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D J Kok

Publications and source records attributed to D J Kok.

At least 19 recordsLinked to original sources
PubMed2001

Indinavir crystallization around the loop of Henle: experimental evidence.

OBJECTIVE: To determine the probable site of the nephron and the plasma indinavir (IDV) concentration at which intrarenal IDV crystallization occurs. DESIGN: We performed in vitro crystallization experiments in IDV solutions simulating conditions found in the nephron. METHODS: To determine intrarenal IDV concentrations at which conditions in the nephron allow crystallization, several concentrations of IDV basic solutions (0-800 mM) were titrated from pH 4.0 to higher pH values until crystals formed within 1 minute. Based on the combination of pH and ionic strength at which crystals formed, we determined the site of the nephron at which this combination was first attained. Based on the capacity for concentration at that site, we were able to measure the corresponding plasma IDV concentration. RESULTS: Under conditions normally found at the proximal tubule (i.e., pH 6.7 and ionic strength of 200 mM), IDV crystallized at 200 mg/L. Under conditions applying to the loop of Henle, pH 7.4 and ionic strength of 200 mM, IDV crystallized at 125 mg/L, which would correspond to a plasma IDV concentration of 8 mg/L. CONCLUSIONS: IDV crystallization is most likely in the loop of Henle and may already start at plasma IDV concentrations as low as 8 mg/L. Increasing hydration does not reduce the risk of IDV crystallization in the loop of Henle but instead prevents IDV crystallization and aggregation in the lower urinary tract. It remains to be confirmed whether prevention of high IDV plasma concentrations will reduce the risk of IDV crystallization in the loop of Henle.

Crystallization↗
PubMed2001

Cytokine production induced by binding and processing of calcium oxalate crystals in cultured macrophages.

Deposition of calcium oxalate (CaOx) crystals in the renal interstitium is common in humans with primary oxalosis and secondary hyperoxaluria, as well as in kidneys of rats with CaOx nephrolithiasis. In vivo, macrophages and multinucleated giant cells mostly encapsulate these crystals. To investigate whether macrophages are able to dispose of CaOx crystals after phagocytosis, we used a nontransformed macrophage cell line derived from mouse spleen progenitors. Cytokine assays showed that in response to crystal binding and phagocytosis, these macrophages release tumor necrosis factor-alpha. This release was evident at 8 hours, maximal at 24 hours, and decreased to control values after 48 hours of incubation with crystals. A very low but significant release of interleukin-6 into the culture medium was only noticed after 32 hours. Radiochemical experiments showed that these cells bind 38.8% of the CaOx crystals added. After 4 days, all internalized crystals had been dissolved and their molecular constituents released into the extracellular environment. Confocal laser scanning microscopy followed by morphometrical analyses confirmed these results. Long-term (survival) analyses showed that in the interval under study and at the crystal doses used, cell viability was not significantly affected. These findings support the view that properly functioning macrophages are able to remove CaOx deposits from the renal interstitium and that these cells produce inflammatory cytokines before crystal dissolution.

Animals↗
PubMed2001

Methods for measuring crystallization in urolithiasis research: why, how and when?

Whereas crystalluria does not distinguish between kidney stone formers and healthy people and thus can be considered a physiologic event, kidney stone formation is a pathologic incident and reflects a specific form of biomineralization. Both single urinary crystals as well as whole kidney stones form under exquisite control of organic macromolecules. Simple crystal formation in the urinary tract is distinguished from stone formation in the kidney by the process of particle retention. The latter occurs either because nucleated crystals strongly aggregate to particles too large to pass freely through the tubules ('free particle' theory), or because crystals become abnormally adherent to tubular cell surfaces ('fixed particle' theory). Since it is impossible to mimic all the processes involved in stone formation in vitro, it is highly important to carefully chose a specific crystallization process for in vitro studies, and to select the most appropriate experimental conditions for measuring the chosen process as reliably as possible. This overview aims at critically reviewing the principles of currently available assay systems for studying crystallization processes involved in stone formation. Consensus is reached by the experts that no in vitro system really mimics what happens in renal stone formation, but that carefully designed in vitro studies will always play an important part in urolithiasis research. For such studies, it is highly important to exactly control the appropriate experimental conditions that are relevant to a specific crystallization process under investigation. Practical guidelines for researchers working with crystallization systems are provided, and it is concluded that international efforts should be made to standardize the terminology, to agree on a set of basic experimental parameters (temperature, pH, artificial urine composition), and to adopt simple tests or conditions are reference points for quality and comparative control.

Calcium Oxalate↗
PubMed2001

Measurement of urinary flow rate using ultrasound in young boys and infants.

PURPOSE: We present a technique for measuring urinary flow rates with ultrasound in male infants and children. MATERIALS AND METHODS: Urinary flow rate was measured simultaneously by an ultrasound probe placed around the base of the penis and by a funnel with a rotating disk at the bottom in 30 boys with a mean age of 6.7 years (range 4.5 to 10.5), and by ultrasound in 8 infants with a mean age of 10 months (range 1 to 28). Voided volume was measured with a graded cylinder or calculated from the weight change of diapers in infants. Ultrasound and rotating disk maximum flow rates were calculated. The ultrasound signal was calibrated by comparing the collected voided volume to the area under the curve for that void. The volume calculated from the rotating disk flow rate curve was also compared with the collected volume. RESULTS: Both methods yielded similar flow curves. However, ultrasound maximum flow rate significantly exceeded rotating disk maximum flow rate (13 +/- 6 ml. per second, range 5 to 22 versus 10 +/- 4 ml. per second, range 4 to 21, t test p <0.001). The underestimation of the flow rate by the rotating disk method may have been due to adherence of urine to the funnel wall. Rotating disk maximum flow rate was lower and voided volume was underestimated by up to 50% (average 15 +/- 2%) in 21 cases. Ultrasound maximum flow rate averaged 6 +/- 3 ml. per second (range 3 to 11.6 [oldest infant]) in the 8 infants. CONCLUSIONS: Urinary flow rates can be measured accurately using ultrasound in boys who produce small volumes and/or who are not toilet trained and also in infants. In future studies ultrasound will be applied to subsets of male infants with bladder dysfunction.

Child↗
PubMed2000

Bladder calculi in augmentation cystoplasty in children.

OBJECTIVES: To determine the best preventive strategies for bladder calculi in children with an augmented bladder, the risk factors and prevention strategies for urolithiasis were evaluated. METHODS: The records of 89 patients following augmentation cystoplasty were reviewed to assess the results of augmentation cystoplasties and in particular the formation and prevention of calculi. RESULTS: The median follow-up was 4.9 years after augmentation. Most patients (71) had an ileocystoplasty. Bladder calculi occurred in 14 of the 89 patients (16%) and recurred in 4 patients. Girls had a higher incidence of urolithiasis. Other risk factors were cloacal malformations, vaginal reconstructions, anal atresia, clean intermittent catheterization problems and retention, bladder neck surgery, and symptomatic urinary tract infections. CONCLUSIONS: Subgroups with cloacal malformations, vaginal reconstructions, ureter reimplantation, and bladder neck surgery were identified that have an increased risk for stone formation and therefore warrant special care in the follow-up after augmentation. This care should include clear emphasis on the role of treating symptomatic urinary tract infections, especially in patients with cloacal malformations and vaginal reconstructions. Girls have a higher incidence of bladder calculi than boys.

Adolescent↗
PubMed2000

Paroxysmal non-epileptic events in children: a retrospective study over a period of 10 years.

OBJECTIVE: To determine the frequency, nature and clinical characteristics of paroxysmal non-epileptic events in children diagnosed by video electroencephalogram (EEG) monitoring at a tertiary referral centre. METHODOLOGY: A retrospective study of children with paroxysmal non-epileptic events, aged 2 weeks to 17 years inclusive was undertaken. The study group consisted of children who had video EEG monitoring during a 10-year period (1988-99). Telemetry files, medical charts, events recorded on video and record sheets were reviewed. RESULTS: A total of 666 children were analysed, 269 had epileptic events recorded, 285 had non-epileptic events and 112 had no events recorded. In children with non-epileptic events, 43% were developmentally delayed, 25% had an abnormal neurological examination and 40% had epilepsy. In the study sample an epileptiform interictal EEG was common (24%). The major subgroups of non-epileptic events were: staring (34%), sleep phenomena - benign sleep myoclonus (15%), arousals (13%), motor tics (11%) and shuddering (7%). Developmental delay (57%) was common in children who presented with staring spells. A diagnosis of a specific non-epileptic event was reached in 96% of cases. CONCLUSION: Paroxysmal non-epileptic events can cause diagnostic confusion, particularly in children with developmental delay, epilepsy or an epileptiform EEG. Accurate diagnosis can be reached in the majority of cases using video EEG monitoring.

Adolescent↗
PubMed2000

Sialic acid and crystal binding.

BACKGROUND: We studied the role of cell surface sialic acid in the adherence of calcium oxalate monohydrate (COM) crystals to Madin-Darby canine kidney (MDCK) cells. METHODS: Studies were performed with undifferentiated (crystal-binding) cells in subconfluent cultures and maturated (noncrystal-binding) cells in confluent cultures. Lectins were used to study the emergence and abundance of oligosaccharides at the cell surface during epithelial development. The effect of neuraminidase treatment on crystal binding was studied with [14C]COM crystals, and the enzyme-induced release of cell surface-associated sialic acid molecules was monitored by labeling the cells metabolically with [3H]glucosamine. RESULTS: Binding studies with lectins derived from Maackia Amurensis II (MALII) and Sambucus Nigra (SNA) demonstrated that the cells expressed terminal sialic acids attached to penultimate galactose through alpha 2,3 and alpha 2,6 bonds at different stages of epithelial development. Neuraminidase treatment strongly reduced the affinity of the cell surface for COM crystals in subconfluent cultures. Nevertheless, neuraminidase cleaved more sialic acids from cells in confluent cultures than from those in subconfluent cultures. Peanut agglutinin (PNA), which binds only to sialylated terminal galactose units, adhered to developing but not to maturated cells, unless the latter were pretreated with neuraminidase. Both results indicate that the surface of maturated MDCK cells is more heavily sialylated than that of undifferentiated cells. Free sialic acid molecules showed little or no affinity for COM crystals and did not affect the adherence of the crystals to undifferentiated cells. CONCLUSIONS: There are at least two models that may explain these results. First, sialic acids are presented at the surface of immature cells in an orientation that specifically matches crystal surface characteristics favoring crystal-cell interactions. Second, sialic acid molecules are not directly associated with the crystals, but may be involved in the exposure of another crystal binding molecule at the cell surface.

Animals↗
PubMed2000

Role of macrophages in nephrolithiasis in rats: an analysis of the renal interstitium.

Interstitial calcium oxalate (CaOx) crystals can be found in primary oxalosis and in secondary hyperoxaluria. In a rat model for nephrolithiasis, we investigated whether such crystals can be removed by the surrounding interstitial cells. CaOx crystals were induced by a crystal-inducing diet based on ethylene glycol (EG) and ammonium chloride (CID). Both lithogenic compounds were added to the drinking water. After 9 days, the animals received normal drinking water for 2 days. Using this CID, only the interstitial crystals are retained. Subsequently, half of the population remained on normal drinking water (normo-oxaluria), whereas the other half received a low dose of EG alone (chronic hyperoxaluria). The rats were killed at regular times thereafter. The results showed that the kidney-associated oxalate significantly declined during normo-oxaluria, but remained high during chronic hyperoxaluria. Interstitial cells positive for the leukocyte common antigen (CD45; which identifies all types of leukocytes), the ED1 antigen (which is specific for monocytes and macrophages), and the major histocompatibility class II antigen (MCHII), respectively, had increased in number, with minor differences between both rat populations. The cells around the interstitial crystals were mostly positive for ED1. Multinucleate giant cells were regularly observed. These cells were positive for CD45 and ED1 and sometimes also for MCHII. The crystals in these cells were moderately positive for acid phosphatase and carbonic anhydrase II. It is concluded that interstitial CaOx crystals can be removed under normo-oxaluric conditions and that, in all likelihood, macrophages and multinucleate giant cells are involved in that process.

Ammonium Chloride↗
PubMed2000

Changes in bladder contractility and compliance due to urethral obstruction: a longitudinal followup of guinea pigs.

PURPOSE: We established the longitudinal changes in bladder contractility and compliance as a result of urethral obstruction using a guinea pig model. MATERIALS AND METHODS: Obstruction was induced in guinea pigs by a silver ring around the urethra. Urodynamic studies were performed longitudinally in individual animals. Bladder contractility and compliance were calculated from the measured bladder pressure and urine flow rate. RESULTS: Bladder contractility developed in distinct phases. It reached a maximum 200% increase after an average of 3.25 weeks concomitant with an almost 2-fold increase in urethral resistance, remained 150% to 200% increased during weeks 4 to 7 and then decreased to starting levels again, while urethral resistance remained almost 2-fold increased. Bladder compliance decreased by 80% during the first 3 weeks and continued to decrease to 5% of its original value after 10 to 11 weeks. CONCLUSIONS: Our data indicate that as a result of obstruction bladder function passes through a specific sequence of stages, including first a compensatory increase in contractility, then a stabilization phase and finally a decompensation state. In contrast bladder compliance shows a continuous decrease. The data suggest that for assessing how far a bladder has deteriorated due to obstruction a combination of functional and structural data may be warranted.

Animals↗
PubMed2000

Control of immature stages of the flea Ctenocephalides felis (Bouché) in carpets exposed to cats treated with imidacloprid.

Fleas cause allergic dermatitis in cats and dogs and therefore warrant control. It has been demonstrated previously that there is marked inhibition of the development of the immature stages of the cat flea Ctenocephalides felis on fleece blankets exposed to cats treated with imidacloprid. This study reports on the efficacy of imidacloprid in suppressing adult flea emergence in carpet exposed to treated cats. Circular discs of carpet pre-seeded with flea eggs and larvae were exposed to 6 untreated control and 6 topically treated (imidacloprid 10% m/v) cats 1 to 2 days after treatment and subsequently fortnightly for 6 weeks. Exposure times on alternate days were either 1 or 6 hours. Adult flea yield from carpets was determined 35 days after exposure. Differences between flea yield on control carpets and those exposed for 1 hour were significant only for days +1 and +14. For the 6-hour exposure, differences were significant at all times except on Day +43. The ability of imidacloprid to suppress the yield of adult fleas on carpets (6-hour exposure) steadily declined from 82 % (Day +2) to 12% (Day +43). For the 1-hour exposure it varied inconsistently between 0 and 83% over the 6-week study period.

Animals↗
PubMed1999

LLC-PK1 cells as a model system to study proximal tubule transport of water and other compounds relevant for renal stone disease.

LLC-PK1 cells were cultured on a permeable support in a two-compartment culture system. Confluent monolayers received an ultrafiltrate-like solution at the apical side and a plasma-like solution at the basolateral side. The distribution of various solutes, including phosphate, calcium, and oxalate over both compartments was measured in time. The transport of water was monitored by alterations in fluid concentrations of radiolabeled inulin. Bicarbonate, glucose, and phosphate were transported rapidly from the apical to basolateral side of the monolayer. Sodium and chloride were reabsorbed without major consequences for the osmolality in the apical and basal fluid. Calcium and potassium were also reabsorbed, but to a smaller extent than sodium. The luminal concentration of oxalate gradually increased to values that were at least three times higher (12.0+/-0.4 micromol/l) than those in the contraluminal fluid (3.8+/-0.1 micromol/l). However, since the luminal rise of oxalate completely matched the rise of inulin in the apical fluid this appeared to be the passive consequence of active water reabsorption rather than of net directed oxalate transport. The LLC-PK1 model could prove useful to study the regulation of proximal tubule water transport and its effect on luminal stone salt concentrations under different physiological conditions.

Animals↗
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↗
PubMed1999

Cell type-specific acquired protection from crystal adherence by renal tubule cells in culture.

BACKGROUND: Adherence of crystals to the surface of renal tubule epithelial cells is considered an important step in the development of nephrolithiasis. Previously, we demonstrated that functional monolayers formed by the renal tubule cell line, Madin-Darby canine kidney (MDCK), acquire protection against the adherence of calcium oxalate monohydrate crystals. We now examined whether this property is cell type specific. The susceptibility of the cells to crystal binding was further studied under different culture conditions. METHODS: Cell-type specificity and the influence of the growth substrate was tested by comparing calcium oxalate monohydrate crystal binding to LLC-PK1 cells and to two MDCK strains cultured on either permeable or impermeable supports. These cell lines are representative for the renal proximal tubule (LLC-PK1) and distal tubule/collecting duct (MDCK) segments of the nephron, in which crystals are expected to be absent and present, respectively. RESULTS: Whereas relatively large amounts of crystals adhered to subconfluent MDCK cultures, the level of crystal binding to confluent monolayers was reduced for both MDCK strains. On permeable supports, MDCK cells not only obtained a higher level of morphological differentiation, but also acquired a higher degree of protection than on impermeable surfaces. Crystals avidly adhered to LLC-PK1 cells, irrespective of their developmental stage or growth substrate used. CONCLUSIONS: These results show that the prevention of crystal binding is cell type specific and expressed only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK cells may mirror a specific functional characteristic of its in situ equivalent, the renal distal tubule/collecting ducts.

Animals↗
PubMed1999

Assessment of cattle owner's perceptions and expectations, and identification of constraints on production in a peri-urban, resource-poor environment.

This questionnaire survey was conducted amongst 200 farmers in the resource-poor, urban and per-urban environments of Botshabelo and Thaba Nchu towns in the Free State Province of South Africa. The questionnaire was divided into seven sections, namely demography, livestock, cattle, parasites, parasite control, livestock diseases and problems experienced. A total of 87.5% of the livestock owners were not employed (unemployed or pensioner). Cattle constituted more than 50% of the live-stock units owned in the area and farmers owned an average of 9.33 +/- 0.812 head of cattle. A total of 193 (96.5%) of the farmers indicated that milk was the most important product from their cattle. Only 26% of them slaughtered their own cattle for meat consumption. Eighty-eight percent of them indicated that external parasites on their livestock presented a problem, but only 72.9% of farmers implemented any tick control measures. Less than half (45.5%) of the farmers who attempted to control ticks used commercial acaricides. The remainder used various other methods, including the application of used engine oil and household detergents. Amongst the clinical diseases observed in their cattle, dry gallsickness was mentioned most often (20%). This figure, however, is believed to be inaccurate because dry gallsickness may be a clinical manifestation of some of the other diseases mentioned by the farmers, such as anaplasmosis, foreign body obstruction of the gastro-intestinal tract by plastic bags, pneumonia and mastitis. Animal husbandry problems experienced by the farmers included pollution (i.e. ingestion of plastic bags and string by their livestock), availability of water and theft.

Agriculture↗
PubMed1999

Gastro-intestinal parasites of cattle in the communal grazing system of Botshabelo in the Free State.

Twelve Bonsmara tracer calves (aged 6-12 months) were used to monitor helminth infections in the communal farming system of Botshabelo in the Free State. One calve was slaughtered each month from December 1995 to November 1996 and processed for helminth recovery. All the calves harboured worms, but the numbers were always low. The order of prevalence of the major parasites was Trichostrongylus axei, Haemonchus placei, Cooperia punctata and Cooperia pectinata.

Animals↗
PubMed1999

Risk factors for crystallization in the nephron: the role of renal development.

Several studies indicate that crystallization, the essential first step for stone formation, starts in the nephron. First a calcium phosphate mineral precipitates in the loop of Henle and this may induce formation of calcium oxalate in the late nephron segments. This study investigated the factors that determine the risk of the first calcium phosphate crystallization step in the loop of Henle. Data from a theoretical model that describes the fluid composition in the different nephron segments are combined with data from nucleation experiments. From this, an assessment was made regarding how changes in plasma and urine composition, tubular functions, and renal anatomy effect the chance of initial crystallization of calcium phosphate in the loop of Henle. The results show that parameters like hypercalciuria and hyperoxaluria do not completely reflect the risk for the initial nucleation step. A combination with data on plasma composition and on tubular function is needed to assess this risk. Renal growth from birth to adulthood and the concomitant increase in renal concentrating capacity are shown to increase the risk for crystallization in the loop of Henle. This coincides with the increasing incidence of calcium oxalate urolithiasis. Treating crystallization and stone formation as a nephron event opens new ways for investigating and understanding the process of urinary stone formation.

Calcium Oxalate↗