Search PubMed⌕ Search

Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 145 records · Page 8Linked to original sources
PubMed1995

Role of the paracrine liver endothelin system in the pathogenesis of CCl4-induced liver injury.

This study analyzed if the paracrine liver endothelin system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar Kyoto rats were divided into four groups: a bosentan (mixed endothelin ETA and ETB receptor antagonist) treated group with CCl4 intoxication, a vehicle treated group with CCl4 intoxication, a nontreated control group and a bosentan treated control group. Hepatotoxicity was assessed by determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) followed by histopathological examinations. Tissue endothelin-1 concentrations and expression of endothelin receptor subtypes were analyzed. The tissue levels of endothelin-1 in the liver of rats with CCl4 intoxication were significantly higher than those in normal rats. Scatchard analysis revealed no differences in the density and binding constant of endothelin ETA and ETB receptor between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in a significant protection against elevation of ALT, AST, LDH and bilirubin. Histopathological examination of live sections for necrotic, swollen and lipid-laden cells revealed findings that were in agreement with the serum enzyme data. In conclusion, this study showed that the paracrine endothelin system is involved in the pathogenesis of CCl4-induced hepatotoxicity and that the blockade of the stimulated liver endothelin systems reduces CCl4-induced liver injury.

Animals↗
PubMed1995

Hypoxia, a novel inducer of acute phase gene expression in a human hepatoma cell line.

Transcriptional regulation of gene expression by hypoxia is an important, but yet only marginally characterized mechanism by which organisms adapt to low oxygen concentrations. The human hepatoma cell line HepG2 is a widely used model for studying hypoxic induction of the hematopoietic growth factor erythropoietin. In an attempt to identify additional genes expressed in HepG2 cells during hypoxia, we differentially screened a cDNA library derived from hypoxic (1% O2) HepG2 cells using probes isolated from either normoxic (21% O2) or hypoxic cells. Two genes were identified, one encoding aldolase, a member of the glycolytic enzymes, and the other encoding alpha 1-antitrypsin which belongs to the family of the acute phase (AP) responsive proteins. Whereas hypoxic induction of glycolytic enzymes is well established, oxygen-dependent regulation of AP genes has not been reported so far. AP proteins are liver-derived plasma proteins whose production during inflammation is either up-regulated (positive AP reactants) or down-regulated (negative AP reactants). In the present study, we demonstrate that on the mRNA level hypoxic stimulation of HepG2 cells led to (i) an induction of the positive AP reactants alpha 1-antitrypsin, alpha 1-antichymotrypsin, complement C3, haptoglobin, and alpha 1-acid glycoprotein; (ii) a down-regulation of the negative AP reactant albumin; (iii) an up-regulation of the negative AP reactant transferrin; and (iv) unchanged levels of the positive AP reactants alpha- and beta-fibrinogen as well as hemopexin. Cycloheximide inhibited hypoxic up-regulation of AP mRNAs demonstrating that de novo protein synthesis is required for hypoxic induction. Nuclear run-on assays indicate that the hypoxic increase in AP mRNAs is mainly due to transcriptional regulation. The hypoxic response was compared to AP stimulation by interleukin 6. The results suggest that the adaptive response to hypoxia overlaps with, but is not identical with, the AP response mediated by interleukin 6.

Acute-Phase Proteins↗
PubMed1995

Modulation of erythropoietin formation by changes in blood volume in conscious dogs.

1. A possible influence of the filling of the circulatory system on the plasma concentration of erythropoietin, which is the major regulator of erythrocyte formation, was investigated in conscious dogs. 2. Over an experimental period of 5 h, the animals were subjected to either haemorrhage (hypovolaemia), blood volume expansion (hypervolaemia), or exchange transfusion of blood with dextran (isovolaemic anaemia). 3. A reduction of blood volume by 20% induced by haemorrhage increased plasma erythropoietin levels approximately 1.5-fold in the absence of significant changes in haematocrit. 4. An expansion of blood volume by 12% induced by an intravenous infusion of dextran did not change plasma erythropoietin levels, although the haematocrit decreased by 0.04. 5. A reduction of the haematocrit by 0.12 in the absence of changes in blood volume induced by an isovolaemic exchange transfusion (dextran vs. blood) increased plasma erythropoietin levels approximately 3-fold. 6. Total renal oxygen supply did not change in any of the three experimental protocols. 7. These data indicate that in dogs the erythropoietin production rate is modulated by changes in blood volume, and suggest a possible role of erythropoietin in the regulation of blood volume.

Anemia↗
PubMed1995

Negative feedback regulation of wild-type p53 biosynthesis.

When growth-arrested mouse fibroblasts re-entered the cell-cycle, the rise in tumour suppressor p53 mRNA level markedly preceded the rise in expression of the p53 protein. Furthermore, gamma-irradiation of such cells led to a rapid increase in p53 protein biosynthesis even in the presence of the transcription inhibitor actinomycin D. Both findings strongly suggest that p53 biosynthesis in these cells is regulated at the translational level. We present evidence for an autoregulatory control of p53 expression by a negative feed-back loop: p53 mRNA has a predicted tendency to form a stable stem-loop structure that involves the 5'-untranslated region (5'-UTR) plus some 280 nucleotides of the coding sequence. p53 binds tightly to the 5'-UTR region and inhibits the translation of its own mRNA, most likely mediated by the p53-intrinsic RNA re-annealing activity. The inhibition of p53 biosynthesis requires wild-type p53, as it is not observed with MethA mutant p53, p53-catalysed translational inhibition is selective; it might be restricted to p53 mRNA and a few other mRNAs that are able to form extensive stem-loop structures. Release from negative feed-back regulation of p53 biosynthesis, e.g. after damage-induced nuclear transport of p53, might provide a means for rapidly increasing p53 protein levels when p53 is required to act as a cell-cycle checkpoint determinant after DNA damage.

3T3 Cells↗
PubMed1995

Localization of specific erythropoietin binding sites in defined areas of the mouse brain.

The main physiological regulator of erythropoiesis is the hematopoietic growth factor erythropoietin (EPO), which is induced in response to hypoxia. Binding of EPO to the EPO receptor (EPO-R), a member of the cytokine receptor superfamily, controls the terminal maturation of red blood cells. So far, EPO has been reported to act mainly on erythroid precursor cells. However, we have detected mRNA encoding both EPO and EPO-R in mouse brain by reverse transcription-PCR. Exposure to 0.1% carbon monoxide, a procedure that causes functional anemia, resulted in a 20-fold increase of EPO mRNA in mouse brain as quantified by competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not influenced by hypoxia. Binding studies on mouse brain sections revealed defined binding sites for radioiodinated EPO in distinct brain areas. The specificity of EPO binding was assessed by homologous competition with an excess of unlabeled EPO and by using two monoclonal antibodies against human EPO, one inhibitory and the other noninhibitory for binding of EPO to EPO-R. Major EPO binding sites were observed in the hippocampus, capsula interna, cortex, and midbrain areas. Functional expression of the EPO-R and hypoxic upregulation of EPO suggest a role of EPO in the brain.

Animals↗
PubMed1995

Characterization of surface antigens of Eimeria nieschulzi (Sporozoa, Eimeriidae) merozoites.

Two surface antigens of Eimeria nieschulzi merozoites were characterized by monoclonal antibodies (Mcab) as follows: an antigen of 31 (reducing conditions), 25 and 31 kDa (nonreducing conditions), by Mcab A1F6; and an antigen of 52 and 30 kDa (reducing conditions) or 42 kDa (nonreducing conditions), by Mcab H7. The localization of the antigens in fluorescence and electron micrographs is presented. Despite being accessible to antibodies on live (nonpermeabilized) parasites, neither antigens were significantly labelled using lactoperoxidase radioiodination.

Animals↗
PubMed1995

Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined for its potential utility in the treatment of cocaine and opioid addiction. However, a clearly defined molecular mechanism of action for ibogaine's putative anti-addictive properties has not been delineated. Radioligand binding assays targeting over 50 distinct neurotransmitter receptors, ion channels, and select second messenger systems were employed to establish a broad in vitro pharmacological profile for ibogaine. These studies revealed that ibogaine interacted with a wide variety of receptors at concentrations of 1-100 microM. These included the mu, delta, kappa, opiate, 5HT2, 5HT3, and muscarinic1 and 2 receptors, and the dopamine, norepinephrine, and serotonin uptake sites. In addition, ibogaine interacted with N-methyl-D-aspartic acid (NMDA) associated ion and sodium ion channels as determined by the inhibition of [3H]MK-801 and [3H]bactrachotoxin A 20-alpha-benzoate binding (BTX-B), respectively. This broad spectrum of activity may in part be responsible for ibogaine's putative anti-addictive activity.

Animals↗
PubMed1995

Limited importance of a learned aversion in the hypophagic effect of interleukin-1 beta.

This study addressed the possible role of a learned aversion in the hypophagic effect of interleukin-1 beta (IL-1 beta) in the rat. Two repetitive intraperitoneal injections of IL-1 beta (2 micrograms/kg body weight = b.wt.) progressively reduced intake of a novel-tasting saccharin diet (SD) presented immediately after injection. When SD and the familiar diet were offered some days after an injection, SD selection was in some but not all trials reduced by IL-1 beta pretreatment. When SD was offered alone several days after an injection, SD intake was not affected by the initial pairing of SD presentation with IL-1 beta injection. In further experiments, the novelty of a flavor added to the diet fed immediately after injection proved to be crucial for the aversive effect of IL-1 beta, and enhanced its hypophagic effect. Finally, lesion of the area postrema and the adjacent nucleus of the solitary tract failed to affect the hypophagia induced by IL-1 beta (1 microgram/kg b.wt.). The results indicate that, under certain conditions, IL-1 beta can induce an aversion to the taste and flavor of the food consumed after injection. This aversive effect of IL-1 beta appears to be rather weak and is presumably not involved in the hypophagic effect of IL-1 beta under normal feeding conditions. It may however enhance IL-1 beta's hypophagic effect under certain conditions, for instance after repeated injections.

Animals↗
PubMed1995

Efficacy of six anthelmintics against luminal stages of Baylisascaris procyonis in naturally infected raccoons (Procyon lotor).

The efficacy of six anthelmintics against natural infections of Baylisascaris procyonis in raccoons (n = 7 per drug) was determined in a series of critical tests. The drugs were given via moist cat food as a single dose or once daily for three consecutive days. Raccoons treated with pyrantel embonate (1 x 20 mg base kg-1 bodyweight (bwt.)), ivermectin (1 x 1 mg kg-1 bwt.), moxidectin (1 x 1 mg kg-1 bwt.), albendazole (3 x 50 mg kg-1 bwt.), fenbendazole (3 x 50 mg kg-1 bwt.) or flubendazole (3 x 22 mg kg-1 bwt.) expelled 1-198, 2-24, 2-14, 3-80, 2-70, or 2-35 B. procyonis stages, respectively, within the faeces. No roundworm was detected in any raccoon at post mortem examinations 7 days after the end of treatment. These results suggest that any of the six anthelmintics can be used at the dose rates tested in a deworming programme for captive raccoons.

Albendazole↗
PubMed1995

[Effects of desflurane on liver microcirculation in comparison with isoflurane and pentobarbital. An intravital microscopy study in the rat].

OBJECTIVE: It is well known that the volatile anaesthetics halothane, enflurane and isoflurane alter hepatic blood flow in a dose-dependent manner. However, there are only a few studies investigating the effect of the new anaesthetic desflurane on the hepatic blood flow. In particular no information is available about the influence of desflurane on liver microcirculation. Therefore, the aim of this study was to evaluate the effects of desflurane in comparison to isoflurane and pentobarbital on microcirculation of the liver in vivo using intravital fluorescence microscopy. MATERIALS: 18 female Sprague-Dawley rats were anaesthetised with pentobarbital sodium, tracheotomised and mechanically ventilated using a rodent ventilator. A midline laparotomy was performed for later intravital microscopy of the liver. At the beginning of the one-hour ventilation period the animals were assigned to one of the following groups: isoflurane 0.75 MAC, desflurane 0.75 MAC and pentobarbital group. Animals of the pentobarbital group received additionally 25 mg/kg pentobarbital intravenously. After 60 min of ventilation and continuous monitoring of the systemic circulation the hepatic microcirculation was investigated by intravital fluorscence microscopy. RESULTS: Mean arterial blood pressure decreased slightly in the isoflurane and the desflurane groups compared to the pentobarbital group. Neither isoflurane nor desflurane did affect the sinusoidal diameters or the sinusoidal blood flow compared to the pentobarbital group. CONCLUSION: Hepatic microcirculation is not affected by one-hour anaesthesia with 0.75 MAC isoflurane or desflurane in comparison to pentobarbital.

Anesthetics, Inhalation↗
PubMed1995

Interleukin-1 receptor antagonist attenuates leukocyte-endothelial interactions in the liver after hemorrhagic shock in the rat.

OBJECTIVE: To evaluate the influence of interleukin-1 on leukocyte-endothelial cell interactions and the microcirculation in the liver after hemorrhagic shock by means of intravital microscopy using an interleukin-1 receptor antagonist (IL-1ra). DESIGN: Prospective, randomized, blinded, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized female Sprague Dawley rats weighing 200 to 230 g. INTERVENTIONS: Hypovolemic shock was induced and maintained for 1 hr (mean arterial pressure 40 mm Hg; cardiac output 50% of baseline). After adequate resuscitation and 5 hrs of reperfusion (mean arterial pressure > 100 mm Hg; cardiac output > 120% of baseline), the microcirculation in liver sinusoids was examined by intravital fluorescence microscopy. Continuous administration of IL-1ra (5 mg/kg/hr) was started at different times in a prospective, randomized, blinded fashion, either as pretreatment 5 mins before shock induction (n = 6), or as therapy at the time of resuscitation (n = 6). An additional bolus injection of 5 mg/kg of IL-1ra was given to the latter group. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, cardiac output, heart rate, and blood gases were comparable in all shock groups during the experiments. The percentage of permanently adherent leukocytes (adhesion time of > 20 secs) in the pretreated group was significantly decreased in comparison with the control group (pretreatment group 16.9 +/- 1.9% vs. control group 42.1 +/- 5.4%; p < .001 by analysis of variance; sham group 9.1 +/- 1.1%). Administration of IL-1ra at the time of resuscitation also reduced firm adhesion of leukocytes to sinusoidal endothelium (treated group 28.8 +/- 3.6%, p < .01). Temporary adhesion rates of leukocytes (adhesion time of < 20 secs) were unaffected by pretreatment or treatment with IL-1ra with respect to control values. Liver microcirculation was impaired after hemorrhagic shock but not improved by IL-1ra. CONCLUSIONS: The results show that adhesion of leukocytes to hepatic sinusoidal endothelium is at least partly regulated by interleukin-1. Adherence was attenuated by the application of IL-1ra, which might be due to diminished expression of adhesion receptors by endothelial cells or leukocytes. Even administration of IL-1ra at the time of resuscitation reduces the early inflammatory response in the liver after shock, thus offering a potentially important therapeutic approach.

Animals↗
PubMed1995

A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion in the liver after hemorrhagic shock.

This study was designed to assess the effect of neutrophil inhibitory factor (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40 mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or placebo control protein administered as a single intravenous bolus (10 mg/kg) at the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in vivo fluorescence microscopy. There were no significant differences observed in hemodynamic parameters between the shock groups throughout the study, however, NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results suggest that NIF may be beneficial in the attenuation of the pathological shock-induced leukocyte adhesion.

Animals↗
PubMed1995

Distribution of endothelin receptor subtypes in the rat kidney. Renal and haemodynamic effects of the mixed (A/B) endothelin receptor antagonist bosentan.

The paracrine renal endothelin system has been implicated in acute and chronic kidney diseases. However, there are only few data about the expression of endothelin receptor subtypes and their impact on renal function in the normal rat kidney. Therefore, we analyzed the age-dependent expression of endothelin receptors (endothelin receptor A and B) using Scatchard analysis, in vitro and in vivo receptor autoradiography. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan on haemodynamic and renal function in conscious chronically instrumented rats. The renal endothelin receptor A and endothelin receptor B expression is age-dependent. The relative amount of endothelin receptor A significantly decreased with age, whereas the endothelin receptor B significantly increased with age. Compared to the other renal structures, a high endothelin receptor density (endothelin receptor B >> endothelin receptor A) was seen in the renal tubules and even more in the glomeruli. Bosentan blocks both the pressor and depressor response of endothelin. Blocking of both endothelin receptor subtypes using bosentan without application of endothelin, on the other hand, did not alter blood pressure, heart rate, renal blood flow, water excretion or glomerular filtration rate, but significantly decreased sodium excretion.

Aging↗
PubMed1995

The oxygen sensor that controls EPO production: facts and fancies.

Oxygen deficit is not simply a pathophysiological incident but is at the same time a physiological event. Adaptations to high altitude or physical endurance exercise are examples of "physiological oxygen deficit". Pathophysiological conditions, on the other hand, are associated with reduced cerebral or cardiac circulation or blood loss. One of the cardinal issues of crucial importance, in this context, is relating to the nature of the "oxygen deficit sensor" which, for example, leads to increased expression of hematopoietic hormones (erythropoietin) or angiogenesis factors (Vascular Endothelial Growth Factors, VEGF). Molecular principles of such oxygen sensors are accurately defined only for certain systems: In the case of erythropoietin, only one fully known section in the 3'-region of the erythropoietin gene is necessary and is sufficient to "transfer" O2-sensitivity to that particular gene. Nuclear proteins (transcription factors), controlled by O2-deficit, are of decisive importance to that process. Additional findings are likely to suggest that a DNA section closely similar to the one regulating the VEGF gene is encoding for hypoxia dependence. In other systems, above all in the central nervous system, there are ATP-dependent Na+ or K+ flows protecting the neurons against oxygen deficit. Drop in intracellular ATP-concentration is followed by hyperpolarization of neurons due to increases in K(+)-conductivity or due to decreases in stress-dependent Na(+)-channels, with both of them apparently ATP-controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin↗
PubMed1995

Erythropoietin--from gene structure to therapeutic applications.

All forms of oxygen deprivation act as a stimulus for the production of the hormone erythropoietin. The main sites of production are specialized renal fibroblasts in adult mammals and hepatic cells in mammalian fetuses and neonates. The hormone's name is a succint description of its main effect: erythropoietin stimulates red cell production from bone marrow precursors and hence controls the O2-carrying capacity of the blood. The peripheral red cell count is kept constant by a closely controlled feedback mechanism involving O2 supply, erythropoietin secretion and erythropoiesis; the system may become unbalanced in conditions such as chronic renal disease, chronic inflammation and prematurity. Recombinant human erythropoietin is used as hormonal replacement therapy to correct various types of anemia and replenish the red cell count following hemorrhage or blood donation for autologous transfusion.

Anemia↗
PubMed1995

[The detection of Toxoplasma gondii in abortion tissues of sheep using the polymerase chain reaction].

A polymerase chain reaction was applied to detect Toxoplasma gondii DNA in placental and fetal tissue samples of 47 unselected ovine abortions of the lambing season 1990/91 (Baden-Württemberg, Rhineland, Hesse). For the amplification a 190 bp or 223 bp sequence of the B1-gene of T. gondii was selected as the target sequence. Both sequences were detected in five abortions. All positive results were immunohistochemically confirmed using the peroxidase antiperoxidase technique (PAP-staining). Thus, in Germany, too, T. gondii infection in sheep during pregnancy should be considered as a possible cause of abortions, particularly in case of abortions of unknown genesis.

Abortion, Veterinary↗
PubMed1995

Protective effects of the mixed endothelin receptor antagonist bosentan in rats with CCL4-induced liver injury.

We determined whether the paracrine liver endothelin (ET) system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar-Kyoto rats were divided into four groups: a bosentan-treated group with CCl4 intoxication, a vehicle-treated group with CCl4 intoxication, a nontreated control group, and a bosentan-treated control group. Hepatotoxicity was assessed by determination of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Tissue ET-1 concentrations and expression of endothelin receptor subtypes were analyzed. The liver tissue levels of ET-1 in rats with CCl4 intoxication were significantly higher than in normal rats. Scatchard analysis revealed no differences in the density and binding constants of ETA and ETB receptors between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in significant protection against elevation of ALT, AST, LDH, and bilirubin. In conclusion, this study showed that the paracrine ET system in involved in the pathogenesis of CCl4-induced hepatotoxicity and that blockade of the stimulated liver endothelin system reduces CCl4-induced liver injury.

Animals↗