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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 163 records · Page 9Linked to original sources
PubMed1995

Renal endothelin system in rats with liver cirrhosis.

Rats with experimental liver cirrhosis have increased endothelin-1 (ET-1) plasma concentrations and show a tendency toward sodium and water retention. We therefore analyzed the renal ET system in cirrhotic rats and control rats, as the renal ET system is involved in the regulation of water and sodium excretion. Cirrhosis was induced by carbon tetrachloride (CCl4) administration. We analyzed the expression of ET receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma and renal tissue ET-1 concentrations using a specific radioimmunoassay. Furthermore, we analyzed the effects of the nonselective (A/B) ET receptor antagonist bosentan on water and sodium excretion and glomerular filtration rate. Our study revealed an overexpression of the ETB receptor in the renal medulla of rats with liver cirrhosis, whereas the density of ETB receptor in the cortex and the ETA receptor in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. The highest ET-1 concentrations were observed in the renal medulla of cirrhotic rats. Glomerular filtration rate decreased in cirrhotic rats but was not altered after bosentan treatment in cirrhotic and control rats. Bosentan decreased sodium excretion in both cirrhotic and control rats to a similar extent, whereas water excretion was reduced by bosentan only in cirrhotic rats. We therefore suggest that the upregulation of medullary ETB in cirrhotic rats is involved int he regulation of water excretion in rats with CCl4-induced cirrhosis.

Animals↗
PubMed1995

Significance of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats: renal and hemodynamic effects of endothelin receptor antagonists.

The renal endothelin (ET) system has been implicated in the maintenance of hypertension in spontaneously hypertensive rats (SHRs). However, little is known about the expression and cellular distribution of the ET receptor subtypes in the kidney of SHRs. We therefore analyzed the expression of ET receptor subtypes in the kidneys of 16-week-old SHRs. Wistar-Kyoto (WKY) rats served as controls. Furthermore, we investigate the effects of the ETA receptor antagonist BQ 123 and the mixed (ETA/ETB) receptor antagonist bosentan on mean arterial blood pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) in conscious, chronically instrumented rats. In SHRs we found overexpression of the ETA in the glomeruli and smooth muscle cells of intrarenal arteries compared to age-matched WKY rats. Furthermore, our study revealed a pronounced upregulation of the ETB in the glomeruli of SHRs. Blockade of ETA and ETB receptors in SHR with bosentan as well as with BQ 123 led to a significant decrease in MAP and a significant increase in RBF, indicating that the ETA receptor plays a major role in the maintenance of high blood pressure and the regulation of RBF in SHRs. The blockade of both ETA and ETB receptors by bosentan has no further effect on MAP reduction or increase in RBF in SHRs compared to ETA blockade by BQ 123. In contrast, combined blockade of ETA and ETB receptors by bosentan significantly decreased GFR in SHRs, whereas no effect on GFR was observed in WKY rats, suggesting that the glomerular ETB overexpression in SHRs is of pathophysiologic relevance.

Animals↗
PubMed1995

Interaction of intermediate filaments with ribosomes in vitro.

Cytoplasmic intermediate filaments (cIFs) should be capable of loosely interacting with negatively charged, macromolecular assemblies, given that the net positive charge of the N-terminal head domains exposed on the surface of the cIFs is not fully neutralized by the neighboring C-terminal tail domains and the filament body proper. In order to substantiate this notion, cIFs reconstituted in vitro from various type III IF proteins and obtained as constituents of whole cell mount preparations were allowed to react at physiological ionic strength with 40S and 60S ribosomal subunits as well as 80S run-off ribosomes of mammalian origin. Electron micrographs of the reaction products show colocalization of all kinds of ribosomal particles with both the reconstituted and the natural cIFs, including the cytokeratin filaments of whole cell mount preparations of epithelial cells. The ribosome-cIF complexes are sensitive to ionic strength higher than physiological as well as to mild treatment with pancreatic RNase A, suggesting the direct involvement of the RNA moieties of the ribosomal particles in the binding reaction via the engagement of ionic bonds. This weak, electrostatic interaction potential of the cIF complement of the cytoskeleton might be exploited by the eukaryotic cell for the storage and distribution in the cytoplasm of non-polyribosomal ribonucleoprotein particles of the protein-synthesizing machinery and possibly also of negatively charged membrane vesicles.

Animals↗
PubMed1994

Comparative efficacy of moxidectin and mebendazole against gastrointestinal nematodes in experimentally infected lambs.

A controlled trial was conducted to determine the anthelmintic efficacies of moxidectin and mebendazole. The compounds were administered orally at doses of 0.2 mg/kg bodyweight and 15.0 mg/kg bodyweight, respectively, to lambs infected experimentally with large numbers of gastrointestinal nematode larvae including a benzimidazole-resistant strain of Haemonchus contortus. Moxidectin was 100 per cent effective against adult H contortus, Ostertagia species, Trichostrongylus colubriformis, Cooperia curticei and fifth stage larvae of Oesophagostomum species and Chabertia ovina, but was only 76 per cent effective against adult Strongyloides papillosus. Mebendazole was 100 per cent effective against adult Ostertagia species and T colubriformis, but reduced the numbers of adult C curticei by only 39 per cent, S papillosus by 58 per cent, H contortus by 76 per cent, and fifth stage larvae of Oesophagostomum species by 79 per cent and C ovina by 72 per cent.

Administration, Oral↗
PubMed1994

Anti-HIV-1 activity of chemically modified heparins: correlation between binding to the V3 loop of gp120 and inhibition of cellular HIV-1 infection in vitro.

Chemically modified heparins were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting the binding to recombinant HIV-1 gp120 of monoclonal antibodies specific for the V3 loop. The results reveal that N-desulfation reduces activity, although this is largely restored on N-acetylation. Selective O-desulfation also markedly reduces activity, whereas carboxyl reduction has little effect. Overall these results show that the anti-HIV-1 activity of heparin does not depend simply on negative density, and indicate instead that particular structures, notably O-sulfates, are involved. Our studies reveal that for chemically modified heparins and heparin-derived fragments there is a striking correlation between anti-HIV-1 activity in vitro and binding to the V3 loop of gp120 in solid phase ELISA. This strongly suggests that the heparin exerts its anti-HIV-1 activity by binding to the V3 loop of gp120.

Acetylation↗
PubMed1994

[Erythropoietin: from gene to therapeutic agent].

Erythropoietin is a hormone whose production is stimulated by all forms of oxygen deficiency. The main production takes place in specialized fibroblasts in the kidney of adults and in liver cells during the fetal and neonatal period. The most important function of the hormone can be derived from its name: It stimulates erythropoiesis in the bone marrow and thus controls O2-capacity of blood. A thoroughly controlled feedback-mechanism between oxygen-supply erythropoietin release and renewal of erythrocytes provides for a constant level of erythrocytes in blood. This feedback mechanism is disturbed by chronic renal diseases, chronic inflammations and also in premature infants. Recombinant human erythropoietin is used as hormonal substitute in order to correct diverse types of anemia and may also be used in the context of re-transfusions.

Erythropoietin↗
PubMed1994

Microinfusion of corticotropin releasing factor into the locus coeruleus/subcoeruleus nuclei stimulates colonic motor function in rats.

Convergent evidence indicates that brain corticotropin-releasing factor (CRF) participates in stress-related alterations of gastric and colonic motor function. CRF in the locus coeruleus has been shown to induce anxiogenic response. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric and colonic transit was investigated in conscious, chronically cannulated rats. CRF (0.2 nmol) microinjected into the LC/SC did not influence gastric emptying of a non-caloric semi-liquid meal while stimulating colonic transit by 57% as assessed by the geometric center in fasted rats. Under the same conditions, i.c.v. injection of CRF (0.2 nmol) delayed gastric emptying by 31% and increased colonic transit by 103%. When colonic transit was evaluated as the time of appearance in the feces of a marker placed in the proximal colon, CRF (0.2 nmol) injected into the LC/SC or i.c.v. stimulated colonic transit by 77% and 48% respectively and fecal output/6h by 3.8 and 2.8 fold respectively. Microinjection of CRF into the medial and lateral parabrachial nucleus, postero-dorsal tegmental nucleus, dorsomedial tegmental area and the ventral part of the nucleus subcoeruleus did not influence colonic transit. These data indicate that CRF acts in the LC/SC to induce a long lasting stimulation of colonic transit and bowel discharge without influencing gastric emptying. These findings suggest a possible role of the LC/SC in the regulation of colonic motor function and of endogenous CRF at these sites in the stress-related activation of colonic motor function.

Animals↗
PubMed1994

Stability of microsomal monooxygenases in murine liver S9 fractions derived from phenobarbital and beta-naphthoflavone induced animals under various long-term conditions of storage.

The aim of this study was to define the long-term stability of metabolizing enzymes in activating preparations for short-term genotoxicity bioassays under various storage conditions. Expressions of cytochrome P450 content, NADPH-cytochrome (P450) c-reductase activity, and of the several monooxygenases, such as aminopyrine N-demethylase (class IIIA P450), p-nitroanisole O-demethylase (mixed), dinemorphan N-demethylase (IIB1), ethoxyresorufin O-deethylase (IA1), ethoxycoumarin O-deethylase (mixed), and pentoxyresorufin O-dealkylase (IIB1), were examined in S9 fractions derived from Na-phenobarbital (PB) plus beta-naphthoflavone (beta-NF) induced male and female mice, stored at -80 degrees C, or lyophilized and stored at -20 degrees C. Lipid peroxidation was also determined. Cytochrome P450 and the associated activities were decreased by 30-82% within 9 months of storage. The pattern and degree of relative stabilities were different for the various isoforms. The IA1-like activity, for example, was much more stable (approximately 49% loss) than IIB1-like activities (up to 82% loss). In general, lyophilized enzymes were less stable than directly frozen preparations. In addition, immediately after freeze-drying (lyophilization), a marked decrease in activity of up to 35% was observed. On the contrary, demethylation of aminopyrine and p-nitroanisole remains almost constant over 6 months storage at -196 degrees C. The results obtained indicate that either fresh, daily made S9 fractions or, alternatively, fractions stored in liquid nitrogen (up to 6 months) are recommended for mutagenesis studies.

Aminopyrine N-Demethylase↗
PubMed1994

Hypoxia and cobalt stimulate lactate dehydrogenase (LDH) activity in vascular smooth muscle cells.

O2 plays a dominant role in the metabolism and viability of cells; changes in O2 supply lead to many physiological responses in the cell. Recent reports have shown that hypoxia induces the transcription of a number of genes, among them those for the glycolytic enzymes. We have investigated signalling events that may lead to enhanced activity of lactate dehydrogenase (LDH) in cultured vascular smooth muscle (VSM) cells derived from rat aorta, grown under hypoxic conditions (1% versus 20% O2). LDH was chosen because this enzyme exhibits one of the largest increases in activity among the glycolytic enzymes after hypoxic stimulation of cells. Hypoxic exposure of VSM cells for 24 h resulted in a 2-fold increase in LDH activity and in a 2.5-fold increase in intracellular cAMP levels. Agents that activate adenylate cyclase, such as forskolin, cholera toxin and 1-methyl-3-isobutylxanthine (IBMX), and thus increase cAMP production, significantly induced LDH activity. Moreover, induction of LDH activity by hypoxia was prevented in the presence of the protein kinase A inhibitor N-[2-(methyl-amino)ethyl]-5-isoquinolinsulphonamide dihydrochloride (H-8), and the cyclooxygenase inhibitor indomethacin. In contrast to the cAMP-stimulating agents, stable cGMP analogues (dibutyryl-cGMP, 8-bromo-cGMP), activators of protein kinase C [12-O-tetradecanoylphorbol-13-acetate (TPA), and 1-oleoyl-2-acetyl-glycerol (OAG), and the calcium ionophore ionomycin did not alter LDH activity in VSM cells kept at 20% O2. A dose-dependent increase in LDH activity was also observed in normoxic cells exposed to cobalt chloride (50-200 microM), indicating that a metal binding protein might be involved in this signalling cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Lack of transport of erythropoietin across the human placenta as studied by an in vitro perfusion system.

The transfer of human recombinant erythropoietin (rhEPO) from the maternal to the fetal side was investigated using the technique of in vitro perfusion of an isolated cotyledon of human placenta, with recirculation of the perfusate (130 ml) in separate closed maternal and fetal circuits. rhEPO (221-512 U), together with [14C]BSA (bovine serum albumin, 44.8 kBq or 2,688,000 dpm), was added to the maternal circuit only. Despite a considerably lower molecular weight of EPO (mol. wt. = 30,400 Da) compared to BSA (mol. wt. = 69,000 Da), no difference was found in their transfer across the placenta from the maternal to the fetal side, which was very low for both macromolecules. The total transfer of rhEPO derived from the concentration measured in the samples taken from the fetal circuit at the end of 4-5 h of perfusion, was in the range of 0.04% of the amount initially added to the maternal compartment. A similar amount of transfer was determined for [14C]BSA (0.04-0.07%, n = 12). In conclusion, by direct determination in a dually in vitro perfused human placental cotyledon, no significant transfer of rhEPO from the maternal to the fetal side could be shown.

Biological Transport↗
PubMed1994

Efficacy of two formulations ('injectable' and 'pour on') of moxidectin against gastrointestinal nematode infections in grazing cattle.

The efficacy of moxidectin, 'injectable' and 'pour on', against gastrointestinal nematodes was determined in cattle in two separate field trials (Trial I in 1990 and Trial II in 1991) with respectively 88 and 94 young grazing cattle of either sex. The efficacy was measured on the basis of the reduction of the egg output and of the evaluation of the results from larval differentiation. Animals in Group MI received 0.2 mg kg-1 body weight (b.w.) moxidectin injectable solution in Trial I on Day 0. Group CI was not given any medication on Day 0, but 0.2 mg kg-1 b.w. ivermectin injectable solution (Ivomec) was applied after 2 weeks to prevent clinical disease. In Trial II, animals in Group MP were treated with pour on moxidectin (0.5 mg kg-1 b.w.) on Day 0. Animals in Group CP serving as controls for Group MP during the first part of the trial received the same formulation at the same dose 2 weeks after treatment of Group MP. When the egg output was compared within treated groups, the egg count reduction was very similar post treatment (p.t.) with both formulations being 96.3% and 96.6% on Day 7 after the application of injectable moxidectin or pour on moxidectin, respectively, and 90.7% and 92.5% on Day 28 p.t. When egg counts of treated and control animals were compared (corrected for the e.p.g. values before treatment) the egg count reduction was 95.4% and 91.5% on Day 7 and 92.9% and 84.8% on Day 14 p.t. with either the injectable or pour on formulation. Pour on moxidectin seemed to be more effective against Ostertagia spp. than against Cooperia spp. Animals treated with injectable moxidectin gained significantly more body weight (4.2 kg per animal) than the controls from Day -7 to Day +14, while no significant difference in weight gain was achieved within 2 weeks after treatment with pour on moxidectin.

Administration, Topical↗
PubMed1994

Lungworm infection in a beagle colony: Filaroides hirthi, a common but not well-known companion.

116 beagle dogs of both sexes were examined for infection with Filaroides hirthi within the framework of several toxicological studies. 98% of the animals demonstrated lung-worm-associated lesions. Most of the macroscopic visible lesions can be subdivided into four groups, representing different histopathological pictures ranging from living worms, different types of granulomatous inflammation to tumorlike lesions. Especially the latter is liable for several misinterpretations in toxicologic studies. This is the first positive evidence of an infection of Beagle dogs with Filaroides hirthi in Germany.

Animals↗
PubMed1994

Hypermutable ligation of plasmid DNA ends in cells from patients with Werner syndrome.

Werner Syndrome is a rare autosomal recessive disorder characterized by an increased cancer risk and by symptoms suggestive of premature aging. Cells from these patients demonstrate a typical pattern of chromosomal instability and a spontaneous hypermutability with a high rate of unusually large deletions. We have studied the in vivo DNA ligation in three lymphoblast cell lines from Werner syndrome patients and three from normal donors. In our host cell ligation assay we transfected linearized plasmid pZ189 and measured the amount of plasmid DNA ends rejoined by these host cells as the ability of the recovered plasmid to transform bacteria. A mutagenesis marker gene close to the ligation site allowed screening for mutations. Subsequent mutation analysis provided information about the accuracy of the ligation process. The cells from Werner syndrome patients were as effective as normal cells in ligating DNA ends. However, mutation analysis revealed that the three Werner syndrome cell lines introduced 2.4-4.6 times more mutations (p < 0.001) than the normal cell lines during ligation of the DNA ends: the mutation rates were 69.4, 97.2, and 58.7%, as compared to 23.6, 21.7, and 24.4% in the normal cell lines. These increased mutation frequencies in plasmids ligated during passage through Werner syndrome cells were mainly due to a significant (p < 0.001) increase in deletions. This error-prone DNA ligation might be responsible for the spontaneous hypermutability and the genomic instability in Werner syndrome cells and related to the apparently accelerated aging and high cancer risk in affected patients.

Cell Line↗
PubMed1994

rh-erythropoietin stimulates immature reticulocyte release in man.

The pharmacodynamics of single intravenous dosing with recombinant human erthropoietin (rhEPO) was investigated in eight healthy volunteers (150 U/kg, n = 2; 300 U/kg, n = 6) with respect to reticulocyte subdivisions (by fluorescence flow cytometry) and serum ferritin over 6.5 d. The present study shows that bolus rhEPO injection produces an immediate release of high and middle fluorescence (immature) reticulocytes with a high RNA content from the marrow into the circulation, whereas the low fluorescence (more mature) reticulocytes were at first not affected. Serum ferritin decreased markedly within 24 h, reaching a nadir 50% of baseline after 120 h (5 d), with no increase in haemoglobin. Our data suggests that rhEPO triggers premature expulsion of immature reticulocytes from the bone marrow into the circulation independent of its effect in stimulating erythropoiesis and that rhEPO has an effect on serum ferritin concentration which in this dynamic situation is dependent not only on the iron stores.

Bone Marrow↗