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Disaccharidase and lysosomal enzyme activities in amniotic fluid, intestinal mucosa and meconium. Correlation between morphology and disaccharidase activities in human fetal small intestine.

Brush border membrane bound disaccharidases (sucrase and maltase) and lysosomal enzyme (alpha-glucosidase, beta-D-fucosidase and N-acetyl-beta-glucosaminidase) activities awere studied in amniotic fluid (AF). The above enzymes except N-acetyl-beta-glucosaminidase showed a decrease in activity with gestational age beginning at about the 19th week. The activities of sucrase and maltase correlate with the morphological maturation of fetal intestinal mucosa. The distribution of disaccharidases and lysosomal alpha-glucosidase in AF and intestinal mucosa showed different patterns suggesting that these enzymes originate in diverse fetal tissues.

Acetylglucosaminidase

Disaccharidase deficiency in infants with cow's milk protein intolerance. Response to treatment.

7 infants, aged 5 weeks to 11 months, with clinically documented intolerance to cow's milk protein, chronic diarrhea, and failure to thrive, underwent small intestinal (peroal, suction) biopsy before and after withdrawal of milk proteins. Mucosal specimens were examined by light microscopy and assayed for disaccharidase activities. In all patients, moderate to severe mucosal changes were presented, associated with marked inflammation of lamina propria and damages to the brushborder. Disaccharidase activities (lactase, sucrase, maltase and palatinase) were markedly depressed in all. Follow-up biopsies were obtained in 6 infants, after 3-5 months on a milk-protein-free diet. At the time of the second biopsy, the disaccharidase activities had risen significantly and histologic improvement had occurred in each instance. In infancy, intestinal mucosal lesions due to intolerance to cow's milk protein are histologically indistinguishable from those seen in gluten-sensitive enteropathy and are associated with marked secondary disaccharidase deficiencies. Following therapy, the activity of the disaccharidases become normal or near normal prior to the complete morphologic recovery of the small intestinal mucosa.

Animals

Parallel between circadian rhythms of intestinal disaccharidases and foot intake of rats under constant lighting conditions.

The relationship between the circadian rhythmic changes in the disaccharidase activities of the small intestine and the circadian feeding pattern was investigated in rats kept in the dark or in the light continuously for 4 weeks. Rats kept continuously in the light and fed ad libitum showed no rhythmic change in food intake or disaccharidase activities, but when they were only fed during a restricted time of day, their disaccharidase activities showed rhythmic changes with higher activities around the feeding time. In contrast, rats kept continuously in the dark and fed ad libitum showed circadian variations in food intake and disaccharidase activities essentially similar to rats kept under the normal light-dark lighting schedule. These findings show that the rhythm of disaccharidase activities is synchronized with the feeding rhythm, not with the lighting rhythm.

Animals

Increased disaccharidase activity in human diabetics.

Disaccharidase activity has been shown to be increased in human diabetics. Diabetics controlled on diet therapy showed no change in disaccharidase activity while two diabetics controlled on insulin or insulin-producing drug, glibenclamide, showed a fall in disaccharidase values toward normal. Possible causes for the increased disaccharidase activity in diabetes are discussed.

Adult

Induction of chick embryonic intestinal disaccharidases by hydrocortisone and sucrose in the organ culture system.

The effect of hydrocortisone and sucrose on the development of chick intestinal disaccharidases was studied using the organ culture system. When intestines of 15- and 17-day-old embryos were cultured in the presence of hydrocortisone, there was significant enhancement of disaccharidases activity compared with the control. However, there was no effect in the 20-day embryonic intestines. On the other hand, the disaccharidase activity of cultured intestines from 20-day-old chick embryos were significantly stimulated by the addition of sucrose. The observed increase in disaccharidase activity induced by the administration of hydrocortisone in 17-day-old embryos in vitro was sensitive to actinomycin D and cycloheximide. The activity induced by the administration of sucrose in 20-day-old embryos in vitro was sensitive to cycloheximide but insensitive to actinomycin D.

Animals

[Rat intestinal disaccharidases during cyclophosphamide treatment (author's transl)].

Rat intestinal disaccharidase activities were investigated during treatment with different doses of 2-[bis-(2-chlorethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (cyclophosphamide). In all experiments, disaccharidase activities decreased--although not too drastically--within 2--3 days after beginning treatment. Loss of activity was not reversed during the period of experimentation. Contrary to previous investigations, cyclophosphamide did not exert direct toxic effects on intestinal disaccharidases. Decrease of intestinal disaccharidase activities can be interpreted to be due to cyclophosphamide effects on the proliferation cycle of epithelial crypt cells resulting in a decreased number of full-function cells.

Animals

Developmental patterns of intestinal disaccharidases in human amniotic fluid.

A close relationship exists between relative disaccharidase activities (maltase, sucrase, trehalase, palatinase, turanase, lactase, and cellobiase) in amniotic fluid and corresponding jejunal mucosa of five human fetuses (16 to 21 weeks of gestation) suggesting that these intestinal enzymes pass into amniotic fluid. Serial determination of disaccharidase activities in amniotic fluid samples collected between 10 and 42 weeks of gestation showed maximum mean activities at 14 to 17 weeks of gestation and a rapid drop to less than 12 per cent maximum values at about 22 weeks. This drop is probably caused by combined effects of decreased extrusion rate of intestinal disaccharidases and increased reabsorption of the enzymes in swallowed amniotic fluid with fetal development.

Amniotic Fluid

Disaccharidase activities in small intestinal mucosa in patients with cystic fibrosis.

The disaccharidase activities in small intestinal biopsies were related to the morphology of the mucosa and the ages of 63 patients with cystic fibrosis and 177 healthy control subjects of Caucasian origin. In patients with CF and in the healthy control subjects under 5 years of age with normal intestinal mucosa, no low lactase activity was found. In those patients with CF who were over 5 years of age, one group had high and one group had low lactase activity, as occurs in healthy Caucasian control subjects of the same age. This finding supports the view that in patients with CF, lactase deficiency is not related to the disease entity. In patients with or without CF who had the same degree of mucosal atrophy, the decrease of disaccharidase activities followed the same pattern, indicating that enzyme activities are affected to the same extent by the damage of the mucosa. In patients with CF with pancreatic insufficiency, the disaccharidase activities were significantly (P less than 0.001) higher when compared to those in control subjects of the same age and ethnic group, although the increase was not uniform in all patients with cystic fibrosis.

Atrophy

Influence of fosfomycin on intestinal disaccharidases in rats.

The influence of orally administered fosfomycin on intestinal disaccharidases in albino rats was studied. The enzymes were evaluated in a homogenate of the intestinal mucosa, using the method of SOLS and DE LA FUENTE which is based on the colored reaction of the glucose that is freed by the disaccharidases from disaccharides with a glucose-oxidase-peroxidase reagent and a chromogen (Glucostat). The results obtained in animals treated with a daily dose of 1 g/kg fosfomycin for 6 consecutive days are compared with the corresponding results of animals that received 1 ml/day of saline solution during the same period. Our conclusion was that fosfomycin has no effect on the intestinal disaccharidases in rats.

Administration, Oral

Effect of various sugars on the induction of chick embryonic intestinal disaccharidases in the organ culture system.

Disaccharidases activities in 20-day-old chick embryonic intestine were induced by the addition of sucrose, maltose, fructose and glucose to the culture medium. However, maltitol, which cannot be digested by intestinal enzymes, showed no effect on the induction of disaccharidase activity. Kinetic study of the enzymes demonstrated that the maximum velocity (Vmax) and the Michaelis constant (Km) of sucrose induced disaccharidases activities of the explants showed changes similar to those observed in the chick of same developmental stage in vivo. Namely, Vmax values of sucrase and maltase were increased. Km values of sucrase did not change, but that of maltase showed a significant decrease during development.

Animals

Intestinal disaccharidase activities in relation to age, race, and mucosal damage.

Studies were undertaken to determine the relationship of intestinal disaccharidase activity to age and race, and the relationship of mucosal damage to a primary low lactase activity. The first study consisted of data on 399 persons (339 whites, 53 blacks, and 7 American Indians) ages 1 month to 93 years, with normal intestinal histology. Among whites, all 117 children 5 years old or under had high lactase levels, whereas low levels were found only in subjects over 5 years of age. No low lactase levels were identified among the 11 black children 3 years old or under, but in comparison to coetaneous white children, their mean lactase activity was signficantly less. The majority of older blacks had low lactases. In whites and blacks alpha-disaccharidases did not participate in the age-related changes demonstrated with lactase. Of the 7 American Indians, none under 26 months old had low lactase levels, whereas the 4 over 10 years old had low activities. Heterozygotes for sucrase-isomaltase deficiency were identified only among whites. Low lactase levels developed during childhood in all races studied, however, many for unknown reasons maintained their lactose tolerance until adulthood. In the second study of 13 additional children with secondary disaccharidase deficiencies, emergence of a primary low lactase was related to age and race, rather than to mucosal damage. It appears that primary low intestinal lactase levels are absent or rare in whites under 5 and blacks under 3 years of age, and the deficiency is not related to mucosal damage.

Adolescent

Developmental pattern of small intestinal enterokinase and disaccharidase activities in the human fetus.

The concomitant appearance of enterokinase (EK) and trypsin activities in the human intestinal mucosa is indicative of the importance of EK as an activator of trypsinogen and therefore as the key enzyme in protein digestion. Enterokinase can be detected in fetal mucosa from the 26th week of gestation on, paralleling appearance of tryptic activity in meconium. The developmental pattern of EK activity increases with age. Between 26 to 30 weeks of gestation, the EK activity is only 6% and full term babies (40 weeks) 20% of that found in older children. In contrast, lactase studies during development show a lactase activity of only 30% in human fetuses between 26 to 34 weeks of gestation as compared to full term babies. During the same gestational period, sucrase and maltase activities reach 70% of the full term. In addition, the distributional pattern of EK differs from the disaccharidases, showing the highest activity in duodenum and the lowest in ileum, whereas disaccharidases are highest in jejunum with lower activity in duodenum and ileum. Differences in topographical distribution and time of appearance of EK and disaccharidases may be attributed to differences in orgin as well as subcellular localization of these enzymes. It is conceivable that the premature infant, between 26 to 30 weeks of gestation, is better equipped to deal with hydrolysis of alpha-glucosides than of lactose.

Disaccharidases

Adequacy of endoscopic biopsy specimens for disaccharidase assays.

Intestinal mucosa from 40 patients obtained by fiber-endoscopic biopsy was assayed for disaccharidases to determine suitability of this tissue for assay. The combined specimens from each patient provided 4.7-38.7 mg of tissue, adequate in all instances for duplicate determinations of protein, lactase, sucrase, and maltase. Tissue remained for assays of palatinase in 39 instances, trehalase and cellobiase in 37, and alkaline phosphatase in 22 cases. Twenty-four subjects had normal lactose tolerance tests and normal sucrase/lactase ratios. Thirteen patients with abnormal oral lactose tolerance tests were identified as having a primary low lactase activity on the basis of elevated sucrase/lactase ratios. This ratio was most helpful in making the diagnosis of a primary low lactase, since the mucosal specimens were not obtained from comparable areas. Tissue from three subjects with an abnormally low maltase was unsuitable for diagnosis. Endoscopic biopsy of mucosa appears to be satisfactory for disaccharidase assays in most instances.

Adult

Intestinal disaccharidases in the rat: effects of pregnancy and diabetes.

Specific and total activities of lactase, sucrase and maltase were determined in the mucosa scraped from the proximal, mid and distal intestinal segments of nonpregnant and pregnant normal control and diabetic rats. In control rats, pregnancy was accompanied by a significant rise in total lactase activity of the entire intestinal mucosa. This was due to increased specific activity of the enzyme in the mid segment of the pregnant rats. In both nonpregnant and pregnant rats, diabetes was associated with marked enhancement of intestinal growth and with elevated specific and total activities of the three mucosal disaccharidases. In the pregnant diabetic rats, specific and total activities of the disaccharidases were about 30% lower than corresponding values in the nonpregnant diabetic rats.

Animals

Ligation or external fistulation of the common bile duct in the rat. II. Intestinal disaccharidase activities.

72 h after ligation or external fistulation of the common duct the activities of maltase, sucrase and lactase in the homogenate of the small intestinal mucosa of the rat were determined. The experiments were performed in connexion with intestinal perfusion studies, and the disaccharidase activities were measured in unperfused intestinal segments as well as in intestinal loops which had previously been perfused with a sucrose-containing solution. After bile duct ligation, the sucrase and maltase activities in a previously perfused intestinal loop were not different from those in sham-operated animals, the lactase activity was diminished. In a nonperfused segment, the sucrase activity was greater, the maltase activity was unchanged, and the lactase activity was lower than in control animals. After bile duct fistulation, the sucrase, maltase and lactase activities in a perfused segment were lower than in sham-operated rats. In a nonperfused loop, the sucrase activity was greater, the maltase activity was unchanged, and the lactase activity was lower then in the corresponding control group. These data suggest that bile is a factor which influences the total mucosal disaccharidase activities, and, probably, the intracellular enzyme distribution.

Animals

Effect of the pesticides phosalone and lindane on the activity of some dipeptidases and disaccharidases in rat intestinal mucosa.

The intestinal dipeptidase and disaccharidase activities were investigated in 120 male albino rats of the Wistar strain after administration of 21 mumol.kg-1 body weight phosalone, 14.8 mumol.kg-1 body weight lindane and 10.5 mumol.kg-1 body weight phosalone combined with 7.4 mumol.kg-1 body weight lindane. The dipeptidase activity under the effect of these comparatively low doses of pesticides reveals slightly to moderate changes. The activity of intestinal disaccharidases after a 90-day phosalone and lindane treatment is markedly decreased, particularly that of sucrase. The mechanism of these changes remains unknown.

Animals

Disaccharidase activity in the intestinal tissue of broilers infected with coccidia.

Maltase and sucrase activities were measured in the intestine of broilers inoculated with sporulated coccidial oocysts. Infection with Eimeria acervulina, E. maxima, E. necatrix, and E. brunetti decreased disaccharidase activity in the intestinal region in which maximum infection was found compared with the activity in uninoculated controls. The maximum reduction occurred on the first or second day of patency followed by a rapid recovery in activity. Disaccharidase activity was inversely proportional to the inoculum dose.

Animals

Symptomatic intestinal disaccharidase deficiency in alcoholics.

Lactase and sucrase activities were measured in jejunal biopsies from a group of alcoholic and nonalcoholic men of similar nutritional status, consisting of American blacks, and whites of northern European origin. When measured withing 10 days of alcohol withdrawal, sucrase activity was decreased by 33% in the alcoholics. Lactase activity was less than 1 U per g in 100% of the black and 20% of the white alcholics as compared to 50% of the black and none of the white control subjects. Lactase activity was virtually absent in 45% of the black alcoholics. A second jejunal biopsy after an additional 2-week period of alcohol abstinenece exhibited significant secondary increases in the activities of both disaccharidases. Oral administration of lactose (1 g per kg of body weight) resulted in significantly lower blood glucose concentration and higher incidence of adverse effects in alcoholics, mainly among the blacks. Although data from larger populations are needed to confirm our observations, these findings suggest that chronic alcohol ingestion decreases intestinal disaccharidase activities even in the absence of overt malnutrition. The decrease in enzyme activity produced by alcohol is associated with increased morbidity after lactose administration.

Adult