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B Koletzko

Publications and source records attributed to B Koletzko.

At least 73 records · Page 4Linked to original sources
PubMed1999

Noninvasive assessment of essential fatty acid status in preterm infants by buccal mucosal cell phospholipid analysis.

BACKGROUND: The dietary supply of long-chain polyunsaturated fatty acids is receiving increased attention since a linkage to infant growth and development has been reported. To avoid repeated blood collections for determination of long-chain polyunsaturated fatty acid status, the authors developed and evaluated a noninvasive method for analysis of buccal mucosal cell phospholipids. METHODS: Oral mucosal cells were gently collected with a soft cotton swab, buccal cell lipids separated by thin-layer chromatography, and fatty acid methyl esters of the phospholipid fraction prepared. Subsequently, the fatty acid methyl esters were analyzed by high-resolution gas chromatography. RESULTS: The method allowed reliable analysis from very small amounts of oral mucosal cells, and results were well reproducible. The intraindividual coefficients of variation in four samples of three subjects were less than 5% for both arachidonic and docosahexaenoic acid. Fatty acid composition was not altered by consumption of milk formula before and after sample collection. The method was applied in a clinical trial with preterm infants fed human breast milk or assigned by double-blind randomization to preterm formula with or without arachidonic and docosahexaenoic acid. Buccal mucosal cells were collected in infants less than 14 days of age and at the postconceptional ages of 52 weeks and 64 weeks. Dietary long-chain polyunsaturated fatty acids showed a lasting influence on buccal cell phospholipid composition. In the course of the study, arachidonic and docosahexaenoic acid decreased significantly in the nonenriched formula group, whereas stable or rising values were observed in the groups receiving breast milk or enriched formula. CONCLUSIONS: Buccal mucosal cell phospholipids are feasible for use as a noninvasive marker for long-chain polyunsaturated fatty acid status in preterm infants and yield reliable results. Dietary long-chain polyunsaturated fatty acids have a lasting influence on fatty acid composition of buccal cells in preterm babies.

Cheek↗
PubMed1999

Oxidation of an oil rich in docosahexaenoic acid compared to linoleic acid in lactating women.

BACKGROUND: We studied the oxidation of an oil rich in docosahexaenoic acid (DHA; DHASCO((R))) in lactating mothers receiving a dietary DHA supplement or a placebo. The results were compared with the oxidation of linoleic acid. METHODS: Breast-feeding mothers received a dietary supplement (DHASCO; 200 mg DHA/day, n = 5) or a placebo (n = 5) for 14 days. Six weeks post partum all 10 mothers received a single dose of 2 mg/kg body weight uniformly (13)C-labeled DHASCO. In a previously reported study 6 mothers received 1 mg/kg body weight uniformly (13)C-labeled linoleic acid. Breath samples were collected over 48 h after tracer application. The total CO(2) production was measured by indirect calorimetry and the (13)C isotopic enrichment of labeled CO(2) by isotopic ratio mass spectrometry. RESULTS: The oxidation of (13)C-labeled DHASCO in the supplemented and placebo groups was similar. Maximal (13)C enrichment was reached earlier in the group receiving (13)C-DHASCO (median 1.0 vs. 3.0 h in the linoleic acid group). The cumulative (13)C recovery in breath was higher in the DHASCO versus the linoleic acid group until 10 h after tracer application and comparable thereafter. CONCLUSIONS: The difference in oxidation of DHASCO versus linoleic acid after tracer ingestion might be partly due to a faster absorption and oxidation of shorter chain saturated fatty acids contained in DHASCO. The cumulative oxidation of DHASCO and linoleic acid 24 and 48 h after tracer ingestion is similar.

Adult↗
PubMed1999

Metabolism of 13C-labeled linoleic acid in newborn infants during the first week of life.

Linoleic acid metabolism was studied during the first week of life in 10 breast-fed, full-term infants. Uniformly 13C-labeled linoleic acid (1 mg/kg body weight) was given orally. The 13C content was determined in expired CO2 over 6 h and in plasma phospholipid fatty acids over 3 d. Total CO2 production determined by indirect calorimetry was 16.7 +/- 10.6 mL/min (mean +/- SE). Over 6 h 7.4 +/- 0.6% of the ingested 13C-labeled linoleic acid was oxidized to CO2. Plasma phospholipid linoleic acid showed maximal 13C enrichment 24 h after tracer application (delta over baseline 178 +/- 24/1000). Enrichment of dihomo-gamma-linolenic acid increased from d 2 to d 5 of life (p < 0.002), with delta over baseline values of 2.1 +/- 0.5/1000 at 24 h, 3.7 +/- 10.9/1000 at 48 h, and 4.4 +/- 1.0/1000 at 72 h. 13C content of arachidonic acid tended to increase insignificantly. Areas under the curve of plasma tracer concentration over time were calculated for plasma n-6 phospholipid fatty acids. Percentages of total areas under the curve of the investigated n-6 fatty acids were 97.3 +/- 0.8% for linoleic acid, 1.5 +/- 0.6% for dihomo-gamma-linolenic acid, and 1.2 +/- 0.6% for arachidonic acid. The proportion of linoleic acid oxidized to CO2 did not correlate with the estimated conversion to long-chain polyunsaturated metabolites. Breast-fed newborn infants synthesize n-6 long-chain polyunsaturated fatty acids already during the first week of life, but the contribution of endogenous synthesis to the total plasma long-chain polyunsaturated pool is small. A major portion of dihomo-gamma-linolenic acid is converted to arachidonic acid.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Nutritional and biochemical properties of human milk, Part I: General aspects, proteins, and carbohydrates.

Human milk provided by healthy and well-nourished mothers is believed to cover the infant's nutrient requirements during the first half year of life. It is composed of a mixture of nutritive components as well as other bioactive factors with relevant physiologic effects in the neonate infant. Human milk composition has a dynamic nature and varies with time postpartum, during a nursing, and with the mother's diet and certain diseases. The changes of human milk composition with time of lactation seem to match the changing needs of the growing infant over time. Human milk proteins are a source of peptides, amino acids, and nitrogen for the infant, but also in the protein fraction reside other properties of human milk that may benefit the breastfeeding infant. Specific whey proteins are involved in the development of the immune response (immunoglobulins), whereas others participate in the nonimmunologic defense (lactoferrin). In addition, human milk contains a complex mixture of oligosaccharides that are present only in minute amounts in other mammal's milk. They may act as inhibitors of bacterial adhesion to epithelial surfaces, and thus play an important role in preventing infectious diseases in the newborn infant. Oligosaccharides may also promote the development of a so-called bifidus flora. In the next years, future research will lead to improved characterization of human milk components and elucidation of their individual mechanisms of action, which will increase our knowledge about the properties of human milk and the benefits of breastfeeding for the infant.

Female↗
PubMed1999

Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors.

Human milk lipids contain preformed LCPUFA in considerable amounts, which serve as precursors for the formation of prostaglandins, prostacyclins, and other lipid mediators, as well as essential components in membrane-rich tissues (such as the brain and the retina), thus affecting functional outcomes. Besides a balanced nutrient composition and a number of conditionally essential nutrients, human milk provides different types and classes of bioactive factors, such as enzymes, hormones, and growth factors, many of which appear to have a role in supporting infantile growth and development. The bioactive agents include antimicrobial factors (e.g., secretory IgA, oligosaccharides, FA); anti-inflammatory agents; transporters (e.g., lactoferrin); and digestive enzymes (e.g., BSSL). Several nonpeptide hormones (thyroid hormones, cortisol, progesterone, pregnanediol, estrogens, and artificial contraceptive) and peptide hormones and growth factors (erythropoietin, hHG, gonadotropin-releasing hormone, epidermal growth factor insulin, insulin-like growth factor-I, nerve growth factor, transforming growth factor-alpha, gastrointestinal regulatory peptides and thyroid-parathyroid hormones) have been isolated and quantitated in human milk. Some of these components are also involved in the maturation of the gastrointestinal tract of the infant. In addition to the passive benefits provided by human milk, several data support the hypothesis that breastfeeding promotes the development of the infant's own immune system, which might confer long-term benefits for the newborn infant. The risk of IDDM, Crohn's disease, and atopic disease is lower in individuals who had been breastfed during infancy. Areas of major interest in human milk research include the study of human milk synthesis and the contributions of dietary composition and maternal metabolism to human milk composition, infantile utilization of human milk components, and the study of bioactive components, such as oligosaccharides, proteins and peptides, and lipids and their in vivo fate and biologic effects in the recipient infant.

Female↗
PubMed1999

The role of research--how much is enough?

A great deal of research is involved in bringing PARNUTs to the marketplace. Research often begins with identifying an unfilled nutritional need, determining if that need is great enough to warrant development of a new product, and then evaluating the efficacy and safety of the potential product in animal models and clinical trials. This approach tends to emphasize short-term outcomes, however, while neglecting the issues of whether a product offers long term benefit or holds long term risks. This article presents discussion centered around the need for selecting appropriate outcomes for nutritional intervention trials, designing trials with a follow-up time sufficient to allow for outcome measurement, and enrolling a patient population large enough to accurately gauge efficacy and tolerability.

Animals↗
PubMed1998

[Hyperlipidemia in children and adolescents: diagnosis and therapy].

Severe hyperlipidemias should be diagnosed and treated even in childhood and adolescence, because vascular lipid deposition in the form of fatty streaks and progressive atherosclerotic lesions start to develop early in life. The heterozygous form of familial hypercholesterolemia found in about 1 of 500 newborn infants, and polygenic forms of hypercholesterolemia, are the most frequent forms of primary genetic hypercholesterolemia found in children. Secondary hyperlipidemias, e.g. in diabetes mellitus, hypothyroidism and renal disease, are relatively frequent in children and adolescents and need to be searched for in the diagnostic evaluation, because they can be influenced by treatment of the underlying disorder. Children and adolescents with severe forms of hyperlipidemias should be diagnosed and treated early in life. Dietary modification is the basis of treatment of affected children and can lower LDL cholesterol by about 15-20%. In patients with severe hypercholesterolemia, dietary cholesterol intake should not exceed 150 mg/day in children or 250-300 mg/day in adolescents. Even more important is a reduction of the intake of saturated fats and trans fatty acids and their replacement by polyunsaturated and particularly monounsaturated fats. Some additional lowering of LDL cholesterol may be achieved by the preferential use of vegetable over animal proteins and of complex carbohydrates over sugars. Repeated motivation, counseling and intensive practical training of the patient and family, supported by appropriate teaching materials, are essential for effective dietary treatment. Additional drug treatment is considered in children from the age of 8-9 years of age onwards if, in spite of adequate dietary modification, LDL cholesterol remains above 190 mg/dl (4.9 mmol/l), or above 160 mg/dl (3.9 mmol/l) in the presence of additional risk factors. The drugs of first choice are anion exchange resins (colestyramine or colestipol) because of their well documented efficacy and safety. More convenient to take but often somewhat less effective is beta-sitosterol. If efficacy or compliance with resins or sitosterin is unsatisfactory, fibrates (e.g. bezafibrate, fenofibrate) may be considered as a drug of second choice. Cholesterol synthesis inhibitors are not recommended for general use in children at this time.

Adolescent↗
PubMed1998

Immaturity alters plasma lipoprotein composition of intravenously alimented newborn infants.

Plasma lipoprotein composition in infants receiving fat-free parenteral nutrition reflects the endogenous synthesis and metabolism of lipids. We studied the composition of plasma lipoproteins in 49 appropriate for gestational age newborn infants after surgery who received only glucose and amino acid solutions for 5.4 +/- 0.3 days (M +/- SE). Of the infants studied, 31 were fullterm (gestational age 39.5 +/- 0.2 weeks) and 18 premature (34.3 +/- 0.7 weeks). Plasma lipid levels (total lipids, triglycerides, free cholesterol, sterol, esters, phospholipids) did not differ between term and premature infants, but triglycerides and cholesterol were markedly lower than in young, fasting adults. The contribution of triglycerides to lipoprotein lipids was strikingly low in chylomicrons (21% vs. 90% in young fasting adults) and VLDL (34 vs 60%) and the infants had a consistently lower cholesterol content of HDL (21 mg/dl vs. 45-50 mg/dl in adults) and LDL (43 mg/dl vs. 100 mg/dl). All infantile lipoproteins were enriched with phospholipids. These results are comparable to those reported for cord plasma. In premature babies, VLDL were markedly reduced and contained less triglycerides, free and esterified cholesterol than in term infants. In contrast, HDL were increased in preterm infants and carried more phospholipids. VLDL contributed to al lesser and HDL to a greater extent to plasma lipid transport in premature infants. We conclude that in premature infants hepatic synthesis of triglycerides and cholesterol and their secretion as VLDL is reduced, which may be caused by low substrate availability or an immaturity of the synthetic pathway. In premature infants, HDL appears to play a major role in transporting plasma lipids to peripheral tissues.

Cholesterol↗
PubMed1998

Fatty acid composition of lipid classes in maternal and cord plasma at birth.

UNLABELLED: The fatty acid composition of plasma phospholipids, triglycerides, cholesterol esters and nonesterified fatty acids was determined by high-resolution capillary gas-liquid chromatography in 41 pairs of mothers and their term infants at time of birth. The total free fatty acid content in maternal and cord plasma was positively correlated, possibly reflecting a passive, gradient dependent transplacental passage of nonesterified fatty acids. Higher percentage values of several saturated and monounsaturated fatty acids in cord than in maternal plasma phospholipids, triglycerides and nonesterified fatty acids may have resulted from an active fetal fatty acid synthesis. Trans fatty acids were found in every lipid class at similar or slightly lower percentages in neonatal as in maternal plasma, thus confirming their placental passage. Long-chain n-6 and n-3 polyunsaturated fatty acids are preferentially incorporated into phospholipids and sterolesters of both maternal and cord plasma. Linoleic and alpha-linolenic acids were found in smaller portions in cord than in maternal fatty acids, in contrast to strikingly higher proportions of their long-chain polyunsaturated metabolites, which may indicate a discriminating placental transport for certain physiologically important long-chain polyunsaturated fatty acids. CONCLUSION: The fetus appears to obtain fatty acids from a combination of de novo synthesis, a passive gradient dependent transplacental passage of nonesterified fatty acids and a selective materno-fetal placental transport for certain fatty acids, such as physiologically important long-chain polyunsaturated fatty acids.

Cholesterol Esters↗
PubMed1998

The use of stable isotope techniques for nutritional and metabolic research in paediatrics.

Stable isotope methods are increasingly used in paediatrics for clinical diagnosis and research due to marked improvements in analytical technologies and better availability of suitable tracers. The safety of stable isotopes is of major importance for use in children. Large amounts of deuterium well above the doses applied under clinical conditions may induce adverse effects. In contrast, heavier stable isotopes such as 13C, 15N or 18O do not induce adverse effects even at the highest enrichments obtained, and they are safe. Breath tests with measurements of 13CO2 enrichment after oral application of a tracer can reliably evaluate helicobacter pylori infection and gastric emptying kinetics. Combined with an estimation of total CO2 production, 13CO2 breath tests allow estimation of the absorption and oxidation of 13C-labelled substrates, such as medium- and long-chain triglycerides, and demonstrates the beneficial effect of carnitine supplements on fat oxidation in primary carnitine deficiency. The study of metabolic processes may require the sampling of blood for isotopic analyses of metabolites of the applied tracer. Gas chromatography-isotope ratio mass spectrometry can detect tracer in individual components from small plasma samples. The high precision enabled us to utilize the small differences in natural 13C-enrichment between dietary fats to study fatty acid turnover in term infants, in whom the dietary fat source was switched to corn oil with a slightly higher 13C-content. With this approach we demonstrated active conversion of linoleic into arachidonic acid. We also applied biotechnologically produced, U-13C labelled linoleic and alpha-linolenic acids to infants and detected the conversion of these essential fatty acids to their longer chain polyunsaturated derivatives, with an apparent change of conversion activity with age. Moreover, it has become possible to measure tissue protein synthesis from small biopsy samples obtained in situ without surgery, such as forceps biopsies of rectal tumors. These few examples of recent developments demonstrate the great clinical and scientific potential of stable isotope methods in future paediatric applications.

Carbon Isotopes↗
PubMed1998

Nutritional support of infants and children: supply and metabolism of lipids.

The quantity and quality of dietary lipids and their metabolism are of major importance for the growth, body composition, development and long-term health of children, both in health and disease. Lipids are the major source of energy in early childhood and supply essential lipid-soluble vitamins and polyunsaturated fatty acids that are required in relatively high amounts during early growth. Lipids affect the composition of membrane structures, and modulate membrane functions as well as the functional development of the central nervous system. Some long-chain polyunsaturated fatty acids serve as precursors for bioactive lipid mediators, including prostaglandins, thromboxanes and leukotrienes, which are powerful regulators of numerous cell functions such as thrombocyte aggregation, inflammatory reactions and immune functions. Here we review some aspects of the biochemistry and physiology of lipids and their implications for lipoprotein metabolism, energy balance and the lipid supply during early childhood through the placenta, human milk, enteral diets and parenteral lipid emulsions.

Absorption↗
PubMed1998

Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers.

Afferent nerves play a major role in the regulation of gastrointestinal motility. The questions remains if specific food ingredients can selectively activate such fibers. The aim of the study was to investigate the effect of intraesophageal application of a capsaicin-containing red pepper sauce (Tabasco) suspension on upper gastrointestinal motility in a controlled trial. After a baseline recording [esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or saline solution was infused intraesophageally in seven healthy volunteers. At 30 min gastric emptying and orocecal transit time were determined using a [13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P < 0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6 mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold of intraesophageal balloon distension, reduced the percentage of normal electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9 +/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the prolongation of gastric emptying, orocecal transit time was not altered, indicating an actual increase of intestinal transit. Esophageal application of capsaicin-containing red pepper sauce suspension had profound changes on upper gastrointestinal motility, which could improve clearance and protection of the esophagus and could lead to retention of the irritant in the stomach and faster transit through the small bowel.

Adult↗
PubMed1998

The effect of under- and overnutrition on essential fatty acid metabolism in childhood.

Both protein-energy malnutrition (PEM) and obesity represent major challenges for paediatric nutrition. The aim of this review is to summarise available data regarding the effect of PEM and obesity on the availability of essential- and long-chain polyunsaturated fatty acids (LC-PUFAs) in childhood. Significantly lower arachidonate (C20:4n-6, AA) values in malnourished children than in controls is a consistent finding in all studies, whereas it is controversial whether the availability of docosahexaenoate (C22: 6n-3, DHA) is also affected. We found significantly lower percentages (% wt/wt) of both AA and DHA in plasma phospholipids [AA: 7.0 (0.7) vs 8.7 (0.8); DHA: 0.90 (0.2) vs 2.6 (0.7), median (interquartile range), P < 0.001] in severely malnourished children aged 29 (7) months than in control subjects. Product/substrate ratios indicated reduced delta-5-desaturation in children with PEM. We speculate that severely malnourished children may benefit from enhanced dietary supply of both n-6 and n-3 LC-PUFAs. In obese adults AA has been reported to constitute a lower percentage of plasma phospholipid fatty acids, and AA supplementation of weight reduction diets has been suggested. In contrast, we found significantly higher plasma phospholipid AA values [12.6 (2.4) vs 8.3 (1.4), P < 0.001] in markedly obese children aged 13.8 (1.1) years than in non-obese controls. Product/substrate ratios of the delta-6-desaturase enzyme indicated enhanced conversion activity. These data suggest that obese children do not require LC-PUFA supplementation to low fat diets. The available data indicates that both PEM and obesity alter fatty acid composition of plasma and erythrocyte membrane lipids. The underlying mechanism appears to be altered activity of the bioconversion of essential fatty acids to their LC-PUFA metabolites.

Child Nutritional Physiological Phenomena↗
PubMed1998

Growth, development and differentiation: a functional food science approach.

Few other aspects of food supply and metabolism are of greater biological importance than the feeding of mothers during pregnancy and lactation, and of their infants and young children. Nutritional factors during early development not only have short-term effects on growth, body composition and body functions but also exert long-term effects on health, disease and mortality risks in adulthood, as well as development of neural functions and behaviour, a phenomenon called 'metabolic programming'. The interaction of nutrients and gene expression may form the basis of many of these programming effects and needs to be investigated in more detail. The relation between availability of food ingredients and cell and tissue differentiation and its possible uses for promoting health and development requires further exploration. The course of pregnancy, childbirth and lactation as well as human milk composition and the short- and long-term outcome of the child are influenced by the intake of foods and particularly micronutrients, e.g. polyunsaturated fatty acids, Fe, Zn and I. Folic acid supplementation from before conception through the first weeks of pregnancy can markedly reduce the occurrence of severe embryonic malformations; other potential benefits of modulating nutrient supply on maternal and child health should be further evaluated. The evaluation of dietary effects on child growth requires epidemiological and field studies as well as evaluation of specific cell and tissue growth. Novel substrates, growth factors and conditionally essential nutrients (e.g. growth factors, amino acids, polyunsaturated fatty acids) may be potentially useful as ingredients in functional foods and need to be assessed carefully. Intestinal growth, maturation, and adaptation as well as long-term function may be influenced by food ingredients such as oligosaccharides, gangliosides, high-molecular-mass glycoproteins, bile salt-activated lipase, pre- and probiotics. There are indications for some beneficial effects of functional foods on the developing immune response, for example induced by antioxidant vitamins, trace elements, fatty acids, arginine, nucleotides, and altered antigen contents in infant foods. Peak bone mass at the end of adolescence can be increased by dietary means, which is expected to be of long-term importance for the prevention of osteoporosis at older ages. Future studies should be directed to the combined effects of Ca and other constituents of growing bone, such as P, Mg and Zn, as well as vitamins D and K, and the trace elements F and B. Pregnancy and the first postnatal months are critical time periods for the growth and development of the human nervous system, processes for which adequate substrate supplies are essential. Early diet seems to have long-term effects on sensory and cognitive abilities as well as behaviour. The potential beneficial effects of a balanced supply of nutrients such as I, Fe, Zn and polyunsaturated fatty acids should be further evaluated. Possible long-term effects of early exposure to tastes and flavours on later food choice preferences may have a major impact on public health and need to be further elucidated. The use of biotechnology and recombinant techniques may offer the opportunity to include various bioactive substances in special dietary products, such as human milk proteins, peptides, growth factors, which may have beneficial physiological effects, particularly in infancy and early childhood.

Adolescent↗
PubMed1998

Essential fatty acid metabolism in infants with cholestasis.

Long-chain polyunsaturated fatty acids are important for the growth and early development of the central nervous system. Cholestatic infants suffer from fat malabsorption and disturbed lipid metabolism and therefore may be at risk of developing polyunsaturated fatty acid depletion. The aims of this study were to determine essential fatty acid status in cholestatic infants and to study the relationship to disease severity, degree of undernutrition, antioxidant status and mode of feeding. Twenty-four-hour dietary records were obtained in 34 cholestatic infants, and measurements were taken of skin fold thicknesses, bilirubin levels, activities of serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, prothrombin time, serum concentrations of albumin, bile acids, total lipids, phospholipids, cholesterol, vitamins A and E, the fatty acid composition of plasma phospholipids and plasma lipid peroxides expressed as thiobarbiturate reactive substance (TBARS). Plasma phospholipid fatty acids and TBARS were also determined in 12 age-matched healthy control infants. The cholestatic patients had very low percentage values of phospholipid essential fatty acids, particularly linoleic acid ( 18:2omega-6, median 14.74% vs 20.76% in controls, p < 0.001) and its major metabolite arachidonic acid (20:4omega-6, 6.80 vs 7.87%, p=0.04). The patients' essential fatty acid depletion was reflected by increased levels of the non-essential fatty acids, Mead acid (20:3omega-9, 0.74 vs 0.21%, p < 0.001) and palmitoleic acid (16:1omega-7, 2.20 vs 0.43%, p < 0.001). Polyunsaturated fatty acid profiles did not differ between infants with biliary atresia (n=13) and those with intrahepatic cholestasis (n=21), or between 17 infants with severe malnutrition (all skin folds < 10th percentile) and mild malnutrition (at least two skin folds > 10th percentile). TBARS were significantly higher in cholestatic patients than in controls (2.74 vs 0.85 nmol ml(-1), p < 0.001) and correlated with direct (r=0.41, p=0.02) and total bilirubin. The daily dietary intake of linoleic acid (per 100 kcal) correlated with plasma phospholipid linoleic acid (r=0.38,p=0.037) and total omega-6 fatty acids (r=0.38,p=0.036). Breastfed cholestatic infants (n=6) had higher values of the omega-3 long-chain polyunsaturated fatty acids docosapentanoic acid (22:5omega-3, 0.47 vs 0.28%, p=0.0006) and docosahexanoic acid (22:6omega-3, 2.39 vs 1.73%, p=0.01) than formula-fed infants, while disease severity was similar in the two groups. In conclusion, cholestatic infants are at high risk of essential fatty acid depletion, which appears to be related to fat malabsorption, hepatic essential fatty metabolism, enhanced lipid peroxidation and dietary intake.

Body Height↗
PubMed1998

Effect of glucagon on protein synthesis in human rectal cancer in situ.

OBJECTIVE: The purpose of this study was to determine the effect of glucagon or placebo on the rate of tumor fractional protein synthesis in situ in patients with localized rectal cancer who were not malnourished, demonstrated normal glucagon concentrations, and could therefore be used as a model to study the glucagon effect. SUMMARY BACKGROUND DATA: Cancer cachexia is associated with an increased concentration of counterregulatory hormones, including glucagon. This altered hormonal milieu may not only contribute to malnutrition, but also promote tumor growth, because previous experimental work suggests that glucagon can cause human colorectal tumor cells to proliferate. Corresponding mechanisms in vivo have, thus far, not been investigated. METHODS: Advanced mass spectrometry techniques (capillary gas chromatography [GC]/combustion isotope ratio mass spectrometry [IRMS]) were used to determine directly the incorporation rate of 1-[13C]-leucine into tissue protein. Because GC/IRMS requires only a small sample volume, three consecutive endoscopic biopsies could be obtained from the same tumor to determine isotopic enrichments at baseline, after a 4-hour glucagon infusion (3 ng/kg/min), or after placebo. RESULTS: In patients with localized rectal cancer, glucagon caused the tumor fractional protein synthetic rate to double (2.25+/-0.49 %/hr, p < 0.05 vs. 1.16+/-0.30 basal). In contrast, tumor protein synthesis declined over time in controls (placebo) (0.67+/-0.09 %/hr, p < 0.05 vs. 1.11+/-0.16 basal). CONCLUSIONS: Tumor protein synthesis and growth can be stimulated by glucagon in situ. Therefore, elevated glucagon concentrations in cachectic cancer patients should be considered detrimental and attempts made to prevent this specific response of the body to the malignant disease.

Aged↗