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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1994

Expression of the erb B oncogene in the Morris hepatoma 7777.

Altered expression of protooncogenes/oncogenes is believed to be involved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v-erb B mRNA of normal rat liver with that of Morris hepatoma 7777 using Northern blot analysis and in situ hybridization. Northern blot analysis revealed a strong overexpression of the v-erb B related mRNA, while the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slightly increased number of silver grains in the hepatoma cells compared with normal rat liver. On the other hand, the v-erb B related mRNA was strongly overexpressed in the hepatoma cells, while the connective-tissue capsule, the blood vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained in liver metastases. The detectable v-erb B hybridization signal was lost by pretreatment with RNase A. We conclude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris hepatoma 7777, while the increased expression of the v-erb B related mRNA is due to a selection of ligand-independent tyrosine kinase activity.

Animals↗
PubMed1994

Immunohistochemical and electronmicroscopic effects of a new 2.1 microns Ho:YAG laser on the rat brain.

Using an experimental animal model, the thermal single-pulse lesion derived from a mid-infrared 1.0 Joule 300 microns fibre-conducted Holmium: Yttrium-Aluminum-Garnet (Ho:YAG) laser was examined, with special emphasis on the orientation and depth of the tissue reaction. Performing biparietal craniotomy in Sprague-Dawley rats weighing 250-300 g, both hemispheres were targeted by different radiant exposures from 20 to 140 J/cm2 derived from a 600-800 microsecond single pulse. After survival periods of one to 30 days, the animals were sacrificed and both hemispheres were processed for light- and electronmicroscopic investigations. To resolve the depth and orientation of the tissue reaction regarding the localization of reactive astrocytes, we looked for the expression of glial proteins like glial fibrillary acidic protein (GFAP), Vimentin and S 100 with a three-step biotin-avidin immunoperoxidase method. Neuronal and secondary axonal damage was investigated by labelling Neurofilament and Synaptophysin. The tissue reaction beneath the ablated material, consisting of a vacuolation and coagulation zone resulting from heat diffusion, was further elucidated by localization of the heat shock protein (HSP 72 kilo Dalton). Revealing the extension of reactive astrocytes and the degree of the electronmicroscopically depicted glial oedema, the depth of the tissue damage was estimated to reach about 700 microns beneath laser excision. Since McKenzie predicted the depth of tissue damage beneath CO2 and YAG laser excisions in a theoretical mathematical model, the authors were able to develop a sensitive model for testing new laser systems and as a promising instrument for neurosurgery.

Aluminum↗