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W Wohlrab

Publications and source records attributed to W Wohlrab.

At least 37 records · Page 2Linked to original sources
PubMed1992

Potassium channels and regulation of proliferation of human melanoma cells.

1. Ion channels and their possible relation to cell proliferation have been studied in a human melanoma cell line (IGR 1). Membrane currents were recorded by the patch-clamp technique using the cell-attached, cell-free and whole-cell mode. Cell growth was monitored by counting the number of cells at different days after seeding and [3H]thymidine incorporation. 2. A voltage-dependent 10 pS non-inactivating potassium channel (delayed rectifier) is the most commonly observed ion channel in this type of human cell. The channel is active at the normal resting potential and can be blocked by tetraethylammonium chloride (TEA) and also by a membrane-permeable cyclic adenosine monophosphate (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, cyclic AMP). A second type of potassium channel shows properties similar to voltage-dependent A-type potassium channels with complete inactivation. 3. A voltage-independent, non-selective cation channel with a single-channel conductance of approximately 20 pS could be seen in only 8% of the patches. Its properties of modulation are still unknown. 4. The incidence of the 10 pS, non-inactivated potassium channel was maximal at the fourth day after seeding (in 89% of the patches) and was significantly reduced at the seventh day (in 35% of the patches). 5. [3H]thymidine incorporation is maximal at the third day after seeding and is reduced when cells are grown in the presence of TEA or cyclic AMP. This peak of maximal [3H]thymidine incorporation correlated with the incidence of non-inactivated potassium channels. 6. In the presence of TEA or cyclic AMP, growth of the cells is inhibited. We suppose that due to block of potassium channels, most of the melanoma cells are not able to enter the S-phase in the cell division cycle. 7. It is concluded that delayed rectifier potassium channels are involved in the control of melanoma cell proliferation. A similar finding has been reported for K+ channels in T-lymphocytes and human breast carcinoma cells. It is suggested that potassium channels may be involved in controlling the driving force for a calcium influx thereby interacting with Ca(2+)-dependent cell cycle control proteins.

Calcium↗
PubMed1992

[Introduction neurodermatitis and urea].

Neurodermatitis is a multiphasic disease, yet despite intensive research, its etiopathogenesis still remains unclear. A large number of immunological and nonimmunological dysfunctions as well as their diverse interplay lead to very different types of manifestation. Consequently, treatment must also be varied and is mainly determined by the clinical picture. External therapy without glucocorticoids is no longer conceivable in acute and subacute dermatological conditions, although attenuated glucocorticoids which have the least amount of side effects should always be used. Improvement in the therapeutic efficacy of hydrocortisone can be achieved by combining it with urea which, depending on the vehicle used, represents one of the most effective penetration promoters for this glucocorticoid. Fighting the symptoms of dry skin and itching are of central importance in the follow-up treatment and prophylaxis of neurodermatitis. Here, urea preparations have been applied with great success. Urea's efficacy in the skin is largely based on its ability to elevate the water-binding capacity of the corneal layer, on its keratoplastic properties, its antipruriginous effect and its proliferation-suppressant action. However, the intensity and the duration of this therapeutic efficacy are dependent on several factors which must be taken into consideration in the galenics of urea preparations. As a whole, there is a multitude of possibilities for the use of urea in the therapy, follow-up and prophylaxis of neurodermatitis which we have only just begun to exploit in full.

Administration, Topical↗
PubMed1990

Properties of a potassium-selective ion channel in human melanoma cells.

Currents through ion channels were measured from cells of a human melanin-producing melanoma cell line (IRG 1) with the patch clamp technique. In these cells the most frequently observed channel is a potassium channel. The channel activates slowly at depolarizing voltage steps but does not inactivate. Single channel potassium currents can be measured in cell-attached patches at the resting potential of melanoma cells. The channel has a conductance of approximately 10 pS. As measured from the reversal potentials of single channel currents, the permeability ratio for sodium and potassium, PNa/PK, is between 0.03 and 0.04. Open probability is increased at positive potentials. Mean open times are prolonged at voltage steps to more positive potentials. Closed time histograms are fitted by two exponentials. The slow shut time is decreased at positive potentials. In whole cell measurements, cell conductance measured between -20 and + 70 mV was reduced by 10 mM tetraethylammonium chloride from 6.4 +/- 1.2 nS (n = 4) to 0.8 +/- 0.3 nS (n = 3). Application of isoproterenol decreases the probability of the channel being open without any change in the single channel conductance. A possible role of the 10 pS potassium channel in the growth of melanoma cells is discussed.

Cyclic AMP↗
PubMed1990

[Results of a randomized polychemotherapy study in malignant melanoma].

A polychemotherapy (DTIC, vincristine, ftorafur, hydroxycarbamide) devised with reference to the results of short-term sensitivity tests in cell culture is compared with single-agent chemotherapy with DTIC in malignant melanoma. Effectiveness was investigated in a randomized prospective study in cases of high-risk melanoma in clinical stage I, in clinical stage II after lymphadenectomy and in clinical stage III after tumour debulking. The results recorded allow no positive effects of either form of chemotherapy in stage I disease compared with surgical treatment only in a control group. In contrast, a statistically significant advantage of the polychemotherapy was noted in stage II compared with a control group. There was no significant difference in the results of treatment between the two forms of chemotherapy in stage III. No complete remissions of long duration have been achieved.

Adolescent↗
PubMed1990

Penetration of salicylic acid and salicylate into the multilayer membrane system and into the human horny layer.

Using a multilayer membrane system and human horny layer the difference in the penetration of salicylic acid (SA) and its sodium (Na-S) and choline (Ch-S) salts from topical formulations was studied. It was found Na-S and Ch-S were markedly accumulated in the first membrane of the three layer membrane system used. In contrast, a rapid penetration into all three membranes was observed when SA was used. Similar penetration profiles were obtained in human horny layer. Hence, the use of the salts of SA appears to be more suitable for the application as keratolytic.

Epidermis↗
PubMed1990

[Effect of zinc on penetration of 8-hydroxyquinoline of topical formulation].

Zinc is able to form complexes with 8-hydroxyquinoline (HC). Therefore the penetration of HC from topical formulations into the ear of guinea-pigs and into a multilayer membrane system was decreased by Zi. Using the AUC a suitable in vitro-in vivo correlation was obtained. An exception was observed when there were interactions between the ointment base and the in vitro model system. Furthermore, it was found that also zincoxinate is able to penetrate into the skin of guinea-pigs.

Animals↗
PubMed1990

[Effect of urea on penetration kinetics of vitamin A acid in human skin].

It is well known that urea can considerably increase the release of drugs from ointment bases and that it is one of the most effective penetration promoters for topically applied drugs. In our present study, therefore, we investigated the influence of urea on the penetration kinetics of vitamin A acid (VAA) into the various layers of human skin. When a vehicle containing urea was applied to the skin, we found increased VAA concentrations depending on the penetration of urea. We discuss the significance of the synergistic properties of VAA and urea in the topical treatment of various skin disease.

Culture Techniques↗
PubMed1990

[Changes in the functional surface markers of lymphocytes in short-term culture].

Cultured human lymphocytes are a suitable system for testing pharmacological, allergological, and toxicological effects of substances in vitro. For such investigations, the knowledge about the behaviour of the test system under standardized conditions is an important prerequisite. In the 72 h short-time-culture, no changes in T-lymphocytes were found. Small decreases occurred in the subpopulations of cytotoxical/suppressor cells, and inducer/helper cells, respectively. Number of cells expressing class II antigens of the main histocompatibility complex decreases, too (to 62%). Tritium thymidine incorporation rates inform about DNA-synthesis.

Antibodies, Monoclonal↗
PubMed1990

[Simultaneous determination of urea and hydrocortisone penetration into human skin].

The effect of different urea concentrations on the skin penetration of hydrocortisone from topically applied vehicle was investigated. Therefore 14C-labeled urea and 3H-labeled hydrocortisone were determined simultaneously in different layers of human skin. It could be shown an increased penetration of hydrocortisone is dependent above all on penetrated urea amount into the horny layer and on the distribution of penetrated urea in the horny layer. Hence follows a strong vehicle dependence from penetration promotion of hydrocortisone as an example for glucocorticoids by urea can be deduced. For the using of the penetration promoting effect of urea at the development of glucocorticoid containing ointments the knowledge of the glucocorticoid and urea penetration in each vehicle is indispensable.

Administration, Topical↗
PubMed1990

[Penetration and effectiveness of hydrocortisone in reduced concentration in vehicles].

Several attempts have been made to optimize the efficiency of topical glucocorticoids (GC) and, at the same time, to minimize their side effects. In this respect, we should first consider attenuated GC. Dependent on the urea concentration, hydrocortisone (HC) in combination with urea results in both a considerable increase of the HC liberation from the ointment base, as well as an increased penetration rate of HC into the individual skin layers. If we apply these mechanisms to a preparation containing low HC concentrations, a given therapeutic effect can be obtained with definitely reduced HC concentrations. On the other hand, the therapeutic efficiency or the penetration rate of GC can not be deduced from the galenic formulation, the drug concentration, or the amount of urea.

Administration, Topical↗
PubMed1989

[The effect of selected irritants on suspended keratinocytes using double vital staining].

Loss of vitality of keratinocytes after influence of strong allergens and irritants was examined. Cell viability was determined by trypan blue exclusion assay and eosintyrode solution. The results of the two methods harmonize essentially, but obviously, single noxa can lead to changes of the dye that exclude the use for an appropriate test. On principle, the method is suitable for testing the substances. The toxic final concentration should constantly be ascertained. Still, the results are recommended to be guaranteed through other methods.

Animals↗
PubMed1989

[Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects].

Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance. M-G seems to be effective especially in combination with other antineoplastic drugs. Its final evaluation may be reserved to further randomized trials. Recently, the psoriasis vulgaris is expected to be an additional field of the application of M-G. In this minireview data on synthesis, preclinical pharmacology, pharmacokinetics, biochemical effects and toxicology of M-G are given. Furthermore, clinical findings on M-G concerning its pharmacokinetic behaviour, antitumor and antipsoriatic activities are described.

Animals↗
PubMed1989

[Significance of urea in external therapy].

Urea affects human skin by penetrating different skin layers. For this a strong vehicle dependence is evident. Therefore, considerable differences could be found in the duration and intensity of increased water-binding capacity after the application of different urea-containing emulsions. For therapy to increase the hydration and water-binding capacity in the horny layer of diseased skin, preparations with 10% urea are better suited than those containing 2% or 5% urea. By altering the functional structure of the horny layer and considerably increasing the drug's liberation from its ointment base, urea is one of the most effective penetration promoters. An increased penetration rate of some corticoids and dithranol from urea-containing ointment were demonstrated in human skin. The resulting penetration promotes two possible applications in topical therapy: an increased therapeutic effect for a given concentration of an active constituent or a given therapeutic effect with a reduced concentration of the active ingredient.

Administration, Topical↗
PubMed1989

[The significance of detecting sex hormone receptors for the treatment and prognostic assessment of malignant melanoma].

The current seek for alternative or supplemented therapy is a corner stone in controlled clinical trials and researches concerning malignant melanoma. The discovery of intracytoplasmatic estrogen receptors in the cells of malignant melanoma raised the hope for the use of sexual hormones to perform this therapeutic aspect. In this paper we report on the nature of these sexual hormone receptors, new methodical possibilities, correlations to clinical data together with their significance in diagnosis, therapy and prognosis of malignant melanoma.

Biopsy↗
PubMed1989

[Cytochrome P-450 dependent drug metabolism--use of an in vitro test system in multiple chemical exposure].

Investigations of the influence of an actual exposure on the in-vitro-activities and the inducibility of cytochrom P-450 dependent enzymes have not been described in the literature until now. First results gained from mitogen-stimulated lymphocytes of exposed and not-exposed individuals suggest such an influence of the given mixture of noxious agents on the basic deethylational ability of the examined cells acting in the sense of inhibition. Possible causes for this phenomenon are discussed.

Air Pollutants, Occupational↗
PubMed1989

The effect of liposomal incorporation of topically applied hydrocortisone on its serum concentration and urinary excretion.

We demonstrated previously, that hydrocortisone incorporated in the phospholipid bilayer of liposomes (liposomal hydrocortisone) shows an improved concentration-time profile in the different skin layers after external application when compared with a conventional ointment. In the present work, it was investigated under in vivo conditions, whether or not the liposomal formulation also enhances the percutaneous absorption rate. The results obtained in guinea pigs clearly demonstrate a decrease in serum concentration and urinary excretion. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system or "drug localizer" increasing the therapeutic efficacy and, simultaneously, decreasing adverse systemic effects. The significance of liposomal attenuative and potent glucocorticoids in topical treatment is discussed.

Administration, Topical↗
PubMed1989

[Skin permeation of liposomal incorporated hydrocortisone].

With the liposomal incorporated hydrocortisone a very much improved concentration-time profile was obtained in the different layers of human skin after topical application when compared with conventional hydrocortisone in the ointment. The increased hydrocortisone penetration into human skin correspond with the degree of blanching results by vasoconstriction test. Under in vivo conditions the influence of liposomal hydrocortisone on percutaneous resorption was investigated. In guinea pigs a decreased serum concentration and urinary excretion of hydrocortisone could be demonstrated. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system, it can be provide increased therapeutic efficacy and, simultaneously, decreased unwanted systemic effects. The significance of liposomal incorporated attenuative and higher potent glucocorticoids in external therapy is discussed.

Animals↗