Effects of lipid formulations on clove extract spray dried powders: comparison of physicochemical properties, storage stability and in vitro intestinal permeation.

Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove's bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25 °C and 40 °C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.

Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets using PEG and hard fat showed sufficient adhesiveness and sustained drug release, those using PEG as the base did not. Drug release was controlled by the amount of hard fat and the saponification degree of PVA. The drug release rate was most increased in a tablet containing PVA with an intermediate degree of saponification, PEG and hard fat. From differential scanning calorimetry and powder X-ray diffraction, IM was considered to exist in the molecular phase. From the results of buccal administration of tablets to rats, highest tissue concentrations were observed in the tablet containing PVA with the intermediate degree of saponification using PEG and hard fat, and the plasma concentrations were sufficiently low in comparison.

Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.

Development and Diagnostic Accuracy of a Breath Test for Pancreatic Exocrine Insufficiency in Chronic Pancreatitis.

OBJECTIVE: To develop a ¹³C-labeled substrate breath test by defining the optimal ¹³C-labeled substrate, substrate dose, test meal, and duration of the test and evaluating its accuracy for the diagnosis of pancreatic exocrine insufficiency (PEI) in chronic pancreatitis (CP). METHODS: Five consecutive prospective comparative studies in patients with known advanced CP and healthy controls were performed to develop the optimal breath test. Coefficient of fat absorption was used as the reference method. The diagnostic accuracy of the optimized breath test was prospectively further evaluated in patients with advanced CP using coefficient of fat absorption as the reference method. RESULTS: The optimal breath test protocol was that using 250 mg of ¹³C-mixed triglyceride as substrate together with a test meal containing 16 g of fat. Coefficient of fat absorption and breath test results correlated significantly (r = 0.736, P < 0.001). The test has sensitivity, specificity, and overall accuracy of 92.9%, 91.7%, and 92.3%, respectively, for the diagnosis of PEI. CONCLUSIONS: The optimized ¹³C-mixed triglyceride breath test is an accurate and simple breath test for the diagnosis of PEI in patients with CP, easily applicable to the clinical routine.

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen.

CONTEXT: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action. OBJECTIVE: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires. MATERIALS AND METHODS: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies. RESULTS AND DISCUSSION: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (Cmax) of 9140.84 ± 614.36 ng/ml at 3 h Tmax and solid dispersion tablets showed Cmax = 11 445.46 ± 149.23 ng/ml at 2 h Tmax. The area under the curve for the control and solid dispersion tablets was 31 495.16 ± 619.92 and 43 126.52 ± 688.89 ng h/ml and the mean resident time was 3.99 and 3.68 h, respectively. CONCLUSION: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.

Loss of claudins 2 and 15 from mice causes defects in paracellular Na+ flow and nutrient transport in gut and leads to death from malnutrition.

BACKGROUND & AIMS: The intestinal symport system moves nutrients across membranes via transporters, and is required for absorption of major nutrients such as glucose, amino acids, and bile acids (which are required for fat absorption). Most of these transporters are regulated by Na(+), but the standard diet does not provide sufficient levels of this ion to the intestinal lumen to support this system. Claudins form paracellular barriers between epithelial cells, and claudin-2 and -15 regulate paracellular ion flow in the intestine. We investigated how cell adherence, tight junction barriers, and claudins regulate the supply of Na(+) to the intestinal lumen in mice. METHODS: We created Cldn2(-/-)Cldn15(-/-) (double-knockout) mice and analyzed intestinal tissues by reverse-transcription polymerase chain reaction, immunoblot, immunofluorescence, electron microscopy, and H&E analyses. We also measured paracellular Na(+) flow, luminal Na(+) concentration, and absorption of glucose, amino acids, and fats, which were administered orally to the mice. RESULTS: Paracellular flow of Na(+) from the intestinal submucosa to the lumen, and therefore the concentration of Na(+) in the lumen, was greatly reduced in intestines of Cldn2(-/-)Cldn15(-/-) mice. Absorption of glucose, amino acids, and fats also decreased in the mice, which died by postnatal day 25 from malnutrition. CONCLUSIONS: The paracellular flow of Na(+) from the intestinal submucosa is regulated by tight junctions that contain claudin-2 and -15. This system is required for the absorption of glucose, amino acids, and fats; disruption of this system in mice leads to infant death as a result of malabsorption.

Dietary fish oil increases fat absorption and fecal bile acid content without altering bile acid synthesis in 20-d-old weanling rats following massive ileocecal resection.

INTRODUCTION: Dietary fish oil (FO) was reported to lower fecal fat excretion in a weanling rat model of short bowel syndrome (SBS) after ileocecal resection (ICR), and to induce changes in secretion and synthesis of bile acid (BA) in adults. We hypothesized that dietary FO, as compared with corn oil (CO), increases intestinal fat absorption in weanling SBS rats in part due to increased hepatic BA synthesis and luminal BA concentrations. METHODS: After undergoing ICR, 20-d-old rats were fed ad lib for 7 d with a CO or FO diet containing 5% sucrose polybehenate (SPB), a marker for dietary fat absorption. Fecal fatty acid, fecal and intestine luminal BA, liver mRNA expressions of cholesterol 7α-hydroxylase (Cyp7α1) and sterol-12α-hydroxylase (Cyp8ß1), and serum 7α-hydroxy-4-cholesten-3-1 (7αC4) levels were determined. RESULTS: As compared with CO-ICR rats, FO-ICR rats had higher intestinal absorption of total fat and most individual fatty acids. Although the BA content per gram of dry stool was increased in FO-ICR rats, there were no differences between groups for the BA content in remnant jejunum, liver mRNA expression of BA biosynthetic enzymes, Cyp7α1 and Cyp8ß1, or serum 7αC4, a marker for BA synthesis. CONCLUSION: Dietary FO increases dietary fat absorption without increasing hepatic BA synthesis in weanling SBS rats.

Significance of lipid matrix aging on in vitro release and in vivo bioavailability.

A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with paracetamol as a model drug, filled into hard gelatin capsules and stored at three different temperatures for various lengths of time. The resultant solidified matrix within the capsule was subjected to thermal analysis using differential scanning calorimetry (DSC) to ascertain its supramolecular structure. Polymorphic transformations towards more stable gelucire forms were observed upon aging the matrices, with samples stored at a temperature near the melting range of the lower temperature gelucire melting fraction showing the most profound changes. The increase in the rate of drug release from aged samples could be correlated to the alterations to the supramolecular structure of the gelucire. Accelerated drug release from aged samples could also be seen from in vivo studies using healthy human volunteers, although the extent of absorption was not affected. Therefore, even though the sustainability of release may be compromised by aging the gelucire matrices, the bioavailability of the incorporated drug is unlikely to be affected.

[Clinical effectiveness of dehelmintization in patients with psoriasis accompanied by chronic opisthorchosis].

The purpose of the study was to prove the appropriateness of dehelmintization in patients with psoriasis accompanied by chronic opisthorchosis (CO). The authors examined 150 patients with psoriasis accompanied by CO, 100 patients having psoriasis without helminthiasis, 100 patients with psoriasis and 30 healthy individuals. Gastric secretion was evaluated by means of the fractional test (both phases) with histamine stimulation; other diagnostic procedures included carbohydrate absorption evaluation (5-gram D-Xylose absorption test), Kamer test of fat absorption and evaluation of small intestine bioelectric activity by means of electromyography. The patients were followed up within 2 to 3 years. The study found negative dynamics in the parameters of gastric secretion, fat and D-xylose absorption and small intestine bioelectric activity in patients with psoriasis and CO within the 2-3-year follow-up, while the group of dehelmintized patients displayed significant improvement of these parameters. Thus, effective dehelmintization allowed improvement of alimentary tract functional condition and the clinical course of psoriasis.

Study of in-vitro release characteristics of carbamazepine extended release semisolid matrix filled capsules based on Gelucires.

Various extended release carbamazepine (CBZ) formulations have been developed previously, in order to reduce the frequency of dosing in chronic therapy and to decrease the variability in drug plasma concentration. In the present study, the suitability of different grades of Gelucires (G, glyceride based excipients) to formulate CBZ extended release capsules by the application of semisolid matrix (SSM) filling capsule technology was investigated. The possible modification of CBZ release kinetics by using Gelucire blends or inclusion of hydrophilic additives in the SSM was studied. The effect of ageing on some selected formulations was also evaluated, using scanning electron microscopy and differential thermal analysis. Twenty-one capsule formulations were prepared and assessed for their release characteristics. The mechanism of drug release from the test formulations was studied. The following results were obtained: a) Release data could not be correlated to the melting point (mp) of Gelucires used, pointing to relative lipophilicity of the base as a more important determinant of drug release. Among Gelucire grades having melting points higher than 37 degrees C, the release rate proved to be highly dependent on the HLB value and matrix composition. b) CBZ release occurred by different mechanisms, including matrix disintegration, diffusion and or erosion depending on the vehicle employed. c) Zero order release profiles of CBZ were obtained from SSM-based on G50/13, G53/10 and their blends in ratios higher than 1:1 and G53/10 containing croscarmellose sodium. d) The ageing study revealed that these latter formulations, except those based on G50/13, also showed high dissolution stability during one year of shelf ageing. e) PVP, as a polymorphic transformation inhibitor, can be used to reduce the storage-induced changes of some grades of Gelucires. From the above data, it can be concluded that different grades of Gelucires and their blends as well as hydrophilic additives could be successfully used to formulate CBZ extended release SSM filled capsules with various release kinetics.

The influence of drug incorporation on the structure and release properties of solid dispersions in lipid matrices.

The effect of incorporating caffeine and paracetamol on the structure and behaviour of Gelucire 50/13 has been studied with a view to establishing whether the choice of drug influences the solid structure and release mechanism. Dispersions containing up to 30% w/w drug were prepared and studied using differential scanning calorimetry (DSC), hot stage differential interference contrast microscopy (HSM), dissolution studies and erosion, water uptake (WU) and diameter change measurements. Gelucire 50/13 alone showed a broad melting endotherm using DSC, with two dominant peaks at 36 and 44 degrees C. While incorporation of caffeine did not result in marked changes to the profile, the presence of paracetamol increased the proportion of material in the lower melting peak. HSM studies indicated that the Gelucire crystallised into two main spherulitic conformations; paracetamol appeared to act as a nucleation site for the lower melting fractions while caffeine particles changed into a needle-shaped morphology on cooling the system from the liquid state. Dissolution studies at 37 degrees C showed the caffeine to be released at a relatively faster rate than the paracetamol. Kinetic modeling and direct measurement of the erosion profile indicated that the caffeine systems showed a greater preponderance for erosion than did the corresponding paracetamol systems. It is suggested that the paracetamol promotes the generation of the lower melting form of Gelucire 50/13 which in turn influences the release rate and mechanism. The study therefore indicates that the influence of the drug should be carefully considered when studying Gelucire matrix systems.

Long-term feeding effects of heated and fried oils on hepatic antioxidant enzymes, absorption and excretion of fat in rats.

Long-term feeding effect of heated and fried peanut (PNO), rice bran (RBO) and palm oil (PO) in the diet on the hepatic antioxidant enzyme status and absorption and excretion of fats were studied in laboratory rats. The rats were fed oils heated to 180 degrees C continuously for a period of 72 h or laboratory fried at 20% level in the diet for 18 weeks. The results of the study indicated a significant increase in the catalase activity in HO groups and decrease in the FRO groups. The GPx activity while significantly low in HO groups was high in FRO groups, whereas, significant decrease in GST activity was observed in both PNO-HO/FRO groups. Increased activity was noted in RBO-FRO and PO-HO/FRO groups. The SOD activity showed a mixed response in different heated/fried oils and a marginal increase in the levels of fecal fat excretion was observed in some of the heated/fried oil groups. The results indicated no appreciable damage with respect to these antioxidant enzymes. Also, feeding heated fats as high as 20% in the diet for long duration does not result either in reduced food intake or excess fecal fat excretion.

Lymphatic absorption of structured triglycerides vs. physical mix in a rat model of fat malabsorption.

Comparison was made between the intestinal absorption and lymphatic transport of a randomly interesterified fish oil and medium-chain triglyceride (MCT) structured triglycerides (STG) vs. the physical mix in rat small intestine following ischemia and reperfusion (I/R) injury. Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both treatment groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 ml of the fish oil-MCT STG or physical mix (7 rats/group) through the gastric tube followed by an infusion of PBS at 3 ml/h for 8 h. Lymph was collected hourly for 8 h. Lymph triglyceride, cholesterol, and decanoic and eicosapentaenoic acids increased rapidly and maintained a significantly higher output (P < 0.01) with STG compared with physical mix in control rats over 8 h. After I/R, lymphatic triglyceride output decreased 50% compared with control. Gastric infusion of STG significantly improved lipid transport by having a twofold higher triglyceride, cholesterol, and decanoic and eicosapentaenoic acids output to lymph compared with its physical mix (P < 0.01). We conclude that STG is absorbed into lymph significantly better than physical mix by both the normal intestine and the intestine injured by I/R.

Molecular interactions and kinetic properties of fats.

This article has reviewed the recent work on the molecular interactions and kinetic properties of the polymorphic transformations of the TAGs in the single and mixed states. Progress has recently been made in the molecular-level understanding of the polymorphic transformations of the TAGs. Particularly, the use of the time-resolved X-ray diffraction with Synchrotron radiation (SR-XRD) has provided precise information of the structural changes of the fat crystals at a time scale of 10 sec. Therefore, fruitful information was obtained on the kinetic and molecular aspects of crystallization and mixing processes of the various types of mixed-acid TAGs, which were not obtained with the traditional thermal and structural techniques because of their complicated structural properties. One may anticipate that, although the experimental sites and machine times are limited, the SR-XRD techniques will be more applied to the fat systems involving the following materials and systems; (a) multicomponent natural fats with and without additives of emulsifiers, proteins and carbohydrates, (b) fats in dispersed phases such as oil-in-water (O/W) and water-in-oil (W/O) emulsions, (c) crystallization and transformation processes under external influences of hydrostatic pressure and shear stress [68].

Effect of the source of dietary fat on postweaning lipogenesis in lean and fat pigs.

Twenty-four male piglets weaned after 21 days, 12 of the Large White lean breed (LW) and 12 of the Alentejano fat breed (AL), have been used to compare the effects of genotype and source of dietary fat on the activities of enzymes involved in lipogenesis and on the composition of selected fatty tissues. During 4 weeks the piglets were fed isoenergetic and isonitrogenous experimental diets, containing 5 % of either olive oil or tallow. In AL piglets the acetylcoenzyme A carboxylase activity was three- and ninefold higher, the malic enzyme activity six- and fivefold, and the glucose-6-phosphate dehydrogenase activity was four- and fivefold higher in the dorsal subcutaneous and in the perirenal fat, respectively, than in LW piglets. In general, fatty tissues of the AL piglets contained a higher proportion of saturated fatty acids. Olive oil induced a significant increase in the activities of malic enzyme and glucose-6-phosphate dehydrogenase in both tissues, but only slightly increased the acetylcoenzyme A carboxylase activity in perirenal fatty tissues (p < 0.05). The fatty acid profile of the subcutaneous and of the perirenal fat was strongly affected by the composition of dietary fat. These observations showed that the source of dietary fat influenced markedly lipid metabolism and body composition since a very early age.

Fat distribution and changes in the blood brain barrier in a rat model of cerebral arterial fat embolism.

This study was designed to determine the distribution of fat which reaches the brain by the internal carotid artery, and the consequent alterations in the blood brain barrier, in a rat model of cerebral arterial fat embolism. The distribution of the blood flow in this model was determined by the injection of radiolabelled microspheres. Over 44% were trapped in the brain, 43% in the extracerebral tissues of the head and neck, and 7% in the lungs. Over 30% of radiolabelled triolein was present within the brain 30 min after injection, and 4% still remained after 17 days. Approximately 25% of the triolein which went to the brain moved through the cerebral vessels and left within the first 15 min. The majority of the triolein distributed to the ipsilateral cerebral hemisphere, with significantly less to the contralateral cerebral hemisphere, brain stem and cerebellum. The blood brain barrier opened, as measured by uptake of 99mTc, within the first 15 min and remained open for at least 3 days. A significant percentage of fat reaching the brain persists for days, and causes rapid and long-lasting damage to the blood brain barrier.

[Enhancement of gut absorptive function by early enteral feeding enriched with L-glutamine in severe burned miniswines].

14 miniswines (with multiple catheterization and 30% TBSA full thickness burns) were randomly and equally divided into N-Gln group and GLN group. Animals of GLN group were supplied with L-glutamine by 0.64%/kg.d and N-GLN group received equal amount of non-glutamine amino acids. Portal venous blood flow and gut absorptions of glucose, amino acids as well as fat were determined on PBD (post burn day) 1, 4, 7 and 10. The results indicated that the gut absorption obviously decreased in both group on PBD1, but the absorption of glucose and amino acids were much higher in Gln group than that of N-Gln group (P < 0.01). The absorptions of glucose, fat amino acids quickly increased in Gln group from PBD4, and tended to reach the preburn level on PBD7 and PBD10, meanwhile N-Gln group exhibited a slow increase of gut absorption. The absorptions of glucose, fat and amino acids were obviously lower than those of preburn on PBD7 and PBD10 (P < 0.01). This result suggests that oral feeding of glutamine improves efficiently the gut absorptive function after severe burns.

Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric subjects.

BACKGROUND/AIMS: Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. METHODS: Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. RESULTS: There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g D-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high alpha 1-antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [14C]D-xylose test was abnormal in 6 out of 17 subjects. CONCLUSIONS: Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.

Respective oxidation of exogenous glucose and fructose given in the same drink during exercise.

We computed the respective amounts of exogenous glucose (G) and fructose (F), which are oxidized during exercise when ingested simultaneously, with the use of 13C labeling. Six subjects exercised for 2 h at 60.7 +/- 2.9% of maximal O2 uptake on a cycle ergometer while ingesting 50 or 100 g of G or F or a mixture of 50 g each of G and F in 500 ml of water. The amount of exogenous G oxidized increased from 37.8 +/- 2.2 to 58.3 +/- 8.1 g when the total amount ingested increased from 50 to 100 g. The amount of F oxidized was significantly lower (32.2 +/- 1.2 and 45.8 +/- 2.6 g for the 50 and 100 g ingested, respectively). When 50 g each of G and F were simultaneously ingested in the same drink, the amounts oxidized (39.5 +/- 4.8 and 34.1 +/- 1.5 g, respectively) were similar to those observed when 50 g of G or F were ingested separately. The cumulative amount of exogenous hexoses oxidized (73.6 +/- 6.6 g) was 21% larger than when 100 g of G were ingested. This finding could be due to the fact that the routes for absorption and metabolism of exogenous G and F are at least partly different, resulting in less competition for oxidation when a mixture of these two hexoses is ingested than when an isocaloric amount of G is ingested. From a practical point of view, these data may provide experimental support for using mixtures of carbohydrates in the energy supplements for endurance athletes.

Increased lymphatic flux of hyaluronan from cat intestine during fat absorption.

During fat absorption, chylomicrons with sizes up to 5,000-10,000 A must traverse an interstitium that has estimated pore sizes of 120-200 A to reach the lacteals. The present experiments were performed to study the behavior of the interstitial matrix component hyaluronan during fat absorption from the intestine. Ileal segments were isolated and autoperfused in pentobarbital-anesthetized cats. A postnodal lymphatic was cannulated, and lymph flow, protein, and hyaluronan concentration in lymph were determined. In group 1, a mixture of oleic acid and taurocholate was infused into the ileal lumen, while in group 2 the animals were fed cream overnight. In group 1, control lymph flow and hyaluronan concentration averaged 53.3 +/- 16.0 (SD) microliters.min-1.100 g intestine-1 and 21.4 +/- 16.0 micrograms/ml, respectively. Administration of taurocholate and oleic acid increased lymph flow and lymph hyaluronan concentration by 100 and 50%, respectively, resulting in a nearly three-fold increase in hyaluronan flux. Subsequent increases in venous pressure increased lymph flow and reduced hyaluronan concentration in lymph to less than 3 micrograms/ml. Hyaluronan flux remained approximately 2 micrograms.min-1.100 g intestine-1 independent of lymph flow. In group 2, no lymph sample was available before administration of fat. Hyaluronan concentration at control venous pressure was 19.3 +/- 6.7 micrograms/ml and fell to 10 micrograms/ml at the highest lymph flow. Hyaluronan flux was approximately 10 micrograms.min-1.100 g intestine-1 at the highest lymph flow and venous pressure (P less than 0.05 compared with the same lymph flow in group 1).(ABSTRACT TRUNCATED AT 250 WORDS)