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PubMed1981

Lactose malabsorption in children and adolescents with inflammatory bowel disease.

Lactose breath hydrogen tests were given to 70 children and adolescents with chronic ulcerative colitis and Crohn's disease in order to determine the prevalence of lactose malabsorption in childhood inflammatory bowel disease. Twenty-nine percent of these patients demonstrated lactose malabsorption; the majority of these children (70%) experienced gastro-intestinal symptoms during the test. The prevalence was not significantly different whether the diagnosis was ulcerative colitis or Crohn's disease. With the exception of those with diffuse small bowel disease, the location of intestinal involvement with Crohn's disease and the severity of clinical symptoms did not affect lactose malabsorption. Lactose malabsorption was not more frequent in patients with inflammatory bowel disease than in a group of children with recurrent abdominal pain and normal gastrointestinal x-rays, although significant differences in the prevalence of lactose malabsorption were observed in relation to ethnic background. Milk incubated with commercially available yeast lactase (lactAid, Surgarlo Co., Atlantic City, N.J.) for greater than 24 h prevented an increase in breath hydrogen when administered to 6 patients previously shown to have lactose malabsorption.

Adolescent↗

PubMedDate not supplied

[Lactose absorption and tolerance to different types of yogurts in adults with hypolactasia].

It is known that lactose is better absorbed in yogurts than in milk by lactase-deficient individuals. This fact is due to the presence of beta-galactosidase activity in the yogurts, that are different concerning the caracteristics of the products. Thus, the aim of this study was to verify the absorption and tolerance of lactose in some yogurts consumed by our population. We studied 12 hypolactasic adults who, after diagnostic confirmation, were submitted to three breath hydrogen tests after ingestion of milk and two yogurts with different levels of beta-galactosidase. These activities were determined in each sample utilized. The lactose absorption was evaluated by the measurement of H2 eliminated in the expired air and the tolerance was assessed by the symptoms reported by the participants. The medians of the H2 maximum increment were 20 ppm/min for the milk, 10.5 for yogurt X and 5.5 for the yogurt Y. The area under the curve of H2 concentration presented a median of 960 in the test with milk, 420 with yogurt X and 270 with yogurt Y. These results showed statistically significant differences for milk and the two yogurts and similar among the yogurts. The score for symptoms also were different between the milk and the two yogurts and similar among the yogurts. A statistically significant association between absorption and tolerance was not observed, because many tolerant subjects were malabsorbers of lactose. These data show that lactose in yogurts is better absorbed and better tolerated than lactose in milk, suggesting that our products are similar to those of the literature concerning their capacity of hydrolising lactose "in vivo". In spite of the differences found "in vitro" among the beta-galactosidase, there were no significant differences of absorption and tolerance between the two yogurts studied.

Adolescent↗

PubMed1998

[Lactose in human nutrition].

The disaccharide lactose is naturally present as a component of foods in milk and dairy products. In the gastrointestinal tract, lactose is hydrolysed by the enzyme beta-galactosidase (lactase) into glucose and galactose. These components are absorbed. In most people lactase activity decreases at the age of approximately 2 years of age. After this lactose intake can cause symptoms of bloating, flatulence, abdominal pain and diarrhoea due to the lactose reaching the large intestine. This phenomenon is called lactose intolerance. It is generally recommended that these people abandon the consumption of milk and dairy products. However, most lactose-intolerant people are able to digest small amounts of milk (approximately 200 ml). They can also consume cheese without (hard and semi-hard cheese) or only low lactose content (only present in 10% of soft cheese). These products are a very important source of calcium.

Adolescent↗

PubMed2002

Production of galacto-oligosaccharides from lactose by Aspergillus oryzae beta-galactosidase immobilized on cotton cloth.

The production of galacto-oligosaccharides (GOS) from lactose by A. oryzae beta-galactosidase immobilized on cotton cloth was studied. The total amounts and types of GOS produced were mainly affected by the initial lactose concentration in the reaction media. In general, more and larger GOS can be produced with higher initial lactose concentrations. A maximum GOS production of 27% (w/w) of initial lactose was achieved at 50% lactose conversion with 500 g/L of initial lactose concentration. Tri-saccharides were the major types of GOS formed, accounting for more than 70% of the total GOS produced in the reactions. Temperature and pH affected the reaction rate, but did not result in any changes in GOS formation. The presence of galactose and glucose at the concentrations encountered near maximum GOS greatly inhibited the reactions and reduced GOS yield by as much as 15%. The cotton cloth as the support matrix for enzyme immobilization did not affect the GOS formation characteristics of the enzyme, suggesting no diffusion limitation in the enzyme carrier. The thermal stability of the enzyme increased approximately 25-fold upon immobilization on cotton cloth. The half-life for the immobilized enzyme on cotton cloth was more than 1 year at 40 degrees C and 48 days at 50 degrees C. Stable, continuous operation in a plugflow reactor was demonstrated for 2 weeks without any apparent problem. A maximum GOS production of 21 and 26% (w/w) of total sugars was attained with a feed solution containing 200 and 400 g/L of lactose, respectively, at pH 4.5 and 40 degrees C. The corresponding reactor productivities were 80 and 106 g/L/h, respectively, which are at least several-fold higher than those previously reported.

Aspergillus oryzae↗

PubMed2006

Kinetics of lactose fermentation using a recombinant Saccharomyces cerevisiae strain.

This work presents a multi-route, non-structural kinetic model for interpretation of ethanol fermentation of lactose using a recombinant flocculent Saccharomyces cerevisiae strain expressing both the LAC4 (coding for beta-galactosidase) and LAC12 (coding for lactose permease) genes of Kluyveromyces lactis. In this model, the values of different metabolic pathways are calculated applying a modified Monod equation rate in which the growth rate is proportional to the concentration of a key enzyme controlling the single metabolic pathway. In this study, three main metabolic routes for S. cerevisiae are considered: oxidation of lactose, reduction of lactose (producing ethanol), and oxidation of ethanol. The main bioprocess variables determined experimentally were lactose, ethanol, biomass, and dissolved oxygen concentrations. Parameters of the proposed kinetic model were established by fitting the experimental data obtained in a small lab-scale fermentor with the initial lactose concentrations ranging from 5 g/dm3 to 50 g/dm3. A very good agreement between experimental data and simulated profiles of the main variables (lactose, ethanol, biomass, and dissolved oxygen concentrations) was achieved.

Bioreactors↗

PubMed2004

A prospective study of dietary lactose and ovarian cancer.

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.

Adult↗

PubMed1994

Evidence that lactose binding to CBP35 disrupts its interaction with CBP70 in isolated HL60 cell nuclei.

We have previously reported that two carbohydrate-binding proteins (CBP35 and CBP70) can, under appropriate conditions of affinity chromatography, be isolated from HL60 cell nuclear extracts as a complex. Moreover, we have demonstrated that, during affinity chromatography, the CBP70-CBP35 association can be modified by the binding of lactose to CBP35. To determine whether the CBP70-CBP35 association could be disrupted in the nucleus upon lactose binding to CBP35, the behaviors of CBP70 and CBP35 were analyzed in membrane-depleted nuclei of HL60 cells, incubated with or without lactose. This study was performed by using an antiserum that cross-reacts with CBP35 and CBP70, an antiserum that was specifically raised against CBP70, and a monoclonal antibody (Mac 2) reactive against CBP35. Taken together, the results of indirect immunofluorescent staining, immunoblotting experiments, and quantitative flow-cytofluorometric analysis show that (i) CBP70 and CBP35 are present and colocalized in the nuclei incubated without lactose, (ii) all the CBP70 molecules left the nuclei incubated in the presence of lactose, while CBP35 molecules, probably bound to RNA, remained inside the nuclei, and (iii) glucose failed to have the same effect as lactose. These results strongly suggest that, in membrane-depleted nuclei, CBP35 and CBP70 interactions can be altered by a conformational change of CBP35 induced by the binding of lactose to its carbohydrate-recognition domain.

Antibodies, Monoclonal↗

PubMed1987

Isolation and characterization of mutants of Kluyveromyces lactis defective in lactose transport.

Mutants of Kluyveromyces lactis defective in lactose transport were identified among lactose-resistant revertants of lactose-sensitive strains. The mutations are closely linked to the beta-galactosidase gene, LAC4, and they are located in a previously identified gene, LAC12, which has been shown to code for a lactose permease. Our data establish that LAC12 is the only lactose permease gene in K. lactis. The lactose permease also transports galactose. LAC12 is transcribed in a direction opposite to that of LAC4, there being about 2.5 kb between their transcription start sites. Transcription of LAC12 is inducible as is that of all other structural genes in the lactose-galactose regulon of K. lactis.

Biological Transport↗

PubMed1998

Sugar cell responses to lactose and sucrose in labellar and tarsal taste hairs of Musca domestica.

Receptor cell responses in the largest labellar (LL) and tarsal (D) taste hairs of the housefly Musca domestica were investigated electrophysiologically using the tip-recording technique. In LL hairs, test series with lactose in concentrations of 12.5-400 mmol.l-1 yielded a threshold concentration around 12 mmol.l-1 and a calculated concentration eliciting half-maximal response of around 40 mmol.l-1, the maximal response varying between 18 and 30 impulses/300 ms. D hairs are more sensitive towards lactose, indicated by a slightly lower threshold and a by 60% higher response to 400 mmol.l-1 lactose. The high variation in the relative stimulating effectiveness of lactose and sucrose and experiments with sugar mixtures imply that these sugars bind to different receptor sites without noticeable cross affinity. A comparison of the concentration response characteristics for sucrose and lactose in LL and D hairs suggests that sucrose can combine with more than one site type, expressed in different proportions in both hair types. Results obtained with p-nitrophenyl-beta-galactoside as stimulus indicate that a beta-galactoside link is not sufficient for a substance to interact specifically with the lactose binding site. The exceptional lactose sensitivity of the sugar cell in M. domestica is discussed in the context of food acquirement and digestion.

Animals↗

PubMed2002

Lactose metabolism and cellulase production in Hypocrea jecorina: the gal7 gene, encoding galactose-1-phosphate uridylyltransferase, is essential for growth on galactose but not for cellulase induction.

Lactose is at present the only soluble carbon source which can be used economically for the production by Hypocrea jecorina (= Trichoderma reesei) of cellulases or heterologous proteins under the control of cellulase expression signals. However, the mechanism by which lactose triggers the formation of cellulases is unknown. To enhance our understanding of lactose metabolism and its relationship to cellulase formation, we have cloned and characterized the gal7 gene (for galactose-1-phosphate uridylyltransferase) of H. jecorina. The gene encodes a polypeptide of 43.8 kDa, the sequence of which exhibits a moderate level of identity (about 50%) to that of the Gal7 proteins of Saccharomyces cerevisiae and Kluyveromyces lactis, and contains an active-site signature typical for galactose-1-phosphate uridylyltransferase family 1. H. jecorina gal7 is not clustered with other genes of galactose metabolism. A single 1.7-kb transcript is synthesized constitutively during the rapid growth phase and accumulated to twice this level during incubation in the presence of D-galactose and L-arabinose and the corresponding polyols (dulcitol, arabitol). A gal7 deletion mutant, constructed by replacing the gal7 reading frame by the H. jecorina pyr4 gene, was unable to grow on D-galactose between pH 4.5 and 7.5, thus proving that in H. jecorina gal7 is essential for metabolism of D-galactose, whereas the growth rate of the mutant on lactose was only reduced by about 50%. The rate of formation of cellobiohydrolase Cel7A and the abundance of the corresponding (cbh1) transcript during growth on lactose was only slightly lower in the absence of gal7, but a significant delay in decay of the cbh1 transcript was noted during later stages of growth. The results suggest that H. jecorina uses only the Leloir pathway for metabolism of D-galactose and lactose. Furthermore, we conclude that metabolism of lactose past the galactose-1-phosphate step is not essential for cellulase formation.

Amino Acid Sequence↗

PubMed1990

Anomerization and hydrolysis of lactose by beta-galactosidase from Saccharomyces lactis.

Beta-Galactosidase from Saccharomyces lactis was found to be able to catalyze both the anomerization of alpha-lactose and the hydrolysis of beta-lactose; the rate of hydrolysis appeared to be four times higher with a 1:1 mixture of alpha and beta lactose than with a freshly prepared solution of alpha-lactose. The enzyme was also found to be unable to hydrolyze alpha-lactose. Thus, it appears that beta-galactosidase from S. lactis has its hydrolytic activity on lactose adapted only to the naturally more abundant beta-lactose.

Galactosidases↗

PubMed2006

Comparison of a real-time polymerase chain reaction assay for lactase genetic polymorphism with standard indirect tests for lactose maldigestion.

BACKGROUND & AIMS: There is a discrepancy in outcome between the lactose tolerance and breath hydrogen tests for lactose maldigestion. The availability of a validated genetic test for lactase polymorphism allows a reevaluation of these tests. METHODS: Thirty healthy adults participated in a 50-g lactose challenge test at a university clinic. Blood was drawn for genetic and timed blood glucose testing (2 hours), and breath hydrogen was measured (4.5 hours). Lactase genetic polymorphism was assessed by a real-time polymerase chain reaction assay. Participants completed a diet questionnaire, and symptoms were recorded during the lactose challenge. Sensitivity and specificity were calculated for each indirect test. The 2-way kappa coefficient between these tests was evaluated. Student t test and Wilcoxon rank sum test were used to compare variables. RESULTS: The lactose tolerance test as a standard had an 87.5% sensitivity and 92.7% specificity for genetic status. Only a moderate agreement between lactose tolerance test and breath hydrogen test was observed (2-way kappa coefficient, .53; 95% confidence interval, .22-.83). When genetic status was used as standard, symptoms had a moderate sensitivity and specificity. Lactose tolerance test had very good sensitivity, and the breath test had excellent specificity. CONCLUSIONS: Both indirect tests independently have good to very good sensitivities and specificities for genetic lactase status. The noted disagreement likely reflects variables that affect the tests independently of intestinal lactase status. The value of these tests in the light of the availability of genetic testing is discussed.

Adult↗

PubMed2005

Rifaximin in patients with lactose intolerance.

BACKGROUND: Abdominal symptoms linked to lactose malabsorption may be caused by metabolic activity of colonic bacteria. Rifaximin, a non-absorbable rifampycin derivative, is active against colonic bacteria, it may be useful in the treatment of lactose intolerance. AIM: The aim of this study has been to evaluate short-term rifaximin therapy in patients with lactose intolerance. METHODS: Thirty-two patients with lactose intolerance diagnosed using the hydrogen lactose breath test were studied. Fourteen patients received rifaximin 800 mg/day for 10 days, 13 patients followed a diet without milk for 40 days and 5 patients received a placebo for 10 days. Total breath H(2) excretion expressed as area under the curve, and the symptom score were evaluated in all patients at the start, and subsequently after 10 and 40 days. RESULTS: In the 14 patients who received rifaximin for 10 days, area under the curve at day 10 and day 40 was statistically significantly lower than the one computed at basal (P<0.01). Diet reduced area under the curve progressively reaching statistical significance at day 40, while the placebo did not change area under the curve throughout the study. The total symptom score significantly improved after rifaximin and diet. CONCLUSION: In patients with lactose intolerance, a 10-day therapy with rifaximin as well as 40-day diet without lactose reduces the area under the curve and the symptom score.

Adult↗

PubMed2004

Compaction of crystallographic forms of pharmaceutical granular lactoses. II. Compacts mechanical properties.

It is well known that the choice of the crystal form affects the physicochemical properties such as compaction behaviour. In this work, the mechanical properties of compacts obtained from compaction of lactoses by using a micropress prototype are calculated. Tensile strength, Young's modulus, toughness and Brinell hardness were measured and used to compare the various crystalline forms: alpha-lactose monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha-lactose (LalphaA) and partly amorphous lactose (FF). With all the mechanical properties measured, the lactoses could be differentiated. Then, the specific energy of failure G*(IC) was obtained from the toughness and the Young's modulus for each lactose. LalphaM showed small specific energy of failure due to its low toughness which is not balanced by its Young's modulus. The highest values were obtained with the two anhydrous forms, LalphaA and LbetaA. Finally, these mechanical properties were linked with general compaction behaviour and cohesive energy density which is a characterization at a molecular level.

Compressive Strength↗

PubMed1999

Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation.

Ternary mixtures composed of coarse lactose (CL) (90.8 microm), salbutamol sulphate (SS) (5.8 microm) and either micronised lactose (ML) (5 microm) or intermediate sized lactose (IML) (15.9 microm) in a ratio of 66.5:1:1 w/w were prepared using different mixing sequences of the various components. In addition, a binary mixture composed of CL and SS (67.5:1 w/w) was also prepared as the control. The in vitro deposition of SS was measured using a twin stage impinger after aerosolisation at 60 and 90 l min-1 via a Rotahaler. The aerodynamic particle size distribution of both the aerosolised SS and lactose was further analysed using an Andersen cascade impactor at 60 l min-1. All ternary mixtures produced a significantly higher (analysis of variance, P<0.01) fine particle fraction (FPF) and fine particle dose (FPD) of SS than the control after aerosolisation at either 60 or 90 l min-1. Formulations containing the ML produced significantly (P<0.05) higher FPF and FPD of SS than those containing the IML at both aerosolisation flow rates. Different mixing sequences were also shown to result in different deposition profiles of both SS and lactose after aerosolisation of the ternary mixtures containing ML at 60 l min-1. The formulation prepared by first blending ML with CL before mixing with SS produced a higher FPF and FPD of SS but a lower FPF of lactose than the same formulation in terms of composition but prepared using different mixing orders of the three components. In contrast, the formulations containing IML produced a similar deposition profile to SS, regardless of the mixing sequences, and so did the formulations containing ML aerosolised at 90 l min-1. These results suggest that the effect of mixing sequences on drug deposition may become more prominent at lower aerosolisation flow rates and by reducing the size of any added fine lactose.

Albuterol↗

PubMed2000

Pulmonary deposition of lactose carriers used in inhalation powders.

Dry powder dosage forms are generally formulated by mixing the micronized drug particles with the larger carrier particles. Lactose is a commonly used carrier. Carriers enhance the flowability of powder mixtures and therefore enable low dosing of active substances. During inhalation, the drug particles are dispersed from the surface of carrier particles. The aim of this study was to compare how different qualities of 99mTc-labelled lactose carrier systems deposit in the lungs. The sizes of the labelled and unlabelled alpha-lactose monohydrate particles were compared by using a laser diffraction method. Distribution of radiolabel between different particle size fractions was determined using the Andersen cascade impactor. The in vivo depositions of lactose carrier systems were investigated in ten healthy men using the technique of gammascintigraphy. In addition, redispersion of budesonide from the carrier materials was evaluated by using the Andersen cascade impactor. According to the validation data the particle size of the lactose carriers remained unchanged during the labelling process. Low pulmonary deposition varying between 2.5 and 3.3% was detected. Only a small amount of lactose was deposited in the lungs, thus pulmonary deposition is not a limiting factor for lactose selection. According to in vitro redispersion data the fine particle fraction of the delivered dose in the impactor varied between 10.3 and 26.0%. Thus, the redispersion of the budesonide particles can be altered by the properties of the carrier system.

Administration, Inhalation↗

PubMed1996

Crystal structures of guinea-pig, goat and bovine alpha-lactalbumin highlight the enhanced conformational flexibility of regions that are significant for its action in lactose synthase.

BACKGROUND: The regulation of milk lactose biosynthesis is highly dependent on the action of a specifier protein, alpha-lactalbumin (LA). Together with a glycosyltransferase, LA forms the enzyme complex lactose synthase. LA promotes the binding of glucose to the complex and facilitates the biosynthesis of lactose. To gain further insight into the molecular basis of LA function in lactose synthase we have determined the structures of three species variants of LA. RESULTS: The crystal structures of guinea-pig, goat and a recombinant from of bovine LA have been determined using molecular replacement techniques. Overall, the structures are very similar and reflect their high degree of amino acid sequence identity (66-94%). Nonetheless, the structures show that a portion of the molecule (residues 105-110), known to be important for function, exhibits a variety of distinct conformers. This region lies adjacent to two residues (Phe31 and His32) that have been implicated in monosaccharide binding by lactose synthase and its conformation has significant effects on the environments of these functional groups. The crystal structures also demonstrate that residues currently implicated in LA's modulatory properties are located in a region of the structure that has relatively high thermal parameters and is therefore probably flexible in vivo. CONCLUSIONS: LA's proposed interaction site for the catalytic component of the lactose synthase complex is primarily located in the flexible C-terminal portion of the molecule. This general observation implies that conformational adjustments may be important for the formation and function of lactose synthase.

Animals↗

PubMed2004

Lactose intolerance associated with adjuvant 5-fluorouracil-based chemotherapy for colorectal cancer.

BACKGROUND & AIMS: Bowel mucosal injury associated with 5-fluorouracil (5-FU) treatment might result in secondary lactose intolerance. The frequency and clinical significance of 5-FU-related hypolactasia are unknown. METHODS: One hundred fifty patients randomly assigned to receive 1 of 2 adjuvant 5-FU-based chemotherapy regimens, the Mayo regimen or the simplified de Gramont regimen, were studied for lactose tolerance by using an oral lactose absorption test, a symptom questionnaire, treatment-related toxicity, and Subjective Global Assessment of Nutritional Status questionnaire before, during, and 2 and 6 months after chemotherapy for colorectal cancer. RESULTS: The frequency of hypolactasia increased from 24% before treatment to 35% during treatment (P < 0.0001). Therapy-related hypolactasia was reversible on discontinuation of chemotherapy. Symptoms compatible with lactose intolerance occurred in 94% of patients with an abnormal lactose absorption test result during chemotherapy. The frequency of hypolactasia increased during chemotherapy in both treatment groups, but was detected more commonly in those for whom therapy included continuous 5-FU infusions (the de Gramont regimen; 45% vs. 25%; P = 0.006). The presence of hypolactasia during chemotherapy was associated with flatulence, diarrhea, and poor nutritional status. CONCLUSIONS: Reversible chemotherapy-related hypolactasia and lactose intolerance are not infrequent in patients treated with 5-FU-based adjuvant chemotherapy for colorectal cancer. Avoidance of lactose during chemotherapy may improve treatment tolerability in these patients.

Adult↗