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PubMed2006

Glial cell line-derived neurotrophic factor-mediated enteric neuronal survival involves glycogen synthase kinase-3beta phosphorylation and coupling with 14-3-3.

Glial cell line-derived neurotrophic factor (GDNF) promotes the growth and survival of enteric neurons, but the mechanisms involved are poorly understood. GDNF is known to promote the survival of enteric neurons through activation of the PI3-Kinase/Akt signaling pathway. We investigated the role of glycogen synthase kinase-3beta (GSK-3beta) in enteric neuronal survival, and the ability of GDNF to regulate the activity of GSK-3beta using primary rat embryonic enteric neurons. GDNF, through activation of the PI3-kinase pathway enhanced the phosphorylation of GSK-3beta at its N-terminal serine-9 residue, and promoted the association of GSK-3beta with 14-3-3. Transfection of a constitutively active S9A-GSK-3beta mutant prevented the survival effects of GDNF, whereas a dominant negative GSK-3beta construct prevented GDNF withdrawal-induced cell death. Increased GSK-3beta activity was associated with an increase in tau phosphorylation. Thus, GDNF promotes enteric neuronal survival by modulating GSK-3beta and its downstream target tau. Inhibitors of GSK-3beta activity may have therapeutic potential in improving enteric neuronal survival.

14-3-3 Proteins↗
PubMed2004

Effects of L-arginine-enriched total enteral nutrition on body weight gain, tumor growth, and in vivo concentrations of blood and tissue metabolites in rats inoculated with Walker tumor in the kidney.

OBJECTIVE: We evaluated the effects of l-arginine-enriched total enteral nutrition (LATEN) on tumor-free and right kidney tumor-bearing rats through the determination of in vivo concentrations of metabolites to better understand intermediary metabolism in this model. METHODS: Rats were individually housed in wire cages within a controlled environment (25 degrees C and 50% relative humidity) and exposed to a 12-h light-and-dark cycle. Rats comprised the following groups: tumor-free on enteral nutrition plus l-amino acid (n = 8); tumor-free on enteral nutrition plus l-arginine (n = 8); tumor bearing on enteral nutrition plus l-amino acids (n = 8); and tumor bearing on enteral nutrition plus l-arginine (n = 8). Rats had their right kidneys inoculated with saline or tumor cells and were subjected to laparotomy or gastrostomy on day 1 and received chow diet for the next 2 days. Gastrostomy with enteral nutrition was performed on days 3 to 9. On day 9, body weight gain, tumor growth as volume, in vivo blood (microM/mL), and tissue (microM/g) metabolite concentrations were determined. The Mann-Whitney U test was used to test significance. RESULTS: LATEN in tumor-free rats decreased liver (0.25 +/- 0.03 versus 0.13 +/- 0.03 micromol/g, P < 0.05) and right kidney (0.13 +/- 0.1 versus 0.04 +/- 0.00 micromol/g, P < 0.05) ketone body concentrations. LATEN in tumor-bearing rats decreased blood pyruvate (0.17 +/- 0.01 versus 0.10 +/- 0.008 microM/mL, P < 0.005), lactate (5.2 +/- 0.3 versus 2.9 +/- 0.28 microM/mL, P < 0.01), and glucose (6.4 +/- 0.8 versus 3.7 +/- 0.5 microM/mL, P < 0.05). Glucose concentrations decreased in liver (13.9 +/- 2.0 versus 4.89 +/- 0.6 microM/g, P < 0.005) and tumor (3.5 +/- 0.8 versus 1.41 +/- 0.3 microM/g, P < 0.05). There were no changes in body weight gain (21 +/- 2.0 versus 30.3 +/- 3.6 g) or tumor growth (1.53 +/- 0.1 versus 1.26 +/- 0.01 cm(3)). CONCLUSIONS: LATEN decreased ketone body concentrations in liver and kidney in tumor-free rats, possibly due to lower ketogenesis and decreased kidney uptake. In tumor-bearing rats, LATEN decreased lacticemia and glycemia and pyruvate blood concentrations. LATEN also reduced liver and tumor glucose concentrations in tumor-bearing animals. The possibility of LATEN-induced insulin and insulin-like growth factor-1 liberation signaling these changes is discussed.

Animals↗
PubMed2004

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

AIM: To review the incidence, timing, and outcome of infectious enteritis after intestinal transplantation (IT). METHOD: A retrospective review of all patients undergoing IT at a single institution between 1991 and 2003 was analyze with standard statistical tools. RESULTS: Among 33 IT recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of infectious enteritis. The recipient demographics were 77% men and median age 2.6 years. Infections were diagnosed at a median of 76 days (32 to 1800) after IT. There were 14 viral (CMV one, rotavirus eight, adenovirus four, EBV one, three bacterial (Clostridium difficile), and three other infections (Giardia lamblia one, cryptosporidium two). Complete resolution was achieved in 17 (94%) infectious after appropriate antimicrobial or conservative therapy. Interestingly, there were six rejection episodes following infectious enteritis. Grafts were lost to rejection after rotaviral enteritis (n = 1) and adenoviral enteritis misdiagnosed as rejection (n = 1). Patient and graft survival were not adversely affected by infections. CONCLUSIONS: Infectious enteritis occurs frequently after IT. Viral agents are the cause in two-thirds of cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection by histopathology can be difficult.

Adult↗
PubMed1997

Early postoperative enteral feeding improves whole body protein kinetics in upper gastrointestinal cancer patients.

BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at increased risk for malnutrition, as well as postoperative morbidity and mortality. As data clearly documenting the benefit of early postoperative enteral feeding in upper GI cancer patients as compared with no feeding are sparse, we examined the protein kinetic effects of early enteral feeding and compared it with standard postoperative care (ie, intravenous fluid). METHODS: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding (FEED, n = 12) starting on postoperative day (POD) 1 via a jejunostomy tube or intravenous fluid (IVF, n = 17). On POD 5, all patients underwent resting energy expenditure determination and a protein metabolic study using the isotope 14C-leucine to determine whole body (WB, micromol leu/kg/min) protein kinetics. RESULTS: Respiratory quotient and insulin (microU/mL) levels were significantly increased in patients receiving enteral feeding (0.85 +/- 0.02, 19.8 +/- 4.5 versus 0.78 +/- 0.02, 9.3 +/- 0.8, FEED versus IVF, P < 0.05). Free fatty acids (meq/dL) were significantly lower in FEED group (0.36 +/- 0.04) as compared with IVF group (0.85 +/- 0.07, P < 0.0001). While there were no significant differences in WB protein oxidation (0.10 +/- 0.01 versus 0.10 +/- 0.02) or synthesis (0.81 +/- 0.09 versus 0.68 +/- 0.08, IVF versus FEED), WB protein catabolism was significantly less (0.91 +/- 0.10 versus 0.37 +/- 0.09, P = 0.002), and WB protein net balance was converted to positive in FEED group (-0.10 +/- 0.01 versus 0.30 +/- 0.03, IVF versus FEED, P < 0.001). CONCLUSIONS: Early enteral feeding decreases fat oxidation and whole body protein catabolism while improving net nitrogen balance. By significantly improving protein metabolism, enteral feeding may decrease postoperative morbidity and mortality in upper GI cancer patients.

Aged↗
PubMed1998

Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes.

BACKGROUND/PURPOSE: Neonates meeting criteria for extracorporeal membrane oxygenation (ECMO) often suffer from variable periods of hypoxia. During ECMO, starvation of the gut is common practice in many centres as splanchnic ischemia results in loss of intestinal integrity, which in turn predisposes for bacterial translocation and sepsis and eventually necrotizing enterocolitis (NEC) and multiorgan failure. However, minimal enteral feeding is thought to be of benefit in the critically ill. Data on intestinal integrity in newborns on ECMO and the effects of enteral nutrition are not available. This study prospectively evaluates the changes in small intestinal integrity in 16 neonatal ECMO patients. METHODS: With 2-day intervals, excretion percentages of lactulose/L-rhamnose (nonmediated diffusion), D-xylose (passive), and 3-O-methyl-D-glucose (active carrier-mediated transport) were measured by gas-liquid chromatography in a 4-hour urine sample. After obtaining baseline data in nine patients, enteral feeding was started in the next seven patients between the third and the ninth day of ECMO. RESULTS: Thirteen patients had increased lactulose/L-rhamnose ratios (>0.05) consistent with increased intestinal permeability. In three patients the lactulose/L-rhamnose ratios were within the normal range. D-xylose excretion percentages were normal (or slightly increased) in 11 patients consistent with normal (or increased) passive carrier-mediated transport. 3-O-methyl-D-glucose excretion percentages were decreased (<10%) in all but one patient, consistent with decreased active carrier-mediated transport. After introduction of enteral nutrition no significant changes of these parameters were seen. CONCLUSIONS: The authors conclude that intestinal integrity is compromised in neonates on ECMO and that introduction of enteral nutrition does not result in further deterioration. This conclusion does not support the practice of withholding enteral nutrition in critically ill newborns supported by ECMO.

3-O-Methylglucose↗
PubMed2004

Neurotrophin-3 in the development of the enteric nervous system.

To date, the only neurotrophin that has been shown to influence the development of the enteric nervous system (ENS) is neurotrophin-3 (NT-3). NT-3 plays an essential role in the development of both the neural-crest-derived peripheral nervous system and the central nervous system (i.e., Chalazonitis, 1996, Mol. Neurobiol., 12: 39-53; Sieber-Blum, 1999, Neurotrophins and the Neural Crest, CRC Press, Boca Raton). This review integrates data obtained from our laboratory and from our collaboration with other investigators that demonstrate a late-acting role for NT-3 in the development of enteric neurons in vitro and in vivo. Studies of the biological actions of NT-3 on enteric neuronal precursors in vitro demonstrate that NT-3 acts directly on the precursor cells and that it also acts in combination with other neurotrophic factors such as glial cell line-derived neurotrophic factor and a ciliary neurotrophic factor-like molecule, to promote the survival and differentiation of enteric neurons and glia. Importantly, bone morphogenetic protein-2 (BMP-2) and BMP-4, members of the transforming growth factor-beta (TGF-beta) superfamily, regulate the onset of action of NT-3 during fetal gut development. Analyzes performed on mice deficient in the genes encoding NT-3 or its transducing tyrosine kinase receptor, TrkC, and conversely on transgenic mice that overexpress NT-3 substantiate a physiological role for NT-3 in the development and maintenance of a subset of enteric neurons. There is loss of neurons in both the myenteric and submucosal plexuses of mice lacking NT-3/TrkC signaling and selective hyperplasia in the myenteric plexus of mice overexpressing NT-3. Analyzes performed on transgenic mice that overexpress noggin, a specific BMP-4 antagonist, show significant decreases in the density of TrkC-expressing neurons but significant increase in overall neuronal density of both plexuses. Conversely, overexpression of BMP-4 is sufficient to produce, an increase in the proportion of TrkC-expressing neurons in both plexuses. Overall, our data point to a regulatory role of BMP-4 in the responses of subsets of myenteric and submucosal neurons to NT-3. NT-3 is required for the differentiation, maintenance and proper physiological function of late-developing enteric neurons that are important for the control of gut peristalsis.

Animals↗
PubMed1994

Comparison of enteral feeding and total parenteral nutrition after liver transplantation.

Total parenteral nutrition is used for nutritional support in patients undergoing orthotopic liver transplantation but is associated with complications. We compared the efficacy and tolerability of early enteral feeding with total parenteral nutrition after liver transplantation. 24 patients were studied: 14 received enteral feeding and 10 total parenteral nutrition. A double-lumen enteral tube was used to deliver the feed directly into the jejunum with the second lumen of the tube being used for gastric aspiration. Enteral feeding was started post-operatively within 18 h, was well-tolerated, and of comparable efficacy to total parenteral nutrition. The median number of days for patients to start eating (4) and to achieve 70% of estimated requirements orally (5) did not differ significantly between the two groups. Mid-arm circumference, triceps skinfold thickness, and biceps skinfold thickness were, by comparison with pre-operative values, maintained on the tenth postoperative day in both groups. Early postoperative absorptive capacity, as assessed by a combined carbohydrate test, was reduced significantly in both groups but insufficiently to be of nutritional concern. Intestinal mucosal integrity, as assessed by an intestinal permeability test, was maintained throughout. We conclude that the practical aspects of enteral feeding after liver transplantation are surmountable and that enteral feeding is as effective at maintaining nutritional status as total parenteral nutrition, and has potential benefits in terms of reduced complications and costs.

3-O-Methylglucose↗
PubMed1998

Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma.

BACKGROUND: Infections are an important cause of morbidity and mortality in patients with multiple trauma. Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections. METHODS: Patients with multiple trauma with an expected survival of more than 48 h, and who had an Injury Severity Score of 20 or more, were randomly allocated glutamine supplemented enteral nutrition or a balanced, isonitrogenous, isocaloric enteral-feeding regimen along with usual care. Each patient was assessed every 8 h for infection, the primary endpoint. Data were analysed both per protocol, which included enteral feeding for at least 5 days, and by intention to treat. FINDINGS: 72 patients were enrolled and 60 received enteral feeding (29 glutamine-supplemented) for at least 5 days. Five (17%) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 (45%) of 31 patients in the control group (p<0.02). Bacteraemia occurred in two (7%) patients in glutamine group and 13 (42%) in the control group (p<0.005). One patient in the glutamine group had sepsis compared with eight (26%) patients in the control group (p<0.02). INTERPRETATION: There was a low frequency of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality.

Adult↗
PubMed2003

Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression.

PURPOSE: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition. METHODS AND MATERIALS: Sixteen patients with radiation enteritis that occurred after radiotherapy for pelvic malignancies and 6 with histologically normal bowel entered the study. Immunohistochemistry, Western blot analysis, and real-time reverse transcriptase-polymerase chain reaction were performed to study CTGF expression, along with other known markers of radiation fibrosis: the pro-fibrogenic cytokine transforming growth factor (TGF)-beta1 and phenotypic markers of the fibroblast differentiation the alpha-sm actin (A), vimentin (V), and desmin (D). Finally, the collagen accumulation was measured by Sirius red staining and colorimetric assay. RESULTS: Radiation enteritis was characterized by increased collagen content within the intestinal wall. CTGF immunoreactivity, protein, and mRNA level were increased in radiation enteritis compared with the healthy bowel. On the contrary, no increase of the TGF-beta1 mRNA level was observed in radiation enteritis compared with healthy bowel, and the level of TGF-beta protein was slightly increased in radiation enteritis. A co-localization of CTGF immunoreactivity and collagen deposition was found in the extracellular matrix and subtypes of activated mesenchymal cells with a fibroblast phenotype (V(+)/D(-)/A(-)) and myofibroblast phenotype (V(+)/D(-/+)/A(+)). CONCLUSION: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis.

Adult↗
PubMedDate not supplied

Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery.

OBJECTIVE: Early enteral nutrition with fiber-containing solutions plus Lactobacillus may reduce bacterial translocation and minimize the incidence of infections after surgery. METHODS: In a prospective, randomized trial in three groups (n = 30/group) of patients after major abdominal surgery, we compared our previous regimen with parenteral nutrition or fiber-free enteral nutrition (group A) with enteral fiber-containing nutrition with living Lactobacillus (group B) and heat-killed Lactobacillus (group C). The main endpoint was the development of bacterial infection. Other analyzed parameters were the durations of antibiotic therapy and hospital stay, non-infectious complications, side effects of the nutrition, and onset of bowel movement. Routine parameters, nutritional parameters, and cellular immune status in the blood were measured preoperatively and on 1, 5, and 10 d postoperatively. RESULTS: The incidence of infections was significantly lower (P = 0.01) in groups B and C with enteral nutrition containing fibers (10% each) than in group A (30%). Patients in group B received antibiotics for a significantly shorter time (P = 0.04) than did the patients in groups A and C. The length of hospital stay and the incidence of non-infectious complications did not differ significantly. Fibers and lactobacilli were well tolerated. There were no general benefits of living Lactobacillus as opposed to heat-killed Lactobacillus in the entire study population, but benefits were observed in the patients with gastric and pancreas resections, although no statistical analysis was done due to their small numbers. CONCLUSIONS: Early enteral nutrition with fiber-containing solutions reduced the rate of postoperative infections in comparison with parenteral nutrition and fiber-free enteral formula. Addition of living Lactobacillus seemed to increase the benefits in patients with gastric and pancreatic resections.

Aged↗
PubMed1997

Inulin as the soluble fiber in liquid enteral nutrition.

Dietary fibers are a necessary part of human nutrition. Inulin is a fermentable fiber that improves bacterial ecology in the large bowel and is also a relevant substrate for short-chain fatty acid (SCFA) production. The aim of the present study was to evaluate the clinical effect of inulin, added as dietary fiber into the fiber-free enteral nutrition (Nutrition Standard). Inulin (30-35 g/d) was administered for 1 wk to a group of patients requiring the nutritional support of a liquid enteral diet. A significant increase in flatulence, an indication of rapid bacterial fermentation, was apparent during its infusion in comparison with a fiber-free enteral diet. Moreover, an increment in ability to dehydrate the cecal stream (stool consistency) was apparent in nearly half of patients. No changes in SCFA concentration in stool and indican output in urine were apparent after 1 wk of inulin administration. Intestinal permeability (51Cr-EDTA absorption test) was not influenced by either enteral nutrition or inulin and enteral nutrition administration. Because of good tolerance inulin seems to be a potential source of dietary fiber in clinical enteral nutrition.

Acetates↗
PubMed1988

Kinetics of release from enteric-coated tablets.

Controlled and localized release of drugs in the intestine can be achieved by enteric coating. The design of enteric-coated tablets has so far remained empirical, in part because of the lack of a quantitative description of the drug release kinetics. In this paper, a mathematical model is presented that describes the dissolution of the polymer coating and release kinetics of weakly acidic drugs from enteric-coated tablets in buffered media. This model can also be used to predict the time of onset of core disintegration. The model assumes that the release rate is limited by diffusion, and furthermore, all the reactions are considered as reversible and instantaneous. Dissolution and reaction are assumed to take place in the polymer layer and a hypothetical stagnant liquid film adjacent to the polymer layer (the classical film theory approach). The dissolution of the enteric coating is found to depend on the intrinsic solubilities and pKa's of the drug and polymer and the medium properties. The release rate of the drug is found to depend on the intrinsic solubilities and pKa's of drug and polymer, the medium properties, i.e., pH and buffer capacity, and a mass transfer coefficient. Explicit relationships between the release rates and all these factors are derived. Successful prediction of experimental data indicates that the model provides an adequate description of release from enteric coated tablets. Limitations of the model and its potential application to the design of appropriate in vitro testing conditions and to the formulation of enteric coated tablets are also discussed.

Buffers↗
PubMed1998

Intestinal absorption of nutrients is not influenced by soy fiber and does not differ between oligomeric and polymeric enteral diets.

Enteric feeding is often associated with diarrhea. To avoid this side effect, isoosmotic and fiber-supplemented enteral diets are recommended. The aims of this study were to determine whether supplementing enteral diets with soy fiber influences nutrient absorption and whether in enteric feeding absorption of nutrients and water fluxes differ between hyperosmotic oligomeric and isoosmotic polymeric diets. In mini pigs intestinal absorption and water fluxes were measured by perfusing a 150-cm length of jejunum. Six noncommercial iso- and hyperosmotic oligomeric and polymeric diets and six commercial polymeric diets, either fiber-free or supplemented with soy fiber, were used. Pancreatic enzymes were infused concomitantly with the polymeric diets. The absorption of nutrients and energy did not differ between oligomeric and polymeric diets. Oligomeric diets of high energy density produced a pronounced secretion of water. Despite lower initial osmolality, polymeric diets produced a similar secretion of water due to rapid pancreatic hydrolysis. Supplementing diets with largely insoluble soy fiber increased viscosity only between 4.6 and 14.5 mPa x sec. Soy fiber did not influence absorption of nutrients and energy and had also no effects on luminal transit and flow rate. The lack of effects was not due to dilution of chyme by intestinal secretion of water because no differences existed between isoosmotic and hyperosmotic oligomeric diets. In conclusion, supplementing enteral diets with soy fiber does not impair the absorption of nutrients. Enteric feeding with isoosmotic polymeric diets provides no advantage compared with hyperosmotic oligomeric diets with respect to absorption of nutrients and secretion of water.

Animals↗
PubMed1989

Small-intestinal function during enteral feeding and starvation in man.

1. Small-intestinal absorption and permeability were measured in nine patients with malnutrition who were receiving liquid enteral nutrition after different periods of starvation, in five patients receiving enteral nutrition without starvation, in six healthy subjects after starvation for 36 h and in two obese subjects starved for 11 days. 2. Absorption, expressed by the plasma 60 min D-xylose level and the plasma 60 min D-xylose/3-O-methyl-D-glucose ratio, was greatly decreased (P less than 0.001) in the nine patients receiving enteral feeding after starvation, whereas permeability, denoted by the 5 h urinary lactulose/rhamnose ratio, was increased (P less than 0.05). 3. The five patients receiving enteral feeds without prior starvation had normal intestinal absorption and permeability. 4. Starvation of the healthy subjects reduced absorption (P less than 0.05) and this was detectable at 36 h. Permeability, however, was not increased by 36 h starvation. Starvation of the obese subjects also progressively reduced absorption, and this was reversed with refeeding. 5. Changes in intestinal function during enteral feeding are similar to those seen in intestinal diseases. They develop rapidly and are not caused or reversed by liquid enteral feeds. Starvation, before beginning feeding, may explain some of the changes found.

Adult↗
PubMed1999

Protection of human gastric mucosa against aspirin-enteric coating or dose reduction?

BACKGROUND: Aspirin is widely used for cardiovascular prophylaxis. AIM: To compare the effectiveness of two widely-used strategies-dose reduction and enteric coating-for the minimization of gastric mucosal injury or toxicity. METHODS: Twelve healthy volunteers were studied. On four separate occasions each received, under blinded conditions, five daily doses of plain aspirin 300 mg, plain aspirin 75 mg, enteric-coated aspirin 300 mg or placebo. Ex vivo prostaglandin E2 synthesis was stimulated by the vortex mixing of gastric mucosal biopsies in Tris saline and measured by radioimmunoassay. Mucosal injury was quantified both by counting erosions and with a visual analogue scale. RESULTS: All three preparations reduced prostaglandin E2 synthesis by day five, by (median) 84% for plain aspirin 300 mg, by 80% for enteric coated aspirin 300 mg and by 63% for plain aspirin 75 mg. There was little mucosal injury prior to the start of each dose and period and no significant change with placebo. Plain aspirin caused a dose-dependent mucosal injury, with two (median, IQR 0-7) gastric erosions after five days of plain aspirin 75 mg, and 18 (2-26) after five days of plain aspirin 300 mg. With enteric-coated aspirin 300 mg there were 0 (0-1) gastric erosions (P = 0.003 compared to plain aspirin 300 mg P = 0.11, compared to plain aspirin 75 mg). CONCLUSION: Enteric coated aspirin reduces acute gastric mucosal injury to placebo levels, despite its inhibition of prostaglandin synthesis. Enteric coating is an appropriate strategy for the prevention of gastric mucosal damage induced by low-dose aspirin, which warrants systematic clinical evaluation.

Adult↗
PubMed2002

Effects of enteric-coated, low-dose aspirin on parameters of platelet function.

BACKGROUND: Aspirin is widely used as an anti-thrombotic drug; however, it has been suggested that enteric-coated formulations of aspirin may be less bioavailable and less effective as anti-thrombotic agents. AIM: To assess the effect of a formulation of enteric-coated, low-dose (81 mg) aspirin on serum generated thromboxane B2 and platelet aggregation in healthy subjects. METHODS: Twenty-four subjects participated in a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study. Twelve subjects in each of two groups received a daily oral dose of enteric-coated aspirin (81 mg) or matching placebo for 7 days. Serum thromboxane B2 and platelet aggregation (using 1 mm arachidonic acid and 1 microg/mL collagen as agonists) were measured 1-3 days prior to day 1, on day 1 (prior to therapy) and 4 h after the last dose on day 7. RESULTS: After seven daily doses of enteric-coated aspirin, the mean percentage inhibition from baseline of ex vivo generated serum thromboxane B2 was 97.4%, compared with a 7.8% increase after placebo treatment. The mean percentage inhibition of arachidonic acid- and collagen-induced platelet aggregation was 97.9% and 70.9%, respectively, following enteric-coated aspirin, compared with - 1.0% and 2.7%, respectively, after placebo. CONCLUSIONS: The anti-platelet effects of multiple, daily, low-dose aspirin (as assessed by inhibition of serum thromboxane B2 and platelet aggregation) are not adversely affected by enteric coating.

Adolescent↗
PubMed2001

Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma.

BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.

Administration, Oral↗
PubMed2001

Cytomegalovirus enteritis among hematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) is a cause of enteritis associated with hematopoietic stem cell transplantation (HSCT), but the natural history is rarely studied and hence poorly understood. CMV infection at this end-organ site is notably less frequent than is pneumonitis. To evaluate the spectrum of CMV enteritis after HSCT, we reviewed the database spanning 11.5 years of 2240 University of Minnesota transplantation patients for cases of gastrointestinal CMV. We identified 46 case-patients. The incidence of CMV enteritis at 2 years following HSCT averaged 2% over the 11.5-year study interval. The median time to diagnosis of CMV enteritis after HSCT was 91 days (range, 17-527 days). The methods used in diagnosis included histopathology (58%) and virology (61%). Viremia was detected in two thirds of patients with CMV prior to the diagnosis of enteritis. Most treatment regimens included ganciclovir. The overall survival rate was 35% at 2 years following the onset of enteritis.

Adolescent↗