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  • 1. Janssen, Pieter
    et al.
    Karlsson, Lisa K. C.
    Nielsen, Maria Astin
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hultin, Leif
    Effect of Muscarinic and Nicotinic Receptor Antagonism on Rat Gastric Motor Activity2010In: Pharmacology, ISSN 0031-7012, E-ISSN 1423-0313, Vol. 85, no 5, 272-279 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach. Methods: Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion. Results: In the presence of N-G-nitro-L -arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean +/- SEM = 0.27 +/- 0.04 ml; n = 6) that could be blocked by atropine (3 mu mol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg(-1)) initially decreased IGP, while during further distension it increased IGP. In the presence of L -NAME (30 mg kg(-1)) atropine consistently decreased IGP.

  • 2. Sakurai, Eiko
    et al.
    Sakurai, Eiichi
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nishiyama, S
    Kato, M
    Watanabe, T
    Yanai, K
    Evidence for the presence of histamine uptake into the synaptosomes of rat brain2006In: Pharmacology, ISSN 0031-7012, E-ISSN 1423-0313, Vol. 78, no 2, 72-80 p.Article in journal (Refereed)
    Abstract [en]

    Histamine has many physiological roles in the brain and periphery. Neuronal histamine is metabolized almost exclusively by histamine N-methyltransferase. Although several neurotransmitter systems such as dopamine and 5-hydroxytryptamine have their specific reuptake system in their neurons and glial cells, a specific histamine reuptake system into the corresponding nerve terminals or glial cells has not yet been clearly elucidated. We characterized the uptake of histamine into the P2 fractions of rat brain homogenized in 0.32 mol/l sucrose using in vitro uptake techniques. [3H]histamine uptake increased with the increment of added protein amount and elapsed time. [3H]histamine uptake was also temperature-dependent. The uptake of [3H]histamine into the P2 fractions occurs by two saturable processes, a high-affinity and a low-affinity, characterized by K(m) values of 0.16 and 1.2 micromol/l, respectively. Na(+), Cl(-) and HCO(3)(-) ions were essential for the uptake of histamine in P2 fractions. [3H]histamine uptake was inhibited in the presence of several tricyclic antidepressants. In accordance with this, the endogenous release of histamine from brain slices evoked by 100 mmol/l K(+) was augmented in the presence of 20 micromol/l imipramine. These results further support the existence of a specific histamine uptake system in the brain, although the precise molecular entities have not been identified until now.

  • 3. Sauermann, Robert
    et al.
    Karch, Rudolf
    Kjellsson, Maria C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Feurstein, Thomas
    Püspök, Andreas
    Langenberger, Herbert
    Böhmdorfer, Michaela
    Jäger, Walter
    Zeitlinger, Markus
    Good penetration of moxifloxacin into human abscesses2012In: Pharmacology, ISSN 0031-7012, E-ISSN 1423-0313, Vol. 90, no 3-4, 146-150 p.Article in journal (Refereed)
    Abstract [en]

    Abscesses are often treated with antibiotics in addition to incision or when incision is unfeasible, but accurate information about antibiotic abscess penetration in humans is missing. This study aimed at evaluating the penetration of moxifloxacin into human abscesses. After administration of a single dose of 400 mg moxifloxacin, drug concentrations were measured in 10 differently located abscesses at incision, and in plasma over 8 h. At incision performed 0.9-4.8 h after administration, moxifloxacin concentrations in abscesses ranged from ≤0.01 to 9.2 mg/l (1.9 ± 3.4 mg/l), indicating pronounced drug accumulation in some abscesses. The degree of abscess penetration could not be explained by covariates like the ratio of surface area to volume or pH of abscesses, or by moxifloxacin plasma concentrations. Concluding, moxifloxacin was detectable in most abscesses and may be a useful antibiotic for this indication. However, antibiotic abscess penetration was highly variable and unpredictable, suggesting surgical abscess incision whenever possible.

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