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Biomedical subjects

R Bauer

Publications and source records attributed to R Bauer.

At least 127 records · Page 7Linked to original sources

[Calculation of renal clearance by dynamic measurement of excreted activity].

AIM: In this paper we present a new method to measure the renal slope-clearance of Tc-99m-MAG-3 in a single-shot model (Excretion-clearance). METHODS: A renal scintigraphy with Tc-99m-MAG-3 was performed in 22 patients. The excreted activity of the tracer in the kidneys and the bladder was dynamically measured using a double-head gamma-camera. Additionally the total absorption over the kidneys and the bladder was determined. The Excretion-clearance was calculated in a differential and an integral variant. Simultaneously the 2-compartment-clearance (Sapirstein-clearance), the Oberhausen-clearance and the Bubeck-clearance were calculated. RESULTS: The Sapirstein-clearance is considered as the "gold standard" in a single-shot model. The correlation of the Bubeck-clearance and the Oberhausen-clearance ranged from r = 0.96 to r = 0.97, the Excretion-clearance (differential-method) correlated with r = 0.90. The absolute difference of the clearance-values was lowest comparing the Bubeck-clearance with the Sapirstein-clearance with an average difference of 11%, whereas the Excretion-clearance revealed at least an average difference of 21% and the Oberhausen-clearance of 24%. DISCUSSION: The Excretion-clearance requires a more complicated protocol measuring the clearance in comparison to the Bubeck-clearance. The results of the excretion-clearance differ more from the Sapirstein-clearance with regard to the examined patient population than the Bubeck-clearance. Regarding the theoretical basis of the methods, we expect advantages of the Excretion-clearance compared with the Bubeck-Clearance in patients with compartmental disproportion or with a low clearance. We are going to prove this in combination with the above mentioned methodical improvements in a further study.

Adult↗

[Extract of the Echinacea purpurea herb: an allopathic phytoimmunostimulant].

In Northamerican folk medicine Echinacea purpurea L. Moench (purple coneflower) was used as a medicinal plant. Nowadays various formulations containing stabilized or dried pressed juice from Echinacea purpurea as an active ingredient are often administered to treat common colds. These preparations are very well tolerated and safe. Allergic reactions, mainly reversible skin reactions, may occur especially in persons showing hypersensibility after contact with plants from the Compositae family. Pharmacological data let assume purple coneflower pressed juice preparations stimulate the innate immune system and increase the resistance to common colds. In this context the stimulation of the oxidative burst as well as the modulation on monokine secretion by the pressed juice of purple coneflower are reviewed. Also relevant clinical studies are presented concerning the treatment of infections respectively of common cold.

Adjuvants, Immunologic↗

Mono- and binuclear Zn-beta-lactamase from Bacteroides fragilis: catalytic and structural roles of the zinc ions.

The Bacteroides fragilis Zn-beta-lactamase is active with a mono- and a binuclear zinc site. The apoenzyme produced by removal of both Zn ions does not recover full activity upon readdition of Zn2+ in contrast to an active mono-Zn form prepared at pH 6.0. Differences in k(cat) values observed are substrate-dependent implying distinct mechanisms for the mono- and binuclear species. The substrate profile of a Zn,Cd hybrid obtained by selective exchange of one zinc ion is different from that of the Zn2 enzyme with a remarkable 15-fold increased activity with cefoxitin as substrate.

Anti-Bacterial Agents↗

Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor.

The AP-2 family of transcription factors (AP-2alpha, AP-2beta and AP-2gamma) is temporally and spatially regulated in mammals and has also been implicated in oncogenesis. Here we report the isolation of genomic and cDNA clones encoding the Drosophila homologue of AP-2, designated DAP-2. The predicted amino acid sequence exhibits 42-45% overall identity with the vertebrate AP-2 proteins. A sequence of 107 amino acids within the DNA binding and dimerization domain of the vertebrate AP-2 proteins is highly conserved (90-92%) with the DAP-2 homologue. An in vitro translation product of DAP-2 cDNA binds specifically to AP-2 consensus binding sites. DAP-2 was also shown to be functionally conserved in vivo because transient transfection of a DAP-2 expression plasmid activated transcription through AP-2 binding sites in both mammalian and Drosophila cell lines. DAP-2 is expressed during early embryogenesis and DAP-2 transcripts are also detected in the adult. Whole-mount in situ hybridizations demonstrated that DAP-2 is expressed initially at stage 9 of Drosophila embryonic development and that DAP-2 transcripts are detected in regions of the brain, eye-antennal disc, optical lobe, antenno-maxillary complex, and in a subset of cells of the ventral nerve cord. The cloning of DAP-2 and the identification of the DAP-2 expression pattern during embryogenesis provides a starting point to address the function of AP-2 during differentiation and development in a well understood model system.

Amino Acid Sequence↗

Vestibular caloric responses and behavioral state in the fetal sheep.

Functional activity of the vestibular system in relation to behavioral state of fetal sheep in utero was studied by cooling and heating of the fetal middle ear and skin (control) with implanted copper-tube heat exchangers. Eye movements and fetal cortical activity were assessed before, during, and after 2 min irrigations with water at 6, 46, or 39.5 degrees C (isothermic). Cold water induced slow-phase eye movements toward the irrigated ear followed by saccades toward the opposite ear after a delay of several seconds. The direction of the response reversed with warm water, and saccades were absent during irrigation with body-temperature water. Cold-water irrigations of the skin over the jaw did not result in nystagmus. Arousal-like responses were elicited with thermal stimulation of the ear or facial skin while the fetus was in either rapid eye movement (REM) or non-REM states. Circulation of 39.5 degrees C water through the ear also produced arousal-like responses, possibly due to turbulence-induced noises in the heat exchanger or slight deviations between the irrigation temperature and the actual fetal inner ear temperature. These results suggest that mechanisms responsible for saccade suppression during depressed levels of consciousness (i.e. sleep) are inactive in utero. Fetal behavioral state responsiveness to vestibular and somatosensory thermal stimulation may be of great significance, especially in the premature neonate.

Animals↗

A Novel Approach to Turbidimetry of Dense Systems: An Investigation of the Enzymatic Gelation of Casein Micelles.

A novel approach to turbidimetry enabling the extraction of structural information about highly turbid systems has been developed. Turbidimetric spectra have been obtained in the wavelength region 500-1100 nm using an acceptance angle of 1 degrees for detecting the transmitted light. It is demonstrated that the influence of multiple scattering can be eliminated by measurement of turbidimetric spectra at several sample thicknesses and subsequent extrapolation to zero thickness. The validity of this method is demonstrated by Monte Carlo simulations of multiple scattering of light using simple Rayleigh-Debye-Gans theory. The simulations demonstrate that turbidimetric spectra are very insensitive to multiple scattering measured with an acceptance angle of 1 degrees when the particles are smaller than about 1 µm. It was further shown that no shape information can be derived from turbidimetric spectra under our condition for objects having diameters up to 6 µm. The turbidimetric spectra of casein aggregation/gelation have been fitted by modeling the aggregates either as homogeneous spheres or as fractals. The turbidimetric averaged mean radii found using the sphere model are at all stages of the process consistently smaller than radii found by either static or dynamic light scattering. This is found to be a consequence of the angular integration involved in turbidimetry which weights larger radii less than in the case of light scattering. Copyright 1998 Academic Press.

Journal Article↗

Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia.

Amino Acids↗

[Hereditary angioedema in the German-speaking region].

A multicentre, retrospective study of hereditary deficiency of C1-esterase inhibitor (C1-INH) function, a deficiency which clinically manifests as hereditary angioedema (HAE), was performed in six centres in Germany, Austria and Switzerland. 242 individuals were registered with proven functional or quantitative deficiency of C1-INH who belonged to kindered with disease manifestation in 2 to 6 generations. Considering the total population in the three countries and the number of registered individuals, a frequency of the deficiency of 0.02 x 10(-4) was calculated. As this epidemiological study involved only 6 centres, a 10 to 100 times higher frequency of C1-INH deficiency is estimated to be a more realistic value. Out of the 242 registered individuals 110 were evaluated for type and location of clinical manifestation of the deficiency, the laboratory data and the therapy outcome. 86 (78.2%) of the patients belonged to the "common type" and 24 (21.8%) to the "variant type" of HAE. In 53.9% of the cases first manifestation of the disease was before the age of 20 years. In only 3.9% of the patient population did the disease begin after 40 years of age. A mean time lag of 5,3 years was observed, between the first manifestation and correct diagnosis. Initial diagnosis was correct in only 31.8% of the cases of which dermatologists provided 51.7%. False diagnoses include urticaria (41.3%), allergy (20%), acute abdomen (18.7%), angina (8%), rheumatoid disease (5.3%) and intracranial haemorrhage, CNS tumour, epilepsy, migraine (5.3%). The distribution pattern of HAE resembled that of intolerance reactions and pseudoallergies. Urticarial lesions were not associated with C1-INH deficiency. 24% of the patients had at least one episode of laryngeal edema. 40% of patients were unable to identify a trigger of edema formation. The others indicated as triggers trauma, hormonal changes, mental stress, insect stings and in a few cases food and drugs. Menstruation and oral contraceptives aggravated or made disease manifestations more frequent. In contrast, during pregnancy in many cases clinical manifestations improved and delivery posed no problems. The possibility of HAO is very much suggested by the tailure of edema to respond to classical anti-allergic therapy. Therapy of choice of acute attacks is C1-INH concentrate. No side reactions, antibody formation or virus transmission have been observed. For long term prophylaxis danazol, an attenuated androgen, or tranexamic acid, a protease inhibitor, was chosen. The daily dose of danazol should be kept as low as possible because of its anabolic, anti-estrogenic, anti-gestagenic, and anti-gonadotropic effects. Indeed, adverse reactions were observed in 41.7% of patients receiving danazol. Frequencies of adverse reactions were twice as common in women as in men. Adverse reactions were dose dependent and reversible except for one woman with irreversible deepening of her voice. Measuring C1r is a effective way to assess C1-INH function and monitor therapy.

Adolescent↗

[ANCA-positive lupus erythematodes profundus. Successful therapy with low dosage dapsone].

A 44-year-old male patient with lupus erythematosus profundus (lupus panniculitis) (LEP) of the right cheek/infraorbital region presented as a recurrent swelling. He had only anti-neutrophil-cytoplasmic antibodies (ANCA), which have not been previously described in association with LEP. There was no indication of systemic lupus erythematosus. While chloroquine produced no benefits, the skin lesions promptly cleared with dapsone. Step by step we reduced dapsone to a final dose of 50-75 mg per week. The ANCA titer decreased in parallel to the clinical improvement.

Adult↗

Management of cutaneous lupus erythematosus with low-dose methotrexate: indication for modulation of inflammatory mechanisms.

There is no consensus about an effective and safe treatment for patients with cutaneous lupus erythematosus (LE) who are refractory to antimalarials and/or low-dose oral glucocorticosteroids. Therefore, we retrospectively analyzed the clinical data and laboratory findings of 12 patients who received weekly administrations of 10-25 mg methotrexate (MTX). Previous treatment with antimalarials and/or glucocorticosteroids was not effective or had to be withdrawn because of side effects. Of 12 patients, ten showed improvement of their skin lesions; two patients did not respond to low-dose MTX; two patients cleared rapidly, and five other patients had long-lasting remissions of 5-24 months after stopping MTX treatment. A reduction of circulating autoantibodies was detected in five patients. In all patients, MTX was well tolerated subjectively and objectively. Weekly low-dose MTX is useful for the treatment of cutaneous LE, particularly in those cases which need long-term treatment and/or do not respond to standard therapeutic regimens.

Administration, Oral↗

Phenylpropanoids and flavonoid glycosides from Lysionotus pauciflorus.

A new phenylpropanoid glycoside, alpha-(3,4-dihydroxyphenyl)ethyl-(2'-O-alpha-L-rhamno-pyranosyl- 3'-O-beta-D-apiofuranosyl-4'-O-E-caffeoyl)-beta-D-glucopyran oside, verbascoside, and two new flavone glucosides, nevadensin 7-O-beta-D-glucoside and nevadensin 7-O-[alpha-L-rhamnosyl(1-->6)]-beta-D-glucoside, have been isolated from the aerial parts of Lysionotus pauciflorus. The structures have been elucidated on the basis of spectroscopic data and chemical correlation.

Carbohydrate Sequence↗

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.

Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.

Animals↗

Cardiovascular function and brain metabolites in normal weight and intrauterine growth restricted newborn piglets--effect of mild hypoxia.

In order to clarify the influence of intrauterine growth restriction on systemic hemodynamics, catecholamine response, and regional distribution of brain energy metabolites per se and during mild hypoxic episodes a study was performed in thirty newborns with a well-characterized state of intrauterine and intra-natal development. Thirty animals were divided into fifteen normal weight piglets (NW) and fifteen intrauterine growth restricted (IUGR) piglets according to their birth weight. Category "NW" covered animals with a birth weight of > 40th percentile; IUGR category covered animals with a birth weight of > 5th and < 10th percentiles. Animals were anesthetized with halothane in 70% nitrous oxide and 30% oxygen and after immobilization artificially ventilated. The acid-base balance and blood gas values at baseline conditions were similar within the different groups investigated and consistent with other data obtained from anesthetized and artificially ventilated newborn piglets. Mild hypoxic hypoxia which was induced by lowering the FiO2 from 0.35 to 0.15 resulted in reduced arterial pO2 (NW: from 115 +/- 37 mmHg to 39 +/- 7 mmHg; IUGR: from 117 +/- 23 mmHg to 39 +/- 3 mmHg; p < 0.05), but arterial pH and pCO2 remained unchanged. Under baseline conditions arterial blood pressure, cardiac output, and myocardial contractility, expressed as dp/dt(max) and plasma catecholamine values were similar in all groups studied. Heart rate was slightly increased in IUGR (p < 0.05). Mild hypoxia led to a strong increase of myocardial contractility in NW as well as IUGR piglets to 2.4 and 2.7 fold and remained increased during recovery (p < 0.05). Moreover, total peripheral resistance was enhanced at the end of recovery period in IUGR animals (p < 0.05). There was a significant increase of epinephrine (E) in NW animals in comparison to sham-operated animals (p < 0.05). Interestingly, during reoxygenation the further increase in E and norepinephrine (NE) levels were enhanced in the animals which suffered from mild hypoxia (p < 0.05). Regional distribution of brain tissue metabolites was partly affected by intrauterine growth restriction. In particular, brain tissue glucose content was strongly reduced by 65 to 72 per cent in all brain regions investigated. Mild hypoxia led to an increase of about 30 percent in NW animals (p < 0.05). In IUGR piglets the percentage increase of brain glucose content was on an average more pronounced but with considerably higher variance. Also, a strong increase of brain lactate content appeared here (p < 0.05). In contrast, brain tissue ATP was quite similar in all groups studied, but brain creatine phosphate was significantly reduced in some forebrain structures of IUGR piglets after mild hypoxia (figure 2, p < 0.05). In summary, this investigation provides information on cardiovascular functions and brain metabolites of normal weight and naturally occurring growth restricted newborn piglets. Mild hypoxemia was well-tolerated from both animal groups. It is suggested that lactate may play a significant role as a source for brain energy production in the newborn IUGR piglets.

Animals↗

Influence of hypoxia and hypoxia/hypercapnia upon brain and blood peroxidative and glutathione status in normal weight and growth-restricted newborn piglets.

Glutathione (reduced (GSH) and oxidized (GSSG)), lipid peroxidation products (TBAR) and in vitro production of reactive oxygen species (ROS, by means of stimulated lipid peroxidation, H2O2 formation and amplified chemiluminescence (CL) in 9000 xg brain supernatants) were studied in the cerebellum (C) and temporoparietal area (TP) of the brain of normal weight (NW) and spontaneously intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour hypoxia (fractional inspired oxygen concentration (FiO2) 8%), and in combination with 10% CO2, followed by 3 hours recovery (FiO2 30%). The strong GSH depletion accompanied by an increased concentration of GSSG and TBAR, more distinct in IUGR, is the most important result in the brain after hypoxia and reoxygenation. Hypercapnia-related acidosis seems to protect the brain of IUGR from hypoxia/reoxygenation induced injury by reducing GSH depletion as well as GSSG and TBAR increases. But stimulated lipid peroxidation and H2O2 formation in 9000 xg supernatants of C and TP were found to be higher in acidosis and hypercapnia. Decreased or unchanged amplified CL, demonstrating lower in vitro production of ROS, cannot explain the GSH depletion after hypoxia and reoxygenation. The scarce changes in erythrocyte GSH and GSSG as well as plasma TBAR concentrations did not reflect the findings in the brain. Nevertheless, the changes in the brain support the hypothesis that oxidative stress plays a role in neuronal damage after hypoxic stress, but the brain of IUGR did not reveal a special response to moderate hypoxia.

Acid-Base Equilibrium↗

Influence of hypoxia and hyperthermia upon peroxidative and glutathione status in growth-restricted newborn piglets.

Normal weight (NW) and spontaneously intra-uterine growth-restricted newborn piglets (IUGR) were submitted to 1 hour hypoxia and hyperthermia followed by 3 hours reoxygenation. Glutathione (GSH, GSSG), lipid peroxidation products (TBAR) and cytochrome P450 dependent production of reactive oxygen species were studied by determination of H2O2 production and amplified chemiluminescence (CL) in brain and peripheral organs of NW and IUGR. A severe decrease of GSH was accompanied by enhanced H2O2 formation and lipid peroxidation in the brain of both NW and IUGR after hypoxia/hyperthermia and reoxygenation. In the other organs studied, only muscles showed enhanced lucigenine amplified CL and TBAR production. Nearly the same results in NW and IUGR reveal no higher risk of IUGR.

Animals↗

Body weight distribution and organ size in newborn swine (sus scrofa domestica) -- a study describing an animal model for asymmetrical intrauterine growth retardation.

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

Animals↗