Biomedical subjects

M Kietzmann

Publications and source records attributed to M Kietzmann.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Phamacokinetics of low-molecular-weight heparins Fragmin D in dogs].

The pharmacokinetics of a low molecular weight heparin (LMWH; Fragmin D) was studied in dogs after intravenous and subcutaneous administration, based on antifactor Xa- (anti-fXa-) activity. Each dosage was examined in 5 adult Beagles. After intravenous application of 25, 50 and 100 anti-fXaU./kg body weight (BW) the mean peak plasma heparin activity of 0.52 +/- 0.12 (x +/- s), 1.08 +/- 0.23 and 1.86 +/- 0.17 anti-fXaU./ml, respectively, was measured. After subcutaneous application of 50, 100 and 200 anti-fXaU./kg BW maximum heparin activity in the plasma was determined after 144-216 minutes (mean values) of 0.28 +/- 0.01, 0.52 +/- 0.06 or 1.09 +/- 0.20 anti-fXaU./ml. Intravenous application of LMWH has a short plasma terminal half-life (t50) between 49 and 76 minutes which depended on the dosage. After administration of 50 anti-fXaU./kg BW (74 minutes) and 100 anti-fXaU./kg BW (76 minutes) no essential difference was shown. A distinctly longer t50 was found after subcutaneous injection. After injection of 50, 100 and 200 anti-fXaU./kg BW t50 values of 81, 123 and 182 minutes were calculated. According to this, with increasing dosage a decrease of the total clearance was found for both application routes. The apparent volume of distribution after intravenously applicated LMWH ranged between 50 and 70 ml/kg BW. The absolute bioavailability calculated for the subcutaneous NMH-injection of 50 and 100 anti-fXaU./kg BW was 107% and 104%, respectively.

Animals↗

PubMed2000

[Drinking water as a medium for drugs].

If drug treatment is necessary in large herd sizes, the administration with feed or drinking water is preferred. The use of the drinking water as a vehicle for drugs may be accompanied by several problems. An important condition for a successful medication is a good water solubility of the administered compound. The solubility is influenced by the quality of the used drinking water. The stability of the dissolved drug and incompatibilities with other water ingredients are additional limiting factors. The success of the treatment is influenced also by the taste of the medicated water which may cause a reduced water consumption. The use of tap water instead of spring water may be helpful to improve the efficacy of drug treatment via drinking water.

Animal Husbandry↗

PubMed2000

[Anti-inflammatory, antibacterial and antimycotic effects of dark sulfonated shale oil (ichthammol)].

Dark sulfonated shale oil (Ichthammol, ammoniumbituminosulfonate) is an active ingredient of natural origin that was included in Annex II of European Council Regulation (EEC) 2377/90. Therefore, this well-tolerated substance is available further on as a dermatological agent for the application to animals from which food is produced for human consumption. The manifold pharmacological actions could be substantiated in numerous in-vitro studies using the Ichthammol from Seefeld, Austria. The antiinflammatory action which is well-known from clinical experience could be traced back to an influence of the substance on the formation, secretion and effect of inflammation mediators. Antibacterial and antimycotic actions which are well-known from clinical use could be confirmed in in-vitro studies as well.

Animals↗

PubMed1999

Involvement of reactive oxygen species in TNF-alpha mediated activation of the transcription factor NF-kappaB in canine dermal fibroblasts.

The cytokine tumor necrosis factor-alpha (TNF-alpha) plays a major role in inflammatory and immune-pathological reactions of the skin. With respect to a possible therapeutic modulation of TNF-alpha mediated activation of Nuclear Factor-kappa B (NF-kappaB) in canine cutaneous inflammation, we investigated the role of NF-kappaB and the involvement of reactive oxygen species (ROS) in the TNF-alpha signalling pathway in dermal fibroblasts of the dog. TNF-alpha treatment resulted in the activation of NF-kappaB as assessed by electrophoretic mobility shift assay (EMSA). Additionally, NF-kappaB translocation was induced with butylhydroperoxide and antimycin A, but not with hydrogen peroxide. TNF-alpha stimulated NF-kappaB activation was partially inhibited by preincubation with the antioxidants alpha-lipoic acid and butylated hydroxyanisol (BHA). No superoxide generation following TNF-alpha stimulation could be detected in the supernatant of canine fibroblasts with the superoxide dismutase-inhibitable cytochrome c reduction test. In contrast, production of TNF-alpha dependent intracellular hydrogen peroxide, the dismutation product of the superoxide radical, was demonstrated spectroscopically by formation of electron dense cerium-hydroperoxide precipitates. With electron energy loss spectroscopy (EELS) significant cerium deposits were detected in the mitochondria, the endoplasmatic reticulum, the cytosol and to a lesser extent on the plasma membrane of canine fibroblasts indicating multiple hydrogen peroxide production sites. Peroxides, therefore, possibly play an important part in the redox-sensitive pathway of TNF-alpha dependent NF-kappaB activation in canine skin. An adjunctive therapy with appropriate antioxidants modulating NF-kappaB overactivation in cutaneous inflammation in the dog is promising.

Animals↗

PubMed1999

Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens.

The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.) and the steady-state plasma and tissue concentrations of both drugs were investigated after continuous administration via the drinking water. The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods. Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half-life (t1/2: approximately 6-7 h), mean residence time (MRT; 6-9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (ClB; 24 vs. 10 mL/min. kg) and volume of distribution at steady state (VdSS; 10 vs. 4 L/kg). Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 micrograms/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin. Steady-state plasma concentrations (mean +/- SD) following administration via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 microgram/mL) compared to danofloxacin (0.12 +/- 0.01 microgram/mL). The steady-state AUC0-24 h values of 12.48 and 2.88 micrograms.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration-time curve (AUC) values after single oral administration. For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g. in the target lung, tissue concentrations of 0.31 +/- 0.07 microgram/g for danofloxacin and 0.88 +/- 0.24 microgram/g for enrofloxacin were detected. Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.

Administration, Oral↗

PubMed1999

Application of deuterated compounds for investigations of percutaneous absorption of chemical substances.

The percutaneous absorption of the xenoestrogen 2,2-bis-(4-hydroxyphenyl)-propane (bisphenol A) 1 has been studied and compared with results on dibenzoyl peroxide 2, a component of drug formulations for topical application. Isolated perfused bovine udders from slaughtered cows were employed as models for human skin. The deuterium labelled compounds 1-d14 and 2-d10 were applied to enhance the reliability of GC-MS trace determinations by use of reverse isotope dilution analysis. 1-d14 was found in perfusate and milk equivalent samples obtained between 60 and 300 min after topical application with maximum concentrations between 120 and 180 min. 1-d14 was enriched in the milk samples by a factor of about 300 compared with the perfusate. The results confirm a possible penetration of 1 from the environment through the skin into the capillary system. 2 studied on the same model system penetrated faster than 1 by a factor of about three.

Animals↗

PubMed1999

[Pharmacokinetics of an unfractionated heparin (Liquemin) in the dog after intravenous and subcutaneous application based on heparin activity].

In this study pharmacokinetic data for the unfractionated heparin Liquemin were obtained after intravenous and subcutaneous application. Each dosage was examined in 5 healthy, adult Beagle dogs. After intravenous application of 25, 50 and 100 I.U./kg body weight heparin plasma activity of 0.65 +/- 0.15 I.U./ml (mean +/- s), 0.91 +/- 0.10 I.U./ml and 1.94 +/- 0.22 I.U./ml was measured. Subcutaneous applications of 250, 500 or 750 I.U./kg revealed maximum plasma heparin activities of 0.25 +/- 0.10, 0.60 +/- 0.15 and 1.29 +/- 0.24 I.U./ml. The maximum heparin activity in the plasma was observed after 3.8 +/- 1.1 (250 und 500 I.E./kg) or 4.0 +/- 1.0 hours (750 I.E./kg), respectively. Intravenously applicated heparin has a short terminal half-life time (t50) between 22 and 44 minutes. The t50 after subcutaneous application of heparin was distinctly longer. After 250, 500 or 750 I.U./kg the t50 was 3.7 +/- 2.4, 3.5 +/- 1.2 or 5.3 +/- 2.4 hours. Corresponding to this result a lower total clearance (Cltot) was found with increasing doses. Especially the Cltot after subcutaneous injection decreased from 2.08 +/- 0.73 ml/min/kg (250 I.E./kg) to 0.83 +/- 0.27 ml/min/kg (750 I.E./kg). The volume of distribution of heparin corresponded approximately to the plasma volume. The total bioavailability of subcutaneously administered UFH was 53-100% depending on the dosage.

Animals↗

PubMed1998

[Pharmacokinetic aspects of mastitis therapy].

Treating mastitis in dairy cattle, most often antibiotics are used systemically or intracisternally, supported by influencing the inflammatory process with other measures. The success of systemic treatment is influenced by the bioavailability of the chemotherapeutic agent. Here, apart from the molecular size and protein binding, the fat-solubility of the active principle as well as its degree of ionisation play a major role. The degree of ionisation is determined by the isoelectric point (pKa) of the substance and by the pH-value of the surrounding medium. Thus, weak acids are mainly ionised in blood and cannot be transferred into udder tissue and milk. Weak bases react in the opposite way. Applied locally, the drug must not irritate the udder to secure deep diffusion into the glandular tissue. Therefore, topically administered drugs are formulated on an oily basis, also for longer prophylaxis during the dry-off-period. The pharmaceutic and pharmacokinetic relevance of the chemical and physical factors as well as the influence of the particle size of the active principle were demonstrated with benzylpenicillin potassium in the in vitro model of the isolated perfused bovine udder.

Animals↗

PubMed1998

Interference of myrtol standardized with inflammatory and allergic mediators.

Myrtol standardized (Gelomyrtol/Gelomyrtol forte) inhibits the activity of 5-lipoxygenase of human basophil and eosinophil leukocytes and the formation of leukotriene C4 as well as 1.8-cineole (eucalyptol). An increase of prostaglandins (PGE2) in mucous membranes of teat cisterns after topical administration of TPA (tetradecanoylphorbol-13-acetate) was inhibited. In vitro and in vivo studies revealed spasmolytic and broncholytic effects of Myrtol stand. After topical administration into the teat cisterns of the isolated bovine udder Myrtol stand. increased the surface temperature, comparable to effects of menthol.

Animals↗

PubMed1997

[Evaluation of the antinociceptive effect of xylazine after epidural administration in dogs under general anesthesia with isoflurane].

Seven dogs anaesthetized with isoflurane in oxygen (1.9 Vol.-% ET) were examined before and after lumbosacral injection of xylazine (0.25 mg/kg) into the epidural space. Over a 240 minute period the dogs were first stimulated in a visceral manner (extension of the colon descendens by a balloon-catheter) every 15 minutes. In a second part, the dogs were stimulated somatically by pressure to the interdigital skin of a hindlimb. Heart rate and mean arterial pressure were used to determine the analgesic properties of epidurally injected xylazine. Furthermore, plasma xylazine concentration was controlled in both series. Before epidural anaesthesia, heart rate and mean arterial pressure increased during stimulation significantly in both groups. After epidural injection of xylazine, hemodynamic reactions were distinctly diminished, in the somatically stimulated group more than in the viscerally stimulated group. Up to 30 minutes after epidural injection, plasma xylazine concentrations of about 100 ng/ml were found in both groups. Up to 60 minutes after epidural injection, plasma xylazine concentrations of more than 60 ng/ml still were found. From the 120th minute on, xylazine concentration decreased below 30 ng/ml. From these results, it can be concluded that there is a well-suited analgesic effect of epidurally applicated xylazine for approximately 240 minutes.

Analgesia↗

PubMed1997

[Effect of flunixin meglumine on plasma prostanoid concentrations in horses with colic in the perioperative period].

In the present study the significance of eicosanoids in the development of shock in horses on the basis of ileus has been investigated using the prostanoids thromboxane B2 (TXB2) and prostaglandine E2 (PGE2) as indicators. The prostanoid synthesis inhibitor flunixin meglumine was to be examined regarding its efficacy in the effective blockade of the synthesis of these mediators within the peri-operative timeframe as well as its effects on clinical signs and laboratory parameters. 21 horses suffering from ileus and ready for surgical intervention received an intravenous flunixin dosis of 1.1 mg/kg body weight immediately after the initial examination and prior to the surgical procedure. 20 colic horses receiving surgical treatment without application of the drug served as control group. Reference data concerning the approximate standard plasma levels of the prostanoids were determined in 10 healthy horses. Plasma levels of thromboxane B2 and prostaglandine E2 in all colic horses, treatment group as well as controls, initially proved to be significantly higher than the reference values in healthy horses. The untreated control group showed plasma levels highly exceeding the standards within the course of investigation. The application of flunixin meglumine resulted in an effective inhibition of the prostanoid synthesis. Post-operatively as well as within the whole period of investigation the plasma levels of PGE2 and TXB2 of the treated group were considerably lower than those of the control group. Flunixin meglumine had a favorable effect on several cardiovascular parameters. The experimental data concerning the effects of flunixin meglumine thus could be validated in a clinical setting, especially the effective inhibition of the cyclooxygenase enzyme system. The application of the prostanoid synthesis inhibitor flunixin meglumine can be judged as being effective in limiting shock progress in the peri-operative setting given reliable diagnosis.

Animals↗

PubMed1996

[Pharmacokinetics and effects of xylazine (Rompun) in dogs].

Six beagle dogs were treated with xylazine hydrochloride (1 mg/kg i.m.). The plasma xylazine concentration was measured by HPLC. Additionally, clinical effects were registered (cardiac rate, respiratory activity, electrocardiogram, body temperature, motoric activity, attention, analgesia). Maximum plasma concentrations were measured after 15 minutes (476 ng/ml). The plasma half-life was 24 minutes. Sedation was registered over one hour (xylazine concentration of more than 150 ng/ml). Within the first 30 minutes after treatment (xylazine concentration of more than 300 ng/ml), a low-grade analgesia was observed. In contrast, cardiac and respiratoric depression and also significantly diminished body temperature were registered over 2 to 3 hours.

Analgesia↗

PubMed1996

[Pharmacokinetics and tolerance of an orally administered combination preparation containing phenylbutazone and prednisolone in the dog].

Tolerance and pharmacokinetics of a combination of phenylbutazone and prednisolone (tablets) were studied in Beagle dogs. For two weeks, the drug was administered orally (3.33 mg/kg phenylbutazone combined with 0.1 mg/kg prednisolone and 6.66 mg/kg phenylbutazone combined with 0.3 mg/kg prednisolone twice daily). The dosage was reduced to 50 per cent after one week. No signs of intolerance were found. After treatment with 3.33 mg/kg phenylbutazone, a plasma concentration of 10 micrograms/ml was reached within 1 to 2 hours. No prednisolone concentration above 2 ng/kg was measured. Additionally, a synergistic antiinflammatory effect of the two ingredients was obvious (hind paw dextran edema in rats). In addition to results of ENGELKE et al. (1995) who studied the clinical efficacy of the combination, the presented data demonstrate a good tolerance.

Administration, Oral↗

PubMed1995

In vivo exposure of rats to a weak alternating magnetic field increases ornithine decarboxylase activity in the mammary gland by a similar extent as the carcinogen DMBA.

Magnetic field (MF) exposure has been discussed in the process of tumor promotion as indicated by epidemiologic data as well as laboratory studies. However, the precise mechanisms of tumor promoting effects of MFs are unknown. Tumor promotion is often accompanied by an increase in the activity of the enzyme ornithine decarboxylase (ODC), i.e. a key enzyme in the biosynthesis of polyamines, which have roles in cell proliferation and control of gene expression. In the present work, we studied if exposure of female rats to a 50-Hz MF with a flux density of 50 microT influences ODC activity in different tissues, including the mamma. Rats were exposed for a period of 6 weeks either with or without oral administration of the chemical carcinogen DMBA and all data were compared with those from sham-exposed controls. Magnetic field exposure resulted in an approximate doubling of ODC in mammary tissue. A significant ODC increase was also seen in the spleen, but not in the liver, small intestine, bone marrow, and ear skin. The ODC increase produced by MF exposure in the mammae was of similar magnitude as that observed after treatment with DMBA. Combined treatment with MF and DMBA was not more effective in increasing ODC than treatment with DMBA alone, except for liver tissue. The present results on in vivo increases of ODC by MF exposure strengthen the hypothesis that weak 50-Hz MFs affect ODC activity and may thus function as a tumor-promoting or co-promoting agent.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Skin atrophy induced by initial continuous topical application of clobetasol followed by intermittent application.

BACKGROUND: The most frequent side effect of a long-term topical corticosteroid therapy is skin atrophy. To avoid or to reduce atrophy often an initial continuous application is followed by an intermittent maintenance therapy. OBJECTIVE: In this study we measured the skin thickness before and after the two-phase application schedule with the superpotent topical steroid clobetasol propionate (CP). For 16 days CP samples were applied twice daily on the test areas of 12 volunteers (phase 1). Then CP was applied to the same skin areas in accordance with the following timing: every 5th day, every 7th day, every 10th day, every 14th day (phase 2). Phase 2 lasted for 45 days. During the entire period of the study the skin thickness was measured regularly by the skin compression and thickness method as described previously. RESULTS: It could be seen that in phase 1 the skin became about 15% thinner. In phase 2 the steroid-induced skin thinning was approximately the same when CP was applied every 5th or 7th day. The skin thickness reached a more or less normal level when CP was applied every 10th day. After the 14th day a completely normal level was found. By measuring the skin thickness every day it was further shown that the skin thinning process lasted for 3 days when CP was applied once only. CONCLUSION: These results demonstrate that skin thinning must be expected by an intermittent maintenance therapy applied at relatively short intervals. The longer the intervals, the weaker the skin thinning. Moreover, these investigations showed that the skin thinning effect after a single CP application persists for nearly 3 days.

Administration, Topical↗

PubMed1995

[Pharmacotherapeutic use of antipruritic drugs in skin diseases].

Pruritus is a predominant and serious phenomenon of various skin diseases. As mediators of pruritus, histamine, serotonin (hydroxytryptamine), eicosanoids, neuropeptides, cytokines and proteases are known. The symptomatic treatment of pruritus is variable. Glucocorticoids are well known antipruritic drugs. H1-antihistaminics are used frequently. But the efficacy of these drugs is questionable in dogs. Additionally, mast cell stabilisators, unsaturated fatty acids (i. e. primrose oil, fish oil) and other antipruritic agents (local anesthetics) are used.

Anesthetics, Local↗

PubMed1995

[Effect of acetylsalicylic acid on platelet aggregation and capillary bleeding in healthy cats].

The influence of acetylsalicylic acid (ASA) in vitro and in vivo on several parameters of the hemostatic system was evaluated in healthy cats. The aggregation response of cat platelets in vitro was not influenced by 10 micrograms ASA/ml plasma, whereas ASA concentrations of 35, 70, 100 micrograms/ml and of 1 mg/ml consistently inhibited the platelet aggregation induced by 0.1 (n = 4 cats) and 0.25 micrograms collagen/ml (n = 6 cats). The aggregation response to ADP and thrombin was partially (n = 2) or completely (n = 8) inhibited by an ASA concentration of 5 mg/ml. Administration of ASA at a dosage of 10 and 25 mg/kg BW orally and intravenously yielded a plasma concentration of salicylic acid of 30-42 micrograms/ml (10 mg/kg BW) and 50-70 micrograms/ml (25 mg/kg BW). All the dosages of ASA produced an inconsistent inhibition of the collagen-induced platelet aggregation (1/5 and 2/5 for the respective groups), whereas the response to ADP and thrombin was not altered. Capillary bleeding time was not significantly altered after the ASA administration. Platelet count and screening tests were not influenced by ASA application. According to the results of this study, ASA as a platelet aggregation inhibitor is not useful for the prophylaxis of thromboembolism in cats.

Adenosine Diphosphate↗

PubMed1995

[Drug residues in untreated swine].

The concentration of sulfadimidine was measured in the urine of pigs which were housed (over five days) in boxes where other pigs have been treated orally with sulfadimidine before. Sulfadimidine was measured in the urine of the unmedicated pigs in a concentration of up to 4 micrograms/ml. Considering these urine concentrations, violative sulfadimidine tissue residues would be expectable in the carcass after slaughter. The practice of fixing withdrawal times must be considered again to ensure that drug residues in tissues are below the MRL before slaughter also in unmedicated animals.

Animal Feed↗