Induced Growth and Precocious Maturation of the Digestive System in Suckling Rats and Pigs after Exposure to Red Kidney Bean Lectin

The timing of the postnatal development of the gastrointestinal (GI) tract in mammals is influenced by dietary and hormonal factors. It was hypothesized that accelerated GI cell turnover during maturation would result in a precoucios conversion to more mature digestive functions. Thus, it was investigated if red kidney bean lectin, phytohaemagglutinin (PHA) - a potent gut mitogen in adult rats - could accelerate the growth and maturation of the digestive system in suckling rats and piglets. Suckling rats and piglets were dosed with PHA either via enteral or parenteral administration for up to three consecutive days prior to natural weaning. The binding of PHA to the GI tract and extra-intestinal organs, GI organ growth, intestinal morphology and proliferation, disaccharidase activity pattern, and macromolecular absorption capacity were studied, as well as the pancreatic enzyme contents. Changes in these parameters were considered to be markers for maturation or development towards an adult-like GI function. Furthermore, the plasma levels of corticosterone and insulin (rat), and cholecystokinin (pig), were investigated. It was concluded that preweaning enteral exposure to PHA in suckling rats accelerated growth and induced precocious functional maturation of the GI tract and the pancreas. Similar results were also achieved when a crude PHA preparation was fed to suckling piglets. PHA treatment induced irreversible changes of the gut resembling those occurring at natural weaning, such as a reduced macromolecular absorption (intestinal closure), altered disaccharidase expression towards an adult-like activity pattern, and enhanced pancreas function. The ability of PHA to induce GI functional maturation in rats was age-dependent. Also, a direct binding and interaction of PHA with the GI epithelium was found to be a prerequisite to induce functional maturation, since parenteral administration had little effect. Shortly after administration, the binding of PHA to the intestinal epithelium temporarily caused mucosal disarrangement and functional impediment of the GI tract, probably resulting in the release of hormones and inflammatory cytokines. During a later phase, this led to a stimulatory response of the GI tract, as seen by an increase in crypt cell proliferation, gut growth, and the emergence of more adult-like enterocytes. Taking into consideration the temporal differences between rats and piglets with respect to natural maturational events, it was suggested that PHA exerted gut maturing effects in piglets and probably also in other mammals. Thus, these findings might lead to a better understanding of the role of the diet in GI functional maturation

Enterally but not parenterally administered Phaseolus vulgaris lectin induces growth and precocious maturation of the gut in suckling rats

Background: The lectin, phytohemagglutinin (PHA) has been shown to induce growth and functional maturation of the gastrointestinal (GI) tract in suckling rats. Objectives: To investigate the effect of the administration route, and whether enteral exposure to PHA was necessary to induce functional maturation. Methods: Fourteen-day-old rats were daily administered PHA via orogastric feeding (0.05 mg PHA/g BW) or via subcutaneous injection (0.05 or 0.005 mg PHA/g BW) for 3 days, while the controls received saline orogastrically. At 17 days of age, organ weight, intestinal and pancreatic function, and plasma corticosterone levels were analyzed. Moreover, 14-days old pups receiving a single dose of PHA, enterally or parenterally, were sacrificed after 12 h and examined for organ PHA binding using immunohistochemistry. Results: Enteral PHA exposure resulted in PHA binding in the epithelial lining of the small intestine, increased gastrointestinal growth, reduced intestinal macromolecular absorption, altered the disaccharidase expression towards an adult-like pattern, and increased the pancreatic protein and trypsin contents. In contrast, parenteral PHA exposure (high dose) resulted in PHA-binding in extra-intestinal organs, increased liver and spleen weight, and decreased thymus weight. Moreover, the intestinal maltase activity increased moderately, and the transfer of BSA to blood plasma was partially reduced. Both PHA treatments led to elevated plasma corticosterone levels. Conclusion: These results demonstrated that enteral exposure to PHA was necessary to induce the precocious maturation of the GI tract and the pancreas, while parenteral administration affects the extra-intestinal organs. Furthermore, the enteral effects were probably not mediated via a corticosteroid dependent pathway

Precocious gut maturation and immune cell expansion by single dose feeding the lectin phytohaemagglutinin to suckling rats.

The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 mug/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 mug/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 mug/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21-28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process

Age-related Effects of the Probiotic Bacterium Lactobacillus plantarum 299v on Gastrointestinal Function in Suckling Rats

The effect of a probiotic bacterium on gut function was studied in neonatal animals by using a model with suckling rats. Lactobacillus plantarum 299v (Lp299v) or saline (controls) was fed (3.0 x 10(6) CFU/g b.wt per day) for one week to rats aged either 3, 7 or 14 days, after which bacterial colonization, gut growth, and functional parameters were analyzed. In rats fed with Lp299v from 3 to 10 days of age, an increase in ceacal lactobacilli was correlated with reduced intestinal macromolecular permeability and increased mucosal protein compared to age-matched controls. Pups treated from 7 to 14 days of age showed a decrease in pancreas weight and protein content, whereas pups treated from 14 to 21 days of age showed little effect of the Lp299v treatment. The results indicated that the bacterial exposure affected the gut function, where the effects were age-related and the youngest rats appeared most sensitive

Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the gastrointestinal tract of suckling rats

Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14 d old, were fed a single dose of PHA (0.05 mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3 d after treatment. Initially, at 1-24 h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3 d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut

Fracture strength of all-ceramic (Y-TZP) three- and four-unit fixed dental prostheses with different connector design and production history.

Brotthållfasthet hos helkeramiska (Y-TZP) tre och fyra-leds broskelett: betydelsen av connectordesign och produktionshistorik. Yttriumoxidstabiliserad zirkoniumdioxid (Y-TZP) används frekvent inom tandvården. Helkeramiska broar måste dimensioneras och designas med hänsyn till bromaterialets specifika materialegenskaper. Särskilt kritisk är utformningen av connectorområdet. Rekommendationerna avseende connectordimensionerna för anteriora 3-4 ledsbroar av Y-TZP varierar mellan 2 till 4 mm i vertikal riktning och mellan 2 till 4 mm i horisontell riktning. Utöver dimensioneringen måste hänsyn tas till connectorns utformning då connectorns gingivala radie har en stor betydelse för konstruktionens totala brotthållfasthet. Vid belastning utsätts broar med liten gingival radie för högre spänningskoncentrationer i connectorområdet jämfört med broar med större gingival radie. Den gingivala utformningen av connectorer kan ha en ännu större betydelse för brotthållfastheten om antalet hängande led utökas från ett till två. Syftet med föreliggande studie var att undersöka hur förinställningarna avseende design av connectorer i två olika CAD/CAM system påverkar brotthållfastheten, hur den gingivala radiens storlek påverkar brotthållfasthet och frakturmönster samt undersöka hur brospannets längd, dvs antalet hängande led påverkar brotthållfastheten hos 3- och 4-ledsbroar av Y-TZP. Två olika CAD/CAM system användes för att framställa totalt 32 broskelett av Y-TZP, varav 16 st 3-ledsbroar med ett hängande led och 16 st 4-ledsbroar med två hängande led. Broskeletten delades in i 4 grupper baserat på antal led och utformning av connectorernas gingivala radie. För framställa grupperna 3Z:1, 4Z:1 användes en mekanisk scanner, Procera®Forte och för grupperna 3Z:2, 4Z:2 användes en optisk scanner, NobelProcera® Scanner. Samtliga broar utsattes för värmebehandling (simulerad porslinspåbränning), termocykling (5°C – 55°C / 5000 cykler), cyklisk förbelastning (30 – 300N / 10 000 cykler) och belastades slutligen till brott. Samtliga broar fakturerade i connectorområdet och efter okulär besiktning kunde man konstatera att samtliga frakturer startat i connectorns gingivala del. Medelvärdena för last vid brott var i grupp 3Z:1 734 N, grupp 4Z:1 405 N, grupp 3Z:2 910 N samt i grupp 4Z:2 520 N. Med reservation för de begränsningar som en In-vitro studie innebär dras följande Slutsatser: Förinställningarna i de olika CAD/CAM systemen hade avgörande betydelse för brotthållfastheten. Eftersom connectorområdet utgör den svagaste punkten i en helkeramisk brokonstruktion är det avgörande att CAD/CAM systemens standardinställningar tillåter en konstruktionsdesign som uppfyller de mekaniska och kliniska kraven. Storleken på den gingivala connectorradien har avgörande betydelse både för brotthållfastheten och för frakturmönster. Genom att öka antalet hängande led från ett till två hängande led minskar brokonstruktionens brotthållfasthet med ca 50 %.Aims: To investigate how different default settings for connector design of two different CAD/CAM systems, i.e. to compare how different radii of curvature in the embrasure area of the connector affect the fracture strength and the fracture mode of 3-unit and 4-unit all-ceramic FDPs made from Y-TZP and to investigate how the number of pontics affect the fracture strength of Y-TZP. Material and methods: 32 all-ceramic three (3Z) and four (4Z) -unit, Y-TZP, FDP cores were made and divided in 4 groups, with 8 FDP in each group. The groups 3Z:1 and 4Z:1 were generated with a mechanical scanner, Procera® Forte and the FDPs in group 3Z:2 and 4Z:2 were generated with an optical scanner, NobelProcera® Scanner. The connector dimensions were set to 3 mm x 3 mm and core was set to 0.7 mm. The design of radius of the gingival and occlusal embrasures in the connector areas was set according to default settings and the manufacturer’s recommendations. All the FDP cores were subjected to heat treatment, thermocycled for 5,000 cycles, preloaded for 10,000 cycles to simulate ageing and finally loaded to fracture. Results: Regarding connector design a significant difference was found between group 3Z:1 and 3Z:2 (P<0.05), and group 4Z:1 (50% of the FDPs fractured during preloading 30-300N) and 4Z:2 (P<0.05). An extra pontic decreased the fracture strength up to 45%. Conclusions: The default settings of the two different CAD/CAM systems had a great impact on the fracture strength. It is important that a CAD/CAM system is equipped with possibilities to design a connector that fulfils the clinical demands of mechanical function and longevity. The most crucial factor for the load-bearing capacity is the design of the radius of the gingival embrasures. Increasing the number of pontics from three to four decreases the load-bearing capacity nearly twice

Influence of core design, production technique, and material selection on fracture behavior of yttria-stabilized tetragonal zirconia polycrystal fixed dental prostheses produced using different multilayer techniques : split-file, over-pressing, and manually built-up veneers

Aim: To investigate and compare the fracture strength and fracture mode in eleven groups of currently, the most commonly used multilayer three-unit all-ceramic yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) fixed dental prostheses (FDPs) with respect to the choice of core material, veneering material area, manufacturing technique, design of connectors, and radii of curvature of FDP cores. Materials and methods: A total of 110 three-unit Y-TZP FDP cores with one intermediate pontic were made. The FDP cores in groups 1–7 were made with a split-file design, veneered with manually built-up porcelain, computer-aided design-on veneers, and over-pressed veneers. Groups 8–11 consisted of FDPs with a state-of-the-art design, veneered with manually built-up porcelain. All the FDP cores were subjected to simulated aging and finally loaded to fracture. Results: There was a significant difference (P<0.05) between the core designs, but not between the different types of Y-TZP materials. The split-file designs with VITABLOCS® (1,806±165 N) and e.max® ZirPress (1,854±115 N) and the state-of-the-art design with VITA VM® 9 (1,849±150 N) demonstrated the highest mean fracture values. Conclusion: The shape of a split-file designed all-ceramic reconstruction calls for a different dimension protocol, compared to traditionally shaped ones, as the split-file design leads to sharp approximal indentations acting as fractural impressions, thus decreasing the overall strength. The design of a framework is a crucial factor for the load bearing capacity of an all-ceramic FDP. The state-of-the-art design is preferable since the split-file designed cores call for a cross-sectional connector area at least 42% larger, to have the same load bearing capacity as the state-of-the-art designed cores. All veneering materials and techniques tested in the study, split-file, over-press, built-up porcelains, and glass–ceramics are, with a great safety margin, sufficient for clinical use both anteriorly and posteriorly. Analysis of the fracture pattern shows differences between the milled veneers and over-pressed or built-up veneers, where the milled ones show numerically more veneer cracks and the other groups only show complete connector fractures

Induced Growth and Maturation of the Gastrointestinal Tract After Phaseolus vulgaris Lectin Exposure in Suckling Rats

Objectives: In mammals, the postnatal development of the gastrointestinal tract is characterized by vast structural and functional changes. Using a suckling rat model, we investigated whether red kidney bean lectin, phytohemagglutinin (PHA), a potent gut mitogen in adult rats, can accelerate the growth and maturation of the gastrointestinal tract. Methods: At either 10 or 14 days of age, suckling rats were daily gavage fed with PHA (0.05 mg/g body weight) or saline for 3 days. At 1 or 3 days after this treatment, gastrointestinal organ growth, intestinal morphology, disaccharidase pattern, macromolecular absorption capacity, and pancreatic enzyme contents were studied. Results: After PHA exposure, increased small intestinal growth and number of crypt cells were observed, whereas the proportion of enterocytes with supranuclear vacuoles in the distal intestine was decreased. The macromolecular absorption of the markers bovine immunoglobulin (Ig)G and bovine serum albumin and plasma levels of maternal IgG decreased, and intestinal disaccharidases switched toward an adult-like pattern. The pancreas weight and pancreatic protein and trypsin contents increased. These changes were partly reversible when the PHA treatment began at 10 days of age, but they persisted when the treatment began at 14 days of age. Conclusions: PHA induced enhanced growth and precocious functional maturation of the gastrointestinal tract in suckling rats. The effects persisted if the PHA treatment started at 14 days of age, but not before, suggesting an age dependent mechanism. These findings may lead to a better understanding of gastrointestinal maturation and constitute a basis for the treatment of mammals having an immature gut