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Effects of structurally different lipid emulsions on human neutrophil migration
April 2000
4159 SUCCESSFUL AVOIDANCE OF TOTAL PARENTERAL NUTRITION BY ADMINISTRATION OF AN AMINO-ACID BASED ENTERAL FORMULA (NEOCATE) IN INFANCY. Gigi A. Veereman-Wauters, Els Van Elsacker, lise Hoffman, Liliane De Swert, Pediatric Gastroenterology, Univ Hospitals Leuven, Leuven, Belgium; Pediatric Allergology, Univ Hospitals Leuven, Leuven, Belgium. Total parenteral nutrition (TPN) is a necessary route for nutritional support in cases of severe food intolerance in infancy but involves life threatening risks (sepsis, hepatotoxicity), a high level of care and high costs. We report 7 infants in whom the use of an amino-acid based enteral formula (Neocate®) allowed discontinuation of TPN. Over a 9 months period (9-98/699) we treated 7 infants (3 girls, 4 boys, mean agel0,7 rno-range 2-23 mo) with Neocate® after failure of feeding attempts with various semi-elemental formulas. Food intolerance was a consequence of short gut syndrome (3), multiple food allergies (2) and status post toxic megacolon with enterocolitis (2). In the 3 infants with short gut syndrome advancing semi-elemental feeds failed blo increased ileostomy output (>50%) or malabsorption (reducing substances >2g%) with less than 20% of total caloric requirements being provided enterally. Introduction of Neocate® allowed increase of enteral caloric intake from 13 to 52 Callkg over 44 days in a baby who subsequently underwent liver transplantation, and from 17 to 95 Cal!kg over 97 days and 12 to 104 Callkg over 226 days respectively in 2 patients in whom TPN was definitely stopped. Two infants with multiple food allergies and 2 patients recovering from severe enterocolitis (I Hirschprung, I unclear) needed TPN blo repeated symptomatic relapse (bloody stools) upon reintroduction of semi-elemental feeds. A similar gradual enteral regimen using Neocate® allowed discontinuation of TPN in all 4. After a period of at least 3 months, reintroduction of other nutrients was thusfar successfull in 2. In infants, with severe intestinal insufficiency (short gut) who receive semi-elemental food but remain TPN dependent or with severe inflammation and who do not tolerate polymeric or semi-elemental nutrition, Neocate® can improve enteral tolerance to full energetic requirements and lead to discontinuation of parenteral support.
4160 HUMAN NEUTROPHIL MEMBRANE FLUIDITY AFTER INCUBATION IN STRUCTURALLY DIFFERENT LIPID EMULSIONS. Geert 1. Wanten, Dirk Roos, Anton H. Naber, Acad Hosp Nijmegen, Nijmegen, Netherlands; Univ of Amsterdam, Amsterdam, Netherlands. Rationale: Medium chain triglyceride (Mj-containing lipid emulsions activate human neutrophils in vitro, contrary to long-chain (L) and structured lipid (SL) emulsions. To test the hypothesis that these distinct responses result from alterations in cell membrane fluidity induced by various emulsions, we performed the present study. Method: Isolated neutrophils from 8 volunteers were incubated for I hour in 2.5 mM emulsions containing L, M, mixed LM, LM enriched with a-tocopherol (LME) or SL emulsions. This lipid concentration is physiological in patients when emulsions are administered intravenously. Thereafter the cells were washed twice and membrane fluidity was measured as the fluorescence polarization of diphenyl-hexatriene (DPH). Results are presented as fluorescence anisotropy r, the reciprocal of membrane fluidity. Results: Compared to lipid-free incubation (0.I82::t:0.023), LM (0.I28::t:0.016), as well as LME (0.124::t:0.019), SL (0. I67::t:0.029) and M (0.095::t:0.038)significantly decreased r (and thus increased membrane fluidity, all p < 0.02 with Wilcoxons signed ranks test), while L (0.I71::t:0.0I7) had no effect (p=0.14). While LM and LME were not different (p=0.33), M further reduced r compared to both previous emulsions (P
4161 EFFECTS OF STRUCTURALLY DIFFERENT LIPID EMULSIONS ON HUMAN NEUTROPHIL MIGRATION. Geert 1. Wanten, Dirk Roos, Anton H. Naber, Acad Hosp Nijrnegen, Nijmegen, Netherlands; Univ of Amsterdam. Amsterdam, Netherlands. Background: While the use of intravenous lipid emulsions has been associated with an increased risk for infectious complications, the imrnunomodulatory characteristics of structurally different emulsions have not been well characterized. Aim: To test the hypothesis that human neutrophil migration is distinctively influenced by structurally different lipid emulsions in physiological concentrations, i.e. concentrations (up to 10 mM) reached in patients when lipids are administered intravenously. Method: Isolated neutrophils from 8 volunteers were incubated in medium or 2.5 mM lipid emulsions containing long-chain- (L), medium-chain- (M), mixed LM-, tocopherol-enriched LM (LME), or structured lipids (SL). The cells were loaded above 3 pm-pore-sized filters and migration was measured after I hour as the percentage filterpassage in the presence (chemotaxis) or absence (random migration) of chemotactic factor (formylated peptide (fMLP) or zymosan-activated serum (ZAS)). Results: fMLP-induced chemotaxis under lipid-free conditions amounted to 61::t: 14% and
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decreased with LM to 11::t:9%, with LME to 18::t:1O%, with SL to 39::t:18%, and with M to 5::t:2% (all p<0.05 with Wilcoxons signed ranks test), while L had no effect (59::t: 10%, p=0.59). ZAS-induced chemotaxis showed similar results. Compared to lipid-free incubation (l9± 10%), random migration significantly decreased with LM (II ::t:2%), LME (12::t:2%)and M (5::t:2%), while L (l8±3) and SL (20± I %) had no effect. Compared to LM, chemotaxis with LME significantly increased (p = 0.004). Chemotaxis decreased in direct proportion to LM concentration, reaching steady state at 2 mM. Conclusion: Human neutrophil migration is distinctively influenced by structurally different lipid emulsions, depending on triglyceride chain-length and -concentration, as well as tocopherol content.
4162 LACTULOSE REDUCES INTRACOLONIC ACETALDEHYDE PRODUCTION AND ETHANOL ELIMINATION RATE IN RATS. Semia H. Zidi, Satu M. Vakevainen, Mikko P. Salaspuro, Kalle Jokelainen, Research Unit of Alcohol Diseases, Helsinki, Finland.
Background: Most of ethanol oxidation takes place in the liver. However, ethanol is also oxidized by normal colonic bacteria possessing alcohol dehydrogenase (ADH) activity. The first metabolite of ethanol oxydation is acetaldehyde, a carcinogen also linked to several organ toxic effects of alcohol. ADH-mediated bacterial reaction is pH dependent and it is inhibited under acid conditions. Lactulose is a non-absorbable disaccharide metabolized by caecal bacteria into short chain fatty acids, mainly lactate, thus acidifying caecal contents. The aims of the present study were to examine the effect of chronic lactulose feeding on the colonic and faecal pH, intracolonic acetaldehyde production and total ethanol elimination rate (EER) in rats. Methods: Forty 8-week-old male Wistar rats weighing 308::t:8g (mean::t:SEM) were divided into four 10-rat-groups. Group I and Group 3 received lactulose (11 g/kg b.w. for 14 days) in drinking water and by daily intragastric intubation. Group 2 and 4 did not receive lactulose. On days 7 and 14, Group I and Group 2 received ethanol (1.5 g/kg b.w. as a 16% vlv solution in saline) intraperitoneally (i.p), whereas Group 3 and 4 received saline i.p. On day 7, blood samples from the tip of the tail were taken after i.p. injection at fixed intervals from each rat, up to 5 hours. On day 14, the rats were anesthetized 60 minutes after the i.p. injection and caecal content samples were taken. Blood ethanol and caecal acetaldehyde levels were determined by head space gas chromatography. Results: Faecal pH was 2: 7 at study entry and decreased within the 2 first days in all the rats on lactulose (range 4.5 to 6. I). Caecal pH ranged between 5 and 5.5 in all lactulose treated rats (6.1 to 6.5 in the others). Lactulose feeding decreased EER by 14.8 % as compared to the rats not receiving lactulose (207::t:0.013 vs 243±0.OO6 mg/kg/h, respectively). The intracaecal acetaldehyde level after ethanol injection was significantly reduced in the rats on lactulose (68::t:48 p,M) as compared to those not receiving lactulose (305::t:73p,M). Conclusion: Lactulose feeding in rats, by changing colonic bacterial pathways, significantly reduces EER and intracolonic acetaldehyde production after ethanol injection. This prebiotic may have a preventive role in the pathogenesis of alcohol-induced damages in the gastrointestinal tract.
4163 ESOPHAGEAL MOTILITY, GASTROESOPHAGEAL REFLUX (GER) AND OBESITY. Franck Zinzindohouee, Michel L. Bouchoucha, Jean-Marie Chevallier, Paul-Henri Cugnenc, Hosp Laennec, Paris, France. BACKGROUND: Severe obesity is frequently associated with GER because of a delay of gastric emptying and an increase of abdominal pressure. AIMS: To estimate the prevalence of GER in severe obesity (BMI>30) and to look for esophageal motility disorders. METHODS: The study was performed in 24 consecutive patients complaining of severe obesity (1l9.2::t:4.0 kg, l63.2:!::2.1 em, BMI 44.2::t: 1.4) before laparoscopic gastroplasty. The clinical evaluation searched for esophageal and gastric symptoms according to Rome II criteria. Esophageal tests (manometry and 24-hour pH-metry) were compared to the standards of our laboratory. RESULTS: Esophageal symptoms were found in 10 patients (42%). In order of frequency: unspecified dyspepsia (7 cases), dysmotiliry-Iike dyspepsia and ulcer-like dyspepsia (3 cases), globus, rumination, chest pain, dysphagia (2 cases). A hiatal hernia «3 em) was found in 7 patients and gastritis in 2 patients during esophageal fibroscopy. HP was never found in these patients. Esophageal pH-metry was found normal in only 6 patients (25%). It showed an increase of number (102.1 ::t:21.5; N<50) and duration (pH<4: 23.1 ::t:5.3%; N<4.2%) of reflux episodes. Esophageal manometric tests showed a weak LES «12 mm Hg) in 8 patients (33%), a decrease of the amplitude «40 mm Hg) in 10 patients (42%) and an increase of the duration (>6 s) of peristaltic waves in 8 patients (33%), and a decrease of the amplitude of the UES «35 mm Hg) in 12 patients (50%). CONCLUSIONS: Despite the absence of typical GER symptoms, GER is found in 75% of patients with severe obesity. This GER is aggravated by the weakness of the LES and of the peristaltic waves.
4159 SUCCESSFUL AVOIDANCE OF TOTAL PARENTERAL NUTRITION BY ADMINISTRATION OF AN AMINO-ACID BASED ENTERAL FORMULA (NEOCATE) IN INFANCY. Gigi A. Veereman-Wauters, Els Van Elsacker, lise Hoffman, Liliane De Swert, Pediatric Gastroenterology, Univ Hospitals Leuven, Leuven, Belgium; Pediatric Allergology, Univ Hospitals Leuven, Leuven, Belgium. Total parenteral nutrition (TPN) is a necessary route for nutritional support in cases of severe food intolerance in infancy but involves life threatening risks (sepsis, hepatotoxicity), a high level of care and high costs. We report 7 infants in whom the use of an amino-acid based enteral formula (Neocate®) allowed discontinuation of TPN. Over a 9 months period (9-98/699) we treated 7 infants (3 girls, 4 boys, mean agel0,7 rno-range 2-23 mo) with Neocate® after failure of feeding attempts with various semi-elemental formulas. Food intolerance was a consequence of short gut syndrome (3), multiple food allergies (2) and status post toxic megacolon with enterocolitis (2). In the 3 infants with short gut syndrome advancing semi-elemental feeds failed blo increased ileostomy output (>50%) or malabsorption (reducing substances >2g%) with less than 20% of total caloric requirements being provided enterally. Introduction of Neocate® allowed increase of enteral caloric intake from 13 to 52 Callkg over 44 days in a baby who subsequently underwent liver transplantation, and from 17 to 95 Cal!kg over 97 days and 12 to 104 Callkg over 226 days respectively in 2 patients in whom TPN was definitely stopped. Two infants with multiple food allergies and 2 patients recovering from severe enterocolitis (I Hirschprung, I unclear) needed TPN blo repeated symptomatic relapse (bloody stools) upon reintroduction of semi-elemental feeds. A similar gradual enteral regimen using Neocate® allowed discontinuation of TPN in all 4. After a period of at least 3 months, reintroduction of other nutrients was thusfar successfull in 2. In infants, with severe intestinal insufficiency (short gut) who receive semi-elemental food but remain TPN dependent or with severe inflammation and who do not tolerate polymeric or semi-elemental nutrition, Neocate® can improve enteral tolerance to full energetic requirements and lead to discontinuation of parenteral support.
4160 HUMAN NEUTROPHIL MEMBRANE FLUIDITY AFTER INCUBATION IN STRUCTURALLY DIFFERENT LIPID EMULSIONS. Geert 1. Wanten, Dirk Roos, Anton H. Naber, Acad Hosp Nijmegen, Nijmegen, Netherlands; Univ of Amsterdam, Amsterdam, Netherlands. Rationale: Medium chain triglyceride (Mj-containing lipid emulsions activate human neutrophils in vitro, contrary to long-chain (L) and structured lipid (SL) emulsions. To test the hypothesis that these distinct responses result from alterations in cell membrane fluidity induced by various emulsions, we performed the present study. Method: Isolated neutrophils from 8 volunteers were incubated for I hour in 2.5 mM emulsions containing L, M, mixed LM, LM enriched with a-tocopherol (LME) or SL emulsions. This lipid concentration is physiological in patients when emulsions are administered intravenously. Thereafter the cells were washed twice and membrane fluidity was measured as the fluorescence polarization of diphenyl-hexatriene (DPH). Results are presented as fluorescence anisotropy r, the reciprocal of membrane fluidity. Results: Compared to lipid-free incubation (0.I82::t:0.023), LM (0.I28::t:0.016), as well as LME (0.124::t:0.019), SL (0. I67::t:0.029) and M (0.095::t:0.038)significantly decreased r (and thus increased membrane fluidity, all p < 0.02 with Wilcoxons signed ranks test), while L (0.I71::t:0.0I7) had no effect (p=0.14). While LM and LME were not different (p=0.33), M further reduced r compared to both previous emulsions (P
4161 EFFECTS OF STRUCTURALLY DIFFERENT LIPID EMULSIONS ON HUMAN NEUTROPHIL MIGRATION. Geert 1. Wanten, Dirk Roos, Anton H. Naber, Acad Hosp Nijrnegen, Nijmegen, Netherlands; Univ of Amsterdam. Amsterdam, Netherlands. Background: While the use of intravenous lipid emulsions has been associated with an increased risk for infectious complications, the imrnunomodulatory characteristics of structurally different emulsions have not been well characterized. Aim: To test the hypothesis that human neutrophil migration is distinctively influenced by structurally different lipid emulsions in physiological concentrations, i.e. concentrations (up to 10 mM) reached in patients when lipids are administered intravenously. Method: Isolated neutrophils from 8 volunteers were incubated in medium or 2.5 mM lipid emulsions containing long-chain- (L), medium-chain- (M), mixed LM-, tocopherol-enriched LM (LME), or structured lipids (SL). The cells were loaded above 3 pm-pore-sized filters and migration was measured after I hour as the percentage filterpassage in the presence (chemotaxis) or absence (random migration) of chemotactic factor (formylated peptide (fMLP) or zymosan-activated serum (ZAS)). Results: fMLP-induced chemotaxis under lipid-free conditions amounted to 61::t: 14% and
AGAA777
decreased with LM to 11::t:9%, with LME to 18::t:1O%, with SL to 39::t:18%, and with M to 5::t:2% (all p<0.05 with Wilcoxons signed ranks test), while L had no effect (59::t: 10%, p=0.59). ZAS-induced chemotaxis showed similar results. Compared to lipid-free incubation (l9± 10%), random migration significantly decreased with LM (II ::t:2%), LME (12::t:2%)and M (5::t:2%), while L (l8±3) and SL (20± I %) had no effect. Compared to LM, chemotaxis with LME significantly increased (p = 0.004). Chemotaxis decreased in direct proportion to LM concentration, reaching steady state at 2 mM. Conclusion: Human neutrophil migration is distinctively influenced by structurally different lipid emulsions, depending on triglyceride chain-length and -concentration, as well as tocopherol content.
4162 LACTULOSE REDUCES INTRACOLONIC ACETALDEHYDE PRODUCTION AND ETHANOL ELIMINATION RATE IN RATS. Semia H. Zidi, Satu M. Vakevainen, Mikko P. Salaspuro, Kalle Jokelainen, Research Unit of Alcohol Diseases, Helsinki, Finland.
Background: Most of ethanol oxidation takes place in the liver. However, ethanol is also oxidized by normal colonic bacteria possessing alcohol dehydrogenase (ADH) activity. The first metabolite of ethanol oxydation is acetaldehyde, a carcinogen also linked to several organ toxic effects of alcohol. ADH-mediated bacterial reaction is pH dependent and it is inhibited under acid conditions. Lactulose is a non-absorbable disaccharide metabolized by caecal bacteria into short chain fatty acids, mainly lactate, thus acidifying caecal contents. The aims of the present study were to examine the effect of chronic lactulose feeding on the colonic and faecal pH, intracolonic acetaldehyde production and total ethanol elimination rate (EER) in rats. Methods: Forty 8-week-old male Wistar rats weighing 308::t:8g (mean::t:SEM) were divided into four 10-rat-groups. Group I and Group 3 received lactulose (11 g/kg b.w. for 14 days) in drinking water and by daily intragastric intubation. Group 2 and 4 did not receive lactulose. On days 7 and 14, Group I and Group 2 received ethanol (1.5 g/kg b.w. as a 16% vlv solution in saline) intraperitoneally (i.p), whereas Group 3 and 4 received saline i.p. On day 7, blood samples from the tip of the tail were taken after i.p. injection at fixed intervals from each rat, up to 5 hours. On day 14, the rats were anesthetized 60 minutes after the i.p. injection and caecal content samples were taken. Blood ethanol and caecal acetaldehyde levels were determined by head space gas chromatography. Results: Faecal pH was 2: 7 at study entry and decreased within the 2 first days in all the rats on lactulose (range 4.5 to 6. I). Caecal pH ranged between 5 and 5.5 in all lactulose treated rats (6.1 to 6.5 in the others). Lactulose feeding decreased EER by 14.8 % as compared to the rats not receiving lactulose (207::t:0.013 vs 243±0.OO6 mg/kg/h, respectively). The intracaecal acetaldehyde level after ethanol injection was significantly reduced in the rats on lactulose (68::t:48 p,M) as compared to those not receiving lactulose (305::t:73p,M). Conclusion: Lactulose feeding in rats, by changing colonic bacterial pathways, significantly reduces EER and intracolonic acetaldehyde production after ethanol injection. This prebiotic may have a preventive role in the pathogenesis of alcohol-induced damages in the gastrointestinal tract.
4163 ESOPHAGEAL MOTILITY, GASTROESOPHAGEAL REFLUX (GER) AND OBESITY. Franck Zinzindohouee, Michel L. Bouchoucha, Jean-Marie Chevallier, Paul-Henri Cugnenc, Hosp Laennec, Paris, France. BACKGROUND: Severe obesity is frequently associated with GER because of a delay of gastric emptying and an increase of abdominal pressure. AIMS: To estimate the prevalence of GER in severe obesity (BMI>30) and to look for esophageal motility disorders. METHODS: The study was performed in 24 consecutive patients complaining of severe obesity (1l9.2::t:4.0 kg, l63.2:!::2.1 em, BMI 44.2::t: 1.4) before laparoscopic gastroplasty. The clinical evaluation searched for esophageal and gastric symptoms according to Rome II criteria. Esophageal tests (manometry and 24-hour pH-metry) were compared to the standards of our laboratory. RESULTS: Esophageal symptoms were found in 10 patients (42%). In order of frequency: unspecified dyspepsia (7 cases), dysmotiliry-Iike dyspepsia and ulcer-like dyspepsia (3 cases), globus, rumination, chest pain, dysphagia (2 cases). A hiatal hernia «3 em) was found in 7 patients and gastritis in 2 patients during esophageal fibroscopy. HP was never found in these patients. Esophageal pH-metry was found normal in only 6 patients (25%). It showed an increase of number (102.1 ::t:21.5; N<50) and duration (pH<4: 23.1 ::t:5.3%; N<4.2%) of reflux episodes. Esophageal manometric tests showed a weak LES «12 mm Hg) in 8 patients (33%), a decrease of the amplitude «40 mm Hg) in 10 patients (42%) and an increase of the duration (>6 s) of peristaltic waves in 8 patients (33%), and a decrease of the amplitude of the UES «35 mm Hg) in 12 patients (50%). CONCLUSIONS: Despite the absence of typical GER symptoms, GER is found in 75% of patients with severe obesity. This GER is aggravated by the weakness of the LES and of the peristaltic waves.