Supplementation of barley-based diets with ß-glucanase for pigs: energy and amino acid digestibility response.

An experiment was conducted to determine the effect of graded levels of ß-glucanase supplementation to barley (Hordeum vulgare)-based diets on the digestibility of DM, GE, N, and AA for growing-finishing pigs. Eight pigs (initial BW: 53.3 ± 3.2 kg) were each fitted with a simple T-cannula at the distal ileum and allotted to a replicated 4 × 4 Latin square design with 4 diets and 4 periods in each square. Diets were based on a barley-soybean (Glycine max) meal (SBM) basal diet (BD) containing 199 g CP and 3286 kcal DE per kilogram of diet. Treatments consisted of the BD and the BD supplemented with 10,000 (10K), 20,000 (20K), or 30,000 (30K) units of ß-glucanase per kilogram at the expense of corn (Zea mays). Chromic oxide (0.5%) was included as an indigestible marker. Each experimental period consisted of 4 d of adaptation, 1 d of feces collection, and 2 d of ileal digesta collection. Apparent total tract digestibility (ATTD) of DM ranged from 81.0 to 82.5% and was not affected by ß-glucanase supplementation. In the BD, ATTD of GE and N was 83.1 and 83.3%, respectively, and was not different in the BD supplemented with up to 30K units of ß-glucanase per kilogram at 83.4 and 83%, respectively. Increasing levels of ß-glucanase supplementation to the barley-SBM-based diet did not affect the ATTD of any criteria measured. Apparent ileal digestibility (AID) for DM, GE, and N ranged from 60.6, 65.4, and 70.8% (10K) to 66.4, 71.0, and 74.9% (20K), respectively. For indispensable AA, AID for Lys (79.9%) and Met (78.1%) was lowest in the BD supplemented with 20K and 10K units of ß-glucanase per kilogram, respectively, and was not different from the digestibility of Lys and Met in the diet with added 30K units of ß-glucanase per kilogram at 80.8 and 80.4%, respectively. There were neither significant linear nor quadratic effects of ß-glucanase supplementation to barley-SBM-based diets on the AID of DM, GE, N, and AA. In conclusion, ß-glucanase supplementation did not affect apparent ileal and total tract nutrient digestibility in grow-finish pigs fed a barley-SBM-based diet.

Growth performance and nutrient digestibilities in nursery pigs receiving varying doses of xylanase and ß-glucanase blend in pelleted wheat- and barley-based diets.

In 2 experiments, dose response efficacy of a xylanase and ß-glucanase blend (XB) on growth performance and ileal nutrient digestibility was investigated in nursery pigs fed pelleted wheat (Triticum aestivum)- and barley (Hordeum vulgare)-based diets. A basal diet (meeting NRC [1998] specifications for 6 to 30 kg BW, except for 5% lower DE) was supplemented with XB to give 4 diets (0, 50, 100, and 200 g/t). The xylanase and ß-glucanase blend was formulated to contain guaranteed activity of 12,200 and 1520 units/g, respectively. In Exp.1, 192 nursery pigs (initial BW of 6.5 kg) were randomly assigned to 4 diets to give 12 pens (4 pigs/pen) per diet to study growth performance for 42 d. In Exp. 2, apparent ileal digestibility (AID) of energy and AA was evaluated in 4 individually housed ileal-cannulated barrows (21 kg BW) according to a 4 × 4 Latin square design. In Exp. 1, XB linearly and quadratically increased (P < 0.05) G:F compared with control. Adding 200 g/t increased overall G:F by 20% compared with control. In Exp. 2, XB linearly increased (P < 0.05) AID of DM, CP, energy, and AA. In conclusion, supplemental xylanase and ß-glucanase in nursery pelleted wheat- and barley-based diets deficient in DE increased energy and nutrient use, resulting in better G:F. In conclusion, an enzyme product containing a combination of xylanase and ß-glucanase allowed young pigs to derive more nutrients and energy in a wheat- and barley-based diet deficient in energy.

Supplementing transglucosidase with a high-fiber diet for prevention of postprandial hyperglycemia in streptozotocin-induced diabetic dogs.

Indigestible oligosaccharides have been shown to normalize blood glucose and insulin concentration thereby promoting good health and preventing diseases, such as diabetes. Transglucosidase (TG, alpha-glucosidase, enzyme code (EC) 3.2.1.20) is an enzyme capable of converting starch to oligosaccharides, such as iso-malto-oligosaccharides from maltose, via the action of amylase. The aim of this study was to evaluate whether oral administration of TG with maltose or dextrin is capable of reducing post-prandial serum glucose concentration in experimentally streptozotocin (STZ)-induced diabetic dogs fed on a high-fiber diet. Five healthy and five STZ-induced diabetic dogs were employed in this study. TG supplementation with dextrin or maltose had no detrimental effect in healthy dogs. In fact, TG and dextrin exhibited a flatlined serum glucose pattern, while reducing mean post-prandial serum insulin and glucose concentration as compared to control diet alone. When TG supplementation was tested in STZ-induced diabetic dogs under the context of a high fiber diet, a 13.8% and 23.9% reduction in mean glucose concentration for TG with maltose and dextrin, respectively was observed. Moreover, TG with dextrin resulted in a 13% lower mean post-prandial glucose concentration than TG with maltose, suggesting that dextrin may be a more efficient substrate than maltose when used at the same concentration (1 g/kg). Our results indicate that TG supplementation with diet can lead to lower postprandial glucose levels versus diet alone. However, the efficacy of TG supplementation may depend on the type of diet it is supplemented with. As such, TG administration may be useful for preventing the progression of diabetes mellitus and in its management in dogs.

Effect of antibiotic pretreatment on glycoside/glycosidase-based colonic drug delivery.

The effect of antibiotic pretreatment on the intestinal distribution and hydrolysis of the prodrug prednisolone-beta-D-glucoside was studied in rats. A combination of neomycin, lincomycin, and metronidazole was administered twice daily by gastric intubation for three days to young adult male rats. On the fourth day, prednisolone-beta-D-glucoside was administered intragastrically. The distribution of prodrug and drug in the intestinal contents was significantly altered by the antibiotic treatment. In comparison with untreated rats, stomach to cecum transit time appeared to be reduced, and more prodrug was hydrolyzed in the small intestine. In addition, an appreciable amount of the dose was retained longer in the small intestine of treated animals. The total recovery of prodrug and drug was unaltered by the pretreatment. Possible explanations for the observed results are presented.

Targeting of synthetically glycosylated human placental glucocerebrosidase.

Human placental beta-glucocerebrosidase modified by covalent attachment of N2-(N2, N6-bis [3-(alpha-D-mannopyranosylthio)propionyl]-L- lysyl)-N6-[3-(alpha-D-mannopyranosylthio)propionyl]-L-lysine was administered to rats by intravenous injection. Comparison of enzyme distribution in isolated liver cell populations indicates an increase in enzyme-specific activity of 18-fold in nonparenchymal cells and only 1.5-fold to hepatocytes compared to uninjected control animals. This macrophage-specific delivery of an active lysosomal enzyme has potential for application in enzyme replacement trials.

Treatment of recurrent aphthous ulcers with Aureomycin mouth rinse or Zendium dentifrice.

Clinical trials with a cross-over double-blind technique were undertaken to test chlortetracycline (Aureomycin) and the enzyme-containing dentifrice Zendium with regard to therapeutic effects on recurrent aphthous ulcers. Aureomycin was found to reduce the number of ulcers and diminish pain when compared with placebo. When groups of patients treated with Zendium and placebo dentifrice, respectively, were compared, no statistically significant difference could be demonstrated. However, when the pH value of Zendium was stepwise changed from 5.9 to 6.8, an increased fraction of patients reported complete relief from pain and ulcer(s) during the trial periods.

Lectin-specific targeting of beta-glucocerebrosidase to different liver cells via glycosylated liposomes.

Galactosylated and mannosylated liposomes were more efficient in transporting liposome-entrapped beta-glucocerebrosidase to liver compared to nonglycosylated liposomes. The enzyme entrapped to glycoside-bearing liposomes was found to be cleared at a much faster rate than that entrapped in liposomes having no sugar on their surface. Asialoorosomucoid and hydrolyzed mannan were found to inhibit both the clearance and the uptake of galactosylated and mannosylated liposomes, respectively, supporting involvement of lectin-sugar interaction. Further studies on the uptake of glucocerebrosidase by isolated liver cells revealed that the enzyme entrapped in mannosylated liposomes has much higher affinity for nonparenchymal cells whereas the assimilation of the entrapped enzyme into hepatocytes is clearly favored for liposomes having galactose on their surface.

Insulin: carrier potential for enzyme and drug therapy.

Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.

Incorporation of glucocerebrosidase into Gaucher's disease monocytes in vitro.

Several carriers were evaluated for use in the delivery of exogenous glucocerebrosidase to monocytes from Gaucher's disease patients. Only gamma globulin-coated, resealed erythrocytes proved to be an effective vehicle for enzyme delivery. Glucocerebrosidase added in this manner normalized intracellular enzyme levels for at least 18 hr. In this model system for the study of enzyme replacement therapy, soluble enzyme, enzyme in uncoated resealed erythrocytes, and enzyme incorporated into liposomes were ineffective.

Treatment of Gaucher's disease with liposome-entrapped glucocerebroside: beta-glucosidase.

An adult with Gaucher's disease was injected with liposomes containing human glucocerebroside: beta-glucosidase. After 13 months of treatment the lower border of the right hepatic lobe and moved up 3 cm, and the left lobe had shrunk. Reduction in the size of the liver was associated with relief of pressure symptoms in the left lower abdomen. Scans obtained after the injection of radiolabelled liposomes suggested improvement in function of the reticuloendothelial system.

[Tumour hyperacidulation through intravenous glucose infusion enhanced by amygdalin and beta-glucosidase application (author's transl)]. / Verstärkung der mit Glukoseinfusion erzielbaren Tumorübersäuerung in vivo durch Amygdalin und beta-Glukosidase

Tumour peracidity in otherwise moderately hyperacidulated tumours or tumour regions of DS carcinosarcoma-bearing Wistar rats attained by glucose infusion was substantially increased by simultaneous infusion of amygdalin and intratumoral i.m. or i.v. application of beta-glucosidase. Here the pH value of healthy tissue, measured at the sceletal muscle, remained unchanged. By means of the said process, tumour hyperacidulation has been raised to a level of deltapH =0.97; attaining a pH difference between tumourous and normal tissue of up to deltapH = 1.6. In one case, the slope of pH reduction in the tumour increased to 870%. Moreover, combined administration of glucose, amygdalin and beta-glucosidase evoked a significant cancerostatic effect hypogenesis, tumour regression) being comparable with the action of an Ifosfamid dosage of 150 mg-kg-1. However, i.m. and i.v. application of beta-glucosidase under narcosis results in an overall process that still remains somewhat too toxic. Hence optimizing studies are intended with the particular aim to further improve the comparability of this process.