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Biomedical subjects

R Neubert

Publications and source records attributed to R Neubert.

At least 19 recordsLinked to original sources

Noninvasive characterization of human stratum corneum of undiseased skin of patients with atopic dermatitis and psoriasis as studied by Fourier transform Raman spectroscopy.

Etiopathogenetic regulatory disorders of epidermal metabolism and the subsequent changes in the molecular pattern of the stratum corneum play an important role in the clinical differentiation of particular dermatoses (e.g., psoriasis, atopic dermatitis). In this study we present in vitro Fourier transform Raman spectra of the stratum corneum from healthy skin, as well as from clinically undiseased skin of the right heel of atopic and psoriatic volunteers. Differences in the averaged spectra were detected, particularly in the spectral ranges of 1112-1142 (lipid band), 1185-1220, and 1394-1429 cm(-1). By using the first derivative of the averaged spectra and/or a statistical evaluation of the spectroscopic data it was possible to distinguish the skin types examined.

Adolescent↗

[Morphological evaluation of posterior capsule opacification in diffractive multifocal intraocular lenses].

BACKGROUND: Diffractive multifocals belong to the first generation of multifocal intraocular lenses. Dure to their optical principle of diffraction multifocals separate the incoming light on two foci (41%) with 18% loss of scattered light. Therefore, reduced contrast sensitivity and glare have been frequently described with this lens. PATIENTS AND METHODS: We evaluated 42 eyes of 25 patients (age at surgery 63.8 +/- 8.8 years) 3 years after implantation of a Pharmacia 811E diffractive multifocal (MIOL). They were tested for functional results including contrast and glare (Mesoptometer II). In addition 22 eyes were evaluated for posterior capsule opacification (PCO) using digitalized retroilluminations photographs and the EPCP image analysis program. RESULTS: Average visual acuity was 0.77 +/- 0.20 (uncorrected distance), 0.93 +/- 0.21 (corrected distance), 0.94 +/- 0.13 uncorrected near) und 0.98 +/- 0.08 (best corrected near). PCO-values quantified by EPCO were 1.13 +/- 0.59 (Range 0.07 to 2.1). On average 18.1 +/- 14.9% of the optic area showed an opacification grade 1, 35.8 +/- 26.6% grade 2 and 7.7 +/- 17.1% grade 3. Contrast sensitivity showed no patient with contrast level 7 or better for monocular evaluation, but 30% for binocular testing. Only 4% met the criteria for night driving when tested for glare. Spearman correlation did not reveal any significant correlation between PCO-values and visual acuity, contrast sensitivity or glare (all p > 0.24, all r < 0.22). CONCLUSIONS: Patients with diffractive multifocal IOLs showed excellent results for near and distance visual acuity three years after implantation. However, contrast and glare results were poor, probably due to a rather high PCO-rate. Future developments of the lens type should include PCO-reducing factors, such as sharp edge optics and foldable materials.

Aged↗

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system: 3. Plasma immunoglobulins and cytokines of workers with quantified moderately-increased body burdens.

The concentrations of immunoglobulins (IgA, IgD, IgG, IgM) and of several cytokines were measured in the plasma of volunteers with clearly, but moderately, increased body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), using monoclonal antibodies and an enzyme-linked immuno-sorbant assay. Two groups of workers with different body burdens of PCDD/PCDF were studied: (trial I) persons with mainly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and (trial II) persons with mainly penta- and hexachlorinated dibenzofurans (P5CDF/H6CDF) in their blood fat. Including the reference group, 158 volunteers were investigated. A slight but statistically significant decrease was observed in the plasma concentration of IgG1 in persons exposed to TCDD, but not in persons exposed to P5CDF/H6CDF. When the data of both groups were pooled and a multi-regression analysis against international TCDD toxicity equivalencies (I-TEq, NATO/CCMS) was performed, taking several confounding factors into account, no influence of the dioxin exposure could be revealed. There were no changes in the plasma concentrations of the other immunoglobulins studied. In the same volunteers, no deviation from the reference range was found for the concentrations of the cytokines: IL-1alpha, IL-1beta, IL-6 and TNFalpha in blood plasma.

Adult↗

Characterization of cephalosporin transfer between aqueous and colloidal phases by micellar electrokinetic chromatography.

A new electrokinetic chromatographic method was applied to the determination of the partition coefficient between water and micelle for a group of cephalosporins (cefmetazol, cephradin, cefaclor, ceftazidim, cefodizim, cephapirin, cephalothin and ceftriaxon) using sodium dodecyl sulphate as an anionic surfactant in microemulsion and in micellar systems. In the new method, the running buffer contains both the micelles and the drug, and the injected solution contains the same concentration of micelles as the running buffer but not the drug. The mobility of the drug can be measured from a negative peak recorded the chromatogram. The required parameters for the determination of the capacity factor (mu(aq) and /mu(me) are the electrophoretic mobilities of the solutes in the aqueous and the micelle phases, mu(eff) is the effective mobility in the micellar system or in the microemulsion) were measured by the new micellar and microemulsion electrokinetic chromatography technique. Linear log-log relationships were found between both the micelle-water partition coefficient and the capacity factor and the n-octanol-water partition coefficient.

Cephalosporins↗

Expression of adhesion receptors on rat limb bud cells and results of treatment with a thalidomide derivative.

The expression of several adhesion surface receptors was studied on cells of early limb bud development of 58 Wistar rats treated orally with two daily doses of the thalidomide derivative EM12 (2 x 50 mg/kg body weight) from day 7 to 10 of pregnancy. EM12 is a more potent teratogen than thalidomide. Limb bud cells of 56 untreated animals served as controls. The studies revealed that the integrins CD11a, CD11b, CD18, CD49d, and CD61, as well as the additional adhesion receptors CD54, CD62L, and the transferrin receptor CD71 were expressed on day 11 of gestation to various degrees on these embryonic cells. In contrast to results of previous studies with a non-human primate (Callithrix jacchus) there was no down-regulation of any of these receptors on the surface of limb bud cells of the rat embryos after treatment with EM12. This result is in accordance with the lack of teratogenicity in this rodent species.

Animals↗

Capillary zone electrophoresis determination of meropenem in biological media using a high sensitivity cell.

A capillary electrophoresis method with a high sensitivity cell (Z-cell) has been developed for the determination of meropenem in aqueous solution and in biological media (urine, plasma). Water samples were analysed using two calibration curves of meropenem with standard capillary and a capillary with a high sensitivity cell. In urine, the samples were only diluted in buffer and were injected without any further sample preparation. For the analysis of plasma samples, a calibration curve was utilized covering the meropenem concentration range of 0.5-200 microg/ml. The detection limit and the relative standard deviation of the migration times and of the peak areas were determined.

Electrophoresis, Capillary↗

In vitro investigation of the liberation of fluoride ions from toothpaste compounds in a permeation model.

The most important requirement for effective topical fluoride prophylaxis from toothpaste containing fluoride is that the active fluoride agent must be chemically free, and the rapid spread of the dissolved fluoride ions over the tooth surface. Abrasive compounds in the toothpastes and the brief residence time at the site of action, the oral cavity and tooth surface must not prevent the liberation. Using a two-chamber diffusion cell and an ion-selective fluoride electrode, the content of fluoride ions in five different fluoride-containing toothpastes was determined by direct potentiometry as a function of time and the different abrasive compounds employed. The investigation has demonstrated that a reduction of the release rate of fluoride ions by nearly 50% is seen when calcium carbonate and calcium hydrogen phosphate dihydrate are used as abrasive compounds and combined with sodium fluoride.

Fluorides↗

Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux.

PURPOSE: This study on the intestinal transport of beta-lactam antibiotics was undertaken to investigate the correlation between cellular transport parameters and the bioavailability. METHODS: Transport of 23 beta-lactam antibiotics was characterized by measuring their ability to inhibit the uptake of glycylsarcosine into Caco-2 cells, their uptake into the cells and their total flux across the cell monolayers. RESULTS: Ceftibuten and cyclacillin were recognized by PEPT1 with affinity constants comparable to those of natural dipeptides (K(i) = 0.3 and 0.5 mM, respectively). Cefadroxil, cefamandole, cephradine, cefaclor, cefuroxime-axetil, cefixime, cephalotin, cephalexin and ampicillin also interacted with PEPTI (K(i) = 7-14 mM). In contrast, cefapirin, cefodizime, cefuroxime, cefmetazole, ceftazidime, benzyl-penicillin, ceftriaxone, cefpirome, cefotaxime, cefepime, cephaloridine and cefsulodin displayed no affinity to the transport system (K(i) > 20 mM). The uptake into the cells and the transepithelial flux was highest for those beta-lactam antibiotics, which showed the strongest inhibition of [14C]Gly-Sar transport (p < 0.0001). Exceptions were cefuroximaxetil and cephalotin. CONCLUSIONS: The probability of oral bioavailability for beta-lactam antibiotics is mainly determined by their affinity to PEPTI. A threshold K(i) value of 14 mM with respect to Gly-Sar uptake is required.

Administration, Oral↗

Characterization of partitioning behavior of cephalosporins using microemulsion and micellar electrokinetic chromatography.

Electrokinetic chromatography (EKC) was introduced to determine the partitioning behavior of various cephalosporins (cefpim, cefpirom, cefaloridin, cefaclor, cephalexin, cefuroxim, cefotaxim) in microemulsions (ME) and micellar (MC) systems. The partitioning behavior of cephalosporins in microemulsions was characterized calculating the capacity factor. The required parameters for the determination of the capacity factor (micro(aq) and micro-me are the electrophoretic mobilities of the solutes in the aqueous phase and the microemulsion phase, micro(eff) is the effective mobility in the microemulsion solution) were measured by EKC using cationic and anionic microemulsion systems consisting of the surfactants/n-heptane/1-butanol/10 mM phosphate buffer solution, pH 7.0. Electrokinetic chromatography was shown to be a useful method to quantify the partitioning behavior of drugs in oil/water microemulsion. The logarithm of the capacity factor was correlated with the logarithm of the 1-octanol/water partitioning coefficients.

Cephalosporins↗

Separation of etoposide phosphate and methotrexate by capillary zone electrophoresis using UV detection with a high sensitivity cell.

Etoposide phosphate and methotrexate are important anti-tumor chemotherapeutic agents. Our previously presented capillary zone electrophoresis (CZE) method using a high sensitivity cell (Z-cell) for quantitative analysis in biological media (urine, plasma) showed good precision and accuracy. The present results show that the investigation using a capillary with high sensitivity cell led to an approximately 10-fold improvement of the detection limit compared to standard capillaries. Plasma and urine samples were analyzed by using a calibration curve for drug concentrations between 0.1 and 100 microg/mL. Good detection limits and good relative standard deviations of the migration times and of the peak areas were observed in these experiments.

Antineoplastic Agents↗

Evaluation of the age-dependent development of lymphocyte surface receptors in children.

Components and functions of the immune system change during postnatal development, not only in the first years of life, but well through adolescence and even into adult life. These age-dependent changes within the immune system greatly complicate any attempt to assess pathological alterations of immunologic variables in children. The need for studies on possible substance-induced changes, including risk assessment of environmental chemicals, has increased the necessity to establish reference ranges for certain immunologic variables against which an abnormal developmental status can be evaluated. In the present study age-related changes of surface receptors on peripheral white blood cells were studied in 82 children, aged between 2 months and 17 years. The blood samples were triple labeled with monoclonal antibodies followed by a whole blood lysis technique and were subsequently analyzed by flow cytometry. Complex statistical analyses were performed in order to determine probability ranges for some immunological variables. In this paper we describe the age-dependent development of components involved in major maturational processes, including the appearance and varying expression of adhesion receptors (CD11a, CD18, CD28, CD29, CD44, CD49d and CD54) on CD4+ "helper" cells and CD8+ "suppressor and cytotoxic" cells. A clear-cut increase of high epitope density expression of the integrins on both CD4+ and CD8+ cells was noted. These results suggest that the components of immune T cells for performing adhesion by interacting with other cells and many matrix components are largely acquired during postnatal development. Maximal levels of adhesion receptor expression are reached at different ages depending on the specific T cell subpopulation.

Adolescent↗

On mathematical modeling of dermal and transdermal drug delivery.

This paper deals with two extensions of diffusion models for the drug delivery process into human skin in order to give a more realistic approach. As one extension several penetrating substances formulated within a vehicle are considered for modeling the case of an applied drug and some penetration modifiers (enhancers and reducers, respectively). A coupling via concentration-dependent diffusivities between the diffusion equations of the involved substances is used to model the dependencies between them. Furthermore, a moving boundary problem for the diffusion equation of the drug delivery process is developed to describe the time-dependent maximum penetration depth of each penetrant marked by a movingboundary. On this basis a model is developed that can predict both the concentration profile and the position of the penetration boundary depending on time. Both concepts are described on a two-dimensional multilayered domain representing a cross section through human skin. The model equations are solved by exploiting a suitable numerical discretization method.

Administration, Cutaneous↗

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↗

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↗

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↗

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↗