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Assessing the re-crystallization behaviour of amorphous lactose using the RH-perfusion cell.

Many different reports have studied the crystallization behaviour of lactose, e.g., by exposing samples of amorphous lactose to different relative humidity at constant temperatures. However, only few reports are available investigating the formation of alpha-lactose monohydrate and beta-lactose during re-crystallization. Applying the static ampoule method in the microcalorimeter, the enthalpies of amorphous lactose were reported to be constantly 32 and 48 J/g, respectively, considering the mutarotation of lactose at 25 degrees C and 58% RH, 75% RH and 100% RH. In this study, an alternative microcalorimetric technique, the relative humidity-perfusion cell (RH-perfusion cell) was chosen. The RH-perfusion cell is able to deliver a constant and controlled flow of humidified air to the sample. Investigated compounds were purely amorphous lactose and different powder mixtures of lactose. They consisted of alpha-lactose monohydrate (Pharmatose 325M), beta-lactose (Pharmatose DCL21) or a combination (1:1) thereof as carriers, and different concentrations of amorphous lactose. The determination of the enthalpy of desorption of the just re-crystallization lactose by the RH-perfusion cell was used to discriminate whether the monohydrate or the anhydrous form of lactose was produced. Differences in the re-crystallization behaviour of lactose at 25 degrees C and 58-100% RH were found. At 60-80% RH purely amorphous lactose showed a high heat of desorption which can be attributed to a very high content of formed beta-lactose. Powder mixtures containing high contents of amorphous lactose (8% and 15%, respectively) blended with alpha-lactose monohydrate as a carrier resulted in similar results at the same RH ranges. The high amount of beta-lactose can be due to the equilibrium anomeric composition. Whereas powder mixtures containing beta-lactose as a carrier and amorphous lactose in a concentration of 1%, 8% and 15%, respectively, formed less beta-lactose than the mixtures containing alpha-lactose monohydrate as a carrier. At a relative humidity of 90% none of the powder mixtures showed desorption as to the fact that in all cases only alpha-lactose monohydrate was formed at the surface of the re-crystallized lactose. Furthermore, mixtures of alpha-lactose monohydrate and beta-lactose (1:1) and 8% amorphous lactose were investigated. An increase in formed alpha-lactose monohydrate by increasing RH was found. To consolidate the results, the same mixtures were re-crystallized at different RH in desiccators and subsequently investigated in the solution calorimeter. The results of the pre-mix were confirmed by the solution calorimeter. In summary, purely amorphous lactose and mixtures containing alpha-lactose monohydrate as a carrier show different re-crystallization behaviour compared to mixtures containing beta-lactose as a carrier.

Adsorption↗

The use of different grades of lactose as a carrier for aerosolised salbutamol sulphate.

Five different grades of lactose namely, anhydrous lactose, medium lactose, regular lactose, lactose crystals and foremost lactose were fractionated under similar conditions to obtain a size range of 63-90 microm and were characterised using laser diffraction and time-of-flight particle sizing techniques, scanning electron microscopy, optical microscopy image analysis, thermal gravimetric analysis and differential scanning calorimetry. Each of these lactose fractions were then blended separately with micronised salbutamol sulphate in a ratio of 67.5:1 (w/w). The mixing uniformity and percentage recovery of salbutamol sulphate in the powder blends were analysed using a validated HPLC method. The deposition profiles of the drug were determined using a 5-stage liquid impinger after aerosolisation at 60 l min(-1) via a Rotahaler. Despite the identical processing conditions, the lactose fractions were shown to differ in particle size, size distribution and concentrations of fine particles. The particles from each fraction also exhibited different surface textures and dissimilar DSC thermograms. However, all the blends of the lactose with salbutamol sulphate were found to have a relatively high uniformity of salbutamol sulphate content, as suggested by a coefficient of variation of less than 3.2%. Anhydrous and medium lactose produced a more efficient delivery of salbutamol sulphate when aerosolised from the Rotahaler in comparison to other grades of lactose. For example, the fine particle fraction (FPF) and fine particle dose (FPD) of drug from formulations containing anhydrous lactose were 13.4+/-4.2% and 57.3+/-17.6 microg, respectively, which were approximately two times higher than the respective values of the formulation containing regular lactose. Medium lactose resulted in drug FPF (7. 9+/-2.7%) and FPD (32.4+/-11.8 microg), which were significantly (ANOVA P<0.05) higher than the same parameters obtained using lactose crystals, foremost lactose and regular lactose. More efficient drug delivery from anhydrous lactose may be partly attributed to the relatively higher concentration of fine lactose in this grade of carrier, although it showed a rougher surface than the other grades of lactose. However, the relatively high FPF of the drug from medium lactose may have been due to the relatively small mean particle size and smooth surface of the particles. Therefore, the source and grade of lactose may have a substantial effect on drug delivery from dry powder inhaler formulations and care should be taken in establishing appropriate quality control parameters when selecting an appropriate grade of carrier.

Adrenergic beta-Agonists↗

Assessment of lactose absorption by measurement of urinary galactose.

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.

Adolescent↗

Lactose hydrolyzed milk.

Lactose intolerance is being reported in many populations. Yet, milk is highly nutritious and methods are being explored to use milk while limiting the lactose content. Thirty-two blacks 13-19 years of age were studied to determine a blood sugar rise with 8 ounces of the following test milks: 1) untreated whole milk (12 g/lactose); 2) 90% lactose hydrolyzed milk (1.2 g/lactose); and 3) 50% lactose hydrolyzed milk (6 g/lactose). In the 22 lactose malabsorbers, the peak blood sugars were: 1) untreated whole milk--4.4 mg/100 ml, 2) 90% lactose hydrolyzed milk--14.5 mg/100 ml, and 3) 50% lactose hydrolyzed milk--8.8 mg/100 ml. The 10 blacks with normal lactose absorption had a comparably high peak blood sugar on all three test milks. Differences between the blood sugar in the lactose absorbing and malabsorbing subjects when drinking untreated whole milk are significant (P less than 0.001); so are differences in the lactose malabsorbing subjects consuming untreated whole milk and 90% lactose hydrolyzed milk (P less than 0.001) as well as 50 and 90% lactose hydrolyzed milk. Symptoms were reported by three lactose malabsorbing subjects with untreated whole milk with two of the three symptomatic with 90% lactose hydrolyzed milk and none with 50% lactose hydrolyzed milk. No symptoms were reported by the lactose absorbers. Significant improvement in absorption with 90% lactose hydrolyzed milk is seen in low lactase subjects. Lactose hydrolyzed milk may serve as an important alternative for food planners wanting to provide milk to high risk populations with low lactase levels.

Adolescent↗

Role of irritable bowel syndrome in subjective lactose intolerance.

It has been suggested that the symptoms of irritable bowel syndrome (IBS) may be wrongly attributed to lactose intolerance. We examined the relations among IBS, demographic factors, living habits, and lactose intolerance. On the basis of a lactose tolerance test with ethanol, 101 of the 427 healthy subjects studied were lactose maldigesters and 326 were lactose digesters. IBS was diagnosed by means of the Bowel Disease Questionnaire, according to the Rome criteria. The use of dairy products and symptoms experienced after their consumption were recorded. IBS was found in 15% of both the lactose maldigesters and lactose digesters. One-third of the subjects reported intolerance to dairy products containing < or = 20 g lactose. About half of this third were lactose maldigesters and about half were lactose digesters. As explanations for this subjective lactose intolerance, the logistic regression model estimated lactose maldigestion (odds ratio: 10.3; 95% CI: 5.2, 20.4), IBS (4.6; 2.1, 10.1), experience of symptoms other than gastrointestinal ones (2.3; 1.2, 4.5), and female sex (2.1; 1.1, 4.0). Characteristics common to both subjective lactose intolerance and IBS were female sex and the experience of abdominal pain in childhood (P < 0.01). Age, regularity of meals, and the amount of physical activity were not associated with either subjective lactose intolerance or IBS. Of the subjects with IBS, the percentage of lactose maldigesters was the same as in the whole study group (24%) but the number who reported lactose intolerance was higher (60% compared with 27%, P < 0.001). We showed a strong relation among subjective lactose intolerance, IBS, the experience of abdominal pain in childhood, and female sex.

Abdominal Pain↗

Effects of diet complexity and dietary lactose levels during three starter phases on postweaning pig performance.

Four experiments involving 1,005 crossbred pigs weaned at 19 +/- 2 d of age evaluated the effect of diet complexity and lactose level on starter pig performances. Experiment 1 was a randomized complete block (RCB) conducted in nine replicates with 135 pigs. A complex diet using several protein sources, a semicomplex diet with fewer protein sources, and a simple diet of corn and soybean meal comprised the three treatment groups. All diets contained 25% lactose (as-fed basis) with lysine (total) constant from d 0 to 14 (1.55%) and d 14 to 28 (1.45%), respectively. Gain, feed intake, and feed efficiency (P < 0.05) improved as diet complexity increased during both periods. In Exp. 2, 240 pigs in eight replicates in a RCB design were fed complex diets, but dietary lactose (total; as-fed basis) levels ranged from 10 to 35% in 5% increments from 0 to 14 d after weaning. From 14 to 30 d, a common 17% lactose diet was fed to evaluate the effects of early lactose level on subsequent responses. Gains (P < 0.05) increased for the 0- to 7- and 0- to 14-d periods as lactose increased to 30%. Similar gains resulted for all treatment groups from 14 to 30 d after weaning, with no evidence of compensatory responses to early lactose levels. In Exp. 3, 330 pigs were fed complex diets. From 0 to 7 d after weaning, the diets contained 25% lactose (as-fed basis), and from 7 to 21 d postweaning, the lactose levels ranged from 7 to 31% in 5% increments. Gain (P < 0.01) and feed efficiency (P < 0.05) increased from 7 to 21 d to the 17% lactose level. In Exp. 4, 300 pigs were fed 25 and 17% (as-fed basis) lactose diets from 0 to 7 and 7 to 21 d postweaning, respectively. From 21 to 35 d postweaning, lactose levels of 0 to 20% in 5% increments were added to a corn-soybean meal diet. The experiment was conducted as a RCB design in 12 replicates. Gain (P < 0.05) and feed intake (P < 0.05) increased to 10 to 15% lactose. When the data from Exp. 4 were partitioned into lighter (15.0 kg) and heavier (17.7 kg) pig weight replicates, only the lighter replicates had significant improvements in gain, feed intake, and feed efficiency (P < 0.05) in response to dietary lactose. These results demonstrated that starter pigs performed better when fed complex diets, that dietary lactose levels of 25 to 30% (to 7 kg BW) during the initial week postweaning, 15 to 20% lactose during d 7 to 21 (to 12.5 kg BW), and 10 to 15% lactose during d 21 to 35 postweaning (to 25 kg BW) resulted in maximum performance.

Animal Feed↗

Intestinal permeability to intact lactose in newborns and adults.

Small amounts of lactose have been shown to be absorbed intact across the intestine and excreted unchanged in the urine of newborns and adults. We designed a study to quantitate the intestinal uptake and urinary excretion of this disaccharide in these age groups. Similar amounts of lactose were given orally to 17 term newborns (age: 24.8 +/- 3.0 h) as a standard infant formula, and to 15 adult lactose absorbers (age: 28.1 +/- 2.6 years) and 11 adult lactose malabsorbers (age: 24.7 +/- 2.9 years) as a 20% water solution. Following lactose ingestion, breath was collected every 30 or 60 min for 3 h and analyzed for hydrogen concentration. Urine was also collected, and lactose and creatinine concentrations were determined. Peak hydrogen concentration was less than 20 ppm above baseline in newborns and adult lactose absorbers and 85 +/- 14 ppm in adult lactose malabsorbers. Urinary lactose excretion, expressed as a function of body weight (mg/ml/kg b.w.), was substantially greater in newborns (4.2 +/- 0.82) than in adult lactose absorbers (0.29 +/- 0.07; p less than 0.001) and adult lactose malabsorbers (0.55 +/- 0.04; p less than 0.01). Similarly, urinary lactose excretion expressed as a ratio of urinary lactose to urinary creatinine (mg/mg) was increased (p less than 0.001) in newborns (2.05 +/- 0.26) when compared to adult lactose absorbers (0.11 +/- 0.02) and adult lactose malabsorbers (0.20 +/- 0.02). Our data demonstrate that the intestinal uptake and urinary excretion of intact lactose is significantly increased in newborns compared to adult subjects.

Adult↗

Effect of dietary lactose on gain, feed conversion, blood, bone and intestinal parameters in postweaning rats and swine.

Two trials were conducted to determine the effect of lactose on performance, bone integrity and certain blood constituents in postweaning rats and swine. The effect of lactose on calcium and phosphorus and percentage ash content of the small intestine was also determined. In both trials, average daily gains were not influenced by the feeding of diets containing 30% lactose. Feed conversion was depressed in both rats and pigs when 30% lactose was fed. Transitory diarrhea was observed in rats fed 30% lactose, but not in swine. In the rat trial, no significant differences due to treatment were observed for serum Ca of P, but a linear increase (P < .01) in alkaline phosphatase was observed as lactose increased in the diet. Analysis of blood constituents from multiple bleedings during the pig trial showed that in the first 2 weeks, alkaline phosphatase was increased (P < .01) in pigs fed lactose and slightly decreased in those not fed lactose. Lactose affected the change in serum Ca for 0 to 10 weeks (P < .05) as indicated by a marked reduction in serum Ca of pigs not fed lactose and a slight increase for those fed lactoss. Serum calcium decreased in the absence of lactose but increased in the presence of lactose (P < .05) in pigs fed .4% Ca diets. In both trials, breaking strength parameters (peak force and stress) were not affected by dietary lactose. Bones from pigs fed no lactose had a higher stress to strain ratio (P < .05) than those from pigs fed lactose. In the rat trial, stress to strain ratio was variable across all treatments. Percentage of bone ash increased (P < .01) as lactose increased in the diet. Dietary treatments did not affect the mineral content of specific gut segments.

Animals↗

Dietary calcium intake in lactose maldigesting intolerant and tolerant African-American women.

BACKGROUND: The relationship between lactose maldigestion, lactose intolerance, and calcium intake in premenopausal African American women is unknown. OBJECTIVE: To determine how intolerance of lactose and dairy products affects intake of calcium in lactose maldigesting premenopausal African American women. DESIGN: Dietary intake of calcium was assessed in 50 premenopausal lactose maldigesting African American women as determined by the breath hydrogen test. Twenty-six women were lactose intolerant and 24 were lactose tolerant by self-reports. RESULTS: The average intake of calcium in lactose maldigesting and intolerant women was significantly lower than in lactose tolerant women (388 +/- 150 mg/day vs. 763 +/- 333 mg/day, p < 0.0001, t test). Neither group reached the newly established Dietary Reference Intake (DRI) for calcium (1,000 mg/day). Major source of dietary calcium in lactose tolerant women were milk and dairy products (45%), and mixed foods containing calcium from non-dairy sources (30%). In lactose intolerant women, 46% of calcium was from mixed foods and only 12% was from milk and dairy products. Lactose intolerant women had higher body mass index (BMI) than lactose tolerant women (p = 0.008, t test), and calcium intake was negatively associated with BMI (R2 = 0.470). CONCLUSIONS: In African American premenopausal women, lactose tolerance facilitates the dietary intake of calcium when compared with their lactose intolerant counterparts. Low calcium intake is associated with higher BMI.

Adult↗

Improvement of lactose digestion in humans by ingestion of unfermented milk containing Bifidobacterium longum.

Fifteen lactose malabsorbers were studied to evaluate the effects of consumption of milk containing different strains of Bifidobacterium longum on lactose digestion. Influences of different growth substrates, bile sensitivity, and lactose transport on lactose digestion by bifidobacteria were also investigated. Lactose malabsorption was determined by measuring breath hydrogen excretion of subjects fed four different test milks (three of which contained 5 x 10(8) cfu/ml of B. longum) on 4 different d using a randomized, double-blinded trial. Test milks included 1) 400 ml of lowfat milk (control), 2) 400 ml of milk containing B. longum B6 that had been grown with lactose, 3) 400 ml of milk containing B. longum B6 grown with lactose plus glucose, or 4) 400 ml of milk containing B. longum ATCC 15708 grown with lactose. beta-Galactosidase activity was highest in milk containing B6 grown with lactose but was extremely low in milk containing B6 grown with lactose and glucose. Consumption of milk containing B6 grown with lactose resulted in significantly less hydrogen production and flatulence than occurring after consumption of control milk or the milk containing B6 grown with both lactose and glucose. Hydrogen production after ingestion of 15708 was also significantly lower than hydrogen production after ingestion of the control milk. We concluded that milks containing B. longum might reduce breath hydrogen response and symptoms from lactose malabsorption when the culture is grown in a medium containing only lactose to induce a higher beta-galactosidase level and increase rate of lactose uptake.

Adult↗

Lactose malabsorption is associated with early signs of mental depression in females: a preliminary report.

Lactose malabsorption is characterized by a deficiency of mucosal lactase. As a consequence, lactose reaches the colon where it is broken down by bacteria to short-chain fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of lactose malabsorbers. Having made the observation that females with lactose malabsorption not only showed signs of irritable bowel syndrome but also signs of premenstrual syndrome and mental depression, it was of interest to establish whether a statistical correlation existed between lactose malabsorption and mental depression. Thirty female volunteers were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and were classified as normals or lactose malabsorbers according to their breath H2 concentrations. All patients filled out a Beck's depression inventory questionnaire. Of the 30 female volunteers, six were lactose intolerant (20%) and 24 were normal lactose absorbers (80%). Subjects with lactose malabsorption showed a significantly higher score in the Beck's depression inventory than normal lactose absorbers did. The data thus suggest that lactose malabsorption may play a role in the development of mental depression. In lactose malabsorption high intestinal lactose concentrations may interfere with L-tryptophan metabolism and 5-hydroxytryptamine (serotonin) availability. Lactose malabsorption should be considered in patients with signs of mental depression.

Adolescent↗

Isomerization of lactose in solid-state by mechanical stress during grinding.

Isomerization during grinding of solid-state alpha-monohydrate, alpha-anhydrate and beta-anhydrate of lactose was investigated. Samples were ground in an agate centrifugal ball-mill at 270 rev min-1 at room temperature (20 degrees C). The crystallinity of ground lactose was measured by Hermans' method from the powder X-ray diffraction profiles. The alpha- and beta-lactose content of the ground lactose was obtained from the specific rotation measured by using angular rotation spectrophotometry. The crystalline lactose samples were transformed into non-crystalline solids by mechanical stress during grinding. After grinding, the water content of all ground lactose samples increased, and the samples had about 2 mol water per lactose after 10 h grinding. After 10 h grinding of alpha-monohydrate and alpha-anhydrate, 10 and 15%, respectively, of alpha-lactose was transformed into beta-lactose by the mechanical treatment. After 10 h grinding of beta-lactose, 20% of beta-lactose was transformed into alpha-lactose. The results suggest that crystalline lactose was transformed into a non-crystalline solid, and water was adsorbed on the non-crystalline lactose. The non-crystalline solids of alpha- or beta-lactose were then transformed into their counterparts by the mechanochemical effects of grinding.

Chemical Phenomena↗

[Selected properties of lactose-fermenting and non-fermenting Salmonella agona strains isolated from specimens from hospitalized infants].

The aim of this study was to compare some of the properties of 28 lactose-positive and 28 lactose-negative Salmonella agona strains isolated from faeces of infants hospitalized in the same hospital. Some of biochemical properties, sensitivity to 14 antibiotics and chemotherapeutic agents and sensitivity to bacteriophages used for typing of this Salmonella genus were tested. Results of biochemical examinations revealed that lactose-fermenting strains retain the remaining of Salmonella of subspecies I. Two biochemical features are of particular importance: the ability to ferment lactose on all lactose containing media and a lack of the ability to produce H2S on Kligler medium. These two features differentiate lactose-fermenting strains of Salmonella from non-lactose fermenting ones. Antibiotic sensitivity pattern differed between lactose-positive and lactose-negative strains. Lactose-positive strains showed higher degree of resistance than lactose-negative strains. The differences in resistance were seen in the case of chloramphenicol, doxycycline, gentamicin and tetracycline. Both lactose-positive and lactose-negative strains were sensitive to colistin, neomycin, nitrofurantoin and nalidixic acid. They were resistant to ampicillin, cloxacillin, rifampicin, streptomycin, sulfatiazol and biseptol. Bacteriophage typing revealed that all lactose-negative strains isolated in this study from clinical samples belonged to the same phage pattern V. Lactose-positive strains belonged to two phage types VB and XI. Type VB prevailed.

Anti-Bacterial Agents↗

The effect of lactose maldigestion on the stools of young Tswana children.

During diarrhoeal disease, stool mass is usually increased. Lactose content of stools and stool pH have been used as tests for secondary lactose maldigestion. The effect of a lactose-free diet and various lactose loads on the stools of 30 children with primary adult-type lactose maldigestion was investigated. Stool mass following the lactose tolerance test was the largest (mean = 80 g/day); that following the milk tolerance test less--62 g (not significantly), that on a milk containing diet significantly less (35 g), while stool mass produced on a lactose-free diet (22 g) was significantly less than that produced on any of the three lactose-containing diets. The stool pH on a milk containing diet (mean = 6.3) was significantly higher than those of the three other diets (after lactose tolerance test, pH = 5.85; after milk tolerance test, pH = 5.86; after lactose-free diet, pH = 5.83). Although stool bulk was greater when these lactose maldigesters were consuming a lactose containing diet, it was still considerably less than the stool mass associated with secondary lactose maldigestion, which is believed to be a cause of diarrhoeal disease. In contrast, the primary adult-type of lactose maldigestion does not commonly cause diarrhoea, as shown in this study.

Africa↗