Higher vitamin D intake is needed to achieve serum 25(OH)D levels greater than 50 nmol/l in Québec youth at high risk of obesity.

BACKGROUND/OBJECTIVES: Vitamin D levels are often observed to be low in Canadian youth, despite the mandatory fortification of fluid milk. We identified modifiable correlates of plasma vitamin D concentrations to inform public health efforts to remediate low-vitamin D status. SUBJECTS/METHODS: We recruited 159 children aged 8-11 years, who were at at high risk of obesity, non-systematically during different seasons. Vitamin D status was assessed by measuring plasma 25-hydroxyvitamin D (25(OH)D) using a radioimmunoassay. Dietary intake, including vitamin supplements, was measured using three dietitian-administered 24 h diet recalls. Fat mass was measured by dual energy X-ray absorptiometry. Accelerometers were worn for 7 days to estimate physical activity. Independent correlates of plasma 25(OH)D concentrations were identified using multiple regression in an analysis controlling for season of measurement. RESULTS: Approximately, 7% of youth had hypovitaminosis D (25(OH)D ≤37.5 nmol/l) during winter and spring when vitamin D levels are at their nadir. Only 55% of participants had vitamin D levels, which the Institute of Medicine considers optimal (25(OH)D >50 nmol/l). The mean dietary vitamin D intake, 6.6 mcg, was well below current recommendations set at 15 mcg. A serving increase in milk consumption and a s.d. increase in physical activity were associated with only a 2.9 and 2.1 nmol/l increase in plasma 25(OH)D, respectively. There was no association between 25(OH)D and adiposity. CONCLUSIONS: Our results indicate the challenges of obtaining adequate vitamin D intake from the current food supply to support a level of 25(OD)D >50 nmol/l.

Point of care testing: transcutaneous bilirubinometry in neonates.

Physicians taking care of infants in the first days of life are often faced with neonatal jaundice, especially in an era where post-partum discharge occurs earlier and assessment of newborn bilirubinemia status is required prior to discharge. The Canadian Pediatric Society and the American Academy of Pediatrics have developed and published guidelines for the diagnosis and management of hyperbilirubinemia in newborns. Point of care testing refers to any test performed outside of laboratory by clinical personnel and close to the site of patient care. Based on a summary of multiple reports during the last twenty years, we realize that devices which provide a non-invasive transcutaneous bilirubin (TcB) measurement have proven to be very useful as screening tools and provide a valid estimate of the total serum bilirubin level (TSB). Published data suggest that these devices provide measurements within 30-50 micromol/L of the TSB levels and can replace laboratory measurement particularly when TSB levels are less than 260 micromol/L. At the present time, in the literature, evidence is insufficient to abandon neonatal serum bilirubin testing and replace it with TcB. Any measurement, TSB or TcB, has potential for error. However, we have evidence that TcB, can help avoiding potential errors associated with even visual assessment of jaundice and may be useful as screening device to detect significant jaundice and decrease a large number of unnecessary skin punctures. The current manuscript is based on a careful comprehensive literature review concerning neonatal hyperbilirubinemia. We consider that this manuscript will help clinicians and laboratory professionals in the management of neonatal jaundice.

Insulin resistance syndrome in a representative sample of children and adolescents from Quebec, Canada.

OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS: In all age-sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION: IRS is highly prevalent in youth, even among children as young as age 9 y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.

[Placenta associated plasma protein-A (PAPP-A): clinical value in cardiovascular medicine]. / La protéine plasmatique placentaire A (PAPP-A): intérêt clinique en médecine cardiovasculaire.

PAPP-A is high molecular weight metalloproteinase originally identified in the serum of pregnant women. During pregnancy, the concentration of PAPP-A increases in maternal circulation with gestational age. Depressed levels, associated with an abnormal placental function, have formed the basis of the first trimester screening for Down syndrome. The role of PAPP-A in tissue other than placenta has only recently been explored. More recently elevated serum concentrations of PAPP-A have been identified in patients with unstable angina or acute myocardial infract. It has thus been proposed as a potential early indicator of acute coronary syndrome.

The Delta>15 Kb deletion French Canadian founder mutation in familial hypercholesterolemia: rapid polymerase chain reaction-based diagnostic assay and prevalence in Quebec.

Approximately one in 500 individuals in Western population has autosomal dominant familial hypercholesterolemia due to mutations in the low-density lipoprotein receptor (LDLR) gene. Screening for these mutations is hampered by their large number, except in founder populations. We identified the breakpoint of the >15 kb deletion involving the LDLR gene promoter and exon 1, responsible for more than 60% of French Canadian hypercholesterolemia cases, as well as the breakpoint of the 5 kb deletion of exons 2 and 3 that accounts for an additional 5% of cases. Both deletions appear to be because of homologous recombination by unequal crossing-over between the left arms of Alu repeats. Using RepeatMasker, we determined that 55% of the LDLR gene is composed of Alu elements; thus, it is not surprising that most LDLR rearrangements involve at least one Alu. Furthermore, we developed a rapid polymerase chain reaction-based assay for the French Canadian-1 (>15 kb) and French Canadian-5 (5 kb) hypercholesterolemia alleles. Screening a representative population sample of 943 French Canadian youths whose LDL cholesterol levels were above the 50th percentile allowed us to estimate the prevalence of the >15 kb allele as 0.11% (95% confidence interval, 0.03-0.38).

Hyperlipidemic profiles during remission in childhood idiopathic nephrotic syndrome.

Hyperlipidemia, an important characteristic of idiopathic nephrotic syndrome in children (NS), is usually observed during the active phase of the disease and disappears with the resolution of the proteinuria. However, persisting lipid anomalies during remission have been reported in a few studies and raise the question of the later development of atherosclerosis. Plasma lipid profiles in 25 children with NS at remission, with or without active prednisone treatment, were compared with those of an age-matched population. The results indicate that plasma total and LDL-cholesterol levels were above the 95(th) percentile for age and sex in 12 of the 25 patients (48%) with 7 of them having apolipoprotein B and triglyceride concentrations above the 95(th) percentile. Moreover, frequently relapsing children were more likely to have abnormal lipid profile during the remission. We conclude that close monitoring of lipid levels during the remission of the NS especially in those with frequent relapses, is necessary to select the high-risk patients.

Vascular responses to alpha-adrenergic stimulation and depolarization are enhanced in insulin-resistant and diabetic Psammomys obesus.

Since vascular complications often accompany diabetes, we examined the influence of the endothelial lining on vascular reactivity in Psammomys obesus, a desert gerbil that acquires insulin resistance and diabetes when exposed to a laboratory diet. Vasoconstriction to phenylephrine and depolarizing KCl, as well as carbachol endothelium-dependent relaxation, were assessed in rings of thoracic aortae obtained from three groups: (i) group A, normoglycemic-normoinsulinemic; (ii) group B, normoglycemic-hyperinsulinemic, and (iii) group C, hyperglycemic-hyperinsulinemic animals. As expected, marked hypertriglyceridemia and hypercholesterolemia characterized groups B and C, which developed enhanced contractile responsiveness to phenylephrine and KCl compared with controls (group A). Furthermore, both experimental groups displayed a significant decrease in endothelium-dependent relaxation to carbachol. Altered lipid profiles are considered to play some role in the observed modification of aortic reactivity. Overall, our data indicate that vascular contractile responsiveness is enhanced early in the development of insulin resistance and diabetes in the female P. obesus.

Effect of human recombinant leptin on lipid handling by fully differentiated Caco-2 cells.

It has been established that leptin displays a number of effects on peripheral tissues. We have investigated the effect of the hormone on lipid synthesis, apolipoprotein biogenesis and lipoprotein secretion in Caco-2 cells. Immunocytochemistry revealed the presence of leptin receptors (Ob-Rb) on the basolateral membrane. Incubation of cells with 200 nM leptin resulted in a decreased export of triglycerides in the basolateral medium without affecting monoglyceride, diglyceride and cholesterol ester lipid classes. It also significantly reduced the output of de novo-synthesized apolipoprotein (Apo)B-100 and ApoB-48 as well as that of newly formed chylomicrons and of low-density lipoproteins. It also enhanced that of ApoA-I, ApoA-IV and ApoE. Our results support the hypothesis that leptin can affect energy balance at the gut level by reducing lipid release into the circulation.

Plasma homocysteine concentration in children with chronic renal failure.

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.

Determinants of lipid level variability in French-Canadian children with familial hypercholesterolemia.

The wide variability in the biochemical expression of familial hypercholesterolemia (FH) is only partly explained by mutational heterogeneity in the low density lipoprotein receptor (LDLR) gene. In the current study, we measured this biochemical variability in a group of children heterozygous for the >15-kb LDLR gene deletion (n=67) and examined the contribution of apolipoprotein (apo) E and B allelic variations to this phenotypic variability. Variances of total cholesterol (TC), LDL-C, and apoB concentrations and of the ratio of TC to high density lipoprotein cholesterol (HDL-C) were increased in FH subjects compared with controls. However, after taking the means into account, the coefficients of variation showed that the variability of LDL-C and apoB concentrations was smaller for FH than for controls and that the variability of TC and of the ratio TC to HDL-C was similar between both groups. The epsilon2/3 genotype was associated with lower mean TC, LDL-C, and apoB concentrations in FH. The magnitude of this effect was smaller in controls than in FH. Indeed, the percentages of total variance of TC, LDL-C, and apoB attributable to the apoE locus were 19.9%, 18.1%, and 11.8%, respectively, in FH cases and 5.9%, 7.4%, and 6.0%, respectively, in controls. We did not detect any effect of the apoB insertion/deletion polymorphism on lipid traits in FH children. However, in controls, we observed a strong interaction between apoE and apoB genotypes on apoB concentrations and on TC to HDL-C ratios. Our study reemphasizes the important role of apoE in lipid metabolism and illustrates that the effects of allelic variations on lipid traits are context dependent.

Immunolocalization, ontogeny, and regulation of microsomal triglyceride transfer protein in human fetal intestine.

To examine the multiple stages of lipoprotein packaging during development, we studied localization, ontogeny, and regulation of microsomal transfer protein (MTP), a crucial protein for lipid transport. With the use of immunofluorescence, MTP was identified in villus and crypt epithelial cells in different regions of human fetal intestine, including colon. Staining was detected as early as the 13th wk of gestation in all gut segments and was almost entirely confined to the columnar epithelial cells of the jejunum and colon. Unlike immunofluorescence, which provides qualitative but not quantitative information on MTP signal, enzymatic assays revealed a decreasing gradient from proximal small intestine to distal, as confirmed by immunoblot. Activity of MTP in small intestinal explants cultured for different incubation periods (0, 4, 8, and 24 h) peaked at 4 h but remained insensitive to different concentrations of oleic acid. Also, a trend toward increasing MTP activity was observed at 20-22 wk of gestation. Finally, in strong contrast to jejunal efficiency, colonic explants displayed impaired lipid production, apolipoprotein biogenesis, and lipoprotein assembly, in association with poor expression of MTP. These findings provide the first evidence that human fetal gut is able to express MTP and emphasize the distinct regional distribution, regulation by oleic acid, and ontogeny of MTP.

Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children.

BACKGROUND: Several studies have examined the association of the methylenetetrahydrofolate reductase (MTHFR) genotype with plasma homocysteine in adults, but few studies have been performed in children. OBJECTIVE: We measured the concentrations of plasma total homocysteine, folate, and vitamin B-12 in a group of healthy fasting children and related these to MTHFR genotype. DESIGN: After the subjects fasted, blood samples were collected into EDTA-containing tubes. Plasma, red blood cells, and the buffy coat were immediately stored at -80 degrees C for biochemical and molecular analyses. Plasma total homocysteine was determined by HPLC. Folate and vitamin B-12 were measured by a double-labeled radioimmunoassay, and the genotypic analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from blood leukocytes. RESULTS: Plasma homocysteine concentrations correlated negatively with folate and vitamin B-12(,) but positively with age (P: < 0. 0001). Whereas folate and vitamin B-12 accounted for 27% and 19% of the variation in homocysteine, respectively, age accounted for 48% of the variation. When the cohort was divided into older (>10 y) and younger (10 y. CONCLUSION: Our data show that in a healthy pediatric population, MTHFR genotype played a significant role in determining homocysteine concentrations in older (>10 y), nutritionally stressed children.

Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency.

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6 deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflamed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1alpha-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resorption) associated with vitamin B6 deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.

Perinatal metabolism of vitamin D.

During pregnancy, maternal serum concentrations of 25-hydroxyvitamin D, the circulating form of vitamin D, correlate with dietary vitamin D intake. Maternal serum concentrations of 1,25-dihydroxyvitamin D, the hormonal circulating and active form of vitamin D, are elevated during pregnancy; 1,25-dihydroxyvitamin D is synthesized mainly by the decidual cells of the placenta and allows for increased calcium absorption. The fetus is entirely dependent on the mother for its supply of 25-hydroxyvitamin D, which is believed to cross the placenta. Hypocalcemia and increased parathyroid hormone secretion induce synthesis of 1,25-dihydroxyvitamin D after birth in both full-term and preterm neonates. Nevertheless, serum concentrations of 25-hydroxyvitamin D are a rate-limiting factor in the synthesis of 1,25-dihydroxyvitamin D. In vitamin D-replete infants, circulating 1,25-dihydroxyvitamin D concentrations are higher than those observed in older infants. In countries where dairy products are not routinely supplemented with vitamin D, maternal vitamin D supplementation during pregnancy is necessary. However, there is no indication for the use of pharmacologic doses of vitamin D or its metabolites in the perinatal period.

Vitamin A and E supplementation in breast-fed newborns.

BACKGROUND: Vitamins A and E are two potent antioxidant nutrients that play a significant role in immune function. In contrast to the numerous studies of vitamin A and E status in children, adolescents, and adults, information on term infants, particularly breast-fed infants, is scarce. The goals of the present investigation were to examine the vitamins A and E nutritional status of term breast-fed infants at birth and to assess retinol and tocopherol plasma levels during a 3-month supplementation trial. METHODS: The study was a prospective, blinded comparison of a supplementation protocol with a placebo in a group of consecutively recruited term newborns. The supplemented group received 3000 IU vitamin A and 5 IU vitamin E orally. The placebo group received a solution of similar viscosity and organoleptic characteristics. Vitamin A and E were separated by reverse-phase high-performance liquid chromatography on a C18 Spectrasyl column and quantified by ultraviolet spectrophotometry. RESULTS: Vitamin A and E levels steadily increased with age in both groups of infants. However, levels at 3 months were higher in the supplemented than in the control group. CONCLUSION: The data show that supplementation with 3000 IU vitamin A and 5 IU vitamin E for 3 months increases circulating vitamin levels in newborn term babies compared with those in nonsupplemented infants.

Modulation of apo A-IV transcript levels and synthesis by n-3, n-6, and n-9 fatty acids in CACO-2 cells.

It has been postulated that apolipoprotein (apo) A-IV plays various significant roles in lipid transport and lipoprotein metabolism. Although it is controlled by fat feeding, so far little else is known about its regulation by specific fatty acids. In this study, we focused on the modulation of apo A-IV mRNA levels, mass, and biogenesis by mono- and polyunsaturated fatty acids (FA) in the human intestinal Caco-2 cell line. In confluent cells incubated with 1 mM oleic (n-9), linoleic (n-6), alpha-linolenic (n-3), or docosahexaenoic (n-3) acids for a long-term period, both apo A-IV protein levels and de novo synthesis were increased. The induction resulted from the up-regulation of apo A-IV mRNA transcripts. In contrast, an inhibitory effect was evident with short-term incubation. FA chain length and degree of unsaturation had little effect altering apo A-IV transcript and biogenesis. These data offer evidence that isolated fatty acids regulate gene expression and the production of apo A-IV in the enterocyte.

Bile duct cells: a novel in vitro model for the study of lipid metabolism and bile acid production.

Immortalized bile duct cells (BDC), derived from transgenic mice harboring the SV40 thermosensitive immortalizing mutant gene ts458, were utilized to investigate the role of the biliary epithelium in lipid and sterol metabolism. This cell model closely resembles the in vivo situation because it expresses the specific phenotypic marker cytokeratin 19 (CK-19), exhibits the formation of bile duct-like structures, and displays well-formed microvilli projected from the apical side to central lumen. The BDC were found to incorporate [14C]oleic acid (in nmol/mg protein) into triglycerides (121 +/- 6), phospholipids (PL; 59 +/- 3), and cholesteryl ester (16 +/- 1). The medium lipid content represented 5.90 +/- 0.16% (P < 0. 005) of the total intracellular production, indicating a limited lipid export capacity. Analysis of PL composition demonstrated the synthesis of all classes of polar lipids, with phosphatidylcholine and phosphatidylethanolamine accounting for 60 +/- 1 and 24 +/- 1%, respectively, of the total. Differences in PL distribution were apparent between cells and media. Substantial cholesterol synthesis was observed in BDC, as determined by the incorporation of [14C]acetate suggesting the presence of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. With the use of [14C]acetate and [14C]cholesterol as precursors, both tauro- and glycoconjugates of bile acids were synthesized, indicating the presence of cholesterol 7alpha- and 26R-hydroxylases, the key enzymes involved in bile acid formation. The transport of bile acids was not limited, as shown by their marked accumulation in the medium (>6-fold of cell content). HMG-CoA reductase (53.0 +/- 6.7), cholesterol 7alpha-hydroxylase (15. 5 +/- 0.5), and acyl-CoA:cholesterol acyltransferase (ACAT; 201.7 +/- 10.2) activities (in pmol. min-1. mg protein-1) were present in the microsomal fractions. Our data show that biliary epithelial cells actively synthesize lipids and may directly contribute bile acids to the biliary fluid in vivo. This BDC line thus represents an efficient experimental tool to evaluate biliary epithelium sterol metabolism and to study biliary physiology.

Accuracy of the [13C]-urea breath test in diagnosing Helicobacter pylori gastritis in pediatric patients.

BACKGROUND: The causal association between Helicobacter pylori (H. pylori) colonization of the gastric mucosa and gastritis is now well established. Histologic examination of endoscopic biopsy specimens has long been regarded as the gold standard for diagnosis. However, the changes can be focal in nature and presence of the organism may be missed in nonsampled areas. The urea breath test, which uses a stable isotope, offers distinct advantages, in that it is noninvasive and measures the activity of the micro-organism. It thus represents a potentially invaluable tool in the initial diagnosis of the infection and in verifying its eradication. METHODS: The study design was that of a prospective, blinded comparison of the [13C]-urea breath test with histologic assessment of antral biopsy specimens using the Warthin-Starry stain, to diagnose H. pylori infection in a group of 79 consecutive pediatric patients. RESULTS: Patients classified as negative by histology (n=67) had breath 13C enrichment of 0.97+/-0.07 delta per thousand (mean+/-SEM), with a range of -0.20 and 2.83 delta per thousand. In contrast, those with a positive histologic results (n=12) had an enrichment of 25.41+/-5.01 delta per thousand (range, 3.43-58.80; p < 0.001). At the chosen cutoff point of 3 delta per thousand, the sensitivity and specificity as well as the positive and negative predictive values of the breath test were uniformly 100%. CONCLUSION: The [13C]-urea breath test is a highly reliable, noninvasive method for the diagnosis of H. pylori gastritis in children and adolescents.

Developmental expression of calcitriol receptors, 9-kilodalton calcium-binding protein, and calcidiol 24-hydroxylase in human intestine.

Human intestinal mucosa consists of highly active epithelial cells in continual renewal and differentiation processes located at different portions of the villi. The crypt contains abundant replicating cells which, upon reaching the villus tip, acquire their fully differentiated state. Besides its well recognized role in bone cell homeostasis, calcitriol has been attributed a role in cellular differentiation and proliferation in normal leukocytes and myeloid leukemia cells. We have previously documented the presence and the distribution of specific calcitriol receptors in the cells of the small and large intestine from 13-20-wk-old human fetuses and that calcitriol was able to promote human intestinal epithelium proliferation or differentiation, in organ culture, depending upon fetal age. We now show that, whereas transcripts for calcitriol receptors are abundant from duodenum to colon, those for the 9-kD calcium-binding protein are present mainly in the duodenum and the jejunum and to a lesser extent in the ileum and the colon. Transcripts for 25-hydroxycholecalciferol-24-hydroxylase could not be detected in any of the intestine segments despite a prolonged exposition of the gels. Immunofluorescence staining for the 9-kD calcium-binding protein was exclusively observed in the epithelial cells of the small intestine and colon, the subepithelial layers being always negative. The 9-kD calcium-binding protein distribution along the crypt-villus axis appeared as a gradient, increasing from the developing crypt to the tip of the villus in the duodenum, jejunum, and ileum. Based on the present observations and on the fact that calcitriol promotes human fetal proliferation and differentiation, the presence of transcripts for calcitriol receptors and 9-kD calcium-binding protein in the intestinal cell opens interesting possibilities as of their role in the in utero human gut development and the control of colorectal cancers.