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Assimilation of lactitol, an 'unabsorbed' disaccharide in the normal human colon.

The fate of orally ingested lactitol, a non-absorbed sugar, was measured in six healthy human subjects by following the three routes of disposal of universally 14C-labelled sugar. Lactitol was given as a 20 g daily dose to six healthy volunteers for 14 days and on the seventh day, 10 muCi of L-[U-14C]-lactitol was given with the unlabelled sugar and excretion of the 14C in breath, urine and faeces was followed. The peak of 14CO2 excretion occurred at six hours and total 14CO2 accounted for 62.9 (5.0)% of isotope given, whilst 6.5 (3.6)% and 2.0 (0.3)% of the label were recovered from faeces and urine respectively. These data suggest that lactitol is extensively metabolised in the human colon and that a significant proportion of the bacterial metabolites are available for colonic absorption. Calculation revealed that 54.5% of the theoretical energy content of this compound was utilised by the subjects. It is suggested that this sugar, and other soluble 'non-absorbed' sugars (lactulose, sorbitol, mannitol), may undergo a similar pattern of colonic metabolism and can be considered as reduced calorie compounds.

Adult↗

Digestion of tripeptides and disaccharides: relationship with brush border hydrolases.

Intestinal digestion of two tripeptides (leucyl-glycyl-glycine, prolyl-glycyl-glycine) and two disacchrarides (sucrose, maltose) was examined in the hamster by intestinal perfusion in vivo and hydrolysis of the substrates by microvillus membranes. Perfusion studies showed that luminal disappearance rates of leucyl-glycl-glycine were significantly higher than prolyl-glycyl-glycine (P less than o.001), sucrose (P less than 0.001), and maltose (P less than 0.005). Hydrolytic products of leucyl-glycyl-glycine, sucrose, and maltose were detected in the gut lumen in appreciable concentrations, whereas negligible concentrations of prolyl-glycyl-glycine products were present. Leucyl-glycyl-glycine hydrolysis in microvillus membranes was markedly higher than prolyl-glycyl-glycine (P less than 0.001), which was predominant in the cytoplasmic fraction. These results indicate that leucyl-glycyl-glycine, like sucrose and maltose, is hydrolyzed at the membrane. With some tripeptides, i.e., leucyl-glycyl-glycine, digestion occurs at the microvillus membrane with subsequent transport of hydrolytic products into the intestinal epithelial cell. Other tripeptides, i.e., prolyl-glycyl-glycine, may cross the membrane and undergo intracellular hydrolysis by cytoplasmic peptidases.

Alkaline Phosphatase↗

Inhibition of disaccharide digestion in rat intestine by the alpha-glucosidase inhibitor acarbose (BAY g 5421).

Administration of the alpha-glucosidase inhibitor, acarbose (BAY g 5421), to rats together with a sucrose load results in a marked retardation of sucrose digestion. The carbohydrate content of the small intestine is dose dependently increased; the time needed for the absorption is doubled. In the large intestine significant amounts of carbohydrate can be found only after administration of high doses of acarbose (2-4 mg/kg p.o.). In oral sucrose and maltose loading tests the blood glucose increase is dose dependently reduced by acarbose (ED50, 1 or 12 mg/kg, respectively). In perfused jejunal loops of rats, acarbose inhibits the absorption of sucrose (4 g/l) and maltose (1 and 2 g/l), the IC50 values being 3.2, 36, and 57 micrograms/ml, respectively. The data indicate that acarbose effectively inhibits sucrose digestion. It is 10-20 times less effective with maltose as a substrate. Slight malabsorption is induced by acarbose only in doses higher than the ED50.

Acarbose↗

Effect of diet upon intestinal disaccharidases and disaccharide absorption.

The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal. Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats.

Adrenalectomy↗

Synthesis and biological activities of analogs of a lipid A biosynthetic precursor: 1-O-phosphonooxyethyl-4'-O-phosphono-disaccharides with (R)-3-hydroxytetradecanoyl or tetradecanoyl groups at positions 2, 3, 2' and 3'.

Two novel analogs of a biosynthetic precursor of lipid A (2) were synthesized. The one analog (3) has acyl groups identical to those of 2, and the other (4) has tetradecanoyl groups in place of the (R)-3-hydroxytetradecanoyl groups of 2. Both 3 and 4 possess an alpha-glycosidically-bound phosphonooxyethyl group in place of the alpha-glycosyl phosphate group of 2. Compounds 3 and 4 exhibited definite antitumor activity against Meth A fibrosarcoma and low toxicity in rabbits, as the original compound 2 does. The replacement of the hydroxytetradecanoyl groups with tetradecanoyl groups barely affected the antitumor activity, but slightly enhanced the toxicity in rabbits.

Animals↗

Isolation and identification of 2-phenylethyl disaccharide glycosides and mono glycosides from rose flowers, and their potential role in scent formation.

2-Phenylethyl 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranoside (1), and its 6-O-beta-D-xylopyraranosyl-beta-D-glucopyranoside (2) were identified in the flowers of Rosa damascena Mill. harvested at the full bloom stage. 2-Phenylethyl beta-D-glucopyranoside (3) and its beta-D-galactopyranoside (4) together with 1 and 2 were also found in the flower buds harvested 44 hrs before the opening stage. Their potential role in scent formation is discussed.

Gas Chromatography-Mass Spectrometry↗

Comparative effects of osmotic and secretory diarrhoea on brush-border disaccharide hydrolases in rat.

The effects of diarrhoea on the activities of brush-border disaccharidases namely lactase (EC 3.2.1.23), maltase (EC 3.2.1.20) and sucrase (EC 3.2.1.48) of Sprague-Dawley strain albino rats were induced in the rats with mannitol while secretory diarrhoea was induced with Salmonella typhimurium after an initial treatment with streptomycin. The activities of the enzymes were significantly reduced by diarrhoea. The extent of reduction in enzyme activity varied in the different segment of the small intestine in all the groups. The jejuno-ileal region had more changes in enzyme activities than in the duodenum. Higher activity levels were observed for maltase than for lactase. In the osmotic diarrhoea model, lactase activity was significantly lowered (P < 0.05) in the experimental group from day 5 to 10. Maltase activity on the other hand was significantly lowered (P < 0.001) at the peak of diarrhoea. Sucrase activity was also lowered significantly (P < 0.025) in the experimental animals within the first 10 days of diarrhoeal induction. In the secretory diarrhoea model, lactase activity was similar in all the experimental groups except for the streptomycin-salmonella-treated groups and control (P < 0.05). Higher lactase activity levels were observed in the secretory diarrhoea model compared to level in the osmotic diarrhoea model. Maltase activity levels were also lowered significantly (P < 0.05) in the experimental animals. Streptomycin had no effect on the activity of maltase.

Animals↗

Effect of two non-steroidal anti-inflammatory drugs, aspirin and nimesulide on the D-glucose transport and disaccharide hydrolases in the intestinal brush border membrane.

The present study was designed to evaluate the effect of two commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) with varying cyclooxygenase-2 (Cox-2) selectivities on enzyme activities and transport properties of rat intestinal brush border membrane (BBM). Female Wistar rats were divided into three different groups, viz: Group I (Control), Group II (aspirin-treated, 50 mg/kg) and Group III (nimesulide-treated, 10 mg/kg). At the end of 28 days of treatment, membranes were isolated from different intestinal segments of all the groups and changes in BBM-associated enzymes such as sucrase, lactase, maltase, alkaline phosphatase and the transport properties of D-glucose and its kinetics were studied. The results indicated a significant decrease in the activities of enzymes and transport of glucose in both the treatment groups as compared to the controls. Changes in Michaelis-Menten parameters, viz:--Km and Vmax and the thermodynamic parameters T(c) and E(a) were also seen which are indicative of adverse effects of these two NSAIDs in the intestinal membrane such as the membrane integrity.

Animals↗

Nephrotoxicity of dactimicin, a novel pseudo-disaccharide aminoglycoside possessing the N-formimidoyl group, compared with that of astromicin, amikacin and other aminoglycoside antibiotics in animals.

The nephrotoxicity of dactimicin, the first aminoglycoside possessing the N-formimidoyl group, was compared with that of astromicin and, in part, amikacin, ribostamycin, kanamycin and gentamicin as reference aminoglycoside antibiotics. When a dose of 200 mg/kg was given intramuscularly to dehydrated mice, dactimicin caused no change of BUN and serum creatinine, while reference aminoglycosides caused significant elevations of the parameters. In the urinalysis of rats at doses of 40 and 80 mg/kg per day for 11 days or 21 days, dactimicin caused little changes in urinary parameters except for nucleated cells and NAG. In a detailed comparison between dactimicin and astromicin at 20, 40, 80, 120, 180 and 270 mg/kg for 11 or 30 days, dactimicin induced fewer changes in nucleated cells and NAG at high dosages. While dactimicin and astromicin caused no significant changes in BUN and serum creatinine at dosages of 20-270 mg/kg, histological observations using light and electron microscopes revealed that dactimicin consistently showed fewer lesions on the proximal tubular cells than those of astromicin for all dosages. When injected intramuscularly in rats, dactimicin and astromicin showed a similar distribution in the blood and main organs, except for the kidney, in which renal accumulation of dactimicin was about 60% of that of astromicin. Dactimicin slowly degraded in vitro and in vivo to give fortimicin B as a main product which was accumulated in the kidney. Through comparative studies with astromicin, it was disclosed that the N-formimidoyl group of dactimicin did not increase but decreased the nephrotoxicity, probably by suppressing reabsorption of dactimicin via proximal tubular cells.

Acetylglucosamine↗