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Low trehalase activity is associated with abdominal symptoms caused by edible mushrooms.

BACKGROUND: The purpose of the study was to evaluate whether maldigestion of trehalose causes abdominal symptoms and which available diagnostic method best distinguishes intolerant from tolerant subjects. METHODS: A 25-g oral trehalose load test was performed in 64 subjects. The 19 experiencing clear symptoms constituted the trehalose-intolerant subjects. Changes from base-line levels of blood glucose, breath hydrogen, and methane and symptoms were recorded after the test. Trehalase activity was determined in serum and on a duodenal biopsy specimen obtained by endoscopy. RESULTS: Intolerant subjects were best differentiated from tolerant subjects by changes in breath gases (hydrogen and methane) and duodenal trehalase to sucrase ratio. The change in breath gases correlated inversely with duodenal trehalase activity, duodenal trehalase to sucrase ratio, and plasma trehalase activity. The correlation between serum and duodenal trehalase activities was on the order of 0.6. Two subjects were found to have trehalase deficiency. CONCLUSIONS: It is obvious that trehalose maldigestion can cause symptoms similar to those of lactose maldigestion and intolerance. Three factors control the genesis of symptoms: 1) the activity of small-bowel trehalase: if it is low, trehalose is maldigested and more trehalose is passed into the colon; 2) the maldigested trehalose, which causes osmotic water flow into the colon, resulting in loose stools and diarrhea; and 3) most importantly, the microflora of the colon, from which symptoms will arise if there are bacteria capable of producing gases from maldigested trehalose. If colonic bacteria cannot produce gases, then distention of the abdomen and intestinal gas expulsion as eructations and flatus will not occur.

Abdominal Pain↗

Conformational flexibility at the substrate binding site in the lactose permease of Escherichia coli.

Glu-126 (helix IV) and Arg-144 (helix V) are charge paired and play a critical role in substrate binding in the lactose permease of Escherichia coli. When Glu-126 is replaced with Asp, the permease has relatively high activity, implying that helix V has sufficient flexibility to allow Arg-144 to accommodate the decreased length of the carboxylate-containing side chain of Asp-126. Helices IV and V contain five Gly residues at positions 115, 121, 141, 147, and 150, all of which are conserved in the oligosaccharide/H(+) symport family of the major facilitator superfamily. To test the notion that these residues may contribute to conformational flexibility, each residue was replaced with Ala in either the wild type or the Glu-126 --> Asp mutant. Although the replacements are well tolerated in the wild type, the mutations severely inactivate substrate binding and transport in the Glu-126 --> Asp background, with the exception of Gly-121 --> Ala, which retains significant activity. Strikingly, moreover, in two instances (Gly-150 --> Ala and Gly-141 --> Ala), significant activity is recovered when Ala residues at approximately parallel positions in helix IV (Ala-122 or Ala-127, respectively) are replaced with Gly. In addition to providing further evidence that the major determinants for substrate binding in the permease are at the interface between helices IV and V, the findings indicate that the region is conformationally flexible.

Binding Sites↗

Construction and in vivo analysis of new split lactose permeases.

The capacity of incomplete segments of Escherichia coli lactose permease to form transport-competent complexes in vivo was further tested. Two series of mutant lacY genes were constructed. One encoded N-terminal lactose permease segments of different length. The proteins specified by the other group contained deletions of different length and location within the N-terminal region. Several pairs of such mutant proteins reconstituted active lactose transport. For certain combinations duplications of protein segments were compatible with the formation of an active carrier. Duplication of helices could also be tolerated, when part of a single polypeptide chain.

Escherichia coli↗

Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants.

OBJECTIVE: To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN: Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING: Ambulatory-care facilities of the participating centers. SUBJECTS: 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION: Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES: Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED: Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS: One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS: This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.

Anthropometry↗

Lactose malabsorption and tolerance of lactose-hydrolyzed milk. A double-blind controlled crossover study.

Eleven lactose-intolerant patients were investigated in a double-blind crossover controlled study. In random sequence they received 500 ml of either ordinary cow milk (lactose content, 25 g) or the same amount of low-lactose milk (85% of the lactose hydrolyzed), which had been processed by Lactozym 3000 L for 24 h at 4 degrees C. A significantly increased blood glucose rise from fasting levels was demonstrated in the low-lactose tests. Similarly, a significant reduction of liquid stool frequency, abdominal colics, distention, borborrhygmia, and flatulence was demonstrated. It was concluded that further studies, including long-term treatment of lactose-intolerant children, are indicated.

Adult↗

Small intestinal permeability in pediatric clinical practice.

Passive permeability of small intestine to lactulose and mannitol was studied in children suspected of having intestinal disease, using a hypertonic differential sugar absorption test. Children with coeliac disease and cows' milk intolerance were shown to have an elevated urinary lactulose/mannitol recovery ratio when compared with controls, children with normal jejunal biopsy, or children in whom alternative explanations for failure to thrive had been demonstrated. The abnormality in permeability ratio principally reflects a reduced urinary recovery of mannitol following oral administration. This study demonstrates that a hypertonic sugar absorption test is well tolerated even by young children, is practicable in routine clinical pediatric practice, and is capable of demonstrating abnormal intestinal function in children with small intestinal disease.

Adolescent↗

Food allergies and food intolerances.

Adverse reactions to foods, aside from those considered toxic, are caused by a particular individual intolerance towards commonly tolerated foods. Intolerance derived from an immunological mechanism is referred to as Food Allergy, the non-immunological form is called Food Intolerance. IgE-mediated food allergy is the most common and dangerous type of adverse food reaction. It is initiated by an impairment of normal Oral Tolerance to food in predisposed individuals (atopic). Food allergy produces respiratory, gastrointestinal, cutaneous and cardiovascular symptoms but often generalized, life-threatening symptoms manifest at a rapid rate-anaphylactic shock. Diagnosis is made using medical history and cutaneous and serological tests but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed. Food intolerances are principally caused by enzymatic defects in the digestive system, as is the case with lactose intolerance, but may also result from pharmacological effects of vasoactive amines present in foods (e.g. Histamine). Prevention and treatment are based on the avoidance of the culprit food.

Food Hypersensitivity↗

Immunotherapy by inhalation of allergen in powder in house dust allergic asthma--a double-blind study.

The authors report the analysis of clinical and immunological parameters during local immunotherapy (LI) by inhalation of an extract in powder in patients with allergic asthma due to D. pteronyssinus (DP). The study was double-blind and lasted 24 months. Twenty-four patients were randomly assigned on a double-blind basis to receive by inhalation increasing doses of a micronized, freeze-dried DP extract in powder (14 patients, active therapy) or capsules of lactose (10 patients, placebo group). Results showed a statistically lower symptom score, a significant increase in bronchial tolerance to the allergen and significant levels of DP-specific IgG in actively treated patients compared to those treated with placebo.

Administration, Inhalation↗

Lactose malabsorption and intolerance and peak bone mass.

BACKGROUND & AIMS: Lactose malabsorption per se is not associated with alterations of bone mineral density (BMD) or calcium intake, but when intolerance symptoms are present a lower calcium intake and reduction of BMD values are evident. The purpose of this study was to evaluate whether lactose intolerance interferes with the achievement of an adequate peak bone mass in young adults. METHODS: Of 103 enrolled healthy subjects, 55 proved to be lactose malabsorbers with H(2) breath test after lactose administration, and 29 of them experienced intolerance symptoms (diarrhea, abdominal pain, bloating, flatulence). Lumbar and femoral BMD by dual-energy X-ray absorptiometry was measured, and calcium intake and biochemical indices of bone and mineral metabolism were evaluated. RESULTS: Lumbar and femoral BMD, calcium intake, and mineral metabolism did not differ between malabsorbers and absorbers, although among malabsorbers, intolerant subjects showed significant alterations of all these parameters in comparison with tolerant subjects. A strict correlation was evident between BMD values and both severity of symptoms and calcium intake and between calcium intake and severity of symptoms. CONCLUSIONS: Lactose intolerance prevents the achievement of an adequate peak bone mass and may, therefore, predispose to severe osteoporosis.

Absorptiometry, Photon↗

Lactose malabsorption from yogurt, pasteurized yogurt, sweet acidophilus milk, and cultured milk in lactase-deficient individuals.

The use of fermented dairy foods is common in areas of the world where lactase deficiency is prevalent. Recently, we have shown that the digestion of lactose from yogurt is enhanced as compared to that from milk. This enhanced digestion is apparently due to inherent B-galactosidase in yogurt which is active in the gastrointestinal tract after consumption of the yogurt. Furthermore, yogurt is well tolerated by lactase-deficient subjects resulting in little or no gastrointestinal distress. Since other fermented and microbial-containing dairy foods are consumed worldwide and may also contain some "lactase" activity, we chose to evaluate the digestion of lactose from three of these products: pasteurized yogurt, cultured milk (buttermilk), and sweet acidophilus milk. Breath hydrogen techniques were used to evaluate lactose malabsorption in nine lactase-deficient subjects. The studies demonstrated that yogurt is unique among the products tested in enhancing the digestion of lactose. Furthermore, pasteurization of yogurt eliminated the enhanced digestion of lactose, reduced the inherent lactase activity of the yogurt by 10-fold and reduced cell counts by 100-fold. Interestingly, eight of nine subjects fed cultured milk experienced gastrointestinal distress, whereas all subjects fed pasteurized yogurt were symptom free, even though the amount of malabsorbed lactose was similar.

Adult↗

One-hour blood xylose in the diagnosis of cows milk protein-sensitive enteropathy.

The 1-hour xylose absorption test was evaluated as method for the diagnosis of cows' milk protein-sensitive enteropathy in a prospective study of 48 infants with diarrhoea clinically suspected to be due to intolerance of cows' milk. The infants were maintained on a lactose and cows milk protein-free diet for 6-8 weeks and then were challenged with cows' milk protein. Jejunal biopsies and the 1-hour xylose absorption test were performed immediately before and 20-24 hours after cows' milk provocation. After milk provocation, 30 infants had clinical, enzymological, and histological relapse, and in 28 of them there was a significant depression of post-provocation blood xylose levels. Six infants had histological and enzymological relapse but clinically they tolerated cows' milk. The post-provocation blood xylose level was depressed in all infants. Ten infants had enzymological relapse without histological or clinical relapse. The post-challenge blood xylose was depressed significantly (greater than 20%) in 3, mildly depressed in 3 (16-18%), and not depressed in four. Two infants clinically, histologically, and enzymologically tolerated cows' milk; in each the post-challenge xylose was depressed (22%, 12%). It appears that the 1-hour blood xylose test is not as reliable as the jejunal biopsy in the diagnosis of cows' milk protein-sensitive enteropathy.

Animals↗

Lactose malabsorption in young Lithuanian children with atopic dermatitis.

AIM: To determine the prevalence of lactose malabsorption in young Lithuanian atopic dermatitis children; to evaluate the relationship between lactose malabsorption and the duration of exclusive breastfeeding, and the relationship between lactose malabsorption and cow's milk intolerance in parents and grandparents. METHODS: 144 children with atopic dermatitis aged 1.5-24 mo (study group) and 32 children without symptoms of allergic diseases aged 1.5-23 mo (control group) were investigated. Lactose and glucose-galactose absorption tests based on serial blood glucose determination, culture of stool, latex agglutination test for rotavirus and microscopic examination of stool for parasites were performed. RESULTS: Lactose malabsorption was determined in 59 (40.9%) and glucose-galactose malabsorption in 17 (11.8%) children with atopic dermatitis. The risk of developing lactose malabsorption was higher in children fed exclusively on breast milk up to 1 mo of age than in children fed exclusively on breast milk for 4 to 6 mo (OR: 2.62; 95% CI: 1.02-6.75). Lactose malabsorption was significantly more frequent in patients whose mothers did not tolerate cow's milk (20/30; 66.7%) than in patients whose mothers were tolerant to it (39/95; 41.1%) (p = 0.02). CONCLUSION: Lactose malabsorption was determined in 40.9% of Lithuanian atopic dermatitis children aged under 2 y. Lactose malabsorption appeared to be associated with the duration of exclusive breastfeeding up to only 1 mo and mothers' milk intolerance.

Child, Preschool↗

Tolerance of symptomatic lactose malabsorbers to lactose in milk chocolate.

OBJECTIVE: To study tolerance to lactose in milk chocolate among symptomatic lactose maldigesters. DESIGN: Randomized cross-over study. SUBJECTS: Twenty-seven adult lactose maldigesters with symptomatic lactose intolerance. METHODS: A 100 g chocolate sample prepared with whole milk (12 g lactose), whole-milk powder (12 g lactose), low-lactose milk powder (2 g lactose) or lactose-free milk powder was eaten after an overnight fast. Gastrointestinal symptoms (flatulence, abdominal bloating, abdominal pain, borgorygmi and nausea) were recorded in a questionnaire during the following 8 h. Bowel movements and stool consistency were also registered during the test day. RESULTS: The numbers of persons reporting different gastrointestinal symptoms or any of the symptoms did not differ significantly after eating the chocolate samples. No statistical differences were found in the estimated strength of the different symptoms or the total strength of all symptoms combined. Differences in the bowel frequency and stool consistency were also non-significant. CONCLUSIONS: Lactose malabsorbers with self-reported lactose intolerence did not differ in their response to milk chocolate samples containing different amounts of lactose.

Cacao↗

Properties of porcine and yogurt lactobacilli in relation to lactose intolerance.

Lactobacilli that had been isolated from the stomach of piglets were tested for properties relevant to the production of fermented milk products for consumption by lactose-intolerant humans. The strains were characterized for beta-galactosidase activity, the ability to reduce the lactose concentration of milk, viability, and pH of the fermented milk over a 30-d period. Strains that had favorable attributes were studied further, and the optimal pH for beta-galactosidase activity, ability to grow in the presence of bile salts, and ability to deconjugate bile salts were determined. Commercial yogurts were also examined to determine whether products varied in characteristics that might affect tolerance of milk products by lactose-intolerant subjects. The Lactobacillus sp. isolated from pigs had lower beta-galactosidase activity than did Lactobacillus delbrueckii ssp. bulgaricus strains ATCC 11842 and NCDO 1489 and strains of lactobacilli isolated from yogurt. The beta-galactosidase activity of all strains decreased rapidly once the fermented milk was stored at 4 degrees C. Strain JB10, originating in the stomach contents of the piglets, had properties that were useful for the manufacture of fermented milk products for lactose-intolerant humans. Milk fermented by this strain had a lactose concentration of about 4.0% and contained 6.6 x 10(6) cfu/ml after storage at 4 degrees C for 20 d. Strain JB10 produced a beta-galactosidase that was active at pH 5.5 (35% of the activity at pH 7.0) and was not inhibited by the presence of bile acids in the culture medium. Beta-Galactosidase activity and lactose concentration varied among yogurts.

Animals↗

[Importance of nutritional status in digestion capacity and lactose tolerance].

The aim of this study is to determine the capacity of undernourished patients to digest and tolerate the lactose in milk administered by tube-feeding. It was a controlled double-blind crossover trial in 25 hospitalized patients who required enteral feeding due to medical reasons. They were divided in two groups differing by nutritional status: 10 patients in Group 1 were malnourished with a mean weight for height of 69% (+/-15% SD) of their ideal one; Group 2 had 15 well nourished patients (mean weight for height of 103 +/- 15%). Each patient received two dietary treatments: intact milk and hydrolyzed milk (> 90% of lactose hydrolyzed). Lactose digestion was measured by the hydrogen breath test. Hydrogen excretion with intact milk was 505 +/- 117 ppm in Group 1 versus 58 +/- 15 ppm in the control group. With hydrolyzed milk, these values were 53 +/- 27 and 14 +/- 23, respectively. The scoring of symptoms after drinking intact milk was 4.3 +/- 0.7 in Group 1 vs 1.5 +/- 0.3 in Group 2, and they were lower with hydrolyzed milk (0.5 +/- 0.2 vs 0.3 +/- 0.2 respectively). The undernourished group had a higher incidence of both lactose maldigestion (p < 0.0001) and lactose intolerance (p < 0.001) than the control group. Our results strongly suggest that undernourishment is accompanied always or almost always by lactose intolerance.

Adult↗

Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in Fgf-23 deficient mice.

To explore further the role of the vitamin D axis for fibroblast growth factor-23 (FGF23) signaling, we mated Fgf-23 deficient (Fgf-23(-/-)) mice and vitamin D receptor (VDR) mutant mice with a non-functioning VDR. To prevent secondary hyperparathyroidism in VDR and compound mutant mice, all mice were kept on a rescue diet enriched with calcium, phosphorus, and lactose. Consistent with previous findings, Fgf-23(-/-) animals showed hypercalcemia, hyperphosphatemia, growth retardation, ectopic calcifications, severe osteoidosis, skin atrophy, and renal dysfunction. In addition, here we describe that Fgf-23(-/-) mice are hypoglycemic, and have profoundly increased peripheral insulin sensitivity and improved subcutaneous glucose tolerance, but normal renal expression of the aging suppressor gene Klotho. Although VDR and double mutants on the rescue diet still had moderately elevated parathyroid hormone serum levels and lower bone mineral density compared to wild-type mice, double mutant mice were normocalcemic and normophosphatemic, and had normal body weight, normal renal function, and no ectopic calcifications. Ablation of vitamin D signaling in compound mutants also normalized subcutaneous glucose tolerance tests and insulin secretory response. In conclusion, our results indicate that the alterations in mineral and carbohydrate metabolism present in Fgf-23(-/-) mice require an intact vitamin D signaling pathway.

Analysis of Variance↗

Response of patients with irritable bowel syndrome and lactase deficiency using unfermented acidophilus milk.

Acidophilus milk has been reported to help patients with irritable bowel syndrome by correcting the "imbalance of flora" and to be tolerated better by lactase-deficient subjects by providing bacterial lactase in the small intestine. In a double-blind randomized study, 61 lactase-sufficient patients with irritable bowel syndrome each ingested 240 ml of milk three times a day for 2 wk and the same amount of acidophilus milk for an additional 2 wk. The degree of symptoms during the two milk-drinking periods was the same as during the control periods. Also, 18 lactase-deficient patients ingested unaltered milk for 1 wk and acidophilus milk for 1 additional wk. There was no difference in the degree of tolerance to the two varieties of milk. In summary, patients with irritable bowel syndrome were not helped by the ingestion of acidophilus milk, and lactase-deficient patients were as intolerant to acidophilus milk as to unaltered milk.

Adolescent↗

Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rats.

The embryotoxicity/teratogenicity of alpha-cyclodextrin (alpha-CD) was examined in Wistar Crl:(WI)WU BR rats. alpha-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The additions to the diet of alpha-CD and lactose were made at the expense of pregelatinized potato starch. Body weight as well as food and water intake were recorded during the treatment period. The rats were killed on day 21 and examined for standard parameters of maternal reproductive performance. The fetuses were examined for external abnormalities, body weight and crown rump length. Fetuses were examined for skeletal and visceral abnormalities. Generally, alpha-CD was well tolerated and no deaths occurred in any group. Weight gain and food consumption were similar in all groups during gestation, except for a slightly yet significantly increased food intake in the 20% alpha-CD group from day 6 to 21. Water intake was similar in all alpha-CD groups; in the lactose group, it was significantly higher than in the controls. Maternal reproductive performance was not affected by the alpha-CD treatment. Examination of the fetuses for external, visceral and skeletal changes did not reveal any fetotoxic, embryotoxic, or teratogenic effects of alpha-CD. In conclusion, no adverse effects were observed at alpha-CD intakes of up to 20% of the diet, the highest dose level tested at which the rats consumed about 13 g/kg bw/day.

Abnormalities, Drug-Induced↗