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Biomedical subjects

K Karzel

Publications and source records attributed to K Karzel.

At least 19 recordsLinked to original sources
PubMed1990

[Effect of preoral and transdermal insulin preparations on blood glucose concentration in mice].

Effects of oral and transdermal insulin applications on blood glucose concentration were investigated in nonconditioned, healthy mice. Insulin was applied in a special lipid formulation which contained no chemical enhancers or protease inhibitors. In comparison to control applications with same volumes of insulin free lipid formulations significant and reproducible blood sugar lowering effects were found with the insulin-lipid formulation. Additional control applications of the same dosages of oral aqueous insulin solutions differed only slightly to the insulin free lipid formulations. Same dosages of s.c.- and p.o.-applications of the insulin-lipid-formulation induced quantitatively comparable blood sugar lowering effects. The maximum oral effects showed dose dependence in a dose range of 0.7 to 9.5 IU/kg bodyweight. Maximal effects after oral application were seen 1-2 h after oral application. Investigations with transdermal insulin applications showed also significant effects in lowering blood glucose concentrations, but these effects were weaker than after oral application and showed a delayed onset.

Administration, Cutaneous↗
PubMed1989

[Mechanisms of transcutaneous absorption. Pharmacologic and biochemical aspects].

Known and potential mechanisms of transcutaneous permeation or resorption of drugs are discussed. The relatively well documented transcellular route is passable for compounds with a low molecular mass (up to about 2000 Da) and sufficient lipid as well as water solubility. Because of the limited absorption capacity of the skin and the slow progress of absorption systemic effects of cutaneously applied drugs with the mentioned properties may be expected only, if they are acting in low concentrations and if a retarded onset of action is tolerable. Further compounds which do not fulfil these conditions sufficiently may be transported through the skin under the aid of exogenic factors such as permeation enhancers. Advantages, disadvantages and limitations of transdermal drug therapy as compared with other routes of application are discussed. Finally the question is dealt with, if the transcutaneous route can be opened also for polar compounds with a higher molecular mass. The permeation of such compounds could take place through intercellular clefts, which are reported to have dimensions permitting the passage of compounds with a molecular mass greater than 2000 Da. The transfer through the masses filling the clefts may require, however, the aid of sorption enhancers.

Animals↗
PubMed1989

[The effect of benzenecarboxylic acids--in particular mellitic acid--in in vitro biological system].

Influence of Benzenecarboxylic Acids, Particularly Mellitic Acid, on Biological in vitro Systems. In a first part of the present paper influences of mellitic acid and some other benzenecarboxylic acids on reduplication of Ehrlich ascites tumor cells cultured in vitro are reported. Mellitic acid in the concentration range between 1 and 5 mmol/l caused an increase, in concentrations of 10 mmol/l and above an inhibition of cell multiplication. Benzoic acid, phthalic acid, hemimellitic acid and pyromellitic acid showed in concentrations above 6 to 10 mmol/l inhibitory effects on cell multiplication. The second part reports studies on potential influences of mellitic acid on growth and mesenchymal metabolism of explanted murine fetal tibiae cultured in vitro for six days. Mellitic acid effected in concentrations between 0.5 and 15 mmol/l as compared with control cultures a concentration dependent inhibition of calcification and in concentrations above 2 mmol/l significant increases of the glycosaminoglycan content and growth of the explants, whereas DNA-, total protein- and hydroxyprolin content were not significantly influenced by concentrations up to 10 mmol/l.

Animals↗
PubMed1988

[Effects of antirheumatics on the glycosaminoglycan distribution pattern of fetal tibia cultured in vitro].

The glycosaminoglycan (GAG) distribution pattern of murine fetal tibiae cultured for 6 days in vitro was determined and the effects of drugs on the growth of the tibia explants in vitro, on their total GAG content and on their GAG distribution pattern were studied. The explants contained chondroitin-4-sulfate and chondroitin-6-sulfate in a relation of about 4:1; hyaluronic acid was not detected. During the incubation period of 6 days in vitro a mean increase in size of 47% and of the total GAG content of about 80-90% was observed; the GAG distribution pattern was practically unchanged. Incubation of the explants in a medium without ascorbic acid by contrast to a medium containing ascorbic acid (5 and 50 micrograms/ml) lead to a reduction of growth and total GAG content. The nonsteroidal antiphlogistic drugs phenylbutazone (20 and 200 micrograms/ml), ibuprofen (25 and 200 micrograms/ml) and alclofenac (25 and 400 micrograms/ml) effected a concentration dependent decrease of the growth and of the GAG content of the explants mainly due to a reduction of chondroitin-4-sulfate. Prednisolone (10 micrograms/ml) caused a significant increase of the GAG content of the explants leaving their GAG distribution pattern nearly unchanged. Aurothioglucose (400 micrograms/ml) induced a reduction of the growth and of the GAG content of the explants without altering the GAG distribution. Under low concentrations of Na-pentosanpolysulfate (5 micrograms/ml) an increase in growth and in the GAG content by a nearly unaltered GAG distribution pattern was observed, high concentrations (200 micrograms/ml), however, caused a reduction of growth and of the GAG content.

Animals↗
PubMed1986

Effects of mellitic acid (MA) and sodium fluoride (NaF) on the histological appearance of murine fetal tibiae cultured in vitro.

The aim of this study was to develop a standardized image analysis method for localization and quantitative measurement of calcified structures of murine fetal tibiae cultured in vitro as a completion and verification of previous biochemical studies. The calcified structures of bone stained by von Kossa silver technique and the epiphyseal cartilages showing intensive metachromasia with toluidine-blue staining were converted with grey-value window programs and afterwards the areas of the selected structures were measured. The histomorphological investigations showed that the murine tibiae, incubated for a period of 6 days in a medium with addition of 5 mmol mellitic acid, showed both a significant reduction of calcium deposits and an increase of epiphyseal intercellular cartilage matrix. The tibiae incubated in a medium with addition of 0.5 mmol sodium fluoride significantly showed an increase of calcium deposits in the thickened lamellae of the compacta. These histomorphological results confirm previous biochemical studies.

Animals↗
PubMed1983

[Collagen metabolism of fetal bone cultured in vitro].

Cultures of murine fetal bone explants were used as experimental model for the investigation of drug effects on mesenchymal metabolic processes, particularly the collagen metabolism. As parameters for growth or metabolic processes, resp., the increase in size, the DNA-, uronic acid- and hydroxyproline content of the explants were determined under various modifications of the culture conditions. Addition of ascorbic acid to the culture medium caused in concentrations from 2.5 micrograms/ml an increase of the hydroxyproline content and of the size and in concentrations from 20 or 40 micrograms/ml, resp., also an increase of the DNA- and uronic acid content of the explants. Proline exerted in concentrations up to 100 micrograms/ml no significant influences on the determined parameters and showed in concentrations from 150 micrograms/ml inhibitory effects. Substitution of the horse serum of the culture medium by chick embryonic extract resulted in a decrease of growth and metabolic activity of the explants. Under the influence of an oxygen content of 10% in the gas phase of the culture system all determined parameters with exception of the DNA-content were significantly increased as compared with 20% oxygen content, whereas concentrations of 30% oxygen or more led to reduction of growth and uronic acid content of the explants.

Animals↗
PubMed1981

[Suspension cultures of Ehrlich ascites tumor cells as a test system for the study of cytotoxic effects of anaesthetics (author's transl)].

Cultures of a permanently in suspension growing line of Ehrlich ascites tumor cells (EATC) were studied regarding their use as a test system for the determination of cytotoxic effects of anaesthetics. These cells, having a comparatively high reduplication rate, are cultured at 37 degrees C in vitro in a chemically defined liquid medium supplemented by 15% horse serum without agitation in a closed system. In order to detect drug effects on the cultures various cellular parameters can be determined due to the suspension character of the cultures without complicated preparatory measures, e.g. cell number or multiplication rate, cell volume, cell volume distribution. Moreover biochemical parameters, such as protein or nucleic acid content, may be estimated after centrifugation of the cultures separately in the cell sediment and the medium supernatant. Applying drugs of various pharmacological groups (cytostatic and anti-inflammatory drugs, local and general anaesthetics) the usefulness of some of these parameters for the detection of cytotoxic effects was studied.

Anesthetics↗
PubMed1981

[In vitro studies on the influence of volatile anaesthetics on cell number, cell volume, and cellular protein, DNA, and RNA content (author's transl)].

The aim of the present investigations was to see, if halothane (h), enflurane (e), isoflurane (i), and methoxyflurane (m) exert cytostatic or cytotoxic effects. The experiments were performed on suspension cultures of an established line of Ehrlich ascites tumor cells, which were gased by a mixture of N2 (78%), O2 (20%), and CO2 (2%) to which the volatile anaesthetics in 5 different concentrations were added by vaporizers. Under standardized conditions (incubation time: 24 or 48 hrs; initial cell density: 2 X 10(5) cells/ml culture medium) the following results were obtained: 1. All anaesthetics exerted dose dependent cytostatic effects, which were reversible up to concentrations of 2.0 vol% (m), 3.0 vol% (h), and 5.0 vol% (e, i). The cytostatic ID50 values (mmol/l) were found to be 0.50 (h), 1.00 (e), 0.72 (i), 1.25 (m). 2. In cell cultures, which were exposed to anaesthetics for 48 hrs cytotoxic effects were observed after doses of 2.0 vol% (m), 3.0 and 4.0 vol% (h), 4.0 and 5.0 vol% (e and i). 3. In contrast to colchicine, which was studied in comparison to the volatile anaesthetics, the mean cell volume of anaesthetic treated cultures showed only minimal deviations from control values. 4. With exception of m, which produced a significant decrease of the cellular protein content in the dose range 1.5-2.0 vol% and of the cellular DNA content in all concentrations applied the 3 other anaesthetics caused an increase of the cellular protein content and a somewhat smaller increase of the cellular nucleic acids content. The obtained results indicate that the effect of anaesthetic agents on dividing cells is not due to the same mode or site of action, but to an influence on different stage of the cell cycle, particularly the interphase. Colchicine-like c-mitosis were not obtained.

Anesthesia, Inhalation↗
PubMed1980

[Glucosamine: its importance for the metabolism of articular cartilage. 2. Studies on articular cartilage].

In healthy individuals there exists a balance between cartilage proteoglycan synthesis and degradation. In arthrotic cartilage this metabolic balance is deteriorated in spite of a sometimes enhanced proteoglycan synthesis, since the catabolic rate exceeds the anabolic rate corresponding to the severity of the disease. The extracellular organic matrix of the cartilage is destroyed. With different experimental models it could be demonstrated, that the non steroidal anti-inflammatory drugs commonly used in the treatment of arthrosis inhibit the synthesis of mucopolysaccharides, intensify the already existing metabolic disorder, prevent a normalization of cartilage composition and thus impair the function of the cartilage. Glucosamine on the other hand increases in a dose-dependent way the ability of cartilage to synthesize both sulfated mucopolysaccharides and protein, thus restoring the catabolic-anabolic balance of the cartilage.

Animals↗
PubMed1980

[Glucosamine: its value for the metabolism of articular cartilage. 1. Biochemistry of proteoglycans, studies on in-vitro cultures of embryonal mouse fibroblasts and bone germs].

Mucopolysaccharides (glycosaminoglycanes) are essential constituents of the cartilage (chondroitin sulfate) and the synovial fluid (hyaluronic acid). They are formed within the chondrocyte preferably from glucosamine or from glucose and bound to protein constituting proteoglycanes. Non steroidal anti-inflammatory drugs and corticosteroids inhibit this synthesis. Primary fibroblast cultures and in vitro cultured mouse embryo tibiae show a dose-dependent increased synthesis of mucopolysaccharides and an enhanced growth of the bones after addition of glucosamine to the culture medium. This finding underlines the importance of a sufficient supply of the joints with glucosamine.

Adrenal Cortex Hormones↗
PubMed1980

[Study on histological and histochemical appearance of fetal mouse tibiae cultured in vitro in comparison with freshly excised tibiae (author's transl)].

The histological and histochemical appearance of murine fetal tibiae was studied in order to furnish the morphological background for biochemical investigations on in vitro cultures of these organs, used as an experimental model for the study of drug influences on metabolic processes of mesenchymal tissues. Freshly excised tibiae until the 14th day of gestation showed solely cartilagenous structures; first signs of calcification were found after 15 days of gestation and ossification of the diaphysis proceeds until the 17th day. A comparison of tibiae explants excised on the 17th day of gestation and cultured for 6 days in vitro with freshly excised tibiae of the same age (17 days) indicates a continuous growth of the explants in vitro without any signs of degenerative processes which could be due to the culture conditions.

Animals↗
PubMed1979

[Cultures of fetal bone sites as a model for studying drug influence on mesenchymal metabolic processes (author's transl)].

Cultures of murine embryonic bone explants were studied regarding their use as experimental model for the investigation of drug effects on metabolic processes of mesenchymal tissues. Embryonic tibiae excised on the 17th day of gestation and grown in a liquid medium for 6 days as organ cultures appeared particularly suited for this purpose. The planimetrically estimated size of the explants increased during this period in the mean by 40.7% and their DNA-content rose by 67.5%. After 6 days of incubation in vitro the mean DNA-content was about 2.5 micrograms/mg wet weight and the mean uronic acid content 10 micrograms/mg wet weight. Using dexamethasone, oxyphenbutazone, acetyl salicylic acid, sodium aurothiomalate and sodium pentosanpolysulfate as test drugs clear differences in the action on the determined parameters (explant growth, DNA- and uronic acid-content, glycosaminoglycan secretion of the explants) could be demonstrated.

Aging↗
PubMed1977

[Influence of antirheumatic phenylacetic acid derivatives on glycosaminoglycan metabolism of fibroblast culture (author's transl)].

Murine embryonic fibroblast monolayer cultures were used to study the influence of the antirheumatic phenylacetic acid derivatives ibufanac, ibuprofen, alclofenac and bufexamac and of phenylbutazone as a reference compound on glycosaminoglycan (GAG) metabolism viability and multiplication of cells cultured in vitro. The phenylacetic acid derivatives as well as phenylbutazone showed in concentrations between 10(-3) and 10(-5) M a significant inhibitory effect on GAG production and in concentrations between 10(-3) and 3.3 X 10(-4) M a cytostatic effect; bufexamac was cytostatically active up to the concentration of 10(-5) M. Ibufenac, ibuprofen and alclofenac exhibited a similar behaviour as other non-steroidal antirheumatic drugs regarding their influence of GAG metabolism and on cell multiplication.

Animals↗