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Biomedical subjects

U Hoppe

Publications and source records attributed to U Hoppe.

At least 55 records · Page 3Linked to original sources
PubMed1997

Regulation of cholinesterase gene expression affects neuronal differentiation as revealed by transfection studies on reaggregating embryonic chicken retinal cells.

In the embryonic chicken neuroepithelium, butyrylcholinesterase (BChE) as a proliferation marker and then acetylcholinesterase (AChE) as a differentiation marker are expressed in a mutually exclusive manner. These and other data indicate a coregulation of cholinesterase expression, and also possible roles of cholinesterases during neurogenesis. Here, both aspects are investigated by two independent transfection protocols of dissociated retina cells of the 6-day-old chick embryo in reaggregation culture, both protocols leading to efficient overexpression of AChE protein. The effect of the overexpressed AChE protein on the re-establishment of retina-like three-dimensional networks (so-called retinospheroids) was studied. In a first approach, we transfected retinospheroids with a pSVK3 expression vector into which a cDNA construct encoding the entire rabbit AChE gene had been inserted in sense orientation. As detected at the mRNA level, rabbit AChE was heterologously overexpressed in chicken retinospheroids. Remarkably, this was accompanied by a strong increase in endogenous chicken AChE protein, while the total AChE activity was only slightly increased. This increase was due to chicken enzyme, as shown by species-specific inhibition studies using fasciculin. Clearly, total AChE activity is regulated post-translationally. As an alternative method of AChE overexpression, transfection of spheroids was performed with an antisense-5'-BChE vector, which not only resulted in the down-regulation of BChE expression, but also strongly increased chicken AChE transcripts, protein and enzyme activity. Histologically, a higher concentration of AChE protein (as a consequence of either AChE overexpression or BChE suppression) was associated with an advanced degree of tissue differentiation, as detected by immunostaining for the cytoskeletal protein vimentin.

Animals↗
PubMed1996

[Speech-specific cortical potentials--methodologic aspects and initial clinical results].

BACKGROUND: The purpose of this study was to find out whether specific cortical potentials can be evoked and identified after word stimulation. The clinical relevance was to be investigated in patients with aphasic syndromes. MATERIALS AND METHODS: In 20 young adults with no signs of hearing impairment and in patients with manifest aphasic syndromes, word-evoked cortical potentials were compared with those after an equivalent noise stimulus. The test words were selected from the Freiburger Speech Comprehension Test. The duration of the words was between 450 and 640 ms. The stimulus was presented monaurally. The peak level was 70 dB HL. The noise stimulus was produced by modifying a low-band noise. Potentials were measured between the ipsilateral mastoid and the contralateral forehead. Data were analysed offline. RESULTS: In healthy persons, the potentials after word and noise stimulation did not differ until 100 ms after the stimulus onset. After noise stimulation a negative maximum could be seen 100 ms after the stimulus onset, and a positive maximum 200 ms after the stimulus onset. After word stimulation, a positive maximum of higher amplitude than after noise stimulation was measured 150 ms after the stimulus onset, and a negative maximum was measured 270 ms after the stimulus onset. In all test persons the difference curve of word-and noise-evoked potentials revealed a speech-specific component 170 ms (N 170) after the stimulus onset. The single-word analysis showed that the potentials depend on the phonemes of the test word. The potentials do not alter when the stimulus side is changed. In patients with aphasia the potentials depend on the grade of the disturbance of speech perception: global and Wernicke's aphasia show no significant difference of speech-and noise-evoked potentials, whereas in Broca's aphasia a speech specific maximum is apparent. CONCLUSION: The speech-specific component may be regarded as a paradigm of cortical speech detection processes. Electrophysiological speech audiometry by means of word-evoked cortical potentials seems possible and may be used for clinical purposes.

Adult↗
PubMed1996

The use of ambulatory blood pressure monitoring to evaluate antihypertensive drugs for drug approval.

So far, the contribution of clinical studies using ambulatory blood pressure monitoring in the registration of a new antihypertensive agent for marketing authorization purposes has been limited. However, pre-registration studies can be particularly useful, especially to study dose and dose interval in relation to peak: trough ratio during phase II and to facilitate comparison with other antihypertensive agents during phase III of the development of a new antihypertensive agent. More attention should be paid to their design and implementation as high standards are recommended. If properly studied, ambulatory blood pressure monitoring could fulfil a major role in the registration process of a new antihypertensive agent.

Journal Article↗
PubMed1995

Texture analysis of the surface of the human skin.

The roughness parameters known from surface engineering often used to describe the microtopography of the surface of the skin do not, by definition, take into account the two-dimensional relationships of the stratum corneum. An approximate description of these relationships can be obtained by scanning several radial profile sections. A more detailed analysis of the characteristic surface relief of the skin can also be based on the texture parameters used to characterize many natural structures. These types of parameters can be extracted from the gray level images of an impression of the surface of the skin--a replica--that has been magnified under a microscope, photographed with a CCD camera and subsequently subjected to image analysis by a digital computer. The purpose of this study is to determine not only the usefulness of texture parameters for describing the morphology of the surface of the human skin but also whether, for example, cosmetically treated skin can be detected by means of texture analysis.

Cosmetics↗
PubMed1993

[Brain abscess in congenital cyanotic heart defect in adulthood].

A 27-year-old patient with pulmonary atresia, ventricular septal defect, and multifocal lung-perfusion suddenly developed headache and left facial sensory disturbances. Using computed tomography and magnetic resonance imaging a temporo-parietal brain abscess was diagnosed. After abscess aspiration and antibiotical therapy neurological signs disappeared immediately and the patient could leave hospital without any neurological deficit. Adult patients with congenital cyanotic heart disease are at risk to develop a brain abscess which should therefore be ruled out if headache, fever of unknown origin or focal neurologic signs occur.

Adult↗
PubMed1993

Comparison of fluorescence polarisation immunoassay (FPIA) and high performance liquid chromatography (HPLC) methods for the measurement of flecainide in human plasma.

The precision and accuracy of HPLC and FPIA for the measurement of flecainide plasma levels were compared below, in and above the therapeutic range (200-1,000 ng/ml). Following a calibration crossover study, five standard plasma solutions of varying flecainide concentrations (SPS) and 99 flecainide containing plasma samples of 24 in-patients (IPS) were analyzed with both methods. The results show that within the range of approximately 500-1,500 ng/ml, the two methods did not differ in either precision (expressed as coefficient of variation, CV) or accuracy (expressed as relative error, RE). Close to the lower limit and below the therapeutic range however, HPLC provided greater precision and accuracy than FPIA.

Chromatography, High Pressure Liquid↗
PubMed1991

A monoclonal antibody against the sulfidopeptide leukotrienes LTC4, LTD4 and LTE4.

A monoclonal antibody (1A-LDR1) against sulfidopeptide leukotrienes (LT) is described. The mAb shows a nearly identical detection limit of about 0.04 ng for LTC4, LTD4, LTE4 and NacLTE4 in standard fluid phase RIA. Steric modifications, however, diminish the sensitivity, as determined for the examples 5-epi-LTC4, 6-epi-LTC4, 5,6-epi-LTC4 and 11-trans-LTC4. No crossreactivity could be observed for LTB4. Crossreactions with components of the LT peptide chain such as L-cysteine or glutathione, as well as with arachidonic acid, were not detectable. In assessing the accuracy of the LT-RIA, recovery experiments with supernatants of mouse peritoneal macrophages and incubates of gastric mucosa showed a good correlation of r = 0.993 and 0.990, respectively. Results of an inhibition experiment with mouse peritoneal macrophages, incubated with several concentrations of indomethacin and nordihydroguaiaretic acid (NDGA), support the reliability of RIA and ELISA. The new LT-mAB allows an almost complete detection of peptide leukotrienes in one assay.

Animals↗
PubMed1991

Elimination of flecainide as a function of urinary flow rate and pH.

In order to evaluate the influence of urinary flow rate at different pH values on the pharmacokinetics of the basic antiarrhythmic drug flecainide 7 healthy men received 50 mg flecainide under 4 different conditions: 1. acidic urine (pH 5) and a high fluid load (125 ml.h-1) 2. acidic urine (pH 5) and a low fluid load (25 ml.h-1) 3. alkaline urine (pH 8) and a high fluid load (125 ml.h-1) 4. alkaline urine (pH 8) and a low fluid load (25 ml.h-1) At acidic pH the half-life, the amount of unchanged drug in the urine (Ae), renal clearance (CLR) and area under the curve (AUC) were independent of the fluid load. At alkaline pH Ae (5.8 vs 2.6 mg) and CLR (73 vs 33 ml.min-1) were significantly affected by fluid load (high vs low), whereas half-life and AUC were not different (15.7 vs 16.0 h, 1480 vs 1540 ng.ml-1.h). When comparing acidic and alkaline urinary pH conditions, half-life, Ae, CLR, and AUC were different. For a high fluid load the values at acidic vs alkaline pH were half-life 10.0 vs 15.7 h; Ae 15.9 vs 5.8 mg; CLR 288 vs 73 ml.min-1; AUC 976 vs 1480 ng.ml-1.h. For a low fluid load the corresponding values at acidic vs alkaline pH were half-life 10.1 vs 16.0 h; Ae 15.9 vs 2.6 mg; CLR 267 vs 33 ml.min-1; AUC 1045 vs 1540 ng.ml-1.h. It is concluded that urinary pH affects flecainide pharmacokinetics independently of urinary flow rate, and that a high flow enhances the elimination of flecainide only with an alkaline urine. This effect of flow rate does not appear to be of clinical relevance.

Ammonium Chloride↗
PubMed1991

In vitro methods for the assessment of primary local effects of topically applied preparations.

Three 'alternative' methods for the screening of the primary irritation potentials of topically applied preparations and raw materials are presented as a test battery and their in vitro endpoints are compared with in vivo data. The first method is the intermediate test on the chorioallantoic membrane of hens' fertilized eggs, which is generally proposed for the prediction of the irritation potential of chemicals. Relevant test parameters, such as the time-dependent appearance of hemorrhages, vascular lysis and coagulation, are used to classify the test substances. Secondly, cytotoxicity tests with Balb/c 3T3 fibroblasts are used to characterize the influence of test materials on cellular homeostasis and viability, which is quantified by the dose-dependent uptake of Neutral red. As a second parameter changes in the cellular protein level can be easily measured by subsequent staining with Kenacid blue. Finally, the third approach to in vitro evaluation is presented in the form of the red blood cell assay, a rapid photometric assay which permits distinguishing basically between damage to the membrane and to proteins as endpoints which correlate with lesions observed on the conjunctiva, iris and cornea in the eye and the acute inflammatory responses evoked during epicutaneous irritancy testing. Changes in the optical behavior of oxyhemoglobin are used as the inherent indicator for monitoring both endpoints and their interrelations. These methods are proposed and can be used advantageously for testing newly developed topical preparations and their ingredients in view of their local irritation potential without further use of animal testing. Moreover, they can also be used for screening chemicals.

Administration, Topical↗
PubMed1990

[Modern cosmetic agents and evidence of their function].

Fluorometers modified by quartz light conductors allow the recording of the skin-intrinsic fluorescence. Signals assigned to the aromatic amino acids permit a prognosis concerning the sensitivity of untreated skin to light and the sunscreen factor to be expected after the application of UV filters. We discuss the microdistribution and skin penetration of UV filters and describe the utilization of the image analysis technique both for the count and size determination of fluorescent sebaceous glands and for the quantification of the effects of antiperspirants. Based both on the selective increase of efficacy of deodorant soaps, analytically controlled, and on the differences of the deodorizing effects found in various test groups, we discuss the possibilities of improving deodorants.

Acne Vulgaris↗
PubMed1990

Standardization of an in vitro red blood cell test for evaluating the acute cytotoxic potential of tensides.

A new bovine red blood cell (RBC) test is presented as a biological in vitro assay for rapid assessment of the membrane and protein damaging effects of tensides. The system uses the hemoglobin released during RBC damage as an indicator to determine quantitatively the concentration at which the tensioactive agents affect and disrupt the plasma membrane. The spectrophotometric assay also considers the denaturation of hemoglobin caused by high concentrations of the tensides. Thus besides the halfmaximal concentrations to cause hemolysis (H50), a denaturation index (DI in %) can be determined for each test agent. The RBC assay was validated by assessing the H50 and DI for 30 randomly selected tensioactive agents from various sources and comparing the in vitro effects with their local irritant activity as assessed by the Draize test in the conjuntiva of conscious rabbits. The relationship between H50 and DI values, expressed as the lysis/denaturation ratio, was found to give a ranking order that best characterized the membrane damaging potency of the agents tested. Tensides known to possess ocular irritancy in the Draize test were characterized by a low lysis/denaturation ratio.

Animals↗
PubMed1988

Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C4 and prostanoid release: relation to ethanol-induced injury.

1. The effects of oral and subcutaneous administration of the non-steroidal anti-inflammatory drugs sodium salicylate, aspirin and indomethacin on ex vivo gastric mucosal release of leukotriene C4 (LTC4) prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) were investigated in rats under basal conditions as well as after challenge with ethanol. 2. Basal release of PGE2, 6-oxo-PGF1 alpha and TXB2 was inhibited by oral administration of aspirin (0.6-400 mgkg-1) and indomethacin (4 or 20 mgkg-1), but not by sodium salicylate (up to 400 mgkg-1), in a dose-dependent manner. Oral administration of aspirin in the dose range 3.2-400 mgkg-1 and of indomethacin (20 mgkg-1) additionally inhibited release of LTC4, while sodium salicylate (up to 400 mgkg-1) had no effect. Indomethacin (20 mgkg-1) and aspirin (400 mgkg-1) administered subcutaneously inhibited generation of cyclo-oxygenase products of arachidonate metabolism, but did not significantly affect LTC4 synthesis. 3. Oral instillation of ethanol caused gastric mucosal damage and simultaneously induced a selective increase in the ex vivo release of LTC4 from rat gastric mucosa, while release of cyclo-oxygenase products of arachidonate metabolism was not significantly affected. Oral pretreatment of rats with sodium salicylate protected the gastric mucosa and simultaneously inhibited the ethanol-stimulated gastric mucosal LTC4 release in a dose-dependent manner. Sodium salicylate had no effects on the release of PGE2 and TXB2, while that of 6-oxo-PGF1 alpha was slightly increased. 4. Pretreatment with indomethacin (4 or 20mg kg- p.o.) or aspirin in doses up to 25mg kg-1 p.o. prior to oral instillation of ethanol did not inhibit gastric mucosal damage and had no effect on the stimulatory action of ethanol on LTC4 release. Higher doses of aspirin (100mgkg-1 or 400mgkg-1 p.o.) reduced the mucosal damaging effect of ethanol and simultaneously inhibited LTC4 release. 5. The results suggest that aspirin and indomethacin in concentrations higher than those necessary to inhibit the cyclo-oxygenase pathway of arachidonate metabolism additionally inhibit gastric mucosal LTC4 synthesis under basal conditions, while sodium salicylate has no such effect. On the other hand, sodium salicylate, but not indomethacin or low doses of aspirin (up to 25mg kg 1), by an unknown mechanism inhibits stimulation of LTC4 biosynthesis by ethanol and simultaneously protects the gastric mucosa against ethanol-induced damage. Similar effects of high oral doses (> 100mgkg- 1) of aspirin might be due to significant formation of salicylate. These results suggest that there is a causal relationship between enhanced LTC4 biosynthesis and the development of ethanol-induced gastric injury.

Animals↗
PubMed1987

Polyneuropathy in Waldenström's macroglobulinaemia. Passive transfer from man to mouse.

To support the hypothesis of an immunopathogenesis of polyneuropathy in Waldenström's macroglobulinaemia (MW), serum IgM fractions of MW patients were applied intraperitoneally to mice for 17 days. Sections of liver, kidney, M. glutaeus maximus, central nervous system (CNS) and both Nn. ischiadici were examined for IgM, IgG, C3 and as control IgD with PAP-immunostaining. IgM deposits were found in every organ except the CNS. In peripheral nerves larger amounts were visualized in perineurium and endoneural space, whereas myelin lamellae and periaxon did not stain. Therefore, perhaps our investigation reveals a greater permeability of the blood-nerve barrier (BNB) compared with the blood-brain barrier (BBB). The involvement of the monoclonal IgM of MW, which has been shown to react in vitro with peripheral nerve constituents, appears possible in the pathogenesis of polyneuropathy.

Animals↗