Effects of neutral pH and low-glucose degradation product-containing peritoneal dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a randomized controlled 1-year follow-up study.

BACKGROUND: The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. METHODS: This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. RESULTS: Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. CONCLUSION: Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

Effect of a dietary nonionic surfactant on small intestinal nutrient transport.

Nonionic surfactants are commonly present in many prepared foods and drug formulations as stabilizing agents. The aim of the current study was to examine the effect of the common nonionic surfactant Tween-80 on jejunal glucose transport. New Zealand White rabbits (800-1200 g) were fasted for 24 hr. Jejunal tissue was stripped and mounted in short-circuited Ussing chambers. Unidirectional 3-O-methyl glucose fluxes were determined during a 15-min basal transport period and a subsequent 15-min experimental period after the mucosal addition of Tween-80 at final concentrations of 0.001%, 0.01%, 0.05%, and 0.1%. Tween-80 at final concentrations of 0.1% and 0.05% significantly increased net 3-O-methyl glucose transport over basal levels. The increase in Jnet was due to a significant increase in the absorptive Jm-s flux. Tween-80 at 0.01% and 0.001% did not significantly alter net glucose transport although Jm-s was significantly increased in the presence of 0.01% Tween-80. Tween-80, in concentrations commonly found in prepared foods, enhances the intestinal absorption of glucose.

Dietary carbohydrate accelerates ethanol elimination, but does not alter hepatic alcohol dehydrogenase.

In naive animals the rate of ethanol elimination is dependent on the hepatic alcohol dehydrogenase activity. Carbohydrates have been shown to modify ethanol metabolism by a mechanism that has not been determined. In this study, adult female rats, fed chow diets supplemented with fructose or glucose in their drinking water for 10 days demonstrated significantly greater ethanol elimination rates (4.85 +/- 0.28 and 4.92 +/- 1.56 microM ethanol/min/g liver, respectively) than rats receiving water (3.65 +/- 0.29). The hepatic alcohol dehydrogenase activity of the fructose (1687 +/- 101 nM ethanol/min/g liver) and the glucose (1832 +/- 15)-supplemented rats were not significantly different from that of control rats (1845 +/- 160). Dietary carbohydrate supplementation, therefore, enhanced ethanol elimination, but did not alter the activity of alcohol dehydrogenase. Thus the changes in the ethanol elimination rate following carbohydrate loading were not the consequence of an alteration in hepatic alcohol dehydrogenase.

The effect of erythromycin in gastric emptying of solids and hypertonic liquids in healthy subjects.

We report our study of the effect of erythromycin on gastric emptying of solid and liquid meals in 10 healthy subjects. On different occasions, subjects consumed either a radiolabeled 50% glucose solution, or a radiolabeled standard solid meal after placebo, and after receiving 200 mg of erythromycin intravenously. Erythromycin accelerated the gastric emptying of the hypertonic liquid meal by significantly decreasing the duration of lag phase (p < 0.0001), by significantly increasing the emptying rate at the postlag period (p < 0.001), and by significantly decreasing the duration of the postlag period (p < 0.0001) and the meal remaining in the stomach at 15 (p < 0.05), 30 (p < 0.001), and 60 (p < 0.01) min postprandially. In addition, erythromycin administration induced a significant plasma fall at 15 (p < 0.05) and 30 (p < 0.01) min and a significant increase in pulse rate at 15 and 30 min (p < 0.01) after consumption of the hypertonic glucose solution, whereas three subjects experienced symptoms suggesting dumping syndrome. Furthermore, erythromycin administration enhanced the gastric emptying of solids by almost abolishing the duration of lag phase (p < 0.0001) and by reducing the overall t1/2 of emptying (p < 0.0001), whereas less food was retained in the stomach at 60 (p < 0.001) and 120 (p < 0.0001) min postprandially. Conversely, the postlag t1/2 of the solid meal emptying was not affected by erythromycin, as compared to placebo. We conclude that erythromycin has gastrokinetic properties, affecting the gastric emptying of both liquids and solids.

Effects of ethanol on glucose utilization by cultured mammalian embryos.

We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)-fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose-dependent reductions of embryo protein content (mean +/- SEM = 212 +/- 5, 171 +/- 11, 141 +/- 16, and 113 +/- 9 micrograms/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 +/- 0.3, 23.4 +/- 0.7, 21.8 +/- 0.7, and 21.1 +/- 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48-hr culture period. After 46 hr in culture, control and ethanol-exposed embryos were incubated with 14C-glucose for 2 hr. Ethanol produced dose-dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r = 0.871, p less than 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer.

[Resorption and hormonal reaction in the perioperative phase following enteral administration of glucose]. / Resorption und hormonelle Reaktion in der perioperativen Phase nach enteraler Glukosegabe.

It was the aim of this study to find out whether a postoperative enteral nutrition with glucose is possible. Therefore, an intraduodenal glucose load (15 g/7.5 min.; 20% solution) was applied in 14 patients with normal weight and no metabolic disorders before and on 4 consecutive days after a medium severe abdominal operation. The results show that the resorption of the enterally applied glucose is reduced only on the first postoperative day. After the peak values have been reached, the decrease of glucose from the blood is delayed up to the second postoperative day, although during the whole testing period the insulin secretion--calculated according to the insulinogenic index - corresponds to the glucose stimulation. Thus, an early postoperative enteral nutrition with glucose seems to be possible, but the reduced absorption over a short period has to be taken into consideration.

The 15-minute dumping provocation test.

Following gastric surgery, the diagnosis of the dumping syndrome (DS) has never been precise. The importance of diagnosis is not only in deciding management, but also in comparing series of incidences. The mainstay of diagnosis has been the gastric emptying and dumping provocation test (DPT); however it requires expensive equipment and the interpretation of the results is subjective and therefore variable. In 38 DPTs the percentage plasma volume and pulse rate changes, 15 min after the ingestion of 150 ml of hypertonic glucose, were expressed as percentages of the maximum values encountered and summed to form a score. The tests were independently interpreted by the authors and where they disagreed the result was defined as equivocal. The score was used with the symptoms provoked to follow a simple algorithm to divide the patients into those with and those without DS. There were six suffering from DS on our current interpretation; the new method identified all of these. Three tests were positive on the scoring scheme only and on review the interpreters agreed that all of these patients were suffering from the dumping syndrome. An accurate test using only the baseline and 15 min samples is simple, cheap and has definite rules of interpretation; the only laboratory measurement needed is the haematocrit estimation of three blood samples.

Short-term effect of 4% hypertonic glucose as compared to 4% mixed hypertonic mannitol solution in conventional peritoneal dialysis.

16 peritoneal dialyses were performed in 14 end-stage kidney disease patients; 6 had diabetic nephropathy, and, of the nondiabetic group, 7 had chronic glomerulonephritis, and 1 had polycystic kidney disease. The peritoneal dialysis performed with conventional 1.5% glucose solution, intervened by four consecutive exchanges using 4% hypertonic glucose solution, was compared to 4% mixed hypertonic mannitol solution in the diabetic and nondiabetic group. There was no significant change of serum glucose, when postdialysis with 1.5% glucose solution was compared to 4% mixed hypertonic mannitol solution; however there was a significant change of serum osmolality in both groups. Postdialysis with both 4% hypertonic solutions showed that there was no significant difference of ultrafiltration volume in both groups of patients, but there was a significant difference in serum glucose in the diabetic group. The transport mechanism of mixed hypertonic mannitol solution as compared to hypertonic glucose solution is discussed. The application of hypertonic mannitol solution for clinical use is not advised.

Effect of truncal vagotomy on GIP release induced by intraduodenal glucose or fat in dogs.

In order to elucidate the role of the vagus nerve in the release of gastric inhibitory polypeptide (GIP), mongrel dogs were given a 4-min intraduodenal infusion of 10 g glucose or 5 g soybean oil before and again 1 month after truncal vagotomy (TV). The basal GIP concentrations were significantly elevated after TV. The plasma GIP levels following glucose infusion in the vagotomized dogs were significantly higher than those in the untreated dogs, whereas the GIP levels following fat infusion were not affected by TV. These results suggest that TV influences glucose-induced GIP release but not fat-induced GIP release, indicating that different mechanisms of the vagus nerve may be involved in glucose- and fat-induced GIP secretions.

Thermogenesis induced by nutrient administration in man.

After ingestion or intravenous infusion of a nutrient, the energy expenditure increases. This nutrient-induced thermogenesis represents 6 to 8% of the energy infused when glucose is infused with insulin (glucose clamp technique) to healthy subjects. At physiological plasma insulin levels (i.e. below 200 microU/ml), glucose induced thermogenesis (GIT) was 6%, whereas at supraphysiological levels (i.e. greater than 400 microU/ml) GIT was 8% of the energy content of glucose infused. This thermogenic response to glucose infusion includes two components: An "obligatory thermogenesis" which accounts for the energy cost of storing the nutrient and a "facultative thermogenesis" which is mainly due to a stimulation of sympathetic activity. The thermogenic response to lipid infusion (Intralipid 20%) was 2 to 3% of the energy infused. The stimulation of energy expenditure following amino acid infusion has been studied less in healthy subjects; in depleted patients, the thermogenic response to amino acids has been evaluated to correspond to about 30 to 40% of the amino acid energy infused. In addition to the concept of the thermogenic response to nutrients, it is of interest to know the cost of nutrient storage; for glucose, it amounted to 12%, for lipid to 4% of the energy stored. It is concluded, that lipid induces a lower thermogenic response and has a smaller cost for storage than glucose. Thus, lipid infusion allows giving energy more efficiently to the patient than large amounts of glucose. In total parenteral nutrition, it is common practice to supply non-protein energy roughly equally between glucose and fat; this is more economical than the infusion of large amounts of glucose.

The importance of the distal stomach in gastric emptying of liquids in man.

The effects of pyloroplasty and vagal denervation of the distal stomach on gastric emptying of 10% dextrose have been compared. In a randomized trial, 38 male patients having elective surgery were treated by proximal gastric vagotomy (PGV, N = 10), proximal gastric vagotomy and pyloroplasty (PGV + P, N = 9), total gastric vagotomy (TGV, N = 9), and total gastric vagotomy and pyloroplasty (TGV + P, N = 10). Gastric emptying was recorded using an external scanning technique before and after operation. Compared with before operation, all four procedures resulted in significantly faster emptying during ingestion of the meal (the filling phase). This is attributable to failure of receptive relaxation of the proximal stomach. The emptying phase (after ingestion of the meal) was unchanged by PGV, but was significantly altered by PGV + P, TGV, and TGV + P (Principal Component Analysis). Before operation and after PGV, emptying fitted a monoexponential curve. In contrast, after PGV + P, TGV, and TGV + P, the emptying phase fitted a double exponential curve. Emptying was precipitate initially, but slowed later, leaving a large residual volume. We conclude that, when the proximal stomach is denervated, the intact, innervated distal stomach can restore the emptying of hypertonic dextrose to normal; however, when the distal stomach is denervated or pyloroplasty has been performed emptying remains uncontrolled. Since pyloroplasty and vagal denervation have the same effect, it is concluded that the mechanism retarding the emptying of hypertonic dextrose is an active mechanism that resides in the terminal antrum or pylorus.

Gastric-emptying characteristics of two glucose polymer-electrolyte solutions.

Inadequate carbohydrate and fluids can limit physical performance; optimal delivery of both should be the goal of any beverage designed especially for the athlete. In this study, the gastric-emptying characteristics of two carbohydrate-electrolyte solutions were compared with water. The 5% carbohydrate solution contained 3% Polycose glucose polymers and 2% fructose, whereas the 7% solution contained 5% Polycose glucose polymers and 2% fructose. Both solutions contained similar amounts of sodium, potassium, calcium, magnesium, and chloride in the range suggested by the American College of Sports Medicine for rehydration solutions. Four hundred milliliters of each solution were administered to six male subjects and the amount of fluid emptied at 30 and 60 min by each subject was calculated. A non-absorbable dye, phenol red, was used to correct for gastric secretion. The gastric emptying of the 7% solution in healthy adult male subjects was not significantly different from the 5% solution or cold water. Inclusion of a polymerized form of glucose in a 7% glucose polymer-fructose solution can supply 70 g of carbohydrate per liter and also maximizes rehydration. This solution may be particularly useful in those activities where fluid and energy loss are particularly important.

Utilization of ketone bodies and glucose by established neural cell lines.

The rates of utilization of [3-14C]-acetoacetate, [3-14C]-3-hydroxybutyrate, and [6-14C]-glucose were measured in four established cell lines from neuroblastoma of rat (B103) and mouse (N4TG1) and from rat astrocytoma (RGC6) and mouse oligodendroglia (G2620). The rates of incorporation of acetoacetate into lipid were 3-5 times higher than glucose in all cell lines. The incorporation of 3-hydroxybutyrate was similar to that of glucose. Thin-layer chromatography of the total lipid extracts showed the same relative rates of use of these substrates for synthesis of various phospholipids and neutral lipids. The rates of incorporation into neutral lipids and phosphatidylcholine were essentially linear for 12 hr; however, that into phosphatidylethanolamine was markedly higher in the second 6 hr interval than in the first. In all cases, the greatest percentage of label (35-50%) appeared in the phosphatidylcholine fraction. The distribution of label from each of the three substrates among the various lipids was similar in the glial cells, but there were marked differences in distribution of the two ketone bodies in the neuroblastoma lines. These cells also synthesized lipids that migrated to the same area on the chromatogram as cholesterol esters and free fatty acids. In three of the four cell lines the rates of oxidation were highest for glucose, intermediate for acetoacetate, and lowest for 3-hydroxybutyrate. The ratios of the rate of incorporation to the rate of oxidation were higher for ketone bodies (3.32 for 3-hydroxybutyrate and 5.29 for acetoacetate) than for glucose (0.41). This indicates that in these cells ketone bodies are directed toward lipid synthesis rather than oxidation, and glucose is preferentially used as an energy source.

Metabolic response to hypertonic glucose administration in Reye syndrome.

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.

The use of a crystalline amino acid mixture for parenteral nutrition in low-birth-weight infants.

Thirty-six preterm, sick, low-birth-weight neonates were given either total or partial parenteral nutrition. The patients were divided into three groups according to their birth weights: group A -less than 1,000 gm, 12 patients: group B--between 1,000 and 1,500 gm, 15 patients: group C--more than 1,500 gm, 9 patients. The solution for total parenteral nutrition contained 20% glucose and 2.6% crystalline amino acids plus appropriate amounts of vitamins and minerals. The volume of infusate given was usually 125 ml/kg/day, but varied depending on the clinical condition of the patient; occasionally it was as high as 150 to 175 ml/kg/day. Infusate of one-half strength was administered initially; its concentrations of glucose and amino acids were increased to three quarters and full strength gradually, if tolerated. The solution for total parenteral nutrition was infused into the superior vena cava via a central venous catheter; that for partial parenteral nutrition was given into a peripheral vein to supplement inadequate oral feedings. The period of parenteral nutrition lasted from 5 to 49 days, with an average of 13.2 days. The intake of 500 mg of nitrogen as crystalline amino acids and 100 kcal as glucose was capable of achieving body weight gain. Positive nitrogen balance of various degrees was also observed. Hyperglycemia of a slight to moderate degree was observed in nine patients; only three required insulin therapy. Two patients had thrombotic occlusion of the central venous catheter. The conclusion was reached that total parenteral nutrition or partial parenteral nutrition, when properly managed, is a safe procedure in small, premature infants. The amino acid solution given as a nitrogen source along with adequate calories was effective in promoting weight gain and nitrogen balance; it was apparently well tolerated by low-birth-weight neonates.

Myocardial utilization of hypertonic glucose during hemorrhagic shock.

Awake pigs were rapidly bled 40% of total blood volume to induce hemorrhagic shock. Immediately after the induction of shock, all pigs received a single intravenous injection of radioactive-labeled glucose-U-14C. Simultaneously with glucose-U-14C injection, ten pigs received single central intravenous injections of unlabeled 50% glucose, four pigs received equiosmolar 25% mannitol, six did not receive either 50% glucose or mannitol, and two received 50% glucose plus insulin. Mean arterial pressure with 50% glucose was 89.9 mm. Hg at 15 minutes of shock and significantly higher than without 50% glucose, 48.3 mm. Hg or after mannitol, 46.7 mm. Hg (P = 0.05). Mean cardiac output at 10 minutes of shock with 50% glucose was 2.24 L. per minute and significantly higher than with mannitol, 1.34 L. per minute, or without 50% glucose, 0.94 L. per minute (P = 0.05.). Evidence for increased anaerobic myocardial utilization of the administered unlabeled 50% glucose was shown by a 12% greater production of unlabeled lactate in the venous coronary sinus blood from unlabeled 50% glucose in contrast to those not given 50% glucose at 10 minutes after shock (P = 0.05). Also, 50% glucose significantly increased mean arterial pressure, cardiac output, and survival over both control groups.