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Sökning: WFRF:(Näslund E.)

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  • Schmidt, P.T., et al. (författare)
  • Circulating ghrelin levels after food intake during different phases of the migrating motor complex in man.
  • 2006
  • Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:7, s. 503-509
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The timing of the migrating motor complexes (MMC) at food intake may influence gastric emptying and release of regulatory hormones. This report studies the relationships between phases I (motor quiescence) and II (intermediate frequency contractions) of MMC and prandial gut hormone response. Materials and methods Seven fasting volunteers ingested a meal during phase I or II of MMC verified by manometry, using paracetamol as a marker for gastric emptying. Blood was sampled before, during and 210 min after food intake for analysis of ghrelin, motilin, insulin and paracetamol. Results The basal level of ghrelin during phase I was 127·5 ± 25·4 pmol L-1 and during phase II was 132·4 ± 24·8 pmol L-1. After food intake during phase I, ghrelin fell to 77·2 ± 10 pmol L-1; in phase II it fell to 82·7 ± 17·8 pmol L-1 within 60 min and returned to baseline levels after 120 min. Baseline levels of motilin were 16 ± 2 pmol L-1 and 18 ± 3 pmol L-1 during phases I and II, respectively. After food, motilin decreased to 8·5 ± 0·7 pmol L-1 and 8·7 ± 1·0 pmol L-1 within 60 min and returned to baseline after 90 min. Insulin levels in phases I and II were 8·1 ± 1·2 mU L-1 and 8·6 ± 0·7 mU L-1, respectively, reaching 138·9 ± 35·6 mU L-1 and 167·4 ± 30·0 mU L-1 at 45 min postprandially. Conclusions The nutritional status of the gastrointestinal tract at food intake had only a limited impact on plasma ghrelin. After food intake, plasma ghrelin drops, similar to motilin, and resumes preprandial levels within 120 min.
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  • Alsmark, Cecilia M., et al. (författare)
  • The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae
  • 2004
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:26, s. 9716-9721
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.
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  • Sanger, G J, et al. (författare)
  • GSK962040 : a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
  • 2009
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:6, s. 657-664, e30-31
  • Tidskriftsartikel (refereegranskat)abstract
    • There is an urgent clinical need for a safe, efficacious stimulant of gastric emptying; current therapies include erythromycin (an antibiotic with additional properties which preclude chronic use) and metoclopramide (a 5-hydroxytryptamine type 4 receptor agonist and an antagonist at brain D2 receptors, associated with movement disorders). To move away from the complex motilide structure of erythromycin, a small molecule motilin receptor agonist, GSK962040, was identified and characterized. The compound was evaluated using recombinant human receptors, rabbit and human isolated stomach preparations known to respond to motilin and in vivo, by measuring its ability to increase defecation in conscious rabbits. At the human motilin receptor, the pEC50 (the negative logarithm to base 10 of the EC50 value, the concentration of agonist that produces 50% of the maximal response) values for GSK962040 and erythromycin as agonists were, respectively, 7.9 and 7.3; GSK962040 had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, GSK962040 300 nmol L−1–10 μmol L−1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L−1. In human-isolated stomach, GSK962040 10 μmol L−1, erythromycin 10 μmol L−1 and [Nle13]-motilin 100 nmol L−1, each caused muscle contraction of similar amplitude. In conscious rabbits, intravenous doses of 5 mg kg−1 GSK962040 or 10 mg kg−1 erythromycin significantly increased faecal output over a 2-h period. Together, these data show that GSK962040, a non-motilide structure, selectively activates the motilin receptor. Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis.
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