Gelucire 44/14 improves fat absorption in rats with impaired lipolysis.

Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire 44/14 - a semi-solid self-micro-emulsifying excipient - could increase fat absorption. In relevant rat models for impaired lipolysis or for impaired solubilization we tested whether administration of Gelucire 44/14 enhanced fat absorption. Rats with impaired lipolysis (lipase inhibitor Orlistat diet) and rats with reduced solubilization (permanent bile diversion) underwent a 72 h fat balance test to assess fat absorption. The absorption kinetics of a stable isotope-labeled fatty acid was assessed in rats with reduced solubilization, in the presence or absence of Gelucire 44/14. Gelucire 44/14 improved fat absorption in rats with impaired lipolysis (from 70% to 82%, p<0.001). In rats with reduced solubilization, Gelucire 44/14 did not increase fat absorption nor did it reconstitute the absorption kinetics of (13)C-labeled palmitate, compared with control rats administered buffer without Gelucire 44/14. The present data show that Gelucire 44/14 might enhance fat absorption under conditions of impaired lipolysis, but not during impaired solubilization. We speculate that, due to its self-micro-emulsification properties, Gelucire 44/14 stabilizes and improves residual lipolytic enzyme activity in vivo, which could be of therapeutic value in clinical conditions of fat malabsorption due to impaired lipolysis.

NBT-PABA test to assess efficiency and kinetics of substituted proteolytic enzyme action in pancreatic duct ligated minipigs.

The NBT-PABA test is an established method for diagnosis of pancreatic exocrine insufficiency. In the present study the NBT-PABA test was used to test and compare the efficacy of two multienzyme preparations (product A and B) differing in galenic preparation in minipigs in which pancreatic exocrine insufficiency (PEI) was induced by pancreatic duct ligation. Without enzyme substitution no distinct increase in PABA was found in blood after oral administration of NBT-PABA. Administration of both enzyme preparations led to a clear dose dependent rise in PABA-concentrations in blood. Interestingly, the two preparations showed different time curves of serum PABA concentration, indicating differences in the kinetic of proteolytic enzyme action. It is concluded that the NBT-PABA test can be a very useful test for indirectly evaluating proteolytic enzyme efficacy in vivo, and also gives information about the kinetics of enzyme action, not only the end-result of enzyme action (like digestibility trials which were used traditionally). A single test is performed in a few hours and there is no need for fistulated animals.

Effects of intraduodenal administration of tarazepide on pancreatic secretion and duodenal EMG in neonatal calves.

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide+/-atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postprandial pancreatic secretion are partly controlled via CCK-A (mainly mucosal) mediated mechanisms.

Induction of apoptotic DNA fragmentation and c-jun downregulation in human myeloid leukemia cells by the permeant Ca2+ chelator BAPTA/AM.

The permeant Ca2+ chelator acetoxymethyl-1,2-bis(2-aminopheoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA/AM), an agent previously used to characterize drug-induced apoptosis in neoplastic cells, has been examined with respect to induction of DNA fragmentation and cytotoxicity in the human leukemia cell lines HL-60 and U937. Exposure of cells to various concentrations of BAPTA/AM for 6 h resulted in a biphasic induction of internucleosomal DNA cleavage, with maximal damage occurring at 10-microM concentrations. Higher BAPTA/AM concentrations were associated with the loss of internucleosomal cleavage products, but with the appearance of larger (i.e., 50-kilobase) fragments on pulsed-field gel electrophoresis. Cells exposed to 10 microM BAPTA/AM exhibited classic apoptotic morphology, whereas cells exposed to 50-microM concentrations displayed atypical features (e.g., cell swelling, chromatin clumping); in each case, substantial cytotoxicity was noted. The actions of BAPTA/AM did not depend upon the presence of extracellular Ca2+, nor were they affected by impermeant Ca2+ chelators. Measurement of cytosolic Ca2+ by Fura-2/AM or Indo-1 revealed late but not early increases in intracellular Ca2+ in BAPTA/AM-treated cells. Finally, BAPTA/AM-induced apoptosis was accompanied by the concentration-dependent downregulation of the immediate early response gene c-jun. These findings suggest a complex role for Ca2+ chelators such as BAPTA/AM in the regulation of human myeloid leukemic cell apoptosis, and indicate that this agent may selectively antagonize internucleosomal DNA fragmentation without interfering with other aspects of the apoptotic response and/or cell lethality.

The response of feline spinal pial arterioles to norepinephrine.

The effect of norepinephrine on the diameter of feline spinal pial arteries and arterioles was studied by microapplication of the drug to the perivascular environment. Vascular diameter was determined by the television image-splitting method. Application of norepinephrine over the range of 5 x 10(-8) M to 5 x 10(-3) M to spinal pial arterioles resulted in constriction of the vessels. The dose-response curve showed a tendency to plateau at concentrations above 5 x 10(-5) M, with a maximal constriction of 28.8 +/- 5.1% at 5 x 10(-3) M. The reduction in vessel diameter to microapplication of norepinephrine was prevented with the inclusion of an equimolar concentration of the alpha-adrenergic blocker, phentolamine, in the injectate. The data indicate the presence of alpha-adrenergic receptors on the smooth muscle of spinal pial arterioles, and it is suggested that the arguments pertaining to the sympathetic control of blood flow in the brain apply also to the spinal cord.

Duodenal infusion of fat, cholecystokinin secretion and satiety in the pig.

The influence of the cholecystokinin (CCK) antagonist L-364,718 (0.1 mg/kg) on short-term control of food intake was studied in 6 pigs. Arterial injection of L-364,718 abolished the inhibition of intake to CCK octapeptide infusion (4 micrograms/kg/hr; from 42% p less than 0.001, to 97% of control intake), but did not alter control intake (99%). Injection of L-364,718 also abolished the inhibition of intake to duodenal infusion of emulsified fat (12 g/hr; from 76% p less than 0.001 to 105%) and of monoglyceride (24 g/hr; from 64% p less than 0.001 to 101%), but did not alter the inhibition to oleic acid (60 g/hr; 48% p less than 0.01 and 61% p less than 0.02), to glycerol (127 g/hr; 84% p less than 0.05 and 89%) or to glucose (144 g/hr; 78% p less than 0.02 and 69% p less than 0.001). These results suggest that monoglyceride-induced CCK secretion is mainly responsible for the satiety to duodenal fat in the pig, but that there is also a CCK-independent effect via the fatty acid. The results further indicate that intake of a normal barley-based diet (2% fat) is controlled via CCK-independent mechanisms.

Relation between gastric emptying and short-term regulation of food intake in the pig.

The relation between gastric emptying (GE), measured by gastric evacuation, and food intake (FI) was studied in pigs fed two meals to appetite per day. Duodenal infusion of emulsified fat (Intralipid; KabiVitrum) inhibited both FI and GE of digestible energy by more than the energy infused, but the gastric volume at satiety was more than 20% below the control. Duodenal infusions of glucose inhibited FI calorically, and generally inhibited GE calorically; but gastric volume at satiety was always equal to control volume. Thus GE (via gastric distension) may regulate FI to duodenal infusion of glucose but not to Intralipid. In pigs given no infusions, removal of the gastric contents immediately prior to the p.m. meal increased intake by 10%, However, when the contents were retained the pigs ate two equal-sized meals in the day, even though the gastric volume after the p.m. meal was 24% greater than after the a.m. meal. Therefore, although gastric volume may influence intake it cannot be the only factor determining satiety on this diet.

A system for adaptive transportation.

In our society, we take for granted the ability to travel with few restrictions. For most travelers, the major factor that limits travel is cost. However, for a significant number of Americans, the phrase "freedom to travel" is meaningless. These are the physically handicapped, a group with special needs that has long been denied what every American assumes to be a natural right.

A new, improved flotation device for deep-water exercise.

The purpose of this study was to determine the position and size of flotation devices that permit deep-water exercise with the exerciser's thoracolumbar spine in a vertical position and without restriction of movement of the arms and legs. The buoyant force of the flotation device had to be at least 94.0 N to allow the exerciser to be suspended in water with the head above water. The position of the flotation devices had considerable influence on the thoracolumbar angle. When the large pad with a buoyant force of 55.0 N covered the lower abdominal wall and the small pad with a buoyant force at 39.0 N was located over the lower back, the exerciser's thoracolumbar spine assumed an almost vertical position. Anterior placement of the flotation devices resulted in marked extension of the thoracolumbar spine. Conversely, posterior placement of the buoyant devices resulted in flexion of the thoracolumbar spine. On the basis of these results, an ideal flotation device for deep-water exercise can now be developed.

The growing pancreatic duct ligated pig as a model for exocrine pancreatic insufficiency in children: investigations to achieve sufficient vitamin A and vitamin E supply.

Human patients suffering from exocrine pancreatic insufficiency (EPI) are susceptible to deficiencies in fat-soluble vitamins. In children with cystic fibrosis, EPI is common and aspects of sufficient vitamin supply are of special interest. The aim of this study was to determine the best application form to maintain vitamin A and E levels in the physiological range in growing pigs with EPI (induced by pancreatic duct ligation) as a model for children. The pancreatic duct was ligated (PL) in twelve 8-wk-old pigs; 4 sham-operated pigs served as controls (Con). Pigs (n = 16) were individually housed and fed a diet containing 13,393 IU vitamin A and 122 mg vitamin E/kg DM. The PL pigs (n = 12) were divided into 3 groups (n = 4) 2 wk after surgery: PL-0, without extra vitamin supply; PL+ORAL, 90,000 IU vitamin A and 600 mg vitamin E/kg of DM plus emulsifier E 484 added to the diet; and PL+IM, intramuscular injection of vitamin A (5,250 IU) and vitamin E [aqueous; 3.15 mg/(kg BW · wk)] plus 700 mg vitamin E (oily)/(animal · wk). All PL pigs were supplemented with the pancrelipase Creon (19.8 g = 1,048,727 IU lipase/kg feed) beginning 2 wk after ligation of the pancreatic duct. Pigs were euthanized at 16 wk of age. Tocopherol levels (mg/kg DM) in liver were reduced (P ≤ 0.005) in PL-0 and PL+IM (6.91 and 8.61, respectively) whereas PL+ORAL did not differ from Con (27.4 and 25.8, respectively; P ≥ 0.77). Compared to control pigs (241 ± 14.1 mg vitamin A/kg DM of liver), the concentration of vitamin A (mg/kg DM) in liver was lower (P < 0.003) in PL-0 (136 ± 18.5) but higher (P < 0.003) in PL+ORAL (375 ± 50.0). In the group PL+IM a high individual variation was observed (288 ± 142 mg vitamin A/kg DM of liver). Extra dietary supply of high doses of vitamin A and E with an efficient emulsifier was adequate to maintain vitamin A and E in liver tissue within reference values. The present data underline the need for extra supplementation of vitamin A and E in juvenile patients with EPI and indicate that oral application is suitable.

Prececal digestibility of various sources of starch in minipigs with or without experimentally induced exocrine pancreatic insufficiency.

Low prececal digestibility of starch leads to a higher starch flux into the hindgut, causing a forced microbial fermentation, energy losses, and meteorism. For exocrine pancreatic insufficiency (EPI), lack of pancreatic amylase can be compensated mostly by hindgut fermentation of starch. Even in pigs with complete loss of pancreatic secretion, starch digestibility over the entire tract is reaching levels of controls. To optimize diets for human patients with EPI, the proportion of starch that is digested by the ileum is important. Minipigs were fitted with an ileocecal reentrant fistula (n = 8) to determine prececal digestibility of starch. In 5 minipigs the pancreatic duct was ligated (PL) to induce EPI; 3 minipigs served as controls (Con). Various starch sources were tested in a 1-d screening test; therefore, disappearance rate (DR) instead of digestibility was used. Test meals consisted of 169 g DM of a basal diet plus 67.5 g DM of the starch (without thermal treatment; purified; starch content of 89 to 94.5%) and Cr(2)O(3). The test meal contained (% of DM) starch, 67; crude fat, 1.69; CP, 15; crude fiber, 2.0; and Cr(2)O(3), 0.25. In PL, prececal DR of starch was lower than in Con (P < 0.05) for all starch sources. In Con, prececal DR of starch was almost complete (>90%) but was lower (P < 0.05) for potato (Solanum tuberosum) starch (75.4%). In PL, prececal DR of starch was higher (P < 0.05) for wheat (Triticum aestivum) starch (61.2%) than corn (Zea mays) starch (43.0%) and rice (Oryza sativa) starch (29.2%) and intermediate for potato and field pea (Pisum sativum) starch. For patients with EPI, wheat starch seems favorable due to the higher prececal digestibility whereas raw corn and rice starch should be avoided.

Inhibition of reticulo-ruminal motility by volatile fatty acids and lactic acid in sheep.

1. A study was made of the influence on reticulo-ruminal motility, recorded by electromyography, of ruminal infusions of volatile fatty acids (VFAs) and lactic acid in twenty-four sheep maintained by intragastric infusion of a complete liquid diet, in three sheep fed grass pellets, and in nine chronically vagotomized sheep; abomasal and duodenal infusions of VFA and lactic acid were tested in five sheep fed grass pellets. 2. Ruminal infusions of VFAs and lactic acid progressively inhibited the amplitude of the reticulo-ruminal contractions. In many experiments there was no effect on contraction frequency until the cessation of all reticulo-ruminal contractions at which point the maximal concentration of VFA recorded in the abomasum was 28 mM, and that of lactic acid was 20 mM. 3. The concentrations of undissociated VFAs causing cessation of reticulo-ruminal contractions in the vagus-intact sheep were very similar to the concentrations causing abolition of the organized intrinsic motility of the chronically vagotomized sheep. 4. The inhibition of reticulo-ruminal motility with ruminal infusions of mixtures of VFAs and of lactic acid together with VFAs could largely be explained by the sum of the effects of the individual acids present. 5. Abomasal infusion of VFA or lactic acid inhibited the amplitude of ruminal, especially primary ruminal, contractions at concentrations of undissociated acid of 60 mM and above and increased the frequency of reticulum and primary ruminal contractions at about 80 mM. 6. Duodenal infusion of VFAs and lactic acid (100 mM, 5 ml/min) strongly inhibited abomasal motility without affecting reticulo-ruminal motility, and at a higher rate (100 mM, 10 ml/min) abolished motility and inhibited both the amplitude and frequency of reticulo-ruminal contractions. 7. It is concluded that the initial inhibition of reticulo-ruminal motility in ruminal acidosis is unlikely to involve any significant influence from duodenal, or abomasal receptors. The final cessation of reticulo-ruminal motility with ruminal acidosis could involve local effects of VFAs in the reticulo-rumen as well as through excitation of acid-sensitive reticulo-ruminal receptors.

Gastrointestinal pH, motility/transit and permeability in cystic fibrosis.

I reviewed the literature (1966-1994) concerning gastrointestinal (GI) pH, motility/transit, and permeability in cystic fibrosis (CF). Most studies reported were performed with very small numbers of patients, but even when considered together the published data do not confirm some generally expressed views on these topics. The only clear findings were a high incidence of gastroesophageal reflux in CF; pre- and postprandial duodenal pH is 1-2 U lower in patients with CF than in healthy controls; and small intestinal paracellular permeability is 4-10 times greater than normal in CF. Some patients showed abnormalities of lower esophageal sphincter pressure and of esophageal motility, but apart from one case study other disturbances of GI motility have not been reported. The results of hydrogen breath tests strongly suggest that oro-cecal transit is slowed in CF, but these results must be confirmed by an alternative test. Measurements of colonic transit and colonic permeability have not been reported. The few studies of gastric emptying reported are controversial. Whether GI pH, apart from duodenal pH, is normal in CF or whether a subset of patients has exceptionally acid intestinal contents requiring specialized pancreatic enzyme supplementation to normalize digestion is not clear. Finally, I briefly discuss the findings in relation to their possible impact on the pathogenesis of fibrosing colonopathy.

Forestomach motility in the chronically vagotomized sheep.

1. The motility of the reticulo-rumen and omasum in conscious sheep was studied by electromyography from chronically implanted nichrome wire electrodes. The sheep were subjected to vagotomy and were maintained totally by intragastric infusion of liquid nutrients before and after vagotomy. Before vagotomy the motility of the forestomach was essentially similar to that seen in roughage-fed sheep.2. Bilateral thoracic vagotomy transiently abolished all electrical activity of the reticulo-rumen and omasum, but within 1 day some activity returned. Frequent periods of rhythmic local small group discharges were seen over the reticulo-rumen, while the omasum showed prolonged (1-5 min) bursts of mainly slow wave activity.3. Within 1-2 weeks of vagotomy strong contractions of the reticulo-rumen were visible by radiography. Electromyographically, they comprised a rhythmic series of some two to five large group discharges recurring approximately once a minute. Each series of activity was separated from the next by a short period of quiescence. The discharges occurred almost simultaneously over the whole reticulo-rumen and so contrasted with the progressive forward or backward spread of activity seen in the intact animal. The bursts of activity in the omasum, lasting 0.5-2 min, were not co-ordinated with the activity of the reticulo-rumen as they are in the intact animal.4. The activity in the reticulo-rumen and omasum was not affected by bilateral section of the splanchnic nerves and removal of the coeliaco-mesenteric ganglia. Reticulo-rumen but not omasal activity was abolished by atropine (0.1 mg/kg) or hexamethonium (2 mg/kg), while both were stimulated by pentagastrin (3 mug/kg).5. Following vagotomy reticulo-rumen motility was no longer influenced by feeding, or by tactile stimulation of the buccal cavity or oesophagus. Severe distension of the abomasum caused a slight acceleration of the motility rhythm compared to the inhibition seen before vagotomy.6. It is concluded that the reticulo-rumen motility observed after vagotomy is an intrinsic cholinergic motility which is dependent upon the activity of the myenteric plexus. The motility of the omasum after vagotomy is similar to that seen in the intact animal and differs from that of the rumen in that it appears not to depend wholly upon cholinergic control.

Control of intrinsic reticulo-ruminal motility in the vagotomized sheep.

The intrinsic motility of the reticulo-rumen was studied by electromyography in nineteen sheep subjected to bilateral thoracic vagotomy and maintained by intragastric infusion of a complete liquid diet. The influences of distension, temperature and tactile and chemical stimuli on the intrinsic reticulo-ruminal motility were investigated. The level of electrical discharge in the reticulum and rumen in the first 3 days after vagotomy was increased progressively with distension without giving rise to the large group discharges characteristic of the long-term vagotomized sheep, and was reduced by atropine (0.1-1 mg kg-1) but not by hexamethonium (2 mg kg-1). In the long-term vagotomized animals, the frequency of the large group discharges over the reticulo-rumen varied with the degree of reticulo-ruminal distension. The discharges were absent below a threshold rumen volume; above the threshold they increased progressively with volume until a maximal rate of six to seven regular discharges per minute was established at large ruminal volumes. The discharges were abolished by atropine (0.1-1 mg kg-1) or hexamethonium (2 mg kg-1). With the rumen volume below the threshold, in all areas of the reticulo-rumen localized distension stimulated local discharge only and did not induce large group discharge. Replacement of rumen contents with an equal volume of 0.2 M-acetic, -propionic or -butyric acid buffered to pH 4.0 rapidly abolished the large group discharges over the entire reticulo-rumen. Replacement of rumen contents by an equal volume of 0.9% NaCl at 30 degrees C immediately abolished the large group discharges; at temperatures between 35 and 43 degrees C this had no effect. Gentle tactile stimulation increased local discharge in the reticulum and cranial dorsal sac but not in other areas of the rumen and did not affect large group discharge in any region. It is concluded that the intrinsic reticulo-ruminal motility of chronically vagotomized sheep is principally regulated by the degree of reticulo-ruminal distension. Like the C.N.S.-controlled motility of the vagus-intact sheep it is inhibited by high concentrations of volatile fatty acids. Local control mechanisms therefore may interact with central control in the over-all regulation of motility in vagus-intact sheep.

The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.

1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine.

Influence of duodenal digesta composition on abomasal outflow, motility and small intestinal transit time in sheep.

1. A study was made of the influence of duodenal infusion of some of the components of the digesta on gastrointestinal motility, abomasal outflow and small intestinal transit time in seven sheep fed 1500 g grass pellets/day. Gastrointestinal motility was recorded by electromyography. Abomasal outflow was estimated according to the rate of dilution of CrEDTA injected and sampled via an abomasal catheter. Small intestinal transit time was measured by the passage of Phenol Red from the duodenum to the terminal ileum. 2. Abomasal outflow was inhibited during 3 h infusions (5 ml/min) of 100 mM-acetic, propionic, butyric and lactic acids, of 50 mM-HCl, of 0.56 M-glucose, and of 2 and 4% protein hydrolysate. Abomasal motility was inhibited by these infusions and by infusion of 234 mM-oleic acid (0.75 ml/min), of a fat emulsion (Intralipid 20% 0.3 ml/min) and of 50 mM-L-tryptophan (7.5 ml/min). 3. Abomasal motility and, where tested, abomasal outflow, were not affected by duodenal infusion of 150 mM-NaHCO3 (5-10 ml/min), 0.28 M-NaC1 (5-7.5 ml/min), distilled water (5-7.5 ml/min), 25 mM-L-tyrosine (5 ml/min), and of 50 mM-acetic, propionic, butyric and lactic acids (5 ml/min). 4. At concentrations or rates of infusion above the threshold dose needed to inhibit abomasal motility, small intestinal motility was altered and the frequency and amplitude of the reticulo-ruminal contractions were inhibited. 5. The transit time through the small intestine was increased during infusion of 100 mM-acetic, propionic, butyric and lactic acids and decreased during infusion of 0.56 M-glucose and Intralipid. 6. Inhibition of abomasal motility and outflow in sheep receiving 1500 g/day grass pellets was calculated to require increases in the duodenal concentration of volatile fatty acids of about 150% and K+ of about 38%, and to require an increase in the rate of delivery to the duodenum of H+ of about 90%, nitrogen of about 22% glucose of about 2000% and fat of about 84%. 7. These findings are discussed in relation to the composition of abomasal and duodenal digesta in sheep fed different diets. 8. It seems likely that components of duodenal chyme, such as H+, volatile fatty acids, glucose and fat only affect abomasal outflow in sheep fed high-grain diets (glucose, volatile fatty acids), or diets highly supplemented with fat (fat), for short periods after meal feeding (volatile fatty acids) or under abnormal conditions (H+).(ABSTRACT TRUNCATED AT 400 WORDS)