Biomedical subjects

M Kietzmann

Publications and source records attributed to M Kietzmann.

At least 19 recordsLinked to original sources

PubMed2007

Pharmacokinetics of altrenogest in horses.

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).

Administration, Oral↗

PubMed2006

Tissue distribution of cefquinome after intramammary and "systemic" administration in the isolated perfused bovine udder.

Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. Cefquinome (88.8mg cefquinome sulphate per 8mL) was administered by the intramammary route to all quarters and/or "systemically" via the perfusion fluid at concentrations similar to those measured in plasma following intramuscular administration of 1mg cefquinome per kg body weight. Samples of the perfusate were taken over a 6-h period and from the regional lymph nodes after 6h. Using a scalpel, sections of glandular tissue - at different distances from and vertical to the teat right up to the udder base - were gathered from four quarters each per route of administration at 2, 4 and 6h. The cefquinome content of the tissue samples was analysed by high performance liquid chromatography with diode array detection and of the perfusate samples by bioassay. After intramammary administration, the concentration of cefquinome in the glandular tissue decreased exponentially with increasing distance from the teat. The addition of cefquinome to the perfusion fluid produced a mean concentration of 0.2-0.5microg/g at all glandular tissue sites. Combined intramammary and systemic treatment ensured that concentrations exceeded the MIC(90) values of the most common mastitis pathogens in all areas of the udder by 2h post-administration. There was considerable variability in the tissue concentrations of cefquinome, particularly after intramammary administration. These results suggest that for the treatment of acute mastitis a combination of both intramammary and systemic administration is likely to be advantageous in order to rapidly produce maximum cefquinome concentrations in all regions of the udder.

Animals↗

PubMed2006

Non-steroidal and steroidal anti-inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis.

The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation.

Animals↗

PubMed2006

[Use of hyaluronic acid cleaving enzymes for absorption acceleration. Results of an in vitro study with xylazine and ketamine].

The so-called "Hellabrunner Mischung", (combination of xylazine and ketamine with hyaluronidase) is frequently used for the immobilisation of wildlife animals. The enzyme hyaluronidase shall improve the distribution of the intramuscularly or subcutaneously administered compounds in the tissue and enhance their absorption. These enhancing effects of two hyaluronate lyases of bacterial origin (Streptococcus agalactiae and Streptococcus equisimilis) and a testicular hyaluronidase were compared in an in vitro test. Using the isolated perfused bovine udder, 2 ml of a solution were administered subcutaneously containing 125 mg/ml xylazine and 100 mg/ml ketamine and one of the above mentioned enzymes (150 I.U.). All three enzymes enhanced the absorption rate of xylazine and ketamine determined by measurement of the concentration in the perfusate. The bacterial hyaluronate lyases were significantly more efficient, especially during the clinically important first minutes after administration.

Adrenergic alpha-Agonists↗

PubMed2006

[Effects of the zinc oxide and cod liver oil containing ointment Zincojecol in an animal model of wound healing].

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.

Animals↗

PubMed2005

Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis.

BACKGROUND: Cilomilast and tacrolimus as well as rapamycin are potential drugs for the treatment of allergic skin diseases like atopic dermatitis and allergic contact dermatitis. OBJECTIVES: To compare the in vitro and in vivo immunomodulatory effects of the phosphodiesterase 4 inhibitor cilomilast with those of tacrolimus and rapamycin. METHODS: The in vitro action of cilomilast, tacrolimus and rapamycin were tested in a mixed leucocyte reaction (MLR). In vivo, the inhibitory action of the immunomodulatory drugs was compared in the toluene-2,4-diisocyanate (TDI)-induced allergic inflammatory response with particular focus on dendritic cell (DC) function. RESULTS: Cilomilast, tacrolimus and rapamycin were all able to inhibit DC-mediated T-cell activation in a MLR. But it was demonstrated for cilomilast that the target cells are T cells rather than DC. In vivo, a combination of systemic and topical administration of each of these three substances significantly inhibited swelling in the murine ear 16 h after TDI challenge. There was also a reduction in the weight of the draining auricular lymph node, in lymphocyte cell count, and in the number of emigrated DC. The density of Langerhans cells in the epidermis was correspondingly higher in mice treated with cilomilast, tacrolimus and rapamycin than in those treated with vehicle. All three substances were found to inhibit DC migration ex vivo in a skin DC migration assay performed on ear tissue after TDI challenge. CONCLUSIONS: DC migration into the draining lymph node also takes place in the elicitation phase of allergic contact dermatitis and this migration can be influenced by tacrolimus and rapamycin, and, to a lesser extent, by cilomilast.

Animals↗

PubMed2005

Noninvasive reflection spectra provide quantitative information about the spatial distribution of skin chromophores.

In this work, a new method of analyzing noninvasive reflection spectra is presented. The approach explicitly models the inhomogeneity of chromophore distributions in living tissues and thus extracts not only apparent chromophore concentrations but also relative chromophore distributions in tissues. Furthermore, it works with spectra obtained with short source-detector separations where the diffusion theory of light transport through turbid media is not valid, and formerly presented methods thus fail. The effect of inhomogeneously distributed chromophores in a multicompartment model of tissues on measured reflection spectra is explained and an algorithm to deconvolute tissue spectra based on this model is presented. It is evaluated using simulated spectra and measurements on phantoms, which are made up of partially printed pieces of paper to simulate inhomogeneous dye distributions. Its applicability to real tissue is proven using reflection spectra obtained with 130 microm source-detector separation from a hemoperfusion stop experiment. The proposed model accurately determines apparent chromophore concentrations and corresponding distributions in simulated spectra and phantoms. Regarding real tissue spectra, the results correspond to former publications and the spectral reconstruction yields only minimal residuals, indicating a complete and accurate spectral deconvolution. In conclusion, the presented approach is a suitable extension and amendment to existing models of light transport through inhomogeneous samples.

Algorithms↗

PubMed2004

[Influence of pharmacologically active substances on food safety].

In the European Community and in Germany drug residues are scarcely found in food of animal origin. Therefore, a high degree of safety is ensured for consumers. Problems may result from imported foods, because limitations of drug use in livestock of the European Community do not exist everywhere. Because antibacterial drugs are administered frequently, the problem of transferred multiple-drug resistance of bacteria has to be especially considered.

Consumer Product Safety↗

PubMed2004

TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines.

BACKGROUND: Skin-infiltrating T cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES (regulation on activation, normal T cell expressed and secreted; CCL5), TARC (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell attracting chemokine; CCL27). OBJECTIVES: To investigate which T-cell-attracting chemokines are involved in allergic contact dermatitis in mice. METHODS: Allergic contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid diflorasone diacetate were studied in mouse ears. RESULTS: RANTES and TARC were elevated in both models of allergic contact dermatitis 24 h after challenge, whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by diflorasone diacetate in the DNCB model but was highly induced in the TDI model; in contrast, TARC was not influenced by cilomilast. CONCLUSIONS: TARC and RANTES, but not CTACK, are involved in these two models of allergic contact dermatitis.

Animals↗

PubMed2003

[Euthanasia of pregnant animals].

For euthanasia of pregnant animals, a rapid and painless death is essential. The technique of euthanasia should minimize stress and anxiety experienced by the animal so far as possible. The death is induced by an anoxia in the central nervous system or by a pharmacologic inhibition of essential neuronal functions. Pentobarbital is the best suited drug for euthanasia of animals and especially of pregnant animals. Combinations with muscle relaxing agents should not be used because of possible apnoe without unconsciousness.

Animals↗

PubMed2002

Concentration of enrofloxacin and its metabolite ciprofloxacin in canine matrices of the locomotor system.

Due to its pharmacodynamic and pharmacokinetic properties, the use of enrofloxacin may be indicated in canine osteomyelitis, but there is insufficient data on its distribution within the musculoskeletal tissues. The dogs used in this study were 31 regular veterinary orthopaedic patients. Four hours after their oral or subcutaneous treatment with 10 mg/kg enrofloxacin (Baytril; Bayer, Leverkusen, Germany) once daily for 1 or 3 days, the concentration of enrofloxacin and its main metabolite ciprofloxacin was quantified in plasma, bone, musculature and other matrices of the locomotor system by high pressure liquid chromatography with fluorescence-detection after homogenization and solid phase extraction of the samples. By oral or subcutaneous administration of enrofloxacin once daily for 3 days, higher concentrations of the active constituents in the samples were achieved than by single treatment. Nevertheless, even after single injection, minimal inhibitory enrofloxacin concentrations of up to 0.5 microg ml or microg/g sample against most pathogens of osteomyelitis were exceeded. In the musculature, on average, higher concentrations of active constituents were detected than in less perfused matrices (bones and synovial membranes) at sampling time. The enrofloxacin diffusion into inflamed bone was higher compared with mechanically damaged bone, whereas for ciprofloxacin it was lower. In conclusion, a dosage of 10 mg/kg enrofloxacin is sufficient to exceed the minimal inhibitory concentrations in osteomyelitic bone against most pathogens that are sensitive in vitro, but clinical efficacy remains to be evaluated.

Administration, Oral↗

PubMed2001

Effects of steroidal and non-steroidal antiphlogistic drugs on eicosanoid synthesis in irritated skin: studies with the isolated perfused bovine udder.

Using the isolated perfused bovine udder as an in-vitro model of skin inflammation, the effects of topically administered arachidonic acid on prostaglandin and leukotriene synthesis have been shown previously. In this study, the effects of indometacin (indomethacin) and clobetasol-17-propionate (administered topically) as well as flunixin meglumine and meloxicam (administered via the perfusion fluid) have been studied. Compared with controls, arachidonic acid caused a significant increase in the dermal prostaglandin E2 (PGE2) and peptidoleukotriene (LTC4/D4/E4) concentration. Topical treatment with indometacin (1.6 mg cm(-2)) and clobetasol-17-propionate (90 microg cm(-2)), which were administered 60 min before arachidonic acid administration, inhibited the inflammatory reaction. Flunixin meglumine (1 microg mL(-1) perfusion fluid) was administered 30 min after and meloxicam (3 microg mL(-1) perfusion fluid) was administered 60 min before arachidonic acid application. Three hours after arachidonic acid administration, a significant inhibition of PGE2 synthesis was induced by flunixin. In contrast, meloxicam showed only a slight effect. The effect of flunixin was comparable with in-vivo results. It is known from animal studies that anti-inflammatory effects of meloxicam are obvious within up to 6 h after treatment. Therefore, the incomplete effect of meloxicam may be explained pharmacokinetically. In conclusion, the described in-vitro model seems to be suitable for studies of pharmacological effects on eicosanoid synthesis in the skin.

Administration, Topical↗

PubMed2001

Amidolytic heparin activity and values for several hemostatic variables after repeated subcutaneous administration of high doses of a low molecular weight heparin in healthy dogs.

OBJECTIVE: To determine effects of SC administration of repeated doses of a low molecular weight heparin (LMWH) in dogs. ANIMALS: 5 healthy dogs. PROCEDURE: Each dog received 6 injections (each injection, 150 U of anti-factor-Xa [anti-FXal/kg of body weight, SC) at 8-hour intervals. Blood samples were collected before and 2 hours after the first, second, third, and sixth injections to measure heparin activity, thrombin time, activated partial thromboplastin time (APTT), antithrombin activity, Hct, and platelet count. RESULTS: Heparin activity varied between 0.36+/-0.10 and 0.77+/-0.08 U of anti-FXa/ml (before and 2 hours after the third injection) and between 0.46+/-0.11 and 0.82+/-0.15 U of anti-FXa/ml (before and 2 hours after the sixth injection). Thrombin time and APTT were influenced only slightly. Platelet count, Hct, and antithrombin activity started to decrease significantly 2 hours after the second LMWH injection. Because of the increased consumption of antithrombin, antithrombin activity continuously decreased from 102.1+/-6.3% before the study to 91.0+/-3.0% at the end of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Heparin plasma activity was only slightly higher than that recommended for LMWH treatment of humans, and none of the dogs had signs of increased bleeding. Thus, administration of heparin in accordance with this dosing regimen can be recommended for use in clinical studies. The screening tests investigated were not suitable for use in monitoring LMWH treatment of dogs. Assays that use chromogenic substrates are necessary to reliably monitor LMWH plasma concentrations in dogs.

Animals↗

PubMed2001

[The tissue distribution of antibiotics in the udder--comparison of the situation in vivo with the isolated perfused bovine udder].

Especially for animal protection reasons, tissue concentrations of intracisternally administered antibiotics in the mammary gland hardly can be determined in the live cow. Therefore, this paper assessed the use of the isolated perfused bovine udder to study the distribution of penicillins in glandular tissue. With this intention, the in vitro results acquired with this model were compared to tissue concentrations as well as absorption data from the few in vivo studies in the literature and differences were interpreted. This approach must consider inevitable deviations of experimental materials and methods. Furthermore, in vivo the udder is included in a closed circulatory system with other metabolism and excretion feasibilities than the isolated model. Moreover, the lower flow rate in the vessels in vitro has to be taken into account with respect to absorption capacities. Nevertheless, the tissue concentrations and the distribution equilibrium across the blood-udder-barrier in both experimental concepts corresponded with each other, if the deviating conditions are considered by calculating correction factors. Advantages and disadvantages of the isolated udder are discussed critically. In conclusion, this method is a useful completion of pharmacokinetic in vivo studies that are supposed to compare intracisternally administered formulations.

Animals↗

PubMed2000

Effects of the phosphodiesterase 4 inhibitor RPR 73401 in a model of immunological inflammation.

The study was performed to investigate effects of the phosphodiesterase 4 inhibitor RPR 73401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyl-oxy-4-methoxybenzamid] on an allergic skin reaction. To simulate an immunological inflammation, BALB/c mice were sensitized to dinitrochlorobenzene or toluenediisocyanate. At first, the abdominal skin was shaved and 50 microliter Freund's adjuvant were injected intracutaneously once. Then, the horny layer was removed by adhesive tape stripping and 100 microliter 0.5% dinitrochlorobenzene or 5% toluenediisocyanate were administered on the epidermis for 4 days. After repeated local treatment of the ear skin with 20 microliter 3% RPR 73401 or intraperitoneal administration of 1 and 5 mg/kg RPR 73401, 20 microliter 1% dinitrochlorobenzene or 0.5% toluenediisocyanate were given topically as a challenge. The vehicle controls showed a high increase in ear thickness over 48 h after challenge, whereas RPR 73401 administered on either route reduced this increase significantly. Nevertheless after topical administration, RPR 73401 had a longer lasting effect. These and other results may point to an indication for RPR 73401 in immunological dermatitis.

Administration, Topical↗

PubMed2000

Tissue distribution of benzylpenicillin after intramammary administration in the isolated perfused bovine udder.

Udders from previously healthy lactating cows were perfused with warmed and gassed Tyrode solution in vitro. Benzylpenicillin was administered in three formulations: an oily suspension with micronized particles of <10 microm diameter, an oily suspension with average particle size of 40 microm and an aqueous solution (3 million IU benzylpenicillin-potassium, volume 15 mL). The antibiotics were administered intracisternally to six front and six rear quarters each. Moreover, a dry-off-ointment (100 000 IU benzylpenicillin-potassium and 100 000 IU benzylpenicillin-benzathine, volume 7.5 mL) was tested in four udder halves. Perfusate samples were collected over 3 h. Furthermore, glandular tissue at different vertical distances from the teat base and the regional lymph node were sampled after 3 h. The determination of benzylpenicillin was performed by high pressure liquid chromatography with UV detection. With increasing distance from the teat base, the concentration of benzylpenicillin in tissue exponentially decreased. Using the aqueous solution or oily suspension that contained micronized active principle, higher concentrations were reached compared to the formulation with particle sizes of 40 microm. In udder lymph nodes, the concentration was highest after treatment with the coarse suspension. The transfer from the dry-off-ointment with benzathine-salt into perfusate was very low. These results suggest that it is possible to study tissue distribution of antibiotics in the isolated perfused bovine udder.

Animals↗

PubMed2000

Tissue distribution of oxacillin and ampicillin in the isolated perfused bovine udder.

In vivo, tissue distribution of intra-mammarily administered antibiotics is mostly only assessed by sampling milk and blood. Therefore, the described study analysed whether measurement of tissue concentrations makes sense in vitro instead. Isolated bovine udders were perfused with gassed and warmed Tyrode solution. To four front and rear quarters each, 1000 mg oxacillin in 7.5 ml vehicle was administered intracisternally, completely formulated as sodium monohydrate in two lactation ointments (with or without sodium dodecylsulphate) or 80% as benzathine salt in a dry-off ointment. Over 3 h, perfusate and glandular tissue from different locations were sampled and analysed by high pressure liquid chromatography. With increasing vertical distance to the teat base, the tissue concentration of antibiotics decreased. With the lactation ointment containing sodium dodecylsulphate, lower oxacillin concentrations were reached in glandular tissue and lymph nodes compared to those without. The ointments led to a higher recovery of oxacillin in glandular tissue than in perfusate. Aluminium monostearate in the dry-off ointment caused an even poorer absorption of oxacillin into perfusate. The isolated perfused bovine udder is suitable to study the tissue distribution of antibiotics, since the results were mainly comparable with the few existing in vivo studies and show the influence of different formulations.

Ampicillin↗

PubMed2000

Deuterium labelled nonylphenols in an in-vitro model of percutaneous absorption of environmental xenoestrogens.

A technical mixture of isomeric nonylphenols NP is formed as rather persistent degradation product of nonionic surfactants and has become widespread in the environment, e.g., in surface waters. Information about possible pathways for incorporation is needed for risk assessments, as NP has estrogenic properties. NP uptake after skin contact was determined using isolated and perfused bovine udders as models for human skin. NP-d2 labelled in the positions ortho to the OH-group was prepared by an exchange procedure which did not measurably change the relative amount of isomers. Samples of udder perfusate, milk equivalent produced during the experiments and skin tissue were taken immediately before administration of 500 mg or 50 mg NP-d2 on an udder skin area of 200 cm2 and then for 5 h. They were analyzed by GC-MS for NP and NP-d2 after cleanup by steam distillation and final extraction with SPME fibres. The results are an unambiguous proof of the penetration of NP into the capillary system of living mammals after skin contact.

Administration, Cutaneous↗