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  • 1
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; IN-VITRO ; SURVIVAL ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; IN-VIVO ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; VITRO ; GENERATION ; VOLUME ; DEATH ; DISEASE ; DISEASES ; DRUG ; DIFFERENTIATION ; LIGAND ; MECHANISM ; RAT ; CELL-SURVIVAL ; CELL-DEATH ; LONG-TERM SURVIVAL ; TRANSIENT GLOBAL-ISCHEMIA ; STEM-CELLS ; CENTRAL-NERVOUS-SYSTEM ; COLONY-STIMULATING FACTOR ; STROKE ; signaling ; ADULT ; FOCAL CEREBRAL-ISCHEMIA ; NEURONS ; cell survival ; CEREBRAL-ISCHEMIA ; NEURAL STEM-CELLS ; cell death ; progenitor ; FUNCTIONAL RECOVERY ; MATURE ; RECOVERY ; NEURONAL DIFFERENTIATION ; HIPPOCAMPAL-NEURONS ; FACTOR G-CSF ; INFARCT ; NEWLY GENERATED NEURONS ; RAT DENTATE GYRUS
    Abstract: G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong antiapoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases
    Type of Publication: Journal article published
    PubMed ID: 16007267
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  43. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung; 20170518-20170520; Wien; DOC17oegu081 /20170403/
    Publication Date: 2017-04-03
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Jahrestagung der Gesellschaft für Medizinische Ausbildung - GMA; 20081002-20081005; Greifswald; DOC08gma102 /20080819/
    Publication Date: 2008-08-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    Keywords: CELLS ; EXPRESSION ; tumor ; BLOOD ; CELL ; Germany ; SYSTEM ; GENE ; GENE-EXPRESSION ; GENES ; DIFFERENTIATION ; TIME ; PATIENT ; TUMOR-NECROSIS-FACTOR ; RESPONSES ; MACROPHAGES ; IMMUNE-RESPONSES ; gene expression ; PLASMA ; PCR ; LYMPHOCYTES ; ADHESION ; PARAMETERS ; POLYMERASE-CHAIN-REACTION ; cholesterol ; LOW-DENSITY-LIPOPROTEIN ; immune response ; CENTRAL-NERVOUS-SYSTEM ; PERIPHERAL-BLOOD ; MONOCYTE ; CD40 LIGAND ; development ; CEREBRAL-ISCHEMIA ; ELEVATED EXPRESSION ; ONSET ; macrophage ; NECROSIS ; HUMAN ENDOTHELIAL-CELLS ; MONOCYTES ; traumatic brain injury ; POLYMERASE ; PBMC ; WELL ; MONONUCLEAR CELLS ; ACTIVATED PARENCHYMAL MICROGLIA/MACROPHAGES ; lymphopenia ; MANGANESE SUPEROXIDE-DISMUTASE ; oxLDL ; PLASMA OXIDIZED LDL
    Abstract: Peripheral blood mononuclear cells (PBMCs), i.e. lymphocytes, monocytes and macrophages are key players in the development of innate and adaptive immune responses. However, little is known about their properties in patients with acute stroke. Experimental procedures: We presently characterized the early time course of PBMC subpopulations in 19 patients with acute ischemic stroke and symptom onset below 6 h compared to 19 age-matched healthy subjects. Immediately after acute ischemic stroke, as well as 1 and 3 days thereafter, PBMC subpopulations (cluster of differentiation [CD]3+, CD14+, CD19+, CD68+) were isolated by magnetic bead system and the expression of proinflammatory (CD40, tumor necrosis factor-alpha [TNF alpha]), proapoptotic (caspase-3 [CPP32], poly(ADP-ribose) polymerase [PARP]) and adhesion relevant (CD38) genes was measured by quantitative polymerase chain reaction (PCR). Furthermore, besides routine parameters, plasma levels of oxidized low-density lipoproteins (oxLDL) were studied. Results: In comparison to healthy subjects, patients revealed (i) twofold elevated plasma oxLDL concentrations, (ii) decreased (15%) blood cholesterol levels, and (iii) a 40% decrease in total number of lymphocytes. Furthermore, the majority of PBMC subpopulations revealed an increased expression of proinflammatory, proapoptotic or adhesion-relevant genes. Significant positive correlations were observed between expression of most of these genes in PBMCs and individual plasma oxLDL concentrations. Conclusion: Elevated expression of proinflammatory, proapoptotic and adhesion genes in subsets of PBMCs after ischemic stroke may contribute to an immunodepressive syndrome, possibly due to increased plasma oxLDL levels. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19258025
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien; 20090524-20090527; Münster; DOCMO.12-01 /20090520/
    Publication Date: 2009-06-30
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    ISSN: 1432-1238
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Ischämischer Schlaganfall ; Hyperbare Sauerstofftherapie ; Hyperbare Oxygenation ; Key words Ischemic stroke ; Hyperbaric oxygen therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary For a large number of patients with stroke no therapeutic option can be offered, even after approval of thrombolytic therapy for treatment of acute ischemic stroke in the US. In cerebral ischemia local anoxia and energy failure lead to further cellular damage and finally to complete stroke. All therapeutic concepts try to salvage structurally intact tissue which is at risk for irreversible damage (so-called penumbra). Hyperbaric oxygen (HBO) treatment has been reported in animal models of cerebral ischemia, and in a few clinical reports. In general, the results of these studies have been promising. This review focuses on the clinical perspective of HBO therapy and summarizes both the clinical and experimental data availabe on HBO therapy following ischemic stroke.
    Notes: Zusammenfassung Trotz der voraussichtlich baldigen Zulassung von rt-PA zur thrombolytischen Behandlung akuter Schlaganfälle sind die therapeutischen Möglichkeiten für die überwiegende Mehrzahl von Patienten nach Schlaganfall nach wie vor ungünstig. Durch die zerebrale Ischämie kommt es zum Zusammenbruch der Sauerstoffversorgung, ebenso wird kein Substrat (Glukose) mehr an das Gewebe abgegeben. Die bekannte Schadenskaskade aus Laktatazidose, Freisetzung exzitatorischer Aminosäuren, Bildung freier Radikale und schließlich dem Zelltod beginnt abzulaufen. Die hyperbare Sauerstofftherapie (HBO) konnte in verschiedenen tierexperimentellen und klinischen Untersuchungen einen positiven Effekt auf den neuronalen Schaden zeigen. Die vorliegende Übersicht bisheriger klinischer und experimenteller Erkenntnisse zu diesem Thema beschreibt den Stellenwert der HBO-Therapie beim akuten ischämischen Schlaganfall und fordert weitere Untersuchungen.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Intrazerebrale Blutung ; Intraventrikuläre Blutung ; Fibrinolyse ; rt-PA ; Externe Ventrikeldrainage ; Key words Intraventricular hemorrhage ; Tissue plasminogen activator ; Ventricular drainage ; Intracerebral hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Intraventricular adminstration of recombinant tissue plasminogen activator (rt-PA) is an experimental therapy to hasten the lysis of intraventricular hemorrhages. We report nine patients (7 male, 2 female, mean age 64a) with intracerebral hematoma with ventricular extension who were treated with intraventricular infusion of rt-PA (2–32 mg, mean dose 17 mg). In two patients, clinically significant bleeding complications were associated with the fibrinolytic therapy. In one of these patients, fibrinolytic therapy was stopped. Other complications could not be observed. In eight of all nine patients, a rapid and extensive reduction of the amount of intraventricular blood occurred. A persistent shunt became necessary in two patients. We conclude, that intraventricular fibrinolysis probably leads to a faster clearance of intraventricular blood. Despite of fibrinolytic treatment, a permanent shunt becomes necessary in some cases. Intraventricular fibrinolysis is a potentially hazardous therapy with the risks of bleeding complications and infection.
    Notes: Zusammenfassung Die intraventrikuläre Fibrinolyse ist eine experimentelle Therapie intraventrikulärer Hämatome zur schnelleren Clearance intraventrikulären Blutes. Wesentliche Komplikationen wurden bisher nicht beobachtet. Wir berichten über 9 Patienten (7 Männer, 2 Frauen, mittleres Alter 64 J.) mit intrazerebralen Hämatomen mit Ventrikeleinbruch, die wir mit intraventrikulärer Infusion mit rt-PA (2–32 mg, mittlere Dosis 17 mg) behandelten. Bei 2 Patienten kam es zu einer mit der Fibrinolyse assoziierten klinisch signifikanten Zunahme des intraventrikulären Blutes; bei einer Patientin wurde die Fibrinolyse deswegen abgebrochen. Andere Komplikationen wurden nicht beobachtet. Bei 8 der 9 Patienten kam es während der Fibrinolyse zu einer raschen und weitgehenden Reduktion des intraventrikulären Blutvolumens. Ein permanenter Shunt wurde bei 2 Patienten notwendig. Wir schließen, daß die intraventrikuläre Lyse wahrscheinlich zu einer schnelleren Clearance des intraventrikulären Blutes führt. Eine Shuntanlage wird nicht in jedem Fall verhindert. Die intraventrikuläre Fibrinolyse ist eine potentiell gefährliche Therapie mit dem Risiko von Infektionen und Blutungen.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Hyperammonämie ; Harnstoffzyklus ; Ornithintranscarbamylasemangel ; Carbamyltransferasemangel ; Citrullinämie ; Key words Hyperammonemia ; Urea cycle defects ; Ornithine transcarbamylase deficiency ; Carbamyl transferase deficiency ; Citrullinemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Six enzyme defects of the urea cycle have been described. Ornithine transcarbamylase deficiency is the most frequent of these diseases. The cumulative frequency is 1:8000. Most patients become symptomatic in childhood, but onset of symptoms may occur later in childhood or even adulthood. The patients present with recurrent episodes of an unspecific acute encephalopathy, seizures and clouding of consciousness to a variable degree. Focal neurological signs such as hemiparesis, aphasia or ataxia may also occur. These episodes may be triggered by infection, protein overload or drugs. Diagnostic are increased blood ammonia levels. Characteristic patterns of plasma amino acids and the determination of orotic acid in the urine mostly discriminate the inidvidual disorders. Further diagnostic steps include the allopurinol challenge test, liver or skin biopsy for measurement of enzyme activity and molecular genetic studies. Treatment requires restriction of protein intake, supplementation of arginine and activation of alternative pathways of nitrogen excretion with benzoate or phenylbutyrate. Untreated, the acute episode may be letal. Long-term treatment improves the clinical outcome considerably. Urea cycle defects should be included in the differential diagnosis of any encephalopathy or coma of unclear origin, and blood ammonia should be determined early in the evaluation of such patients.
    Notes: Zusammenfassung Es sind 6 angeborene Enzymdefekte des Harnstoffzyklus bekannt. Die kumulative Häufigkeit beträgt ca. 1:8000; der häufigste Enzymdefekt ist der Ornithintranscarbamylasemangel. Betroffene Patienten werden überwiegend im Kindesalter symptomatisch, späte Erstmanifestationen werden jedoch bis ins Erwachsenenalter beobachtet. Die Patienten präsentieren sich mit rezividierenden Episoden einer unspezifischen Enzephalopathie, Anfällen und Bewußtseinstrübungen bis zum Koma. Fokalneurologische Symptome wie Hemiparese, Aphasie oder Ataxie können ebenfalls vorkommen. Die akute Dekompensation, die durch Eiweißbelastung, Infektionen oder Medikamente ausgelöst werden kann, kann ohne Therapie letal verlaufen. Entscheidend für die Diagnose ist der Nachweis eines erhöhten Ammoniakspiegels. Die Differenzierung erfolgt mittels charakteristischer Plasmaaminosäurenprofile und der Orotsäurebestimmung im Urin. Weiterführende Untersuchungen sind der Allopurinolbelastungstest, die Messung der Enzymaktivität in Fibroblasten oder in der Leberbiopsie und molekulargenetische Analysen. Therapeutisch wird versucht, den Ammoniakspiegel medikamentös oder bei starker Erhöhung mittels Hämodialyse zu senken. Als Dauertherapie erhalten die Patienten eine proteinrestringierte Diät, Arginin wird supplementiert und Stickstoff zusätzlich mittels Natriumbenzoat und Natriumphenylbutyrat eliminiert. Die Dauertherapie verbessert die unbehandelt oft ungünstige Prognose. Hyperammonämien sind eine wichtige Differentialdiagnose von unklaren Enzephalopathien und Komazuständen in jedem Lebensalter. Eine Bestimmung des Ammoniaks sollte in der initialen Evaluation dieser Patienten rasch erfolgen.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Hypothermie ; Hirnödem ; Intensivmedizin ; Therapie ; Key words Brain edema ; Hypothermia ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Moderate hypothermia was induced in 30 patients with malignant middle cerebral artery (MCA) territory infarction. Patients were kept at 33°C body-core temperature for 48 to 72 h, and ICP, CPP, and brain temperature were monitored. Outcome at 4 weeks and at 3 months after the stroke as well as side effects of moderate hypothermia were analysed. Mortality of malignant MCA infarction could be reduced from 80% in historical controls, to 43% (13/30) under hypothermia. During hypothermia elevated ICP values could be significantly reduced. Herniation due to a secondary rise of ICP after rewarming was the cause of death in all 13 patients. The most frequent complication of moderate hypothermia was pneumonia in 12 of the 30 patients (40%). Other severe side effects of hypothermia could not be detected. Moderate hypothermia may improve clinical outcome in patients with malignant MCA infarction.
    Notes: Zusammenfassung Es wurde die Wirksamkeit moderater Hypothermie nach ausgedehnter zerebraler Ischämie bei 30 Patienten untersucht. Über eine 48 bis 72 h dauernde Hypothermie von 33°C Körperkerntemperatur gelang es, die Mortalität von Patienten mit malignem Mediainfarkt, die bei einer historischen Kontrollgruppe ca. 80% betrug, auf 43% zu senken. Durch moderate Hypothermie konnte der intrakraniellen Druck signifikant gesenkt werden. Die Wiedererwärmung hypothermer Patienten ist eine besonders kritische Phase in der Hypothermiebehandlung. Todesursache der 13 Patienten, die trotz der Hypothermiebehandlung verstarben, war ein nicht beherrschbarer ICP-Anstieg nach Wiedererwärmung. Wichtigste Nebenwirkung der Behandlung war eine relativ hohe Anzahl von Pneumonien (40%). Daneben kam es regelhaft zu einem Anstieg verschiedener Infektionsparameter, wie CRP, Leukozytenzahl und Fibrinogen. Darüber hinaus wurden keine wesentlichen sonstigen systemischen Nebenwirkungen der Hypothermiebehandlung beobachtet. Durch moderate Hypothermie kann der Verlauf des malignen Mediainfarktes günstig beeinflußt werden.
    Type of Medium: Electronic Resource
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