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R Neubert

Publications and source records attributed to R Neubert.

At least 19 recordsLinked to original sources
PubMed1997

Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. II. Mixtures of ceramides and saturated fatty acids.

Fourier transform (FT) Raman spectroscopy and differential scanning calorimetry (DSC) were used to study the thermotropic phase behaviour of mixtures of ceramides type IV (CER) and stearic acid (SA). For comparison the melting behaviour of SA was re-examined. The Raman spectra of all mixtures in the solid state show sharp bands associated with trans sequencies of the alkyl chain residues of both lipids. These features demonstrate that the hydrocarbon chains are highly ordered in the mixtures, too. The temperature dependence of the conformationally sensitive bands is used to estimate the degree of order in terms of the relative population of trans and gauche conformations. The DSC heating curves for the mixtures show two endothermic transitions which are typical for eutectic melting. The factor group splitting of the CH2 scissoring mode, arising from the orthorhombic subcell packing of SA, disappears in the course of the eutectic melting of samples with a SA content lower than 90 mol%. Both DSC and Raman spectroscopic studies reveal that CER and SA are immiscible in the solid state. The phase diagram of the system is a simple eutectic type one. The addition of SA to CER shifts the melting temperature of ceramides to lower values. However, though SA is a major component of stratum corneum (SC) it is not efficient enough to increase the fluidity of ceramides.

Calorimetry, Differential Scanning↗
PubMed1997

Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. III. Mixtures of ceramides and cholesterol.

The thermotropic and lyotropic phase behaviour of mixtures of ceramides type IV and cholesterol was investigated using Fourier transform (FT) Raman spectroscopy and differential scanning calorimetry (DSC). In the dry and in the fully hydrated state of these mixtures the DSC-curves exhibit an eutectic melting followed by the melting of the residual solid component. The Raman spectrum of the mixtures is complex, nevertheless, the appearance of the conformationally dependent bands indicates the ordered structure of the hydrocarbon chains. The temperature dependence of the conformationally sensitive bands in the CH2 stretching region (2800-2975 cm-1) and in the chain C-C stretching region (1050-1150 cm-1) was used to estimate the degree of order in terms of the relative population of trans and gauche conformers. The spectrum of the pure cholesterol shows only a weak temperature dependence in the CH2 stretching region and, therefore, the decrease of the intensity of the asymmetric CH2 stretching mode at 2880 cm-1 can be attributed to the melting of the alkyl chains of ceramides. The temperature and width of the phase transition, derived from Raman data, are similar to those of the DSC study.

Calorimetry, Differential Scanning↗
PubMed1997

Separation and quantitation of glycolipids as penetration modifiers in human skin using high-performance liquid chromatography-mass spectrometry with electrospray ionization.

An high-performance liquid chromatography-mass spectrometry method is presented for the measurement of glycolipids used as modulators of the penetration of drugs into human skin. In methanol extracts from different skin layers a detection limit of 100-400 pg/ml could be achieved. A routine analytical procedure could be set up with good quantitation reliability (relative standard deviation 6.6%).

Adjuvants, Pharmaceutic↗
PubMed1997

Application of capillary zone electrophoresis in cephalosporin analysis.

Cephalosporins have structures and antibiotic activity similar to those of penicillins which represent a class of compounds with closely related structures. Most of the cephalosporins contain aromatic groups and show distinctive UV spectra. Separating the different types of cephalosporins is a challenging task for HPLC. but the resolving power of capillary zone electrophoresis (CZE) makes this separation fast and simple. The present study reports the application of CZE for cephalosporin analysis and the separation of cephalosporins from plasma. Both field strength and temperature were shown to influence the plate number. The influence of injection time on the peak height was studied. Furthermore, the influence of pH value on the separation of cephalosporins by CZE was investigated. The low sample amount required and the relatively short analysis time are the main advantages of this method.

Cefotaxime↗
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

Comparative study on age-dependent development of surface receptors on peripheral blood lymphocytes in children and young nonhuman primates (marmosets).

General conformity was found concerning age-dependent changes in the major subsets (CD4, CD8, CD2, CD20) and the adhesion molecules CD11a and CD29 on peripheral blood lymphocytes in children and young marmosets (Callithrix jacchus). Differences exist in the expression of the surface receptors CD45RA and CD56. Taking the total number of white blood cells into account, an age-related increase in the absolute numbers of peripheral blood lymphocytes was found in marmosets whereas in children, an age-dependent decrease was observed. The definition of reference ranges for different stages of maturation in children and young marmosets may serve as a basis on which comparative risk assessment of possible effects on lymphocyte subsets after pre- or perinatal drug exposure can be estimated.

Adolescent↗
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↗
PubMed1997

Capillary zone electrophoresis in skin fatty acid analysis.

The development of a method for analyzing C12-C18 fatty acid alkali salts by capillary zone electrophoresis is described. Organic solvents were added to the aqueous separation buffer to achieve solubility of the fatty acids together with higher temperatures. Detection of these poorly UV absorbing species could be achieved by indirect photometric detection adding a highly UV absorbing co-ion to the separation buffer. Thus detection limits of 6 microM were recorded. The dynamic range of quantitation was limited to 10(1) due to association and micelle formation at higher concentrations. The relative standard deviation of the method was in the range of 4 to 10%. The described method could be successfully applied to the analysis of free fatty acids in human stratum corneum after solid phase extraction of the lipid fraction.

Calibration↗
PubMed1996

Down-regulation of adhesion receptors on cells of primate embryos as a probable mechanism of the teratogenic action of thalidomide.

In spite of ongoing speculation, there has been no evidence that adhesion receptors are expressed on the cells of mammalian embryos. In this report, we provide the first proof that a variety of such receptor (beta 1-, beta 2-, and beta 3-integrins and selectin) are indeed expressed on cells of essentially all primordia of marmoset embryos at early organogenesis (developmental stages 11 to 13, or even earlier). Treatment with low doses (20 or as little as 1 mg/kg body weight) of a highly teratogenic derivative (EM12) of thalidomide, the most notorious human teratogen, triggers a dramatic and statistically highly significant down-regulation of several surface adhesion receptors (e.g. CD11a/CD18, CD49d/CD29, CD61, etc.) on early limb bud cells and on cells of some other primordia during early organogenesis of embryos of a primate (marmoset, Callithrix jacchus). Some of these receptors almost disappear, or they are expressed at a lower epitope density in the exposed embryos. These down-regulations of surface adhesion receptors may be expected to alter cell-cell- and cell-extracellular matrix interactions, and they are suggested to be a long-sought primary mechanism of the teratogenic action of thalidomide-type substances.

Animals↗
PubMed1996

Cross-reactivity of antihuman monoclonal antibodies with cell surface receptors in the common marmoset.

In this report we demonstrate that a large number of monoclonal antibodies (mAbs) against human epitopes cross-react with surface receptors on white blood cells of Callithrix jacchus, indicating species similarities. However, a variety of other mAbs do not exhibit any cross-reactivity, thus also providing evidence for distinct differences in the structure of these receptors among nonhuman primates. Such differences have to be known and taken into consideration when attempting extrapolations between species. The results presented provide the prerequisite for performing extensive studies on immunological structures and functions in marmosets under normal and pathological conditions. We conclude that the immune system of Callithrix jacchus is a convenient model for studies on immunotoxicity with relevance for man, and for this purpose it is clearly superior to that of any rodent species.

Animals↗
PubMed1996

Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets.

The two thalidomide (Thd) derivatives beta-EM12 and phthalimidophthalimide (Phtpht), which exhibit no obvious teratogenicity, were tested for their ability to induce changes in the pattern of lymphocyte subpopulations, and especially changes in integrin receptors, in marmosets (Callithrix jacchus). Previously, Thd and its highly teratogenic derivative alpha-EM12 had been found to alter the expression of adhesion molecules, such as CD2 (LFA-2) or CD11a/CD18 (LFA-1). None of these typical effects on adhesion receptors were observed following administration of the relatively high daily doses of 50 mg/kg body wt beta-EM12 and Phtpht. Nevertheless, there were some minor effects, such as alterations in the receptor density on peripheral blood mononuclear cells, which were often contrary to the effects induced by Thd. Mainly affected were: CD8 cells, B cells bearing the CD54 receptor and CD4 cells bearing the CD56 (NCAM) surface marker. We observed an increase in the receptor density of CD11c (p150,95) on monocytes with Phtpht but not with beta-EM12. The inability of the two substances with no obvious teratogenic potential to typically modify beta 2-integrin receptors on white blood cells at comparatively high doses is consistent with our hypothesis, that the teratogenicity of Thd may also be linked to alterations in the expression of adhesion molecules.

Animals↗
PubMed1996

Studies on the immunoglobulin-E system of the common marmoset in comparison with human data.

In the common marmoset (Callithrix jacchus jacchus) immunoglobulin E (IgE) serum levels and IgE synthesis of peripheral blood mononuclear cells (PBMC) in vitro were investigated in order to look for homologies to the human system. While IgE was not found in marmoset blood plasma with three commercial antihuman IgE-kits with monoclonal antibodies (mAbs), two other kits using polyclonal antibodies against human IgE revealed detectable IgE concentrations of up to 10 kU/liter in plasma samples of 19 out of 21 marmosets. In accord with human data, rhIL-4 showed biological functions under in vitro conditions in PBMC of the New World monkey. Proliferation, measured by 3H-thymidine incorporation, of isolated PBMC of marmosets could be induced by rhIL-4. FACScan analysis showed an enhanced expression of the low affinity IgE receptor CD23 (Fc epsilon RII) on CD20+ B lymphocytes after incubation with rhIL-4. Furthermore, PBMC from marmosets could be stimulated by IL-4 alone or in combination with dexamethasone as well as with lipopolysaccharide (E. coli) to produce IgE in culture. The results indicate that Callithrix jacchus is using an IgE system that is rather similar to that of humans, although not completely identical. Antihuman mAbs and rhIL-4 can be used to investigate IgE regulation in vitro of marmoset PBMC. These data encourage the development of a primate animal model for studying possible modifications of the IgE system under pathological conditions to find new therapeutic strategies in atopic diseases.

Animals↗
PubMed1996

Application of capillary zone electrophoresis for analyzing biotin in pharmaceutical formulations--a comparative study.

The detection limit and reproducibility of capillary zone electrophoresis (CZE) measurement of biotin were compared to those of a spectrophotometric method and those of the determination of the sulphur content by combustion of the biotin sample followed by coulometric titration of the formed SO2. Drug analysis showed that all three methods gave consistent results and were suitable for the determination of biotin. CZE was found to be the best method for the determination of pharmaceutical formulations containing biotin because of its high separation efficiency, short analysis time, ease of instrumentation and sample preconditioning, and good precision.

Biotin↗
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

Thalidomide and the immune system. 4. Down-regulation of the CD26 receptor, probably involved in the binding of HIV components to T cells in primates.

Thalidomide (Thd) is capable of down-regulating the CD26 receptor on CD4+ lymphocytes after treatment of healthy volunteers. Similar effects are observed when marmosets (Callithrix jacchus) are treated with Thd. The Ta1 epitope of the CD26 receptor has recently been shown to bind the HIV-1 Tat trans-activating protein, and CD26 has also been suggested to be a coreceptor for the binding of the V3 loop of the gp120 HIV envelope protein. This might provide a hint for possible therapeutic interventions.

Animals↗