M Kietzmann

University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany

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Publications (92)104.69 Total impact

  • Article: The isolated perfused equine distal limb as an ex vivo model for pharmacokinetic studies.
    M Friebe, J Stahl, M Kietzmann
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    ABSTRACT: Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered as BM disodium phosphate intra-articularly to the fetlock joint (4 mg BM/joint), was investigated. The concentration of BM in the venous perfusate of the radial vein was measured by means of high-performance liquid chromatography. The average BM efflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mg BM had left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies.
    Journal of Veterinary Pharmacology and Therapeutics 08/2012; · 1.18 Impact Factor
  • Article: Characterization of MgNd2 alloy for potential applications in bioresorbable implantable devices.
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    ABSTRACT: The aim of this study is to investigate and demonstrate the mechanical and corrosive characteristics of the neodymium-containing magnesium alloy MgNd2 (Nd2), which can be used as a resorbable implant material, especially in the field of stenting applications. To determine the mechanical characteristics of Nd2, tensile and compression tests were initially carried out in the hot extruded state. Here a unique elongation ratio (~30%) of the alloy could be observed. Subsequent T5 and T6 heat treatments were arranged to reveal their effect on the alloy's strengths and elongation values. The general degradation behaviour of Nd2 in a 0.9% NaCl solution was investigated by means of polarization curves and hydrogen evolution. In addition to this, by using various in vivo parameters, a corrosion environment was established to determine the alloy's degradation in vitro. Here, the mass loss per day in (MgF(2) and Bioglass)-coated and uncoated states and the corresponding maximum forces resulting from subsequent three-point bending tests revealed slow and steady corrosion behaviour. The cell viability and proliferation tests carried out on L-929 and MSC-P5 cells also showed good results. The mechanical and corrosive characteristics determined, as well as the in vitro test results obtained within the scope of this study, led to the development and successful in vivo testing of an MgF(2)-coated Nd2 mucosa stent which was introduced as an appropriate resorbable application.
    Acta biomaterialia 06/2012; 8(10):3852-64. · 3.98 Impact Factor
  • Article: [The use of fluoroquinolones in bacterial urinary tract infections in cats].
    S Kramer, M Kietzmann, W-R Pankow
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    ABSTRACT: Older cats (>10 years) with FLUTD (Feline Lower Urinary Tract Disease) symptoms are often affected by urinary tract infections. In most of these cats organ diseases (e.g. chronic renal failure, diabetes mellitus) or iatrogenic factors (immunosuppressive drugs, indwelling catheter) are found that clearly predispose cats to this kind of infection. From a diagnostic point of view, urinalysis and urine culture are the most important tools in detecting bacteriuria. The microbiological spectrum is thereby comparable to that found in dogs, revealing Escherichia ( E. ) coli but also Staphylococcus spp. and Enterococcus spp./ Streptococcus spp. Antibiotic therapy should be based on the results of susceptibility testing. If this kind of information is not available, drug selection has to be decided on an empirical basis unless it is a complicated urinary tract infection. Preferred antibiotics should have a high renal excretion rate and thus ensure therapeutically effective drug levels in the urine. In this respect, the fluoroquinolones belong to the group of appropriate drugs to be used in cats. The relevance of therapeutical drug concentrations achievable in the urine is discussed for the example of marbofloxacin, a third-generation fluoroquinolone. New pharmacokinetic data showed that marbofloxacin concentrations of ≥2µg/ml are maintained in the urine of healthy cats for 72 and 103 hours after administration of 2 and 4mg/kg BW s.c., respectively.
    Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere 04/2012; 40(2):113-21.
  • Article: The correlation between epidermal lipid composition and morphologic skin characteristics with percutaneous permeation: an interspecies comparison of substances with different lipophilicity.
    J Stahl, F Niedorf, M Kietzmann
    Journal of Veterinary Pharmacology and Therapeutics 10/2011; 34(5):502-7. · 1.18 Impact Factor
  • Article: Distribution of permethrin in hair and stratum corneum after topical administration of four different formulations in dogs.
    Journal of Veterinary Pharmacology and Therapeutics 08/2011; 35(2):206-8. · 1.18 Impact Factor
  • Article: Histamine H1, H3 and H4 receptors are involved in pruritus.
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    ABSTRACT: Histamine has long been recognised as a classical inducer of pruritus. However, the specific mechanism of histamine-induced itch has still not been fully understood. The H1 and H4 receptor appear to be key components in the induction of itch. The specific role of the H3 receptor in histamine-induced itch remains unclear. The aim of our study was to investigate the role of the four known histamine receptors (H1-4) in acute itch in mice. Intradermal injection of the selective H3R inverse agonist pitolisant induced strong itch in mice. Pitolisant (50 nmol/injection)-induced pruritus could be completely blocked by a combined treatment with the H1R antagonist cetirizine (15 mg/kg) and the H4R antagonist JNJ 7777120 (15 mg/kg), whereas the H2R antagonist ranitidine (15 mg/kg) failed to inhibit the scratch response. Next, expression and function of histamine receptors on sensory neurons isolated from dorsal root ganglia of mice were investigated. As the itch sensation results from the excitation of sensory nerves in the skin, we further focused on skin specific sensory neurons. Therefore, neurons were retrograde labelled from the skin by means of a fluorescent tracer. Expression of H1R, H3R and H4R on skin innervating sensory neurons was detected. By single-cell calcium imaging, it was demonstrated that histamine induces a calcium increase in a subset of (skin-specific) sensory neurons via activation of the H1R and H4R as well as inhibition of the H3R. It is assumed that the decreased threshold in response to H3R antagonism activates H1R and H4R on sensory neurons, which in turn results in the excitation of histamine-sensitive afferents and therefore elicits the sensation of itch.
    Neuroscience 06/2011; 190:89-102. · 3.38 Impact Factor
  • Article: Absorption of Isosorbide Dinitrate after Administration as Spray, Ointment and Microemulsion Patch. An In‐vitro Study Using the Isolated Perfused Bovine Udder
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    ABSTRACT: The isolated perfused bovine udder is an in-vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in-vitro model, the percutaneous absorption and metabolism of isosorbide dinitrate (ISDN) was studied.The organ was perfused with gassed Tyrode solution for up to 6 h. A region of udder skin was treated topically with 60 mg ISDN as a spray, 60 mg ISDN as an ointment and with 120mg ISDN as a microemulsion patch of 30 cm2. Spray and ointment were applied onto a skin region of 400 cm2. The concentrations of ISDN and its metabolites isosorbide-2-mononitrate and isosorbide-5-mononitrate were measured in perfusate fractions by capillary column gas-liquid chromatography with electron capture detection.Following topical administration of the different formulations, ISDN as well as its metabolites were detected in the perfusate fractions, thus demonstrating that ISDN is metabolized by the udder skin in-vitro. A maximum amount of ISDN was absorbed after administration as a spray followed by ointment and microemulsion (5, 2·5 and 1·8 μmol total organic nitrate, respectively). In contrast, the ISDN flux per cm2 skin was significantly higher after administration of the microemulsion (64·4 pmol cm−2 min−1 for the microemulsion compared with 21·9 and 10·2 pmol cm−2 min−1 for spray and ointment).
    Journal of Pharmacy and Pharmacology. 04/2011; 47(1):22 - 25.
  • Article: Untersuchungen über streßabschirmende Wirkungen von oral verabreichtem Zinkbacitracin bei Ratten
    K. Kaemmerer, M. Kietzmann
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    ABSTRACT: ZusammenfassungDer Katecholamin- und der Corticosterongehalt des Plasmas wird in Versuchen an Ratten durch Streß deutlich gesteigert; gleichzeitig sinkt die Proteinsyntheserate im Lebermikrosomenzellsaft ab.Zinkbacitracin fördert die Proteinsyntheserate bei unbelasteten Ratten im Lebermikrosomenzellsaft deutlich.Werden mit Zinkbacitracin vorbehandelte Ratten einem Streß ausgesetzt, so liegt die Syntheserate im Bereich der Kontrollwerte unbehandelter und nicht gestreßter Tiere. Der Plasmagehalt an Katecholaminen und Corticosteron steigt bei mit Zinkbacitracin vorbehandelten Ratten im Streß weniger an als bei nicht vorbehandelten Tieren.Es erscheint aufgrund der hier erzielten Ergebnisse möglich, daß der nutritive Effekt des Zinkbacitracins mit einer streßabschirmenden Wirkung in Zusammenhang steht.SummaryStudies on stress-protecting effects of orally administered zinc bacitracin to ratsThe catecholamine and corticosteroid concentrations in plasma rose significantly in rats subjected to stress; at the same time protein synthesis rate in liver microsome cell juice was reduced.Zinc bacitracin significantly increased the rate of protein synthesis in the liver microsome cell juice in unstressed rats.If rats previously given zinc bacitracin were subjected to stress the rate of synthesis of protein was similar to the control values in undosed unstressed animals. The plasma concentrations of catecholamines and corticosteroids rose in rats given zinc bacitracin to a less extent when the rats were stressed than in undosed rats.These findings suggest that the nutritive benefits of zinc bacitracin may be related to a stress protecting effect of the agent.RésuméRecherches sur les effets protecteurs contre un stress d'une application orale de zinc-bacitracine chez des ratsLe taux de Katécholamine et de corticostérone du plasma est fortement augmenté par un stress lors de recherches sur des rats; le taux de synthèse des protéines diminue en même temps dans le liquide cellulaire des microsomes hépatiques.La zinc-bacitracine favorise nettement le taux de synthèse des protéines dans le liquide cellulaire des microsomes hépatiques chez des rats non stressés.Si des rats traités à la zinc-bacitracine sont soumis à un stress, le taux de synthèse se situe dans les valeurs de contrôle des animaux non traités et non stressés. Les taux du plasma en Katécholamine et en corticostérone augmente moins lors d'un stress chez des rats prétraités avec la zinc-bacitracine que chez des animaux non traités.Il semble sur la base de ces résultats que l'effet nutritif de zinc-bacitracine puisse être en rapport avec un effet protecteur contre un stress.ResumenEstudios sobre los efectos protectores contra un stress de la bacitracina de eine administrada por vía oral en ratasEn los ensayos realizados en ratas con stress se aumentan fuertemente los contenidos de catecolamina y corticosterona en el plasma sanguíneo; al mismo tiempo disminuye la tasa de síntesis de proteínas en el líquido celular de los microsomas hepáticos.La bacitracina de eine favorece de forma neta la tasa de síntesis de proteínas en el líquido celular de las microsomas hepáticas de ratas no gravadas.Al exponer ratas pretratadas con bacitracina de eine a un stress, se halla la tasa de síntesis dentro del ámbito de los valores de control de los animales no tratados y no sometidos a un estado de tensión. El contenido plasmático en catecolaminas y corticosterona aumenta menos en las ratas con stress, que habían sido pretratadas con bacitracina de eine, que en los animales que no habían sido pretratados.A la vista de los resultados obtenidos aquí, parece posible que el efecto nutritivo de la bacitracina de eine esté relacionado con un efecto protector contra el stress.
    Journal of Veterinary Medicine Series A 05/2010; 30(8):712 - 721. · 0.93 Impact Factor
  • Article: Untersuchungen mit Magnesium
    K. Kaemmerer, M. Kietzmann, M. Kreisner
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    ABSTRACT: ZusammenfassungMagnesium-Aspartat-Hydrochlorid vermindert die Anstiegsraten von Corticosteron, Dopamin, Noradrenalin und Adrenalin im durch Immobilisation erzeugten Streß deutlich. Hierbei erweist sich eine Vorbehandlung mit 1000 mg Mg++als Aspartat-Hydrochlorid pro kg Futter ( 200mg/kg Kgw) über drei Tage als wirkungsvoll. Im Gegensatz zu Magnesium-Aspartat-Hydrochlorid hat MgCl2 keine oder nur geringe Effekte auf die Corticosteron- und Katecholamin-Spiegel im Streß. Mit Hilfe der Meßparameter kann die streßabschirmende Wirkung von Mg-asp-HCl experimentell bewiesen werden, was für die Anwendung in der Tierproduktion (Schweinemast) von erheblicher Bedeutung sein wird.SummaryStudies on magnesium 2. Influence of magnesium chloride and magnesium aspartate hydrochloride on stress reactionsMagnesium-aspartate-hydrochloride reduced the rate of increase of corticosterone, dopamine, noradrenaline and adrenaline markedly in stress induced by immobilization in rats. For this purpose pre-treatment with 1000 mg Mg++as aspartate hydrochloride per kg of feed (200 mg/kg body wt.) over a period of 5 days was effective. In contrast to Mg-aspartate-hydrochloride, no or little effect was produced on the corticosterone and catecholamine levels by stress. With the help of measurement parameters the stress-protecting effect of Mg aspartate HC1 can be shown experimentally which could be of significant concern for its use in animal production.RésuméRecherches avec le magnésium Communication 2: L'effet du chlorure de magnésium et du chlorure d'aspartate de magnésium sur des réactions de stressL'hydrochlorure d'aspartate de magnésium diminue nettement les taux d'augmentation de la corticostérone, de la dopamine, de la noradrénaline et de l'adrénaline lors d'un stress provoqué par immobilisation. Un pré-traitement avec 1000 mg Mg++comme hydrochlorure d'aspartate par kg d'aliment ( 200 mg/kg de poids) sur trois jours est efficace. A l'encontre de l'hydrochlorure d'aspartate de magnesium. MgCl2 n'a pas ou que peu d'effet sur le taux de la corticostérone et de la catécholamine lors d'un stress. L'effet de bouclier contre le stress de Mg-asp-HCl a pu être expérimentalement prouvé grâce à des paramètres de mesure, ce qui autorise une utilisation significative dans la production animale (engraissement de porcs).ResumenEstudios con magnesio Comunicación 2a: La acción de cloruro de magnesio y clorhidrato-aspartato de magnesio sobre reacciones de stressEl clorhidrato-aspartato de magnesio disminuye de forma pronunciada las tasas de incremento de córticosterona, dopamina, noradrenalina y adrenalina en el stress producido por inmovilidad. En esta ocasión se muestra como eficaz un tratamiento previo a base de 1000 mg Mg++en forma de clorhidrato-aspartato por kg de pienso ( 200 mg/kg peso en vivo) durante tres días. En contraste con el clorhidrato-aspartato de magnesio no ejerce Cl2Mg ningún efecto o éste es muy escaso sobre el nivel de córticosterona y catecolamina en el stress. Con ayuda de los parámetros mensurables se puede demostrar experimental-mente la acción protectora de stress de ClH-asp-Mg, lo cual tendrá una importancia considerable cuando sea aplicado en la producción animal (engorde de porcinos).
    Journal of Veterinary Medicine Series A 05/2010; 31(1‐10):321 - 333. · 0.93 Impact Factor
  • Article: Untersuchungen mit Magnesium 1. Mitteilung: Beiträge zur pharmakologischen Wirkung
    K. Kaemmerer, M. Kietzmann
    Journal of Veterinary Medicine Series A 05/2010; 31(1‐10):251 - 268. · 0.93 Impact Factor
  • Article: Untersuchungen über die Kinetik von Sulfonamidkombinationen bei Ratte, Kalb und Schwein 2. Mitteilung: Untersuchungen mit Sulfonamiden*
    K. Kaemmerer, M. Kietzmann
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    ABSTRACT: ZusammenfassungDas pharmakokinetische Verhalten von Sulfonamiden nach Applikation von Einzelsubstanzen und von Kombinationsprodukten wird beschrieben. In Versuch 1 wird gezeigt, daß nach Applikation einer Kombination von Sulfathiazol und Sulfadimidin ein den Maximalwert nach alleiniger Sulfadimidingabe übersteigender Anfangsgipfel erreicht wird. Die Sulfonamidspiegel im Serum bzw. Plasma unterschreiten nach Applikation einer Kombination von Sulfamerazin, Sulfadiazin, Sulfathiazol und Trimethoprim den Grenzwert von 0,1 ppm nach 4 Tagen beim Kalb bzw. 2 Tagen beim Schwein. Drei verschiedene Sulfonamid-Kombinations-produkte führen bei Ratten nach bestimmungsgemäßer Dosierung zu Serumspiegeln in vergleichbarer Höhe.SummaryStudies on the kinetics of sulphonamide combinations in the rat, calf and pig 2. Studies with sulphonamidesThe pharmacokinetic behaviour of sulphonamides after the administration of single drugs and combination products is described. In this first study it is shown that after administration of a combination of sulphathiazole and sulphadimidine the maximum of the initial peak is greater than that occurring when sulphadimidine alone is given. The sulphonamide picture in serum or plasma after giving a combination of sulphamerazine, sulphadiazine, sulphathiazole and trimethoprim falls short of the limiting value of 0.1 ppm. after 4 days in calves and 2 days in pigs. Three different sulphonamide combinations given to rats in equivalent dosages result in comparable serum levels.RésuméRecherches sur la cinétique des combinaisons de sulfonamide chez le rat, le veau et le porc Communication 2: Recherches avec des sulfonamidesLe comportement pharmacocinétique de sulfonamides est décrit après une application d'une seule substance et de produits de combinaison. L'essai 1 a montré qu'un pic initial supérieur à la valeur la plus haute obtenue après une seule application de sulfadimine a été obtenu après avoir donné une combinaison de sulfathiazol et de sulfadimidine. Le taux de sulfonamide sérum et du plasma dépasse la limite inférieure après l'application d'une combinaison de sulfamerazine, sulfadiazine, sulfathiazol et triméthoprime à la valeur limite de 0,1 ppm après 4 jours chez le veau et après 2 jours chez le porc. Trois différents produits de combinaison de sulfamide conduisent chez des rats à des taux sériques variables.ResumenEstudios sobre la cinética de las combinaciones de sulfonamidas en la rata, ternera y cerdo Comunicación 2°: Investigaciones con sulfonamidasSe describe el porte farmacocinético de las sulfonamidas tras la aplicación de substancias individuales y de productos de combinación. En el ensayo 1 se señala que tras aplicación de una combinación de sulfatiazol y de sulfadimidina se consigue un valor cumbre inicial que rebasa el valor máximo tras una administración única de sulfadimidina. Los niveles de sulfonamida en el suero sanguíneo resp. plasma descienden tras aplicación de una combinación de sulfamerazina, sulfadiazina, sulfatiazol y trimetoprima del valor límite de 0,1 ppm. al cabo de 4 días en la ternera resp. 2 días en el cerdo. Tres productos diferentes de combinaciones de sulfonamidas conducían en ratas tras dosificación idónea a niveles séricos de altura comparable.
    Journal of Veterinary Medicine Series A 05/2010; 29(10):779 - 790. · 0.93 Impact Factor
  • Article: Effects of degradable Mg-Ca alloys on dendritic cell function.
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    ABSTRACT: Degradable magnesium alloys are new materials for implants used in orthopedic and trauma surgery. The aim of this study was to investigate the influence of degradable magnesium alloys on the function of dendritic cells (DC) as these cells represent the major antigen presenting cells of the body. MgP (pure magnesium), MgCa 0.6 (0.6% calcium), MgCa 0.8 (0.8% calcium), MgCa 1.0 (1% calcium), and MgCa 1.2 (1.2% calcium) alloys were degraded in cell culture medium. In parallel, murine bone marrow-derived DC were incubated with increasing concentrations (0.1-10 mmol/L) of magnesium chloride and calcium chloride, respectively. Incubation of DC with degradation media over 6 days had no influence on cell viability and only marginal influence on DC migration. Also, the production of TNFα and expression of CD86 was not enhanced by incubation with degraded magnesium alloys. The mixed leukocyte reaction revealed that there was also no increase of the T-cell proliferation in comparison to untreated controls. However, there was a trend toward macrophage development at the expense of DC expansion and an enhanced DC migration was induced by incubation with higher magnesium concentrations. Particularly the latter should be verified in in vivo experiments.
    Journal of Biomaterials Applications 03/2010; 25(7):685-97. · 2.08 Impact Factor
  • Article: Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function.
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    ABSTRACT: Histamine is an important mediator of allergic reactions, and recent studies indicated that the function of different types of antigen presenting cells (APC) can be modulated by histamine, in particular via the newly described histamine H(4) receptor (H(4)R). Therefore, we investigated possible interactions of histamine via the H(4)R on Langerhans cells (LC), which represent the professional APC in the skin and therefore have an important role in the initiation and maintenance of allergic skin diseases. The expression of the H(4)R was evaluated by real-time PCR, flow cytometry and immunofluorescence staining. The function of the H(4)R was determined by intracellular flow cytometric measurement of chemokine production and LC migration assays. Here, we show H(4)R expression on in vitro generated monocyte-derived LC (mRNA and protein) and on primary LC from murine and human skin samples (protein). The immunofluorescence staining in murine and human skin samples clearly proved that LC express the H(4)R in situ. Stimulation with histamine or a H(4)R agonist downregulated the chemokine (C-C motif) ligand 2 (CCL2) in human monocyte-derived LC and primary LC. Prestimulation with a selective H(4)R antagonist abolished this effect. Moreover, migration of LC from the epidermis was increased after H(4)R agonist stimulation in ex vivo migration assays using human epidermis and murine in vivo assays. Our findings show that LC express a functional H(4)R and point towards a possible pathogenic relevance of the H(4)R in inflammatory and allergic diseases.
    Allergy 11/2009; 65(7):840-9. · 6.27 Impact Factor
  • Article: Detection and pharmacokinetics of tetrahydrogestrinone in horses.
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    ABSTRACT: The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid-liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A THG excretion study on horses was conducted to verify the method capability for the analysis of postadministration urine samples. In addition, blood samples were collected to allow for determination of the pharmacokinetics of THG in horses. Following the administration of a single oral dose of 25 microg THG per kg bodyweight to 10 horses, samples were collected at appropriate intervals. The plasma levels of THG reached maximal concentrations of 1.5-4.8 ng/mL. Twenty-four hours after the administration plasma levels returned to baseline. In urine, THG was detectable for 36 h. Urinary peak concentrations of total THG ranged from 16 to 206 ng/mL. For the 10 horses tested, the mean plasma clearance of THG was 2250 mL/h/kg and the plasma elimination half-life was 1.9 h.
    Journal of Veterinary Pharmacology and Therapeutics 05/2009; 32(2):197-202. · 1.18 Impact Factor
  • Article: Histamine H4 receptors modulate dendritic cell migration through skin--immunomodulatory role of histamine.
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    ABSTRACT: Dendritic cells (DC) are the major antigen-presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H(4) receptor (H4R) is present on human monocyte-derived DC and that chemotaxis and T-helper (Th)1-Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet. The histamine receptor expression on murine bone marrow (BM)-derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R-mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared. The mRNA of the H1R, H2R and H4R could be detected in murine BM-derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed by in vitro migration experiments with BM-derived DC. Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti-inflammatory, immunomodulatory strategy.
    Allergy 11/2008; 63(10):1387-94. · 6.27 Impact Factor
  • Article: Characterisation of epidermal lipid composition and skin morphology of animal skin ex vivo.
    J Stahl, F Niedorf, M Kietzmann
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    ABSTRACT: Epidermal lipids and skin morphology are assumed to substantially influence skin permeability. Although these parameters have been studied extensively, available data are hard to interpret as data have been gathered at different experimental conditions. Therefore, the aim of this study was to provide detailed information on these parameters for four different mammalian skin types. Lipids were extracted from heat separated epidermis, the total epidermal lipid content was measured and the epidermal lipid composition was quantitatively determined by high-performance thin-layer chromatography. Furthermore, vertical and horizontal cryostate skin slices were analysed by light microscopy for thickness of the horny layer, epidermal thickness, density, depth of anchorage and diameter of the hair follicles. The highest total epidermal lipid content was detected in rat epidermis, followed by bovine udder, dog and pig epidermis. Considering the amount of single lipid fractions, cholesterol, cholesteryl ester and free fatty acids were found to be the major constituents of epidermal lipids in all the examined species. However, as confirmed by hierarchical cluster analysis the epidermal lipid profile and morphology showed marked differences between all the examined species.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 11/2008; 72(2):310-6. · 3.15 Impact Factor
  • Article: Tolerance and pharmacokinetics of cephalexin in cats after oral administration
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    ABSTRACT: The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.
    Journal of Small Animal Practice 04/2008; 33(11):521 - 525. · 1.00 Impact Factor
  • Article: Reactivity of equine airways--a study on precision-cut lung slices.
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    ABSTRACT: A study was performed to evaluate the use of precision-cut lung slices (PCLS) for studies on the contraction of equine airways. Lungs of 10 horses were taken to prepare PCLS of approximately 250 microm from equine lung tissue using a special microtome. The lung slices were cultured and the enclosed small airways were monitored using a microscope with coupled digital camera, which was used to determine the airway luminal area and diameter from digital images. As indicated by the beating of the ciliated epithelium and reactivity of airways on methacholine challenge, the tissue slices were found to be viable for at least 24 h. The airways were not precontracted, as indicated by a missing dilatory effect of 1 mmol/L clenbuterol. Bronchoconstriction induced by both methacholine and histamine was found to be dose dependent. EC(50) values based on luminal area were 1.12 micromol/L x / / 3.82 for methacholine and 0.68 micromol/L x / / 6.99 for histamine. In conclusion, the PCLS technique is promising for studies on small airways in the equine lung. In the present study the basic principles of in vitro (ex vivo) examinations with equine PCLS on airway reactivity were developed.
    Veterinary Research Communications 08/2007; 31(5):611-9. · 0.82 Impact Factor
  • Article: Pharmacokinetics of altrenogest in horses.
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    ABSTRACT: The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentrations were measured by liquid chromatography-tandem mass spectrometry. The plasma levels of altrenogest reached maximal concentrations of 23-75 ng/mL. Baseline values were achieved within 3 days after the final administration. Urine peak concentrations of total altrenogest ranged from 823 to 3895 ng/mL. Twelve days after the final administration concentrations were below the limit of detection (ca 2 ng/mL).
    Journal of Veterinary Pharmacology and Therapeutics 03/2007; 30(1):86-90. · 1.18 Impact Factor
  • Article: [Effects of the zinc oxide and cod liver oil containing ointment Zincojecol in an animal model of wound healing].
    M Kietzmann, M Braun
    [show abstract] [hide abstract]
    ABSTRACT: The effects of Zincojecol an ointment containing zinc oxide and cod liver oil on wound healing were compared with ointments that either contained no active ingredients or zinc oxide or cod liver oil alone. All formulations enhanced the epidermal proliferation after mechanical irritation of the tail skin. The combination of zinc oxide and cod liver oil was found to be superior to the vehicle control and formulations containing only one active ingredient. This combination was also found to be most efficient in accelerating wound healing being retarded by repeated dexamethasone treatment.
    DTW. Deutsche tierärztliche Wochenschrift 10/2006; 113(9):331-4. · 0.41 Impact Factor

Institutions

  • 1990–2012
    • University of Veterinary Medicine Hannover
      • Institut für Pharmakologie,Toxikologie und Pharmazie
      Hannover, Lower Saxony, Germany
    • Institut für Pharmakologie und Toxikologie der Bundeswehr
      München, Bavaria, Germany
  • 1999
    • University of Leipzig
      • Institut für Virologie (Veterinärmedizinische Fakultät)
      Leipzig, Saxony, Germany
  • 1988–1997
    • Medizinische Hochschule Hannover
      Hannover, Lower Saxony, Germany