.

    Science.gov (United States)

    Tóth, Eszter N; Lohith, Akshar; Mondal, Manas; Guo, Jia; Fukamizu, Akiyoshi; Pourmand, Nader

    2018-01-29

    In highly polarized cells such as neurons, compartmentalization of mRNA and of local protein synthesis enables remarkably fast, precise, and local responses to external stimuli. These responses are highly important for neuron growth cone guidance, synapse formation, and regeneration following injury. Because an altered spatial distribution of mRNA can result in mental retardation or neurodegenerative diseases, subcellular transcriptome analysis of neurons could be a useful tool for studying these conditions, but current techniques, such as in situ hybridization, bulk microarray, or RNA-Seq, impose tradeoffs between spatial resolution and multiplexing. To obtain a comprehensive analysis of the cell body versus neurite transcriptome from the same neuron, we have recently developed a label-free, single-cell nanobiopsy platform based on scanning ion conductance microscopy (SICM), that uses electrowetting within a quartz nanopipette to extract cellular material from living cells with minimal disruption of the cellular membrane and milieu. In this study, we used this platform to collect samples from the cell bodies and neurites of human neurons and analyzed the mRNA pool with multiplex RNA-Seq. The minute volume of a nanobiopsy sample allowed us to extract samples from several locations in the same cell and to map the various mRNA species to specific subcellular locations. In addition to previously identified transcripts, we discovered new sets of mRNAs localizing to neurites, including nuclear genes such as Eomes and Nap1l3. In summary, our single-neuron nanobiopsy analysis provides opportunities to improve our understanding of intracellular mRNA transport and local protein composition in neuronal growth, connectivity, and function. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

  17. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Giuseppe eGangarossa

    2013-02-01

    Full Text Available The nucleus accumbens (NAc is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP or the Cre-recombinase (Cre under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific ERK phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist, quinpirole (a D2R-like agonist, apomorphine (a non-selective DA receptor agonist, raclopride (a D2R-like antagonist, and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.

  18. Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.

    Science.gov (United States)

    Bahouth, Suleiman W; Nooh, Mohammed M

    2017-08-01

    Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second "barcode" imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the "sequence-dependent pathway". Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second "barcode". Here we will review recent developments in GPCR trafficking in general and the human β 1 -adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction

  19. Anaesthesia for vascular emergencies.

    Science.gov (United States)

    Ellard, L; Djaiani, G

    2013-01-01

    Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  20. Pediatric vascularized composite allotransplantation.

    Science.gov (United States)

    Doumit, Gaby; Gharb, Bahar Bassiri; Rampazzo, Antonio; Papay, Francis; Siemionow, Maria Z; Zins, James E

    2014-10-01

    Vascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. Papers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. Although the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. Considering the non-life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.

  1. Spinal Cord Vascular Disease

    Directory of Open Access Journals (Sweden)

    Abdoreza Ghoreishi

    2017-02-01

    Full Text Available The spinal cord is subject to many of the same vascular diseases that involve the brain, but its anatomy and embryology render it susceptible to some syndromes that do not have intracranial counterparts.The embryonic arterial supply to the spinal cord derives from intradural vessels that enter at each spinal level and divide to follow the dorsal and ventral roots. SPINAL CORD ISCHEMIA: The midthoracic levels of the spinal cord are traditionally considered to be the most vulnerable to compromise from hypoperfusion, but more recent evidence suggests that the lower thoracic cord is at greater risk . The actual prevalence of spinal cord infarction is unknown, but is generally cited as representing 1% to 2% of all central neurovascular events and 5% to 8% of all acute myelopathies. Weakness (100%, sensory loss (89%, back pain at onset (82%, and urinary complaints requiring catheterization (75% were the most common symptoms of cord ischemia at the time of presentation . Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction. Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction.   Aortic pathologies with regional hemodynamic compromise are the most common cause of spinal cord infarction, accounting for 30% to 40% of cases.                                                                                 The medical management of spinal cord ischemia is generally supportive and focused on reducing risk for

  2. Our vascular surgery experiences in Syrian civil war

    Directory of Open Access Journals (Sweden)

    İyad Fansa

    2014-12-01

    Full Text Available Objective: Due to the ongoing civil war in Syria, numerous vascular injured patients are admitted to our hospital with gunshot wounds. In this study, patients who admitted our hospital, diagnosed with vascular trauma due to gunshot were evaluated with the respect of injury site, additional injuries, surgical interventions and outcomes. Methods: The study included 58 patients wounded in Syrian war and admitted to our hospital between 01.01.2012 and 01.09.2014. Results= There were 5.1% (n=3 female and 94.9% (n=55 male patients. Age range is 5-75 years and the average of age was identified as 28.61. In 12.1% (n=7 of patients with extensive tissue defects of the muscle-nerve-bone injury has been identified, despite the vascular interventions in these patients, 8.6% (n=5 of patients, the limb has been amputated. Totally 15.5% (n=9 of 58 operated patients died. Two patients died because of major vascular injury with intra-abdominal organ injuries. In one patient; infection induced sepsis and multi organ failure was detected. Six patients were lost due to hypovolemic shock as a result of late arriving. Conclusion: In patients admitted with gunshot vascular injury arrival time, the presence of additional injuries and the location of injury affect mortality rates.

  3. Dual roles of heparanase in vascular calcification associated with human carotid atherosclerosis

    DEFF Research Database (Denmark)

    Aldi, S.; Eriksson, L.; Kronqvist, M.

    2017-01-01

    Vascular intimal calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of heparanase in osteogenesis and bone remodeling...... is controversial. Previously, we have reported the upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed that the HPSE expression levels correlated with markers of inflammation and increased thrombogenicity....

  4. Effectiveness of ultrasonography in detecting intraosseous vascularization: an in-vitro study

    OpenAIRE

    Baladi, Marina Gazzano; Tucunduva, Maria Jose Albuquerque Pereira de Souza e; Tucunduva Neto, Renato; Cortes, Arthur Rodriguez Gonzalez; Aoki, Eduardo Massaharu; Arita, Emiko Saito; de Freitas, Claudio Fróes

    2014-01-01

    Ultrasonography is useful to diagnose lesions, insofar as it detects the type of injury, and to assess the degree of vascularization of tumors. However, intraosseous lesions may represent a challenge, since the surrounding bone thickness could prevent ultrasound signal capture. The aim of this study was to evaluate the infl uence of surrounding bone thickness on the ability of ultrasonography in capturing the echo signal of blood vessels. Macerated porcine hemimandibles (n = 20) with differen...

  5. Systemic zoledronate treatment both prevents resorption of allograft bone and increases the retention of new formed bone during revascularization and remodelling. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Aspenberg Per

    2006-08-01

    Full Text Available Abstract Background In osteonecrosis the vascular supply of the bone is interrupted and the living cells die. The inorganic mineral network remains intact until ingrowing blood vessels invade the graft. Accompanying osteoclasts start to resorb the bone trabeculae and gradually replace the bone. If the osteonecrosis occurs in mechanically loaded parts, like in the subchondral bone of a loaded joint, the remodelling might lead to a weakening of the bone and, in consequence to a joint collapse. Systemic bisphosphonate treatment can reduce the resorption of necrotic bone. In the present study we investigate if zoledronate, the most potent of the commercially available bisphosphonates, can be used to reduce the amount or speed of bone graft remodeling. Methods Bone grafts were harvested and placed in a bone chamber inserted into the tibia of a rat. Host tissue could grow into the graft through openings in the chamber. Weekly injections with 1.05 μg zoledronate or saline were given subcutaneously until the rats were harvested after 6 weeks. The specimens were fixed, cut and stained with haematoxylin/eosin and used for histologic and histomorphometric analyses. Results By histology, the control specimens were almost totally resorbed in the remodeled area and the graft replaced by bone marrow. In the zoledronate treated specimens, both the old graft and new-formed bone remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft+ new bone within the remodelled area was 35 % (SD 13 in the zoledronate treated grafts and 19 % (SD 12 in the controls (p = 0.001. Also the amount of new bone was increased in the treated specimens (22 %, SD 7 compared to the controls (14 %, SD 9, p = 0.032. Conclusion We show that zoledronate can be used to decrease the resorption of both old graft and new-formed bone during bone graft remodelling. This might be useful in bone grafting procedure but also in other orthopedic

  6. [Skillful care for chronic vascular wounds].

    Science.gov (United States)

    Goullet de Rugy, C; Lazareth, I; You, C; Stansal, A; Priollet, P

    2016-09-01

    In vascular medicine, wound care requires pluridisciplinary expertise and nursing skill. Care must be perfectly adapted to each individual patient, the specificities of each particular wound, and the underlying vascular disease. The goal is to achieve wound healing. Inappropriate care can retard healing or even aggravate the wound. The skin should be cleaned with water a non-allergic detergent and should concern the entire limb in addition to the wound itself. Fibrin or necrosis detersion is an important step that can be painful. Different tools are available. The skin around the wound should be hydrated and protected, focusing on fragile areas, such as the tibial crest and heals, in order to prevent the development of new wounds. Other more complex interventions include tenosynovectomy, bone gouging and reduction of the necrotic toe that when properly performed can prevent a new passage in the operating room. If the ischemia becomes critical, the foot should be held warm with a carded cotton, taking care to separate the toes with dry dressings in order to preserve the healthy tissue and avoid induced wounds. Finally, compression bands are indispensable in cases with edema or venous hyperpressure. A skillful banding technique is essential, especially for legs with complex morphology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    Five patients with non-viable limbs had the vessel ligated. Conclusions. A TIVS in the damage control setting is both life- and limb-saving. These shunts can be inserted safely in a facility without access to a surgeon with vascular surgery experience if there is uncontrollable bleeding or the delay to definitive vascular surgery ...

  8. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    part of a damage control procedure, 7 patients were referred from a hospital without access to vascular surgical facilities with the TIVS in situ, and in the remaining 6 patients the TIVS was inserted during repair of a lower limb fracture with an associated vascular injury. Damage control procedure. Twenty-two patients had a ...

  9. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  10. Updates in biological therapies for knee injuries: bone.

    Science.gov (United States)

    Kfuri, Mauricio; de Freitas, Rafael Lara; Batista, Bruno Bellaguarda; Salim, Rodrigo; Castiglia, Marcello Teixeira; Tavares, Ricardo Antonio; Araújo, Paulo Henrique

    2014-09-01

    Bone is a unique tissue because of its mechanical properties, ability for self-repair, and enrollment in different metabolic processes such as calcium homeostasis and hematopoietic cell production. Bone barely tolerates deformation and tends to fail when overloaded. Fracture healing is a complex process that in particular cases is impaired. Osteoprogenitor cells proliferation, growth factors, and a sound tridimensional scaffold at fracture site are key elements for new bone formation and deposition. Mechanical stability and ample vascularity are also of great importance on providing a proper environment for bone healing. From mesenchymal stem cells delivery to custom-made synthetic scaffolds, many are the biological attempts to enhance bone healing. Impaired fracture healing represents a real burden to contemporary society. Sound basic science knowledge has contributed to newer approaches aimed to accelerate and improve the quality of bone healing.

  11. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2016-10-01

    that underlie these responses will further enable tissue engineers to develop viable bone graft substitutes in vitro through bioreactor culture [189...Terheyden H. Tissue engineering of a vascularized bone graft of critical size with an osteogenic and angiogenic factor-based in vivo bioreactor . Tis- sue...331–9. 182. Roy R, Boskey AL, Bonassar LJ. Non-enzymatic glycation of chondrocyte-seeded collagen gels for cartilage tissue engineer - ing. J Orthop

  12. Case report 433: Aneurysmal bone cyst of T8

    Energy Technology Data Exchange (ETDEWEB)

    Daffner, R.H.; Linetsky, L.; Zabkar, J.H.

    1987-07-01

    A case of aneurysmal bone cyst involving the vertebral body and posterior elements of T8 in a 14-year-old boy has been presented. The case is interesting from the standpoint of the use of multiple imaging techniques to narrow the diagnostic possibilities. The combination of an expansile, vascular lesion as visualized on CT and an MR examination, demonstrating high signal at T2 parameters is strongly suggestive of either aneurysmal bone cyst or hemangioma. (orig./SHA).

  13. [Bone and Nutrition. A novel function of phosphorus].

    Science.gov (United States)

    Taketani, Yutaka; Imi, Yukiko; Abuduli, Maerjianghan

    2015-07-01

    Phosphorus is an essential nutrient for bone formation by forming hydroxyapatite with calcium. Simultaneously, phosphorus is also a component of high energy bond of ATP, nucleic acids, and phospholipids. Recent studies have demonstrated that excess or lack of dietary phosphorus intake may cause vascular dysfunction, cardiac hypertrophy, and impaired glucose tolerance. Here, we introduce recent findings about the effects of high or low dietary phosphorus intake on several organs except for bone.

  14. Nutrition and vascular dementia.

    Science.gov (United States)

    Perez, L; Heim, L; Sherzai, A; Jaceldo-Siegl, K; Sherzai, A

    2012-04-01

    The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies. Vascular dementia (VaD) is the second most common type of dementia. The prevalence of VaD continues to increase as the US population continues to grow and age. Currently, control of potential risk factors is believed to be the most effective means of preventing VaD. Thus, identification of modifiable risk factors for VaD is crucial for development of effective treatment modalities. Nutrition is one of the main modifiable variables that may influence the development of VaD. A systematic review of literature was conducted using the PubMed, Web of Science, and CINAHL Plus databases with search parameters inclusive of vascular dementia, nutrition, and vascular cognitive impairment (VCI). Fourteen articles were found that proposed a potential role of specific nutritional components in VaD. These components included antioxidants, lipids, homocysteine, folate, vitamin B12, and fish consumption. Antioxidants, specifically Vitamin E and C, and fatty fish intake were found to be protective against VaD risk. Fried fish, elevated homocysteine, and lower levels of folate and vitamin B12 were associated with increased VaD. Evidence for dietary lipids was inconsistent, although elevated midlife serum cholesterol may increase risk, while late-life elevated serum cholesterol may be associated with decreased risk of VaD. Currently, the most convincing evidence as to the relationship between VaD and nutrition exists for micronutrients, particularly Vitamin E and C. Exploration of nutrition at the macronutrient level and additional long term prospective cohort studies are warranted to better understand the role of nutrition in VaD disease development and progression. At present, challenges in this research include limitations in sample size, which was commonly cited. Also, a variety of diagnostic criteria for VaD were employed in the studies

  15. The Danish Vascular Registry, Karbase

    Directory of Open Access Journals (Sweden)

    Eldrup N

    2016-10-01

    Full Text Available Nikolaj Eldrup,1,2 Charlotte Cerqueira,3 Louise de la Motte,2,4 Lisbet Knudsen Rathenborg,2,4 Allan K Hansen2,5 1Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, 2Karbase, The Danish Vascular Registry, Aarhus, 3Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Capital Region of Denmark, 4Department of Vascular Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 5Department of Vascular Surgery, Aalborg University Hospital, Aalborg, Denmark Aim: The Danish Vascular Registry (DVR, Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry for quality assessment and research. Study population: All patients undergoing vascular interventions (surgical and endovascular at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ~9,000 procedures are added. By January 2016, .180,000 procedures have been recorded. Since 2001, data completeness has been .90% (compared to the Danish National Patient Register. Main variables: Variables include information on descriptive patient data (ie, age, sex, height, and weight and comorbidity (ie, previous cardiovascular disease and diabetes. Process variable includes waiting time (time from event to medical contact and treatment and the type of procedures conducted. Outcome variables for in-hospital complications (ie, wound complications, myocardial infarction, stroke, amputation, respiratory complications, and renal insufficiency and 30-day patency are submitted. Variables for medical treatment (antithrombotic and statin treatment, amputation, and survival are extracted from nationwide, administrative registers. Conclusion: The DVR reports outcome on key indicators for

  16. Acute radiographic workup of blunt temporal bone trauma: maxillofacial versus temporal bone CT.

    Science.gov (United States)

    Dempewolf, Ryan; Gubbels, Sam; Hansen, Marlan R

    2009-03-01

    To evaluate the radiographic workup of blunt temporal bone trauma and determine the utility of maxillofacial computed tomography (CT) versus temporal bone CT in identifying carotid canal fractures. Retrospective review. The charts of 227 patients evaluated at a level I trauma center receiving a temporal bone CT for blunt head trauma within 48 hours of admission were reviewed. Acute evaluation findings and complications were noted. Sensitivity, specificity, positive predictive value, and negative predictive (NPV) value were calculated for maxillofacial CT's ability to identify carotid canal fractures compared to temporal bone CT. One hundred forty fractures were found. Physical exam findings of blood in the external auditory canal as the sole finding, and blood in the external auditory canal with associated hemotympanum were significantly associated with absence and presence of fracture respectively. The sensitivity and specificity of maxillofacial CT for identifying carotid canal fractures, when compared to temporal bone CT, were 90.3% and 94.4% respectively (NPV > 95%). Only 6% of all patients either did have or should have had their management changed based on the temporal bone CT findings. All of these changes were regarding further workup for blunt carotid artery injury. A combination of helical computed tomography and physical exam findings can allow for judicious use of temporal bone CTs when no maxillofacial CT is indicated. Temporal bone CTs rarely change acute management. But when they do, it is in regard to the need for further workup of possible vascular injury. Lastly, maxillofacial CTs are adequate for identifying carotid canal fractures.

  17. Vascular network remodeling via vessel cooption, regression and growth in tumors

    CERN Document Server

    Bartha, K

    2016-01-01

    The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts, that microvascular density (MVD, regarded as an important diagnostic tool in cancer treatment, does not necessarily determine the tempo of tumor progression. Instead it is suggested, that the MVD of the original tissue as well as the metabolic demand of the individual tumor cell plays the major role in the initial stages of tumor growth.

  18. Diagnostic criteria for vascular dementia

    NARCIS (Netherlands)

    Scheltens, P.; Hijdra, A. H.

    1998-01-01

    The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria

  19. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings

    2012-01-01

    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  20. Association between findings on palmarodorsal radiographic images and detection of a fracture in the proximal sesamoid bones of forelimbs obtained from cadavers of racing Thoroughbreds.

    Science.gov (United States)

    Anthenill, Lucy A; Stover, Susan M; Gardner, Ian A; Hill, Ashley E; Lee, Christina M; Anderson, Mark L; Barr, Bradd C; Read, Deryck H; Johnson, Bill J; Woods, Leslie W; Daft, Barbara M; Kinde, Hailu; Moore, Janet D; Farman, Cynthia A; Odani, Jenee S; Pesavento, Patricia A; Uzal, Francisco A; Case, James T; Ardans, Alex A

    2006-05-01

    To determine the distribution for limbs and bones in horses with fractures of the proximal sesamoid bones and relationships with findings on palmarodorsal radiographic images. Proximal sesamoid bones obtained from both forelimbs of cadavers of 328 racing Thoroughbreds. Osteophytes; large vascular channels; and fracture location, orientation, configuration, and margin distinctness were categorized by use of high-detail contact palmarodorsal radiographs. Distributions of findings were determined. Relationships between radiographic findings and fracture characteristics were examined by use of chi2 and logistic regression techniques. Fractures were detected in 136 (41.5%) horses. Biaxial fractures were evident in 109 (80%) horses with a fracture. Osteophytes and large vascular channels were evident in 266 (81%) and 325 (99%) horses, respectively. Medial bones typically had complete transverse or split transverse simple fractures, indistinct fracture margins, > 1 vascular channel that was > 1 mm in width, and osteophytes in abaxial wing and basilar middle or basilar abaxial locations. Lateral bones typically had an oblique fracture and distinct fracture margins. Odds of proximal sesamoid bone fracture were approximately 2 to 5 times higher in bones without radiographic evidence of osteophytes or large vascular channels, respectively. Biaxial fractures of proximal sesamoid bones were common in cadavers of racing Thoroughbreds. Differences between medial and lateral bones for characteristics associated with fracture may relate to differences in fracture pathogeneses for these bones. Osteophytes and vascular channels were common findings; however, fractures were less likely to occur in bones with these features.

  1. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?★

    Science.gov (United States)

    Li, Yi; Hua, Xuming; Hua, Fang; Mao, Wenwei; Wan, Liang; Li, Shiting

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor. PMID:25206414

  2. [CLINICAL APPLICATION OF OXFORD MOBILE-BEARING BIPOLAR PROSTHESIS UNICOMPARTMENTAL KNEE ARTHROPLASTY FOR SINGLE COMPARTMENTAL KNEE OSTEOARTHRITIS].

    Science.gov (United States)

    Wang, Shangzeng; Cheng, Shao; Wang, Yisheng

    2016-01-01

    To evaluate the effectiveness of Oxford mobile-bearing bipolar prosthesis unicompartmental knee arthroplasty (UKA) in the treatment of single compartmental knee osteoarthritis. Between June 2011 and July 2013, 22 cases of single compartmental knee osteoarthritis were treated by Oxford mobile-bearing bipolar prosthesis UKA. Of 22 cases, 8 were male and 14 were female with an average age of 65 years (range, 45-80 years); the left knee was involved in 12 cases, and the right knee in 10 cases, with a mean disease duration of 32.5 months (range, 8-90 months). The mean weight was 55.2 kg (range, 50-65 kg), and the mean body mass index was 20.8 kg/m2 (range, 17-25 kg/m2). Osteoarthritis involved in the single knee medial compartment in all patients. Knee society score (KSS) and range of motion (ROM) were measured to evaluate the knee joint function. Primary healing of incision was obtained in all patients, and there was no complication of infection, bedsore, or deep venous thrombosis. Postoperative follow-up was 2-4 years (mean, 3.2 years). The X-ray films showed good position of prosthesis, no prosthesis dislocation, or periprosthetic infection during follow-up. Knee ROM, KSS function score, and KSS clinical score were significantly improved at 1 week after operation and at last follow-up when compared with preoperative ones (P 0.05). Oxford mobile-bearing bipolar prosthesis UKA is an effective method to treat single compartmental knee osteoarthritis, with the advantages of less trauma, earlier rehabilitation exercise, near physiological state in joint function, and less risk of complications.

  3. Purkinje Cell Compartmentation in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant Mouse (Nax - Naked-Ataxia Mutant Mouse)

    Science.gov (United States)

    Bailey, Karen; Rahimi Balaei, Maryam; Mannan, Ashraf; Del Bigio, Marc R.; Marzban, Hassan

    2014-01-01

    The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous mutation in Acp2 results in severe cerebellar defects. These include a reduced size, abnormal lobulation, and an apparent anterior cerebellar disorder with an absent or hypoplastic vermis. Based on differential gene expression in the cerebellum, the mouse cerebellar cortex can normally be compartmentalized anteroposteriorly into four transverse zones and mediolaterally into parasagittal stripes. In this study, immunohistochemistry was performed using various Purkinje cell compartmentation markers to examine their expression patterns in the Acp2 mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin II and PLCβ4 showed similar expression patterns in the nax mutant and wild type cerebellum. However, fewer stripes were found in the anterior zone of the nax mutant, which could be due to a lack of Purkinje cells or altered expression of the stripe markers. HSP25 expression was uniform in the central zone of the nax mutant cerebellum at around postnatal day (P) 18–19, suggesting that HSP25 immunonegative Purkinje cells are absent or delayed in stripe pattern expression compared to the wild type. HSP25 expression became heterogeneous around P22–23, with twice the number of parasagittal stripes in the nax mutant compared to the wild type. Aside from reduced size and cortical disorganization, both the posterior zone and nodular zone in the nax mutant appeared less abnormal than the rest of the cerebellum. From these results, it is evident that the anterior zone of the nax mutant cerebellum is the most severely affected, and this extends beyond the primary fissure into the rostral central zone/vermis. This suggests that ACP2 has critical roles in the development of the anterior cerebellum and it may regulate anterior and central zone compartmentation. PMID:24722417

  4. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-01-01

    Full Text Available Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial.

  5. The Danish Vascular Registry, Karbase

    DEFF Research Database (Denmark)

    Eldrup, Nikolaj; Cerqueira, Charlotte; de la Motte, Louise

    2016-01-01

    AIM: The Danish Vascular Registry (DVR), Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry...... for quality assessment and research. STUDY POPULATION: All patients undergoing vascular interventions (surgical and endovascular) at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ∼9,000 procedures are added. By January 2016, >180,000 procedures...... have been recorded. Since 2001, data completeness has been >90% (compared to the Danish National Patient Register). MAIN VARIABLES: Variables include information on descriptive patient data (ie, age, sex, height, and weight) and comorbidity (ie, previous cardiovascular disease and diabetes). Process...

  6. Social media in vascular surgery.

    Science.gov (United States)

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  7. Impact of bone harvesting techniques on cell viability and the release of growth factors of autografts.

    Science.gov (United States)

    Miron, Richard J; Gruber, Reinhard; Hedbom, Erik; Saulacic, Nikola; Zhang, Yufeng; Sculean, Anton; Bosshardt, Dieter D; Buser, Daniel

    2013-08-01

    Autogenous bone grafts obtained by different harvesting techniques behave differently during the process of graft consolidation; the underlying reasons are however not fully understood. One theory is that harvesting techniques have an impact on the number and activity of the transplanted cells which contribute to the process of graft consolidation. To test this assumption, porcine bone grafts were harvested with four different surgical procedures: bone mill, piezosurgery, bone drilling (bone slurry), and bone scraper. After determining cell viability, the release of molecules affecting bone formation and resorption was assessed by reverse transcription polymerase chain reaction and immunoassay. The mitogenic and osteogenic activity of the conditioned media was evaluated in a bioassay with isolated bone cells. Cell viability and the release of molecules affecting bone formation were higher in samples harvested by bone mill and bone scraper when compared with samples prepared by bone drilling and piezosurgery. The harvesting procedure also affected gene expression, for example, bone mill and bone scraper samples revealed significantly higher expression of growth factors such as bone morphogenetic protein-2 and vascular endothelial growth factor compared with the two other modalities. Receptor activator of nuclear factor kappa B ligand expression was lowest in bone scraper samples. These data can provide a scientific basis to better understand the impact of harvesting techniques on the number and activity of transplanted cells, which might contribute to the therapeutic outcome of the augmentation procedure. © 2012 Wiley Periodicals, Inc.

  8. Natural isotopic signatures of variations in body nitrogen fluxes: a compartmental model analysis.

    Directory of Open Access Journals (Sweden)

    Nathalie Poupin

    2014-10-01

    Full Text Available Body tissues are generally 15N-enriched over the diet, with a discrimination factor (Δ15N that varies among tissues and individuals as a function of their nutritional and physiopathological condition. However, both 15N bioaccumulation and intra- and inter-individual Δ15N variations are still poorly understood, so that theoretical models are required to understand their underlying mechanisms. Using experimental Δ15N measurements in rats, we developed a multi-compartmental model that provides the first detailed representation of the complex functioning of the body's Δ15N system, by explicitly linking the sizes and Δ15N values of 21 nitrogen pools to the rates and isotope effects of 49 nitrogen metabolic fluxes. We have shown that (i besides urea production, several metabolic pathways (e.g., protein synthesis, amino acid intracellular metabolism, urea recycling and intestinal absorption or secretion are most probably associated with isotope fractionation and together contribute to 15N accumulation in tissues, (ii the Δ15N of a tissue at steady-state is not affected by variations of its P turnover rate, but can vary according to the relative orientation of tissue free amino acids towards oxidation vs. protein synthesis, (iii at the whole-body level, Δ15N variations result from variations in the body partitioning of nitrogen fluxes (e.g., urea production, urea recycling and amino acid exchanges, with or without changes in nitrogen balance, (iv any deviation from the optimal amino acid intake, in terms of both quality and quantity, causes a global rise in tissue Δ15N, and (v Δ15N variations differ between tissues depending on the metabolic changes involved, which can therefore be identified using simultaneous multi-tissue Δ15N measurements. This work provides proof of concept that Δ15N measurements constitute a new promising tool to investigate how metabolic fluxes are nutritionally or physiopathologically reorganized or altered. The

  9. Structural localization and origin of compartmentalized fluid flow, Comstock lode, Virginia City, Nevada

    Science.gov (United States)

    Berger, B.R.; Tingley, J.V.; Drew, L.J.

    2003-01-01

    Bonanza-grade orebodies in epithermal-style mineral deposits characteristically occur as discrete zones within spatially more extensive fault and/or fracture systems. Empirically, the segregation of such systems into compartments of higher and lower permeability appears to be a key process necessary for high-grade ore formation and, most commonly, it is such concentrations of metals that make an epithermal vein district world class. In the world-class silver- and gold-producing Comstock mining district, Nevada, several lines of evidence lead to the conclusion that the Comstock lode is localized in an extensional stepover between right-lateral fault zones. This evidence includes fault geometries, kinematic indicators of slip, the hydraulic connectivity of faults as demonstrated by veins and dikes along faults, and the opening of a normal-fault-bounded, asymmetric basin between two parallel and overlapping northwest-striking, lateral- to lateral-oblique-slip fault zones. During basin opening, thick, generally subeconomic, banded quartz-adularia veins were deposited in the normal fault zone, the Comstock fault, and along one of the bounding lateral fault zones, the Silver City fault. As deformation continued, the intrusion of dikes and small plugs into the hanging wall of the Comstock fault zone may have impeded the ability of the stepover to accommodate displacement on the bounding strike-slip faults through extension within the stepover. A transient period of transpressional deformation of the Comstock fault zone ensued, and the early-stage veins were deformed through boudinaging and hydraulic fragmentation, fault-motion inversion, and high- and low-angle axial rotations of segments of the fault planes and some fault-bounded wedges. This deformation led to the formation of spatially restricted compartments of high vertical permeability and hydraulic connectivity and low lateral hydraulic connectivity. Bonanza orebodies were formed in the compartmentalized zones of

  10. Foliar or root exposures to smelter particles: Consequences for lead compartmentalization and speciation in plant leaves

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Eva [Université de Toulouse, INP, UPS, EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement), ENSAT, Avenue de l' Agrobiopole, 31326 Castanet-Tolosan (France); CNRS, EcoLab, 31326 Castanet-Tolosan (France); Géosciences Environnement Toulouse (GET), Observatoire Midi Pyrénées, Université de Toulouse, CNRS, IRD, 14 Avenue E. Belin, F-31400 Toulouse (France); Dappe, Vincent [LASIR (UMR CNRS 8516), Université de Lille 1, Bât. C5, 59655 Villeneuve d' Ascq Cedex (France); Sarret, Géraldine [ISTerre, UMR 5275, Université Grenoble I, CNRS, F-38041 Grenoble (France); Sobanska, Sophie [LASIR (UMR CNRS 8516), Université de Lille 1, Bât. C5, 59655 Villeneuve d' Ascq Cedex (France); Nowak, Dorota; Nowak, Jakub; Stefaniak, Elżbieta Anna [Department of Chemistry, John Paul II Catholic University of Lublin, Al. Kraśnicka 102, 20-718 Lublin (Poland); Magnin, Valérie [ISTerre, UMR 5275, Université Grenoble I, CNRS, F-38041 Grenoble (France); Ranieri, Vincent [CEA-INAC, 17 rue des Martyrs, 38054 Grenoble Cedex 9 (France); Dumat, Camille, E-mail: camille.dumat@ensat.fr [Université de Toulouse, INP, UPS, EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement), ENSAT, Avenue de l' Agrobiopole, 31326 Castanet-Tolosan (France); CNRS, EcoLab, 31326 Castanet-Tolosan (France)

    2014-04-01

    better assess the health risks involved. - Highlights: • Plants were exposed to factory process particles via atmosphere or soil transfer. • Pathways of Pb uptake were investigated using microscopy and spectroscopy. • Contrary to lettuces, Pb speciation has changed in the leaf surfaces of rye-grass. • In the case of root exposure, pyromorphite was formed in the leaves of rye-grass. • Pb compartmentalization and speciation depend on transfer way and plant species.

  11. Radical pathway in catecholase activity with zinc-based model complexes of compartmental ligands.

    Science.gov (United States)

    Guha, Averi; Chattopadhyay, Tanmay; Paul, Nanda Dulal; Mukherjee, Madhuparna; Goswami, Somen; Mondal, Tapan Kumar; Zangrando, Ennio; Das, Debasis

    2012-08-20

    Four dinuclear and three mononuclear Zn(II) complexes of phenol-based compartmental ligands (HL(1)-HL(7)) have been synthesized with the aim to investigate the viability of a radical pathway in catecholase activity. The complexes have been characterized by routine physicochemical studies as well as X-ray single-crystal structure analysis: [Zn(2)(H(2)L(1))(OH)(H(2)O)(NO(3))](NO(3))(3) (1), [Zn(2)L(2)Cl(3)] (2), [Zn(2)L(3)Cl(3)] (3), [Zn(2)(L(4))(2)(CH(3)COO)(2)] (4), [Zn(HL(5))Cl(2)] (5), [Zn(HL(6))Cl(2)] (6), and [Zn(HL(7))Cl(2)] (7) [L(1)-L(3) and L(5)-L(7) = 2,6-bis(R-iminomethyl)-4-methylphenolato, where R= N-ethylpiperazine for L(1), R = 2-(N-ethyl)pyridine for L(2), R = N-ethylpyrrolidine for L(3), R = N-methylbenzene for L(5), R = 2-(N-methyl)thiophene for L(6), R = 2-(N-ethyl)thiophene for L(7), and L(4) = 2-formyl-4-methyl-6-N-methylbenzene-iminomethyl-phenolato]. Catecholase-like activity of the complexes has been investigated in methanol medium by UV-vis spectrophotometric study using 3,5-di-tert-butylcatechol as model substrate. All complexes are highly active in catalyzing the aerobic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ). Conversion of 3,5-DTBC to 3,5-DTBQ catalyzed by mononuclear complexes (5-7) is observed to proceed via formation of two enzyme-substrate adducts, ES1 and ES2, detected spectroscopically, a finding reported for the first time in any Zn(II) complex catalyzed oxidation of catechol. On the other hand, no such enzyme-substrate adduct has been identified, and 3,5-DTBC to 3,5-DTBQ conversion is observed to be catalyzed by the dinuclear complexes (1-4) very smoothly. EPR experiment suggests generation of radicals in the presence of 3,5-DTBC, and that finding has been strengthened by cyclic voltammetric study. Thus, it may be proposed that the radical pathway is probably responsible for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complexes of redox-innocent Zn(II) ion. The ligand

  12. Effects of unfractionated heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats.

    Science.gov (United States)

    Meng, Yan; Zhang, Hao; Li, Yingbin; Li, Qingnan; Zuo, Li

    2014-01-01

    Unfractionated heparin (UFH) is the most widely used anticoagulant in hemodialysis for chronic kidney disease (CKD) patients. Many studies have verified that UFH can induce bone loss in subjects with normal bone, but few have focused on its effect on renal osteodystrophy. We therefore investigated this issue in adenine-induced CKD rats. As CKD also impairs mineral metabolism systemically, we also studied the impacts of UFH on serum markers of CKD-mineral and bone disorder (CKD-MBD) and vascular calcification. We administered low and high doses of UFH (1U/g and 2U/g body weight, respectively) to CKD rats and compared them with CKD controls. At sacrifice, the serum markers of CKD-MBD did not significantly differ among the two UFH CKD groups and the CKD control group. The mean bone mineral densities (BMDs) of the total femur and a region of interest (ROI) constituted of trabecular and cortical bone were lower in the high-dose UFH (H-UFH) CKD group than in the CKD control group (Prats indicated secondary hyperparathyroidism, and the femoral trabecular bone volume, but not cortical bone volume, significantly decreased with increasing UFH dose. The same decreasing trend was found in osteoblast parameters, and an increasing trend was found in osteoclast parameters; however, most differences were not significant. Moreover, no distinct statistical differences were found in the comparison of vascular calcium or phosphorus content among the CKD control group and the two UFH CKD groups. Therefore, we concluded that UFH could induce bone loss in CKD rats with secondary hyperparathyroidism, mainly by reducing the trabecular volume and had little effect on cortical bone volume. The underlying mechanism might involve inhibition of osteoblast activity and promotion of osteoclast activity by UFH. We did not find any effect of UFH on vascular calcification in CKD rats with secondary hyperparathyroidism. © 2013.

  13. A biphasic compartmentation of neuro-transmission associated metabolic patterns during electro-induced axoplasmic transport in sheep medulla oblongata.

    Science.gov (United States)

    Narasimham, P V; Mohanachari, V; Swami, K S; Indira, K

    1983-01-01

    In the sheep medulla oblongata, on the induction of polarity by the applied voltage gradient of direct current along the length, the enzymes such as acetylcholinesterase and glutamate dehydrogenase showed anodal transport while the enzyme arginase showed cathodal transport indicating the possession of negative and positive charge densities on the enzymes. These studies indicated that the glutamate bound metabolism, one towards ammonia formation and the other towards the energy production and neural transmission, have opposed electro-characteristics. The acetylcholinesterase system had anodal characteristics coupled to the glutamate dehydrogenase patterns. The existence of two charge based compartmentation is envisaged in the neural tissue.

  14. Noninfarct vascular dementia and Alzheimer dementia spectrum.

    Science.gov (United States)

    Emery, V Olga; Gillie, Edward X; Smith, Joseph A

    2005-03-15

    Vascular dementia is an overarching superordinate category of which multiinfarct vascular dementia is only one subtype. To contribute to the definition of vascular dementia, method involved investigation of mental status, oral language and comprehension in 81 consecutive vascular patients comprising two vascular samples: cerebral infarct sample (n=43) and cerebral noninfarct sample (n=38). To determine baseline, method also involved investigation of 36 demographically equivalent normal elderly. Results indicate both vascular samples performed significantly worse than normal elderly. Results further indicate there were no robust, reliable, significant differences between cerebral infarct and cerebral noninfarct patients. The lack of significant differences between cerebral infarct and cerebral noninfarct vascular samples brings into focus the ambiguous transition between diffuse, generalized disease and the multifocality underlying the vascular dementia-Alzheimer dementia spectrum. Cross-cutting infarct and noninfarct vascular populations were vascular factors of arteriosclerosis, abnormal blood pressure, diabetes mellitus, abnormal electrocardiogram, peripheral vascular disease, and other variables implicated in the distal causality of both infarct and noninfarct vascular dementias. Results indicate cerebral infarction is not the only path to the final common phenotype of vascular dementia. Vascular dementia is reconceptualized so as to include noninfarct vascular dementia: vascular dementia caused by underlying vascular factors other than cerebral infarction. It is suggested that one form of the subtype of noninfarct vascular dementia is Alzheimer-type vascular dementia.

  15. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  16. Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

    Science.gov (United States)

    Stein, Koen; Prondvai, Edina

    2014-02-01

    palaeohistological studies, we introduce new osteohistological terms as well as revise widely used but incorrect terminology. To infer the role of woven bone in the bone formation of fast-growing tetrapods, we review some aspects of the interrelationships between the vascularity of bone tissues, basal metabolic rate, body size and growth rate. By putting our findings into the context of osteogenesis, we provide a new model for the diametrical limb bone growth of sauropods and present new implications for the evolution of fast growth in vertebrates. Since biomechanical studies of bone tissues suggest that predominant collagen fibre orientation (CFO) is controlled by endogenous, functional and perhaps phylogenetic factors, the relationship between CFO and bone growth rate as defined by Amprino's rule, which has been the basis for the biological interpretation of several osteohistological features, must be revised. Our findings draw attention to the urgent need for revising widely accepted basic concepts of palaeohistological studies, and for a more integrative approach to bone formation, biomechanics and bone microstructural features of extant and extinct vertebrates to infer life history traits of long extinct, iconic animals like dinosaurs. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  17. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... used to guide the exact placement of the biopsy instrument. The health care provider applies a numbing ... is sent to a lab for examination. Bone biopsy may also be done under general anesthesia to ...

  18. Anorexia nervosa and bone

    National Research Council Canada - National Science Library

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk...

  19. Menopause and Bone Loss

    Science.gov (United States)

    ... up bone loss. After menopause your ovaries stop producing the hormone estrogen, which helps to keep your ... you minimize and treat bone loss? Diet and lifestyle can help prevent and treat bone loss. Successful ...

  20. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Giant recurrent aneurysmal bone cyst of the mandible.

    Science.gov (United States)

    Banu, Khurshida; Sham, Mohammed Ehtaih; Hari, Sri; Sharad, Veena

    2012-07-01

    The Aneurysmal bone cyst (ABC) is an infrequent but well defined lesion occurring most commonly in the long bones, the pelvis and vertebrae. Only 1-2% of the lesions are known to occur in the maxillofacial region. Clinically, the lesion usually occurs in young adults below 20 years of age. Though there does not seem to be any marked gender predilection and slight preponderance towards females has been reported. Here we present a case of giant recurrent aneurysmal bone cyst in a 19 year old male patient treated by segmental resection and reconstruction with vascularized fibular graft.

  2. Histochemical and Morphological Aspects of Fresh Frozen Bone: A Preliminary Study

    OpenAIRE

    De Ponte, F.S.; Cutroneo, G.; Falzea, R.; Rizzo, G.; Catalfamo, L.; Favaloro, A.; Vermiglio, G.; Runci, M.; Centofanti, A.; Anastasi, G.

    2016-01-01

    Bone graft are used in dentistry for the reconstruction of severely atrophic jaws. Fresh frozen bone has no osteogenic property but it has osteoconductive and osteoinductive properties because its matrix contains growth factors such as vascular endothelial growth factor. The purpose of the present study was to evaluate morphological and protein expression characteristics of fresh frozen bone before graft and after six months of graft in patients who needed maxillary reconstruction. After 6 mo...

  3. Temporal aneurysmal bone cyst: cost-effective method to achieve gross total resection.

    Science.gov (United States)

    Sodhi, Harsimrat Bir Singh; Salunke, Pravin; Agrawal, Parimal; Gupta, Kirti

    2016-08-01

    Aneurysmal bone cyst (ABC) is a vascular benign bony expansile lesion. The treatment is gross total resection. Surgery for a skull base aneurysmal bone cyst poses a significant challenge because of its vascularity and the adjacent neurovascular structures. We present the case of a young male with a temporal aneurysmal bone cyst who underwent gross total resection of the lesion. The external carotid artery (ECA) was temporarily clamped to cut off the vascular supply. There was no intraoperative event, and the patient made a good postoperative clinical recovery. This technique was used as an alternative to subselective endovascular embolization of the ECA branches. This case represents a simple yet cost-effective surgical technique to control bleeding for a highly vascular lesion such as ABCs, especially in resource-deficient countries.

  4. Segurança do transplante autólogo, intra-arterial, de células mononucleares da medula óssea na fase aguda do acidente vascular cerebral isquêmico Intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Maria Lúcia Furtado de Mendonça

    2006-01-01

    Full Text Available O acidente vascular cerebral (AVC é a terceira causa de óbito e a principal causa de incapacidade em indivíduos adultos. Embora a mortalidade do AVC esteja diminuindo em alguns países, a morbidade tem aumentado em razão do envelhecimento da população e do aumento da sobrevida dos pacientes¹. O tratamento com ativador do plasminogênio tissular recombinante (rt-PA é eficaz quando instituído em até 3 horas após o início dos sintomas², porém seu uso está limitado a cerca de 5% dos pacientes na fase aguda do AVC isquêmico. Além disso, nenhum agente para neuroproteção teve sua eficácia comprovada em estudos clínicos em humanos. Portanto, outras estratégias terapêuticas precisam ser desenvolvidas. Em modelos animais, o uso de células-tronco correlacionou-se com melhora funcional após o AVC³. Publicações recentes têm demonstrado a segurança do tratamento com células mononucleares da medula óssea (CMMO injetadas via intracoronária em pacientes portadores de cardiopatia isquêmica aguda ou crônica4,5. Baseado nesses dados iniciais, há crescente interesse no estudo do transplante com CMMO na fase aguda do AVC. Relatamos o primeiro caso de transplante autólogo de CMMO via intra-arterial na fase aguda do AVC isquêmico.Stroke is the third cause of death and the leading cause of disability in adult subjects. Although stroke mortality has been declining in some countries, stroke morbidity has been increasing due to the aging of population and patients improved survival.¹ Treatment with recombinant tissue plasminogen activator (rtPA is successful provided it is administered within 3 hours of symptoms onset,² but its use is limited to about 5% of the patients with acute ischemic stroke. Furthermore, no neuroprotective agent has yet been proven effective in human clinical trials. The development of other therapeutic strategies is, therefore, warranted. The use of stem cells in animal models has led to functional improvement

  5. Depression in vascular dementia.

    Science.gov (United States)

    Naarding, Paul; de Koning, Inge; dan Kooten, Fop; Dippel, Diederik W J; Janzing, Joost G E; van der Mast, Rose C; Koudstaal, Peter J

    2003-04-01

    To study the presence of different dimensions of depression in subjects with vascular dementia. After a stroke, cognitive, affective and behavioural disturbances are common. It has been suggested that the nature of affective symptomatology can help to differentiate organic from psychological depression. Cognitive and affective symptoms were assessed in 78 stroke patients and a principal component analysis was performed on these symptoms. Also, a discriminant analysis was carried out to establish the contribution of different symptoms on the diagnosis 'depressive disorder' and 'dementia'. (1) Principal component analysis revealed three distinct sub-syndromes: one with predominantly mood symptoms, one with essentially psychomotor symptoms, and one with vegetative symptoms; (2) mood, psychomotor and vegetative symptoms were all independently and strongly related to a diagnosis of major depressive disorder according to DSM-III-R criteria; (3) the psychomotor factor was also firmly associated with dementia; and (4) discriminant analysis gave further support for our conclusion that some of the depressive features, in particular the psychomotor factor, are at least partly related to the organic brain damage from stroke. The results indicate that different dimensions of depression could be discerned in a group of stroke patients and that the symptom profile of depression in these patients can be affected by the presence of dementia. Copyright 2003 John Wiley & Sons, Ltd.

  6. Epigenetic Diabetic Vascular Complications

    Directory of Open Access Journals (Sweden)

    Ali Ahmadzadeh-Amiri

    2016-01-01

    Full Text Available Diabetic vascular complications (DVC influence several vital organ systems including cardiovascular, renal, ocular and nervous systems making it a major public health problem. Although extensive researches were performed in this field, the exact mechanisms responsible for these organ damages in diabetes remain obscure. Several metabolic disturbances have been involved in its complication and change in genes associated with these pathways occurred. Gene expression to produce a biologically active protein can be controlled by transcriptional and translational alteration on the head of genes without change in nucleotide composition. These epigenetic adjustments are steady, but possibly reversible and can be transmitted to future generation. Gene expression can be regulated by three epigenetic mechanisms including DNA methylation, histone modifications and noncoding microRNAs (miRNAs activity. Epigenetic studies must be directed to better realize the role of epigenetic changes to the etiology of DVC and knowledge of epigenetic would play a pivotal role in the application of individualized medicine. Application and development of high technology sequencing combined with more sensitive and advanced methodologies for epigenome studying help to determine specific epigenetic events that stimulate gene responses in patients with diabetes mellitus.

  7. [Extremity vascular traumas].

    Science.gov (United States)

    Angelini, Romeo; Rutolo, Ferdinando; Cozzolino, Giuseppe; D'Amario, Vanessa; Spigonardo, Francesca

    2005-01-01

    The Authors report on a series of 61 vascular traumas treated over a 7 years, separated in two groups. The first one includes 35 cases, that are street accidents, on the work and gunshot wounds. The second group includes 26 iatrogenic causes due to arterial catheterism. All patients underwent ecocolor Doppler directly in the operating theatre and, when this diagnostic procedure was not enough, pre-operating angiography was used (10 cases of complex traumas of the lower limb). One death was reported far each groups (3.27%). In 55 cases (90.1%), limb savage was achieved. In the others 4 (6.93%) of the first group, limb demolition was necessary for different causes. In the first group, severe neurological sequelaes were observed in 2 cases and motor deficits caused by tendon lesions in 1 case. The good results obtained are the result of the short ischemic interval between the acute event and treatment, thanks to a multidisciplinary approach of a specific equipe, that is rapid as possible.

  8. The association of mineral metabolism with vascular access patency.

    Science.gov (United States)

    Rosenberg, Joel E; Astor, Brad C; Deluca, Hector F; Yevzlin, Alexander S

    2016-09-21

    Declining kidney function leads to progressively dysregulated mineral homeostasis and contributes to vascular calcification and a pro-inflammatory milieu, both of which play a critical role in loss of dialysis vascular access patency. We designed this study to examine the relationship between markers of bone and mineral metabolism, vitamin D replacement medications, and vascular access outcomes. We hypothesized that higher levels of calcium, phosphorous, parathyroid hormone (PTH), and albumin are independently associated with vascular access patency and that vitamin D supplementation is associated with lower risk of access failure. We abstracted data on 204 consecutive patients referred for angiographic evaluation of their permanent arteriovenous access over a 25-month period. We followed patients from the time of access salvage until subsequent referral for access failure. The incidence of vascular access failure did not differ by serum phosphorus, PTH, calcium, calcium-phosphorus product or albumin level. Patients receiving any vitamin D replacement therapy, however, had a lower incidence of access failure compared to those receiving no therapy. Those receiving vitamin D3 therapy with or without paricalcitol (Zemplar, Abbot Laboratories, Abbot Park, IL) or calcitriol had an adjusted HR = 0.18 compared to those receiving no vitamin D therapy. This study suggests a relationship between vitamin D3 usage and better vascular access patency, independent of the effect of vitamin D on PTH. Though this relationship needs more rigorous investigation prior to clinical application, the known differences in the pro- and anti-inflammatory effects of various vitamin D metabolites provide a potential mechanism for these clinical observations.

  9. Aneurysmal bone cyst of the frontal bone

    OpenAIRE

    Perić Predrag; Antić Branislav; Radić-Tasić Olga

    2005-01-01

    Background. Aneurysmal bone cyst (ABC) is a benign, expansive, osteolytic lesion that mainly occurs in young people, and involves the skull bones only exceptionally. The origin of ABC is controversial: secondary reactive bone lesion, or primary disease that represents an independent nosological entity. Blunt head trauma was suggested as a possible etiological factor. Case report. A case of a 19-year old man with primary ABC of the right frontal bone was reported. The lesion was totally excise...

  10. Multi-compartmental nanoparticles-in-emulsion formulation for macrophage-specific anti-inflammatory gene delivery.

    Science.gov (United States)

    Attarwala, Husain; Amiji, Mansoor

    2012-06-01

    To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy. Solid nanoparticles-in-emulsion (NiE) multi-compartmental delivery system was designed using plasmid DNA-encapsulated type B gelatin nanoparticles suspended in the inner aqueous phase of safflower oil-containing water-in-oil-in-water (W/O/W) multiple emulsion. Control and NiE formulations were evaluated for DNA delivery and transfection efficiency in J774A.1 adherent murine macrophages. Using green fluorescent protein (GFP) and murine interleukin-10 (mIL-10) expressing plasmid DNA constructs, the NiE formulation was found superior in enhancing intracellular delivery and gene transfection efficiency in cells. Anti-inflammatory effects of transfected mIL-10 were examined by suppression of tumor necrosis factor-alpha (TNFα) and interleukin 1-beta (IL-1β) production in lipopolysaccharide (LPS)-stimulated cells. Overall, the results were very encouraging towards development of a macrophage-specific NiE-based multi-compartmental gene delivery strategy that can potentially affect a number of acute and chronic inflammatory diseases.

  11. Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Giraudeau, Celine; Leporq, Benjamin; Doblas, Sabrina [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Lagadec, Matthieu; Daire, Jean-Luc; Van Beers, Bernard E. [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Beaujon University Hospital Paris Nord, Department of Radiology, Clichy (France); Pastor, Catherine M. [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Hopitaux Universitaires de Geneve, Departement d' Imagerie et des Sciences de l' Information Medicale, Geneva (Switzerland)

    2017-05-15

    Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. (orig.)

  12. An empirically adjusted approach to reproductive number estimation for stochastic compartmental models: A case study of two Ebola outbreaks.

    Science.gov (United States)

    Brown, Grant D; Oleson, Jacob J; Porter, Aaron T

    2016-06-01

    The various thresholding quantities grouped under the "Basic Reproductive Number" umbrella are often confused, but represent distinct approaches to estimating epidemic spread potential, and address different modeling needs. Here, we contrast several common reproduction measures applied to stochastic compartmental models, and introduce a new quantity dubbed the "empirically adjusted reproductive number" with several advantages. These include: more complete use of the underlying compartmental dynamics than common alternatives, use as a potential diagnostic tool to detect the presence and causes of intensity process underfitting, and the ability to provide timely feedback on disease spread. Conceptual connections between traditional reproduction measures and our approach are explored, and the behavior of our method is examined under simulation. Two illustrative examples are developed: First, the single location applications of our method are established using data from the 1995 Ebola outbreak in the Democratic Republic of the Congo and a traditional stochastic SEIR model. Second, a spatial formulation of this technique is explored in the context of the ongoing Ebola outbreak in West Africa with particular emphasis on potential use in model selection, diagnosis, and the resulting applications to estimation and prediction. Both analyses are placed in the context of a newly developed spatial analogue of the traditional SEIR modeling approach. © 2015, The International Biometric Society.

  13. Perfusion–diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep

    Science.gov (United States)

    Doolette, David J; Upton, Richard N; Grant, Cliff

    2005-01-01

    This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion–diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain. PMID:15649976

  14. Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2011-12-01

    Full Text Available In this review we analyze the recent important and remarkable advancements in studies of compartmentation of adenine nucleotides in muscle cells due to their binding to macromolecular complexes and cellular structures, which results in non-equilibrium steady state of the creatine kinase reaction. We discuss the problems of measuring the energy fluxes between different cellular compartments and their simulation by using different computer models. Energy flux determinations by 18O transfer method have shown that in heart about 80% of energy is carried out of mitochondrial intermembrane space into cytoplasm by phosphocreatine fluxes generated by mitochondrial creatine kinase from adenosine triphosphate (ATP, produced by ATP Synthasome. We have applied the mathematical model of compartmentalized energy transfer for analysis of experimental data on the dependence of oxygen consumption rate on heart workload in isolated working heart reported by Williamson et al. The analysis of these data show that even at the maximal workloads and respiration rates, equal to 174 µmol O2 per min per g dry weight, phosphocreatine flux, and not ATP, carries about 80–85% percent of energy needed out of mitochondria into the cytosol. We analyze also the reasons of failures of several computer models published in the literature to correctly describe the experimental data.

  15. Disrupted compartmental organization of axons and dendrites within olfactory glomeruli of mice deficient in the olfactory cell adhesion molecule, OCAM.

    Science.gov (United States)

    Walz, Andreas; Mombaerts, Peter; Greer, Charles A; Treloar, Helen B

    2006-01-01

    There is an overall topographic connectivity in the axonal projections of olfactory sensory neurons from the olfactory epithelium (OE) to the olfactory bulb (OB). The molecular determinants of this overall topographic OE-OB connectivity are not known. For 20 years, the intriguing expression pattern of the olfactory cell adhesion molecule (OCAM) has made it the leading candidate as determinant of overall topographic OE-OB connectivity. Here, we have generated a strain of OCAM knockout mice by gene targeting. There were no obvious alterations in the distribution of olfactory sensory neurons within the OE or in the coalescence of axons into specific glomeruli. However, the compartmental organization of dendrites and axons within the glomeruli was disrupted. Surprisingly, the mutant mice exhibited an increase in olfactory acuity; they appeared to have a better sense of smell. Thus, despite its striking expression pattern, OCAM is not essential for overall topographic OE-OB connectivity. Instead, OCAM is required for establishing or maintaining the compartmental organization and the segregation of axodendritic and dendrodendritic synapses within glomeruli.

  16. Dynamics of the risk of smoking-induced lung cancer: a compartmental hidden Markov model for longitudinal analysis.

    Science.gov (United States)

    Chadeau-Hyam, Marc; Tubert-Bitter, Pascale; Guihenneuc-Jouyaux, Chantal; Campanella, Gianluca; Richardson, Sylvia; Vermeulen, Roel; De Iorio, Maria; Galea, Sandro; Vineis, Paolo

    2014-01-01

    To account for the dynamic aspects of carcinogenesis, we propose a compartmental hidden Markov model in which each person is healthy, asymptomatically affected, diagnosed, or deceased. Our model is illustrated using the example of smoking-induced lung cancer. The model was fitted on a case-control study nested in the European Prospective Investigation into Cancer and Nutrition study, including 757 incident cases and 1524 matched controls. Estimation was done through a Markov Chain Monte Carlo algorithm, and simulations based on the posterior estimates of the parameters were used to provide measures of model fit. We performed sensitivity analyses to assess robustness of our findings. After adjusting for its impact on exposure duration, age was not found to independently drive the risk of lung carcinogenesis, whereas age at starting smoking in ever-smokers and time since cessation in former smokers were found to be influential. Our data did not support an age-dependent time to diagnosis. The estimated time between onset of malignancy and clinical diagnosis ranged from 2 to 4 years. Our approach yielded good performance in reconstructing individual trajectories in both cases (sensitivity >90%) and controls (sensitivity >80%). Our compartmental model enabled us to identify time-varying predictors of risk and provided us with insights into the dynamics of smoking-induced lung carcinogenesis. Its flexible and general formulation enables the future incorporation of disease states, as measured by intermediate markers, into the modeling of the natural history of cancer, suggesting a large range of applications in chronic disease epidemiology.

  17. Cellular compartmentation follows rules: The Schnepf theorem, its consequences and exceptions: A biological membrane separates a plasmatic from a non-plasmatic phase.

    Science.gov (United States)

    Moog, Daniel; Maier, Uwe G

    2017-08-01

    Is the spatial organization of membranes and compartments within cells subjected to any rules? Cellular compartmentation differs between prokaryotic and eukaryotic life, because it is present to a high degree only in eukaryotes. In 1964, Prof. Eberhard Schnepf formulated the compartmentation rule (Schnepf theorem), which posits that a biological membrane, the main physical structure responsible for cellular compartmentation, usually separates a plasmatic form a non-plasmatic phase. Here we review and re-investigate the Schnepf theorem by applying the theorem to different cellular structures, from bacterial cells to eukaryotes with their organelles and compartments. In conclusion, we can confirm the general correctness of the Schnepf theorem, noting explicit exceptions only in special cases such as endosymbiosis and parasitism. © 2017 WILEY Periodicals, Inc.

  18. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development...... at 146 days of life and five left and right ribs (fourth to eighth) were removed for analysis. The influence of AKG on skeletal system development was evaluated in relation to both geometrical and mechanical properties, as well as quantitative computed tomography (QCT). No significant differences between...

  19. Vascular injuries during gynecological laparoscopy: the vascular surgeon's advice

    Directory of Open Access Journals (Sweden)

    Marcello Barbosa Barros

    Full Text Available CONTEXT: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services. CASES: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period. DISCUSSION: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

  20. Trauma vascular, visión del cirujano vascular

    Directory of Open Access Journals (Sweden)

    Dr. D. Cristián Salas

    2011-09-01

    Full Text Available El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesiones de vasos torácicos y abdominales requieren de imágenes de apoyo, siempre que el paciente se encuentre estabilizado, generalmente tomografía axial computada. La mayoría de las lesiones vasculares son por trauma penetrante, comprometiendo principalmente las extremidades. Con el desarrollo de los procedimientos invasivos vasculares en los últimos años se ha observado un aumento de lesiones vasculares iatrogénicas. Hoy en día muchos pacientes con trauma vascular son manejados por vía endovascular.

  1. Role of preoperative vascular ultrasonography in hemodialysis vascular access operation.

    Science.gov (United States)

    Siribumrungwong, Boonying; Tomtitchong, Prakitpunthu; Kanpirom, Kitti

    2010-12-01

    Preoperative vascular mapping increase rate of successful hemodialysis vascular access operation. Several studies recommend using this procedure routinely. But some studies recommend using this procedure in selected patients. So this study aims to determine the impacts of preoperative vascular mapping in unfavorable-examined patients. 55 patients were studied retrospectively from August 2006 to October 2009. Before April 2008, the operative plans were based on physical examination (group 1). After April 2008, the surgeon did preoperative vascular mapping prior to the operation in unfavorable-examined patients (group 2). The results were compared. There were high maturation rates in favorable-examined patients. In unfavorable-examined patients, preoperative vascular mapping can identified nonpalpable favorable vein which successful maturation of 18.75%. Complementary duplex scan decrease rate of unsuccessful operation significantly (p = 0.037) but does not increase maturation rate. Careful physical examination is important part before operation. Preoperative vascular mapping has benefit only in patients with unfavorable-examined patients. It finds some nonpalpable favorable vein and decrease unsuccessful exploration.

  2. Bone graft in the treatment of nonunion of the scaphoid with necrosis of the proximal pole: a literature review.

    Science.gov (United States)

    Severo, Antônio Lourenço; Lemos, Marcelo Barreto; Lech, Osvandré Luiz Canfield; Barreto Filho, Danilo; Strack, Daniel Paulo; Candido, Larissa Knapp

    2017-01-01

    Scaphoid fractures are the most common fractures of the carpal bones, corresponding to 60%. Of these, 10% progress to nonunion; moreover, 3% can present necrosis of the proximal pole. There are various methods of treatment using vascularized and non-vascularized bone grafts. To evaluate and compare the rate of scaphoid consolidation with necrosis of the proximal pole using different surgical techniques. The authors conducted a review of the literature using the following databases: PubMed and BIREME/LILACS, where 13 case series were selected (ten with use of vascularized bone grafts and three of non-vascularized bone grafts), according to inclusion and exclusion criteria. In most cases VBGs were used, especially those based on the 1,2 intercompartmental supraretinacular artery, due to greater reproducibility in performing the surgical technique.

  3. Vascular Endothelial Growth Factor from Embryonic Status to Cardiovascular Pathology

    Directory of Open Access Journals (Sweden)

    Mohsen Azimi-Nezhad

    2014-05-01

    Full Text Available Vascular endothelial growth factor (VEGF is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene, consisting of 121, 145, 165, 183, 189, or 206 amino acids. VEGF121, VEGF145, and VEGF165 are secreted whereas VEGF183, VEGF189, and VEGF206 are cell membrane-bound. VEGF145 has a key role during the vascularization of the human ovarian follicle and corpus luteum, in the placentation and embryonic periods, and in bone and wound healing, while VEGF165 is the most abundant and biologically active isoform. VEGF has been linked with a number of vascular pathologies including cardiovascular diseases such ischemic heart disease, heart failure, stroke, and diabetes and its related complications. In this review we aimed to present some important roles of VEGF in a number of clinical issues and indicate its involvement in several phenomena from the initial steps of the embryonic period to cardiovascular diseases.

  4. The cell cycle of the planctomycete Gemmata obscuriglobus with respect to cell compartmentalization

    Directory of Open Access Journals (Sweden)

    Fuerst John A

    2009-01-01

    Full Text Available Abstract Background Gemmata obscuriglobus is a distinctive member of the divergent phylum Planctomycetes, all known members of which are peptidoglycan-less bacteria with a shared compartmentalized cell structure and divide by a budding process. G. obscuriglobus in addition shares the unique feature that its nucleoid DNA is surrounded by an envelope consisting of two membranes forming an analogous structure to the membrane-bounded nucleoid of eukaryotes and therefore G. obscuriglobus forms a special model for cell biology. Draft genome data for G. obscuriglobus as well as complete genome sequences available so far for other planctomycetes indicate that the key bacterial cell division protein FtsZ is not present in these planctomycetes, so the cell division process in planctomycetes is of special comparative interest. The membrane-bounded nature of the nucleoid in G. obscuriglobus also suggests that special mechanisms for the distribution of this nuclear body to the bud and for distribution of chromosomal DNA might exist during division. It was therefore of interest to examine the cell division cycle in G. obscuriglobus and the process of nucleoid distribution and nuclear body formation during division in this planctomycete bacterium via light and electron microscopy. Results Using phase contrast and fluorescence light microscopy, and transmission electron microscopy, the cell division cycle of G. obscuriglobus was determined. During the budding process, the bud was formed and developed in size from one point of the mother cell perimeter until separation. The matured daughter cell acted as a new mother cell and started its own budding cycle while the mother cell can itself initiate budding repeatedly. Fluorescence microscopy of DAPI-stained cells of G. obscuriglobus suggested that translocation of the nucleoid and formation of the bud did not occur at the same time. Confocal laser scanning light microscopy applied to cells stained for membranes as

  5. Computer Modeling of Sand Transport on Mars Using a Compart-Mentalized Fluids Algorithm (CFA)

    Science.gov (United States)

    Marshall, J.; Stratton, D.

    1999-01-01

    of sand comminution on Mars. A multiple-grain transport model using just the equations of grain motion describing lift and drag is impossible to develop owing to stochastic effects --the very effects we wish to model. Also, unless we were to employ supercomputing techniques and extremely complex computer codes that could deal with millions of grains simultaneously, it would also be difficult to model grain transport if we attempted to consider every grain in motion. No existing computer models were found that satisfactorily used the equations of motion to arrive at transport flux numbers for the different populations of saltation and reptation. Modeling all the grains in a transport system was an intractable problem within our resources, and thus we developed what we believe to be a new modeling approach to simulating grain transport. The CFA deals with grain populations, but considers them to belong to various compartmentalized fluid units in the boundary layer. In this way, the model circumvents the multigrain problem by dealing primarily with the consequences of grain transport --momentum transfer between air and grains, which is the physical essence of a dynamic grain-fluid mixture. We thus chose to model the aeolian transport process as a superposition of fluids. These fluids include the air as well as particle populations of various properties. The prime property distinguishing these fluids is upward and downward grain motion. In a normal saltation trajectory, a grain's downwind velocity increases with time, so a rising grain will have a smaller downwind velocity than a failing grain. Because of this disparity in rising and falling grain proper-ties, it seemed appropriate to track these as two separate grain populations within the same physical space. The air itself can be considered a separate fluid superimposed within and interacting with the various grain-cloud "fluids". Additional informaiton is contained in the original.

  6. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Živadinović Milka

    2016-01-01

    Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present

  7. Diabetes and Retinal Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    2014-01-01

    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  8. ( Elaeis guineensis Jacq ) vascular wilt

    African Journals Online (AJOL)

    Effet de la jachére sur l'expérimentation de la fusariose vasculaire du palmier à huile ( Elaeis guineensis Jacq ) : Effects of the fallow in the expression of oil-palm ( Elaeis guineensis Jacq ) vascular wilt.

  9. Non-invasive optical modulation of local vascular permeability

    Science.gov (United States)

    Choi, Myunghwan; Choi, Chulhee

    2011-03-01

    For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

  10. The Vascularized Medial Femoral Corticoperiosteal Flap for Thumb Reconstruction

    Science.gov (United States)

    Amin, Kavit; Darhouse, Nagham; Sivakumar, Bran; Floyd, David

    2015-01-01

    Summary: We present an interesting method of shaping a vascularized medial femoral condyle (MFC) flap into a “neophalanx” for phalangeal reconstruction. Our patient presented with limited strength and function secondary to fracture nonunion of the proximal phalanx of the dominant thumb. Following excision of the pseudarthrosis, an MFC corticoperiosteal flap was harvested, sculpted into a prism shape and inset. The superomedial genicular pedicle was anastomosed to the princeps pollicis artery and a cephalic tributary. On follow-up, new bone growth was seen on radiographs and the patient had substantially improved function, with full metacarpophalangeal extension, a Kapandji score of 9, and a markedly reduced Disabilities of the Arm, Shoulder and Hand score of 2.68. The MFC flap is useful for reconstruction of bony defects, with minimal donor morbidity. This versatile vascularized flap can be crafted to requisite shapes and is useful for small defects in the hand, including phalangeal reconstruction. PMID:26495205

  11. Study of irradiated bone. I. Histopathologic and physiologic changes

    Energy Technology Data Exchange (ETDEWEB)

    King, M.A.; Casarett, G.W.; Weber, D.A.

    1979-11-01

    Histologic and tracer techniques were used to investigate and document alterations in bone pathophysiology subsequent to irradiation of the left hind limb of rabbits. Numerous time-dependent changes were observed. Among these were an inflammatory response shortly after irradiation, and an increase in the remodeling of cortical bone, which peaked between 3 and 6 mo after irradiation. The changes in bone remodeling correlated with changes in vascular patency in a manner consistent with the hypothesis that radiation damage in mature bone is mediated primarily through alterations in the fine vasculature. The findings of this study provide important information on the time course of changes in bone pathophysiology following regional irradiation. They are used in the second of this series of papers to help establish which mechanisms are responsible for postirradiation alterations in the localization of Tc-99m pyrophosphate in these rabbits.

  12. Bilateral aneurysmal bone cyst of the mandible: A case report

    Directory of Open Access Journals (Sweden)

    Gopal HK Sharma

    2015-01-01

    Full Text Available An aneurysmal bone cyst (ABC, usually considered a reactive lesion of bone rather than a cyst or true neoplasm, is believed to represent an exaggerated, localized, proliferative response of vascular tissue in bone. The case described here is of a 40-year-old female patient presenting with gradually increasing bilateral mandibular swelling of more than 1 year duration. The radiographic and cone beam computed tomography (CBCT images showed bilateral, multilocular expansile radiolucent lesions in the mandible in the premolar-molar region. On considering the blood aspirate obtained and the histopathologic findings, the patient was diagnosed with bilateral aneurysmal bone cysts in the mandible, with probable pre-existing bone lesion.

  13. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... vasculature may affect the retinal response to potential vascular disease in later life....

  14. The Danish Vascular Registry, Karbase

    Science.gov (United States)

    Eldrup, Nikolaj; Cerqueira, Charlotte; de la Motte, Louise; Rathenborg, Lisbet Knudsen; Hansen, Allan K

    2016-01-01

    Aim The Danish Vascular Registry (DVR), Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry for quality assessment and research. Study population All patients undergoing vascular interventions (surgical and endovascular) at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ∼9,000 procedures are added. By January 2016, >180,000 procedures have been recorded. Since 2001, data completeness has been >90% (compared to the Danish National Patient Register). Main variables Variables include information on descriptive patient data (ie, age, sex, height, and weight) and comorbidity (ie, previous cardiovascular disease and diabetes). Process variable includes waiting time (time from event to medical contact and treatment) and the type of procedures conducted. Outcome variables for in-hospital complications (ie, wound complications, myocardial infarction, stroke, amputation, respiratory complications, and renal insufficiency) and 30-day patency are submitted. Variables for medical treatment (antithrombotic and statin treatment), amputation, and survival are extracted from nationwide, administrative registers. Conclusion The DVR reports outcome on key indicators for monitoring the quality at all vascular departments in Denmark for the purpose of quality improvement. Furthermore, data are available for research and are being used in international collaborations on changes in clinical practices. PMID:27822118

  15. [Cutaneous vascular anomalies in children].

    Science.gov (United States)

    Yilmaz, L; Kacenelenbogen, N

    2015-09-01

    Vascular anomalies, which are erroneously categorized under the term angiomas, are a highly heterogeneous group of lesions that are poorly understood and affect a mean of 5 to 10 % of children. The fortuitous discovery of propranolol's efficacy in one of these entities has made them a topical issue. The paper's main objective is to inform family doctors of the various types of vascular anomalies, clarify their classification, and provide a common terminology. Its secondary objective is to provide a decision tree that enables primary care doctors to avoid diagnostic pitfalls, successfully detect cases, and optimize management. Systematic review. According to a recent study, 71,3 % of publications use the term hemangioma erroneously, regardless of the authors' field. The key for family doctors is to use one international classification only, that of the International Society for the Study of Vascular Anomalies (ISSVA), in order to facilitate management and comprehension between the different healthcare levels. The diagnosis of vascular anomalies is clinical in 90 % of cases, so all family doctors can, whilst using a decision tree, diagnose a vascular anomaly and refer only those that are complex for specialist care. The most common vascular anomaly is infantile hemangioma in infants, which spontaneously regresses around the age of 5-7 years in 90 % of cases. Watchful waiting and regular follow-up suffice, therefore, in such settings.

  16. Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.

    Directory of Open Access Journals (Sweden)

    Eduardo K Moioli

    Full Text Available Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs and mesenchymal stem/progenitor cells (MSCs were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP scaffolds, followed by infusion of gel-suspended CD34(+ hematopoietic cells. Co-transplantation of CD34(+ HSCs and CD34(- MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromised mice yielded vascularized tissue. The average vascular number of co-transplanted CD34(+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34(+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34(+ cells. Based on additional in vitro results of endothelial differentiation of CD34(+ cells by vascular endothelial growth factor (VEGF, we adsorbed VEGF with co-transplanted CD34(+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34(+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone

  17. Stromal stem cells and platelet-rich plasma improve bone allograft integration.

    Science.gov (United States)

    Lucarelli, Enrico; Fini, Milena; Beccheroni, Amira; Giavaresi, Gianluca; Di Bella, Claudia; Aldini, Nicolò Nicoli; Guzzardella, Gaetano; Martini, Lucia; Cenacchi, Annarita; Di Maggio, Nunzia; Sangiorgi, Luca; Fornasari, Pier Maria; Mercuri, Mario; Giardino, Roberto; Donati, Davide

    2005-06-01

    Early vascular invasion is a key factor in bone allograft incorporation. It may reduce the complications related to slow and incomplete bone integration. Bone-marrow-derived stromal stem cells associated with platelet-rich plasma are potent angiogenic inducers proven to release vascular endothelial growth factor. Our goal was to test whether the combination of stromal stem cells and platelet-rich plasma is able to increase massive allograft integration in a large animal model with sacrifice at 4 months. A critical defect was made in the mid-diaphysis of the metatarsal bone of 10 sheep; the study group received an allograft plus stromal stem cells, platelet-rich plasma, and collagen (six animals) and the control group received only the allograft (four animals). Investigation was done with radiographs, mechanical tests and histomorphometric analysis, including new vascularization. Results showed substantial new bone formation in the allograft of the study group. Bone formation is correlated with better vascular invasion and remodeling of the graft in the study group. These results confirm the key role played by stromal stem cells and platelet-rich plasma in bone repair. Further studies are needed to better define the role stromal stem cells play when implanted alone.

  18. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  19. Blood perfusion and remodelling activity in canine tibial diaphysis after filling with a new bone cement compared to bone wax and poly(methyl methacrylate) cement.

    Science.gov (United States)

    Stürup, J; Nimb, L; Jensen, J S

    1995-07-01

    Six dogs each had one tibia filled with standard poly(methyl methacrylate) (PMMA) bone cement and the contralateral tibia filled with a new methyl methacrylate-n-decyl methacrylate-isobornyl methacrylate (MMA-DMA-IBMA) bone cement (Boneloc) with lowered polymerization heat and monomer leakage. An additional six dogs each had one tibia filled with MMA-DMA-IBMA and the contralateral tibia filled with bone wax. There was a higher diaphyseal blood flow, measured with a microsphere technique, in the legs filled with MMA-DMA-IBMA than in those filled with PMMA. The wax-filled bones presented higher blood perfusion than those with MMA-DMA-IBMA. We found a tendency towards higher 99mtechnetium-labelled methylene diphosphonate (99mTcMDP) uptake, and autoradiograms revealed a tendency towards larger subperiosteal apposition and more blackening, both at the subperiosteal apposition and the cortex, in the bones filled with new bone cement in the first series, but in wax-filled bone in the second series. It is concluded that the new bone cement, compared to standard acrylic bone cement, seems to inhibit the vascular response and bone remodelling activity less, making earlier remodelling possible. However, the new bone cement still seems to inhibit bone blood perfusion compared to bone wax.

  20. Labeling the human skeleton with {sup 41}Ca to assess changes in bone calcium metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Denk, E.; Hurrell, R.F.; Walczyk, T. [Institute of Food Science and Nutrition, ETH Zurich, Laboratory of Human Nutrition, Zuerich (Switzerland); Hillegonds, D.; Vogel, J. [Lawrence Livermore National Laboratory, Center for Accelerator Mass Spectrometry, Livermore, CA (United States); Synal, A. [Paul Scherrer Institute/ETH Zurich, Laboratory of Particle Physics, Zuerich (Switzerland); Geppert, C.; Wendt, K. [Johannes Gutenberg University, Institute of Physics, Mainz (Germany); Fattinger, K. [University Hospital Bern, Department of General Internal Medicine, Inselspital, Bern (Switzerland); Hennessy, C.; Berglund, M. [Institute for Reference Materials and Measurements (IRMM), European Commission Joint Research Centre, Geel (Belgium)

    2006-11-15

    Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using {sup 41}Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary {sup 41}Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of {sup 41}Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary {sup 41}Ca/{sup 40}Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary {sup 41}Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) {sup 41}Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary {sup 41}Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the {sup 41}Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary {sup 41}Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated {sup 41}Ca/{sup 40}Ca isotope ratios in urine were significantly lower than the observed {sup 41}Ca/{sup 40}Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying