Biomedical subjects

U Bagge

Publications and source records attributed to U Bagge.

At least 19 recordsLinked to original sources

PubMed2001

Disturbance of purine nucleotide metabolism: a possible early key event in development of intestinal damage induced by chemotherapy.

Protective strategies to minimize the hematological toxicity in connection with bone marrow transplantation (BMT) have been successful, but toxicity to the gastrointestinal tract prevents further dose escalation and therefore limits the application of the treatment. As it is known that chemotherapy leads to disruption of the intestinal barrier and morphological changes of mitochondria in enterocytes, this study was conducted in order to investigate intestinal energy metabolism and permeability after intensive cytotoxic therapy in rats. Intestinal damage was produced by intraperitoneal administration of the cytostatic etoposide. Intestinal permeability was assessed by a [51Cr]EDTA absorption test and intestinal purine nucleotide content by a high-performance liquid chromatography (HPLC) technique. Four hours after the administration of etoposide, and the next 48 hr, there was a significant increase in the intestinal permeability (P < 0.05) and a significant reduction of the purine nucleotide content in the intestinal epithelial cells (P < 0.01) as compared to control animals. This early disturbance in enterocyte energy metabolism may be a key event in the development of the intestinal damage, induced by chemotherapy, and an explanation for the early disruption of the intestinal barrier demonstrable before morphological changes are evident.

Animals↗

PubMed2000

Adaptation of normal and hypofunctional masseter muscle after bite-raising in growing rats.

The aim of this study was to analyze the effects of prolonged muscular elongation induced by bite-raising on the length of the muscle belly, sarcomeres and aponeurosis of the anterior deep masseter in the growing rat. Another aim was to determine the role of different functional conditions of this muscle in the adaptation process. Ninety-six young male rats were split into two groups: one was fed a hard diet and the other a soft diet to develop different functional capacities in the masticatory muscles. After 2 wk, half of the rats in both groups were fitted with an appliance that raised the bite by 2 mm. The measurements on the muscles were performed in situ. The insertion of the appliance stretched the anterior masseter muscle. After 4 wk, the vertical dentoskeletal dimension, the muscle belly, and the sarcomeres showed no difference in length among the groups. However, the aponeurosis was longer in the rats wearing the appliance compared to the controls, and among the bite block groups it was longer in the rats fed a hard diet. Length adaptation occurred in the aponeurosis. Clinically this may imply a need for reactivation of functional appliances to increase their efficiency, at a rate possibly depending on masseter muscles functional condition.

Acrylic Resins↗

PubMed1999

Effects of hyperbaric oxygen treatment on neutrophil activation and pulmonary sequestration in intestinal ischemia-reperfusion in rats.

Treatment with hyperbaric oxygen (HBO) has shown promising results in some models of ischemia, the major effect being a reduction in the local ischemic damage. The present study investigated the effects of HBO treatment on neutrophil activation and leukosequestration during reperfusion following intestinal ischemia in a rat model. The superior mesenteric artery was clamped for 2 h and subsequently reperfused for 90 min. One group of male Sprague-Dawley rats (n = 9) was given HBO and another group (n = 9) served as controls. Prior to ischemia, leukocytes and erythrocytes were separated, radiolabelled with 111ln and 51Cr, respectively, and reinfused. Leukocyte transit factor, the ratio between the mean passage time of leukocytes and erythrocytes was used to quantitate leukosequestration and the fraction of circulating, spontaneously nitroblue tetrazolium (NBT)-reducing neutrophils was used to measure the degree of neutrophil preactivation. HBO treatment reduced the level of leukocyte pooling significantly, especially in the lungs but also, to a minor degree, in the systemic vascular bed. The percentage of NBT-positive cells increased in all animals after reperfusion, but the increase was significantly reduced by HBO treatment. In conclusion, HBO treatment reduces leukosequestration and neutrophil preactivation following intestinal ischemia-reperfusion.

Animals↗

PubMed1998

Vasoconstriction during acute hypervolemic hemodilution in hypertensive patients is not prevented by calcium blockade.

The reduction of blood viscosity by moderate acute hypervolemic hemodilution in untreated hypertensives can be associated with a secondary vasoconstriction. The aim of this study was to examine whether a vasodilating therapy prevents this hemodynamic reaction. Twelve hypertensive patients (WHO stage II) were treated with the vasoselective calcium channel blocker isradipine in a placebo-controlled, double-blind, crossover study. Acute hypervolemic hemodilution was performed twice: at the end of the placebo period and after two months of treatment. Hemodilution was achieved by the intravenous infusion of 1000 mL saline over a 10- to 15-minute period. Arterial blood pressure, heart rate, cardiac output (dye dilution), renal blood flow, glomerular filtration, natriuresis, hematocrit, whole blood, and plasma viscosity were assessed before and after infusion. Flow resistance and vascular hindrance in the central and renal circulation were calculated. Acute hemodilution associated with a significant reduction of blood (P<0.01) and plasma (P<0.01) viscosity did not influence the mean arterial pressure and cardiac output. Consequently, the total flow resistance remained unchanged. However, as a result of hemodilution, the calculated vascular hindrance index in the systemic circulation increased, indicating a vasoconstrictive reaction, both with placebo (from 5.22 to 6.07 U x mPa(-1) x s(-1), P < 0.05) and during chronic treatment with calcium blockade (from 3.75 to 4.22 U x mPa(-1) x s(-1), P<0.02). Vasoconstriction was not observed in the renal circulation, either during the placebo or active treatments. The results of this study indicate that the systemic vasoconstriction evoked by the acute moderate hypervolemic hemodilution in hypertensive patients was not prevented by a calcium channel blockade.

Antihypertensive Agents↗

PubMed1996

Spontaneous nitroblue-tetrazolium (NBT) reduction related to granulocyte priming and activation.

The aim of the present study was to explore the relationship between the increasing level of spontaneous NBT-reduction and the tendency for PMNs to marginate during experimental hemorrhagic shock in rats. Rat PMNs, isolated on Percoll density gradients or suspended in blood, were examined by chemiluminescence (CL), NBT-test and by their CD-18 expression and F-actin formation. The NBT-test generally produced higher numbers of activated PMNs when the cells were suspended in buffer than in whole blood, probably due to the scavenging properties of blood. The level of spontaneous NBT-reduction of PMNs in blood correlated with the magnitude of the NBT-response to f-MLP stimulation in blood and buffer. On the contrary, there were no significant correlations between spontaneous NBT reduction, CD18 expression and F-actin content. Thus, high levels of spontaneous NBT reduction in blood were associated with priming of the separated PMNs rather than increased rigidity (F-actin) or adhesiveness (CD18).

Actins↗

PubMed1996

Hemorheologic effects of vasodilation in essential hypertension.

Arterial hypertension is often associated with plasma volume contraction and hemoconcentration, which negatively affect the vascular flow resistance and microcirculation. Since some antihypertensive drugs can affect blood rheology, the purpose of this study was to evaluate whether acute and long-term arterial vasodilation with cadralazine influences rheologic parameters in essential hypertension. Twelve patients with unsatisfactorily controlled essential hypertension were studied. In the acute double-blind phase of the study the patients were allocated to treatment with either cadralazine or placebo. Intraarterial blood pressure, cardiac output (dye dilution), and blood rheology (viscosity, hematocrit) were registered before and after the first dose of cadralazine. Then 9 patients (3 dropouts) were treated with cadralazine and placebo during two four-week crossover periods and continued with cadralazine medication during the eight-week open phase of the study. Blood pressure and blood hemoglobin were followed during long-term treatment. A single oral dose of cadralazine caused vasodilation (total peripheral resistance index decreased from 45 to 33 U x m2, P < 0.05), which was accompanied by hemodilution (hematocrit declined from 46.9% to 42.5%, P < 0.05) and a blood viscosity reduction of more than 10%. Viscosity of 45% suspension of erythrocytes in plasma was also reduced, suggesting a possible modification of the microrheologic factors. The changes in total peripheral resistance correlated negatively with the changes in hematocrit. An antihypertensive effect of cadralazine was still observed during the chronic phase of the study, which was not accompanied by hemodilution. It is concluded that arterial vasodilation with cadralazine reduces flow resistance in the circulatory system in hypertension and has acute rheologic effects that disappear during chronic medication.

Antihypertensive Agents↗

PubMed1996

Heat-sterilized PD fluid blocks leukocyte adhesion and increases flow velocity in rat peritoneal venules.

Data from cell culture experiments indicate that heat sterilization of peritoneal dialysis (PD) fluids produces cytotoxic glucose degradation products. The present vital microscopic study investigated the effects of different sterilization methods on the biocompatibility of PD fluids. Thus, heat-sterilized (commercially obtained and experimentally produced) and filter-sterilized PD fluids (pH = 5.30-5.40; 1.5% glucose) were compared with Tyrode buffer, with respect to the effects on microvascular blood flow velocity and leukocyte adhesion in the rat mesentery. Exteriorization of the mesentery produced a mild inflammation, known from the literature and characterized by the adhesive rolling of leukocytes along venular walls. Superfusion of the mesentery with filter-sterilized PD fluid had no significant effects on leukocyte rolling or flow velocity in venules 25-40 microns in diameter compared with buffer superfusion. Heat-sterilized PD fluid decreased the concentration of rolling leukocytes and increased flow velocity significantly, as compared with buffer and filter-sterilized PD fluid. The results indicate that heat sterilization of PD fluids produces substances that interact with microvascular tone and leukocyte-endothelial adhesion, which hypothetically could impair the acute, granulocyte-mediated defense against bacterial infections.

Animals↗

PubMed1995

NBT reactivity correlates to the distribution of PMNs between rat pulmonary and systemic circulation.

The rat systemic and pulmonary vascular transit times of radiolabeled polymorphonuclear granulocytes (experimental population referred to as "Polys") and mononuclear leukocytes (experimental population referred to as "Monos") (111In) in relation to those of erythrocytes (51Cr) were measured under physiological conditions. Results were also expressed as "circulating" pool and "marginated" pool of the two leukocyte fractions, and it was investigated whether the degree of spontaneous granulocyte activation, measured with the nitro blue tetrazolium (NBT) reduction test, was of importance for the retention of Polys in the lungs. The measured mean vascular transit was similar for Monos and Polys and several times slower than that of the erythrocytes in the pulmonary (17.4 times) and the systemic (4.1 times) vascular beds. The percentage of NBT-positive cells was < 10% in most animals, indicating a low level of spontaneous granulocyte activation. Increasing levels of NBT-positive cells correlated with a redistribution of granulocytes from the systemic marginated cell pool to the pulmonary marginated cell pool. Microscopic evaluation of sections from embedded lung tissue biopsies, obtained after intravital staining of the leukocytes, confirmed the isotope data on pulmonary transit.

Animals↗

PubMed1995

Ascorbate preserves gastric mucosal metabolism and microcirculation after hemorrhagic shock and retransfusion in rats.

The gastric mucosal microcirculation and purine nucleotide metabolism were studied in rats after hemorrhagic shock and retransfusion. The mucosal surface density of perfused vessels (SDPV) and the mucosal levels of ATP, ADP, AMP, IMP, hypoxanthine and uric acid were measured following 15 min of hemorrhagic shock and 10 and 30 min after retransfusion, and the effects of pretreatment with allopurinol or ascorbate were studied. During shock there was a dephosphorylation of nucleotides and a decline in the SDPV. Retransfusion led to an additional reduction in the SDPV, but a complete restoration of preshock nucleotide levels 30 min after retransfusion. Allopurinol accelerated early rephosphorylation of nucleotides without effects upon SDPV while ascorbate completely preserved the mucosal level of energy-rich nucleotides 15 min after hemorrhagic shock and increased SDPV during early reperfusion. The results showed that there was a renewal of energy stores in gastric mucosa after hemorrhagic shock and retransfusion although parts of the vascular bed were not reperfused. The mucosal energy depletion after 15 min of hemorrhagic shock and part of the mucosal vessel injury after retransfusion were prevented by pretreatment with ascorbate.

Allopurinol↗

PubMed1995

Leukocyte margination during hemorrhagic shock correlates to preshock margination and is reduced by fucoidin.

Systemic and pulmonary circulation kinetics for 51Cr-erythrocytes and 111In-leukocytes were measured in rats during experimental hemorrhagic shock and normotension with or without pretreatment with the antirolling agent fucoidin. Leukocyte margination was expressed as transit factors (white blood cell transit time/red blood cell transit time) for polymorphonuclear and mononuclear cells. There was an increased pooling of leukocytes in the pulmonary and systemic vascular beds during shock with a maximum after 60 min when the transit factors had increased 2.90-3.72 times in the pulmonary vascular bed and 2.00-3.52 times in the systemic vascular bed for mononuclear and polymorphonuclear cells, respectively. High preshock pooling levels lead to a more pronounced increase in pooling during shock. Pretreatment with fucoidin significantly reduced the pooling increase in the systemic vascular bed. Granulocyte oxidative activity (nitro blue tetrazolium test) invariably increased during shock and was not affected by fucoidin.

Animals↗

PubMed1994

Neutralization of the cytolytic and myotoxic activities of phospholipases A2 from Bothrops asper snake venom by glycosaminoglycans of the heparin/heparan sulfate family.

Basic phospholipases A2 from the venom of Bothrops asper exhibit skeletal muscle damaging activity in vivo, and cytolytic activity to a variety of cell types in culture. Glycosaminoglycans of the heparin/heparan sulfate family were found to be potent blockers of the cytolytic action in vitro, and, as well, to be able to neutralize the muscle damaging activity of purified myotoxins and crude venom in vivo. However, the neutralizing effect of heparins was more potent in vitro than in vivo. The cytolytic activity of myotoxin II (a lysine-49 phospholipase A2 isoform) and its inhibition by heparin was characterized. The neutralizing effect of heparin did not depend on its anticoagulant activity, since both standard heparin and heparin with low affinity for antithrombin (LA-heparin) had a similar efficiency. Heparan sulfate and low molecular mass heparin (5 kDa) also neutralized myotoxin II. In contrast, different heparin-derived disaccharides were unable to block cytolysis, implying a requirement for a longer carbohydrate chain structure for the interaction with the protein. By affinity chromatography and gel diffusion, it was demonstrated that heparins form a complex with all isoforms of basic venom myotoxins, held at least in part by electrostatic interactions. The phospholipase A2 activity of myotoxin III, a related aspartate-49 isoform from the same venom, was unaffected by heparins, despite the fact that its myotoxic activity was inhibited, indicating a dissociation of the two actions.

Animals↗

PubMed1994

The dynamics of local tissue damage induced by Bothrops asper snake venom and myotoxin II on the mouse cremaster muscle: an intravital and electron microscopic study.

The acute tissue damaging effects of Bothrops asper snake venom and a myotoxic Lys-49 phospholipase A2 (myotoxin II) on the mouse cremaster muscle were studied by intravital and electron microscopy. Both venom and myotoxin induced local contractions of the muscle fibres within 10-60 sec after exposure, which disappeared after 1-2 min. This observation is consistent with the hypothesis that Bothrops myotoxins act initially at the sarcolemma by affecting its permeability and allowing an influx of calcium. The venom also induced an early but transient vasoconstriction of arterioles. The development of edema was monitored using i.v. FITC-dextran as a marker. Plasma leakage started after about 2 min of exposure to venom or myotoxin, was extensive by 4-5 min, and originated from small venules and their adjoining capillary segments. The venom induced formation of thrombi and emboli in venules, but not in arterioles. Haemorrhage appeared after 4-6 min of exposure, the bleedings always originating from capillaries and small venules. The microbleedings were explosive, appearing as rapid bursts of erythrocytes into the extravascular space, and suggesting a per rhexis type of haemorrhage. This was confirmed by electron microscopy evaluation of the same microvessels observed intravitally, which showed erythrocyte extravasation through gaps in damaged endothelial cells. Other phenomena in the microcirculation included blood-flow disturbances, crenation and sphering of erythrocytes, and stasis with dense packing of cells in capillary networks. Muscle necrosis, caused by either venom or myotoxin, started 3-4 min after application. The first sign of damage in the fibres was the development of a narrow, transverse band with local loss of striation. This was followed by slow retraction of myofibrils until there was a complete transverse rupture of the fibre. This process was often repeated along the same fibre, leaving a row of fragments separated by spaces apparently devoid of myofibrillar material. The results confirm the rapid tissue damaging effects of B. asper venom, implying that potentially useful blocking agents must be administered early and have the ability to diffuse rapidly into the tissues.

Animals↗

PubMed1994

Blocking of endothelial-leukocyte interaction (rolling) does not improve reflow in the rat gastric mucosa after hemorrhagic shock and retransfusion.

The polymorphonuclear neutrophilic granulocyte (PMN) has been implicated as one possible cause of the no-reflow phenomenon seen upon reperfusion after ischemia, by, for instance, the release of toxic substances and/or microvascular flow obstruction. In the present study we studied the effects of ascorbate (an antioxidant) and fucoidin (an inhibitor of leukocyte rolling in microvessels) on the rat gastric mucosal and submucosal PMN content and vascular patency (the latter assessed as the surface density of perfused vessels) in connection with hemorrhagic shock (15 min) and retransfusion (5 or 10 min). The effect of fucoidin on the leukocyte rolling in small venules was studied separately with vital microscopy in the rat mesentery. As found in earlier studies, shock and retransfusion led to a decrease in the surface density of perfused vessels, whereas the number of PMNs in the mucosa or the submucosa was not affected by shock and retransfusion. Ascorbate improved vascular patency without affecting the PMN content. In the mesentery, fucoidin caused a 76% reduction in the number of rolling PMNs and it reduced significantly the number of PMNs in the mucosa, but not in the submucosa, after 10 min of retransfusion. Fucoidin had no effect on the vascular patency at that or any other time point. On the basis of these experiments it is concluded that PMN accumulation cannot be singled out as the cause of no-reflow in the rat gastric mucosa after shock and retransfusion of the degree and duration analyzed in this investigation.

Animals↗

PubMed1994

Ascorbate reduces gastric bleeding after hemorrhagic shock and retransfusion in rats.

The rat gastric mucosa, superfused with 0.1 N HCl, was investigated following 15 min of hemorrhagic shock and 30 min of retransfusion after pretreatment with ascorbate (1 mg/100 g b.w. or 5 mg/100 g b.w.). The size of the ischemic areas and the amount of mucosal bleeding using 51Cr labeling of red blood cells were assessed. Ischemic areas developed during shock. Following retransfusion, bleedings occurred at the border zones between ischemic and surrounding circulated areas. Ascorbate in both doses protected the gastric mucosa by reducing the amount of bleeding following 30 min of retransfusion as well as by reducing the area of ischemia 5 min after retransfusion.

Animals↗

PubMed1993

Gastric mucosal microcirculation and purine nucleotide metabolism after retransfusion of rats in hemorrhagic shock.

Gastric mucosal microcirculation and purine nucleotide metabolism were studied after hemorrhagic shock and retransfusion in rats. The number of perfused microvessels and the concentration of adenosine triphosphate, adenosine monophosphate, inosine monophosphate, inosine, hypoxanthine, xanthine, and uric acid were investigated in mucosal biopsy specimens after 15 or 45 min of hemorrhagic shock and after 15 min of shock followed by 30 min of retransfusion. During shock a dephosphorylation of nucleotides and a decrease in the number of perfused microvessels occurred, the more the longer the duration of the shock period. Retransfusion led to an additional reduction in the number of perfused microvessels, but there was a partial restoration of high-energy phosphate metabolites in those areas of the mucosa which maintained a blood flow. The results indicate that there is a renewal of energy stores in gastric mucosa after hemorrhagic shock and reperfusion, although parts of the vascular bed are not reperfused.

Animals↗

PubMed1993

Erythrocyte-leukocyte interactions in the vascular bed of isolated perfused rat lungs.

An earlier study of perfused rat lungs showed that leukocytes, given as bolus injections, seemed to become more or less permanently trapped in the pulmonary microvascular bed under erythrocyte-free perfusion. The aim of the present study was, therefore, to investigate the rheologic effects of erythrocytes on the leukocyte microcirculation of perfused rat lungs. Leukocyte and erythrocyte suspensions were given as bolus injections during cell-free, constant pressure perfusion of ventilated rat lungs. Leukocyte numbers were counted in samples of the venous effluent and flow resistance changes were computed from registrations of flow rate, arterial and venous pressures. The preparations showed a continuous efflux of leukocytes which had been trapped in the pulmonary microcirculation before the perfusion was started. A bolus infusion of erythrocytes (3 ml, hematocrit: 30%) caused a transient flow resistance increase during the passage of the erythrocyte bolus through the vascular bed. This initial peak was accompanied by an increased venous efflux of leukocytes and followed by a lower second peak, attributed to a redistribution of trapped leukocytes in the capillary bed. Infusions of mixed cell suspensions (20-30 x 10(6) leukocytes in 30% hematocrit) caused a transient resistance increase similar to that caused by erythrocytes and a sustained resistance increase, less persistent than that caused by leukocytes. The present data suggest that the infusion of erythrocytes caused a re-distribution and an increased efflux of leukocytes, pooled in the pulmonary microcirculation. The rheological effects of erythrocytes could, hypothetically, result from mechanical interactions with the leukocytes in the pulmonary microvessels.

Animals↗

PubMed1992

Inhibition of leukocyte phagocytosis by serotonin and its possible role in tumor cell destruction.

Intraportal tumour cell (TC) injection activates platelets which release serotonin (5-HT). Thrombocytopenia or 5-HT blockade decrease the hepatic lodgement of the injected TCs. A hypothetical explanation of this is 5-HT inhibition of TC killing by phagocytes (e.g. leukocytes and Kupffer cells). In this study, leukocyte phagocytosis was analysed by a chemiluminescence technique at different 5-HT concentrations. Significant inhibition of phagocytosis occurred at 5-HT concentrations of 10(-4) M to 10(-8) M, with maximum inhibition at 10(-4) M. Comparable concentrations of 5-HT may be found locally in the liver during TC infusion, supporting the hypothesis that 5-HT has an inhibitory effect on phagocyte-mediated TC killing.

Animals↗

PubMed1992

Lethal deformation of cancer cells in the microcirculation: a potential rate regulator of hematogenous metastasis.

The hypothesis has been advanced that deformation-induced lethal mechanical trauma, resulting in surface-membrane rupture, is inflicted on circulating cancer cells trapped in the microcirculation, and that this rapid cell-killing mechanism is a potentially important rate regulator for hematogenous metastasis. We describe and discuss an in vivo test of this hypothesis. Vital fluorescence microscopy was performed on the microcirculation of cremaster muscle preparations in mice, following retrograde injections into the femoral artery of acridine orange-stained sarcoma cells. Cancer cells having mean diameters of 16.5 microns in suspension, were deformed from spheres into cylinders having a mean length of 53 microns, in 7-microns diameter capillaries. Most of these cells were dead several minutes after injection. It was estimated that sphere-to-cylinder shape-transitions of this magnitude required an average increase of 52% in apparent cell surface area. Evidence is presented that most of this apparent increase was achieved by non-lethal surface "unfolding", utilizing membrane "excess". That cancer-cell deformation of the magnitude observed in vivo is the direct cause of lethal, surface-membrane rupture was indicated by the observed loss of membrane integrity in cells deformed from spherical to cylindrical shape in vitro, by aspiration into micropipettes of capillary dimensions. The experimental observations are therefore consistent with the hypothesis.

Animals↗