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Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Item does not contain fulltext Onderzoek toont aan dat jongeren met een licht verstandelijke beperking (LVB) een drie tot vier keer grotere kans hebben op het ontwikkelen van emotionele en gedragsproblemen en/of psychische stoornissen dan jongeren zonder een LVB (Emerson, Einfeld, & Stancliffe, 2011). Tot de groep jongeren met een LVB rekenen we ook jongeren die functioneren op het niveau van een LVB, zelfs wanneer niet alle drie de criteria voor een LVB bij hen zijn vastgesteld, te weten verminderde intelligentie, verminderd sociaal adaptief vermogen, en problemen reeds in de vroege ontwikkeling aanwezig (Kaal, Nijman, & Moonen, 2015). 16 p.

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Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Over the past decade we have demonstrated numerous times that calcium phosphates can be rendered with osteoinductive properties by introducing specific surface microstructures1. Since most of these calcium phosphates contained hydroxyapatite, they are either slowly or not resorbable2. Resorbability is an often sought after characteristic of calcium phosphates so that they can be gradually replaced by newly formed bone. The objective of this study was to prepare a resorbable surface microstructured tricalcium phosphate (TCP) ceramic and evaluate its osteoinductive property and resorption rate after intramuscular implantation in dogs. This material was then compared to the established and slowly resorbable osteoinductive biphasic calcium phosphate ceramic (BCP).

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An in vitro rat bone marrow cell system was used to examine the interfacial ultrastructure established between various calcium phosphates and mineralized tissue. The investigated calcium phosphates comprised hydroxyapatite (HA), fluorapatite (FA), tricalcium phosphate (TCP), tetracalcium phosphate (TECP) and magnesium whitlockite (MWL). Both scanning and transmission electron microscopy were used to examine the elaborated interface. The time in which a mineralized extracellular matrix was formed on the various materials differed from 2 weeks on HA, TCP and TECP, to 8 weeks on FA. It was only occasionally observed in some areas on MWL, which might have been due to aluminum impurities in the coating. With transmission electron microscopy, three distinct interfacial structures were observed. They differed in the presence or absence of a collagen free, 0. 7 to 0. 8 J.Lm wide, amorphous zone and a 20 to 60 nm thick electron dense layer , interposed between the material surface and the mineralized extracellular matrix. The electron dense layer was considered to be at least partially caused by protein adsorption , which would precede or concur with biological mineralization events , while the amorphous zone was regarded to represent partial degradation of the calcium phosphate surfaces. The results of this study show that plasma sprayed calcium phosphates will display different bone-bonding and biodegradation properties , depending on their chemical composition and crystal structures .

Calcium phosphate powders were used to produce three groups of experimental substrata for the culture of primary rat bone marrow cells in conditions which permitted the survival and function of osteoclasts. Each of the three experimental groups were subdivided by differences in substratum surface roughness and following a culture period of 7 to 11 days, the culture units were stained for tartrate-resistant acid phosphatase activity. In all samples both small, sometimes mononuclear, and large multinucleate cells stained positive for tartrate-resistant acid phosphatase activity and the numbers and types of cells were quantified and statistically analyzed. Following histochemical staining the samples were dehydrated and gold coated for examination by scanning electron microscopy. Cells were found to create distinct resorption lacunae in most substrata, but not on the dense, high temperature sintered hydroxyapatite, and cells responsible for this activity were confirmed as exhibiting positive tartrate resistant acid phosphatase activity. Statistical analyses showed that both the total number of tartrate-resistant acid phosphatase positive cells and the number of multinucleate tartrate-resistant acid phosphatase positive cells was greater on the rougher than the smoother surfaces.

Screw implants of commercially pure titanium and titanium alloy together with rods of slip-cast dense hydroxyapatite were implanted transfemorally in young adult rats. The femora were harvested after fixation and freeze-fractured in liquid nitrogen to create two tissue fragments of each specimen. The first contained the implant while the second enabled examination of the tissue immediately adjacent to the implant. In all cases, the tissue abutting the implant was a cement line-like layer which separated the implant from the surrounding bone proper. Greater adherence of this interfacial tissue was demonstrated to hydroxyapatite samples compared with the titanium screws, while no adherence was demonstrated to the titanium alloy implants. The differences in adhesion of interfacial tissue to titanium and titanium alloy were attributed, in some areas, to localized increase in surface roughness, and in others to subtle chemical differences between the oxide-covered metal surfaces. The cement line-like layer was composed of globular accretions which were clearly visible on the apparently smooth grain surfaces of the retrieved hydroxyapatite rods. However, modification of the ceramic, during the implantation period, to produce a micropitted surface, also suggested that microtopographical features were implicated in interfacial tissue adhesion.

Bone formation onto poly(L-lactide), which was plasma-spray coated with various quantities of hydroxyapatite (0%, 15%, 36% and 100% coverage), was investigated in an in vitro assay. Rat bone marrow cells were grown on the different coatings and the cellular response and elaborated extracellular matrix was examined at the light and electron microscopical level after 1, 2 , 4 and 8 weeks of culture. Proliferation of cells into multilayers was seen on the 0% , 36% and 100% , but not on the 15 % coatings. Coinciding with this was the sparse formation of extracellular matrix on the latter, and its abundant appearance on the former three coatings. Scanning and transmission electron microscopy revealed a mineralized extracellular matrix on the 100% and 36% coatings after 2 and 4 weeks , respectively, and on the 15 % coating after 8 weeks. Mineralization was not observed on uncoated poly(L-lactide). At the interface between hydroxyapatite and the mineralized extracellular matrix, one or more electron dense layers were frequently observed , which showed morphological similarities with structures between these two entities in vivo. The results of this in vitro study show that, in the model used, hydroxyapatite is required to obtain the elaboration of mineralized extracellular matrix on poly(L-lactide) .

The nature of kidney lesions in BD IX rats infected with Trypanosoma brucei was investigated. Proteinuria developed and increased up to 236 +/- 35 mg/24 hr at 7 wk after the infection. Antibodies were found to be deposited along the glomerular basement membrane (GBM) predominantly in a linear fashion, which changed to a more granular pattern 7 wk after the infection. At this stage of the disease, electron-dense deposits were found subendothelially along the GBM. In the sera and kidney eluates of diseased rats, anti-GBM antibodies were present. Enzyme-linked immunosorbent assay (ELISA) studies showed antibodies which reacted with GBM components laminin and type IV collagen and not with fibronectin. The antibody specificity was confirmed by using competitive and cross-absorption ELISA techniques, as well as immunoblotting. With the use of indirect immunofluorescence, no common antigenic sites were found on trypanosomes and GBM components. The observed linear immunofluorescence pattern seems to be caused by glomerular binding of antibodies directed against laminin and type IV collagen, which are known to be able to induce renal disease. Subendothelial complex formation in later stages of the disease might result from a molecular rearrangement of GBM components after in situ binding of the antibodies. The formation of auto-antibodies directed against laminin and type IV collagen is probably caused by restricted polyclonal B cell stimulation, a well known feature of trypanosomiasis.

Catalous van de gelijknamige tentoonstelling in het hoofdgebouw van de Vrije Universiteit, 14 januari t/m 26 februari 1999.

Rat bone marrow cells, capable of forming bonelike tissue, were cultured on three types of plasma sprayed hydroxyapatite that differed in degree of crystallinity from 15%, 43% to 69%. The interface between the mineralized extracellular matrix and the hydroxyapatite was studied with scanning and transmission electron microscopy. At the onset of bone formation, calcium and phosphorous-rich afibrillar globules, with a diameter varying from 0.2 to 0.8 μm, were produced and deposited onto the different substrata. These globules subsequently fused to form a homogeneous layer to which collagen fibres became anchored. Individual globules could be distinguished on the non-degrading 69 % crystalline hydroxyapatite, but were partially fused with the degrading surfaces of 15 % and 43 % crystalline materials. Transmission electron microscopy revealed distinctly different interfacial structures with the various types of hydroxyapatite. A 20 to 60 nm thick, glycosaminoglycan containing electron dense layer was clearly visible on 69 % crystalline hydroxyapatite, but was less well defined on the more amorphous materials. On the latter, a 0.4 to 1 μm wide amorphous zone was regularly seen to which both parallel and oblique aligned collagen fibres were attached . The results of this study show that the crystallinity of plasma sprayed hydroxyapatite is an important parameter which influeces the establishment of the bony interface and may, as a result, have an effect on the bone formation rate and bonding strength between hydroxyapatite and bone tissue.

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Autophagy is a highly conserved recycling mechanism essential for maintaining cellular homeostasis. The pathophysiological role of autophagy has been explored since its discovery 50 years ago, but interest in autophagy has grown exponentially over the last years. Many researchers around the globe have found that autophagy is a critical pathway involved in the pathogenesis of cardiac diseases. Several groups have created novel and powerful tools for gaining deeper insights into the role of autophagy in the aetiology and development of pathologies affecting the heart. Here, we discuss how established and emerging methods to study autophagy can be used to unravel the precise function of this central recycling mechanism in the cardiac system.

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Background. We reported previously that in renal disease in relation to antineutrophil cytoplasm auto-antibodies (ANCA)-associated vasculitis, renal outcome correlates better with the percentage of normal glomeruli than with separate active lesions. This may imply that glomeruli, once affected by necrotizing and crescentic lesions, are irreversibly damaged. We quantified and evaluated the course of renal lesions in the present study. Methods. We retrospectively analysed 31 patients with renal disease in relation to ANCA-associated vasculitis, all treated with immunosuppressive drugs. In all patients, a renal biopsy was performed at diagnosis. A follow-up biopsy was performed in all patients on the indication of a suspected renal relapse, after a mean interval of 31 months. Results. The mean percentage of normal glomeruli in the renal biopsy did not change over time (29% in the initial and 30% in the follow-up biopsy). The mean percentage of glomeruli with crescents, however, significantly decreased from 57 to 30% (P < 0.001). The percentage of glomerulosclerosis significantly increased from 12 to 39% (P < 0.001). The data were independent of diagnosis, gender, age, time interval between the biopsies, and treatment. Conclusions. This is the first study to quantify glomerular changes between two time points in patients with renal vasculitis. Our results suggest that, on average, no new glomeruli are recruited into the active disease process. The sum of the percentage of crescentic and sclerotic glomeruli in the initial biopsies is larger than the percentage of sclerotic glomeruli in the follow-up biopsies. Thus, therapy seems not only to prevent normal glomeruli from being recruited into the active disease process for a certain time, but seems also to allow part of the active lesions to revert into a normal phenotype, although another part of the active lesions will be transformed to a chronic phenotype

Item does not contain fulltext G. Abma Hoedemaker herdacht Baarn:Ten Have ,1994