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Biomedical subjects

E R Boevé

Publications and source records attributed to E R Boevé.

At least 19 recordsLinked to original sources
PubMed1999

Calcium oxalate nephrolithiasis: effect of renal crystal deposition on the cellular composition of the renal interstitium.

Urinary calcium oxalate (CaOx) crystals and crystal agglomerates are normally harmlessly excreted, but in nephrolithiasis they are retained by tubular epithelial cells and shifted into the renal interstitium. This crystalline material induces an inflammatory response consisting of an increase in the number of interstitial cells and an expansion of the extracellular matrix. The newly arrived cells either derive from the blood or the connective tissue or they are formed by local proliferation. Identification of the cells that surround the interstitial crystals is a first step in investigating the question of whether the interstitial cells could remove the crystalline material. Therefore, we performed an immunohistochemical study on the kidneys of rats made hyperoxaluric by ethylene glycol (EG) and ammonium chloride (AC). Attention was paid to expression of the leukocyte common antigen (LCA), which identifies all types of leukocytes, the ED1 antigen, which is specific for monocytes and macrophages, and the major histocompatibility class II antigen (MHC II), which is present on dendritic cells, B lymphocytes, and activated macrophages. The results obtained were compared with those seen in two human kidney specimens with acute and chronic oxalosis. In both rat and humans, macrophages and multinucleated giant cells are the major cells that encapsulate the interstitial crystals. This similarity in response underlines the relevance of the rat nephrolithiasis model. The rat experiments showed, furthermore, that the number of interstitial crystals and the amount of biochemically measured kidney-associated oxalate both decrease with time, if the nephrolithiatic agents EG and AC are omitted from the drinking water. Further studies must clarify whether macrophages and multinucleated giant cells are able to remove the interstitial crystals and how these cells are recruited at the inflammatory site.

Adult↗
PubMed1997

Does urinary oxalate interfere with the inhibitory role of glycosaminoglycans and semisynthetic sulfated polysaccharides in calcium oxalate crystallization?

OBJECTIVES: Previously it was shown that the polysaccharide G872 in vitro strongly inhibits calcium oxalate monohydrate crystallization processes. However, when rats on a stone-inducing diet of ethylene glycol plus vitamin D3 are given this polysaccharide, no changes in the urine capacity for crystallization inhibition were found. We investigated here how the inhibitory action of polysaccharides changes under high oxalate conditions, as they exist in the stone inducing diet. METHODS: Calcium oxalate monohydrate (COM) crystals were incubated in a series of 0.05 M PBS buffers containing polysaccharides with increasing oxalate concentrations (0-0.4 mmol/l). The coated crystals were collected, washed and resuspended in an artificial urine. We then measured the zeta potential of the crystals, using a Coulter DELSA 440, and the initial rates for crystal growth and agglomeration, using the Coulter Multisizer II. RESULTS: Addition of oxalate to the medium shifts the negative zeta potential distribution of COM crystals coated by polysaccharides in positive direction. Particle size analysis demonstrated that the initial rates of COM crystal growth and agglomeration responding to oxalate concentration changes (0.1-->0.4 mmol/l) in the presence of G872 (0.2 mg/l) are approximately 2.5 times faster than that in the absence of G872. CONCLUSIONS: Oxalate interferes with the binding of polysaccharides to crystals. This can be envisioned to occur through changes in the crystal surface properties or by induction of functional and secondary structural changes of urinary macromolecular inhibitors such as GAGs, resulting in a decrease of their inhibitory activity against COM crystallization. Thus, in urine, a high oxalate may increase the rate of crystallization both by increasing the supersaturation and by decreasing the inhibitory potential of the urine.

Calcium Oxalate↗
PubMed1997

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans.

TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27 normal subjects, 21 control patients, and 12 patients with carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because serum was kept for at least 2 h at room temperature, which causes degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate. Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high-performance liquid chromatography revealed that most TRH-LI in urine was < EEP-NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary creatinine, and the urinary clearance rate of TRH-LI was similar to the glomerular filtration rate. In addition, serum TRH-LI was increased in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is cleared by glomerular filtration with little tubular resorption. The possible role of the prostate as a source of urinary TRH-LI was evaluated in 11 men with prostate cancer, showing a 25% decrease in urinary TRH-LI excretion after prostatectomy (0.19 +/- 0.02 vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/- SEM). However, TRH-LI was similar in spontaneously voided urine and in urine obtained through a nephrostomy cannula from 16 patients with unilateral urinary tract obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2, which is cleared by renal excretion; 2) part of urinary < EEP-NH2 is derived from prostatic secretion into the blood and not directly into urine; and 3) urinary < EEP-NH2 can be used as marker for carcinoid tumors.

Adult↗
PubMed1997

Ultrastructural osteopontin localization in papillary stones induced in rats.

OBJECTIVES: To detect in situ the precise osteopontin (OPN) localization in papillary stones. METHODS: Immunocytochemical labelling procedures are applied to detect OPN localizations in crystalline material of renal papillary stones. The tissue-processing procedure for electron microscopy, which includes OsO4 postfixation, preserves both immunocytochemical OPN reactivity and cellular membrane contrast up to the ultrathin section. Reflection-contrast light microscopical images are correlated with high resolution transmission-electron microscopical observations from consecutive ultrathin epon sections. RESULTS: Preserved crystalline material in interstitial and peripheral papillary stones is recognized as calcium oxalate monohydrate. After section incubation with markers conjugated to an antibody against OPN (alpha OPN) the crystals are converted into ghosts. In the ghosts, alpha OPN markers are present around microcrystals. The size of these microcrystals ranges from several nanometers to micrometers. It is observed (due to the OsO4-preserved membranes) that interstitial cells are separated from the stone surfaces by unidentified extracellular material, also present in the center as a stone matrix. CONCLUSION: The microcrystal-growth inhibitor OPN is detected in situ in interstitial stones induced in the rat's papilla and at the surface of the papilla.

Animals↗
PubMed1996

Effect of two new polysaccharides on growth, agglomeration and zeta potential of calcium phosphate crystals.

PURPOSE: To study the effect of semisynthetic sulphated polysaccharides in the different calcium phosphate crystallization processes in vitro. MATERIALS AND METHODS: Crystallization of hydroxyapatite (HAP) and brushite (DCPD) in the presence and absence of 2 new semisynthetic sulphated polysaccharides (G871, G872) were defined by a constant composition technique, particle size analysis and zeta potential measurement. RESULTS: These polysaccharides demonstrated strong inhibitory effect on HAP and DCPD crystal growth and agglomeration. The increase of negative zeta potential values after addition of polysaccharides suggests the binding of these polysaccharides to HAP and DCPD crystals. CONCLUSION: We conclude that both G871 and G872 could be of potential use for calcium phosphate urolithiasis prevention in addition to their use for calcium oxalate.

Calcium Phosphates↗
PubMed1996

Crystal-cell interaction inhibition by polysaccharides.

PURPOSE: We studied the effect of polysaccharides on interactions between calcium oxalate monohydrate (COM) crystals and cultured renal cells. MATERIALS AND METHODS: Monolayers of Madin-Darby canine kidney (MDCK) cells were incubated with radiolabeled crystals in the presence of various concentrations of natural glycosaminoglycans (GAGs) and semisynthetic polysaccharides (SSPs). RESULTS: While most GAGs were found to have relatively little effect, SSPs (SP54, G871 and G872) were potent inhibitors of crystal-cell association. Pretreatment of crystals, but not of cells, was similarly effective, suggesting polysaccharide-induced modification of crystal surface properties. CONCLUSIONS: This result further supports the idea that SSPs, and especially G872, are of potential interest for treatment of recurrent stone disease.

Analysis of Variance↗
PubMed1996

Zeta potential measurement and particle size analysis for a better understanding of urinary inhibitors of calcium oxalate crystallization.

To better understand urinary inhibitors of calcium oxalate crystallization, both zeta potential measurement and particle size analysis were chosen to illustrate: (1) the potential therapeutic efficacy of G872, a semi-synthetic sulfated polysaccharide, in stone prevention; and (2) the relative contribution of various urinary fractions ¿e.g., ultrafiltered urine (UFU), Tamm-Horsfall protein (THP), urinary polyanions precipitated with cetylpyridinium chloride (CPC), urinary macromolecular substances with different concentration ratios (UMS10,50,90 and UMS'10,50,90) and THP-free urine (THPFU)¿ to total urinary inhibitory activity. The results showed: (1) addition of G872 significantly enhances urinary inhibitory activity and negative zeta potential values; (2) re-addition of the CPC to UFU completely restores urinary inhibitory activity; and (3) artificial urines prepared by mixing UMS'10,50,90 from THPFU with UFU differed in inhibitory activity from that prepared by mixing UMS10,50,90 from a pooled normal urine with UFU. Based on these experimental results, the following speculations can be made: (1) normal human urines are considered to be a protective colloidal system; (2) urinary inhibitory activity originates mainly from CPC and/or UMS; (3) normal THP is a protective material to maintain urinary inhibitory activity; and (4) mutual interaction between urinary inhibitors may change the total urinary inhibitory activity.

Calcium Oxalate↗
PubMed1996

Lectin-cytochemistry of experimental rat nephrolithiasis.

Lectin reactivity in epithelial apical cell coats of normal rat kidneys was compared to that from animals subjected to crystal inducing diets (CID). The aim was to see whether the absence of lectin reactivity in cell coats is related to intratubular calcium oxalate crystal retention. In normal rat kidneys, after a pre-embedding procedure, it was observed that at the ultrastructural level, reactivity was present but that the lectin specificity for the various parts of the nephron might have to be reconsidered. There was heterogeneity between the epithelial cells with respect to the presence of coat material in the tubular cell apices. Tubular epithelial cell apices from CID rats showed no obvious changes in lectin reactivity pattern. Lectin reactivity was present at the periphery of intratubular crystals but undetectable at true crystal attachment sites or reduced at cell apices in the vicinity of recently attached crystals or agglomerates. After a post-embedding reaction procedure, wheat-germ agglutinin (WGA)-lectin reactivity confirmed the presence of coat material in the cleft between cell apex and retained crystal at crystal-attachment sites. The WGA/Au-10 nm reaction products were also seen inside epithelial cells. WGA/Au-10 nm reaction products mark a crystal matrix component inside intratubular and retained crystals. A similar matrix was also marked by an alpha-osteopontin (alpha OPN/Au-10 nm) reaction product.

Animals↗
PubMed1996

Pathological and immunocytochemical changes in chronic calcium oxalate nephrolithiasis in the rat.

In the present study, we exposed rats to a crystal-inducing diet (CID) consisting of vitamin D3 and 0.5% ethylene glycol (EG), and we investigated histologically the kidney damage induced by the deposition of calcium oxalate (CaOx) crystals. After 28 days, 50% of the animals had renal CaOx crystals, of which 60% also had small papillary stones. Most crystals were present in the cortex. The occurrence of these crystals coincided with morphological and cytochemical changes: glomerular damage, tubular dilatation and necrosis, and an enlargement of the interstitium. The number of epithelial and interstitial cells positive for the proliferating cell nuclear antigen (PCNA) was increased. Tamm-Horsfall protein (THP) was not only demonstrable in the thick ascending limb of the loop of Henle (TAL), but also frequently in glomeruli, in the proximal tubular epithelium, and in the papilla. In the lumen of the tubular system, it was associated with urinary casts. Reflection contrast microscopy (RCM) showed that the crystals were coated with a thin layer of THP. In spite of the high urinary oxalate concentrations, the above described cellular changes were not observed in CID-fed rats without renal crystals. We conclude, therefore, that in the kidney, the retained CaOx crystals rather than the urinary oxalate ions are responsible for the observed morphological and immunocytochemical changes.

Animals↗
PubMed1996

Experimental nephrolithiasis in rats: the effect of ethylene glycol and vitamin D3 on the induction of renal calcium oxalate crystals.

Using ethylene glycol (EG) and vitamin D3 as crystal-inducing diet (CID) in rats, we investigated the effect of the dosage of EG on the generation of chronic calcium oxalate (CaOx) nephrolithiasis. We collected weekly 24 hour urines and measured herein the amount of oxalate, calcium, glycosaminoglycans (GAG's), creatinine, protein, alkaline phosphatase (AP), gamma-glutamyl transpeptidase (gamma-GT), and N-acetyl-beta-glucosaminidase (NAG). The potential of these urines to inhibit crystal growth and agglomeration was also evaluated. After four weeks, the kidneys were screened by histology and radiography for the presence of CaOx crystals and the amount of kidney-associated oxalate was biochemically measured. Using 0.5 vol.% EG, only a part of the rats showed CaOx deposition in the renal cortex and/or medulla, without obvious differences between Wistar and Sprague-Dawley (SD) rats. If a dietary EG concentration of 0.75, 1.0, or 1.5 vol.% was used, the amount of kidney-associated oxalate was proportionally higher and CaOx crystal formation was consistently found in all rats. Most crystals were encountered in the cortex, whereas in the medulla and the papillary region, crystals were only occasionally detected. From these data, we conclude that in the chronic rat model, based on EG and vitamin D3, a consistent deposition of CaOx crystals is obtained using a EG concentration of at least 0.75%.

Animals↗
PubMed1995

Association of calcium oxalate monohydrate crystals with MDCK cells.

Many factors are presently known which determine the risk of calcium oxalate (CaOx) stone formation in the kidney, although the early events in the pathogenesis of this disease are still to be elucidated. One of these early events is the interaction of intraluminal crystals with the epithelial cells lining the renal tubules. In this study we determined the interaction of approximately 2 microns calcium oxalate monohydrate (COM) crystal with monolayers of Madin-Darby canine kidney (MDCK) cells grown on porous supports in a two-compartment culture system. Crystal-cell interaction studies were performed after the monolayers reached their highest level of gamma-glutamyltranspeptidase (gamma GT) enzyme activity, a marker for brush border development. Technical aspects were evaluated, such as the size and morphology of the crystals and the influence of incubation time, temperature and pH on crystal-cell interaction. Kinetic data demonstrated that an equilibrium between free and associated particles was reached within 30 minutes. Crystal-cell interaction was often associated with cell damage. However, evidence is provided that in an environment that was saturated with calcium oxalate, MDCK cells in an environment that was a certain amount of COM crystals without sustaining measurable injury. After initial attachment to the cell surface, crystals were taken up and subsequently eliminated again from the monolayers. The model system described in this paper provides a tool for detailed studies of processes that are involved in renal cellular handling of luminal COM crystals.

Analysis of Variance↗
PubMed1995

The analytical and clinical performance of the new Boehringer Mannheim Enzymun-Test PSA assay for prostate-specific antigen.

A combined evaluation effort of the Boehringer Mannheim Research and Development and Evaluation Departments and the University Hospital Rotterdam is described regarding the new, fully automated Enzymun-Test PSA assay for prostate-specific antigen. The study consisted of an analytical and a clinical part. At both sites, the vast majority of intra-assay coefficients of variation ranged from 2 to 3% above prostate-specific antigen = 1 microgram/l. Below that concentration higher coefficients of variation were measured. Comparable results were obtained for the interassay imprecision. The analytical sensitivity (lower limit of detection) was found to be 0.02 microgram/l at both sites. Regarding the linearity of the assay no systematic drift to either elevated or lower values which increasing dilution was found. Deviations remained well in the range between 100 +/- 10%. The correlation with the Abbot IMx PSA assay as performed with a large set of clinical specimens revealed: y (= Enzymun) = 1.16x (= IMx) + 0.0; r = 0.985; n = 245. In this comparison study small differences between benign prostatic hyperplasia patients and prostate cancer patients were detected, perhaps partly based on the differences in recognition patterns of various molecular prostate-specific antigen forms in both assays. A follow-up after radical prostatectomy with 17 patients (50 serum samples) also showed a good comparability between the Enzymun-Test and the IMx assay. The limited check of the reference range resulted in data comparable to what can be found in the literature: out of 100 samples originating from healthy males, aged 20-60 years, 99 had prostate-specific antigen values lower than 4 micrograms/l. Based on our findings it can be concluded that the new Enzymun-Test PSA assay meets the current state-of-the-art criteria in prostate-specific antigen methodology.

Adult↗
PubMed1995

Etiology of calcium oxalate nephrolithiasis in rats. I. Can this be a model for human stone formation?

Crystal retention is studied in a rat-model system as a possible mechanism for the etiology of human nephrolithiasis. A crystal-inducing diet (CID) of ethylene glycol plus NH4Cl in their drinking-water is offered to healthy rats to generate intratubular crystals. Subsequently, the fate of retained crystals is investigated by allowing the rats a tissue recovery/crystalluria phase for three, five and ten days, respectively, on normal drinking water. The process of exotubulosis is observed in cortex and medulla of aldehyde-fixed kidneys after three days recovery. After five days, crystals are predominantly seen there in the interstitium. After ten days, cortex and medulla are virtually free of crystals. However, in the papillary regions after five and ten days recovery, three types of calcium oxalate monohydrate (COM) crystals are present: (1) free in the calycine space, (2) sub-epithelially located surrounded by interstitial cells within, and (3) covered by macrophage-like cells, outside the original papillary surface. After a CID plus three days recovery, a further thirty-seven days extra oxalate challenge with solely 0.3 vol% ethylene glycol induced intratubular and interstitial oxalate crystals. In the papillary region, large sub-epithelial crystals are seen. However, no crystals are seen in kidneys from rats given solely (0.5 or 0.8 vol.%) ethylene glycol for thirty days. An oxalate re-challenge retards crystal removal.

Ammonium Chloride↗
PubMed1995

Etiology of calcium oxalate nephrolithiasis in rats. II. The role of the papilla in stone formation.

In kidneys of healthy rats submitted to a crystal-inducing diet (CID) with ethylene glycol (EG) and NH4Cl, the fate of retained crystals in the papillar region is studied during a recovery period of one, five or ten days, as model system for human nephrolithiasis. Scanning electron microscopy (SEM) shows, at papillary tips bulging into the calycine space, crystal masses covered either by the epithelium or a thin fibrous veil, or by unidentified mobile cuboidal cells. After CID plus one or five days recovery, small sub-epithelial swellings are seen of large sub-epithelial crystals at or around the papillary tip. After CID plus ten days, massive sub-surface crystal-containing micrometer-sized stones are seen in which the presence of calcium is confirmed by X-ray microanalysis. The papillary tip of rats after a re-challenge with an oxalate load from 0.1 vol% EG for twelve or forty-two days shows minor lesions. But a re-challenge with 0.3 vol% EG for thirty-seven days induces large sub-epithelial papillary millimeter-sized stones. The Von Kossa section staining converts the crystals into a black precipitate, but large peri-tubular or peri-vascular calcium deposits are absent. A new hypothesis about the etiology of an inductive calcium oxalate monohydrate nephrolithiasis is formulated which differs from the one proposed by Randall based on his deductive human kidney studies.

Ammonium Chloride↗
PubMed1994

Glycosaminoglycans and other sulphated polysaccharides in calculogenesis of urinary stones.

Naturally occurring glycosaminoglycans (GAGs) and other, semisynthetic, sulphated polysaccharides are thought to play an important role in urolithiasis. Processes involved in urinary stone formation are crystallization and crystal retention. Oxalate transport and renal tubular cell injury are determining factors in these processes. In this article experimental results concerning the possible mechanisms of action of GAGs and other sulphated polysaccharides are reviewed. GAGs are inhibitors of crystal growth and agglomeration and possibly also of nucleation. They can prevent crystal adherence, correct an abnormal oxalate flux and prevent renal tubular cell damage.

Animals↗
PubMed1994

Zeta potential distribution on calcium oxalate crystal and Tamm-Horsfall protein surface analyzed with Doppler electrophoretic light scattering.

The zeta potential distribution (ZPD) and particle size of Tamm-Horsfall protein (THP) and of calcium oxalate monohydrate (COM) crystals were measured using a Doppler Electrophoretic Light Scattering Analysis Instrument. The studies showed differences in the ZPD pattern between THP derived from normal subjects (nTHP) and from stone patients (pTHP). Both nTHP and pTHP can shift the zeta potential of calcium oxalate crystals towards more negative values; nTHP is significantly more potent than pTHP. The zeta potential of both nTHP and pTHP becomes less negative with decreasing pH and with increasing calcium concentration or ionic strength. Tamm-Horsfall protein particle size measurements showed that nTHP particles are significantly smaller than pTHP particles. The size of both nTHP and pTHP increases with increasing calcium concentration or increasing ionic strength and with decreasing pH. The differences between nTHP and pTHP in surface charge and particle size may be based on differences in molecular structure and may cause functional differences in their ability to inhibit calcium oxalate crystal aggregation.

Calcium Oxalate↗