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Biomedical subjects

A Walther

Publications and source records attributed to A Walther.

At least 19 recordsLinked to original sources
PubMed2001

Effects of histamine-1 receptor antagonism on leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: The purpose of this study was to investigate the role of histamine in mediating leukocyte-independent microvascular permeability and mast cell activation during endotoxemia. Microvascular permeability and mast cell activity were determined after inhibition of the L-selectin mediated leukocyte-adherence by fucoidin and after inhibition of histamine effects by the histamine H1-receptor antagonist diphenhydramine. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, microvascular permeability, and mast cell activity were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the histamine H1-receptor antagonist diphenhydramine, animals in the ETX/H1-ANT group received a continuous infusion of endotoxin. Animals in the ETX group underwent the same procedure, but received saline 0.9% instead of diphenhydramine. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the control group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to control group. In the ETX group and the ETX/H1-ANT group both microvascular permeability and mast cell activity increased significantly, starting at 60 minutes. Differences in mast cell activity between the ETX group and the ETX/H1-ANT group were significant at 60 minutes and at 120 minutes. Differences in microvascular permeability between the ETX/H1-ANT group and the ETX group were not significant. CONCLUSIONS: The leukocyte-independent microvascular damage during early endotoxemia cannot be inhibited efficiently by the H1-receptor antagonist diphenhydramine, indicating that histamine seems to play only a minor role in that pathophysiology. Furthermore, mast cells do not seem to be involved in the development of leukocyte-independent plasma extravasation during endotoxemia.

Animals↗
PubMed2001

Methysergide attenuates leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: During endotoxemia, the early endothelial damage has been shown to be leukocyte independent. Therefore, it was the aim of our study to investigate the role of serotonin in mediating leukocyte-independent microvascular permeability during endotoxemia. Microvascular permeability was determined after inhibition of the L-selectin mediated leukocyte adherence by fucoidin and after inhibition of serotonin effects by the serotonin (5HT)-receptor antagonist methysergide. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, and macromolecular leakage were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the serotonin-receptor antagonist methysergide, animals in the FUCO/ETX/5HT-ANT group received a continuous infusion of endotoxin. Animals in the FUCO/ETX group underwent the same procedure but received saline 0.9% instead of methysergide. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the saline group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to saline group. In the FUCO/ETX group, macromolecular leakage increased significantly, starting at 60 minutes. Values in the saline group increased slightly, being significant at 120 minutes, whereas vascular permeability remained unchanged in the FUCO/ETX/5HT-ANT group. Differences in macromolecular leakage between the FUCO/ETX-group versus the FUCO/ETX/5HT-ANT group and the saline group were significant at 120 minutes. Differences in macromolecular leakage between the FUCO/ETX/5HT-ANT group and the saline group were not significant. CONCLUSIONS: The leukocyte-independent endothelial damage during early endotoxemia can be inhibited efficiently by the 5-HT-receptor antagonist methysergide, indicating that serotonin plays an important role in that pathophysiology.

Animals↗
PubMed2001

Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat.

OBJECTIVE: To test the effects of dobutamine and dopexamine on hepatic portal and sinusoidal blood flow in a model of normodynamic endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats (250-350 g). INTERVENTIONS: A total of 40 male Wistar rats were randomized into four groups: a control group, which only received Ringer's solution; an endotoxin group, which received a continuous infusion of 2 mg/kg body weight (bw)/hr of endotoxin; a dobutamine group, which received endotoxin and a continuous infusion of dobutamine (3 microg/kg bw/min); and a dopexamine group, which received endotoxin and dopexamine (2 microg/kg bw/min). The experimental period was 120 min. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) were detected. Portal blood flow was measured using an ultrasonic flow probe positioned around the portal vein, and sinusoidal blood flow was detected in the left liver lobe using intravital microscopy. All detected variables remained stable in the control group. In the endotoxin group, HR increased significantly and MAP decreased significantly from 111 +/- 10 mm Hg to 95 +/- 8 mm Hg at 120 mins, whereas CO remained unchanged. Both in the dobutamine and the dopexamine group HR increased and MAP decreased more than in the endotoxin group. CO increased in both groups significantly. Portal blood flow (23 +/- 4 mL/min to 16 +/- 3 mL/min) and sinusoidal blood flow (38.6 +/- 2.5 to 22.8 +/- 1.2 10(3) microm(3)/sec) decreased significantly in the endotoxin group. In the dobutamine and the dopexamine group portal and sinusoidal blood flow remained at baseline values. CONCLUSIONS: In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow. These preservations of hepatic blood flow during endotoxemia could portend beneficial effects but need to be studied further.

Adrenergic beta-Agonists↗
PubMed2001

Angle eikonals for a perfect zoom system.

I show that it is possible to choose the eikonals for the lens groups of a zoom lens such that extended objects at infinity are imaged perfectly, without any aberrations, at all zoom settings.

Journal Article↗
PubMed2000

Influence of amrinone on tissue oxygenation of jejunal mucosa during endotoxemia.

BACKGROUND: The intestinal mucosa is the portion of the gut most susceptible to impaired perfusion and oxygen delivery. The phosphodiesterase (PDE) inhibitor amrinone has been proposed to improve oxygen delivery and tissue perfusion during sepsis. The objective of this study was to investigate the effects of amrinone on arterial oxygenation (Pao(2)) and tissue oxygenation (Ptio(2)) of jejunal mucosa during endotoxemia. MATERIALS AND METHODS: Forty anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark-type microcatheter Po(2) probe and a microthermocouple were placed on the mucosa to measure Ptio(2). The animals were randomly assigned to receive one of the four treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without amrinone pretreatment (LPS group); infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 min before LPS infusion, amrinone + LPS group); no treatment with either amrinone or LPS (control group); treatment with amrinone without LPS infusion (amrinone group). Mean arterial pressure (MAP), heart rate (HR), Pao(2), and Ptio(2) were measured 30 min before and 0, 60, and 120 min after induction of endotoxemia. RESULTS: MAP remained stable in the control and LPS groups. In the amrinone + LPS group MAP decreased within the first 30 min of amrinone infusion and decreased further during endotoxemia. Pao(2) remained stable in the control group and decreased in the LPS group. This endotoxin-induced decrease in Pao(2) was attenuated in the amrinone + LPS group. The mucosal Ptio(2) decreased in the LPS group but remained stable in both the control and amrinone + LPS groups. CONCLUSIONS: Pretreatment with amrinone was able to diminish a decrease in Pao(2) during endotoxemia, indicating that pulmonary dysfunction was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa, however, could be fully prevented, indicating that an additional improvement in compromised tissue perfusion had occurred.

Amrinone↗
PubMed2000

Role of platelet-activating factor in leukocyte-independent plasma extravasation and mast cell activation during endotoxemia.

BACKGROUND: Independently from leukocyte adherence, endothelial factors and mast cell activation seems to promote microvascular permeability. Platelet-activating factor (PAF) has been shown to play a significant role in endotoxin-induced leukocyte adherence. The aim of our study was to investigate if there is also a role for PAF in mediating leukocyte-independent microvascular permeability changes and activation of mast cells during endotoxemia. Therefore, during endotoxemia microvascular permeability and mast cell activation were determined after inhibition of L-selectin-mediated leukocyte adherence by fucoidin and after inhibition of PAF effects by the PAF receptor antagonist BN52021. MATERIALS AND METHODS: In male Wistar rats, red cell velocity (V(RBC)), venular wall shear rate, microvascular permeability, leukocyte adherence, and mast cell activation were determined in mesenteric postcapillary venules using intravital microscopy at baseline and 60 and 120 min after start of a continuous infusion of endotoxin (ETX; 2 mg/kg/h, Escherichia coli O26:B6) (ETX group). Animals in the FUCO/ETX group received fucoidin (25 mg/kg body wt) in addition to the procedure described above. Animals in the FUCO/ETX/PAF-ANT group received fucoidin and the PAF receptor antagonist BN52021 (5 mg/kg body wt) prior to the continuous endotoxin infusion. Control animals (control group) received only equivalent volumes of NaCl 0.9%. RESULTS: There were no microhemodynamic and macrohemodynamic differences between groups. In all endotoxin-challenged groups macromolecular leakage and mast cell activity increased significantly, starting at 60 min. Both macromolecular leakage and mast cell activity were significantly higher in the FUCO/ETX group than in the FUCO/ETX/PAF-ANT group and control group. Differences in macromolecular leakage between groups were significant at 120 min. Differences in mast cell activity between groups were significant at 60 and 120 min. CONCLUSIONS: The results of our study demonstrate a leukocyte-independent plasma extravasation that can be inhibited by the PAF receptor antagonist BN52021, indicating the involvement of PAF in the pathophysiology of leukocyte-independent microvascular damage during early endotoxemia. Mast cell activity seems to precede leukocyte-independent macromolecular leakage.

Animals↗
PubMed2000

A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR.

The glucocorticoid-regulated protein annexin I (lipocortin I) has been shown to mediate antiinflammatory activities of glucocorticoids, but the molecular basis of its action has remained elusive. Here we show that annexin I acts through the formyl peptide receptor (FPR) on human neutrophils. Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. Lower peptide concentrations possibly found in inflammatory situations elicit Ca2+ transients without fully activating the MAP kinase pathway. This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. These findings identify annexin I peptides as novel, endogenous FPR ligands and establish a mechanistic basis of annexin I-mediated antiinflammatory effects.

Amino Acid Sequence↗
PubMed2000

Leukocyte-independent plasma extravasation during endotoxemia.

OBJECTIVES: To determine the meaning of leukocyte-endothelial interactions for the development of endotoxin-induced vascular leakage. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-four male Wistar rats. INTERVENTIONS: After application of fucoidin to prevent leukocyte rolling and adherence (25 mg/kg; n = 8; fucoidin/LPS group) or saline 0.9% (n = 8; LPS group), animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 8) received an equivalent volume of saline 0.9%. MEASUREMENTS AND MAIN RESULTS: Leukocyte rolling and leukocyte adherence, red cell velocity, vessel diameters, venular wall shear rate, volumetric blood flow, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline, 60 mins, and 120 mins after start of a continuous endotoxin infusion. Fucoidin prevented leukocyte rolling (baseline, 3+/-2 rollers; 120 mins, 3+/-1 rollers; not significant vs. baseline; p < .01 vs. LPS group) and reduced the adherence of leukocytes at baseline and during endotoxemia and showed only a slight increase in adherent leukocytes (baseline, 100+/-38 cells/mm2; 120 mins, 244+/-68 cells/mm2; p < .05 vs. baseline; p < .01 vs. LPS group). In the LPS group, endotoxin exposure induced a marked increase in adherent leukocytes (baseline, 248+/-24 cells/mm2; 120 mins, 560+/-57 cells/mm2; p < .01). Leukocyte adherence in control animals (control group) did not increase significantly. Macromolecular leakage, expressed as the ratio of perivenular to intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.16+/-0.03 to 0.49+/-0.04 (p < .01 vs. baseline; p < .05 vs. control) during the infusion of endotoxin in the LPS group. Fucoidin application did not diminish the extravasation of albumin (baseline, 0.09+/-0.03; 120 mins, 0.61+/-0.10; p < .01 vs. baseline; p < .01 vs. control). CONCLUSIONS: These results demonstrate that despite a significant reduction of adherent leukocytes to the endothelium by fucoidin, there is no reduction in macromolecular leakage, indicating that leukocyte-endothelial interactions only play a minor role for the development of macromolecular leakage and microvascular damage in the early phase of endotoxemia.

Animals↗
PubMed2000

Plasma levels of eicosanoids after transfusion of intraoperatively salvaged blood.

BACKGROUND: The interest in autologous red blood cell salvage is increasing rapidly, but it is well known that platelets and white cells are activated during cell washing. Therefore, we aimed to determine whether or not eicosanoids transfused together with the salvaged blood are responsible for nonhemolytic immunological transfusion reactions. MATERIALS AND METHODS: In 11 patients who underwent radical prostatectomy we studied the release of eicosanoids, prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TxB(2)), in association with reinfusion of intraoperatively salvaged blood. Blood samples were taken before operation, on days 1 and 3 after operation and before and after cell washing. RESULTS: There was a twofold increase in PGE(2) and a twentyfold increase in TxB(2) in the unwashed salvaged blood. Washing caused a reduction in eicosanoid plasma levels of up to 95%, but a significantly lower level in relation to its corresponding preoperative value was only found for PGE(2). After transfusion of an average of 420 ml RBC sediment from washed blood, the patients' plasma concentrations of PGE(2) and TxB(2) on the 1st and 3rd postoperative day did not significantly differ compared to baseline values. CONCLUSION: Our data support the notion that RBC sediment from 'salvaged' and washed autologous blood contains increased amounts of PGE(2) and TxB(2). It remains, however, questionable if these passively infused eicosanoids become biologically active. According to our study, the PGE(2) and TxB(2) transfused are apparently not responsible for nonhemolytic immunological transfusion reactions.

Aged↗
PubMed1998

Influence of N-acetylcysteine treatment on endotoxin-induced microcirculatory disturbances.

OBJECTIVES: To determine the influence of N-acetylcysteine (NAC) in a treatment model, its effects on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 40 male Wistar rats. INTERVENTIONS: The rats randomly received one of four treatments: infusion of saline (SAL) or Escherichia coli lipopolysaccharides (LPS) followed by treatment with saline (SAL) or NAC (150 mg.kg-1 body weight) 30 min after induction of endotoxemia. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were evaluated every 30 min over a period of 120 min using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from red cell velocity, and vessel diameter. NAC in rats without endotoxemia (SAL + NAC group) compared to the control group (SAL + SAL) did not change microcirculatory parameters in postcapillary venules of rat mesentery. In both LPS-treated groups (LPS + SAL and LPS + NAC), leukocyte adherence increased after just 30 min. NAC treatment prevented a further increase in leukocyte adherence and attenuated the extravasation of fluorescence-labeled albumin during endotoxemia. Venular diameters remained unchanged, while erythrocyte velocity decreased in the LPS + SAL group. This led to a lower venular wall shear rate in this group. CONCLUSIONS: Treatment with NAC attenuates endotoxin-induced leukocyte adherence and macromolecular leakage in postcapillary venules of rat mesentery, showing that NAC is also effective after the onset of endotoxemia.

Acetylcysteine↗
PubMed1998

Assignment of the auxin binding abilities of ABP44 in gel.

Several approaches were successfully performed to directly assign and characterize auxin binding of ABP44 in gel. The 44 kDa high affinity auxin binding protein ABP44 from pea was tested for its ability to bind 5-azido-[7-3H]-IAA in photoaffinity labeling experiments. Competition experiments with several auxin analogues confirm data published previously (Reinard and Jacobsen 1995). Critical reflections of the limitations of the method are also discussed. Immunostaining using the antibody D16 (Napier and Venis 1992), which is directed against the putative binding site of ABP1, revealed that ABP44's auxin binding site is at least partially related to the corresponding site of ABP1. Nevertheless, both proteins do not share any further immunological relationships. Our results with D16 recommend a careful reconsideration of data published by other authors. Furthermore, a 80 kDa, dimeric glutathione dependent formaldehyde dehydrogenase (FDH) from mung bean, described recently, was found to be different from ABP44. In contrast to the described FDH, ABP44 exhibited no FDH activity.

Gels↗