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C Bauer

Publications and source records attributed to C Bauer.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Deferoxamine-conjugated hydroxyethyl starch reduces reperfusion injury to the liver following hemorrhagic shock].

UNLABELLED: Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model. METHODS: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation. RESULTS: Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO. CONCLUSION: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.

Animals↗
PubMed1997

[Organ specific expression pattern of a carbon monoxide generating stress protein (hemoxygenase-1/heatshock protein 32) following hemorrhagic shock].

OBJECTIVE: Recent evidence suggests a possible role for Haeme oxygenase (HO)-derived carbon monoxide (CO) in the regulation of vascular tone through elevation of cyclic 3'-5' guanosine monophosphate (cGMP). Previous work from our laboratory has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after resuscitation from hemorrhage leads to a specific and profound increase in portal resistance while neither systemic nor hepatic arterial resistance are affected. We therefore investigated the organ-specific expression pattern of the stress-inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and resuscitation. MATERIALS AND METHODS: After approval of the protocol by the local review board, male Sprague-Dawley rats (n = 6/group) were anaesthetised with pentobarbitone, instrumented for assessment of central haemodynamics and subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by resuscitation with 60% shed blood and Ringer's solution or a time-matched sham protocol. Samples of liver, spleen, kidney intestine, aorta, and lungs were harvested 5 h after the onset of resuscitation and subjected to Western-blot analysis using a specific anti-rat HO-1/hsp 32 antibody (StressGen, Sidney, Canada). RESULTS: Resuscitation with shed blood/Ringer's solution restored central haemodynamics and acid-base status while significant haemodilution was observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the liver and slight induction in aortic tissue, while no increase in steady-state protein levels was observed in the other organs studied. CONCLUSION: These results suggest a specific contribution of the HO/CO pathway to maintenance of low hepatic portal resistance in vivo in a clinically relevant model of haemorrhagic shock and adequate resuscitation.

Animals↗
PubMed1997

Role of nitric oxide in the regulation of the hepatic microcirculation in vivo.

BACKGROUND/AIMS: Nitric oxide (NO) is an important mediator in the regulation of vascular tone. However, no data exist on the physiological role of NO in the regulation of the hepatic microcirculation. This study was designed to evaluate the role of NO in the hepatic microcirculation in vivo under physiological conditions. METHODS: The hepatic microcirculation was investigated in anesthetized rats by intravital fluorescence microscopy after injection of fluorescein-isothiocyanate-labeled erythrocytes. Following assessment of baseline sinusoidal perfusion, animals were randomly treated with L-NMMA (n=6), L-arginine (n=6), nitroprusside sodium (NPS, n=5) or a comparable volume of NaCl (n=4). Drugs were given through a portal vein catheter at three doses (Dx), each followed by intravital microscopy. L-NMMA was given: 5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3); L-arginine 30 mg/kg (D1), 150 mg/kg (D2), 300 mg/kg (D3); and NPS continuously 80 microg x kg(-1) x h(-1). RESULTS: L-NMMA induced a significant increase of mean arterial blood pressure (MAP) (114 vs. 129 mm Hg; p<0.05). In contrast, MAP of NPS-treated animals decreased (107 vs. 91 mm Hg; p<0.01) whereas MAP of animals receiving L-arginine did not significantly differ. Sinusoidal blood flow revealed dose-dependent changes: L-NMMA significantly decreased perfusion of sinusoids (D1: 65%, D2: 57%, D3: 50% of baseline, p<0.05). Injection of L-arginine increased the sinusoidal flow even with the lowest dose (D1: 137%, D2: 133%, D3: 123%, p<0.05). Continuous infusion of NPS had little effect on sinusoidal blood flow at the first and second times of microscopy but sinusoidal blood flow was significantly increased at the third time (D1: 103%, D2: 106%, D3: 122%). CONCLUSIONS: Inhibition of NOS results in a dose-dependent disturbance of the hepatic microcirculation despite significantly increased MAP, whereas L-arginine increases the sinusoidal blood flow. The results indicate an important role for NO in the regulatory mechanisms of hepatic sinusoidal perfusion under physiological conditions.

Animals↗
PubMed1997

Detection of erythropoietin in human liquor: intrinsic erythropoietin production in the brain.

Until now, erythropoietin (EPO) was thought to be produced exclusively in fetal liver and adult kidney and to regulate mammalian erythropoiesis. However, we recently showed that steady state levels of EPO mRNA could be induced up to 100-fold in primary mouse astrocytes cultured under hypoxic conditions, and also reported the presence of mRNA for EPO and its receptor in the brain of mouse, monkey and human. In extending these studies on humans we now show that immunoreactive EPO is present in ventricular cerebrospinal fluid (CSF) of 5 patients with traumatic brain injuries: EPO was found in 15 out of 15 CSF samples. There was no correlation between the serum EPO concentration and the concentration in the CSF. However, EPO concentrations in CSF correlated with the degree of blood-brain-barrier dysfunction. This suggests that EPO does not cross the intact blood-brain-barrier, implying that EPO is produced in the brain itself, most probably by astrocytes in an oxygen-dependent manner. In view that neuronal cells carry the EPO receptor, we propose that EPO acts in a paracrine fashion in the central nervous system and might function as a protective factor against hypoxia-induced damage of neurons.

Adult↗
PubMed1997

Recombinant N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) prevents shock-induced microcirculatory alterations in the liver.

OBJECTIVE: To investigate the effects of the recombinant 21-kilodalton N-terminal fragment of recombinant bactericidal and permeability increasing protein (rBPI21) on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock. DESIGN: Prospective, randomized, blinded, and placebo-controlled experimental study. SETTING: University research laboratory. SUBJECTS: Anesthetized Sprague-Dawley rats, weighing 220 to 250 g. INTERVENTIONS: Rats were subjected to 60 mins of hemorrhagic shock and subsequent resuscitation to sufficiently restore systemic circulation. The microcirculation of the liver was investigated by intravital fluorescence microscopy 5 hrs after hemorrhagic shock. Four shock groups were compared with a sham-control group. Shock groups received either rBPI21 (10 mg/kg) or placebo either before or after shock period. MEASUREMENTS AND MAIN RESULTS: No differences were observed in hemodynamic, respiratory, or metabolic parameters between the shock groups. However, the hepatic microcirculation showed severe deterioration 5 hrs after shock, indicated by significantly narrowed sinusoids in all shock groups compared with controls (8.5 +/- 0.3 microm vs. 10.0 +/- 0.4 pm). Leukocyte adhesion was markedly increased to comparable values in both placebo groups (619 cells/mm2 and 644 cells/mm2; sham, 168 cells/mm2). Neutralization of endotoxin by administration of rBPI21 before or after shock resulted in plain reduction of pathologic leukocyte-endothelial interaction (138 cells/mm2 and 85 cells/mm2). CONCLUSION: The results support the hypothesis that endotoxin induces microcirculatory alterations after shock, and further suggest a potentially beneficial role of rBPI21 in the treatment of posttraumatic endotoxin-induced inflammatory reactions.

Animals↗
PubMed1997

In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal microcirculation.

BACKGROUND: It has been proposed that halogenated anaesthetics interfere with the endothelium-dependent circulatory control by attenuating the effects of endothelium-derived relaxing factor (EDRF/NO). This study was designed to determine whether or not volatile anaesthetics in vivo influence the microvascular tone in hepatic sinusoids. METHODS: Using epifluorescence videomicroscopy, we compared the effects of the volatile anaesthetics halothane, enflurane, and isoflurane on hepatic microcirculation halothane, enflurane, and Animals were initially anaesthetized with pentobarbitone (50 mg.kg-1 i.p.) to allow instrumentation and laparotomy and were randomly allocated to one of 4 groups (n = 5-6 each) to receive either a supplementary dose of i.v. pentobarbitone (25 mg.kg-1; control group) or 0.75 MAC halothane, enflurane or isoflurane (1.5 MAC.h). RESULTS: Halothane decreased significantly the volumetric blood flow as compared with isoflurane (P < 0.05) or pentobarbitone controls (P < 0.05). The decrease in sinusoidal blood flow caused by halothane was largely attributable to a decrease in sinusoidal diameter (P < 0.05), while red blood cells velocity remained unchanged. Isoflurane led to a significant decrease in sinusoidal width compared with controls (P < 0.05) but an increase in red cell velocity offset the effect of sinusoidal narrowing of volumetric blood flow, while enflurane had no significant effect on any of the measured parameters. CONCLUSION: This study provides the first direct evidence that the volatile anaesthetics halothane and isoflurane in vivo shift the hepatic microvascular tone toward a more constricted state; however, flow velocity is enhanced with isoflurane, offsetting this effect. As a result the volumetric flow is at least affected by isoflurane, then enflurane and most significantly by halothane. Furthermore, our data are consistent with the concept that volatile anaesthetics in clinically relevant concentrations may influence the balance between endothelium-derived vasoactive factors which control microvascular tone.

Anesthetics, Inhalation↗
PubMed1997

Adenosine kinase inhibitor GP515 attenuates hepatic leukocyte adhesion after hemorrhagic hypotension.

Adhesion of leukocytes to the vascular endothelium hallmarks a key event in neutrophil-mediated organ injury after ischemia-reperfusion. The autacoid adenosine has been shown to inhibit activated neutrophil function and to interfere with leukocyte-endothelial adherence. Its therapeutic use in ischemia-reperfusion, however, has been limited by severe cardiovascular side effects. We therefore investigated the effects of the adenosine kinase inhibitor GP515 in vivo on hepatic leukocyte-endothelial interactions in a rat model of hemorrhagic hypotension and resuscitation, using intravital microscopy. Rats were pretreated with either GP515 (0.25 mg/kg) or saline in a randomized and blinded manner and subjected to pressure-controlled hemorrhagic hypotension at a mean arterial pressure of 40 mmHg for 60 min followed by 5 h of resuscitation. Five hours after resuscitation in saline-treated animals, firm leukocyte-sinusoidal adhesion was strongly enhanced in the periportal and midzonal sublobular regions, and sinusoidal diameters were also markedly reduced. Compared with saline treatment, GP515 significantly attenuated shock and resuscitation-induced leukocyte adhesion in both sublobular regions. Moreover, although GP515 did not significantly affect macrohemodynamical and hematological parameters, it enlarged narrowed sinusoidal diameters and tended to improve sinusoidal blood flow. We propose that the adenosine-regulating agent GP515 has a therapeutic potential to attenuate ischemia-reperfusion-induced inflammation by capitalizing on the beneficial anti-inflammatory effects of endogenous adenosine.

Adenosine Kinase↗
PubMed1997

Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid.

Exogenous cholecystokinin (CCK) injected peripherally mimics effects of lipid entering the intestine on food intake and gastric motility via vagal afferents and induces c-fos expression in the locus ceruleus complex (LCC), nucleus of the solitary tract (NTS), area postrema (AP), and paraventricular nucleus (PVN). However, the role of peripheral endogenous CCK in induction of c-fos expression in the brain at ingestion of nutrients is controversial. In awake rats, intraduodenal lipid infusion markedly increased Fos protein-like immunoreactivity (FLI) in these brain nuclei. Perivagal capsaicin pretreatment reduced the increase of FLI in the LCC, NTS, and PVN by 66-86% and in the AP by 46%. The CCK-A receptor antagonist MK-329 (0.1 mg/kg i.p.) diminished the FLI increase in LC, NTS, AP, and PVN by 39-100%; the CCK-B receptor antagonist L-365,260 reduced the increased FLI in the AP by 54%. After capsaicin pretreatment, both CCK antagonists had additional inhibitory effects only on FLI in the AP. These findings suggest that entry of lipid into the intestine activates c-fos in the LCC, NTS, and PVN predominantly via CCK-A receptors on vagal afferents and in the AP via vagal and nonvagal pathways, as well as CCK-B and CCK-A receptors.

Animals↗
PubMed1997

Modification of hypothalamic-pituitary-adrenocortical activity by serotonergic agents in the rat.

The effects of tandospirone, enciprazine, gepirone, buspirone (5-HT1A agents) and carvotroline (5-HT2) on hypothalamic-pituitary-adrenocortical activity (HPA) activity were studied. These drugs increased the plasma corticosterone levels in a dose-dependent manner. Their ED50 values were 3.8, 31.8, 3.1, 3.4 and 7.0 mg/kg, respectively. Drug effects peaked between 30 min and 1 h, and plasma corticosterone levels returned to control levels after 2 h. When the drugs were given in conjunction with a rotatory stress, gepirone and enciprazine increased and carvotroline decreased plasma corticosterone levels. Dexamethasone (0.1 mg/kg) pretreatment reduced drug-activated HPA axis activity.

Adrenal Cortex↗
PubMed1997

Pulmonary infection due to Mycobacterium gordonae in an adolescent immunocompetent patient.

We report the case of 17-year-old male adolescent immunocompetent patient with an operated transposition of the great arteries after the Mustard technique admitted to our hospital because of a cough and hemoptysis. Two nodules and an area of ground glass appearance located in the lower lobe of the left lung were diagnosed by ultrafast computed tomography (UF-CT) after ruling out cardiovascular complications. The gastric aspirate revealed acid-fast bacilli despite a repeatedly negative tuberculin skin test identified as Mycobacterium gordonae by the Gen-Probe Rapid Diagnostic Test. After an initial standard antimycobacterial therapy with isoniazid, rifampin and pyrazinamide the therapy was changed to clarithromycin and after a treatment course of 14 days, the UF-CT revealed a normal scan of both lungs. The case described suggests that one has to consider M. gordonae as a rare cause of infection even in immunocompetent patients.

Adolescent↗
PubMed1997

Innovation in the management of soft tissue sarcomas in infants and young children: high-dose-rate brachytherapy.

PURPOSE: Conventional low-dose-rate (LDR) brachytherapy is effective in treating childhood sarcomas, but often not practical (due to the associated radiation hazards) in the young children who require continuous observation and sedation. Fractionated high-dose-rate brachytherapy (HDR) was used to deliver adequate tumoricidal radiation while preserving bone and organ growth in children. MATERIALS AND METHODS: Twelve children with diverse sarcomas were treated with fractionated HDR. The median age at diagnosis was 18 months (range, 1 to 42). Nine patients had rhabdomyosarcoma and three had other soft tissue sarcoma (STS) variants. Ten patients had microscopic residual disease at the time of brachytherapy. All patients were treated with appropriate chemotherapy and surgery. HDR was delivered in 3-Gy fractions twice a day to a total dose of 36 Gy in 8 days. External-beam radiation therapy (EBRT) was avoided. Patients were monitored for a median of 61 months (range, 30 to 78). RESULTS: One patient developed local recurrence and distant metastases to the lungs. The 6-year actuarial local control and overall survival rates were 91% and 81%, respectively. Brachytherapy-related morbidity occurred in 50% of patients. The morbidity was mild to moderate in 42% of patients and consisted primarily of acute skin and mucosal reaction. One patient experienced severe (grade III to IV) toxicity. Another child, treated to the tongue, had delayed dentition only in the teeth adjacent to the brachytherapy site. The other children have exhibited only minimal or none of the bone growth retardation expected with EBRT. CONCLUSION: The combination of conservative surgery, chemotherapy, and exclusive HDR to postchemotherapy tumor volume with a modest margin, avoiding EBRT, provided disease control in carefully selected young children, while preserving bone growth and organ function. The short duration of therapy and small volume irradiated allowed chemotherapy to be resumed shortly after brachytherapy. The use of HDR challenges the present philosophy of radiotherapy treatment volume, which holds that the prechemotherapy tumor volume should be treated with an acceptable margin. Brachytherapy should be included in multicentric clinical trials in young children.

Brachytherapy↗
PubMed1997

Out of balance: consequences of a partial keratin 10 knockout.

Recently we generated keratin 10 knockout mice which provided a valuable model for the dominantly inherited skin disorder epidermolytic hyperkeratosis. Here we investigated the molecular basis for their phenotype. Hetero- and homozygotes expressed a truncated keratin 10 peptide which has been identified directly by microsequencing. Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distribution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy. This revealed that keratin 10T was restricted to complexes with keratin 1 but did not mix with keratin 6. The latter did not form extended filaments with keratins 16/17 but aggregates. Keratins 6/16 were unable to compensate for the lack of normal keratin 1/10 filaments. Remarkably keratin 6 aggregates strictly colocalized with keratohyalin granules. Residual keratin 1/10T clumps were located in the cell periphery and at desmosomes which maintained a normal architecture. Surprisingly keratin 2e, a keratin tailored to sustain mechanical stress, was completely lost in paw sole epidermis of homozygous keratin 10 knockout mice, pointing to keratin 10 as its partner. The selective pairing of keratin 10T and the loss of keratin 2e indicate that in vivo keratins are less promiscuous than in vitro. Skin fragility in keratin 10 knockout mice and in epidermolytic hyperkeratosis is probably the consequence of two complementing mechanisms namely a decrease of normal keratin 1/10 filaments and an increase in keratins 6/16 with a poor filament-forming capacity.

Amino Acid Sequence↗
PubMed1997

The paracrine endothelin system: pathophysiology and implications in clinical medicine.

Apart from the initially described vasoconstriction, endothelins have been shown to cause a variety of biological activities in non-vascular tissues. A rapidly growing body of data supports the concept of endothelin as a paracrine acting hormone. In this review, we will discuss the impact of this local endothelin system for various cardiovascular pathophysiological states, especially atherosclerotic vascular disease, restenosis, myocardial infarction, congestive heart failure, and arterial hypertension. In addition, the endothelin system is a modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine/autocrine factor in the regulation of renal blood flow, glomerular haemodynamics, and sodium and water homeostasis. The renal endothelin system is involved in kidney diseases such as impaired renal function in liver cirrhosis, cyclosporin toxicity, acute renal failure and renal glomerular and interstitial fibrosis. Therapeutic approaches with new orally active endothelin receptor antagonists are also discussed.

Amino Acid Sequence↗
PubMed1996

Control of Filaroides hirthi infections in Beagle dogs by ivermectin.

The efficacy of ivermectin against Filaroides hirthi was evaluated in a series of three trials using Beagle dogs of a breeding colony known to be endemically infected with this lungworm. Ivermectin was subcutaneously given at a dosage of 1 mg kg-1 bodyweight once to 40 (group A) or, at a one week interval, twice to 32 dogs (group B) 14-15 weeks prior to necropsy; another 40 dogs (group C) remained untreated. All animals were necropsied and lungs were digested using the pepsin-hydrochloride method and qualitatively examined for Filaroides spp. stages. A 44.8% and 74.1% reduction of the prevalence of lungworm infection as well as a 87.5% and 94.8% reduction of the proportion of dogs harbouring first-stage Filaroides spp. larvae were found in groups A and B, respectively, as compared to group C. These results suggest that repeated treatments of breeding dogs with ivermectin might reduce the transmission of F. hirthi infection to their offspring.

Animals↗
PubMed1996

Microinfusion of corticotropin-releasing factor into the locus coeruleus/subcoeruleus nuclei inhibits gastric acid secretion via spinal pathways in the rat.

Brain corticotropin-releasing factor (CRF) is involved in stress-related alterations of gastric acid secretion. CRF in the locus coeruleus has been shown to induce anxiogenic behavioral responses and to mimic stress-induced alterations of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric acid secretion was investigated in urethane-anesthetized gastric fistula rats. In sham-operated animals, CRF (126-420 pmol) microinfused bilaterally into the LC/SC induced a dose-dependent inhibition of pentagastrin (PG)-stimulated gastric acid secretion of 60-81% within the first hour after microinjection. At the 420 pmol dose, this inhibitory effect of CRF into the LC/SC lasted throughout the whole observation period of 120 min. After bilateral vagotomy, basal and PG-stimulated gastric acid secretion at microinjection of vehicle was reduced. Nevertheless, microinfusion of 420 pmol CRF into the LC/SC still inhibited significantly gastric acid secretion by 62.1%. In contrast, in spinal cord transected animals bilateral microinfusion of 420 pmol CRF into the LC/SC did not reduce PG-stimulated gastric acid secretion. These data indicate that CRF acts in the LC/SC to induce a long lasting inhibition of peripherally stimulated gastric acid secretion via spinal pathways. These findings suggest a possible role of the LC/SC in the regulation of gastric secretion and of endogenous CRF at these sites in the stress-related inhibition of gastric acid secretion by affecting autonomic nervous system activity.

Animals↗