Biomedical subjects

M Kietzmann

Publications and source records attributed to M Kietzmann.

At least 55 records · Page 3Linked to original sources

PubMed1993

The isolated perfused bovine udder as an in vitro model of percutaneous drug absorption. Skin viability and percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate.

Using udders from slaughtered cows as a new in vitro model of percutaneous drug absorption, the tissue viability and the percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by a histological examination. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetration of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic acid, ointment without salicylic acid, and acetone solution. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. In conclusion, the isolated perfused bovine udder is a new in vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to compare the dermal penetration, metabolism, and absorption of substances after topical administration of different drug formulations.

Animals↗

PubMed1993

[The use of the organs of slaughtered animals for the testing of drugs: suitability of the bovine udder for the study of substances active through the skin].

Various in vitro models are used to study the transdermal penetration and absorption of test compounds. The isolated perfused bovine udder is described as a new in vitro model. Using bovine udders from slaughtered healthy cows, the percutaneous absorption of dexamethasone, benzoyl peroxide and isosorbide dinitrate was measured. For further validation of the described model, additional studies are necessary.

Animal Testing Alternatives↗

PubMed1992

Effects of the phthalazinone azelastine on epidermal metabolism after mechanical skin irritation.

In female NMRI mice, the phthalazinone azelastine was administered orally once daily over 7 days. The drug influenced the epidermal thymidine triphosphate and amino acid incorporation rates at doses between 1 and 5 mg/kg. In control mice, an epidermal hyperproliferation induced by abrasion of superficial epidermal layers was characterized by enhanced prostaglandin and leukotriene concentrations in epidermal homogenate, an increase in thymidine triphosphate and amino acid incorporation and an increase in epidermal thickness. In mice treated with 1 mg/kg azelastine HCl, this epidermal reaction was changed. Compared to controls, the increase in leukotriene concentration was diminished, and that of prostaglandins was enhanced. The incorporation of thymidine triphosphate and of amino acids as well as the epidermal thickness and the ratio cell count/epidermal thickness were increased in irritated skin of azelastine-treated mice. In conclusion, azelastine influences the epidermal metabolism in irritated and unirritated skin. Therefore, a beneficial role of this phthalazinone in the treatment of psoriasis and related skin disorders seems to be possible.

Administration, Oral↗

PubMed1992

Steroid-induced dermal thinning: discontinuous application of clobetasol-17-propionate ointment.

The skin thinning effect of discontinuous topical clobetasol-17-propionate applications was tested in human volunteers. Application frequencies were daily (1/0), every third day (1/2), every fifth day (1/4), every seventh day (1/6) and every ninth day (1/8). Clobetasol-17-propionate was administered topically under occlusion for 1 h. The treatment period was 41 days. There were no differences of the skin thinning effect of daily and 1/2 administration. The skin thinning effect of 1/4, 1/6 and 1/8 was smaller but also significant compared to controls. The curves demonstrating skin thinning effects initially were dropping off and reached a plateau within about 2 weeks. After finishing application, skin thickness normalized within 2 weeks. Because of these findings, a treatment interval of 3 days is discussed as therapeutically efficient.

Administration, Topical↗

PubMed1992

[The pharmacokinetics and bioavailability of acepromazine in the plasma of dogs].

Acepromazine is extensively used in veterinary practice. In dogs, it is used mainly as a preanaesthetic and sedative agent, without the knowledge of pharmacokinetic data in this species. We studied the disposition both after oral and intravenous administration. It was shown, that the sedative effect after an oral dose of 1.3-1.5 mg/kg lasted for about 4 hours. The elimination was slower after oral administration (half-life 15.9 h) than after i. v. injection (half-life 7.1 h). The bioavailability of the orally administered drug formulation averaged 20%. The calculation of the pharmacokinetic parameters was performed computer-aided, using conventional compartmental analysis and non-compartmental statistical moment analysis and the results were compared.

Acepromazine↗

PubMed1992

[Effect of etretinate on the activity of intestinal disaccharidases].

The retinoid etretinate influences the proliferation and differentiation of epithelial cells. Therefore, the activity of disaccharidases maltase and sucrase was measured in duodenum and jejunum after oral retinoid application to female mice. The enzymes are localized in the brush border of differentiating mucosal cells. The etretinate dose ranged from 0.1 to 1 mg/kg. The treatment with etretinate induced a decrease of the duodenal and jejunal disaccharidase activity. A correlation between the influence in intestinal enzyme activity and undesired gastrointestinal side effects which were described by GOLD et al. (1988) is supposed.

Animals↗

PubMed1991

[Significance of pharmacokinetic parameters for effective drug therapy in house and domestic animals].

Aspects of pharmacokinetics (absorption, distribution, metabolism and excretion) and pharmacokinetic parameters (half-life time, elimination time, volume of distribution and bioavailability) are discussed. Treatment with food or drinking water demands additionally considerations to obtain a suitable drug level in the organism. Age- and sickness-dependent variations cause important changes of pharmacokinetic parameters. For an efficacious therapy, pharmacokinetic considerations are essential.

Animals↗

PubMed1991

Incorporation of tritiated thymidine, leucine and histidine in murine tail epidermis after skin irritation (histoautoradiography).

Thymidine incorporation into epidermal DNA as well as leucine and histidine incorporation into epidermal protein were studied by histoautoradiography in female mice tail epidermis. Prior to in vitro incubation of skin samples with labelled precursors, tail skin was irritated mechanically by rubbing with fine sand paper, chemically by repeated topical administration of n-hexadecane and by feeding an essential fatty acid deficient diet. After these skin irritations, an increased thymidine labelling index and skin thickening were found. Leucine was shown to be incorporated into protein predominantly in basal epidermal cell layers, while histidine was incorporated predominantly in the granular layer. Especially after mechanical skin irritation, this difference was obvious.

Alkanes↗

PubMed1991

Inhibition of n-hexadecane-induced epidermal hyperplasia due to systemically administered ciclosporin.

Epidermal hyperplasia was induced in hairless mice (hr/hr) by topical n-hexadecane treatment of tail and back skin. Following this skin irritation, a granular layer developed in interfollicular regions of the tail epidermis. An increase of ornithine decarboxylase activity, of thymidine triphosphate incorporation into DNA and of amino acid incorporation into protein was found. Shown histologically and by measurement of the called biochemical parameters, ciclosporin (cyclosporin A, CAS 59865-13-3; pretreatment with 30 mg/kg b.w. per day subcutaneously for 7 days) inhibited the development of epidermal hyperplasia in back and tail epidermis.

Alkanes↗

PubMed1990

[Peculiarities of pharmacokinetics in young animals].

In young animals, especially in newborns, absorption, distribution, metabolism and elimination of drugs differ markedly from adults. Respective differences and the cause of these differences are described, including some examples of drug pharmacokinetics in young and adult animals of different species. However, the estimation of pharmacokinetic differences and their pharmacological consequences in young animals is not generally possible, because published data on characteristics of pharmacokinetics in young animals are available only for relatively few drugs. Furthermore, such estimation is complicated by an interaction of different pharmacokinetic processes. Thus, a generally accepted adaptation of dosage schedules for drugs in young animals cannot be offered as yet. In any event, veterinarians should consider the age-dependency of drug pharmacokinetics when drugs, dosages and dosage intervals for treatment of young animals are chosen.

Age Factors↗

PubMed1990

Drug plasma levels following administration of trimethoprim and sulphonamide combinations to broilers.

Trimethoprim (TMP) was administered in combination with either sulphadiazine or sulphadimidine to broilers, and plasma concentrations were determined simultaneously by newly developed thin-layer and/or high-performance liquid-chromatographic procedures, which also allowed quantification of the N4-acetyl metabolites of the sulphonamides. After i.v. injection of TMP (20 mg/kg body wt) and sulphadiazine (100 mg/kg body wt), both compounds were rapidly eliminated from plasma with half-lives of 1 and 2.7 h, respectively. Apparent volumes of distribution (3.3 and 0.96 l/kg, respectively) indicated that the tissue distribution of TMP was more extensive than that of the sulphonamide. After oral administration of the same dosages, elimination appeared to be slower compared to the i.v. injection, but this was obviously related to delayed absorption. Bioavailability after oral administration was approximately 100% of sulphadiazine, but only about 60% for TMP. Oral dosing of TMP in combination with sulphadimidine yielded similar maximum plasma concentrations of both compounds to those obtained with the combination of TMP with sulphadiazine, but the plasma concentration decline of sulphadimidine appeared to be more rapid than that of sulphadiazine after oral administration. During prolonged administration of different dosages of TMP-sulphadiazine combinations via drinking water, only low plasma concentrations were attained by the recommended dosage of the combination. Up to 10-fold higher dosages were tolerated by the animals without side-effects. In view of the fact that the sensitivity of bacterial strains to TMP-sulphonamide combinations differs widely, the plasma concentrations determined in the present study during prolonged drinking-water medication with different dosages of a TMP-sulphadiazine combination can be used to select effective doses for treatment of different poultry diseases.

Absorption↗

PubMed1990

Influence of ciclosporin on epidermal proliferation after mechanical skin irritation.

In mice (NMRI and hr/hr), ciclosporin, subcutaneously administered once daily over 7-10 days, influenced epidermal hyperproliferation induced by abrasion of superficial epidermal layers. While in vehicle-treated control animals the mechanical irritation of skin caused an increase in 3H-thymidine triphosphate incorporation rate into DNA and also in epidermal thickness of tail and flank skin, the hyperproliferative response was diminished in ciclosporin-treated animals. Thus, only a slight increase of the 3H-thymidine triphosphate incorporation rate and of epidermal thickness was measured after pretreatment with ciclosporin, the effect being dose-dependent. The strongest inhibitory activity was found after application of 30 mg/kg BW. These findings indicate that the immunosuppressive peptide ciclosporin inhibits the epidermal proliferation in vivo.

Animals↗

PubMed1990

The mouse epidermis as a model in skin pharmacology: influence of age and sex on epidermal metabolic reactions and their circadian rhythms.

The influence of age and sex on epidermal metabolism and histology was studied in mice (NMRI). Within a few weeks postpartum, thymidine triphosphate incorporation into DNA and amino acid incorporation into epidermal protein decreased. Differences between tail epidermis and other skin regions (back, abdomen, ear) were found. Sex dependent differences could not be demonstrated. A circadian rhythm of the studied epidermal metabolic processes was shown (artificial 12L:12D light/dark cycle). Maximum incorporation of thymidine triphosphate and of amino acids was found at the end of the light period at 1800 h, while a minimum incorporation was demonstrated at the end of the dark period. Considering described biological variations, the mouse tail assay seems to be suited to study influences of drugs in epidermal metabolism and histology.

Age Factors↗

PubMed1990

[Modification of catecholamine metabolism in rats by magnesium aspartate hydrochloride].

The metabolism of catecholamines was studied in rats treated with magnesium aspartate hydrochloride (MAH). For 3 days, MAH was administered via food (1000 mg magnesium/kg food). An enhanced renal elimination of catecholamine metabolites was found in MAH-treated rats as well as in rats stressed by immobilisation. Measured in vitro, hepatic monoaminoxidase activity was enhanced. The catechol-O-methyltransferase activity was not altered. In conclusion, oral treatment with MAH is followed by enhanced hepatic metabolism and increased renal elimination of catecholamines.

Animals↗

PubMed1990

[Problems with malachite green use in fish].

The arylmethane dye malachite green oxalate is used as an antimycotic and antiparasitic substance for treatment of fish diseases. The therapeutical use of malachite green is not licensed by the German drug act. A decree fixes a limit of tolerance of 0.01 mg malachite green/kg food produced from fish. A so-called standard license will be prepared for malachite green as a drug for fishes. By trout and carp, malachite green is eliminated slowly. Therefore a long withdrawal time is necessary. The toxicology of the arylmethane dye and the low tolerance to observe in trout and carp is to mind.

Animals↗

PubMed1989

Comparative investigation of the antiproliferative efficacy of alclometasone.

In this study, the antiproliferative activity of a 0.05% alclometasone ointment (Alc, Delonal) on the epidermis of the mouse tail was investigated. We have found that Alc thins the epidermis to approximately the same extent as hydrocortisone acetate (1%), but has an extremely slighter epidermal thinning effect than betamethasone (betametasone-17,21-dipropionate, 0.064%, Diprosis). The incorporation rate of 3H-thymidine triphosphate into the DNA was inhibited to almost the same extent. In conclusion the small antiproliferative effect of Alc shows no correlating effects compared with its high vasoconstrictory efficacy.

Animals↗

PubMed1989

Influence of magnesium gluconate on stress reactions in rats.

During the tests carried out with rats the organic complex magnesium gluconate was examined for its bioavailability and its stress-reducing properties after oral application. The increase of magnesium concentration in serum achieved by means of magnesium gluconate turned out to be higher than the increase of concentration due to the administration of magnesium chloride. Just like other organic magnesium complexes, magnesium gluconate, administered for three days via feed to rats under stress conditions of immobilization, the substance causes a significant reduction in the increase in catecholamine and corticosterone concentration in serum. Regarding the reduction of stress in rats, the optimal concentration in feed is between 500 and 1000 mg of magnesium as magnesium gluconate per kg.

Animals↗

PubMed1988

Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses.

Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 +/- 0.016 (mean +/- SD) units of heparin/ml of plasma (U/ml) after 60 U/kg, 0.035 +/- 0.025 U/ml after 80 U/kg, 0.023 +/- 0.004 U/ml after 100 U/kg, 0.034 +/- 0.019 U/ml after 125 U/kg, and 0.053 +/- 0.019 U/ml after 150 U/kg. Data from groups given 60 and 100 U/kg could not be used for kinetic calculations. Elimination constant (l/h), elimination half-life (h), and elimination time (h) calculated to reach base-line values after 80 U/kg were 0.182 +/- 0.041 l/h, 3.8 +/- 0.9 h, and 9.7 +/- 2.2 h. After 125 U/kg, corresponding values were 0.211 +/- 0.019 l/h, 3.3 +/- 0.3 h, 13.4 +/- 1.2 h, and after 150 U/kg 0.098 +/- 0.015 l/h, 7.1 +/- 1.1 h, and 20.6 +/- 3.2 h. Calculated heparin concentrations 12 h after administration of 80, 125, and 150 U/kg were 0.011 +/- 0.002, 0.010 +/- 0.001, and 0.027 +/- 0.004 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗