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Biomedical subjects

R van der Meer

Publications and source records attributed to R van der Meer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Randomized, double-blinded, placebo-controlled intervention study with supplemental calcium in families with hereditary nonpolyposis colorectal cancer.

BACKGROUND: A high-fat diet has been recognized for some time as a major risk factor for colorectal cancer. It is thought that fat promotes this disease by increasing the levels of fatty and bile acids within the colon. These acids irritate and damage the epithelial cells of the colon. As a result of this cellular destruction, an increase in the rate of cellular proliferation occurs. Oral calcium supplementation has been proposed as a dietary intervention for individuals at high risk of colorectal cancer because of its ability to reduce rectal epithelial cell proliferation through the binding of fatty and bile acids. Placebo-controlled studies, however, have yielded varying results. PURPOSE: We conducted a randomized, double-blinded, placebo-controlled trial to test oral calcium supplementation in patients at high risk of developing hereditary nonpolyposis colorectal cancer. METHODS: Thirty subjects at risk for this cancer, with an increased epithelial cell proliferation along the colon and rectum, were randomly assigned to either a placebo group (n = 15) or a treatment group (n = 15). They received either oral calcium carbonate (CaCO3) supplements (1.5 g) or placebo (cellulose and starch) three times a day during a 12-week period. Colonic biopsy specimens (rectal, sigmoidal, and descending) were obtained prior to and after the intervention trial, during endoscopy, for determination of labeling index (LI) of whole crypts and crypt compartments by 5-bromo-2'-deoxyuridine incorporation and immunohistochemistry. Proportional bile acid compositions in duodenal bile and cytolytic activity of fecal water were also determined. All P values represent two-tailed tests of statistical significance. RESULTS: Statistically significant reductions, comparing before with after intervention, in rectal whole-crypt LI after receiving either calcium supplements (from 10.9% +/- 5.2% [mean +/- SD] to 6.2% +/- 1.5%; P < .02) or placebo (from 11.7% +/- 4.7% to 8.2% +/- 3.1%; P < .05) were observed. In the three bowel segments, no statistically significant differences were observed between the supplemental calcium and placebo groups. A statistically significant reduction in cytolytic activity was determined during calcium supplementation (from 57% +/- 41% to 32% +/- 30%; P < .05), whereas in the placebo group, it did not change (from 42% +/- 41% to 36% +/- 27%; P > .10). CONCLUSIONS: Oral calcium supplementation was shown to cause only a minor nonstatistically significant reduction of epithelial cell proliferation in the rectum, compared with placebo, and to have no effect on the same parameter in the sigmoid and descending colon in first-degree relatives of hereditary nonpolyposis colorectal cancer patients. IMPLICATION: These results cast doubt on the value of calcium supplementation in the prevention of colorectal cancer, especially in individuals already consuming an adequate amount of dietary calcium.

Adolescent↗
PubMed1995

School screening for scoliosis: the value of quantitative measurement.

Several studies advocate quantification of the bending test or performing surface topography to reduce the referral rate and to increase the specificity of the bending test in screening for scoliosis. Within the framework of a school screening project all children with a positive bending test were reexamined with measurement of rib hump height, angle of trunk rotation and moiré topography. In the period 1983-1986, out of three cohorts of 10,000 children of 10, 12 and 14 years of age, 3,069 were reexamined, of whom 1931 again tested positive (63%). The value of the three techniques in terms of sensitivity and specificity within the reexamined group was evaluated with regard to the Cobb angle on a spinal radiograph, which was made in 671 cases. A reduction in referrals of 37% was found. No significant difference in the ability to detect scoliosis was found between the three techniques mentioned. It is concluded that measurement techniques are valuable in school screening programmes. In particular, if instead of a single cut-off value, a range within which the examination should be repeated is chosen, high sensitivity and high specificity can be combined. Angle of trunk rotation measurement seems to be the easiest method of screening.

Adolescent↗
PubMed1995

Rapid association of unconjugated bilirubin with amorphous calcium phosphate.

The association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP) rapidly binds and precipitates UCB in a dose-dependent way. The results indicate that binding of UCB to ACP is specific: binding to barium phosphate was negligible and addition of low amounts of Mg2+ before formation of the calcium phosphate precipitate (Ca:Mg = 5:1) inhibited binding by 80%. Free Ca2+ stimulated binding, whereas free phosphate ions inhibited binding of UCB in taurocholate solutions and to a lesser extent in glycocholate solutions. The apparent affinity of UCB for amorphous calcium phosphate was different in the various bile salt solutions. Binding of UCB decreased at pH > 8.5 in taurocholate solutions, but not in glycocholate solutions where binding of UCB was constant from pH 7.5-10.5. We propose a model in which UCB directly binds to amorphous calcium phosphate in the presence of bile salts that weakly interact with ACP, like taurocholate. In the presence of bile salts that strongly interact with ACP, such as glycochenodeoxycholate, binding of UCB may also occur via the bile salt. In conditions of unconjugated hyperbilirubinemia, such as the Crigler-Najjar syndrome, neonatal jaundice, and in the Gunn rat, considerable amounts of UCB diffuse across the intestinal mucosa. Binding of UCB to calcium phosphate in the intestine may stimulate its excretion and thereby constitute a relevant mechanism of excretion.

Bile Acids and Salts↗
PubMed1994

Variation in Cobb angle measurements in scoliosis.

In order to determine the reliability of the Cobb angle measurement as it is used in the clinical management of scoliosis, a methodological survey was carried out. In the measurement of a Cobb angle two phases can be distinguished: (a) the production of a spinal radiograph and (b) the measurement of the angle itself. In respect of the first phase, the variation in production of the radiographs was calculated on Cobb angle measurements made by one investigator on serial radiographs of patients who underwent spinal fusion for scoliosis and therefore had a fixed spinal curvature. For the second phase, the accuracy of Cobb angle measurement was investigated by comparing measurements on the same radiographs of 46 scoliosis patients obtained by three investigators, namely two orthopaedic surgeons and an orthopaedic fellow who was assigned to a school screening project. Results were expressed as a Spearman correlation coefficient and a standard deviation of the differences. The Spearman correlation coefficient was 0.98 for the repeated radiographs (production variation) and also 0.98 for the repeated measurements on one radiograph (interobserver measurement variation). The standard deviation of the differences in Cobb angle for the repeated radiographs amounted to 3.2 degrees and for the repeated measurements on one radiograph it was 2.0 degrees. Although there is a good reproducibility of the Cobb angle measurement between different investigators, the variation in production of a spinal radiograph is an important source of error. This should be taken into account when making decisions in scoliosis management.

Humans↗
PubMed1994

Effects of supplemental dietary calcium on quantitative and qualitative fecal fat excretion in man.

Oral calcium supplementation is thought to be a useful interventional agent to decrease colon cancer risk. This is supposedly due, at least in part, to the binding of bile acids and fatty acids by calcium in the colon, thus prohibiting the damaging effects of these substances to the epithelium. To determine the effects of calcium supplementation on fecal fat excretion, 24 subjects kept a fat and calcium constant diet for one week and were supplemented with either 0, 2 or 4 g elemental calcium as calcium carbonate in a double-blind fashion. At the end of the week 72-hour feces was collected, and total fat, neutral fat, fatty acids and the ratio of polyunsaturated and saturated fatty acids (P/S ratio) were measured. Calcium dose-dependently increased the percentual excretion of total fat as related to fat intake: 6.8 +/- 0.9% during 0 g, 7.4 +/- 1.0% during 2 g and 10.2 +/- 1.4% during 4 g, r = 0.44, p = 0.03. This was due to increased fatty acid excretion, excretion of neutral fat was not affected, nor was the P/S ratio. It is concluded that calcium supplementation modestly increases fecal fatty acid excretion. No adverse metabolic effects are to be expected from this in case of long-term calcium supplementation in subjects at increased risk for colon cancer.

Adult↗
PubMed1993

Epithelial cell proliferation in the sigmoid colon of patients with adenomatous polyps increases during oral calcium supplementation.

To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5-bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P < 0.02). This was due to increased labelling in the basal third of the crypts (11.9 vs 16%), whereas labelling in mid and luminal compartments was not affected. Labelling index remained increased after 1 year calcium supplementation at 8.8%. Crypt length was not affected by calcium. These results are in contrast to those of others, who have shown a decrease of rectal epithelial proliferation during similar doses of calcium. Therefore, the effect of nutritional intervention on colonic epithelial proliferation should be studied in biopsies taken not only from the rectum, but also from more proximal parts of the colon. Caution with respect to large scale intervention studies with calcium in high risk groups is mandatory.

Administration, Oral↗
PubMed1993

The assumed assimilation of cholesterol by Lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity.

To study the mechanism of the propsed assimilation of cholesterol, we cultured various strains of Lactobacillus acidophilus and a Bifidobacterium sp. in the presence of cholesterol and oxgall. During culturing, both cholesterol and bile salts were precipitated. Because of bacterial bile salt deconjugation, no conjugated bile salts were observed in either the culture fluids or the pellets. During incubation, the cell count and optical density decreased. The degree of precipitation of bile salts and of cholesterol was dependent on the culture conditions. If L. acidophilus RP32 was cultured under acidifying conditions, the degree of precipitation of deconjugated bile salts was higher than if the pH was maintained at 6.0. Under acidifying conditions, cholesterol was coprecipitated with the bile salts, whereas in pH-controlled cultures, no coprecipitation of cholesterol was observed. From control experiments with different mixtures of bile salts, it appeared that coprecipitation of cholesterol during culturing was a result of formation of deconjugated bile salts, which have a decreased solubility at pH values lower than 6.0. It is concluded that the removal of cholesterol from the culture medium by L. acidophilus RP32 and other species is not due to bacterial uptake of cholesterol, but results from bacterial bile salt-deconjugating activity.

Bifidobacterium↗
PubMed1992

Interaction of calcium and phosphate decreases ileal magnesium solubility and apparent magnesium absorption in rats.

We tested the hypothesis that increased intakes of calcium and phosphate lower magnesium solubility in the intestinal lumen, causing a decreased magnesium absorption. In in vitro experiments at a constant magnesium concentration, increasing calcium concentrations reduced magnesium solubility. This effect did not occur in the absence of phosphate. Increasing phosphate concentrations decreased the solubility of magnesium in the presence, but not in the absence, of calcium. These results suggest that the formation of an insoluble calcium-magnesium-phosphate complex determines magnesium solubility. To extend this concept to in vivo conditions, rats were fed purified diets containing a constant concentration of magnesium (16.4 mumol/g) but different concentrations of calcium (25, 100 or 175 mumol/g) and phosphate (58, 103 or 161 mumol/g). Increased intakes of calcium decreased magnesium solubility in the ileal lumen and lowered magnesium absorption. The latter result occurred only if the dietary phosphate concentration was at least 103 mumol/g. Increasing dietary phosphate concentrations reduced both magnesium solubility in the ileum and magnesium absorption, but only if the dietary calcium concentration was at least 100 mumol/g. These results support those obtained in vitro. We conclude that increased intakes of calcium and phosphate decrease magnesium absorption by the formation of an insoluble calcium-magnesium-phosphate complex in the intestinal lumen.

Animals↗
PubMed1992

Bile secretion of sulfated glycolithocholic acid is required for its cholestatic action in rats.

To test our hypothesis that the cholestatic action of sulfated glycolithocholic acid (SGLC) in the rat is related to its interaction with calcium in the biliary tree [R. van der Meer, R. J. Vonk, and F. Kuipers. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G644-G649, 1988], we have now compared its effects on bile formation in control Wistar rats and mutant Groningen Yellow (GY) Wistar rats. Intravenous injection of 0.6 mumol/100 g body wt of [14C]SGLC in unanesthetized rats with permanent biliary drainage did not induce cholestasis in either of the strains; however, its biliary secretion was strongly impaired in GY rats (12% dose at 1 h after injection vs. 95% dose in controls). Injection of 6.0 and 12.0 mumol/100 g body wt of [14C]SGLC caused an almost complete cessation of bile flow in control rats within 3 and 1 h, respectively. In contrast, administration of the same doses did not cause cholestasis in GY rats. Cholestasis in control rats was preceded by coprecipitation of [14C]SGLC and calcium in bile and incomplete biliary recovery of radioactivity. The hepatic content 15 min after injection of [14C]SGLC (6.0 mumol/100 g body wt) was similar in control and GY rats, 51 and 49% of the dose, respectively. Administration of glycolithocholic acid, the unsulfated parent compound of SGLC (6.0 mumol/100 g body wt), induced a rapid but reversible cessation of bile flow in both controls and GY rats; in this case no precipitation was observed in bile. This study shows that rapid bile secretion of SGLC is required for the induction of cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

School screening for scoliosis: methodologic considerations. Part 1: External measurements.

In order to determine the applicability of school screening techniques for scoliosis, a methodologic survey was carried out within the framework of a school screening project. The accuracy of the measurements of rib hump height, angle of trunk rotation, and of moiré topography was investigated by assessing the intraobserver and interobserver variation. The validity of these techniques was tested by comparing their outcome to the Cobb angle. Intraobserver variation was measured over both short and long time intervals. The interobserver variation was determined among two orthopaedic surgeons and among a group of six doctors. Results are expressed in a Spearman correlation coefficient and a standard deviation. The Spearman correlation ranges from 0.46 (moiré) to 0.75 (rib hump height) in intraobserver variation, and from 0.60 (rib hump height) to 0.70 (angle of trunk rotation) in interobserver variation. The standard deviations illustrate the interobserver range of the measurements, for rib hump height, 3.7 mm, for rotation, 2.3 degrees, and for moiré, 0.7 lines. The validity of the three methods varied from 0.40 to 0.53 as correlated with the angle of Cobb. The conclusion is that these methods can be applied in school screening techniques, but that they do not allow a sharp distinction between normal and pathologic cases. Instead, it is preferable to define the borderline in terms of a danger zone rather than a strict single value. The danger zone for the rib hump height should be 5-10 mm, for the rotation 3-7 degrees, and for the moiré topography 1-3 lines. Recordings in these zones should be repeated within a few months.

Child↗
PubMed1991

Cell type-dependent effect of phospholipid and cholesterol on bile salt cytotoxicity.

The effect of phosphatidylcholine and cholesterol on bile salt-induced cytotoxicity was investigated. Experiments were performed in both human erythrocytes and cultured CaCo-2 cells, a model system for gastrointestinal epithelium. Hemolysis induced by 50 mmol/L sodium-taurocholate was reduced by both lecithin and cholesterol in a concentration-dependent manner. Cholesterol was 10 times more effective than phosphatidylcholine. Addition of only small amounts of the sterol to phosphatidylcholine/taurocholate solutions eliminated all cytotoxicity. The protective influence of cholesterol is probably mediated through a direct effect on the membrane. Incubation of erythrocytes with a cholesterol/taurocholate mixture greatly increased the cholesterol content of the membrane. With respect to sensitivity to bile salts and the protective effect of lecithin, CaCo-2 cells behaved very similar to erythrocytes. However, cholesterol failed to have any cytoprotective effect when used in combination with taurocholate or phosphatidylcholine/taurocholate solutions. Interestingly, at relatively high concentrations of cholesterol (cholesterol saturation index greater than 1.0), the sterol even increased cytotoxicity. This correlated with a cholesterol-induced shift of phosphatidylcholine from micelles to vesicles, which normally occurs in supersaturated model and human bile. The different sensitivity of the two cell types to the effect of cholesterol on bile salt damage might be caused by the difference in lipid membrane composition. In conclusion, CaCo-2 cells represent a physiologically more relevant model system to study bile cytotoxicity than erythrocytes. When extrapolated to gallbladder epithelial cells, these results could be relevant for the pathogenesis of gallstone disease. The increased cytotoxicity might be the signal by means of which supersaturated bile induces mucin hypersecretion by gallbladder epithelial cells.

Bile Acids and Salts↗
PubMed1991

Dietary calcium phosphate inhibits cytotoxicity of fecal water.

The effects of dietary steroid and CaHPO4 supplementation on the solubility of bile acids and cytotoxicity of fecal water were studied in rats. Dietary steroid supplementation increased the bile acid concentration of both feces and fecal water. CaHPO4 supplementation produced a slight increase in total fecal bile acid concentration but resulted in a drastic decrease in soluble bile acid concentration. Cytotoxicity of fecal water on control and steroid-supplemented diets decreased with CaHPO4 supplementation analogous to the decrease in soluble bile acid concentration. The concentrations of precipitated Ca and Pi were highly correlated (r greater than 0.90) with the concentration of precipitated bile acids and with inhibition of cytotoxicity. However, there was no significant correlation between the logarithms of soluble calcium and soluble bile acids, indicating that solubility of bile acids is not determined by soluble calcium. Concentrations of calcium and phosphate in fecal water indicated the formation of insoluble calcium phosphate in the intestine. Thus dietary CaHPO4 causes a decrease in soluble bile acid concentration, which is probably due to the formation of an insoluble bile acid calcium phosphate complex. Consequently, cytotoxicity of fecal water is inhibited, which might have implications for the protective effect of dietary calcium with regard to colonic cancer in humans.

Animals↗
PubMed1989

Plasmodium berghei: gametocyte production, DNA content, and chromosome-size polymorphisms during asexual multiplication in vivo.

In this study the DNA content and the karyotype of clones of Plasmodium berghei, which differed in the capability to produce gametocytes, were determined. The DNA content per haploid genome was established by cytofluorometric methods after staining of the haploid merozoites with DNA-specific fluorescent dyes. Field inversion gel electrophoresis was used to establish the number and size of the chromosomes. Parasites of a high gametocyte producer clone (original HP) and a low producer clone (original LP) contained 13 to 14 chromosomes in the size range of 0.5-3.8 megabase. In four independent experiments parasites of the original HP clone were maintained in mice and were mechanically transmitted for prolonged periods of time (up to 90 weeks). During the transmission period the capability to produce gametocytes decreased in all four lines. After mosquito transmission of parasites from these low producer lines, the gametocyte production returned to the level of the original HP clone. The total DNA content per haploid genome of low producer parasites was not significantly different from that of HP parasites. During prolonged periods of asexual multiplication of the HP clone in vivo, changes in the relative size of several chromosomes were detected. Mosquito transmission of the original HP clone did not result in a change of the karyotype. However, novel karyotypes were readily observed after mosquito transmission of parasites of the low producer lines. The decrease of the capability to produce gametocytes did not necessarily involve detectable changes in DNA content or in karyotype.

Animals↗
PubMed1989

Digestibility of casein, formaldehyde-treated casein and soya-bean protein in relation to their effects on serum cholesterol in rabbits.

Adult male rabbits were fed on semi-purified diets containing soya-bean protein isolate, casein or formaldehyde-treated casein as the protein source and 1 g cholesterol and 5 g of the non-absorbable marker chronic oxide/kg diet. The concentration of cholesterol in serum and in liver was increased on both the casein and formaldehyde-treated-casein diets. Excretion of bile acids and their concentration in faeces were lower in rabbits fed on casein or formaldehyde-treated casein when compared with rabbits fed on soya-bean protein. Apparent digestibility of nitrogen was lowest when formaldehyde-treated casein was fed, and highest on the casein diet. In rabbits fed on casein treated with formaldehyde, higher proportions of N were found in the water-soluble and trichloroacetic acid-insoluble protein fractions of the gastrointestinal tract contents compared with rabbits on the other two diets. Absorption of phosphate from the gastrointestinal tract was higher in rabbits fed on casein than in rabbits fed on soya-bean protein or formaldehyde-treated casein. The results indicate that, in rabbits, protein digestibility may not be an important determinant of serum cholesterol.

Animals↗
PubMed1989

Comparison of the hypocholesterolemic effects of dietary soybean protein with those of formaldehyde-treated casein in rabbits.

Treatment of casein with formaldehyde changes its tertiary structure and decreases its hypercholesterolemic properties in rabbits. To investigate whether formaldehyde-treated casein exerts this hypocholesterolemic effect in the same manner as soybean protein, rabbits were fed high or low cholesterol diets containing soybean protein, casein, formaldehyde-treated casein or a mixture of casein and formaldehyde-treated casein. Formaldehyde-treated casein was hypocholesterolemic when fed in a low, but not in a high, cholesterol diet. The hypocholesterolemic effect of soybean protein was independent of the amount of cholesterol included in the diet. In contrast to rabbits fed soybean protein, steroid absorption in those fed formaldehyde-treated casein did not differ from that in rabbits fed native casein. Furthermore, the absorption of phosphorus and nitrogen was lower in rabbits fed formaldehyde-treated casein than in those fed native casein, whereas the absorption found in rabbits fed soybean protein resembled that of their casein-fed counterparts. The diets containing soybean protein and formaldehyde-treated casein produced a comparable ratio of lysine to arginine in serum. The results presented in this paper indicate that the hypocholesterolemic action of dietary formaldehyde-treated casein does not resemble that of soybean protein.

Amino Acids↗
PubMed1988

Cholestasis and the interactions of sulfated glyco- and taurolithocholate with calcium.

To elucidate possible mechanisms of the differential cholestatic effect of sulfated glyco- and taurolithocholate (SGLC and STLC) the interactions of these bile acids with calcium were studied both in vitro and in vivo. In vitro, SGLC was readily precipitated by Ca in physiological concentrations (less than 5 mM). It appeared that only micelles of SGLC were precipitated and that both the sulfate and the carboxylate anionic groups participated in Ca binding. Conjugation with taurine almost completely prevented this Ca-dependent precipitation. Intravenous infusion of SGLC (12 mumol/h) in unanesthetized rats with permanent biliary drainage induced cholestasis, which was preceded by the formation of a biliary Ca-SGLC precipitate, suggesting a causal relationship. Taurine conjugation prevented this biliary precipitation as well as cholestasis. Furthermore, we studied in vitro the binding of the sulfated bile acids to insoluble calcium phosphate, simulating interactions with Ca at the intestinal level. Compared with STLC, micellar SGLC was bound with much higher affinity. This high-affinity binding was probably due to the involvement of both the sulfate and the carboxylate group. This might also explain that the apparent critical micellar concentration of SGLC, in contrast to that of STLC, was extremely Ca dependent. The present findings indicate that 1) interaction with calcium might be responsible for the differential cholestatic properties of SGLC and STLC and 2) binding of sulfated lithocholic acid conjugates to insoluble calcium phosphate in the intestinal lumen is likely to prevent their accumulation in the enterohepatic circulation.

Animals↗