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At least 577 records · Page 32Linked to original sources
PubMed2006

Novel approach to DPI carrier lactose with mechanofusion process with additives and evaluation by IGC.

The effect of lactose carrier surface property on the inhalation profile of dry powder inhaler (DPI) was evaluated using a micronized drug (Compound A) by inverse gas chromatography (IGC). Mechanofusion with magnesium stearate (Mg-St) or sucrose stearate increased the fine particle fraction (FPF), considered to be due to decrease in the interaction between Compound A and the lactose carrier. The effect of Compound A concentration on FPF was smaller in mechanofusion-processed lactose compared to intact lactose, especially when processed with Mg-St. The relationship between the IGC parameters of the lactose and FPF was also investigated. FPF increased as both the dispersive component of the surface energy and acidity similarity between the lactose carriers and Compound A increased. Although further investigation is necessary, it could be suggested that acidity similarity decreases the interaction between Compound A and lactose, thus contributing to the increase in the FPF. In conclusion, (1) mechanofusion with Mg-St or sucrose stearate could be an effective method to improve FPF of a DPI drug formulation; (2) IGC would be a valuable method to investigate the interaction between a drug and the DPI carrier; and (3) a relationship between surface acidity and inhalation profile was suggested.

Chromatography, Gas↗
PubMed1995

[Determination of partial solubility parameters of lactoses and its application to solubility evaluation].

Partial solubility parameters of lactose packed into a glass column were calculated from adsorption energies of n-decane, acetonitrile and ethyl alcohol determined by gas-solid chromatography. Three kinds of crystalline lactoses, alpha-lactose monohydrate, anhydrous alpha-lactose (desiccated) prepared by desiccation with methyl alcohol, and anhydrous alpha-lactose (heated) prepared by heating, were used. It was characterized from the results that the partial solubility parameter, delta p, due to dipole interaction, of anhydrous forms had two-fold value than that of the hydrous form. In addition, it was suggested that the affinity of lactose for water vapor and the solubility of lactose for water were able to be evaluated using the three dimensional plot of partial solubility parameters and the interaction radius calculated from partial solubility parameters. It was shown that the appropriate information for the evaluation of physicochemical properties of active ingredients and excipients in the formulation study could be obtained from the data determined using partial solubility parameters.

Adsorption↗
PubMed2004

Genetic variation and lactose intolerance: detection methods and clinical implications.

The maturational decline in lactase activity renders most of the world's adult human population intolerant of excessive consumption of milk and other dairy products. In conditions of primary or secondary lactase deficiency, the lactose sugars in milk pass through the gastrointestinal tract undigested or are partially digested by enzymes produced by intestinal bacterial flora to yield short chain fatty acids, hydrogen, carbon dioxide, and methane. The undigested lactose molecules and products of bacterial digestion can result in symptoms of lactose intolerance, diarrhea, gas bloat, flatulence, and abdominal pain. Diagnosis of lactose intolerance is often made on clinical grounds and response to an empiric trail of dietary lactose avoidance. Biochemical methods for assessing lactose malabsorption in the form of the lactose breath hydrogen test and direct lactase enzyme activity performed on small intestinal tissue biopsy samples may also be utilized. In some adults, however, high levels of lactase activity persist into adulthood. This hereditary persistence of lactase is common primarily in people of northern European descent and is attributed to inheritance of an autosomal-dominant mutation that prevents the maturational decline in lactase expression. Recent reports have identified genetic polymorphisms that are closely associated with lactase persistence and nonpersistence phenotypes. The identification of genetic variants associated with lactase persistence or nonpersistence allows for molecular detection of the genetic predisposition towards adult-onset hypolactasia by DNA sequencing or restriction fragment length polymorphism analysis. The role for such genetic detection in clinical practice seems limited to ruling out adult-onset hypolactasia as a cause of intolerance symptoms but remains to be fully defined. Attention should be paid to appropriate interpretation of genetic detection in order to avoid potentially harmful reduction in dairy intake or misdiagnosis of secondary lactase deficiency.

Adult↗
PubMed2006

Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on Cheddar cheese quality: changes in residual sugars and water-soluble organic acids during ripening.

Cheddar cheese ripening involves the conversion of lactose to glucose and galactose or galactose-6-phosphate by starter and nonstarter lactic acid bacteria. Under ideal conditions (i.e., where bacteria grow under no stress of pH, water activity, and salt), these sugars are mainly converted to lactic acid. However, during ripening of cheese, survival and growth of bacteria occurs under the stressed condition of low pH, low water activity, and high salt content. This forces bacteria to use alternate biochemical pathways resulting in production of other organic acids. The objective of this study was to determine if the level and type of organic acids produced during ripening was influenced by calcium (Ca) and phosphorus (P), residual lactose, and salt-to-moisture ratio (S/M) of cheese. Eight cheeses with 2 levels of Ca and P (0.67 and 0.47% vs. 0.53 and 0.39%, respectively), lactose at pressing (2.4 vs. 0.78%), and S/M (6.4 vs. 4.8%) were manufactured. The cheeses were analyzed for organic acids (citric, orotic, pyruvic, lactic, formic, uric, acetic, propanoic, and butyric acids) and residual sugars (lactose, galactose) during 48 wk of ripening using an HPLC-based method. Different factors influenced changes in concentration of residual sugars and organic acids during ripening and are discussed in detail. Our results indicated that the largest decrease in lactose and the largest increase in lactic acid occurred between salting and d 1 of ripening. It was interesting to observe that although the lactose content in cheese was influenced by several factors (Ca and P, residual lactose, and S/M), the concentration of lactic acid was influenced only by S/M. More lactic acid was produced in low S/M treatments compared with high S/M treatments. Although surprising for Cheddar cheese, a substantial amount (0.2 to 0.4%) of galactose was observed throughout ripening in all treatments. Minor changes in the levels of citric, uric, butyric, and propanoic acids were observed during early ripening, whereas during later ripening, a substantial increase was observed. A gradual decrease in orotic acid and a gradual increase in pyruvic acid content of the cheeses were observed during 12 mo of ripening. In contrast, acetic acid did not show a particular trend, indicating its role as an intermediate in a biochemical pathway, rather than a final product.

Acetic Acid↗
PubMed1983

Relationship of lactose to nitrogen metabolism of artificially reared beef calves.

The purpose was to study the relationship of lactose to nitrogen metabolism of artificially-reared beef calves. Calves from 35 market heifers were fed whole milk at 12% of body weight daily to 14 days and then at 8% of body weight to 28 days. An 18.3% crude protein dry diet was fed for ad libitum consumption on days 1 to 28. For days 29 to 84, nine calves were assigned to each of three treatments: A) 60:40 grain:hay dry diet, B) 60:40 grain diet with liquid lactose fed separately, and C) 60:40 dry diet containing dried lactose. During days 1 to 28, body weights were not reduced. Calves compensated for reduction of whole milk intake by increasing their intakes of dry diet. gamma-Glutamyl transferase and urea nitrogen in blood serum were reduced when milk intake was decreased. Beef calves can be adapted to early weaning and artificial rearing if started soon after birth. Lactose treatments decreased dry matter intakes and vitamin E in blood, but body weights were not different. Feed conversion was improved; nitrogen balance and urinary nitrogen excretion were decreased by liquid lactose. Urea nitrogen in blood was related to nitrogen balance. Liquid lactose increased serum alkaline phosphatase and serum glucose. The role of liquid lactose was to supply adequate energy for improved utilization of retained nitrogen.

Analysis of Variance↗
PubMed1997

Differences in the hydrolysis of lactose and other substrates by beta-D-galactosidase from Kluyveromyces lactis.

The hydrolysis of o-nitrophenyl galactopyranoside and lactose by beta-D-galactosidase from Kluyveromyces lactis was enhanced by the addition of Mg2+ and Mn2+, but the rates of activation by each metal on both substrates were not the same. The Co2+, Zn2+, and Ni2+ activated the o-nitrophenyl galactopyranoside-hydrolyzing activity of the enzyme, but these same metals inhibited the lactose-hydrolyzing activity. The addition of Mg2+ and EDTA to the assay buffer increased the hydrolysis of o-nitrophenyl galactopyranoside and lactose at different rates. The responses of o-nitrophenyl galactopyranoside and lactose to the enzyme activity were different as a function of pH. The hydrolyzing activity toward both substrates also was influenced by the concentration of the phosphate in the assay buffer. However, the profile of the enzyme activity toward each substrate was different as a function of concentration. Because the assay of beta-galactosidase using o-nitrophenyl galactopyranoside is fast and convenient, the estimation of lactose-hydrolyzing activity of the enzyme has frequently been made based on the assay of o-nitrophenyl galactopyranoside hydrolysis. As shown in this study, a slight change in the conditions of the assay system and the enzyme application may cause changes in the ability of the enzyme to hydrolyze both lactose and o-nitrophenyl galactopyranoside. The change in o-nitrophenyl galactopyranoside-hydrolyzing activity is not always consistent with that of the lactose-hydrolyzing activity under the given condition, which may cause an inaccurate estimation of the enzyme activity in the enzyme preparation as well as in actual applications of the enzyme.

Enzyme Activation↗
PubMed1993

Effect of dietary lactose on cecal morphology, pH, organic acids, and Salmonella enteritidis organ invasion in Leghorn chicks.

The effect of 14 or 19 days of 10% dietary lactose administration on Salmonella enteritidis (SE) colonization and histological, morphometric, and organic acid changes of the ceca were investigated. At Day 13 or 18, chicks were challenged with 10(8) cfu of SE. Chicks were killed and cultured 24 h later. A reduction in the total number of positive SE organ invasions was observed following 14 days (P < .001) or 19 days (P < .005) of treatment in chicks fed with lactose. Histological examination revealed a marked reduction in lamina propria thickness of ceca, as well as subjective epithelial cell proliferation from chicks following either 14 or 19 days of lactose administration. Using morphometric analysis, a reduction in the mean lamina propria thickness in chickens fed with lactose during 14 or 19 days was observed as compared with controls (P < .05). Yet, an increase (P < .05) in the mean epithelial cell length in both lactose-treated groups was observed as compared with controls. Lactose decreased luminal pH (P < .05) and increased the concentration of acetic, propionic, butyric, and lactic acid (P < .05). These data indicate that lactose-induced resistance to SE organ invasion is associated not only with an increase in organic acid concentration but also with measurable morphological changes of the cecal mucosa.

Animals↗
PubMed2001

Lactose supports Muller cell protein expression patterns in the absence of the retinal pigment epithelium.

PURPOSE: We have previously shown that lactose, but not mannose, promotes the assembly of nascent photoreceptor outer segments in the absence of the retinal pigment epithelium (RPE). The purpose of the present study was to determine if, in addition to the improved outer segment assembly observed in the presence of lactose, biosynthetic changes in Muller cells could also be detected. METHODS: The RPE was removed from intact isolated Xenopus embryonic eyes that were allowed to complete differentiation in Niu-Twitty medium, Niu-Twitty with mannose, or Niu-Twitty with lactose. Control retinas matured in vitro with an adherent RPE. Retinal morphology was evaluated for organized folding of outer segment membranes and cell loss. In addition, the expression of three Muller cell proteins, glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), and glutamine synthetase, was examined. RESULTS: In control retinas, GFAP is undetectable, CRALBP heavily immunolabels Muller cells, and radial patterns of glutamine synthetase immunoreactivity are present. In the absence of the RPE, Muller cells upregulate GFAP expression, CRALBP labeling is present at a slightly reduced level, and glutamine synthetase immunolabeling is negligible. Neither mannose nor lactose modify significantly the expression of CRALBP. Similarly, both compounds completely prevent the upregulation of GFAP. However, normal glutamine synthetase expression was observed only in the presence of lactose, but not in the presence of mannose. Statistical analyses of slot blot-based protein quantification confirmed our immunochemical results. CONCLUSIONS: In RPE-deprived retinas supplemented with lactose, Muller cells were morphologically normal. The proper photoreceptor outer segment morphogenesis observed under these conditions was uniquely associated with normal levels of glutamine synthetase expression. The exact significance of this finding with respect to photoreceptor outer segment morphogenesis is unknown. We suggest that glutamine synthetase may be a marker of Muller cell metabolic or structural integrity that may reflect the enhanced ability of these cells, in the presence of lactose, to support photoreceptor outer segment morphogenesis.

Animals↗
PubMed1975

Clinical implications of lactose-positive breast secretions in nonpuerperal females.

Inappropriate milk-like secretion from the breasts is not infrequently encountered in patients. Usually these secretions have been identified as milk on the basis of their characteristic appearance, and only rarely has their identity as milk been proven by appropriate analysis. Since milk is chemically defined as a lactose-containing mammary secretion, the presence of lactose in a breast secretion identifies it as milk irrespective of its appearance or the presence of other constituents. Lactose can be readily identified by thin-layer chromatographic methods, which despite their inherent speed and sensitivity have not been widely utilized. A method using commercially prepared cellulose layers and a sandwich developing apparatus is presented in detail. This method utilizes current advances in chromatographic techniques and permits rapid and accurate identification of lactose in breast secretions. Such secretions from 10 nonpuerperal women were screened for the presence of lactose. The milk-like secretions from 8 contained varying amounts of lactose, which was not detectable in the secretions from the other 2. There was no correlation between the appearance of the secretion and the presence of lactose.

Breast↗
PubMed1999

[Study on the incidence of lactose intolerance of children in China].

1168 healthy children of 3-13 years old were selected as subjects from Beijing, Shanghai, Guangzhou and Haerbin. Total subjects were challenged by 25 gram lactose test. The breath hydrogen was determined, the symptoms of lactose intolerance were recorded. The results showed that the incidences of lactase deficiency of children of 3-5, 7-8 and 11-13 years old were 38.5%, 87.6% and 87.8% respectively. The incidences of lactose intolerance were 12.3%, 33.2% and 30.5% respectively. Lactase activity decreasing of Chinese children occurred at the age of 7-8 years old, and the symptom of lactose intolerance depended on lactose dose. But, there still are 39%-41.7% children with lactose maldigestion and 14%-16% children with intolerance symptom, after taking 50 gram milk powder (12 g lactose). The relationship between lactase activity and milk intake was not found.

Adolescent↗
PubMed1992

Functional role of arginine 302 within the lactose permease of Escherichia coli.

Within the lactose permease, an arginine residue is found on a transmembrane segment at position 302. Based upon the effects of mutations at or in the vicinity of Arg-302, this residue has been implicated to be involved with H+ and/or sugar recognition. To further elucidate the role of this residue, we have substituted Arg-302 with serine, histidine, and leucine via site-directed mutagenesis. All three of these substitutions result in an impaired ability to transport galactosides as evidenced by their poor growth on minimal plates supplemented with lactose or melibiose. Furthermore, in vitro transport assays revealed substantial alterations in the kinetic constants for downhill lactose transport. The wild-type strain exhibited a Km for lactose transport of 0.30 mM and a Vmax of 267 nmol of lactose/min.mg of protein. The Ser-302, His-302, and Leu-302 were observed to have Km values of 0.18, 2.3, and 2.8 mM, and Vmax values of 11.6, 56.4, and 22.0 nmol of lactose/min.mg of protein, respectively. In uphill transport assays, all three mutants were unable to accumulate beta-methyl-D-thiogalactoside. However, both the Ser-302 and His-302 mutants were able to accumulate lactose against a concentration gradient. During H+ transport assays, all three mutants were shown to transport H+ in conjunction with thiodigalactoside. In addition, the Ser-302 and His-302 strains exhibited small alkalinizations upon the addition of lactose. However, for the Leu-302 mutant, the addition of lactose did not result in a significant level of H+ transport. Finally, experiments were conducted which were aimed at measuring the ability of the mutant permeases to catalyze an H+ leak. In this regard, a comparison was made between the wild-type and mutant strains concerning their steady state pH gradient and their rates of H+ influx following oxygen pulses. The results of these experiments suggest that mutations at position 302 cause a sugar-dependent H+ leak.

Arginine↗
PubMed1991

Lactose malabsorption and calcium intake as risk factors for osteoporosis in elderly New Zealand women.

OBJECTS: to evaluate the prevalence of lactose malabsorption and to assess dietary calcium intake, in elderly New Zealand women with hip fractures, in age matched case controls without hip fractures drawn from general practice, and in healthy young women. METHODS: lactose malabsorption was assessed by measuring breath hydrogen after a 50 g oral lactose tolerance test. Dietary calcium was estimated from a food frequency questionnaire. RESULTS: the elderly fracture cases (n = 15), and their elderly controls (n = 16), showed a similar (60% and 63% respectively), but significantly higher prevalence (p less than 0.001), of lactose malabsorption than young women (12%, n = 50). Dietary calcium intake was similar in lactose absorbers and malabsorbers. CONCLUSIONS: malabsorption of lactose occurs commonly in elderly New Zealand women but is scarce in young adults. A high prevalence of lactose malabsorption may be a risk factor for exacerbation of type II osteoporosis in the elderly.

Adolescent↗
PubMed1990

Breath hydrogen test for assessment of lactose malabsorption following rotavirus gastroenteritis.

Ninety infants and young children with acute gastroenteritis were investigated for lactose malabsorption. Each of them was given an oral lactose load of 2g per kg of body weight after which breath hydrogen excretion was measured, and each was observed for clinical symptoms of lactose intolerance. Only 2 patients, given 2g per kg of lactose, had clinical lactose intolerance. Forty-nine of the 90 patients studied were found to have the rotavirus antigen in their stools. Forty-five of them were found to have an abnormal lactose breath hydrogen test (LBHT). Twenty-three patients with abnormal LBHT were restarted on a diluted lactose-containing formula for oral feeding. They required longer hospitalization (mean 6.7 days, range 3-14 days) and were free of diarrhea in 14 days (mean 7.5 days). Twenty-two patients found to have an abnormal LBHT were given a nonlactose-containing formula (Isomil, Nursoy, Alsoy, ProSobee, or Bebelac FL) when restarted on oral feeding. All patients require less than 5 days of hospitalization and free of diarrhea in 5 days (mean 3.4 days). The difference was statistically significant (p less than 0.05).

Breath Tests↗
PubMed1990

Lactose maldigestion: increased age-related prevalence in institutionalized children.

A study was performed to determine whether the age-related prevalence of lactose maldigestion is increased in healthy institutionalized children. Previous malnutrition did not exclude children from study. The control children had no prior history of malnutrition or hospital admissions for diarrhea. The anthropometric comparison showed the institutionalized children to be shorter and lighter than the controls, but they were of normal weight by stature, suggesting a normal recent nutritional state. Fasting breath hydrogen tests were performed following an oral dose of lactose 1 g/kg, given as a 10% solution. A rise of breath hydrogen of greater than or equal to 20 ppm was considered to indicate lactose maldigestion. Twenty-two of 44 controls and 39 of 49 study children were lactose maldigesters (p less than 0.01). The control children showed an age-related increase in the prevalence of lactose maldigestion, from 31.6% at age less than 5 years to 75% at age greater than 9 years. The institutionalized children, by comparison had an increased prevalence of 78.8% in the group under 5 years of age (p = 0.002). Equally high prevalence rates were found at all ages tested. At follow-up, lactose maldigestion was persistent in the majority of the study children. This had no nutritional impact despite a regular milk intake. The distinction between acquired and primary lactose maldigestion is of no practical significance in these children.

Adolescent↗
PubMed1987

Changes in alpha-lactalbumin, total lactose, UDP-galactose hydrolase and other factors in tammar wallaby (Macropus eugenii) milk during lactation.

alpha-Lactalbumin was isolated from milk of M. eugenii and its concentration in milk samples taken at various times during lactation (0-40 weeks post partum) was determined by single radial immunodiffusion using rabbit antiserum to the purified protein. The alpha-lactalbumin concentration remained almost constant throughout lactation even though the concentration of total lactose (free lactose plus lactose contained in oligosaccharides) fell to zero after 34 weeks post partum. This fall in lactose was accompanied by a rise in the free galactose and glucose concentrations and marked increases in UDP-galactose hydrolase, nucleotide pyrophosphatase, alkaline phosphatase and acid beta-galactosidase activities. It is suggested that the in vitro hydrolysis of UDP-galactose was due to nucleotide pyrophosphatase and that this enzyme may also play a role in vivo late in lactation by making UDP-galactose unavailable for the synthesis of lactose. Alternatively, lactose and lactose-containing oligosaccharides might be degraded by the acid beta-galactosidase during or after secretion.

Animals↗
PubMed1977

More evidence for the recessive inheritance of selective adult type lactose malabsorption.

Selective adult type lactose malabsorption appears in childhood or adolescence because of the great decline in jejunal lactase activity. There is strong evidence that this is a genetically determined disorder. Specifically, selective adult type lactose malabsorptions seem to be inherited by a single autosomal recessive gene. In the present prospective study the transition from the state of lactose absorption to that of lactose malabsorption was documented for the first time in two Finnish boys who were at risk for selective adult type lactose malabsorption because the parents of both boys had the disorder. At the age of 14 and 9 years, respectively, the boys had normal lactose absorption. Three years and 7 months and 4 years and 5 months later, respectively, the boys were shown to have lactose malabsorption. The period of documented transition averaged less than 4 years. These manifestations clearly strengthen the genetic model proposed.

Adolescent↗
PubMed1983

Primary lactose intolerance in Zulu adults.

The incidence of lactose intolerance in a sample of 47 Zulu patients from a general medical ward and 14 healthy members of the Zulu population in Durban was investigated. Eighty-nine percent of patients and 93% of control subjects were diagnosed as having lactose intolerance because of failure to increase blood glucose more than 1,1 mmol/l during the 2 hours following 50 g lactose ingestion. Ninety-two per cent of the female and 64% of the male patients complained of symptoms of lactose intolerance, and 61% of the female and 75% of the male patients passed stools with a pH of less than 6. Glucose tolerance (50 g) was normal in 87% of patients and 92% of controls; 2 patients had a diabetic response while 5 patients and 1 control had 'flat' glucose and lactose responses, suggesting delayed absorption. Analysis of nutritional status showed that male patients were significantly more malnourished than female patients, and patients more so than controls. The results indicate that lactose intolerance is a normal observation in the Zulu and that it is primary in origin since there was no association between intolerance, sickness or malnutrition. Practical implications that arise from the study are that milk-based diets should be avoided in refeeding malnourished Zulu patients and that lactose may find a useful place in the treatment of constipation and liver failure in such patients.

Adult↗
PubMed1994

Functional roles of Glu-269 and Glu-325 within the lactose permease of Escherichia coli.

Acidic residues which are found on transmembrane segments within the lactose permease may play an important role in H+ and/or sugar recognition. To examine the functional roles of Glu-269 and Glu-325, we have constructed a variety of amino acid substitutions (e.g. aspartate, glycine, alanine, serine, or glutamine) via site-directed mutagenesis. At position 269, all mutations appear to have a detrimental effect on sugar affinity, downhill transport, and counterflow. The Asp-269 mutant was able to accumulate lactose against a concentration gradient, whereas all of the nonionizable substitutions at position 269 were completely defective. Nevertheless, in spite of their inability to actively accumulate sugars, Gly-269, Ala-269, and Gln-269 mutants were observed to transport H+ upon the addition of galactosides. Mutations at position 325 had a markedly different phenotype. For example, the Asp-325, Gly-325, and Gln-325 mutants exhibited an apparent Km for lactose transport (e.g. 0.21, 0.47, and 0.50 mM, respectively), which was actually lower than that of the wild-type strain (1.44 mM). In counterflow assays, all position 325 mutants also appear to catalyze lactose exchange. Similar to the results obtained at position 269, the Asp-325 mutant exhibited moderate levels of accumulation, whereas none of the nonionizable mutations at position 325 were able to accumulate galactosides against a concentration gradient. However, unlike the position 269 mutants, no H+ transport was observed in the Gly-325, Ala-325, Ser-325, or Gln-325 strains upon the addition of lactose, S-beta-D-galactopyranosyl-(1,1)-beta-thiogalactopyranoside, 1-O-methyl-beta-D-galactopyranoside, or melibiose. Furthermore, in these mutants, the efflux of lactose during counterflow assays became insensitive to delta pH. Overall, these results are consistent with the notion that an acidic residue at position 325 is required for H+ transport via the lactose permease. Alternative hypotheses are also discussed.

Biological Transport↗