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Biomedical subjects

W Wohlrab

Publications and source records attributed to W Wohlrab.

At least 19 recordsLinked to original sources
PubMed1999

Identification of ether à go-go and calcium-activated potassium channels in human melanoma cells.

Ion channels and intracellular Ca2+ are thought to be involved in cell proliferation and may play a role in tumor development. We therefore characterized Ca(2+)-regulated potassium channels in the human melanoma cell lines IGR1, IPC298, and IGR39 using electrophysiological and molecular biological methods. All cell lines expressed outwardly rectifying K+ channels. Rapidly activating delayed rectifier channels were detected in IGR39 cells. The activation kinetics of voltage-gated K+ channels in IRG1 and IPC298 cells displayed characteristics of ether à go-go (eag) channels as they were much slower and depended both on the holding potential and on extracellular Mg2+. In addition, they could be blocked by physiological concentrations of intracellular Ca2+. In accordance with these electrophysiological results, analysis of mRNA revealed the expression of a gene coding for h-eag1 channels in IGR1 and IPC298 cells, but not in IGR39 cells. At elevated Ca2+ concentrations various types of Ca(2+)-activated K+ channels with single-channel characteristics similar to IK and SK channels were detected in IGR1 cells. The whole-cell Ca(2+)-activated K+ currents were not voltage dependent, insensitive for 100 nm apamin and 200 microm d-tubocurarine, but were blocked by charybdotoxin (100 nm) and clotrimazole (50 nm). Analysis of mRNA revealed the expression of hSK1, hSK2, and hIK channels in IGR1 cells.

Calcium↗
PubMed1997

[Intratumor pO2, S-phase fraction and p53 status in cervix carcinomas].

PURPOSE: Investigation whether tumor tissue oxygenation is influenced by proliferation or p53-status in cervical cancers. MATERIAL AND METHODS: From April 1995 through December 1996, 28 patients with locally advanced cervical cancers (age 36 to 78 years; FIGO stages: 10 patients IIB, 16 patients IIIB, 2 patients IVA) underwent intratumoral measurement of pO2 prior to definitive radiotherapy. The histological specimens were examined for grading and quantitative immunohistological expression of the MIB-antigen and p53-protein. Proliferation was estimated by measuring the S-phase fraction with flow cytometry. RESULTS: The median pO2-values showed a broad variation from 2.2 through 60.4 mm Hg, median 19.7 mm Hg. The S-phase fraction varied from 4.2 through 34.2% (median 11.6%), MIB-positive cells from 20 through 100% (median 74%), and immunohistologically p53-positive cells from 0 through 95% (median 2%). The patients were divided in 2 groups according to the pretreatment pO2. Tumors with a pO2 above the median had a lower S-phase fraction than tumors with a pO2 below the median, 10.4 +/- 3.8% versus 16.3 +/- 5.5%, p < 0.02. MIB and p53 were not different in both groups (MIB: 68.1 +/- 27.7% versus 75.0 +/- 18.4%, p = 0.1; p53: 26.4 +/- 38.5% versus 18.1 +/- 19.8%, n. s.). Grade of differentiation and FIGO stage had no impact on pO2. CONCLUSION: Locally advanced cervical cancers with a poor oxygenation have a higher proliferative activity. Tumor proliferation may play a causative role for the development of hypoxia as suspected from radiobiological theories.

Adult↗
PubMed1997

[Fatty acids and the epidermis].

Fatty acids play a central role among the epidermal lipids because of their considerable contribution to structural and functional features of the epidermis. They are important components of cell membranes, the intercellular stratum corneum lipids and the hydro lipid skin surface film. Additionally, endogenous fatty acids act as mediators of the epidermal cell proliferation and differentiation and therefore, lipid synthesis and also as mediators of inflammatory and immunological processes. The topical application of certain fatty acids leads to interactions at the structural and functional level. On the one hand, fatty acids may be of importance to restore a disturbed stratum corneum barrier. On the other hand, fatty acids are able to modulate dermal and transdermal drug transport. Mechanisms of the interaction between exogenous fatty acids and epidermal cells, especially keratinocytes, and effects on their proliferation and differentiation are currently under investigation or largely unknown, respectively.

Acne Vulgaris↗
PubMed1997

Analytical methods for measuring urea in pharmaceutical formulations.

Two new methods are described for the routine determination of urea that utilize HPTLC-densitometry and colorimetry. The methods involve derivatization of urea with p-dimethylaminobenzaldehyde to a yellow-coloured compound. Validation of the methods was accomplished with respect to linearity, accuracy, reproducibility and limit of detection/quantification. Both methods were compared with an enzymatic method previously described in the literature and were found to be in close agreement. The proposed methods have the advantages of being simple, rapid and involve a single step sample preparation. Under experimental conditions HPTLC was the most sensitive method.

Chromatography, Thin Layer↗
PubMed1996

DNA image cytometry on sections as compared with image cytometry on smears and flow cytometry in melanoma.

DNA measurements of 130 melanomas were carried out by flow cytometry (FCM) and image cytometry (ICM). ICM was applied to cytological preparations of fresh material (cICM) and to sections of formalin-fixed paraffin embedded tissue (sICM). The DNA ploidy, the DNA index of G0/G1 peaks (DI), and the proliferation index (PI) were used to compare all the methods. The following parameters reflecting malignancy were calculated only from ICM histograms: the 5c exceeding rate (5cER) and the malignancy grade (MG). In cases found to be DNA aneuploid by FCM, the PI values (FCM versus cICM) and the DIs (between all methods) showed a high correlation, and the concordance in relation to the DNA ploidy status was 96% (FCM versus cICM) and 94% (FCM versus sICM). However, we ascertained essential differences between FCM and ICM in melanomas classified as DNA diploid by FCM. The concordance in DNA ploidy was only 66% (FCM versus cICM) and 64% (FCM versus sICM). In contrast, cICM and sICM yielded similar results in most cases. With the exception of the near diploid range, ICM is superior to FCM in detecting DNA aneuploidy. In particular, DNA tetraploid stem lines can easily be overlooked by FCM. Therefore, DNA measurements of tumours judged to be DNA diploid by FCM must be verified by ICM. ICM on sections proved to be applicable and yielded reliable results provided that a suitable thickness was used, and the measuring of sectioned and overlapping nuclei was largely avoided by careful focusing in either direction.

Aneuploidy↗
PubMed1996

Influence of ion pairing on ex vivo penetration of erythromycin into sebaceous follicles.

Microorganisms play an important role in the pathomechanism of acne vulgaris which is treated with antibiotics, particulary erythromycin (ERY). The main problem in the topical use of ERY lies in achieving sufficient penetration of the drug into sebaceous follicles. Doubly enhanced penetration of an ion pair composed of ERY and octadecansulfonate (OS) in contrast to the commonly used ERY base was observed, using a multilayer membrane model (MMM). The aim of the present study was to evaluate the results obtained on the MMM using excised human skin. The amount of ERY penetrating into sebaceous follicles of freshly excised human skin was measured using [N-methyl-14C]erythromycin. The ex vivo penetration of the ion pair ERY/OS into the sebaceous follicles was observed to be doubly enhanced compared with the penetration of the ERY base. The model was shown to be suitable for predicting in vivo penetration of anti-acne formulations into sebaceous glands.

Administration, Topical↗
PubMed1996

[Modulation of drug penetration in the skin].

Drugs administered topically on skin should act either dermally or transdermally. They have to cross the stratum corneum (SC) which is responsible for the barrier function of the skin. Most of the drugs are not able to penetrate the SC. For this kind of drugs it is necessary to search for penetration enhancers to increase drug absorption. Sometimes systemic side effects caused by drugs applied topically have to be reduced or prevented. In these cases, so called retarders or reducers are applied as penetration modulators. Penetration into and through the SC may be influenced by physical means (hydration, iontophoresis, phonophoresis, temperature) or chemical substances. Alcohols, sulphoxides, fatty acids, esters, Azone, pyrrolidones, urea and polyoles are applied as penetration enhancers. The objectives for the use of a penetration modulator are to change the solubility and diffusivity of the drug in the SC reversibly. It is necessary to distinguish between modulators which influence the lipid pathway and those which are able to modify diffusion via the polar pathway.

Administration, Cutaneous↗
PubMed1995

Modelling of drug penetration into human skin using a multilayer membrane system.

In this article, a new in vitro model system is presented with a multilayer membrane system serving as acceptor. Matrix-stabilized membranes are applied with dodecanol as lipid and collodion as matrix. Using the drug dithranol it was shown that the acceptor system can be varied over a wide range by changing the dodecanol content of the membranes and by addition of the hydrophilic substance propylene glycol to the membranes. It was demonstrated that the variability of the acceptor system can be used to adapt the penetration profiles of dithranol in a six-layer membrane system to those in excised human skin. It is shown that it is possible to study the penetration of dithranol from different semisolid formulations using the 'adapted' model system.

Anthralin↗
PubMed1995

Optimization of topical erythromycin formulations by ion pairing.

Erythromycin (ERY) is used in the topical treatment of acne vulgaris. In order to decrease the amount of microorganisms markedly, the antibiotic must penetrate into the sebaceous follicles. Firstly, the aim of this study was to improve the lipophilicity of ERY by ion pairing. Secondly, a formulation with optimized penetration of the ion pair was developed. Thirdly, the optimized formulation was compared with formulations containing ethanol and with the commercial product Zineryt. The determination of lipophilicity was based on partition coefficients (PC) and on the penetration of ERY into a modified multilayer membrane system (MMS). It was shown that the penetration of ERY into a lipophilic acceptor system was three times higher when ion pairing between ERY and octadecansulfonate was used in comparison with the penetration of the ERY base alone. The dosage of the antibiotic used can be markedly reduced by optimizing a vehicle for the ion pair.

Acne Vulgaris↗
PubMed1993

[DNA flow cytometry of malignant melanoma of the choroid].

Thirty-five choroidal melanomas were analyzed by flow cytometry. DNA euploidy, aneuploidy and polyploidy were found in approximately 54, approximately 46, and approximately 20% of the tumors, respectively. No correlation between histological type and ploidy was found. The synthesis phase was irregular in approximately 25 and approximately 38% of the spindle and the mixed cell melanomas, respectively. The G2M peak was broadened in approximately 50% and in approximately 23% of the spindle and the mixed cell melanomas. About 20% of the malignant melanomas were highly proliferative. In 25% of the melanomas chemotherapy seemed to be useful.

Brachytherapy↗
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↗