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Biomedical subjects

P de Vos

Publications and source records attributed to P de Vos.

At least 19 recordsLinked to original sources
PubMed2006

Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis.

BACKGROUND: Oxidation of low-density lipoprotein (LDL) and the subsequent processing of oxidized LDL (oxLDL) by macrophages results in activation of specific T cells, which contributes to the development of atherosclerosis. Oral tolerance induction and the subsequent activation of regulatory T cells may be an adequate therapy for the treatment of atherosclerosis. METHODS AND RESULTS: Tolerance to oxLDL and malondialdehyde-treated LDL (MDA-LDL) was induced in LDL receptor-/- mice fed a Western-type diet by oral administration of oxLDL or MDA-LDL before the induction of atherogenesis. Oral tolerance to oxLDL resulted in a significant attenuation of the initiation (30% to 71%; P<0.05) and progression (45%; P<0.05) of atherogenesis. Tolerance to oxLDL induced a significant increase in CD4+ CD25+ Foxp3+ cells in spleen and mesenteric lymph nodes, and these cells specifically responded to oxLDL with increased transforming growth factor-beta production. Tolerance to oxLDL also increased the mRNA expression of Foxp3, CTLA-4, and CD25 in the plaque. In contrast, tolerance to MDA-LDL did not affect atherogenesis. CONCLUSIONS: OxLDL-specific T cells, present in LDL receptor-/- mice and important contributors in the immune response leading to atherosclerotic plaque, can be counteracted by oxLDL-specific CD4+ CD25+ Foxp3+ regulatory T cells activated via oral tolerance induction to oxLDL. We conclude that the induction of oral tolerance to oxLDL may be a promising strategy to modulate the immune response during atherogenesis and a new way to treat atherosclerosis.

Administration, Oral↗
PubMed2006

Monocyte activation, but not granulocyte activation, is inhibited in the presence of developing ovarian follicles.

This study was set up to evaluate the influence of ovarian factors on the acute phase of the endotoxin-induced glomerular inflammatory reaction. Six groups of rats with permanent jugular vein cannulas were used. This included three groups with increased progesterone and/or 17beta-oestradiol concentrations (day 14 pregnant rats, pseudopregnant rats and lactating rats), one group with the presence of developing ovarian follicles (cyclic rats), and two groups with both increased sex hormone concentrations and the presence of developing ovarian follicles (day 14 pregnant rats treated with FSH and day 21 pregnant rats). Rats were infused for 1h with either saline or endotoxin (1 microg/kg body weight) and sacrificed 4h after the infusion. Kidney sections were snap-frozen and prepared for immunohistochemistry. Endotoxin-induced glomerular granulocyte infiltration was increased only in the groups of rats with increased progesterone and/or 17beta-oestradiol concentrations. This could be due to endotoxin-induced ICAM-1 and/or VCAM-1 expression, which was observed in all endotoxin-treated groups and in all endotoxin-treated groups with increased sex hormone concentrations, respectively. It could also be due to an effect on granulocytes per se, since the number of endotoxin-induced CD11b-positive cells in the glomeruli was increased only in the groups with increased sex hormone concentrations. Endotoxin-induced glomerular monocyte infiltration, however, was seen only in those groups in which developing ovarian follicles were lacking (i.e. day 14 pregnant, pseudopregnant and lactating rats), suggesting that developing ovarian follicles produce anti-inflammatory factors. These factors did not have an effect on endothelial or leukocyte adhesion molecule expression. We hypothesize that the presence of elevated progesterone concentrations increased the endotoxin-induced glomerular granulocyte infiltration, while endotoxin-induced glomerular monocyte infiltration was inhibited in the presence of developing ovarian follicles.

Acute-Phase Reaction↗
PubMed2005

Delivery of Chlamydia pneumoniae to the vessel wall aggravates atherosclerosis in LDLr-/- mice.

OBJECTIVE: The role of Chlamydia pneumoniae in atherosclerosis is still debated. In this study a novel mouse model was applied to determine the direct impact of C. pneumoniae on the arterial wall and the development of atherosclerosis. METHODS: Direct effects of C. pneumoniae on collar-induced atherosclerosis were studied after local delivery of C. pneumoniae to carotid arteries of LDL receptor-deficient (LDLr-/-) mice. RESULTS: The presence of C. pneumoniae in the vessel wall was quantified by RT-PCR (6.2 x 10(4) copies/artery) and resulted in a 2.0-fold increase in intima/media ratios (p<0.05) and a 1.7-fold increase in stenosis (p<0.05). Immunostaining revealed a 2.98-fold (p<0.01) increased macrophage content and a tendency towards lower numbers of smooth muscle cells and collagen in lesions of infected carotid arteries. Direct delivery of another respiratory pathogen, Mycoplasma pneumoniae, to the carotids did not affect size or composition of the atherosclerotic lesions. Presence of C. pneumoniae in the carotid arteries resulted within 7 days in a marked upregulation of the expression of MCP-1 (p<0.01) and ICAM-1 as determined on mRNA and protein levels. These in vivo data were in line with data obtained with in vitro infections of macrophages and endothelial cells with C. pneumoniae. CONCLUSIONS: We conclude that C. pneumoniae in carotid arteries leads to more pronounced atherosclerotic lesions with a more vulnerable morphology and that this model is suitable to monitor direct effects of C. pneumoniae on atherogenesis.

Animals↗
PubMed2005

Blockade of interleukin-12 function by protein vaccination attenuates atherosclerosis.

BACKGROUND: Interleukin-12 (IL-12) has been identified as a key inducer of a type 1 T-helper cell cytokine pattern, which is thought to contribute to the development of atherosclerosis. We sought to study the role of IL-12 in atherosclerosis by inhibition of IL-12 using a newly developed vaccination technique that fully blocks the action of IL-12. METHODS AND RESULTS: LDL receptor-deficient (LDLr(-/-)) mice were vaccinated against IL-12 by 5 intramuscular injections of IL-12-PADRE complex in combination with adjuvant oil-in-water emulsion (low dose)/MPL/QS21 every 2 weeks. Two weeks thereafter, atherogenesis was initiated in the carotid artery by perivascular placement of silicone elastomer collars. IL-12 vaccination resulted in the induction of anti-IL-12 antibodies that functionally blocked the action of IL-12 as determined in an IL-12 bioassay. Blockade of IL-12 by vaccination of LDLr(-/-) mice resulted in significantly reduced (68.5%; P<0.01) atherogenesis compared with control mice without a change in serum cholesterol levels. IL-12 vaccination also resulted in a significant decrease in intima/media ratios (66.7%; P<0.01) and in the degree of stenosis (57.8%; P<0.01). On IL-12 vaccination, smooth muscle cell and collagen content in the neointima increased 2.8-fold (P<0.01) and 4.2-fold (P<0.01), respectively. CONCLUSIONS: Functional blockade of endogenous IL-12 by vaccination resulted in a significant 68.5% reduction in atherogenesis in LDLr(-/-) mice. Vaccination against IL-12 also improved plaque stability, from which we conclude that the blockade of IL-12 by vaccination may be considered a promising new strategy in the treatment of atherosclerosis.

Animals↗
PubMed2005

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Alginates↗
PubMed2003

Biocompatibility and surface structure of chemically modified immunoisolating alginate-PLL capsules.

Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.

Acrylic Resins↗
PubMed2003

Association between macrophage activation and function of micro-encapsulated rat islets.

AIMS/HYPOTHESIS: Survival of microencapsulated islet grafts is limited, even when inflammatory reactions against the capsules are restricted to a small portion of less than 10%. METHODS: This study investigates both in vivo in rat recipients and in vitro whether cellular overgrowth on this minority of the capsules contributes to limitations in the functional survival of the 90% of the encapsulated islets which remain free of any cellular overgrowth. RESULTS: In successful rat recipients of an allogenic microencapsulated islet graft we found that the vast majority of cells in the capsular overgrowth were activated ED-1 and ED-2 positive macrophages which were found in numbers of approximately 1500 per capsule. Co-culture of encapsulated islets with 1500 (nr8383) rat-macrophages per capsule showed that the activation of macrophages was caused by islet-derived bioactive factors since TNF-alpha and IL-1beta secretion by macrophages was induced by islet-containing capsules and not by empty capsules. This activation of macrophages was associated with a decrease in function of the encapsulated islets as evidenced by a quantitatively reduced (35%) insulin response in static incubation and a slower response in perifusion. CONCLUSION/INTERPRETATION: Present research aims to design strategies for the temporary inhibition of macrophage activation since macrophages are predominantly present in the first two months after implantation. These strategies will serve as a pertinent basis for future clinical application of microencapsulated islets.

Animals↗
PubMed2002

Considerations for successful transplantation of encapsulated pancreatic islets.

Encapsulation of pancreatic islets allows for transplantion in the absence of immunosuppression. The technology is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. Encapsulation offers a solution to the shortage of donors in clinical islet transplantation because it allows animal islets or insulin-producing cells engineered from stem cells to be used. During the past two decades three major approaches to encapsulation have been studied. These include intravascular macrocapsules, which are anastomosed to the vascular system as AV shunt; extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites; and extravascular microcapsules transplanted in the peritoneal cavity. The advantages and pitfalls of these three approaches are discussed and compared in the light of their applicability to clinical islet transplantation. All systems have been shown to be successful in preclinical studies but not all approaches meet the technical or physiological requirements for application in human beings. The extravascular approach has advantages over the intravascular because since it is associated with less complications such as thrombosis and infection. Microcapsules, due to their spatial characteristics, have a better diffusion capacity than macrocapsules. Recent progress in biocompatibility of microcapsules has brought this technology close to clinical application. Critical issues such as limitations in the functional performance and survival are being discussed. The latest results show that both issues can be solved by the transplantation of microencapsulated islets close to blood vessels in prevascularized solid supports.

Animals↗
PubMed2002

MTS colorimetric assay in combination with a live-dead assay for testing encapsulated L929 fibroblasts in alginate poly-L-lysine microcapsules in vitro.

Biomaterials such as applied in microcapsules may have harmful effects on encapsulated cells. Up to now, there are no adequate assays available for testing the function and viability of cells in capsules. Therefore, we investigated whether the combination of MTS proliferation assay and live-dead viability assay is suitable for testing microencapsulated L929 fibroblasts in long-time culture. Proliferation of L929 cells was shown by a significant increase of formazan absorbance within the first 3 weeks (Day 0: 0.132 +/- 0.047; Day 7: 0.404 +/- 0.101; Day 14: 0.728 +/- 0.239; Day 21: 0.877 +/- 0.224) followed by stagnation and decrease thereafter. This was confirmed by an increasing proportion of dead cells measured by the live-dead assay. Thus, proliferation of encapsulated L929 can be reliably investigated by the MTS assay. In combination with life-dead assays, the proliferation can be correlated to the survival rate of the encapsulated cells.

Alginates↗
PubMed2001

Preparation and certification of a reference material on PCBs in pig fat and its application in quality control in monitoring laboratories during the Belgian "PCB-crisis".

In this article, the production and validation of a new certified reference material "PCBs in animal fat" for the control of the maximum level of 200 ng/g setup by the European Communities for veterinary products from Belgium is described. Three materials are established: a blank, one material with about 100 ng/g and one with about 200 ng/g (sum of seven PCBs). Data on the production and certification are given. Additionally, this material was used as an unknown test material in the quality assurance program of the Belgium meat monitoring system (before the certification of the material). While the certification was performed with an uncertainty of less than 10%, the round robin exhibited larger deviations. However, these deviations were less than 20% for most of the 30 participating laboratories. Only two had significantly higher deviations.

Adipose Tissue↗
PubMed2000

Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat.

OBJECTIVE: To assess the effect on the function and immunologic status of potential donor livers of the duration of brain death combined with the presence and absence of hemodynamic instability in the donor. SUMMARY BACKGROUND DATA: Brain death, regarded as a given condition in organ transplantation, could have significant effects on the donor organ quality. METHODS: Brain death was induced in Wistar rats. Short or long periods of brain death in the presence or absence of hemodynamic instability were applied. Sham-operated rats served as controls. Organ function was studied by monitoring standard serum parameters. The inflammatory status of the liver was assessed by determining the immediate early gene products, the expression of cell adhesion molecules, and the influx of leukocytes in the liver. RESULTS: Progressive organ dysfunction was most pronounced in hemodynamically unstable brain-dead donors. Irrespective of hemodynamic status, a progressive inflammatory activation could be observed in brain-dead rats compared with controls. CONCLUSIONS: Brain death causes progressive liver dysfunction, which is made worse by the coexistence of hemodynamic instability. Further, brain death activates the inflammatory status of the potential donor liver, irrespective of the presence of hypotension. The changes observed may predispose the graft to additional damage from ischemia and reperfusion in the transplant procedure.

Animals↗
PubMed1999

Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: a model to study marginal organ donors.

BACKGROUND: Marginal donors exposed to the full array of effects induced by brain death are characterized by low success rates after transplantation. This study examined whether organs from marginal brain dead animals show any change in organ function or tissue activation making them eventually more susceptible for additional damage during preservation and transplantation. METHODS: To study this hypothesis we first focused on effects of brain death on donor organ quality by using a brain death model in the rat. After induction of brain death, Wistar rats were ventilated for 1 and 6 hr and then killed. Sham-operated rats served as controls. Organ function was studied using standard serum parameters. Tissue activation of liver and kidney was assessed by staining of immediate early gene products (IEG: FOS, JUN), and inflammatory markers; cell adhesion molecules (Intercellular adhesion molecule-1, vascular cell adhesion molecule-1), leukocyte infiltrates (CD45, T cell receptor, CD8, CD4), and MHC class II. RESULTS: During brain death progressive organ dysfunction was observed that coincided with a significant increase in activation of immediate early genes, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD45, and MHC class II versus nonbrain dead controls. In liver tissue also the markers for T cell receptor and CD8 significantly increased. CONCLUSIONS: These findings suggest that an immune activation with increased endothelial cell activation and immediate early gene expression occurs in marginal donors after brain death induction. We suggest that brain death should not longer be regarded as a given nondeleterious condition but as a dynamic process with potential detrimental effects on donor organs that could predispose grafts for increased alloreactivity after transplantation.

Animals↗
PubMed1999

Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets.

There are several approaches of immunoprotection of pancreatic islets for the purpose of successful allo- or xenotransplantation in the absence of immunosuppressive medication. Extravascular approaches are either macroencapsulation (large numbers of islets together in one device) or microencapsulation. The latter approach is to envelop each individual islet in a semipermeable immunoprotective capsule. Quite promising results have been achieved with polylysine-alginate microencapsulated islet grafts in rodents, but clinical application is still restricted to a very small number of cases. Relevant considerations regard the following aspects. The biocompatibility of the microcapsules is influenced by the chemical composition of the materials applied and by mechanical factors related to the production process. With purified instead of crude alginates, the percentage of capsules with fibrotic overgrowth is reduced to approximately ten percent, and the remaining overgrowth is mainly explained by mechanical factors, i.e. inadequate encapsulation of individual islets. Even with purified alginates, however, the duration of encapsulated graft function is limited to a period of six to twenty weeks. Obviously, other factors than bioincompatibility play a role, which factors have to be identified. The limited duration of graft survival cannot be explained by rejection since, in rats, survival times of encapsulated isografts are similar, if not identical, to those of encapsulated allografts. An important factor is probably insufficient nutrition as a consequence of insufficient blood supply of the encapsulated and thus isolated islet. This also influences the functional performance of encapsulated islet grafts. Although normoglycemia can be readily obtained in streptozotocin diabetic rat recipients, glucose tolerance remains severely impaired, as a consequence of an insufficient increase of insulin levels in response to intravenous or oral glucose challenge. Important factors are the characteristics of the capsules applied in view of optimal diffusion kinetics, and the fact that an encapsulated islet graft can only be implanted in the peritoneal cavity because of its volume. Further studies should focus on finding a practically applicable method to reduce the barrier between encapsulated islets and the bloodstream, in order to improve both the functional performance and the survival of encapsulated islet grafts.

Alginates↗
PubMed1999

Amplified rDNA restriction analysis and further genotypic characterisation of metal-resistant soil bacteria and related facultative hydrogenotrophs.

The level of genotypic relationship between czc+ soil bacteria mainly resistant to zinc (but also to various other metals), and related facultative hydrogenotrophs previously assigned to the genera Alcaligenes, Ralstonia, and Burkholderia was evaluated using ARDRA (Amplified Ribosomal DNA Restriction Analysis). The analysis included 44 strains isolated from harsh industrial environments in sediments, soils and wastes with high content of heavy metals. These strains were selected by their ability to grow in the presence of high concentrations of multiple heavy metals and to hybridise with czc or ncc probes. The czc operon confers resistance to cadmium, zinc and cobalt in strain Ralstonia eutropha CH34. The ncc operon confers resistance to nickel, cobalt and cadmium in strain 31A known as Alcaligenes xylosoxidans. The analysis showed a close phylogenetic clustering of the czc+ strains inside the Ralstonia genus despite of their different origins and that the Ralstonia genus contained also the hydrogenotrophs and some catabolic strains assigned to the genus Ralstonia eutropha, strains up to now registrated as CDC IV c-2 strains as well as reference strains belonging to Ralstonia solanacearum and Ralstonia pickettii. The ncc+ strains are phylogenetically less related to each other compared to the czc+ strains. This suggests that the tested czc+ strains and some of the ncc+ strains may be considered as belonging to the genus Ralstonia. Inside this major Ralstonia cluster, a subcluster gathers most of the czc+ isolates maybe giving a clue to define a new species. Besides, from 30 tested strains, 15 metal resistant strains of this subcluster proved to display the unusual mutator phenotype characteristic of the representative strain CH34.

Genotype↗
PubMed1996

A polyphasic reassessment of the genus Paenibacillus, reclassification of Bacillus lautus (Nakamura 1984) as Paenibacillus lautus comb. nov. and of Bacillus peoriae (Montefusco et al. 1993) as Paenibacillus peoriae comb. nov., and emended descriptions of P. lautus and of P. peoriae.

Seventy-seven strains representing 10 species in the Paenibacillus polymyxa 16S rRNA group and 3 other species that exhibit phenetic relatedness to members of this group, Bacillus lautus, "Bacillus longisporus," and Bacillus peoriae, were characterized genotypically and phenotypically by performing an amplified ribosomal DNA restriction analysis, a randomly amplified polymorphic DNA analysis, a fatty acid methyl ester analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins, pyrolysis mass spectrometry, and API and other routine phenotypic tests. These analyses revealed distinct clusters representing Paenibacillus alvei, Paenibacillus amylolyticus, Paenibacillus azotofixans, Paenibacillus durum, Paenibacillus larvae subsp. larvae, Paenibacillus larvae subsp. pulvifaciens, B. lautus, Paenibacillus macerans, Paenibacillus macquariensis, B. peoriae, P. polymyxa, and Paenibacillus validus, which confirmed the distinctness of these species, but appreciable within-species heterogeneity was observed in P. alvei, B. lautus, P. macerans, P. polymyxa, and P. validus. The type strain of Paenibacillus pabuli did not cluster with other strains of this species, and in several analyses a relationship between strains of P. pabuli and "B. longisporus" was observed. As the analyses showed that B. lautus and B. peoriae are closely related to the genus Paenibacillus, these species are reclassified as members of this genus.

Bacillus↗