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A Verheyen

Publications and source records attributed to A Verheyen.

At least 19 recordsLinked to original sources

Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing.

The epidermis is a stratified squamous epithelium in which keratinocytes progressively undergo terminal differentiation towards the skin surface leading to programmed cell death. In this respect we studied the role of caspases. Here, we show that caspase-14 synthesis in the skin is restricted to differentiating keratinocytes and that caspase-14 processing is associated with terminal epidermal differentiation. The pro-apoptotic executioner caspases-3, -6, and -7 are not activated during epidermal differentiation. Caspase-14 does not participate in apoptotic pathways elicited by treatment of differentiated keratinocytes with various death-inducing stimuli, in contrast to caspase-3. In addition, we show that non-cornifying oral keratinocyte epithelium does not express caspase-14 and that the parakeratotic regions of psoriatic skin lesions contain very low levels of caspase-14 as compared to normal stratum corneum. These observations strongly suggest that caspase-14 is involved in the keratinocyte terminal differentiation program leading to normal skin cornification, while the executioner caspases are not implicated. Cell Death and Differentiation (2000) 7, 1218 - 1224

Animals↗

Experimental reproduction of polymorphous light eruption and benign summer light eruption by whole-body UVA irradiation.

The entity 'benign summer light eruption' (BSLE) has been introduced to make a clinical subdivision in the heterogeneous group of polymorphous light eruptions (PLE). Provocation tests for PLE are not always easy to perform and require expensive apparatus. Our purpose was to evaluate a provocation test that could be readily done by a dermatologist with a UVA cabin. Provocation tests are currently required in order to obtain a financial contribution from the social security services in Belgium. In addition, we were interested in determining whether the results of the provocation test would permit us to differentiate between the clinical entities of BSLE and PLE. We studied the efficacy of whole-body UVA irradiation for BSLE and PLE patients. A total of 45 patients was tested, of whom 26 were diagnosed as having BSLE and 19 PLE. In the BSLE group, 24 patients (92%) presented lesions. In the PLE group, 15 patients (79%) had a reaction, but 3 had a positive UVB test. The mean dose to induce lesions was 65.96 J/cm2 for the BSLE group and 52.86 J/cm2 for the PLE group. We conclude that the whole-body UVA test is a high-performance provocation test for both BSLE and PLE patients although it cannot differentiate the two entities from one another.

Adolescent↗

Viral infection in guinea pigs induces a sustained non-specific airway hyperresponsiveness and morphological changes of the respiratory tract.

In the present study an animal model is described in which a sustained non-specific airway hyperresponsiveness is induced. Guinea pigs were inoculated intratracheally with parainfluenza type 3 (PI-3) virus or control solution. Two, 4, 8, and 16 days after inoculation the tracheae, bronchi, and lung strips were isolated and mounted in organ baths. Two days after inoculation no difference between the control solution and PI-3 virus group was observed, with respect to the histamine concentration/response curve obtained from tracheae, bronchi and lung strips of the respective groups. However, histamine concentration/response curves were significantly (P less than 0.01) shifted upwards in all parts of the airways 4, 8, and 16 days after PI-3 inoculation as compared with the control solution. The excessive contraction of the trachea was not specific for histamine, since an increase in the maximal response was obtained also for the cholinergic receptor agonist, arecoline on day 4 (32%, P less than 0.05), day 8 (24%, P less than 0.05), and day 16 (28%). Morphological examination of the central airways obtained from control solution-inoculated animals revealed no signs of inflammation. However, 2, 4, and 8 days, but not 16 days, after the viral infection, epithelial damage with loss of cilia and mucus-depleted goblet cells were observed. Thus, morphological changes were not directly associated with changes in airway responsiveness. Histological examination of the peripheral airways revealed an influx of inflammatory cells, as shown by typical lesions of patchy alveolitis and bronchiolitis. Bronchiolar epithelium was variously hyperplastic and dysplastic with degenerative changes, and the lumens of the bronchioli were occluded with mucus and inflammatory cells. In conclusion, the virus-induced airway hyperresponsiveness in guinea pigs shows similarities with the human situation, in which a sustained non-specific airway hyperresponsiveness is observed after a respiratory viral infection. In addition, the hyperresponsiveness seems to be accompanied by an influx of inflammatory cells in the airways but not with other morphological changes.

Animals↗

Virus-induced airway hyperresponsiveness in the guinea pig can be transferred by bronchoalveolar cells.

For the investigation of whether inflammatory cells were responsible for virus-induced airway hyperresponsiveness, tracheal spirals from healthy guinea pigs were incubated in organ baths with different numbers of bronchoalveolar cells obtained from guinea pigs 4 days after their inoculation with parainfluenza-3 (P-3) virus or control solution. Airway responsiveness was measured by performance of histamine concentration/response (C/R) curves on the tissues. Preparations incubated with 5 x 10(5) cells/ml obtained from guinea pigs treated with P-3 virus demonstrated a significant upward shift of the histamine C/R curve. The maximal contraction was increased by 26% as compared with the tissues incubated with the same number of cells from animals inoculated with control solution. When the number of cells was increased further to 5 x 10(6) cells/ml, no additional upward shift of the C/R curve was seen; the increase in maximal contraction was 24%. Tracheal spirals incubated with 5 x 10(4) cells/ml did not affect the histamine C/R curves. Addition of P-3 virus to the organ bath during the incubation period with the cells did not affect the histamine C/R curve either, irrespective of the inoculation solution or the number of bronchoalveolar cells used. The relative number of alveolar macrophages in bronchoalveolar lavage fluid decreased significantly from 86.3% +/- 2.6% in the control group to 71.8% +/- 3.3% in the P-3 virus group as a consequence of a significant increase in the percentage of monocytes, lymphocytes, and eosinophils. These results suggest that bronchoalveolar cells are causally involved in the virus-induced airway hyperresponsiveness.

Animals↗

Cholesterol-lowering effects and utilization of protein, lipid, fiber and energy in rats fed unprocessed and baked oat bran.

The effects of the addition of 15% or 30% non-heated oat bran or 30% baked oat bran to a purified diet on apparent digestibility of dry matter, protein, lipid and fiber were measured in balance experiments with male Wistar rats. The effects of oat bran on dietary metabolizable energy, fecal bulking capacity and transit time of the ingested food were also studied. Heat processing of oat bran occurred in conditions of moisture and temperature similar to those of bread baking. Compared with the unprocessed oat bran, the baked product had a higher content of insoluble fiber, mainly due to higher Klason lignin content and a shift from soluble to insoluble beta-glucans. Relative to the fiber-free control diet, feeding the oat bran diets increased wet and dry fecal weight and decreased the transit time of the food. Fecal bulking capacity increased proportionally with oat fiber intake. Metabolizable energy of the diets, as well as apparent digestibility of dry matter and protein decreased with oat bran supplementation; on the other hand, lipid digestibility was not significantly changed. Baking of oat brain resulted in no statistically significant effects on dietary metabolizable energy or apparent digestibility of dry matter, protein, lipid and fiber. The measured metabolizable energy of oat bran ranged between 12.7 and 13.2 MJ/kg. Total plasma cholesterol concentration diminished with oat brain intake; non-heated and baked oat bran had comparable effects on plasma cholesterol. An inverse linear relationship (r = -0.80, P less than 0.1) was found between plasma cholesterol concentration and fecal excretion of bile acids.

Animals↗

Oversensitivity to serotonin of the collateralized vascular bed in rat hindquarters: mechanisms of increased vasoconstriction.

A buffered solution was perfused at a constant flow rate (2 ml/min) through both iliac arteries in rat hindquarters. Perfusion pressures were measured in normal and collateralized vascular beds of the left and right hind-leg, respectively. Bolus injections of various agonists produced concentration-dependent increases in perfusion pressure in both collateralized and normal circulatory beds. Serotonin, in particular, and noradrenaline, to a lesser extent, produced more pronounced vasoconstriction on the collateral side than on the normal side. The difference in vasoreactivity to serotonin was related to a difference in both vascular structure and sensitivity of both types of vascular bed. Vasoconstriction induced by serotonin was inhibited by 5-HT2 antagonists. Selective blockade of alpha 1,alpha 2,beta 1-beta 2 adrenoceptors and amine uptake blockade were ineffective. This study indicates that, in rat hind-legs, the collateralized vascular bed is superreactive to serotonin in comparison with the normal bed. This resetting of reactivity to serotonin is due to the specific vascular structure as well as to an increased 5-HT2 receptor-mediated sensitivity.

Animals↗

Arachidonic acid metabolites, ADP and thrombin modulate occlusive thrombus formation over extensive arterial injury in the rat.

Platelet-dependent occlusive thrombosis at sites of deep vessel wall injury elicited by electrical stimulation of rat carotid arteries was significantly reduced by thromboxane A2 (TXA2) synthetase inhibition and/or TXA2/prostaglandin endoperoxide receptor antagonism (ridogrel 1.25 mg/kg i.v.; dazoxiben 5 mg/kg i.v.; sulotroban 20 mg/kg i.v.), by inhibition of ADP-dependent platelet responses (ticlopidine 3 x 200 mg/kg orally) and by anticoagulation (heparin 250 U/kg i.v.; warfarin 1.25 mg/kg i.p.). This points to an involvement of arachidonic acid metabolites, ADP and thrombin as modulators of the thrombotic process. The antithrombotic effect of ridogrel (IC50 = 0.22 mg/kg i.v.) was abolished by cyclooxygenase inhibition (suprofen 5 mg/kg i.v.) but enhanced by cAMP phosphodiesterase inhibition (HL 725 6 micrograms/kg/min i.v.), demonstrating the importance of platelet inhibitory prostanoids such as PGD2, and prostacyclin formed after TXA2 synthetase inhibition. High doses of ridogrel (1.25 mg/kg i.v.) producing additional TXA2/prostaglandin endoperoxide receptor antagonism were more effective than lower doses (0.16 mg/kg i.v.) providing TXA2 synthetase inhibition alone. The antithrombotic effect of ridogrel, when combined with ticlopidine or heparin, exceeded that of the single compounds, pointing to interactions between arachidonic acid metabolites, ADP and thrombin in the formation of occlusive thrombosis at sites of arterial injury.

Adenosine Diphosphate↗

Ultrastructural evaluation of the effects of diclazuril on the endogenous stages of Eimeria maxima and E. brunetti in experimentally inoculated chickens.

The ultrastructural morphology of the different endogenous stages of Eimeria maxima and E. brunetti was evaluated after oral treatment of inoculated chickens with a single dose of 5 mg/kg diclazuril. The drug induced no ultrastructural change in the growth or differentiation of the various schizont stages of both Eimeria spp. In E. maxima, the micromorphological appearance of micro- and macrogamonts developing from the blast from to maturation also remained unaffected by drug treatment. However, in all fertilized macrogamonts the normal pattern of oocyst wall establishment was completely disturbed, resulting in the formation of an abnormally thickened, incomplete oocyst wall and the necrosis of the zygote. In E. brunetti, the growth and nuclear division during microgametogenesis were not affected but differentiation was clearly abnormal. In comparison with the controls, this abnormal differentiation was characterized by a less extensive enlargement of the parasite surface area, aberrant morphological configurations of condensed heterochromatin, intracytoplasmic flagella formation, and glycogen accumulation. Finally, the complete degeneration of all microgamonts ensued. The growth and differentiation leading to mature macrogamonts was not disturbed; however, subsequent oocyst wall formation was largely precluded and the macrogamonts proceeded to degenerate completely. We conclude that diclazuril treatment primarily affected particular stages in the sexual development of both Eimeria spp., resulting in the complete eradication of these coccidian species.

Animals↗

Differential vasoreactivity to the thromboxane A2 mimic U-46619 of collateral and normal peripheral blood vessels in situ perfused rat hindquarters.

In situ perfusion of rat hindquarters was performed through both iliac arteries. Perfusion pressures were measured concomitantly in the normal vascular bed and in the ligation-induced collateral bed of the left and right hindleg, respectively. An increased vaso-constrictive response of the collateral versus normal blood vessels was found after bolus injections of increasing concentrations of the thromboxane A2 (TXA2) mimic U-46619. This increased reactivity was related to a difference in vascular structure and in receptor-mediated sensitivity. The vasoconstrictive effect of U-46619 was dose-dependently inhibited by the combined TXA2 synthetase inhibitor-TXA2/prostaglandin endoperoxide (PGH2) receptor antagonist ridogrel and the single TXA2/PGH2 receptor antagonist sulotroban. Selective blockade of alpha 1-, alpha 2-, beta 1-beta 2- and S2-receptors, cyclooxygenase inhibition, TXA2 synthesis inhibition, amine depletion and amine uptake blockade had no influence on the vasoconstrictive action of U-46619. Ca2+ entry blockade by flunarizine and nifedipine significantly reduced the vasoconstriction. This study shows that (1) rat peripheral collaterals in relation to normal arterial blood vessels are significantly more reactive to TXA2; (2) the vasoconstrictive effect of U-46619 is mediated predominantly by TXA2/PGH2 receptors; (3) the activation of these receptors elicits indirectly transmembrane Ca2+ entry to trigger vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

In vivo action of the anticoccidial diclazuril (Clinacox) on the developmental stages of Eimeria tenella: an ultrastructural evaluation.

A single 5-mg/kg oral dose of diclazuril affected both the asexual and sexual development of Eimeria tenella in experimentally inoculated chickens. In second-generation schizonts, early growth and nuclear divisions progressed normally, but a marked inhibition of merozoite formation was observed. Exogenesis of merozoites was largely prevented, whereas production of micronemes, amylopectin granules, and dense bodies and the formation of rhoptries, conoid, and pellicle continued. All these subcellular organelles accumulated, together with differentiated nuclei, within the main cytoplasmic mass. In the end, complete necrosis of the schizonts occurred. In macrogamonts, dilation of the rough endoplasmic reticulum around type II wall-forming bodies, fusion of type II wall-forming body contents, disturbance of the normal parallel arrangement of rough endoplasmic reticulum, and disruption of row formation of amylopectin granules became evident. In the microgamonts, normal evagination of microgametes was prevented; the flagellar complex formed within the main cytoplasmic mass and the differentiated nuclei remained present within the parasite body. The macro- and microgamonts also ended up in a stage of complete necrosis. These data indicate that diclazuril treatment primarily affects the normal differentiation of the respective endogenous stages during parasite development. This leads to complete degeneration of schizonts and gamonts indicating the lethal effect of this new anticoccidial compound.

Animals↗

Determination of areal densities of blood vessel wall components in histological sections by means of image analysis.

A technique is described which allows quantification of specifically stained, intermingled vessel wall components in paraffin-embedded tissue. The dissociation of elastic, muscular and connective tissue and the determination of their areal densities in the superior vena cava and in the ascending aorta of the dog, was performed by automated image analysis. The percentages of elastic+connective tissue, determined by this technique, correlated significantly with the data derived from biochemical measurements. It was further found that the structure of the vena cava wall was a function of the distance from the right atrium.

Animals↗

Radioactive colloidal gold as a tool to quantify extravasation of macromolecules in the rat cremaster muscle.

Since previously described simple methods were too insensitive to quantify the extent of microvascular permeability increase in the rat cremaster muscle, we applied a new quantitative technique using radioactive colloidal gold (198Au) as the macromolecular tracer. Dose-response effects on microvascular permeability were found with increasing doses of subscrotally injected serotonin or histamine. The presence of colloidal gold particles in the subendothelial space of the postcapillary venules, as verified ultrastructurally, indicated endothelial permeation of the tracer macromolecules. The increased permeability elicited by serotonin was inhibited in a dose-dependent way by serotonin receptor antagonists (potency: methysergide greater than or equal to ketanserin = ritanserin greater than cinanserin), suggesting the presence of functional S2-serotonergic receptors on postcapillary venular endothelial cells. A dose-related inhibition of the histamine-induced extravasation was seen with the H1 antagonists astemizole and azatidine (astemizole greater than azatidine); the H2 antagonists cimetidine and ranitidine had no inhibitory effect. The radioactive colloidal gold technique is a sensitive and reliable tool for pharmacological experiments aimed at investigating the extravasation phenomenon in small tissue samples such as the rat cremaster muscle.

Animals↗

Biphasic response of intimal prostacyclin production during the development of experimental atherosclerosis.

Feeding a cholesterol rich diet (0.3%) to rabbits for up to 10 weeks resulted in morphological changes of the vascular wall. Microscopic evaluation of the aorta revealed a lipid infiltration and an intimal thickening containing foam cells, which both became more pronounced as the cholesterol feeding was more prolonged. The intimal prostacyclin production showed a transient increase after 2 weeks, but was significantly decreased after 6 weeks of diet and remained at this low level during the rest of the experiment. No significant changes in formation of thromboxane B2 by the platelets could be observed, whereas the production of 12-HETE was enhanced.

Animals↗

Correlation between mechanical properties and wall composition of the canine superior vena cava.

The mechanical properties (modulus of elasticity and stress-relaxation) of different venous segments of the canine superior vena cava were determined as well as the composition of the vessel wall by means of physical, biochemical and histological methods. It was found that the wall of the vena cava was structurally and mechanically a function of the metric position with respect to the right heart: the modulus of elasticity increased, the stress-relaxation decreased, the concentration of hydroxyproline, collagen and elastin increased and the amount of muscle fibres decreased with increasing distal distance from the right heart. A significant linear correlation coefficient was observed between the modulus of elasticity and the structural wall components. The data presented show the axial heterogeneity and the dependency of the mechanical properties upon the venous vessel wall composition.

Animals↗

Spontaneous adenocarcinoma of the ascending colon in Wistar rats: the intracytoplasmic presence of a Campylobacter-like bacterium.

Campylobacter-like bacteria were demonstrated in the neoplastic cells in 15 of 17 naturally occurring endophytic adenocarcinomas of the ascending colon in Wistar rats. These bacteria were also present in the cytoplasm in metastases in the regional lymph nodes. The microorganisms penetrated the epithelial layer and their presence was associated with a chronic productive inflammatory reaction. A possible causal association of Campylobacter-like organisms in carcinoma of the colon in man and in the Wistar rat is discussed.

Adenocarcinoma↗

Enzyme cytochemistry.

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Adenosine Triphosphatases↗

Thromboxane A2-induced vascular endothelial cell damage and respiratory smooth muscle cell contraction: inhibition by flunarizine, a Ca2+-overload blocker.

The fast intravenous injection of arachidonic acid (AA) in mice produces, in a dose-related way, mortality due to respiratory distress. Upon electron microscopical examination an extensive oedematous damage of the capillary endothelium was found; thrombotic platelet obstructions were present in a minority of pulmonary capillaries only. Protection against this toxic AA-effect is obtained with inhibitors of fatty acid cyclo-oxygenase and of thromboxane (TXA2) synthetase, suggesting involvement of TXA2 as a causative mediator. The Ca2+-entry blockers flunarizine, niludipine and nimodipine, not affecting TXA2 synthesis by murine platelets, also provide protection, but not the antiplatelet drugs ticlopidine, dipyridamole or suloctidil; thrombocytopenia induced by busulphan does not affect the AA-induced mortality nor the protection obtained with flunarizine. Platelet-independent bronchoconstriction induced by AA in guinea-pigs is also inhibited by flunarizine. This study suggests that the AA-induced mortality test reflects pulmonary conversion of AA to TXA2 producing endothelial cell damage and respiratory smooth muscle cell contraction rather than a thrombotic phenomenon. The protective effect of flunarizine against TXA2 induced changes in vivo may contribute to its effectiveness in particular hypoxic conditions associated with liberation of AA.

Animals↗