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PubMed2001

Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.

The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.

Adult↗

PubMed2004

The gastrointestinal tract "tastes" nutrients: evidence from the intestinal taste aversion paradigm.

To develop and use a behavioral paradigm for assessments of what nutrient properties are detected by intestinal chemoreceptors, we combined features of the "electronic esophagus" preparation (Elizalde G and Sclafani A. Physiol Behav 47: 63-77, 1990) and the conditioned taste aversion protocol (Garcia J and Koelling RA. Psychon Sci 4: 123-124, 1966). In four experiments, separate groups of food-deprived rats with gastric (experiments 1-4) or duodenal (experiment 4) catheters were infused with either carbohydrates (maltodextrin) or fats (corn oil) into their stomachs or small intestines, either while they consumed nonnutritive flavored solutions (experiments 1 and 2) or in the absence of any intake (experiments 3 and 4). For some animals, one of the macronutrient infusions was paired with lithium chloride injections shown to support conventional conditioned aversions. After training, in various oral preference test trials, animals were given opportunities to taste and consume the nonnutritive solutions that had served as oropharyngeal conditioned stimuli as well as the nutrients that had been infused intragastrically, with or without poisoning, but never sampled by mouth. As previously established, preferences for the nonnutritive flavors were enhanced by association with intragastric infusions of macronutrients, with carbohydrates producing the greater preference. On first exposure to the two macronutrients for oral consumption, animals reduced their intake of the nutrient that had been previously poisoned when it was infused into the gastrointestinal tract. These results, along with additional controls, suggest that nutrient tastes detected in the intestines can be recognized centrally based on oropharyngeal gustatory stimulation.

Animals↗

PubMed1970

Pancreozymin bioassay in man based on pancreatic enzyme secretion: potency of specific amino acids and other digestive products.

The ability of products of digestion to stimulate pancreozymin secretion in man was investigated using a bioassay procedure, based on duodenal perfusion, which quantified the total outputs of pancreatic enzymes evoked by intraduodenal stimuli under steady-state conditions. Patterns of response resulting from physiologic intraduodenal concentrations of test material were basal output (with isotonic saline), washout of enzymes (with dextrose, micellar fatty acid, and amino acids), and sustained output of enzymes (with amino acids and micellar fatty acid). The sustained secretion of pancreatic enzymes found during the 2nd hr of perfusion and subsequently was characteristic of pancreozymin-induced secretion. The enzyme output in response to a mixture of essential and nonessential amino acids was significantly higher than that evoked by micellar fatty acid and was comparable with that resulting from the maximally tolerated dose of pancreozymin given by vein. Perfusion with essential amino acids caused enzyme outputs comparable to those induced by perfusion with the original amino acid mixture, whereas perfusion with nonessential amino acids had no effect. When the essential amino acids were tested individually, only phenylalanine, methionine, and valine caused significant increases in pancreatic enzyme output; the effect of tryptophan was indeterminate. However, the pancreatic enzyme output was less in response to these three essential amino acids than to mixtures containing all of them.

Adult↗

PubMed1989

Nonsurgical palliation of jaundice in pancreatic cancer.

The endoscopic approach to biliary drainage came late on the scene; some of the published results reflect early experience with inadequate techniques. Now it is clear that the endoscopic approach is preferable to the percutaneous method. When palliation of jaundice is required (in a patient without impending duodenal obstruction), there is a simple choice between surgical bypass or endoscopic stenting. Stenting is substantially cheaper than surgery--at least for the initial admission. Recovery from stenting is almost immediate, which cannot be said for surgical intervention. Time will tell how far the need for readmission (stent blockage, duodenal obstruction) will erode these advantages. The main factor influencing our decision (stent or surgery), apart from the hope of resection, is the patient's general status, or "operative risk." Unfortunately, there is no accepted risk factor scale or template against which our experiences can be compared. There are no absolutes, only a spectrum of patients who differ according to the tumor load and their general medical condition. A fit patient with a relatively small tumor is best served by surgical intervention. The diagnosis and its unresectable nature can be established beyond doubt, and anastomoses (biliary and gastroduodenal) can be established of such a size that subsequent obstruction is unlikely. The operative mortality rate will be low. Patients with a large tumor load and poor general condition are best served by an endoscopic stent. Between these positions lies a spectrum of patients and plenty of room for discussion and personal opinions. Drainage procedures are unwarranted in patients who are truly terminal. Specialist vested interests have seriously jaundiced the view of many people in this field--and obstructed attempts at consensus. As in the management of patients with gallstone disease, it is important that surgeons, endoscopists, and radiologists work together as teams in the best interests of our patients, present and future.

Cholestasis↗

PubMed1999

Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion.

Major features of pancreatic secretion stimulated by a meal depend on intestinal phase mechanisms. However, an intrajejunal (i.j.) meal infusion is widely used for the treatment of inflammatory pancreatic diseases when the resting of the gland is desired. This study was undertaken to compare the effects of an intragastric (i.g.) and an i.j. complete fluid (Lundh) test meal on pancreatic enzyme secretion. Eight men (mean age, 43 years; range, 31-48) free from pancreatic disease were studied. Pancreatic secretion was measured via a multiple-lumen tube by aspiration of the duodenal juice. After a fasting period, the Lundh test meal was placed in the stomach or the upper jejunum. After the i.g. administration of the test meal, the aspirated duodenal juice was reinfused into the jejunum. The effect of atropine infusion (0.5 microg/kg/h) on the pancreatic enzyme secretion was studied. The pancreatic amylase, trypsin, and lipase outputs were determined. The plasma levels of cholecystokinin (CCK) and of gastrin were measured by bioassay and radioimmunoassay, respectively. The trypsin, amylase, and lipase secretions increased significantly after either an i.g. or an i.j. test meal intake. The trypsin, amylase, and lipase outputs were significantly decreased during the i.j. perfusion as compared with i.g. administration. The gastrin levels increased significantly after i.g., but remained unchanged after i.j. administration. The CCK release attained its maximum 40 and 60 min after the i.g. and i.j. test meal, respectively. However, the CCK release was significantly lower during the i.j. administration as compared with i.g. perfusion. An atropine infusion significantly reduced the i.g. and i.j. test meal-stimulated enzyme outputs. An i.j.-administered meal stimulates the pancreatic enzyme secretion, but this effect is significantly lower than that which occurs on i.g. administration. The i.j. meal-stimulated secretion of pancreatic enzymes is subject to both cholinergic and peptidergic regulation. The deficiency of gastrin and the delayed and decreased CCK release are believed to account for the reduced enzyme output.

Adult↗

PubMed2002

Postprandial hypotension in response to duodenal glucose delivery in healthy older subjects.

Postprandial hypotension occurs frequently in older people and may lead to syncope and falls. Some recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate of gastric emptying. The aim of this study was, therefore, to determine whether the fall in blood pressure induced by intraduodenal glucose is influenced by the rate of nutrient delivery into the small intestine, bypassing the effects of gastric emptying. Eight healthy elderly subjects (four male and four female, age 70.3 +/- 3.4 years) were studied on two separate days, in double-blind, randomised order. Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min(-1), for 60 min, (0-60 min) followed by 0.9 % saline for a further 60 min (60-120 min). Blood pressure and heart rate were recorded at baseline and every 3 min during the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal min(-1) infusion caused a significant fall in systolic (P < 0.001) and diastolic (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations were greater during the 3 kcal min(-1) infusion. We conclude that in healthy older subjects, the magnitude of the fall in blood pressure and increase in heart rate induced by intraduodenal glucose infusion is dependent on the rate of nutrient delivery into the small intestine. These results may have relevance to the treatment of postprandial hypotension.

Aged↗

PubMedDate not supplied

Variability in the composition of physiologic duodenogastric reflux.

Duodenogastric reflux has long been associated with various diseases of the foregut. Even though bile is often used as a marker, duodenogastric reflux consists of other components such as pancreatic juice and duodenal secretions. The aim of this study was to investigate the occurrence of duodenogastric reflux, its components, and the variability of its composition in normal subjects. Twenty healthy volunteers (7 men and 13 women) whose median age was 24 years underwent combined 24-hour bilirubin and gastric pH monitoring and intraluminal gastric aspiration. All probes were placed at 5 cm below the lower border of the lower esophageal sphincter. Aspiration was performed hourly and at any time when bilirubin and/or pH monitoring showed signs of duodenogastric reflux. Elastase and amylase were measured in the aspirate. All volunteers had episodes of physiologic duodenogastric reflux. A total of 70 episodes of duodenogastric reflux were registered with a median of three episodes (range 1 to 8) per subject. Most bile reflux occurred separately from pancreatic enzyme reflux. Pancreatic enzyme aspirate was significantly more often associated with a rise in pH in comparison to bile reflux (P <0.01). Duodenogastric reflux is a physiologic event with varying composition. Both bile and pancreatic enzyme reflux frequently occur separately. These findings could explain the disagreement regarding assessment and interpretation of duodenogastric reflux in the past. Thus monitoring of duodenogastric reflux requires more than the detection of just one component.

Adult↗

PubMed1994

Pharmacokinetics of levodopa and carbidopa in rats following different routes of administration.

This study examined the pharmacokinetics of levodopa and carbidopa in the rat after different modes of administration. The drugs were given simultaneously by the intravenous, intraarterial, oral, duodenal, and intraperitoneal routes, as single doses. The ratio of levodopa to carbidopa given was always 4:1. Two iv doses (5 and 15 mg/kg of levodopa) were given to test for nonlinearity. Three ip doses of levodopa were given (5, 7.5, and 15 mg/kg), and the 15 mg/kg dose was given in three volumes (2, 4, and 20 mL/kg). One oral dose and two intraduodenal doses of 15 mg/kg were given. The drugs were dissolved in saline in one of the intraduodenal doses and suspended in 1.8% methylcellulose in the other. The elimination of levodopa was nonlinear. There was a comparatively high degree of interindividual variability in absorption with the oral route, but this was substantially reduced when levodopa was given intraduodenally. There was also much less variability with the intraperitoneal route compared to the oral, and the degree of absorption was generally high. There was a significantly higher extent and slower rate of absorption when levodopa was administered ip in a large volume of vehicle. These results suggest that the oral route may not be the optimal method of delivering levodopa to patients who have a fluctuating response and that a continuous delivery system via the intraperitoneal or intraduodenal routes might be a better alternative.

Absorption↗

PubMed2005

Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.

OBJECTIVES: To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). METHODS: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/carbidopa gel for 3 + 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from -3 to 0 to +3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. RESULTS: Median percentage of ratings in a functional "on" interval (-1 to +1) was increased from 81 to 100% by infusion therapy (p < 0.01). This improvement was accompanied by a decrease in "off" state (p < 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p < 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p < 0.01). Adverse events were similar for both treatment strategies. CONCLUSIONS: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Administration, Oral↗

PubMed1986

Gastric processing and emptying of fat.

This study was undertaken to determine whether fat leaves the stomach within or bound to the surface of particles of solid food. We studied gastric emptying of fat in 6 human subjects and in 6 dogs with Roux-en-Y duodenojejunostomies so that chyme leaving the stomach could be collected free of bile and pancreatic enzymes. Humans were studied with a duodenal multilumen tube so that phase-specific, nonabsorbed markers in the meal could be tracked with corresponding, phase-specific markers perfused into the duodenum. In this way, we observed the separate time-courses of gastric emptying of the aqueous and solid phases, as well as the extracellular fat (ECF) and intracellular fat (ICF) phases of the meal. In the dogs, all chyme leaving the stomach was collected from a Roux-en-Y fistula and was analyzed directly for aqueous, solid, ECF, and ICF markers in the meal. In both the humans and the dogs, the aqueous phase emptied promptly, whereas the solid, ECF, and ICF phases emptied together, in parallel, after an initial lag. In humans, 22% of the ECF versus 51% of the ICF (p less than 0.02) emptied on or in the solid food particles. In dogs, 81% of the ECF emptied as an oil, 13% emptied on the solid particles, and only 6% emptied as a stable, aqueous emulsion. Sixty-six percent of the ICF emptied in the solid food particles, 20% as a stable, aqueous emulsion, and 14% as an oil. We conclude that most of the ICF empties within the solid food phase, whereas most of the ECF empties as an oil phase.

Animals↗

PubMed2007

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.

OBJECTIVE: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. MEASUREMENTS AND MAIN RESULTS: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. CONCLUSIONS: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.

APACHE↗

PubMed2001

Evaluation of the immunomodulatory effects of the macrolide antibiotic, clarithromycin, in female B6C3F1 mice: a 28-day oral gavage study.

The macrolide antibiotic, clarithromycin, is used extensively to treat bacterial infections associated with pneumonia, duodenal ulcers, and the advanced stages of human immunodeficiency viral (HIV) infection. In addition to its antimicrobial properties, several studies have indicated that clarithromycin also has anti-inflammatory and immunomodulatory properties. In this study, clarithromycin's immunomodulatory properties were evaluated using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate, and acquired cellular and humoral immune responses. Female B6C3F1 mice were treated daily by gavage with clarithromycin (0, 125, 250, and 500 mg/kg) for 28 days then evaluated for immunomodulation. Minimal immunological changes were observed after 28 days of treatment. A slight increase in the number of spleen antibody-forming cells was observed at the 250 mg/kg treatment level, but not at other doses. Serum IgM levels were unaffected by the clarithromycin treatment. A significant increase in the number of splenic macrophages was also observed in mice treated with 125 mg/kg of clarithromycin, but this increase was not observed at the other treatment levels. Innate and cell-mediated immunity, as measured by natural killer cell activity, and mixed leukocyte and cytotoxic T cell response, respectively, were unchanged following treatment with clarithromycin. These results suggest that the immune system is not a target for clarithromycin at doses of 500 mg/kg or below.

Adjuvants, Immunologic↗

PubMed1997

Effect of cisapride on oesophageal motility and duodenogastro-oesophageal reflux in patients with Barrett's oesophagus.

OBJECTIVE: Both gastric acid and duodenal juice have been implicated in Barrett's oesophagus. The aim of this study was to look at duodenal reflux in the oesophagus together with motility characteristics in a group of patients with Barrett's oesophagus and compare them with a mild oesophagitis group and to assess the effect of cisapride on any abnormalities. DESIGN: A prospective study comparing the two groups of patients was carried out. METHODS: Twenty patients with histologically proven Barrett's oesophagus and 20 patients with Savary-Miller grade 2 oesophagitis were studied. Standard oesophageal manometric measurements were carried out and on a separate occasion duodenogastro-oesophageal reflux (DGOR) was measured over a 4-h period using a sodium ion selective electrode. Patients with more than 5% DGOR were given cisapride (10 mg four times daily) and the studies repeated after 7 days of treatment. RESULTS: Barrett's patients showed more DGOR, 12.2% of the study time compared to 5.1% in the mild oesophagitis group, P = 0.012, but manometric findings were not significantly different. Sixteen patients were treated with cisapride. DGOR was reduced in 8 out of 12 Barrett's patients and 2 out of 4 oesophagitis patients, and proximal amplitude and distal oesophageal pressures were significantly elevated (P = 0.05 and P = 0.03, respectively). CONCLUSION: Monitoring of sodium ions in the oesophagus shows that patients with Barrett's oesophagus have significantly more DGOR than patients with uncomplicated oesophagitis and cisapride may be effective in removal of this reflux.

Adult↗

PubMed2005

Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake.

Ondansetron, a selective serotonin-type 3 (5-HT(3)) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose suppressed intake through 5-HT(3) receptors. Polycose suppressed sucrose intake across both concentrations infused (132 mM, 7.6 +/- 0.6 ml; 263 mM, 2.3 +/- 0.5 ml), compared with intake under control conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 +/- 0.8 ml, P = 0.004). Dose-response testing revealed that suppression of food intake by 263 mM Polycose was equally attenuated by ondansetron administered at 1.0, 2.0, and 5.0 mg/kg but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake, and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake after 990 mM glucose but not mannitol infusion was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT(1) inhibitor, phloridzin, had no effect on 60-min 990 mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT(3) receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.

Animals↗

PubMed2006

Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine.

Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

Pharmacokinetics, tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration.

PURPOSE: The aim of this research was to study whether the bioavailability of nitrendipine (NDP) could be improved by administering nitrendipine solid lipid nanoparticles (SLN) duodenally to rats. METHODS: Nitrendipine was incorporated into SLN prepared by hot homogenization followed by ultrasonication method. SLN were produced using various triglycerides (trimyristin, tripalmitin and tristearin), soy phosphatidylcholine 95%, poloxamer 188 and charge modifiers (dicetyl phosphate, DCP and stearylamine, SA). Particle size and charge measurements were made with a Malvern Zetasizer. Pharmacokinetics of nitrendipine SLNs (NDP-SLNs) after intravenous (i.v.) and intraduodenal (i.d.) administration to conscious male Wistar rats were studied. Tissue distribution studies of NDP-SLNs were carried out in Swiss albino mice after i.v. administration and compared to nitrendipine suspension (NDP-Susp). RESULTS: Average size and zeta potential of SLNs of different lipids, with and without charge modifiers ranged from 101.9 +/- 3.0 to 123.5 +/- 3.0 nm and - 35.1 +/- 0.5 to +34.6 +/- 2.3 mV, respectively. AUC(0-infinity) was increased (up to 4.51-folds) and clearance was decreased (up to 4.54-folds) after i.v. administration of NDP-SLNs with and without charge modifiers compared to NDP-Susp. Effective bioavailability of NDP-SLNs were 2.81-5.35-folds greater after i.d. administration in comparison with that of NDP-Susp. In tested organs, the AUC and MRT of NDP-SLNs were higher than those of NDP-Susp especially in brain, heart and reticuloendothelial cells containing organs. CONCLUSIONS: SLN are suitable drug delivery systems for the improvement of bioavailability of nitrendipine. Negatively and positively charged SLN were better taken up by the liver and brain, respectively.

Animals↗

PubMed2000

The specific activities of human digestive lipases measured from the in vivo and in vitro lipolysis of test meals.

BACKGROUND & AIMS: The lipolytic potential of digestive lipases in vivo has always been deduced so far from their in vitro activities under nonphysiologic conditions. In the present study, the specific activities of human gastric lipase (HGL) and pancreatic lipase (HPL) were measured on dietary triglycerides (TGs) during test meal lipolysis. METHODS: Healthy human volunteers ingested a liquid or solid meal. The specific activities of HGL and HPL were estimated from the lipase and free fatty acid (FFA) outputs at the postpyloric and duodenal levels, respectively. Based on the in vivo data, lipolysis was also performed in vitro by mixing the meal either with gastric juice and subsequently with pancreatic juice and bile or with purified HGL and HPL. FFAs were measured by thin-layer chromatography, and the specific activities of HGL and HPL were expressed as micromoles of FFA per minute per milligram of lipase. RESULTS: In vitro, the specific activities on the liquid meal TGs were 32 (gastric juice) and 34 (pure lipase) micromol x min(-1) x mg(-1) with HGL and 47 (pancreatic juice) and 43 (pure lipase) micromol x min(-1). mg(-1) with HPL. The specific activities on the solid meal TGs were 33 (gastric juice) and 32 (pure lipase) micromol x min(-1) x mg(-1) with HGL and 12 (pancreatic juice) and 15 (pure lipase) micromol x min(-1) x mg(-1) with HPL. The in vivo values obtained were in the same range. The secretory lipase outputs were 21.6+/-14.5 mg HGL and 253.5+/-95.5 mg HPL with the liquid test meal and 15.2+/-5.1 mg HGL and 202.9+/-96.1 mg HPL with the solid test meal. CONCLUSIONS: The specific activities of HGL and HPL on meal TGs were much lower than those measured in vitro under optimized assay conditions (1300-8000). However, these low specific activities are enough for the meal TGs to be completely lipolysed, given the amounts of HGL and HPL secreted during a meal.

Adult↗

PubMed2001

Duodenal tube test in the diagnosis of biliary atresia.

BACKGROUND: Biliary atresia (BA) is the main cause of severe liver damage in infants. Successful surgical treatment is related directly to an early and rapid diagnosis. The aim of this study was to determine specificity, sensitivity, and predictive value of the duodenal tube test (DTT) in the diagnosis of BA in a series of infants with cholestatic jaundice. METHODS: This was a descriptive study of a series of infants with cholestatic jaundice created to validate the sensitivity, specificity, and predictive value of the DTT in the diagnosis of BA. A total of 254 patients were identified from 1988 to 1998. The study cohort included 137 male infants (53.9%), and the mean age on admission was 8.3 weeks +/- 2.47 weeks (standard deviation). Study protocol included liver function tests, liver ultrasound, metabolic screening and serology for viral hepatitis, and toxoplasma, rubella, cytomegalovirus, herpes, and others. A nasoduodenal tube was, placed at the distal duodenum and the fluid was collected for 24 hours. DTT was considered bile positive when yellow biliary fluid was observed; the test was concluded at this time. When no yellow biliary duodenal fluid was observed, the collection was continued for 24 hours and, if negative, was reported as bile negative. The patients with a bile-positive DTT were not explored surgically, and the cholestasis workup was completed. Laparotomy and a surgical cholangiogram were indicated in patients with bile-negative DTT. If BA was verified, portoenterostomy was performed. The gold standard for BA diagnosis was the following: obstruction of the biliary tract confirmed by laparotomy and a surgical cholangiogram, and clinical outcome in patients without laparotomy (followed for a minimum of 18 months). RESULTS: The results are as follows. BA: bile-positive DTT, n = 3; bile-negative DTT, n = 108. No BA: bile- positive DTT, n = 134; bile-negative DTT, n = 9. The following values were also determined: sensitivity, 97.3%; specificity, 93.7%; positive predictive value, 92.3%; and negative predictive value, 98.5%. The final diagnoses were as follows: BA, n = 111 (43.7%); neonatal hepatitis syndrome, n = 103 (40.6%); cholestasis associated with inspissated bile syndrome, n = 13 (5.1%); choledochal cyst, n = 11 (4.3%); galactosemia, n = 9 (3.5%); cirrhosis of unknown etiology, n = 5 (2%), and Alagille syndrome, n = 2 (0.8%). CONCLUSIONS: The data obtained from this series validate the DTT as a useful clinical tool for the differential diagnosis of the infant with cholestasis, particularly for indicating laparotomy and cholangiogram to substantiate BA. This diagnostic test is quick and simple, and offers the clinician valuable information with which to determine whether surgical intervention is necessary.

Bile Ducts, Extrahepatic↗