R. Gregg Settle

Effect of a Glutamine-Supplemented Enteral Diet on Methotrexate-Induced Enterocolitis

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.

Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acids.

Dietary fiber, which stimulates intestinal mucosal growth, is fermented by anaerobic bacteria in the rat hindgut to the short-chain fatty acids (SCFA) acetate, propionate, and butyrate. Butyrate is the preferred oxidative fuel of the colonocyte in vitro, and the provision of preferred intestinal fuels has been shown to stimulate mucosal proliferation in vivo. This study determined whether chronic colonic infusion of butyrate or a combination of SCFA would stimulate intestinal mucosal growth in an animal deprived of its normal source of SCFA, fiber fermentation in the cecum. Adult male Sprague-Dawley rats were fed a fat- and fiber-free elemental liquid diet and underwent cecectomy, ileocolic anastomosis, and insertion of a proximal colonic infusion catheter. Rats were then assigned to receive either a continuous infusion of butyrate (20 mM, 40 mM, or 150 mM), SCFA (70 mM acetate + 35 mM propionate + 20 mM butyrate), or saline, or to receive no infusion. A seventh group underwent proximal colonic transection and reanastomosis. After 7 days, jejunal, ileal, and proximal colonic segments were analyzed for mucosal weight, protein, RNA, and DNA. In the colon, the 40-mM butyrate infusion resulted in significant elevations in all mucosal parameters relative to all three control groups, saline infusion, no infusion, and transection. Both the 20-mM butyrate and the SCFA groups showed increased colonic mucosal DNA compared to controls. In the jejunum and ileum, mucosal DNA content was significantly greater in the SCFA group than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex differences in odor identification ability: a cross-cultural analysis.

To ascertain the generality of a sex difference noted in odor identification ability, the University of Pennsylvania Smell Identification Test (UPSIT) was administered to four groups of subjects: Black Americans (n = 438), White Americans (n = 1559), Korean Americans (n = 106), and Native Japanese (n = 308). The women of all four groups outperformed the men to the same relative degree. The Korean American group performed better than the Black and White American groups, which, in turn, outperformed the Native Japanese. Analyses of the proportions of subjects correctly answering each of the test items revealed considerable similarity of relative item difficulty among the subject groups. Taken together, these data suggest that sex differences in odor identification ability are probably not due to ethnic or cultural factors, per se.

Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection

After massive small bowel resection, total parenteral nutrition (TPN) is prescribed to maintain nutritional status. However, TPN reduces the mass of the remaining intestinal mucosa, whereas adaptation to small bowel resection is associated with increased mucosal mass. Short-chain fatty acids (SCFAs) have been shown to stimulate mucosal cell mitotic activity. This study determined whether the addition of SCFAs to TPN following small bowel resection would prevent intestinal mucosal atrophy produced by TPN. Adult rats underwent an 80% small bowel resection and then received either standard TPN or TPN supplemented with SCFAs (sodium acetate, propionate, and butyrate). After 1 wk, jejunal and ileal mucosal weights, deoxyribonucleic acid, ribonucleic acid, and protein contents were measured and compared with the parameters obtained at the time of resection. Animals receiving TPN showed significant loss of jejunal mucosal weight, deoxyribonucleic acid, ribonucleic acid, and protein and ileal mucosal weight and deoxyribonucleic acid after small bowel resection, whereas animals receiving SCFA-supplemented TPN showed no significant change in the jejunal mucosal parameters and a significant increase in ileal mucosal protein. These data demonstrate that SCFA-supplemented TPN reduces the mucosal atrophy associated with TPN after massive bowel resection and thys may facilitate adaptation to small bowel resection.

Tube Feeding-Related Diarrhea in Acutely III Patients

Acutely ill patients received tube feeding for an average of 15.8 days and, on average, 35% of those days were spent in the intensive care unit (ICU). Patients were prospectively assigned either a fiber-free formula (FFF-OSMOLITE HN, Ross; n = 50) or a fiber-supplemented (soy polysaccharide 14.4 g/L) formula (FSF = JEVITY, Ross; n = 50). Diarrhea was defined as three or more loose or watery stools per day and occurred in 30% of all patients. Diarrhea developed in 29 (41%) of the 71 patients who received antibiotics during, or within 2 weeks prior to, the feeding period, whereas only 1 (3%) of the 29 patients not receiving antibiotics developed diarrhea (p less than 0.005); and this patient developed diarrhea on the day of death. Among the 30 patients with diarrhea, stool Clostridium difficile (CD) toxin was positive in 15 (50%), negative in 11 (37%), and was not measured in four. The mean serum albumin was significantly lower in patients with diarrhea (2.43) than in those without diarrhea (2.75) (p = 0.043). There were no significant differences in age, sex, diagnoses, number of feeding days, and percent ICU days between patients with and without diarrhea. While not statistically significant, patients who received FSF were observed to have a lower incidence of diarrhea, a lower percentage of diarrhea days per total feeding days, and a lower frequency of positive CD toxin assays than patients who received FFF. In this patient population, antibiotic usage was the factor most strongly associated with diarrhea during tube feedings.

Nutritional assessment: Whole body impedance and body fluid compartments

Abstract Measures of total body water and extracellular fluid volume would provide valuable information for the assessment of nutritional status in patients. Time and cost factors make the use of tracer dilution techniques impractical in routine nutritional assessment batteries. Some studies suggest that measurements of the electrical impedance properties of the body can be used to estimate total body water and extracellular fluid volume. The observed and predicted relationships between whole body impedance and body fluid compartment volumes are discussed, and problems which may limit the accuracy of prediction of body fluid compartment volume from whole body impedance measures are discussed. With further improvements, whole body impedance measurement could provide a practical bedside method for measurement of body fluid compartment volumes.

Assessing burn wound depth using in vitro nuclear magnetic resonance (NMR)

There is no accurate noninvasive method for differentiating between partial-thickness and full-thickness cutaneous burn wounds. Full-thickness burns (FTB) result in slower resorption of wound edema than partial thickness burns (PTB). Since proton NMR parameters, particularly the T1 relaxation time, correlate with tissue water content (TWC), the present study determined whether proton NMR could distinguish PTB from FTB. An area of upper dorsum (approximately 15% BSA) of 35 adult rats was immersed in boiling water for either 3 sec (PTB) or 10 sec (FTB). In 10 control rats, the same area was immersed in room temperature water. Rats were sacrificed at either 3 or 48 hr after burn, and skin samples were analyzed to determine spin-lattice (T1) and spin-spin (T2) relaxation times. TWC was then measured gravimetrically by desiccation. Both T1 and T2 times significantly correlated with TWC (T1: r = 0.74, P less than 0.0001; T2: r = 0.75; P less than 0.0001). Both PTB and FTB resulted in significant elevations of T1, T2, and TWC 3 hr after injury (P less than 0.001). At 48 hr postburn the T1, T2, and TWC of the PTB group had decreased to control values (P less than 0.05), while all FTB parameters remained significantly elevated as compared to both the control and the 48-hr PTB parameters (P less than 0.001). In vitro NMR measurements distinguish PTB from FTB in this rat model within 48 hr. These data provide a basis for investigating in vitro NMR techniques for the noninvasive assessment of burn wound depth.

Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin

Total parenteral nutrition (TPN) is associated with intestinal mucosal atrophy. Acetoacetate is oxidized in preference to glucose by both enterocytes and colonocytes and is not present in TPN. The purpose of this study was to determine whether replacement of a portion of glucose calories with monoacetoacetin, the glycerol ester of acetoacetate, could inhibit TPN-associated intestinal atrophy. Male Sprague-Dawley rats (200-250 g) underwent superior vena caval cannulation and were assigned to receive chow ad libitium (CHOW), TPN with 0.86 M monoacetoacetin (ACAC), or TPN with 0.86 M glycerol to control for the glycerol component of monoacetoacetin (GLYC). Nitrogen balance was measured over 7 days after which time the animals were weighed and sacrificed. Jejunal and colonic segments were harvested and the mucosal weight, protein, RNA, and DNA contents measured. All groups showed comparable weight gain. Cumulative nitrogen balance was positive for both TPN groups. Significant decreases in mucosal parameters occurred in both TPN groups compared to the CHOW group, but atrophy was significantly inhibited in both jejunum and colon of the ACAC group compared to the GLYC group. Thus, the substitution of monoacetoacetin for glucose calories in parenteral nutrition solutions inhibited TPN-related atrophy of intestinal mucosa while maintaining normal growth.

An Examination of Intertrial Interval and Gender Influences on Sucrose Detection Thresholds Established by a Modified Staircase Procedure

The influence of intertrial interval durations ranging from 7 to 30 s upon sucrose detection thresholds of sixteen subjects was investigated by means of a modified staircase procedure with intertrial rinses. In addition, the influence of the sex of the subject was examined. Neither the intertrial interval nor the sex of the subject significantly affected sucrose detection thresholds. The results suggest that, in sucrose detection threshold studies using the present procedure, one can employ intertrial intervals as short as 7 s without significantly affecting the threshold value.

Short-Chain Fatty Acids

The short-chain fatty acids (SCFA), also called the volatile fatty acids (VFA), are the C1–6 organic fatty acids. These are formed in the gastrointestinal tract of mammals by microbial fermentation of carbohydrates (Wolin, 1981 ; Wrong, 1981 ; Cummings and Branch, 1986). Acetate, propionate and butyrate account for 83% of SCFA so formed (Nyman and Aso, 1982; Demigne and Remesy, 1985) and are produced in a nearly constant molar ratio 60: 25 : 15, respectively (Cummings and Branch, 1986). Among their various properties, SCFA are readily absorbed by intestinal mucosa (Cummings et al., 1987), are relatively high in caloric content (Yang et al., 1970), are readily metabolized by intestinal epithelium and liver (Cummings, 1981), stimulate sodium and water absorption in the colon (Roediger and Rae, 1982), and are trophic to intestinal mucosa (Sakata, 1987; Kripke et al., 1988d).