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  • 1
    Abstract: As a part of EU-project ReProTect, a comparison of the dual re-circulating human placental perfusion system was carried out, by two independent research groups. The detailed placental transfer data of model compounds [antipyrine, benzo(a)pyrene, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline] has been/will be published separately. For this project, a comparative re-analysis was done, by curve fitting the data and calculating two endpoints: AUC(120), defined as the area under the curve between time 0 and time 120 min and as t(0.5), defined as the time when the fetal to maternal concentration ratio is expected to be 0.5. The transport of the compounds from maternal to fetal circulation across the perfused placenta could be ranked in the order of antipyrine〉IQ〉PhIP in terms of both t(0.5) and AUC(120) by both partners. For benzo(a)pyrene the curve fitting failed. These prevalidation results give confidence for harmonization of the placental perfusion system to be used as one of the test methods in a panel for reproductive toxicology to model placental transfer in humans.
    Type of Publication: Journal article published
    PubMed ID: 20434538
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  • 2
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Glucagon-like peptide-1 ; analogue ; dipeptidyl peptidase IV ; non-insulin-dependent diabetes mellitus ; therapy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucagon-like peptide 1 (GLP-1) has great potential in diabetes therapy due to its glucose-dependent stimulation of insulin secretion, but this is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. Four analogues, N-terminally substituted with threonine, glycine, serine or α-aminoisobutyric acid, were synthesised and tested for metabolic stability. All were more resistant to dipeptidyl peptidase IV in porcine plasma in vitro, ranging from a t1/2 of 159 min (Gly8 analogue) to undetectable degradation after 6 h (Aib8 analogue; t1/2 for GLP-1 (7–36) amide, 28 min). During i. v. infusion in anaesthetised pigs, over 50 % of each analogue remained undegraded compared to 22.7 % for GLP-1 (7–36) amide. In vivo, analogues had longer N-terminal t1/2 (intact peptides: means, 3.3–3.9 min) than GLP-1 (7–36) amide (0.9 min; p 〈 0.01), but these did not exceed the C-terminal t1/2 (intact plus metabolite: analogues, 3.5–4.4 min; GLP-1 (7–36) amide, 4.1 min). Analogues were assessed for receptor binding using a cell line expressing the cloned receptor, and for ability to stimulate insulin or inhibit glucagon secretion from the isolated perfused porcine pancreas. All bound to the receptor, but only the Aib8 and Gly8 analogues had similar affinities to GLP-1 (7–36) amide (IC50; Aib8 = 0.45 nmol/l; Gly8 = 2.8 nmol/l; GLP-1 (7–36) amide = 0.78 nmol/l). All analogues were active in the isolated pancreas, with the potency order reflecting receptor affinities (Aib8 〉 Gly8 〉 Ser8 〉 Thr8). N-terminal modification of GLP-1 confers resistance to dipeptidyl peptidase IV degradation. Such analogues are biologically active and have prolonged metabolic stability in vivo, which, if associated with greater potency and duration of action, may help to realise the potential of GLP-1 in diabetes therapy. [Diabetologia (1998) 41: 271–278]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-069X
    Keywords: Atopic dermatitis ; Cromones ; Clinical trial ; Immediate hypersensitivity ; Intra- and epicutaneous tests ; Atopische Dermatitis ; Kromone ; klinischer Versuch ; unmittelbare Hypersensibilität ; intra- und epicutane Tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Drei neue Kromone mit einer vermutlich besseren Absorption und einem vermutlich weiteren Spektrum antiallergischer Aktivität als Disodium Cromoglycate wurden untersucht. Die Vorbehandlung mit intradermaler Injecktion von 10 μg FPL 52758 hat in 11 Patienten mit atopischer Dermatitis die durch spezifisches Antigen hervorgerufene ≫weal and flare≪-Reaktion signifikant reduziert. Lokale Applikation von 1,5 mg von FPL 52758 unter Okklusion während 24 h vor ≫challenge≪ hat in denselben Patienten die ≫weal and flare≪-Reaktion nicht reduziert. Der durch die Antigeninjektion verursachte Juckreiz und leichte Schmerz wurde an den mit FPL 52758 vorbehandelten Stellen nicht bemerkt. Vorläufige klinische Erfolge wurden durch Behandlung mit dem Kromone FPL 52757 erhalten. Wegen möglicher Lebertoxicität wurde aber die Untersuchung nicht weitergeführt. Ein ähnliches Kromon ohne Lebertoxicität wurde in einem ≫double-blind within-patient≪-Versuch benutzt, wo 9 Patienten mit minder bis schwachausgeprägter atopischer Dermatitis mit FPL 57787 (5%) Salbe und identischer Grundlage während 4 Wochen ohne signifikante Besserung behandelt wurden.
    Notes: Summary Three new cromones have been studied that are supposed to be better absorbed and to have a wider spectrum of anti-allergic activity than disodium cromoglycate. Pretreatment with i.d. injection of 10 μg FPL 52758 significantly reduced the weal and flare reaction induced by specific antigen in 11 patients with atopic dermatitis. The weal and flare reaction was not reduced in the same patients when 1.5 mg of FPL 52758 was applied topically under occulusion for a 24-h period prior to challenge with antigen. The itch and slight pain caused by antigen injection was not experienced in the FPL 52758 pretreated areas. Preliminary clinical results were obtained with the cromone FPL 52757, but due to possible hepatotoxicity this trial was not completed. Another similar cromone without hepatotoxicity was used in a double blind within-patient study. Nine patients with mild to moderate atopic dermatitis were treated with FPL 57787 (5%) ointment and matching placebo ointment. No significant improvement was observed after 4 weeks of treatment with the cromone containing ointment.
    Type of Medium: Electronic Resource
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  • 6
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    Springer
    Urological research 20 (1992), S. 335-339 
    ISSN: 1434-0879
    Keywords: Insulin-like growth factor I ; Obstructive nephropathy ; Pigs ; Kidney growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kidney growth was investigated in 30-kg pigs after 72 h of unilateral ureteral obstruction. The data were compared to control kidneys from normal non-operated pigs at same weight. Kidney wet weight was determined. Cortex and medulla were separated, and from both regions RNA, DNA, protein and kidney tissue insulin-like growth factor I was determined. Unilateral obstruction caused a doubling of the wet hydronephrotic kidney weight and an ipsilateral 76% increase in total kidney protein content. RNA increased by 45% in the cortex and 76% in the medulla. Kidney protein in the contralateral cortex increased by 23% and RNA by 42%. In the hydronephrotic kidney DNA was reduced by 13% in the cortex and by 21% in the medulla. Contralaterally, DNA was the same as in the controls. Mean kidney insulin-like growth factor I increased sevenfold in the ipsilateral medulla but in the cortex it was the same as in the controls. Serum insulin-like growth factor I concentration was 1.7 ±1.1 μg/l in the hydronephrotic animals and 1.2±0.8 μg/l in controls. At this stage of obstruction, our data demonstrate (1) hydronephrotic growth that is most probably hyperplastic in the medulla, associated with an increase in medullary insulin-like growth factor I, (2) hyperplastic growth in the cortex, and (3) contralateral kidney growth that is mainly hypertrophic after 72 h of contralateral ureteral obstruction.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-0879
    Keywords: Cystometry ; Reproducibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fifty-six patients were investigated by repetitive cystometry in the supine or sitting position. The incidence of detrusor hyperreflexia and the circumstances under which it was found did not differ from previous studies. The cystometry data concerning volumes showed a remarkable degree of variability. Values for first sensation and maximal capacity could vary more than 500%. An increment from the first cystometry to the fourth was consistently found. The increments were most pronounced when cystometry with fast filling followed cystometry with medium filling regardless of the patient's position. The major factor in the changes is considered to be the patient's adaptation to the investigational situation. This finding might have major significance in the evaluation of drug studies where repeated cystometries with different time intervals are used.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1590-3478
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1590-3478
    Keywords: multiple sclerosis ; neuropsychology ; affective disorder ; symptom
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Scopo del presente lavoro è stato quello di esaminare la correlazione tra ansia e disabilità e di valutare se gli stati ansiosi fossero correlati con forme specifiche di disturbi cognitivi. Novantaquattro pazienti (42 femmine e 52 maschi) con SM definita sono stati reclutati nel presente studio. L'ansia è stata valutata secondo lo State-Trait Anxiety Inventory, la disabilità fisica mediante la scala di Kurtzke e per i disturbi cognitivi sono stati somministrati i seguenti test: Trail Making, Symbol Digit Modalities, Auditory Verbal Learning, Story Recall e Recurring Figures. I pazienti con un handicap moderato (DSS 4–5) mostravano segni di ansia e il disturbo era correlato con lo stato di ansia (p〈0.05; d.f. 1. 92). Pure il test Trail Making era correlato con l'ansia (p〈0.01; d.f. 1.86). Sulla base di questi e di precedenti studi, si conclude che l'ansia quò essere un segno di disfunzione cognitiva, di disturbi fisici o di pressione sociale.
    Notes: Abstract The aim of the study was to examine the correlation between anxiety and physical impairment and to discover whether anxiety correlated with specific forms of cognitive dysfunction. Ninetyfour patients (42 females, 52 males) with definite MS entered the study. Anxiety was measured using the State-Trait Anxiety Inventory, physical impairment by means of the Kurtzke Disability Status scale, and cognitive impairment by using the Trail Making, Symbol Digit Modalities, Auditory Verbal Learning, Story Recall and the Recurring Figures tests. Moderately handicapped patients (DSS 4–5) showed signs of anxiety, and physical impairment correlated with anxiety (p〈0.05; d.f. 1.92). Trail Making also correlated with anxiety (p〈0.01; d.f. 1.86). On the basis of the results of this and previous studies, it is concluded that anxiety can be a sign of cognitive dysfunction, physical impairment or social strain.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1590-3478
    Keywords: Multiple sclerosis ; Pain ; Symptoms ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario L'occorrenza di sindromi dolorose acute (durata inferiore a 1 mese) o croniche (durata superiore a 1 mese) è stata indagata in 49 pazienti (22 maschi e 27 femmine) con sclerosi multipla definita. Ciascun paziente è stato esaminato due volte con un intervallo di 5 anni tra i due controlli. Tra il primo e il secondo controllo si è osservato un significativo aumento di sindromi dolorose acute e croniche comprendenti tensione e dolore alle estremità, spasmi, lombalgia, segno di Lhermitte e dolori neuralgici. Tale aumento si è verificato sia nei maschi che nelle femmine ed è particolarmente evidente nei pazienti con deterioramento e disabilità.
    Notes: Abstract Forty-nine (22 males, 27 females) patients with definite multiple sclerosis were examined twice with 5 years interval regarding acute (less than 1 month duration) and chronic (more than 1 month duration) pain syndromes. From the first to the second examination a significant increase was found in the number of acute and chronic pain syndromes, including tension and pain in the extremities, spasms, low back pain, Lhermitte's sign and neuralgia. The increase included both men and women. The increase was especially found in patients with deterioration of disability.
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