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Evaluation of flow properties of dry powder inhalation of salbutamol sulfate with lactose carrier.

The effects of the flow and packing properties of a drug/carrier powder mixture on emission of drug adhering to the carrier from capsules and inhalation devices were investigated. Model powder mixtures were designed consisting of lactose carriers with different particle shapes were prepared by surface treatment and micronized salbutamol sulfate. These powder mixtures were aerosolized by a Spinhaler, and in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The flow properties of the mixed powders were evaluated by the Carr's flowability index (FI) and Hausner's ratio (HR). The packing properties of the mixed powders were determined employing the tapping method. Compared with the powder mixed with the untreated lactose carrier, the FI, HR, and the constant K in Kawakita's equation of the powder mixture prepared using the surface-treated lactose carrier were significantly different, showing that the flow and packing properties of the drug/carrier powder mixture were improved. Using this surface-treated system, the handling of the powder mixture when packing into capsules is improved, which is desirable for handling dry powder inhalants. The fraction (%) of drug emitted from capsules and devices (EM) and the FI of the powder mixture were correlated. As the flow properties improved, the outflow of the powder mixture from capsules and devices became easier, and emission of drug adhering on the carrier from capsules and devices improved. Improvement of the inhalation process, such as the drug particles emitted from the inhalation system, is valuable for increasing inhalation properties of dry powder inhalation.

Aerosols↗

Production of a mixture of antimicrobial organic acids from lactose by co-culture of Bifidobacterium longum and Propionibacterium freudenreichii.

The antimicrobial activities of standard solutions of three organic acids (lactic, acetic, and propionic acids) were compared using Micrococcus luteus, Pseudomonas sp. and Staphylococcus aureus as test microorganisms. At the same concentrations of the undissociated form, the antimicrobial activities of acetic and propionic acids were higher than that of lactic acid, irrespective of test microorganisms. In a single cultivation of Bifidobacterium longum, a mixture of lactic (17 g/l) and acetic (20 g/l) acids was produced from 50 g/l lactose and its antimicrobial activities against M. luteus, Pseudomonas sp., and S. aureus correspond to that of 32, 19, and 25 g/l of acetic acid, respectively. To increase the total antimicrobial activity, a co-culture of B. longum and Propionibacterium freudenreichii, in which lactic acid produced once from lactose by B. longum was converted to acetic and propionic acids by P. freudenreichii, was done using TPY medium containing commercially available peptones as a nitrogen source. By the sequential conversion of lactose using the two microorganisms, the culture supernatant containing a mixture of acetic (27 g/l) and propionic (13 g/l) acids without lactic acid was produced. The antimicrobial activities of the mixture against M. luteus, Pseudomonas sp., and S. aureus were 35, 30, and 26 g/l as a concentration of acetic acid, respectively, higher than that obtained in the cultivation of B. longum alone. When the medium containing an enzymatic hydrolyzate of whey proteins with a protease was used in the co-culture of B. longum and P. freudenreichii, the culture supernatant containing the mixture of organic acids was also obtained in the same manner as the co-culture using TPY medium and the activities were 43, 29, and 29 g/l as a concentration of acetic acid for M. luteus, Pseudomonas sp. and S. aureus, respectively.

Acetic Acid↗

On the interaction of the vanadyl(IV) cation with lactose: inhibition effects of vanadyl(IV)/monosaccharide and disaccharide complexes upon alkaline phosphatase activity.

A new vanadyl(IV) complex of the disaccharide lactose was obtained in aqueous solution at pH = 13. The sodium salt of the complex, of composition Na4[VO(lactose)2].3H2O, has been characterized by elemental analysis and by ultraviolet-visible, diffuse reflectance, and infrared spectroscopies. Its magnetic susceptibility and thermal behavior were also investigated. The inhibitory effect on alkaline phosphatase activity was tested for this compound as well as for the vanadyl(IV) complexes with maltose, sucrose, glucose, fructose, and galactose. For comparative purposes, the free ligands and the vanadyl(IV) cation were also studied. The free sugars and the sucrose/VO complex exhibited the lowest inhibitory effect. Lactose-VO, maltose-VO, and the free VO2+ cation showed an intermediate inhibition potential, whereas the monosaccharide/VO complexes appeared as the most potent inhibitory agents.

Alkaline Phosphatase↗

Changes in daily energy amounts of main milk components (lactose, protein and fat) during the lactation of high-yielding dairy cows.

The aim of this study was to examine the changes of the daily energy amount of lactose, protein and fat throughout the lactations, and compare them to each other. A total of 309 Israeli Holstein-Friesian cows from one kibbutz were investigated in three lactations, and information was given for a period of five years from 1996 to the end of 2000. The distribution of milk components and milk yield during lactation, and changes of the absolute and relative energy amount in the different milk components were calculated and evaluated. The results showed changes in the energy content of milk and its different components throughout the lactation. Each component (fat, lactose and protein) is dominant in different periods during the lactation. The energy amount from fat reaches a peak first, between days 40 and 50. Lactose has a peak at about day 66 of lactation, and protein reaches the peak last, approximately at day 104 of lactation. It seems that this peak sequence is constant and it is considered to be physiological. It might be suggested that there is a regulation governing the secretion of the different components at different times, and only one component is dominant in a given period. Each component exerts negative and positive influences on the secretion of the other components, which interact with each other and are not fully independent.

Animals↗

Secondary lactose intolerance in a neonatal goat.

A 2-week-old Toggenburg kid was evaluated for persistent diarrhea and poor body condition. The herd had high morbidity and mortality associated with diarrhea in neonatal kids. Lactose intolerance was diagnosed on the basis of results of a lactose tolerance test and glucose absorption test. Clinically normal herdmates were used as control animals. The kid responded to lactase supplementation. Cryptosporidium organisms were detected in feces of several affected kids during episodes of acute diarrhea. Lactose intolerance was presumed to have developed secondary to intestinal cryptosporidiosis.

Animals↗

Efficacy of dried whey and its lactalbumin and lactose components at two dietary lysine levels on postweaning pig performance and nitrogen balance.

Two experiments were conducted to determine the efficacy of lactalbumin and lactose components of dried whey on gain and feed performance responses and N retention of weanling swine. In Exp. 1, a 2 x 5 factorial arrangement of treatments in a randomized complete block design in seven replicates was used to evaluate the efficacy of two dietary lysine levels (.90 and 1.30%) in 1) a corn-soybean meal (C-SBM) mixture, 2) C-SBM and 20% dried whey (C-SBM-DW), or the dried whey component replaced with 3 lactalbumin and cornstarch, 4) lactose and an amino acid mixture, or 5) the combination of lactalbumin and lactose. A total of 420 pigs weaned at 23 +/- 2 d of age, weighing an average of 6.87 kg BW, were used in a 3-wk experiment. Experiment 2 was a balance trial conducted as a 3 x 2 x 3 factorial arrangement in a split-plot design in three replicates. The negative (i.e., C-SBM) and positive (i.e., C-SBM-DS) control diets and the C-SBM-lactalbumin-cornstarch diets at the two lysine levels of Exp. 1 were the main plots, each evaluated for a 3-wk postweaning period. Growth rate (P less than .05), feed intake (P less than .01), N retention (P less than .01), and apparent N digestibility (P less than .05) were increased when pigs were fed the C-SBM-DW compared with the C-SBM diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Insulin resistance, hyperglycemia, glucosuria, and galactosuria in intensively milk-fed calves: dependency on age and effects of high lactose intake.

Calves intensively fed milk replacers frequently develop postprandial insulin resistance, characterized by excessively elevated plasma insulin concentrations, hyperglycemia, and glucosuria. To test the hypothesis that insulin secretion and insulin-dependent dependent glucose metabolism are modified by age and carbohydrate intake, 20 male calves (Simmental x Red Holstein) were fed a milk replacer containing 290 and 423 g lactose/kg DM from 60-70 to 190-200 kg BW. Responses of insulin and glucose to milk replacer intake and orally administered glucose and pre- and postprandial glucose responses to i.v. infused glucose and i.v. injected insulin were tested at 75-105 and 160-200 kg BW. Urine was collected during 24h to determine glucose, galactose, dopamine, noradrenaline, and creatinine excretion. Insulin resistance, hyperinsulinemia, hyperglycemia, glucosuria, and galactosuria developed with increasing age and occurred primarily postprandially. High lactose intake enhanced postprandial hyperglycemia but did not significantly increase glucosuria, galactosuria, and hyperinsulinemia. Based on urinary excretion of dopamine and noradrenaline there was a marked age-dependent increase in the activity of the sympathetic nervous system, which was not modified by lactose intake. high feeding intensity and lactose intake, excessive hyperinsulinemia per se and enhanced activity of the sympathetic nervous system possibly contributed to the development of insulin resistance. Glucose-dependent insulinotropic polypeptide, growth hormone and cortisol concentrations, and iron intake were low and comparable in both groups and therefore were etiologically not involved in the development of insulin resistance. Increasing circulating concentrations of insulin-like growth factor I during growth may have in part allowed high growth rates in the presence of insulin resistance.

Aging↗

Lactose malabsorption after bypass operation for obesity.

After bypass operation for obesity the remaining lactose-hydrolyzing capacity of the functioning shunt is very low, especially if the shunt is constructed from a shorter jejunal and a longer ileal segment. In most cases a temporary decrease in the lactase activity of the jejunal part of the shunt occurs during the first postoperative months. In the present study lactose provoked or aggravated diarrhoea and other symptoms in 20 of 33 shunt-operated patients, and 10 patients reported milk intolerance postoperatively. Oral glucose tolerance tests indicated that the lactase activity was rate limiting for lactose absorption postoperatively.

Diarrhea↗

Clinical picture of hypolactasia and lactose intolerance.

Selective adult-type hypolactasia, the main cause of primary malabsorption of lactose, shows considerable variation in terms of its symptoms, which mainly depend on the amount of milk consumption. The article discusses congenital lactase deficiency and familial lactose intolerance. Links between hypolactasia and non-specific abdominal complaints, coronary heart disease and cataract are presented. The decrease in lactase activity in the brush border of jejunal mucosa, associated with diseases of the mucosa or any other condition which damages the enterocytes, is discussed as a cause of secondary hypolactasia. It is shown that adult-type primary hypolactasia and selective lactose malabsorption represent a major problem in the everyday work of general practitioners, particularly in populations where hypolactasia is common. Therefore, the examination and treatment of non-selected patients with vague abdominal complaints is important in primary health care. As the need for calcium in humans is largely met by the intake of milk, the consumption of milk has to be in amounts that are tolerable for the individual.

Abdominal Pain↗

Characterization and tissue distribution of liposomes containing lactose mono-fatty acid derivatives.

In this study we characterized liposomes containing the synthetic glycolipids, lactose mono-fatty acid esters (LFEs), whose structures were the most simple ones compared to the other synthetic glycolipids. Gel filtration chromatography was used to confirm that 78 per cent of lactose monostearic acid ester (LSE) or 85 per cent of lactose monoarachidic acid ester (LAE) existed in the liposomal fraction. The size distribution of liposomes containing LFEs was similar to that of the control liposomes which did not contain LFEs. Liposomes containing LFEs were aggregated by Ricinus communis agglutinin from caster bean (RCA120) while the control liposomes were not, with the agglutinability of the liposomes containing LAE being greater than that of those containing LSE. These findings therefore suggested that the LFEs were incorporated into the liposomal membrane with the galactose residues exposed to the outer aqueous phase. Next, the tissue distribution of liposomes containing LAE at 30 min after intravenous administration was compared to that of the control liposomes in rats. Hepatic uptake was 2-fold higher than that of the control liposomes. These results thus demonstrate that liposomes containing LFEs represent potential drug carriers to the liver.

Animals↗

Water-solid interactions. III. Effect of glass transition temperature, Tg, and processing on tensile strength of compacts of lactose and lactose/polyvinyl pyrrolidone.

The effect of moisture sorption at different relative humidities on the tensile strength and the physical stability of compacts of crystalline and partly amorphous lactose, alone and in binary mixtures with PVP, has been studied. Furthermore, the role of moisture as a plasticizer and its effect on the glass transition temperature, Tg, are related to the compactibiltiy. Samples were conditioned for 2 hr using a climate test chamber at different relative humidities. Moisture sorption was determined, the radial crushing strength for compacts was measured immediately and after storage, and the tensile strength was calculated. The glass transition temperature, Tg, was determined using DSC. The tensile strength of the compacts was found to depend on both the conditioning humidity and the humidity during storage. An increase in humidity to a level at which the glass transition temperature, Tg, fell below the operating temperature, T, resulted in transition from a rigid glassy state to a mobile rubbery state. For compacts of partly amorphous lactose, an increase in the tensile strength was observed during storage of tablets, due to recrystallization of the amorphous regions above Tg. Tablets of mixtures of lactose and PVP exhibit a sharp decrease in tensile strength at humidities above 70% RH, due to the glass-to-rubber transition of PVP.

Calorimetry, Differential Scanning↗

A three-cascaded-enzymes biosensor to determine lactose concentration in raw milk.

The increasing demand for on-line measurement of milk composition directs science and industry to search for practical solutions, and biosensors may be a possibility. The specific objective of this work was to develop an electrochemical biosensor to determine lactose concentration in fresh raw milk. The sensor is based on serial reactions of three enzymes--beta-galactosidase, glucose oxidase, and horseradish peroxidase--immobilized on a glassy carbon electrode. The sequential enzymatic reactions increase the selectivity and sensitivity of the sensor. The sensor requires dilution of the raw milk and the addition of 5-aminosalicylic acid. Lactose concentrations in raw milk measured by the sensor were in good agreement with those measured by a reference laboratory using infrared technology. The results were obtained in milk samples that varied in fat and protein composition. From the results, we conclude that an electrochemical biosensor for determination of lactose concentration in fresh raw milk can be developed, and that the biosensor presented in this study maintained the qualities required for further development into an online sensor in the milking parlor.

Animals↗

Configuration of a bioreactor for milk lactose hydrolysis.

Permeabilized microbial cells can be used as a crude enzyme preparation for industrial applications. Immobilization and process recycling can compensate for the low specific activity of this preparation. For biomass immobilization, the common support is alginate beads; however, its low surface area and the low biomass concentration limit the activity. We here describe a biocatalyst consisting of a paste of permeabilized Kluyveromyces lactis cells gelled with manganese alginate over a semicircular stainless steel screen. A ratio of wet permeabilized biomass to alginate of 50:4 (wt/wt) resulted in a paste with maximum immobilized beta-galactosidase activity and maximum gel biomass retention. The biocatalysts retained activity better when stored in milk at 4 degrees C than in 50% glycerol. The unused biocatalysts stored in milk did not lose activity after 50 d. However, repeated use of the same biocatalyst 40 times resulted in almost 50% loss of activity. A bioreactor design with two different conditions of operation were tested for milk lactose hydrolysis using this biocatalyst. The bioreactor was operated at 40 degrees C as packed bed or with recirculation, similar to a continuous stirred tank reactor. The continuous system with recirculation resulted in 82.9% lactose hydrolysis at a residence time of 285.5 min (flow of 2.0 ml/min), indicating the potential of this system for processing low lactose milk, or even in processing other substrates, using an appropriate biocatalyst.

Alginates↗

Feeding lactose to increase ruminal butyrate and the metabolic status of transition dairy cows.

Twenty-four multiparous Holstein cows (775 +/- 24 kg body weight; 3.4 +/- 0.11 body condition score) were used in a randomized complete block design experiment to determine the impact of increased ruminal butyrate from the fermentation of lactose on metabolism and lactation. Dietary treatments were either a corn-based control diet (CON) or a diet containing lactose at 15.7% of diet dry matter (LAC). Experimental diets were fed from 21 d before expected calving through 21 d in milk (DIM). Blood was sampled at -21, -14, -7, -2, 2, 7, 14, and 21 DIM, rumen fluid at -21, -7, and 7 DIM, and liver tissue via biopsy at 7 and 14 DIM. Pre- and postpartum dry matter intake (DMI) through 28 DIM averaged 12.8 and 17.7 kg/d, respectively, and did not differ between treatments; however, cows fed LAC did not exhibit a prepartum decrease in DMI. Milk yield was unaffected by treatments and averaged 45.7 kg/d during the first 70 DIM. Plasma glucose, insulin, and non-esterified fatty acids were not affected by dietary treatments. Feeding LAC increased the ruminal proportion of butyrate both pre- (11.3 vs. 9.2 +/- 0.45%) and postpartum (13.0 vs. 10.3 +/- 0.67%). Likewise, circulating plasma beta-hydroxybutyrate was increased both pre- (6.1 vs. 4.2 +/- 0.31 mg/dL) and postpartum (14.6 vs. 8.34 +/- 1.7 mg/dL) when feeding LAC compared with CON. Liver lipid content was decreased (8.6. vs. 14.7 +/- 1.5% of wet weight) in cows fed LAC relative to those fed CON, whereas liver glycogen was not affected by dietary treatments. Feeding lactose to transition dairy cows increased the proportion of butyrate in the rumen and beta-hydroxybutyrate in plasma and decreased liver lipid but did not affect lactation performance.

3-Hydroxybutyric Acid↗

Cellular studies of mammary tissue from cows hormonally induced into lactation: lactose and fatty acid synthesis.

Temporal changes in ability of mammary gland to synthesize lactose and fatty acids were identified during the treatment of cows hormonally induced to lactate, and animal differences were compared to subsequent milk production. Hormonal treatment involved 17 beta-estradiol + progesterone on days 1 to 7 and dexamethasone on days 17 to 19. Mammary tissue obtained by biopsy on days 0, 8, 16, and 26 of treatment was examined for biosynthetic capacity by tissue slice incubations. In terms of peak daily milk yield, one cow was very successful (greater than 30 kg), two were intermediate (9 to 10 kg), and one cow was unsuccessful (less than 3 kg). Differences between cows in the capability to synthesize lactose and fatty acids were evident as early as day 8 and were further magnified by day 16. In particular, the tissue from the successful cow was undergoing lactogenesis by day 8 while this was not evident until the day 16 biopsy sample in the less successful cows. In contrast to the other cows, tissues from the unsuccessful animal regressed in its ability to synthesize lactose and fatty acids between day 16 and 26. Relative differences between animals in measurements of metabolic capacity were consistent with subsequent milk production.

Acetates↗

Relationship between N-acetyl-beta-D-glucosaminidase activity and cell count, lactose, chloride, or lactoferrin in cow milk.

Activity of N-acetyl-beta-D-glucosaminidase was measured in foremilk samples collected from cows. A total of 64 samples were collected from these cows, some of which were affected by mastitis. They were examined for N-acetyl-beta-D-glucosaminidase activity, cell count in whole milk, and milk chloride, lactose, and lactoferrin. The correlation coefficient was .72 between activity and cell count, -.80 between activity and lactose, and .88 between activity and chloride. Therefore, the correlations between N-acetyl-beta-D-glucosaminidase activity and milk components, chloride and lactose, were larger than that between N-acetyl-beta-D-glucosaminidase activity and cell count. The correlation coefficient was high (.91) between N-acetyl-beta-D-glucosaminidase and lactoferrin. The N-acetyl-beta-D-glucosaminidase activity in cow's milk has potential for diagnosis of mastitis.

Acetylglucosaminidase↗

Mammary function during the nonlactating period: enzyme, lactose, protein concentrations, and pH of mammary secretions.

Composition of the aqueous phase of mammary secretions during the nonlactating and postpartum periods was determined in nine cows. Protein concentrations increased until several days before parturition and then declined precipitously. Lactose declined rapidly in early involution, remained low during the middle of the nonlactating period, and increased rapidly prepartum. The pH of secretions followed an inverse pattern to lactose and was negatively correlated with lactose during the nonlactating period but not the postpartum period. Peroxidase activity initially increased in secretions in early involution, then declined until parturition when peroxidase activity again increased. Activities of the glycosidic enzymes N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and alpha-mannosidase increased through the nonlactating period until 2 to 3 wk prepartum, from which time all three enzyme activities declined through the postpartum period. The magnitude of increase in the glycosidases was not the same; peak activity of N-acetyl-beta-D-glucosaminidase increased 20-fold over the activity at d 1 of involution, whereas beta-glucuronidase and alpha-mannosidase increased 4 to 5-fold over the same period.

Acetylglucosaminidase↗

Effect of fat and lactose supplementation on digestion in dairy cows. 1. Nonlipid components.

Seven cows, of which five were fitted with rumen and duodenal cannulae, alternately received "milk" diet with 10% fat and 13% lactose, and control diet with 2% fat and no lactose. Both diets were 60% hay. Organic matter and crude fiber digestibilities were not different between milk diet (73.4 and 68.1%) and control diet (74.1 and 70.5%). The quantity of organic matter degraded in the rumen (percent of intake) was higher with control diet (51%) than with milk diet (44%). Ratio of duodenal nonammonia nitrogen to nitrogen intake was higher with milk diet. Both diets gave the same rumen pH. The milk diet increased butyrate and minor volatile fatty acids and decreased acetate proportions. The milk diet increased plasma beta-hydroxybutyrate and decreased plasma acetate. These differences were significant only after feeding. Changes in the characteristics of digestion with milk diet were related more to lactose than to fat. No decrease in fiber digestion was seen with the milk diet despite its high fat content.

Animals↗