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Nutritional interrelationships between calcium, phosphorus and lactose in rats.

From the age of 3 months, six groups of rats consisting of six animals each were fed one of three types of diet with either 15% lactose or dextrose. The diets used were a control diet containing 0.6% calcium and 0.45% phosphorus and two high-phosphorus (1.3%) diets with either a normal (0.6%) or a low (0.2%) calcium content. Whereas calcium retention and femur mass appeared to be unaffected, feeding the high-phosphorus diets resulted in significant (P less than or equal to 0.05 or P less than or equal to 0.01) biochemical changes including: decreased plasma phosphorus almost throughout the whole of the study; increased plasma alkaline phosphatase, and urinary total hydroxyproline after 17 and 42 weeks; nephrocalcinosis; depressed urinary calcium, and reduced femur density. With the excretion of nephrocalcinosis and depressed urinary calcium, these changes were more marked if the calcium content of the diet was low than when it was normal, and this difference was associated with a significant (P less than 0.01) inhibiting effect of dietary calcium on the intestinal absorption and urinary excretion of phosphorus. Although lactose, as compared with dextrose, significantly (P less than 0.01) improved the intestinal absorption and retention of calcium during body weight gain, which was reflected by an increased femur mass after 42 weeks, this sugar did not reduce the detrimental effects on bone and soft tissue resulting from feeding the high-phosphorus diets. The results of the study in line with the induction of nutritional secondary hyperparathyroidism and increased bone turnover in rats fed high-phosphorus diets and indicate that lactose-stimulated calcium absorption will not prevent or diminish the biochemical changes associated with this disease; the results also stress the significance of the calcium content of the diet as a factor that may protect the body against excessive dietary phosphorus.

Alkaline Phosphatase↗

Intestinal brush border membrane catalyzes hydrolysis of pyridoxine-5'-beta-D-glucoside and exhibits parallel developmental changes of hydrolytic activities toward pyridoxine-5'-beta-D-glucoside and lactose in rats.

Pyridoxine-5'-beta-D-glucoside (PNG) is a major form of vitamin B-6 in plant foods that exhibits partial bioavailability as vitamin B-6 in humans. We previously identified an intestinal mucosal cytosolic PNG hydrolase that catalyzes the partial hydrolysis of PNG absorbed without prior deglycosylation. Recent observations that the brush border membrane also catalyzes PNG hydrolysis led to the hypothesis that PNG hydrolysis may be another function of the beta-glucosidase lactase-phlorizin hydrolase (LPH) and, thus, brush border PNG hydrolysis would undergo a developmental decline similar to that of lactose hydrolysis. In this study, the relationships among hydrolytic activities in small intestinal cytosolic and brush border fractions in rats (n = 9 per group) of various ages (1-2 d and 2, 4, 8, 12 and 24 wk) were examined. In vitro specific activities toward PNG and lactose were greater in brush border than cytosol, and these were greater in newborn rats than in all other age groups (P < 0.01). Brush border activities toward PNG and lactose and were closely correlated (r = 0.84; P < 0.0001). These findings suggest that the hydrolysis of PNG is catalyzed at least partially at the brush border and that the bioavailability of PNG may be influenced by the residual LPH activity in children and adults.

Animals↗

Studies of gene control regions. III. Binding of synthetic and modified synthetic lac operator DNAs to lactose repressor.

Chemically synthesized lactose operator DNA was tested for binding with lactose repressor protein. These operator DNAs were found to (1) bind specifically to lactose SQ repressor as measured by release of binding with the inducing ligand isopropyl-beta-D-thiogalactoside, (2) have dissociation half-lives of 37 seconds (21 base-paired duplex) and 46 seconds (26 base-paired duplex) and (3) have dissociation half-lives with x86 repressor of 9 minutes (21 base-paired duplex) and 18 minutes (26 base paired duplex). Modified operators containing 5-bromodeoxyuridine and deoxyuridine at specific sites were also prepared. These analogs bound both repressors about as tightly as the wild type sequence.

Base Sequence↗

The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk.

The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years.

Adult↗

Lactose intolerance and the genetic regulation of intestinal lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase, which hydrolyzes lactose, the major carbohydrate in milk, plays a critical role in the nutrition of the mammalian neonate. Lactose intolerance in adult humans is common, usually due to low levels of small intestinal lactase. Low lactase levels result from either intestinal injury or (in the majority of the world's adult population) alterations in the genetic expression of lactase. Although the mechanism of decreased lactase levels has been the subject of intensive investigation, no consensus has yet emerged. Recent studies have begun to define the cellular and molecular biology of this enzyme. In animals and humans, a glycosylated precursor is proteolytically cleaved to yield the mature enzyme on the microvillus membrane of the enterocyte, bound to the lipid bilayer only by a hydrophobic anchor sequence. The enzyme hydrolyzes lactose, phlorizin, and glycosylceramides. A decline in lactase specific activity occurs at the time of weaning in most mammalian species; in most humans who have low lactase activity as adults, the decline occurs at approximately 3-5 years of age. In a few human groups, the elevated juvenile level of lactase specific activity persists throughout adulthood. These developmental patterns of lactase expression are most likely regulated at the level of gene transcription.

Animals↗

Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis.

BACKGROUND: Patients with active Crohn's disease (CD) often report having abdominal symptoms after ingestion of milk products, but the pathomechanism for lactose malabsorption seems to be complex. GOALS: To investigate the prevalence of clinical milk intolerance and to objectify symptoms with hydrogen (H 2 ) breath testing, analysis of lactase protein, and enzyme activity in the duodenal mucosa in patients with CD and in healthy controls. STUDY: In 49 patients with CD and 24 controls, H 2 breath testing was performed. All individuals underwent endoscopy of the upper gastrointestinal tract, in which multiple pinch samples were taken from the distal duodenum. Lactase activity was measured using the method of Dahlquist. The lactase protein expression was analyzed by gel electrophoresis using the monoclonal antibody mlac 10 and by immunochemistry using the monoclonal antibody mlac 4. RESULTS: Prevalence of milk intolerance in healthy controls was 16.6% versus 46.9% in patients with CD, with a high frequency (83.3%) in patients with active disease (CD activity index >150). Milk intolerance was correlated to the duration of inflammatory bowel disease ( p = 0.023) but not to the location or previous bowel resection. Hydrogen breath testing had a moderate sensitivity in detecting lactose maldigestion (70.4%) and a high specificity (95.6%). Duodenal lactase levels were also correlated to disease activity, whereas correlations to clinical symptoms remained poor. Patients with milk intolerance had a significantly reduced bone density at the lumbar spine (z-score, -1.33 +/- 0.92 vs. -0.19 +/- 0.95 [mean +/- SD]; p = 0.002) CONCLUSIONS: Milk intolerance is a frequent problem in active CD, which can be objectified accurately by H 2 lactose breath testing. Decreased lactase levels in the duodenal mucosa may be found during an acute flare but are not the predominant cause of milk intolerance in CD.

Adult↗

Lactose malabsorption is not a cause of diarrhea during phototherapy.

Lactose malabsorption is not a cause of diarrhea during phototherapy. Jaundiced neonates under phototherapy develop diarrhea or loose stools during the treatment. These phenomena were attributed to an induced lactase deficiency caused by bilirubin breakdown products. We investigated lactose malabsorption in 59 neonates--29 normals and 30 jaundiced under phototherapy. Five-hour hydrogen breath tests were performed. Preprandial and postprandial (at 30, 60, 120, 180, 240, and 300 min) expired air samples were analyzed for hydrogen. Ten controls and five jaundiced neonates had positive hydrogen breath tests. Eighteen controls and 16 neonates under phototherapy had preprandial hydrogen (concentrations above 5 ppm). In our hands, lactase deficiency and lactose malabsorption were not induced by phototherapy. Lactase deficiency is therefore not the cause of diarrhea associated with phototherapy.

Breath Tests↗

Milk lactose malabsorption in Gabon measured by the breath hydrogen test.

It is usual to consider that the greatest part of the black African population is lactose intolerant. Also, milk lactose malabsorption was studied by a breath hydrogen technique in 87 Gabonese children and 20 Gabonese adults (central Africa). The prevalence of malabsorption was 64.2% in rural schoolchildren, 65% in the urban hospitalized, and 60% in adults. Twelve children and six adults had clinical symptoms after a lactose load. All subjects were Bantus, with no tradition of consuming dairy products. These data must be considered in programs of nutritional support in Africa.

Adolescent↗

Variations in oligosaccharides and lactose in human milk during the first week of lactation.

Variations in oligosaccharides and lactose in human milk were studied in 15 mothers during the first week of lactation. The neuraminyloligosaccharides and heavy neutral oligosaccharides increased slightly from days 2 to 5 postpartum and appeared to decrease until day 7. The lacto-N-difucohexaoses, lacto-N-fucopentaoses, and lacto-N-tetraose increased until day 5 and then decreased. Lactodifucotetraose and the fucosidolactoses decreased substantially until day 5 (p less than 0.05) and appeared to stablize in the following days. Lactose increased until day 5 (p less than 0.05) and continued to increase thereafter. Lactose was negatively correlated with total oligosaccharides (p less than 0.10). The fluctuations observed in total oligosaccharides from days 2 to 5 postpartum and their subsequent stabilization and regular decrease during lactation confirm the hypothesis of Kulski and Hartmann that mammary secretion occurs in three periods: colostrum for the first 36 h postpartum, transitional milk from days 2 to 5 postpartum, and mature milk after day 5. The oligosaccharide variations we found corresponded to those of other milk constituents observed by other authors. The significance of the oligosaccharide variations is discussed.

Adult↗

Clinical trial of modified whole milk, lactose-hydrolyzed whole milk, or cereal-milk mixtures for the dietary management of acute childhood diarrhea.

A randomized, double-masked clinical trial was completed to compare the effects of four dietary regimens for the nutritional management of 116 Peruvian children between 3 and 24 months of age with acute diarrhea. Diets consisted of a modified whole milk formula (group M), a lactose-hydrolyzed milk formula (HM), wheat noodles and whole milk (N-M), or wheat noodles and lactose-hydrolyzed whole milk (N-HM), all offered in amounts up to 55 kcal/kg body weight/day for the first 2 days of treatment and up to 110 kcal/kg/day for 4 days thereafter. The clinical characteristics of the patients in each group were similar initially. Treatment failure rates in the two milk groups combined (M = 14.3%, HM = 20.0%) were greater than in the two noodle-milk groups combined (N-M = 3.4%, N-HM = 3.4%), p = 0.03. The average stool outputs by children in both M groups (range 40-66 g/kg body weight per day on all study days) were consistently greater than those by children in both N-M groups (range 29-50 g/kg/day). The differences by dietary group were statistically significant on days 3 and 4 (p less than 0.04, analysis of variance). The estimated median durations of illness [and 95% confidence limits (CL)] in each milk group (M = 138 h, CL: 88-214; HM = 113 h, CL: 75-170) were significantly greater than in each noodle-milk group (N-M = 52 h, CL: 35-76; N-HM = 67 h, CL: 45-100), p less than 0.001-0.071. In this group of patients, noodle-milk mixtures produced fewer treatment failures, lower fecal outputs, and shorter durations of diarrhea than did milk alone, regardless of the lactose contents of the respective milks or mixed diets. Small differences in intestinal absorption and changes in body weight by dietary group that were identified were of minor clinical importance during the short duration of study. Thus, the noodle-milk diets employed during this study were safer than the milk diets for the dietary management of children with acute diarrhea.

Acute Disease↗

Metabolites of lactose synthesis in milk from women during established lactation.

Metabolites in the lactose synthesis pathway were measured in human milk during established lactation. The mean concentrations (range) were: lactose, 198 mM (175-233); glucose, 1.5 mM (0.1-2.4); glucose 6-phosphate, 11 microM (4-23); glucose 1-phosphate, 2.7 microM (1.6-6.8); UDP-glucose, 2.7 microM (0.6-6.0); UDP-galactose, 0.7 microM (less than 0.1-2.5); inorganic phosphate, 2.2 mM (0.8-2.9). During storage of milk within the breast for 2 h, glucose 6-phosphate concentration increased by 1.4 +/- 0.5 microM, while UDP-glucose decreased by 1.0 +/- 0.4 microM. None of the other metabolites showed significant changes in concentration during this period. Only glucose showed a circadian rhythm in concentration, with the highest concentrations between 1400 and 1800 h. The volumes of milk produced by the mothers ranged from 178 to 1,739 ml/24 h. Despite this variation, there were no significant relationships between the 24-h average concentrations of glucose, glucose 6-phosphate, glucose 1-phosphate, UDP-glucose, UDP-galactose, or inorganic phosphate and the amount of lactose produced over 24 h.

Analysis of Variance↗

Ab initio structure determination of the hygroscopic anhydrous form of alpha-lactose by powder X-ray diffraction.

Annealing of alpha-lactose monohydrate at 408 K yielded a mixture of this compound with hygroscopic anhydrous alpha-lactose. A powder X-ray diffraction pattern of this mixture was recorded at room temperature. The starting structural model of hygroscopic alpha-lactose was found by a Monte Carlo simulated-annealing method. The final structure was obtained through Rietveld refinements, with soft restraints on interatomic bond lengths and bond angles, and crystalline energy minimization to locate the H atoms of the hydroxy groups. The crystalline cohesion is achieved by networks of O-H...O hydrogen bonds that differ from those of the monohydrate phase. The width of the Bragg peaks is interpreted by a phenomenological microstructural approach in terms of isotropic size effects and anisotropic strain effects.

Hydrogen Bonding↗

Structure determination of the 1/1 alpha/beta mixed lactose by X-ray powder diffraction.

The mixed form of alpha/beta lactose was obtained by heating amorphous alpha-lactose at 443 K. NMR spectroscopy determined the stoichiometry of this mixed compound to be 1/1. The X-ray powder diffraction pattern was recorded at room temperature with a sensitive curved detector (CPS 120). The structure was solved by real-space methods (simulated annealing) followed by Rietveld refinements with soft constraints on bond lengths and bond angles. The H atoms of the hydroxyl groups were localized by minimization of the crystalline energy. The cell of 1/1 alpha/beta lactose is triclinic with the space group P1 and contains two molecules (one molecule of each anomer). The crystalline cohesion is achieved by networks of O-H...O hydrogen bonds. The width of the Bragg peaks is interpreted through a microstructural approach in terms of isotropic strain effects and anisotropic size effects.

Carbohydrate Conformation↗

Molecular analysis of the lac operon encoding the binding-protein-dependent lactose transport system and beta-galactosidase in Agrobacterium radiobacter.

The genes coding for the binding-protein-dependent lactose transport system and beta-galactosidase in Agrobacterium radiobacter strain AR50 were cloned and partially sequenced. A novel lac operon was identified which contains genes coding for a lactose-binding protein (lacE), two integral membrane proteins (lacF and lacG), an ATP-binding protein (lacK) and beta-galactosidase (lacZ). The operon is transcribed in the order lacEFGZK. The operon is controlled by an upstream regulatory region containing putative -35 and -10 promoter sites, an operator site, a CRP-binding site probably mediating catabolite repression by glucose and galactose, and a regulatory gene (lacl) encoding a repressor protein which mediates induction by lactose and other galactosides in wild-type A. radiobacter (but not in strain AR50, thus allowing constitutive expression of the lac operon). The derived amino acid sequences of the gene products indicate marked similarities with other binding-protein-dependent transport systems in bacteria.

Amino Acid Sequence↗

Protein, lactose and fat concentration of breast milk of mothers of term and premature neonates.

The protein, lactose and fat concentrations in the milk of seven mothers giving birth at term and six mothers giving birth prematurely were determined. Samples were obtained during the first 31 days of lactation. The protein, lactose and fat concentrations of preterm milk were found to be similar to those of fullterm milk over this period. For both term and preterm groups, protein concentration decreased with increasing age, while lactose concentration increased. Fat concentration did not show a consistent pattern of change in the preterm group, but tended to increase with advancing age in the term group.

Adult↗

Galacto-oligosaccharide production from lactose by Sirobasidium magnum CBS6803.

Galacto-oligosaccharide (Gal-OS) was produced from lactose by a yeast, Sirobasidium magnum CBS6803. With toluene-treated resting cells, 136 mg ml-1 of Gal-OS was produced from 360 mg ml-1 of lactose at 50 degrees C for 42 h. Then, the yield of Gal-OS was increased by a culture method in which cell growth followed the enzymatic reaction: 224 mg ml-1 of Gal-OS was produced at 30 degrees C for 60 h. Finally, combination of the toluene-treated resting cells and glucose oxidase plus catalase was applied to improve productivity by the removal of a by-product, glucose, which inhibits the Gal-OS production, from the reaction mixture. In this case, 242 mg ml-1 of Gal-OS was produced at 50 degrees C for 42 h without cell growth. The structure of the major product was identified as 4'-galactosyl-lactose.

Basidiomycota↗

OmpF changes and the complexity of Escherichia coli adaptation to prolonged lactose limitation.

The disaccharide lactose has no specific diffusion pathway across the outer membrane of Escherichia coli. At least three classes of spontaneous mutation affecting outer membrane permeability arose with each of three independent E. coli populations adapting to prolonged lactose limitation in chemostats. Both structural and regulatory mutations affecting OmpF porin predominated in isolates after 210-280 generations of culture. Six types of ompF mutation were found, including in-frame deletions and substitutions at Arg82 and Asp113, all affecting the channel constriction residues of OmpF. Isolates had increased susceptibility to antibiotics and were affected in the quantity of OmpF, LamB and OmpA proteins. A minimum of three or four mutations was evident in all isolates after 280 generations in a lactose-limited environment, in addition to lac mutations defined in previous studies.

Adaptation, Physiological↗

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula.

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM (n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula (n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 +/- 7.4 versus 20.4 +/- 8.7 mg kg-1 day-1, mean +/- SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 +/- 2.1 versus 2.9 +/- 0.9 mg kg-1 day-1); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g. lacto-N-tetraose, and lacto-N-fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.

Chromatography, High Pressure Liquid↗