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Biomedical subjects

R G Settle

Publications and source records attributed to R G Settle.

At least 19 recordsLinked to original sources

Supplementation with gum arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet.

In chronic renal failure (CRF), plasma concentrations of the products of protein metabolism are increased. Current dietary management is to prescribe a decrease in protein intake. The use of dietary fiber to increase fecal excretion of retained metabolites in CRF may be a beneficial adjunct to a low-protein diet (LPD). Colonic bacteria ferment dietary fiber, providing them with energy for growth and nitrogen incorporation, in turn, increasing nitrogen excretion in feces. Sixteen CRF patients consuming an LPD were randomly assigned to receive a supplement of a highly fermentable fiber, gum arabic (50 g/d), or a placebo (1 g pectin/d) in a prospective, single-blind, crossover design. Fecal bacterial mass and fecal nitrogen content were significantly increased during supplementation with gum arabic compared with the baseline LPD or supplementation with pectin. Serum urea nitrogen was significantly decreased during supplementation with gum arabic compared with the baseline LPD or supplementation with pectin. Nitrogen balance did not change significantly.

Adult

The effect of insulin-like growth factor-1 on protein metabolism and hepatic response to endotoxemia in parenterally fed rats.

To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190-230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats.

7-Alkoxycoumarin O-Dealkylase

Identification of glucose response proteins in two biological models of beta-cell adaptation to chronic high glucose exposure.

High resolution 2-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with computerized analysis of gel images was used to search for proteins whose biosynthesis was induced or repressed in pancreatic islet cells chronically exposed to high glucose in an in situ and a tissue culture model of islet cell adaptation to excessive fuel load. The in situ model involved a 4-day intravenous infusion of either 50% glucose or 0.45% saline solution, followed by islet isolation, [35S]methionine labeling at 3 and 18 mM glucose for both groups, and protein analysis by 2-dimensional SDS-PAGE. The tissue culture model involved a 7-day culture of isolated rat islets in RPMI 1640 with 10% fetal calf serum containing either 3 or 30 mM glucose, followed by radiolabeling and 2-dimensional PAGE of proteins as in the in situ model. A small fraction of about 1.5% of the approximately 2000 identifiable proteins can be characterized as adaptive proteins. Of these altogether 58 proteins in the two models, 5 proteins were demonstrable in both models and two of these (proteins 1526 and 7622) are particularly noteworthy. Protein 1526 (Mr 57,000; pI 5.09) showed the same response pattern in both models and its expression was most enhanced when islets from chronically glucose-infused animals or those cultured for 7 days at 30 mM were radiolabeled at 18 mM glucose. Protein 7622 (Mr 68,000; pI 6.50) (also known as GSP-65; Collins, H.W., Buettger, C., and Matschinsky, F.M. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5494-5498) showed a different labeling pattern in the two models: stimulation of [35S]methionine incorporation by 18 mM glucose both in control and experimental islets from the infusion study, but lack of such stimulation of radiolabeling in islets cultured for 7 days at 30 mM glucose in contrast to islets cultured at 3 mM. The experimental strategy and the methodology are evaluated and the significance of the results is discussed. Potentials of the approach and plans for future experiments are considered.

Animals

Defining and reporting diarrhea in tube-fed patients--what a mess!

The frequency and consistency of stools of all patients at a VA Medical Center who were tube-fed during a 3-mo period were recorded prospectively and analyzed in terms of eight definitions of diarrhea derived from the literature. The extent of diarrhea, reported as incidence and as percentage of days with diarrhea, was used to determine differences among the definitions. The relationship between extent of diarrhea and duration of monitoring patients was also determined. Results of 29 patients monitored for 13.0 d (6.5 d) [median (interquartile range)] indicated that the definition of diarrhea significantly influenced the reported incidence of and percentage of days with diarrhea. Duration of monitoring showed a significant, positive relationship to the incidence of diarrhea (ie, the longer the duration, the more likely that diarrhea was observed). When diarrhea was reported as the percentage of days with diarrhea, the influence of monitoring duration virtually disappeared.

Anti-Bacterial Agents

Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center.

Smell and taste disorders are common in the general population, yet little is known about their nature or cause. This article describes a study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia. Major findings suggest that: chemosensory dysfunction influences quality of life; complaints of taste loss usually reflect loss of smell function; upper respiratory infection, head trauma, and chronic nasal and paranasal sinus disease are the most common causes of the diminution of the sense of smell, with head trauma having the greatest loss; depression frequently accompanies chemosensory distortion; low body weight accompanies burning mouth syndrome; estrogens protect against loss of the sense of smell in postmenopausal women; zinc therapy may provide no benefit to patients with chemosensory dysfunction; and thyroid hormone function is associated with oral sensory distortion. The findings are discussed in relation to management of patients with chemosensory disturbances.

Burning Mouth Syndrome

Experimental short-bowel syndrome: effect of an elemental diet supplemented with short-chain triglycerides.

To determine whether short-chain triglycerides (SCTs, 1:1 triacetin:tributyrin, wt:wt) enhance intestinal adaptation in short-bowel syndrome (SBS), male Sprague-Dawley rats underwent 60% distal small-bowel resection with cecectomy and received either a chemically defined diet (CD) or a CD containing 40% of nonprotein energy as either medium-chain triglycerides (MCTs) or SCTs. After 12 d the SCT group had significantly increased jejunal mucosal weight compared with the MCT and CD groups and had significantly increased segment weight and mucosal protein compared with the CD group. In the colon the SCT group had significantly increased segment and mucosal weights and mucosal protein and DNA compared with both the MCT and CD groups. Body-weight change and measurements of serum ketones, albumin, glucose, and triglycerides revealed no significant differences among groups. SCTs improved jejunal and colonic adaptive growth and maintained comparable nutritional status in SBS when compared with CD alone or CD with MCTs.

3-Hydroxybutyric Acid

Identification of human appendicitis by in vitro nuclear magnetic resonance.

The spin-lattice relaxation time, T1 as determined by nuclear magnetic resonance techniques, correlates positively with tissue water content. The latter relationship has been observed in rabbits with experimentally induced appendicitis whose inflamed appendiceal tissues had significantly higher T1's and water contents than tissue from normal controls. The present experiment studied these relationships in humans. Tissue water content and T1 were measured on appendiceal tissue from 10 patients with documented appendicitis and from 6 controls without the disease. All T1's were determined within 30-60 min of removal of the appendix at operation. The mean in vitro T1 of appendiceal tissue from patients with appendicitis was significantly higher than that of controls (527 +/- 15 msec versus 430 +/- 17 msec, mean +/- SEM, P less than 0.002). In addition, a strong positive correlation was noted between T1 and tissue water content (r = 0.70, P less than 0.01). Based on these findings, the use of in vivo magnetic resonance imaging techniques to detect human appendicitis noninvasively warrants investigation.

Adolescent

Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.

When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.

Animals

Burning mouth symptoms: a clinical review, Part I.

The multiple etiologies proposed in the literature for burning mouth symptoms (BMS) make definitive clinical diagnosis and treatment difficult. Proposed etiologies can be divided into local systemic, and psychogenic factors. Part I of this two-part article provides a review of the BMS literature focusing on local etiological factors and possible approaches to their treatment.

Burning Mouth Syndrome

Burning mouth symptoms, Part II: A clinical review.

Part I of this series presented a review of the literature on Burning Mouth Symptoms (BMS) focusing on its prevalence, its symptoms, and proposed local etiologic factors associated with the condition. Part II will focus on the possible systemic and psychological etiologic factors in order to provide the dental clinician with a perspective on the alternative factors that may cause BMS.

Burning Mouth Syndrome

The effect of pectin on hepatic lipogenesis in the enterally-fed rat.

The fermentation of pectin by colonic bacteria produces short-chain fatty acids (SCFA) which are then absorbed by the host. The purpose of this study was to determine whether pectin, added to a chemically defined diet, would increase hepatic lipogenesis and whether this effect is mediated by intestinal bacteria. Eighteen Sprague-Dawley rats underwent placement of a feeding gastrostomy and a swivel apparatus. Postoperatively, rats were randomly assigned to one of three groups: 1) No Pectin received a fat-free chemically defined diet, 2) Pectin received the same diet with the addition of 1% (w/v) pectin, and 3) Neomycin received the same diet with 1% w/v pectin and neomycin (80 mg/kg of body weight daily). On the 5th postoperative d, all diets included 12.5% (v/v) deuterium as D2O. After the infusion of the labeled diets for 24 hr, the content and deuterium enrichment of liver palmitate, stearate and oleate were measured and the production rates calculated. The liver content and production rates of these fatty acids were higher in Pectin animals than in either the No Pectin or Neomycin animals. Since the effect of pectin on hepatic lipogenesis was reduced by the concomitant administration of the intestinal antibiotic neomycin, it appears that this effect depends on the bacterial fermentation of pectin. It is postulated that the SCFA produced during pectin fermentation promote lipogenesis via a direct stimulatory effect, in addition to being carbon donors.

Animals

In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.

Adenosine Triphosphate

Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon.

Exogenous glucocorticoids markedly increase the in vivo uptake and utilization of glutamine by the intestine. Since glutamine is the major oxidative fuel for the small intestine, we investigated whether glucocorticoids induce changes in the specific activity of the enzymes that mediate glutamine degradation (glutaminase) and synthesis (glutamine synthetase). Male Sprague-Dawley rats received a 7-day elemental diet. On Day 5, animals were randomized to one of four groups and received either saline (Control) or one of three doses of dexamethasone im: 0.1 mg/kg (Lodex); 0.3 mg/kg (Middex); or 0.6 mg/kg (Hidex). Forty-eight hours later jejunal and colonic segments were assayed for protein, glutaminase, and glutamine synthetase activity. A stress dose of dexamethasone (Hidex) produced a significant increase in both jejunal and colonic glutaminase specific activity (P less than 0.02 vs Control and P less than 0.05 vs Control, respectively). These data suggest a mechanism whereby glucocorticoids increase the intestinal utilization of glutamine by increasing the specific activity of intestinal glutaminase.

Animals

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.

Acetoacetates

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.

Adaptation, Physiological

Small bowel disaccharidase activity in the rat as affected by intestinal resection and pectin feeding.

This study investigated the effects of small bowel resection (SBR) and a pectin-supplemented elemental diet (ED) on intestinal disaccharidase activity. Rats underwent placement of feeding gastrostomy and swivel apparatus. Control animals were returned to their cages while resected animals underwent an 80% SBR. Postoperatively, animals received either a pectin-free ED or the ED supplemented with 2% pectin. After 2 wk jejunal and ileal mucosal sucrase, maltase, and lactase activities and protein content were determined. Feeding the ED after SBR resulted in significant increases in all three ileal segmental disaccharidase activities but only maltase activity was significantly increased in the jejunum. The pectin-supplemented ED, however, significantly enhanced the adaptation of jejunal and ileal segmental sucrase, maltase, and lactase activity to SBR with the increase in all three jejunal disaccharidase activities being significantly greater than that of the resected animals fed the ED alone.

Adaptation, Physiological

Comparison of parenteral nutrition and enteral feeding with pectin in experimental colitis in the rat.

The effect of a pectin-supplemented enteral diet on experimental colitis was compared with parenteral nutrition and with a pectin-free enteral diet. Forty-five rats had feeding catheters placed into either the stomach (IG, n = 31) or the superior vena cava (IV, n = 14) and then received acetic acid (colitis) or saline (control) enemas. After the enema, all rats received the same diet, either IG or IV, for 6 d except for 15 rats (IGP, 9 colitis and 6 controls), which had 1% pectin added to the diet. At the end of the feeding period the IGP group had significantly less colonic inflammation and/or necrosis than either IV (p less than 0.03) or IG (p less than 0.04) groups. Nitrogen balance, serum albumin, total iron-binding capacity and body weight did not differ significantly among dietary regimens. Thus, the degree of bowel injury in experimental colitis was decreased when animals were fed a pectin-supplemented enteral diet and this effect was independent of nutritional status.

Animals