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  • Acute and chronic treatments  (3)
  • Dynamic MR imaging  (2)
  • 1
    ISSN: 1432-2072
    Keywords: Imipramine ; Fluoxetine ; 5-HT reuptake inhibitors ; Flight ; Antipredator defense ; Fear ; Anxiety ; Panic ; Predator assessment ; Acute and chronic treatments ; Swiss-Webster mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Mouse Defense Test Battery (MDTB) has been designed to assess defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat. Primary measures taken before, during and after predator confrontation comprise escape attempts, predator assessment, defensive attack and flight. Previous reports from this laboratory have shown that the panic-promoting drug yohimbine potentiated flight behavior, while long-term treatment with the panicolytic agent alprazolam reduced this response. In order to evaluate further the possibility that the MDTB may represent an effective animal model of panic attacks, the present study investigated the behavioral effect of imipramine and fluoxetine, two serotonin reuptake inhibitors (SRIs) known to alleviate panic symptoms when given on a repeated basis. Both drugs were administered acutely and chronically (one daily IP injection for 21 days) at 5, 10 and 15 mg/kg. Our results showed that a single dose of imipramine or fluoxetine strongly potentiated flight reactions in response to an approaching predator and increased defensive attack toward the rat. This was in contrast to chronic treatment with each drug which dramatically decreased flight responses and defensive attack behaviors. In addition, long-term administration with both SRIs produced a reliable attenuation of predator assessment activities. Taken together, these findings suggest an acute anxiogenic-like effect of imipramine and fluoxetine followed by a fear/anxiety reducing effect after repeated administrations. These results support clinical observations revealing an acute anxiogenic effect of SRIs followed by an anxiolytic and/or panicolytic effect after chronic use, and support previous results suggesting that the MDTB may be useful for the investigation of panic-modulating agents.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Befloxatone ; Moclobemide ; Reversible monoamine oxidase inhibitors ; Defensive behaviours ; Flight ; Risk assessment ; Panic ; Anxiety ; Acute and chronic treatments ; Swiss mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study compared the behavioural effects of acute and chronic (one daily IP injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) and befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDTB) which has been designed for screening anxiolytic and anti-panic drugs. In the MDTB, Swiss mice were confronted with a natural threat (a rat) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flight, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behaviours were observed. This was in contrast to chronic treatments, where moclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a significant reduction in one flight measure (avoidance distance when the rat was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but not moclobemide, increased RA responses when mice were constrained in one part of the apparatus facing the rat, which remained at a constant distance. No other drug effects were observed with either compound. Although these behavioural profiles are consistent with an anxiolytic-like effect, the finding of an action upon a limited number of defence responses suggests a weaker anxiolytic-like potential compared to that of classical anxiolytics. However, in view of previous data with panic-modulating compounds on flight behaviours in the MDTB, the present results are in line with clinical results showing that moclobemide is effective in panic disorders and suggest that befloxatone may have some efficacy in the clinical management of panic.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Cianopramine ; Citalopram ; 5-HT reuptake inhibitors ; Light/dark choice procedure ; Elevated plus-maze test ; Anxiety ; Neophobia ; Acute and chronic treatments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated behavioural effects of very potent 5-HT reuptake inhibitors after acute treatment (cianopramine and citalopram), as well as after chronic treatment (cianopramine), in two behavioural models of anxiety: 1) the light/dark choice procedure in mice and 2) the elevated plus-maze test in rats. In addition, the responses of mice to novelty in a free exploration paradigm were assessed after acute administration of both drugs. A single injection of cianopramine or citalopram increased neophobic reactions in the free exploration test. Furthermore, these drugs increased the avoidance reaction to a brightly illuminated chamber in the light/dark choice procedure as well as to open arms in the elevated plus-maze test. In contrast, after chronic treatment (10 mg/kg IP, once daily for 21 days) of cianopramine, anxiogenic-like effects were no longer produced in the light/dark choice paradigm whereas in the elevated plus-maze test, anxiolytic-like effects appeared. These results shed more light on the 5-HT hypothesis of anxiety, insofar as the increased availability of 5-HT resulting here from reuptake inhibition seems to initially result in an increased emotional reactivity which, however, subsequently disappears during chronic treatment.
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  • 4
    ISSN: 1439-099X
    Keywords: Schlüsselwörter: Tumormikrozirkulation ; Blutfluss ; Dynamische MR-Messungen ; Rektumkarzinom ; Präoperative Strahlentherapie ; Perfusionsindex ; Prognosefaktor ; Key Words: Tumor microcirculation ; Blood flow ; Dynamic MR imaging ; Rectal carcinoma ; Preoperative chemoradiation ; Perfusion index ; Prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Purpose: The aim of our study was to evaluate in vivo the influence of tumor microcirculation data on therapy outcome. Patients and Methods: Tumor perfusion data of primary rectal carcinoma (n = 14, cT3) who underwent preoperative chemoradiation have been analyzed (Table 1). The perfusion data were acquired at the beginning and at the end of therapy by use of an ultrafast T1-mapping sequence on a whole-body magnetic resonance imager. The gadolinium-DTPA concentration-time-curves were evaluated for arterial blood and tumor before, during and after intravenous constant rate infusion and from that the perfusion index (PI) was calculated. Subsequent resection of the tumors allowed for a correlation of perfusion index values with the pathological classification. Results: Nine patients showed a T downstaging (ypT0–2, group 1), 5 patients did not (ypT3, group 2). The initial mean perfusion index value of group 1 (n = 9) was 8.2 ml/min/100 g (±2) and for group 2 (n = 5) 10.4 ml/min/100 g (±0.4). The difference in perfusion index values before chemoradiation between group 1 and group 2 was significant different (p = 0.012, Mann-Whitney test). The perfusion index value at the end of therapy of group 1 (n = 6) was 9.6 ml/min/100 g (±2.8) and for group 2 (n = 4) 10.7 ml/min/100 g (±1.6). The difference in perfusion index values after chemoradiation between group 1 and group 2 was not significant different (Table 2). Conclusion: Our used perfusion index value combines 2 parameters: tumor perfusion and extraction fraction. Therefore a significant negative influence on therapy outcome of high perfusion index values could be explained possibly by areas with a high portion of high perfusion (e.g. av-shunts) and a low extraction fraction (= low exchange of nutrients). However, we could show a significant negative influence of high perfusion index values on therapy outcome (p = 0.012). Because the tumor stage has a significant influence on tumor-free survival, there is a possibility for using initial perfusion index values as a new prognostic factor in rectal carcinoma without sphincter infiltration undergoing a preoperative chemoradiation. To examine this hypotheses a prospective trial is in preparation.
    Notes: Fragestellung: Ziel unserer Untersuchung war es, den Einfluss in vivo erhobener Tumormikrozirkulationsdaten auf ein Therapieansprechen zu evaluieren. Patienten und Methode: Bei primären Rektumkarzinomen (n = 14, cT3) wurden Tumorperfusionsdaten bei Beginn und am Ende einer präoperativen kombinierten Radiochemotherapie mittels ultraschneller T1-Mapping-Sequenzen an einem 1,5-Tesla-Ganzkörperkernspintomographen erhoben. Gadolinium-DTPA-Konzentrations-Zeit-Kurven wurden vor, während und nach einem prolongierten Bolus im arteriellen Blut und im Tumor erhoben und daraus der Perfusionsindex (PI) berechnet. Die anschließende chirurgische Resektion ermöglichte eine pathologische Klassifizierung und somit einen Vergleich der Perfusionsindexwerte mit dem Therapieansprechen. Ergebnisse: Bei neun Patienten konnte ein Tumor-Downstaging (ypT0–2) (Gruppe 1), bei fünf Patienten kein Tumor-Downstaging (ypT3) (Gruppe 2) nachgewiesen werden. Der mittlere Perfusionsindexwert für Gruppe 1 (n = 9) betrug 8,2 mg/min/100 g (± 2) und für Gruppe 2 (n = 5) 10,4 ml/min(100 g (±0,4). Es zeigte sich ein signifikanter Unterschied Gruppe 1 versus Gruppe 2 bezüglich Tumor-Downstaging (p = 0,012). Der bei Therapieende erhobene mittlere Perfusionsindexwert für Gruppe 1 (n = 6) betrug 9,6 ml/min/100 g (± 2,8) und für Gruppe 2 (n = 4) 10,7 ml/min/100 g ± 1,6). Hier konnte kein signifikanter Unterschied nachgewiesen werden. Schlussfolgerung: Der Perfusionsindexwert kombiniert zwei Parameter: Tumorperfusion und Extraktionsfraktion. Der überraschende negative Einfluss hoher Perfusionsindexwerte auf ein Therapieansprechen kann somit möglicherweise durch einen hohen Anteil an Arealen hoher Perfusion (eventuell arteriovenösen Shunts) mit niedriger Extraktionsfraktion (= minimaler Stoffaustausch) erklärt werden. Wir konnten aufzeigen, dass hohe Perfusionsindexwerte bei Therapiebeginn einen signifikanten negativen Einfluss (p = 0,012) auf ein Therapieansprechen haben. Da das Tumorstadium einen signifikanten Einfluss auf die tumorfreie Überlebenszeit hat, könnte möglicherweise der Perfusionsindexausgangswert als neuer Prognosefaktor bei primären Rektumkarzinomen ohne Sphinkterinfiltration, die präoperativ mit einer kombinierten Radiochemotherapie behandelt werden, zugezogen werden. Zur Überprüfung dieser Hypothese ist eine prospektive Studie in Vorbereitung.
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  • 5
    ISSN: 1439-099X
    Keywords: Schlüsselwörter: Tumorperfusion ; Blutfluß ; Dynamische MR-Messungen ; Rektumkarzinom ; Strahlentherapie ; Key Words: Tumor microcirculation ; Blood flow ; Dynamic MR imaging ; Rectal carcinoma ; Radiation therapy ; Chemotherapy ; Trancer kinetic modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Purpose: This study was aimed at measuring microcirculatory parameters and contrast medium accumulation within the rectal carcinoma during fractionated radiotherapy in the clinical setting. Materials and Methods: Perfusion data were observed in patients with rectal carcinoma (n = 8) who underwent a properative combined chemo/radiotherapy. To acquire perfusion data, an ultrafast T1 mapping sequence was carried out on a 1.5-Tesla whole body imager to obtain T1 maps at intervals of 14 or 120 seconds. The overall measurement time was 40 minutes. The transaxial slice thickness (5mm) was chosen in such a way that both arterial vessels and the tumor could be clearly identified. The gadolinium-DTPA (Gd-DTPA) concentration time curve was evaluated for arterial blood and tumor after intravenous constant rate infusion. The method allows a spatial resolution of 2 × 2 × 5 mm and a temporal resolution of 14 seconds. Patients underwent MR imaging before and at constant intervals during fractionated radiotherapy. Results: Spatial and temporal resolution of dynamic T1 mapping was sufficient to reveal varying CM accumulation levels within the tumor and to identify the great arteries in the pelvis. In 6 patients Gd-DTPA concentration-time-curves were evaluated within the tumor during radiation. Pi index of Gd-DTPA versus radiation dose showed a significant increase in the first or second week of treatment, then either returned slowly to pretreatment level or a renewed increase was observed. The average Pi-value at the beginning was 0.16 (±0.049), reaching highest level of 0.23 (±0.058). In all groups the rise from the Pi-value to the Pi-maximum was statistically significant. The relative increase in perfusion ranged between 20 to 83%. Conclusion: The results show, that the ultrafast MR-technique described above provide a suitable tool for monitoring tumor microcirculation during therapeutic interventions and offers the potential for an individualized optimization of therapeutic procedures.
    Notes: Ziel: Entwicklung und Anwendung dynamischer Magnetresonanztomographiemessungen zur Erhebung von Perfusionsparametern bei Rektumkarzinomen unter Bestrahlung in der klinischen Routine. Patienten und Methode: Bei Rektumkarzinompatienten (n = 8), die sich einer präoperativen kombinierten Radiochemotherapie unterzogen, wurden Perfusionsdaten erhoben. An einem 1,5-Tesla-Ganzkörperkernspintomographen wurden ultraschnelle T1-Mapping-Sequenzen zum Erhalt von T1-Maps mit Intervallen von 14 und 120 Sekunden implementiert. Die Meßzeit der dynamischen Messungen betrug 40 Minuten. Die Maßschicht (Schichtdicke 5mm) wurde so gewählt, daß sowohl Tumor als auch arterielle Gefäße dargestellt wurden. Gadolinium-DTPA-(Gd-DTPA-)Konzentrations-Zeit-Kurven wurden nach einem prolongierten Bolus im arteriellen Blut und im Tumor berechnet. Die angewendete Methode erlaubte eine räumliche Auflösung von 2 × 2 × 5 mm und eine zeitliche Auflösung von 14 Sekunden. Die Meßdaten wurden vor und in konstanten Intervallen während Therapie erhoben. Ergebnisse: Die räumliche und zeitliche Auflösung der T1-Maps war ausreichend, um Areale mit unterschiedlicher Kontrastmittelkinetik innerhalb des Tumors zu erfassen sowie die großen Beckenarterien sicher zu identifizieren. Bei sechs Patienten konnten Gd-DTPA-Konzentrationskurven im Tumor unter Therapie erhoben werden. Der Perfusionsindex (Pi) versus Strahlendosis zeigte eine signifikante Zunahme in der ersten oder zweiten Woche der Bestrahlung, bevor er entweder kontinuierlich absank oder nach anfänglichem Abfall einen erneuten Anstieg aufwies. Der durchschnittliche Pi-Ausgangswert betrug 0,16 (±0,049), das durchschnittliche Pi-Maximum war 0,23 (± 0,058). Die relativen Perfusionsveränderungen betrugen zwischen 20 und 83%. Schlußfolgerung: Unsere Ergebnisse zeigen, daß sich die verwendete Methode zur Erfassung von Perfusionsparametern unter Bestrahlung eignet und in der klinischen Routine anwendbar ist. In der Zukunft könnte mittels der gewonnenen Daten eine individualisierte tumor- und perfusionsangepaßte Therapieoptimierung bei kombinierter Radiochemotherapie durchgeführt werden.
    Type of Medium: Electronic Resource
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