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Diagnosis of lactose intolerance through the quantification of hydrogen in exhaled air.

Considerations are made on diarrhea secondary to intestinal malabsorption of carbohydrates and on the diagnostic means available in our environment, among which are the reactive strip, the clinitest tablet, tolerance curves and research of intestinal enzymes. The quantification of exhaled hydrogen is mentioned as a diagnostic method, used by several other authors, and a review of the literature on the subject is made. Considerations are made on a hydrogen quantification in the breath of patients with a transitory lactose intolerance. 16 patients were studied, 15 of whom showed an increase in the exhaled H2. 32 children with diarrhea, free from lactose intolerance, were studied. The method used did not show a significant increase in the exhaled hydrogen. 27 patients showed no H2 in their breath. In 4 there was elimination of H2 (false positives). 17 diarrhea-free children were studied. A significant difference was found when comparing the children with diarrhea and lactose intolerance to the other two groups who were free from lactose-intolerance. It is considered that this method can be useful in the diagnosis of intolerance to lactose and other sugars.

Chromatography, Gas↗

The effects of dietary lactose and rye on cecal colonization of Clostridium perfringens in chicks.

Five experiments were conducted to determine the effects of dietary lactose and rye on cecal colonization of Clostridium perfringens in white leghorn chickens. Six days after oral inoculation of the organism, the numbers of C. perfringens organisms in the cecal contents were significantly lower in chickens on 2% and 10% lactose-supplemented feed than in chickens on unsupplemented feed. When C. perfringens was given in drinking water, 10% lactose supplementation was needed to significantly reduce the counts of C. perfringens 4, 6, and 8 days after feeding began. Effect of rye-ration on cecal colonization of C. perfringens was also examined. Counts of C. perfringens in cecal contents of chickens fed a diet containing 50% rye were significantly higher than control values 4, 6, and 8 days after feeding began. When chicks were fed a diet containing both 10% lactose and 50% rye, C. perfringens counts in cecal contents were lower than in chickens fed 50% rye only at 6 days after feeding began. Results led to the conclusion that dietary lactose is effective in reducing the cecal colonization of C. perfringens.

Animal Feed↗

Lactose intolerance in idiopathic ulcerative colitis in north Indians.

The incidence of lactose intolerance in 60 patients with idiopathic ulcerative colitis (IUC) from northern India and the effect of disease activity and extent of colonic involvement on the occurrence of lactose intolerance, was studied. Twenty controls matched for age and sex were also studied using 50 g lactose hydrogen breath test. The incidence of lactose intolerance in patients with IUC (41.7%) was no different from that in the control group (40%). There was however, a significant difference (P < 0.05) in the incidence of lactose intolerance in patients with active colitis (59.1%) as compared to those with quiescent disease (31.5%).

Adolescent↗

Determination of lactose and xylose malabsorption in preruminant diarrheic calves.

In preliminary studies feeding the poorly absorbed carbohydrate sorbitol at 2.3 g/kg body weight as an indication of maximal fermentative capacity failed to produce the expected large increase in breath hydrogen excretion but did produce a transient diarrhea in five out of six control calves. Twelve healthy control and eighteen diarrheic calves were fed lactose or D-xylose on consecutive days at 1.15 g/kg body weight and a concentration of 46 g/L. Breath and blood samples were collected at 1 h intervals from 0 to 7 h. After administration of lactose, there was a significant increase in breath hydrogen excretion in diarrheic versus control calves. The increase in plasma glucose concentrations was delayed in diarrheic calves but the area under the absorption curve was similar in control and diarrheic calves. After administration of D-xylose, breath hydrogen excretion did not increase significantly but plasma D-xylose concentrations were significantly reduced in diarrheic calves. The pathogens commonly isolated from the feces were Cryptosporidium species, rotavirus and coronavirus. The number of pathogens and the severity of the calves' acid-base deficit were not related to the severity of carbohydrate malabsorption. Decreased absorption of lactose and D-xylose may be the result of intestinal villous atrophy caused by viral or parasite infection. It was concluded that carbohydrate malabsorption rather than a specific lactose maldigestion is a significant problem in diarrheic calves. Diarrheic calves appear to digest and absorb lactose when fed in small amounts.

Animals↗

[Diagnosis and therapy of lactose malabsorption].

Examinations of faeces (pH, Clinitest and Clinistix) are liable to contribute to the diagnosis of lactose malabsorption. To confirm the diagnosis the test is to be repeated while Lactase 500 is added to the child's milk. The enzyme does not split the lactase into the two monosaccharides, thus eliminating the malabsorption. The new drug Lactase 500 was used as a diagnostic parameter and for the treatment of lactose malabsorption in 20 infants. The effect on both groups was confirmed as mentioned by foreign authors. In addition to a very simple diagnostic method, which can be performed in the practitioner's office, there are two methods of treating lactose malabsorption: 1. feeding milk free of lactose, 2. feeding milk with an addition of Lactase 500. As in an earlier publication we assumed that about 10 per cent of the population suffers from secondary malabsorption of lactose, it seems advisable to check with the help of the described to simple methods all children with chronic diarrhoea.

Child, Preschool↗

Effects of oral lactose and xylose loads on blood glucose, galactose, xylose, and insulin values in healthy calves and calves with diarrhea.

OBJECTIVE: 2 hypotheses were tested: calves with acute, mild diarrhea digest lactose less efficiently than healthy calves, and they are in a catabolic state, which influences plasma glucose concentration after glucose absorption. DESIGN: Clinical study; 2 treatments with 10 repetitions/treatment. ANIMALS: 20 preruminant Brown Swiss and Simmental Red Holstein calves; 10 calves with mild diarrhea, and 10 age-matched healthy calves. PROCEDURE: Blood metabolite and hormone concentrations were determined before and after an oral lactose load. Plasma xylose concentration was determined after an oral xylose load. III calves were tested 1 day after the onset of diarrhea. RESULTS: Calves with diarrhea (cryptosporidia, coronavirus) had lower preprandial concentrations of plasma glucose, insulin-like growth factor 1, and 3,5,3-triiodothyronine (P < 0.01) and a higher concentration of free fatty acids (P < 0.03) than did healthy calves. After the oral lactose and xylose loads, blood galactose and plasma xylose concentrations were lower in ill calves (P = 0.10 and P = 0.07, respectively). In calves with diarrhea, there was a larger increase of plasma glucose concentration (P = 0.12) and a smaller increase of plasma insulin concentration (P = 0.04) above baseline values after lactose ingestion. CONCLUSIONS: Lactose digestion is slightly impaired in calves with mild diarrhea. Calves with acute diarrhea are in a catabolic state and, therefore, respond with a larger increase of plasma glucose concentration to a given amount of absorbed glucose than do healthy calves. CLINICAL-RELEVANCE: Plasma glucose concentration is not a reliable measure for glucose absorption in animals that are in a catabolic state.

Acute Disease↗

[Yogurt as source of lactose autodigestion].

Microorganisms in yogurt have the capacity of quantitatively digest in vivo in the small intestine the lactose from yogurt. The process of autodigestion of lactose in yogurt reduces both lactose maldigestion and lactose intolerance in lactase deficient individuals. Enzyme activity in yogurt depends upon the buffer capacity of the yogurt, microbial cells resistance to acid and enzymatic activity and to the effect of bile in the microbial cell that release beta-galactosidase activity. Lactose autodigestion capacity of yogurt is significantly reduced in pasteurized yogurt and it is also affected by the type and amount of microorganism that is added to milk and by the presence of fat. Yogurt intake represents an important food alternative for lactase deficient individuals.

Digestion↗

[Lactose-free formula products available in Mexico. Their significance and applications].

Lactose in milk and dairy products can be significantly reduced by the utilization of microbial beta-galactosidases. These enzymes can be used to treat milk during its processing or they can be administered with milk at meal time as an enzyme replacement therapy in which case hydrolysis occurs in vivo in the gastrointestinal tract. Lactose in milk can alternatively be eliminated by ultrafiltration, a process that divides milk components based on their size. A third way of reducing or eliminating lactose content is formulating a product or even "milk" from ingredients which avoid the use of lactose. Technologies like these are used to develop infant formula, enteral formula products and low-lactose milks. In this paper products of this kind available in Mexico are described.

Food Handling↗

Age and continuous lactose challenge modify lactase protein expression and enzyme activity in gut epithelium in the rat.

The activity of lactase enzyme declines after weaning. This study was to investigate changes in the lactase expression in the whole gastrointestinal tract during the development and the possibility that this and activity can be induced by lactose. Expression of lactase protein in the gut of 1-12-weeks old rats was studied by immunocytochemistry. Possible induction was evaluated by immunohistochemical and biochemical techniques in 8-week-old rats after lactose challenge for seven days. Lactase immunoreactivity was detected only in the small intestine and it decreased 20% during the week after weaning. A steady level of 40% lower than in the sucklings was found in the adult rats. In the lactose-challenged rats the optical density of immunoreactivity increased by about 30% in those that consumed the highest concentration of lactose. In the proximal jejunum, elevation of the enzymatic activity was three-fold. In the rat lactase protein expression decreased rapidly after weaning and expression and activity were induced by lactose-rich diet, most notably in the proximal jejunum.

Age Factors↗

Lactose, oligosaccharide and monosaccharide content of milk from mothers delivering preterm newborns over the first month of lactation.

BACKGROUND: Monosaccharide, lactose and oligosaccharide content of milk from mothers delivering prematurely (PT milk) was studied to evaluate whether changes occur during lactation, as observed in milk from mothers delivering at term (T milk). METHODS: To study a homogeneous population, women having the most common phenotype (secretory both Lewis and A, B, or H phenotype) were selected. Milk samples from 26 mothers who delivered between the 27th and 35th week of gestation were collected at the 4th, 10th, and 30th post-partum days. Monosaccharides, lactose and oligosaccharides were measured by high-pressure liquid chromatography. RESULTS: Lactose concentration increased significantly (p < 0.05) from 52.81 +/- 8.2 g/L on day 4 to 69.24 +/- 9.36 g/L on day 30. During the same period of time oligosaccharide content decreased significantly (p < 0.05) from 25.61 +/- 5.19 g/L to 15.83 +/- 6.05 g/L. Monosaccharides did not show statistically significant variations. CONCLUSIONS: Our results indicate that PT milk contains in addition to lactose, a substantial amount of oligosaccharides and a lower percentage of monosaccharides. Compared to T milk, in the colostral phase PT milk presents significantly lower lactose concentration (p < 0.0001); on the contrary its oligosaccharide content is significantly higher (p < 0.0001). The physiological role of human milk carbohydrates in view of the peculiar needs of the preterm newborn is also discussed.

Female↗

[Absorptive pattern of individual fatty acids and total fat in full term babies. Its stability in the absence of lactose].

OBJECTIVE: Lactose absence implies a decrease in calcium absorption. If not absorbed, calcium soaps can be produced with the intestinal fatty acids. Absorption and retention of total fat, individual fatty acids, calcium, magnesium and phosphate have been compared between two groups of children, one fed with lactose free formula and higher levels of calcium (FSL) and the other with standard starting formula (FI). None of them had additional arachidonic or docosahexaenoic acids. PATIENTS AND METHODS: A randomized prospective study was made on 19 term newborn babies by means of metabolic balance measurement during an 8 day period (four days of a stabilization period on the formula, 3 days of the balance period and the final day for feces collection). Both groups were selected following the same criteria for gestational age, balance age, and weight and length at both time periods. Aliquos from the formula were collected daily, as well as all feces and urine during the balance period. Calcium and magnesium quantification of the corresponding ashed products was performed by means of atomic absorption, while Pi was with a colorimetric assay. Total fat was extracted by organic solvents and quantified by gravimetry. Lipid phase fatty acids were methylated, extracted and quantified by means of gas chromatography with a detector of flame ionization. RESULTS: Total fat content and the percentages of each fatty acid did not differ, only calcium concentration in FSL was slightly higher (64.9 +/- 6.9 vs 58.9 +/- 7.0 mg/100 g). No differences were found between groups in relation to ingestion, excretion and retention. The percentages of calcium and total fat retention, however, were slightly superior in the FI in relation to the FSL group. Ca: 68 +/- 22 mg/kg/d, 49 +/- 14% vs 56 +/- 23 mg/kg/d, 48 +/- 17% and total fat: 6.6 +/- 1.2 g/kg/d, 92 +/- 8% vs 6.8 +/- 1.5 g/kg/d, 90 +/- 9%. Absorption of MC fatty acids was 99% for C8. Linoleic and alfalinolenic acid showed an absorption of around 90% despite the big differences in their intake (10/1). Net retention of linoleic acid was 933 +/- 168 mg/kg/d (FI) and 963 +/- 190 mg/kg/d (FSL) and the amount of alpha-linolenic acid was 95 +/- 16 (FI) and 100 +/- 22 mg/kg/d (FSL). No correlation could be found between the amount of excreted calcium and the total amount of fat in feces or with any of the fatty acids studied. This was true for each group studied separately or when considered as a single group. CONCLUSIONS: The absorptive pattern of fatty acids in full term babies, when quantified did not show any conspicous alterations in relation to the accepted values of other ages. The absence of lactose (FSL) in a formula does not make any change in the absorption of total fat and the individual fatty acids when compared to lactose containing formula (FI), when these are present in the same proportions. Supplemented calcium in the formula without lactose could compensate for its lower absorbtion. The absorptive pattern of fatty acid in full term babies did not show any conspicuos alterations in relationship to the accepted values of other ages.

Absorption↗

[Calcium absorption by the rat from various milks in relation to their total phosphorus and lactose contents].

The absorption of calcium corresponds to a strictly determined mechanism inhibited by phosphates and activited by carbohydrates. We investigate in what extent the absorption of milk calcium from various species has the same proceeding. 4 months old rats are given orally solutions of CaCl2 alone or in combination with sodium dihydrogen phosphate or lactose or these both compounds. We compare calcium absorption of these solutions to that of milk from woman, cow or sow, or to dilutions of these two latter milks. All these fluids are dosed so that they correspond each other by their respective content in total calcium, total phosphorus and lactose. Each solution contains 45Ca. Blood samples 1,30, 4, 6 and 24 hours after ingestion allow establishing the variations of plasma radioactivity. Rats are sacrified after 24 hours. In certain cases, samples from digestive tube contents and feces provide a coefficient of calcium absorption. The osseous retention is obtained from femur radioactivity. In breif, we may consider that milks from cow and sow provide calcium the absorption of which is settled after their respective content of total phosphorus and lactose. Opposed effects of these inhibitors and activators of calcium absorption compensate so that calcium from these milks is just a little better utilized by adult rat than calcium from an isocalcic solution of CaCl2. Calcium from woman milk, rich in carbohydrates, poor in total phosphorus is better absorbed than that from the two latters, however less than we might expect from its high lactose content. We may wonder that calcium utilization from cow milk is as moderate as that of a solution of CaCl2. But skeleton mineralization which may be fulfilled by milk is made better because of that: it is not chloride but calcium phosphate which ensures this mineralization, a phosphate which alone would impair this mineralization without the compensative role of lactose.

Animals↗

The role of colonic microbiota in lactose intolerance.

In a previous study we observed a clear difference in lactose intolerance symptoms after a 25-g lactose load in two groups of persons with lactase nonpersistence and similar small intestinal lactase activity. From this observation we hypothesized a colon resistance factor. To identify this factor, the microbial composition of fecal samples of the two lactose intolerant groups (one with mild symptoms, n = 16, and one with diarrhea-predominant symptoms, n = 11) was compared using the fluorescent in situ hybridization technique. Large interindividual differences were found in the numbers of total bacteria and main groups of bacteria (CV: 0.65 and 0.64-0.82 respectively). The bacterial numbers were not significantly different between the two groups. A significant negative correlation, however, was found between the individual symptom scores of the intolerant persons and the numbers of total hybridizable bacteria (r(s) = -0.42, P = 0.03). The results suggest that an increased number of bacteria might contribute--by means of a higher fermentative capacity--to the reduction of lactose intolerance symptoms.

Adult↗

Comparison of lactose intolerance in healthy Kuwaiti and Asian volunteers.

OBJECTIVE: To study and compare the incidence of lactose intolerance among Kuwaiti and Asian healthy volunteers as measured by breath hydrogen level following challenge with lactose drink. SUBJECTS AND METHODS: The study involved 70 Kuwaiti and 79 Asian healthy volunteers. The volunteers were physicians, medical students and other hospital workers. The study was carried out prospectively at Amiri Hospital, Kuwait. None of the volunteers was sick or had taken antibiotics or any other drug that could influence breath hydrogen level 2 weeks prior to the study. After an overnight fast 20-ml baseline samples of exhaled air were collected from each volunteer prior to oral administration of 40 g of lactose drink. Following this, the same amount of exhaled air was collected at 30-min intervals for 2 h. All samples were analyzed for hydrogen level using a Quintron microlyzer. Hydrogen level of 20 ppm more than baseline value was considered positive. RESULTS: The basal breath hydrogen levels were 12.49 +/- 8.4 and 6.97 +/- 6.9 for Kuwaitis and Asians, respectively. Thirty-three (47%) of the 70 Kuwaitis and 46 (58%) of the 79 Asians were positive for the breath hydrogen test. The clinical symptoms of flatulence, abdominal pain, and diarrhea were associated with high levels of breath hydrogen. CONCLUSION: The findings indicate that the Kuwaiti volunteers had higher breath hydrogen levels than Asians, but the incidence of lactose intolerance was similar in both groups.

Abdominal Pain↗

The prevalence of lactase deficiency and lactose intolerance in Chinese children of different ages.

OBJECTIVE: To determine lactose metabolism and lactase activity in Chinese children of different ages, prevalence of lactase deficiency (LD), and lactose intolerance (LI). METHODS: All 1168 healthy subjects between 3 and 13 years were recruited from schools in four large cities in China. They were screened by a 25 g lactose tolerance test. Some subjects were challenged with 50 g milk powder on different days. Both indicators, the expiratory H2 concentration and intolerance symptoms, were analyzed. RESULTS: LD occurred in 38.5% of children in the 3-5 year age group, and 87% of the 7-8 year and 11-13 year old groups. The age of occurrence for LD may be at 7-8 years among Chinese children. The prevalence of LI among Chinese children was 12.2% at age 3-5 years, 33.1% at age 7-8 years, and 30.5% at age 11-13 years, respectively. CONCLUSION: The results demonstrate that LD is very common in Chinese children from these four cities. LD and LI have a dose dependent response: lactose absorption and symptoms are based on lactase activity. The relationship between breast feeding history (or the history of cow milk intake) and lactase activity among Chinese children has not been established.

Adolescent↗

The conserved motif in hydrophilic loop 2/3 and loop 8/9 of the lactose permease of Escherichia coli. Analysis of suppressor mutations.

The major facilitator superfamily (MFS) of transport proteins, which includes the lactose permease of Escherichia coli, contains a conserved motif G-X-X-X-D/E-R/K-X-G-R/K-R/K in the loops that connect transmembrane segments 2 and 3, and transmembrane segments 8 and 9. In three previous studies (Jessen-Marshall, A.E., & Brooker, R.J. 1996. J. Biol. Chem. 271:1400-1404; Jessen-Marshall, A.E., Parker, N., & Brooker, R.J. 1997. J. Bacteriol. 179:2616-2622; and Pazdernik, N., Cain, S.M., & Brooker, R.J. 1997. J. Biol. Chem. 272:26110-26116), suppressor mutations at twenty different sites were identified which restore function to mutant permeases that have deleterious mutations in the conserved loop 2/3 or loop 8/9 motif. In the current study, several of these second-site suppressor mutations have been separated from the original mutation in the conserved motif. The loop 2/3 suppressors were then coupled to a loop 8/9 mutation (P280L) and the loop 8/9 suppressors were coupled to a loop 2/3 mutation (i.e., G64S) to determine if the suppressors could restore function only to a loop 2/3 mutation, a loop 8/9 mutation, or both. The single parent mutations changing the first position in loop 2/3 (i.e., G64S) and loop 8/9 (i.e., P280L) had less than 4% lactose transport activity. Interestingly, most of the suppressors were very inhibitory when separated from the parent mutation. Two suppressors, A50T and G370V, restored substantial transport activity when individually coupled to the mutation in loop 2/3 and also when coupled to the corresponding mutation in loop 8/9. In other words, these suppressors could alleviate a defect imposed by mutations in either half of the permease. From a kinetic analysis, these suppressors were shown to exert their effects by increasing the V(max) values for lactose transport compared with the single G64S and P280L strains. These results are discussed within the context of our model in which the two halves of the lactose permease interact at a rotationally symmetrical interface, and that lactose transport is mediated by conformational changes at the interface.

Amino Acid Motifs↗

Galactoside-dependent proton transport by mutants of the Escherichia coli lactose carrier: substitution of tyrosine for histidine-322 and of leucine for serine-306.

The lac Y genes from two Escherichia coli mutants, MAB20 and AA22, have been cloned in a multicopy plasmid by a novel 'sucrose marker exchange' method. Characterization showed that the plasmids express a lactose carrier with poor affinity for lactose. Neither mutant carried out concentrative uptake with methyl beta-D-galactopyranoside, lactose, or melibiose as the substrate. Nor did the mutants catalyze counterflow or exchange with methyl beta-D-galactopyranoside. Both mutants did, however, retain the capacity to carry out facilitated diffusion with lactose or melibiose. DNA sequencing revealed that MAB20 (histidine-322 to tyrosine) and AA22 (serine-306 to leucine) have amino acid substitutions within the putative 'charge-relay' domain thought to be responsible for proton transport. Galactoside-dependent H+ transport was readily measured in both mutants. We conclude, therefore, that the presence of a histidine residue at position 322 of the lactose carrier is not obligatory for H+ transport per se.

Binding Sites↗

Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli.

Using a lactose permease mutant devoid of Cys residue ("C-less permease"), we systematically replaced putative intramembrane charged residues with Cys. Individual replacements for Asp-237, Asp-240, Glu-269, Arg-302, Lys-319, His-322, Glu-325, or Lys-358 abolish active lactose transport. When Asp-237 and Lys-358 are simultaneously replaced with Cys and/or Ala, however, high activity is observed. Therefore, when either Asp-237 or Lys-358 is replaced with a neutral residue, leaving an unpaired charge, the permease is inactivated, but neutral replacement of both residues yields active permease [King, S. C., Hansen, C. L. & Wilson, T. H. (1991) Biochim. Biophys. Acta 1062, 177-186]. Remarkably, moreover, when Asp-237 is interchanged with Lys-358, high activity is observed. The observations provide a strong indication that Asp-237 and Lys-358 interact to form a salt bridge. In addition, the data demonstrate that neither residue nor the salt bridge plays an important role in the transport mechanism. Thirteen additional double mutants were constructed in which a negative and a positively charged residue were replaced with Cys. Only Asp-240-->Cys/Lys-319-->Cys exhibits significant activity, accumulating lactose to 25-30% of the steady state observed with C-less permease. Replacing either Asp-240 or Lys-319 individually with Ala also inactivates the permease, but double mutants with neutral substitutions (Cys and/or Ala) at both positions exhibit essentially the same activity as Asp-240-->Cys/Lys-319-->Cys. In marked contrast to Asp-237 and Lys-358, interchanging Asp-240 and Lys-319 abolishes active lactose transport. The results demonstrate that Asp-240 and Lys-319, like Asp-237 and Lys-358, interact functionally and may form a salt bridge. However, the interaction between Asp-240 and Lys-319 is clearly more complex than the interaction between Asp-237 and Lys-358. In any event, the findings suggest that putative transmembrane helix VII lies next to helices X and XI in the tertiary structure of lactose permease.

Amino Acid Sequence↗