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  • 1
    Online Resource
    Online Resource
    Molecular Mechanisms of Angiogenesis : From Ontogenesis to Oncogenesis. (2014)
    Paris :Springer Paris,
    Details
    Keywords: Neovascularization. ; Electronic books.
    Description / Table of Contents: This book reviews recent advances in understanding of the molecular and cellular mechanisms of angiogenesis, with a focus on how to integrate these observations into the context of developmental, post-natal and pathological neovascularization.
    Type of Medium: Online Resource
    Pages: 1 online resource (501 pages)
    Edition: 1st ed.
    ISBN: 9782817804668
    URL: https://ebookcentral.proquest.com/lib/geomar/detail.action?docID=1730933
    DDC: 612.13
    Language: English
    Note: Intro -- Contents -- Angiogenesis: An Ever-Challenging Research Field -- Acknowledgment -- References -- Part I: Angiogenesis During Embryonic Development -- Chapter 1: Emergence of Endothelial Cells During Vascular Development -- 1.1 Introduction -- 1.2 Vasculogenesis -- 1.3 Hemangioblast -- 1.4 Remodeling of the Primary Capillary Plexus into Arteries and Veins -- 1.5 Role of Hemodynamic Forces in Remodeling -- 1.6 Guidance of Capillaries by Endothelial Tip Cells -- 1.7 Circulating Endothelial Cells in the Embryo -- 1.8 Perspectives -- References -- Chapter 2: Lymphatic Vascular Morphogenesis -- 2.1 Early Steps of Lymphatic Vascular Development -- 2.1.1 Lymphatic Endothelial Cell Specification -- 2.1.2 Lymphatic Vessel Sprouting from the Veins -- 2.1.3 Separation of Lymphatic and Blood Vasculatures -- 2.1.4 Non-venous Origins of Lymphatic Vasculature -- 2.2 Lymphatic Vessel Remodelling -- 2.2.1 Sprouting and Growth of Lymphatic Vessels -- 2.2.2 Regulation of Lymphatic Endothelial Cell-Cell Junctions -- 2.2.3 Valve Morphogenesis -- 2.2.4 Smooth Muscle Cells Recruitment to Collecting Lymphatic Vessels -- 2.3 Lymphatic Vasculature and Diseases -- 2.3.1 Lymphoedema -- 2.3.2 Inflammation -- 2.3.3 Tumour Metastasis -- 2.3.4 Lipid Absorption -- 2.4 Concluding Remarks -- References -- Part II: The Physiological Angiogenic Signal: Cellular and Molecular Mechanisms -- Chapter 3: Finding New Partnerships: The Function of Individual Extracellular Receptor Domains in Angiogenic Signalling by VEGF Receptors -- 3.1 Biology of VEGF Family Growth Factors and Their Receptors -- 3.1.1 Introduction to VEGF -- 3.1.2 Structure-Function Relationship of VEGF and VEGF Receptors -- 3.1.2.1 Receptor Specificity of VEGFs -- 3.1.2.2 Structural Analysis of VEGF Binding to VEGFR-1, VEGFR-2 and VEGFR-3 -- 3.1.2.3 Activation of VEGF Receptors. , 3.2 VEGFR-2 as Part of a Signalling Platform -- 3.2.1 Neuropilins (NRPs) -- 3.2.2 Ephrin-B2 -- 3.2.3 VE-Cadherin -- 3.2.4 Dopamine Receptor D2 -- 3.2.5 CD146 -- 3.2.6 CD44 -- 3.3 Extracellular Components of the VEGF/VEGFR Signalling Cascade as Targets for Therapy and Functional Inhibition -- 3.3.1 VEGF/VEGFRs in Disease -- 3.3.2 VEGF/VEGFRs as Targets in Therapeutic Inhibition -- 3.3.2.1 VEGF-Neutralising Agents -- 3.3.2.2 Anti-VEGFR-1 Agents -- 3.3.2.3 Anti-VEGFR-2 D23 Agents -- 3.3.2.4 Anti-VEGFR-2 D4-7 Agents -- 3.3.3 Limitations to VEGF/VEGFR Targeted Therapy -- 3.3.4 Outlook and Conclusions -- References -- Chapter 4: Wnt/Frizzled Signaling in the Vasculature -- 4.1 Introduction -- 4.1.1 Wnt Signal Transduction -- 4.1.1.1 The Canonical Pathway: Wnt/β-Catenin -- 4.1.1.2 The Planar Cell Polarity Pathway -- 4.1.1.3 The Calcium-Mediated Pathway -- 4.1.2 Wnt Inhibitors and Modulators -- 4.1.3 Atypical Receptors Kinases -- 4.2 Role of the Wnt/Frizzled in Vascular Development -- 4.2.1 Evidence of Wnt/Fzd Expression and Signaling in Endothelial Cells -- 4.2.2 Placental Development -- 4.2.3 Postnatal Retinal Angiogenesis -- 4.2.4 Brain Vasculature -- 4.3 Role of Wnt Regulation in Vascular Pathology -- 4.3.1 Choroidal Neovascularization and Oxygen-Induced Retinopathy -- 4.3.2 Wound Healing -- 4.3.3 Hind Limb and Cardiac Ischemia -- 4.4 Conclusion -- 4.5 Online Databases -- References -- Chapter 5: BMP9, BMP10, and ALK1: An Emerging Vascular Signaling Pathway with Therapeutic Applications -- 5.1 Bone Morphogenetic Proteins (BMPs) -- 5.2 BMP9/BMP10/ALK1 Signaling Complex -- 5.3 The Role of BMP9 and BMP10 in Vascular Development -- 5.3.1 Knowledge from Human Vascular Diseases -- 5.3.2 Knowledge from Animal Models: Mice and Zebrafish -- 5.3.2.1 Mice -- 5.3.2.2 Zebrafish -- 5.3.3 In Vitro Roles of BMP9 and BMP10 in Endothelial Cells. , 5.4 Therapeutic Applications of the BMP9/BMP10/ALK1 Signaling Pathway -- 5.4.1 HHT -- 5.4.2 BMP9, BMP10, and ALK1 as Biomarkers in Cancer -- 5.4.3 Therapeutic Applications of the BMP9/BMP10/ALK1 Signaling Pathway in Tumor Angiogenesis -- 5.4.3.1 ALK1 Extracellular Domain (ALK1 ECD) -- 5.4.3.2 Anti-ALK1 Antibody (PF-03446962) -- 5.4.3.3 Anti-endoglin Antibody (TRC105) -- 5.5 Conclusions and Perspectives -- References -- Chapter 6: Apelin Signaling in Retinal Angiogenesis -- 6.1 Apelin Signaling -- 6.1.1 Receptor Discovery and Isolation of the Endogenous Ligand -- 6.1.2 Multiple Active Ligands and Receptor Heterodimers -- 6.1.3 Gene Transcription and Mode of Signaling -- 6.1.4 Physiological Functions of Apelin Signaling -- 6.2 The Retina -- 6.2.1 Anatomy and Development -- 6.2.2 Astrocyte: The Key Mediator of Neuron/Endothelial Cell Interactions -- 6.2.3 Developmental Patterning of Retinal Vessels -- 6.2.4 Subpopulations of Endothelial Cells -- 6.3 Apelin Signaling and Formation of Retinal Vessels -- 6.3.1 Apelin: A Bona Fide Angiogenic Factor -- 6.3.2 Vascular Phenotype of Apelin or APJ Gene Invalidation -- 6.3.3 Temporal Expression of Apelin Signaling Coincides with the Angiogenic Phase -- 6.3.4 Apelin Receptor Gene: An Early Marker of the Venous Phenotype -- 6.3.5 Receptor and Ligand Gene as Potential Markers of Tip or Stalk Phenotype -- 6.3.6 Apelin Signaling as a Linker Between VEGF-Secreting Astrocytes and Proliferating Stalk Cells -- 6.3.7 Apelin Signaling Regulates LIF Secretion and Controls Astrocyte Maturation -- 6.4 Apelin Signaling and Pathological Retinal Angiogenesis -- 6.4.1 The Retinopathy of Prematurity -- 6.4.2 Diabetic Retinopathy -- 6.4.3 Telangiectatic Vessels -- 6.5 Clinical Implications -- References -- Chapter 7: Emerging Role of the Two Related Basic Helix-Loop-Helix Proteins TAL1 and LYL1 in Angiogenesis -- 7.1 Introduction. , 7.2 Properties of LYL1 and TAL1 -- 7.3 Hematopoietic Functions of Tal1, Lyl1, and Lmo2 -- 7.4 Tal1 and Lmo2 Are Required for Cardiovascular Development -- 7.5 TAL1 Activity Is Required in the Early Steps of Angiogenesis -- 7.5.1 TAL1 and LMO2 Initiate Tubulogenesis Through VE-Cadherin Upregulation -- 7.5.2 TAL1-LMO2 Complexes Controls Angiopoietin-2 Expression -- 7.6 LYL1 Is Required for the Maturation of New Blood Vessels -- 7.6.1 Lyl1 Deficiency Leads to Increased Angiogenic Responses -- 7.6.2 LYL1 Contributes to Vessel Maturation and Stabilization -- 7.7 Coordinated Activity of TAL1 and LYL1 to Regulate Angiogenic Processes -- References -- Part III: Hypoxia, Ischemia and Angiogenesis -- Chapter 8: Hypoxia and Extracellular Matrix Remodeling -- 8.1 Hypoxia Induction of Angiogenesis -- 8.2 Establishment of the Vascular BM -- 8.3 Extracellular Matrix Proteolytic Degradation -- 8.4 Regulation of Hypoxia-Induced Growth Factor Sequestration in the Extracellular Matrix -- 8.5 Matricellular Proteins -- 8.5.1 Group A Thrombospondins -- 8.5.2 Group B Thrombospondins -- 8.6 Conclusion -- References -- Chapter 9: Sphingosine-1-Phosphate in Hypoxic Signaling -- 9.1 Hypoxia Significance and Impact on Clinical Outcome -- 9.2 The Hypoxia-Inducible Factors -- 9.3 Sphingosine 1-Phosphate Metabolism in Cancer -- 9.4 Sphingosine 1-Phosphate Signaling in Hypoxia -- 9.5 Sphingosine 1-Phosphate Signaling as a Target for Anti- hypoxic Strategy -- 9.6 Concluding Remarks -- References -- Chapter 10: Reciprocal Crosstalk Between Angiogenesis and Metabolism -- 10.1 Regulation of Angiogenesis by Oxygen and Metabolism -- 10.1.1 PHDs and HIF: The Molecular Players of Angiogenesis Are Regulated by Oxygen and Metabolic Intermediates -- 10.1.2 Modulators of HIF and PHDs by Nonhypoxic Stimuli -- 10.1.2.1 TCA Cycle and Other Metabolic Intermediates. , 10.1.2.2 Reactive Oxygen Species -- 10.1.3 Modulation of Angiogenesis by Metabolic Regulators -- 10.2 EC Metabolism Impacts Vessel Sprouting -- 10.2.1 EC Survival and Functions Are Dependent on Glycolysis -- 10.2.2 Metabolic Changes During Vascular Sprouting -- 10.3 Regulation of Metabolism by Angiogenesis -- Bibliography -- Chapter 11: Endothelial Progenitor Cells and Cardiovascular Ischemic Diseases: Characterization, Functions, and Potential Clinical Applications -- 11.1 Introduction -- 11.2 Cultured EPC -- 11.3 Recruitment of EPCs to the Ischemic Tissue -- 11.3.1 CXCL12/CXCR4 -- 11.3.2 Integrins and Selectins -- 11.3.3 Hemostatic Partners, Thrombospondin, and Thrombin Interaction with EPCs -- 11.3.4 Other Factors -- 11.4 Mechanisms of EPC-Related Effects on Postischemic Revascularization -- 11.4.1 Differentiation into Endothelial Cells -- 11.4.2 Paracrine Effects -- 11.4.3 Interaction with the Host Environment -- 11.5 EPCs as Diagnostic and Prognostic Tools -- 11.5.1 EPCs as Biomarkers of Cardiovascular Diseases -- 11.5.1.1 EPCs and Cardiovascular Risk Factors -- 11.5.1.2 EPCs and the Prevalence of CVDs -- 11.5.2 Are EPCs a Useful Prognostic Factor for Cardiovascular Diseases? -- 11.6 EPCs as Therapeutic Tools -- 11.6.1 Adult Stem/Progenitor Cells -- 11.6.2 Alternative Sources of EPCs -- 11.6.2.1 Embryonic Stem Cells (ESCs) -- 11.6.2.2 Induced Pluripotent Stem Cells (iPSCs) -- 11.6.2.3 Local Source of Stem/Progenitor Cells -- 11.7 Conclusion -- References -- Part IV: Tumor Angiogenesis -- Chapter 12: Endothelial Cell Reactions to Oxygen: Implications for Cancer -- 12.1 Overview of Oxygen-Mediated Pathways -- 12.2 Hypoxia-Inducible Factors Mediate Cellular Oxygen Signaling -- 12.3 The Function of Prolyl Hydroxylase Domain Proteins and Factor Inhibiting HIF as Oxygen Sensors. , 12.4 Role of Oxygen Signaling in Physiological and Pathophysiological Angiogenesis.
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  • 2
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    Species-specific physiological response by the cold-water corals Lophelia pertusa and Madrepora oculata to variations within their natural temperature range (2014)
    Elsevier
    In:  Deep-Sea Research Part II-Topical Studies in Oceanography, 99 . pp. 36-41.
    Details
    Publication Date: 2017-06-19
    Description: The scleractinian cold-water corals (CWC) Lophelia pertusa and Madrepora oculata represent two major deep-sea reef-forming species that act as key ecosystem engineers over a wide temperature range, extending from the northern Atlantic (ca. 5–9 °C) to the Mediterranean Sea (ca. 11–13 °C). Recent research suggests that environmental parameters, such as food supply, settling substrate availability or aragonite saturation state may represent important precursors controlling habitat suitability for CWC. However, the effect of one principal environmental factor, temperature, on CWC key physiological processes is still unknown. In order to evaluate this effect on calcification, respiration, and dissolved organic carbon (DOC) net flux, colonies of Mediterranean L. pertusa and M. oculata were acclimated in aquaria to three temperatures (12, 9 and 6 °C), by consecutive decrements of 1 month duration. L. pertusa and M. oculata maintained at Mediterranean control conditions (i.e. 12 °C) displayed constant rates, on average respiring 4.8 and 4.0 µmol O2 cm−2 coral surface area d−1, calcifying 22.3 and 12.3 µmol CaCO3 g−1 skeletal dry weight d−1 and net releasing 2.6 and 3.1 µmol DOC cm−2 coral surface area d−1, respectively. Respiration of L. pertusa was not affected by lowered temperatures, while M. oculata respiration declined significantly (by 48%) when temperature decreased to 9 °C and 6 °C relative to controls. L. pertusa calcification at 9 °C was similar to controls, but decreased significantly (by 58%) at 6 °C. For M. oculata, calcification declined by 41% at 9 °C and by 69% at 6 °C. DOC net flux was similar throughout the experiment for both CWC. These findings reveal species-specific physiological responses by CWC within their natural temperature range. L. pertusa shows thermal acclimation in respiration and calcification, while these mechanisms appear largely absent in M. oculata. Conclusively, species-specific thermal acclimation may significantly affect the occurrence and local abundance of cosmopolitan CWC species, consequently influencing their important role in habitat engineering and ecosystem functioning in various thermal environments. Keywords
    Type: Article , PeerReviewed
    Format: text
    DOI: 10.1016/j.dsr2.2013.05.025
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    OceanRep: Article in a Scientific Journal - peer-reviewed
  • 3
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    Uptake of dissolved free amino acids by four cold-water coral species from the Mediterranean Sea (2014)
    Elsevier
    In:  Deep-Sea Research Part II-Topical Studies in Oceanography, 99 . pp. 42-50.
    Details
    Publication Date: 2017-06-19
    Description: Dissolved organic matter, which contains many compounds such as lipids, sugars and amino acids, is an important source of carbon and nitrogen for several symbiotic and asymbiotic tropical coral species. However, there is still no information on its possible uptake by cold-water coral species. In this study, we demonstrated that dissolved organic matter, in the form of dissolved free amino acids (DFAA), is actively absorbed by four cold-water coral species from the Mediterranean Sea. Although the uptake rates observed with 3 µM DFAA concentration were one order of magnitude lower than those observed in tropical species, they corresponded to 12–50% of the daily excreted-nitrogen, and 16–89% of the daily respired-carbon of the cold-water corals. Consequently, DFAA, even at in situ concentrations lower than those tested in this study, can supply a significant amount of carbon and nitrogen to the corals, especially during periods when particulate food is scarce.
    Type: Article , PeerReviewed
    Format: text
    DOI: 10.1016/j.dsr2.2013.06.007
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    OceanRep: Article in a Scientific Journal - peer-reviewed
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    Li/Mg systematics in scleractinian corals: Calibration of the thermometer (2014)
    Elsevier
    In:  Geochimica et Cosmochimica Acta, 132 . pp. 288-310.
    Details
    Publication Date: 2015-09-22
    Description: We show that the Li/Mg systematics of a large suite of aragonitic coral skeletons, representing a wide range of species inhabiting disparate environments, provides a robust proxy for ambient seawater temperature. The corals encompass both zooxanthellate and azooxanthellate species (Acropora sp., Porites sp., Cladocora caespitosa, Lophelia pertusa, Madrepora oculata and Flabellum impensum) collected from shallow, intermediate, and deep-water habitats, as well as specimens cultured in tanks under temperature-controlled conditions. The Li/Mg ratios observed in corals from these diverse tropical, temperate, and deep-water environments are shown to be highly correlated with temperature, giving an exponential temperature relationship of: Li/Mg (mmol/mol) = 5.41 exp (−0.049 * T) (r2 = 0.975, n = 49). Based on the standard error of the Li/Mg versus temperature correlation, we obtain a typical precision of ±0.9 °C for the wide range of species analysed, similar or better than that of other less robust coral temperature proxies such as Sr/Ca ratios. The robustness and species independent character of the Li/Mg temperature proxy is shown to be the result of the normalization of Li to Mg, effectively eliminating the precipitation efficiency component such that temperature remains as the main controller of coral Li/Mg compositions. This is inferred from analysis of corresponding Li/Ca and Mg/Ca ratios with both ratios showing strong microstructure-related co-variations between the fibrous aragonite and centres of calcification, a characteristic that we attribute to varying physiological controls on growth rate. Furthermore, Li/Ca ratios show an offset between more rapidly growing zooxanthellate and azooxanthellate corals, and hence only an approximately inverse relationship to seawater temperature. Mg/Ca ratios show very strong physiological controls on growth rate but no significant dependence with temperature, except possibly for Acropora sp. and Porites sp. A strong positive correlation is nevertheless found between Li/Ca and Mg/Ca ratios at similar temperatures, indicating that both Li and Mg are subject to control by similar growth mechanisms, specifically the mass fraction of aragonite precipitated during calcification, which is shown to be consistent with a Rayleigh-based elemental fractionation model. The highly coherent array defined by Li/Mg versus temperature is thus largely independent of coral calcification mechanisms, with the strong temperature dependence reflecting the greater sensitivity of the KdLi/Ca partition coefficient relative to KdMg/Ca. Accordingly, Li/Mg ratios exhibit a highly coherent exponential correlation with temperature, thereby providing a more robust tool for reconstructing paleo-seawater temperatures.
    Type: Article , PeerReviewed , info:eu-repo/semantics/article
    Format: text
    DOI: 10.1016/j.gca.2014.02.005
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    OceanRep: Article in a Scientific Journal - peer-reviewed
  • 5
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    Neuropsychological outcome after carbon monoxide exposure following a storm: a case-control study (2014)
    BioMed Central
    Details
    Publication Date: 2014-07-22
    Description: Background: The cognitive consequences of carbon monoxide (CO) poisoning are well described. However, most studies have been carried out without an ad-hoc group of control subjects. The main aim of this study was to evaluate cognitive and psychiatric outcome after CO exposure during the storm Klaus in the South West of France (January 2009) in a homogeneous group of patients compared to a group of 1:1 paired controls. Methods: Patients and controls were asked to fill out questionnaires about quality of life and cognitive complaints. They then underwent a cognitive assessment derived from the Carbon Monoxide Neuropsychological Screening Battery. Psychiatric assessment was performed using subtests of the Mini International Neuropsychiatric Interview. Results: 38 patients and 38 paired controls were included (mean age 38.8 years) and evaluated 51 days after the poisoning. No difference was found between groups on the cognitive complaint questionnaire but patients had a lower quality of life than controls. Patients showed significantly lower cognitive performance than controls on processing speed, mental flexibility, inhibition and working and verbal episodic memories. Patients were more depressed than controls, and suffered more from post-traumatic stress disorder. Conclusions: We report the first study investigating cognitive and psychiatric outcome in consecutive patients after CO poisoning during a natural disaster, using a group comparison method. CO poisoning during storms needs to be dealt with adequately and clinicians should be aware of its possible consequences.
    Electronic ISSN: 1471-2377
    Topics: Medicine
    Published by BioMed Central
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  • 6
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    Digital Transmission Techniques for a Long Haul HF Link: DS-SS vs. OFDM (2014)
    Wiley-Blackwell
    Details
    Publication Date: 2014-07-02
    Description: This paper presents two digital transmission techniques for long haul ionospheric links. Since 2003 we have studied the HF link between the Antarctic Spanish Base, Juan Carlos I, and Spain and we have described the link in terms of availability, signal to noise ratio (SNR) and delay and Doppler power profile. Based on these previous studies we have developed a test bed to investigate two digital transmission techniques, i.e. Direct Sequence Spread Spectrum and Orthogonal Frequency Division Multiplexing, which can provide a low power, low rate ionospheric data link from Antarctica. Symbol length, bandwidth and constellation are some of the features that are analyzed in this work. Data gathered from the link throughout the 2010/2011 and 2011/2012 Antarctic surveys show that spread spectrum techniques can be used to transmit data at low rate when the channel forecast is poor but when the channel forecast is good multicarrier techniques can be used to transmit sporadic bursts of data at higher rate.
    Print ISSN: 0048-6604
    Electronic ISSN: 1944-799X
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 7
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    Remote Sensing, Vol. 6, Pages 7233-7259: Remote Geophysical Observatory in Antarctica with HF Data Transmission: A Review (2014)
    MDPI Publishing
    Details
    Publication Date: 2014-08-05
    Description: The geophysical observatory in the Antarctic Spanish Station, Juan Carlos I (ASJI), on Livingston Island, has been monitoring the magnetic field in the Antarctic region for more than fifteen years. In 2004, a vertical incidence ionospheric sounder completed the observatory, which brings a significant added value in a region with low density of geophysical data. Although the ASJI is only operative during the austral summer, the geomagnetic station records the data throughout the year. A High Frequency (HF) transmission system was installed in 2004 in order to have the geomagnetic data available during the whole year. As the power supply is very limited when the station is not operative, we had to design a low-power HF transceiver with a very simple antenna, due to environmental aspects. Moreover, the flow of information was unidirectional, so the modulation had to be extremely robust since there is no retransmission in case of error. This led us to study the main parameters of the ionospheric channel and to design new modulations specially adapted to very low signal to noise scenarios with high levels of interference. In this paper, a review of the results of our remote geophysical observatory and associated transmission system in Antarctica during the last decade is presented.
    Electronic ISSN: 2072-4292
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by MDPI Publishing
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  • 8
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    Thermally tolerant corals have limited capacity to acclimatize to future warming (2014)
    Wiley-Blackwell
    Details
    Publication Date: 2014-03-12
    Description: Thermal stress affects organism performance differently depending on the ambient temperature to which they are acclimatized, which varies along latitudinal gradients. This study investigated whether differences in physiological responses to temperature are consistent with regional differences in temperature regimes for the stony coral Oculina patagonica . To resolve this question we experimentally assessed how colonies originating from four different locations characterized by 〉3°C variation in mean maximum annual temperature responded to warming from 20 to 32°C. We assessed plasticity in symbiont identity, density, and photosynthetic properties, together with changes in host tissue biomass. Results show that, without changes in the type of symbiont hosted by coral colonies, O. patagonica has limited capacity to acclimatize to future warming. We found little evidence of variation in overall thermal tolerance, or in thermal optima, in response to spatial variation in ambient temperature. Given that the invader O. patagonica is a relatively new member of the Mediterranean coral fauna our results also suggest that coral populations may need to remain isolated for a long period of time for thermal adaptation to potentially take place. Our study indicates that for O. patagonica , mortality associated with thermal stress manifests primarily through tissue breakdown under moderate but prolonged warming (which does not impair symbiont photosynthesis and, therefore, does not lead to bleaching). Consequently, projected global warming is likely to causes repeat incidents of partial and whole colony mortality and might drive a gradual range contraction of Mediterranean corals. This article is protected by copyright. All rights reserved.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley-Blackwell
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  • 9
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    How To Minimize Toxic Exposure to Pyridine during Continuous Infusion of Ceftazidime in Patients with Cystic Fibrosis? [Clinical Therapeutics] (2014)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2014-04-11
    Description: Ceftazidime is particularly efficient against Pseudomonas aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4°C, 22°C, or 33°C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro . In model 1, we administered 12 g of ceftazidime infused over 23 h (once-daily infusion) compared to 6 g infused over 11.5 h in model 2 (twice-daily regimen). Samples were collected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using an ultraviolet high-performance liquid chromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratio close to 1/6 and 1/3 between 33°C and 4°C in models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount of ceftazidime is significantly higher at 4°C and 33°C compared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: (i) exposing a solution of ceftazidime to over 22°C should be strictly avoided, (ii) a divided dose of 6 g over 11.5 h instead of a once-daily administration is preferred, and (iii) infusion should be administered immediately after reconstitution.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
    Published by The American Society for Microbiology (ASM)
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  • 10
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    Gradual Dysregulation of the VHL-HIF Pathway in Oncogenesis (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-11-15
    Description: The classic model of tumor suppression implies that malignant transformation requires full “two-hit” inactivation of a tumor-suppressor gene. However, more recent work in mice has led to the proposal of a “continuum” model that involves more fluid concepts such as gene dosage-sensitivity and tissue specificity. Mutations in the tumor-suppressor gene von Hippel-Lindau (VHL) are associated with a complex spectrum of conditions. Homozygotes or compound heterozygotes for the R200W germline mutation in VHL have Chuvash polycythemia, whereas heterozygous carriers are free of disease. Individuals with classic, heterozygous VHL mutations have VHL disease and are at high risk of multiple tumors (e.g., CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma). We report here an atypical family bearing two VHL gene mutations in cis (R200W and R161Q), together with phenotypic analysis, structural modeling, functional, and transcriptomic studies of these mutants in comparison with classical mutants involved in the different VHL phenotypes. We demonstrate that the complex pattern of disease manifestations observed in VHL syndrome is perfectly correlated with a gradient of VHL protein (pVHL) dysfunction in hypoxia signaling pathways. Thus, by studying naturally occurring familial mutations, our work validates in humans the “continuum” model of tumor suppression. Cancer Res; 74(22); 6554–64. ©2014 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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