The fatty acid imbalance of cystic fibrosis exists at birth independent of feeding in pig and ferret models.

Persons with cystic fibrosis (CF) exhibit a unique alteration of fatty acid composition, marked especially among polyunsaturates by relative deficiency of linoleic acid and excess of Mead acid. Relative deficiency of docosahexaenoic acid is variably found. However, the initial development of these abnormalities is not understood. We examined fatty acid composition in young CF ferrets and pigs, finding abnormalities from the day of birth onward including relative deficiency of linoleic acid in both species. Fatty acid composition abnormalities were present in both liver and serum phospholipids of newborn CF piglets even prior to feeding, including reduced linoleic acid and increased Mead acid. Serum fatty acid composition evolved over the first weeks of life in both non-CF and CF ferrets, though differences between CF and non-CF persisted. Although red blood cell phospholipid fatty acid composition was normal in newborn animals, it became perturbed in juvenile CF ferrets including relative deficiencies of linoleic and docosahexaenoic acids and excess of Mead acid. In summary, fatty acid composition abnormalities in CF pigs and ferrets exist from a young age including at birth independent of feeding and overlap extensively with the abnormalities found in humans with CF. That the abnormalities exist prior to feeding implies that dietary measures alone will not address the mechanisms of imbalance.

Liver X receptor ß regulates bile volume and the expression of aquaporins and cystic fibrosis transmembrane conductance regulator in the gallbladder.

The gallbladder is considered an important organ in maintaining digestive and metabolic homeostasis. Given that therapeutic options for gallbladder diseases are often limited to cholecystectomy, understanding gallbladder pathophysiology is essential in developing novel therapeutic strategies. Since liver X receptor ß (LXRß), an oxysterol-activated transcription factor, is strongly expressed in gallbladder cholangiocytes, the aim was to investigate LXRß physiological function in the gallbladder. Thus, we studied the gallbladders of WT and LXRß-/- male mice using immunohistochemistry, electron microscopy, qRT-PCR, bile duct cannulation, bile and blood biochemistry, and duodenal pH measurements. LXRß-/- mice presented a large gallbladder bile volume with high duodenal mRNA levels of the vasoactive intestinal polypeptide (VIP), a strong mediator of gallbladder relaxation. LXRß-/- gallbladders showed low mRNA and protein expression of Aquaporin-1, Aquaporin-8, and cystic fibrosis transmembrane conductance regulator (CFTR). A cystic fibrosis-resembling phenotype was evident in the liver showing high serum cholestatic markers and the presence of reactive cholangiocytes. For LXRß being a transcription factor, we identified eight putative binding sites of LXR on the promoter and enhancer of the Cftr gene, suggesting Cftr as a novel LXRß regulated gene. In conclusion, LXRß was recognized as a regulator of gallbladder bile volume through multiple mechanisms involving CFTR and aquaporins.NEW & NOTEWORTHY This report reveals a novel and specific role of the nuclear receptor liver X receptor ß (LXRß) in controlling biliary tree pathophysiology. LXRß-/- mice have high gallbladder bile volume and are affected by a cholangiopathy that resembles cystic fibrosis. We found LXRß to regulate the expression of both aquaporins water channels and the cystic fibrosis transmembrane conductance regulator. This opens a new field in biliary tree pathophysiology, enlightening a possible transcription factor controlling CFTR expression.

Is the ENaC Dysregulation in CF an Effect of Protein-Lipid Interaction in the Membranes?

While approximately 2000 mutations have been discovered in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), only a small amount (about 10%) is associated with clinical cystic fibrosis (CF) disease. The discovery of the association between CFTR and the hyperactive epithelial sodium channel (ENaC) has raised the question of the influence of ENaC on the clinical CF phenotype. ENaC disturbance contributes to the pathological secretion, and overexpression of one ENaC subunit, the ß-unit, can give a CF-like phenotype in mice with normal acting CFTR. The development of ENaC channel modulators is now in progress. Both CFTR and ENaC are located in the cell membrane and are influenced by its lipid configuration. Recent studies have emphasized the importance of the interaction of lipids and these proteins in the membranes. Linoleic acid deficiency is the most prevailing lipid abnormality in CF, and linoleic acid is an important constituent of membranes. The influence on sodium excretion by linoleic acid supplementation indicates that lipid-protein interaction is of importance for the clinical pathophysiology in CF. Further studies of this association can imply a simple clinical adjuvant in CF therapy.

Serum n-6 and n-9 Fatty Acids Correlate With Serum IGF-1 and Growth Up to 4 Months of Age in Healthy Infants.

OBJECTIVE: The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy. METHODS: Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores). RESULTS: At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age. CONCLUSIONS: Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.

Chapter 2. ESPGHAN: 50 Years Memories-The Early Years.

Thirty-six founding members from Europe were present in 1968, when the European Society of Paediatric Gastroenterology (ESGA) had its first meeting in Paris. The aim was to create a forum for presentations and discussions of research activities in paediatric gastroenterology in Europe. At the second meeting of ESGA 1969 in Interlaken, an important landmark was set for all gastroenterologists in the world. In this conference, the first ever criteria for "the Diagnosis of Coeliac Disease" (CD) were established. In 1990, the revised criteria for the diagnosis of CD were published. After the introduction of new noninvasive techniques, like tissue transglutaminase 2-antibodies and the HLADQ2/HLADQ8 determinations in blood, "new" criteria for the diagnosis of CD were published in 2012 by the European society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Close collaboration of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition led to mutual meetings. The first combined meeting was 1978 in Paris, followed by meetings in New York, Amsterdam, Houston, and last in Toulouse. The first World Congress of Paediatric Gastroenterology took place in Boston 2000 followed by congresses in Paris, Iguazu, Taipeh, and Toronto. The creation of specialised committees (Nutrition Committees, GI-Committee, and Hepatology-Committee) enabled the society to elaborate numerous guidelines for standards in the diagnosis and treatment of diseases within the subspecialties. The Journal of Paediatric Gastroenterology and Nutrition, as organ of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition since 1991, serves as the voice for these worldwide accepted guidelines. Growing educational activities with summer schools, the Young Investigator Forum and the creation of working groups have distributed our current knowledge among the younger generation and led to fruitful reports, guidelines, and syllabus. In 1992, ESPGHAN was 1 of the founding 7 members of the United European Gastroenterology Federation (UEGF), which developed into a successful organisation for gastroenterology in Europe. This year we celebrate the 50th anniversary of ESPGHAN at our annual Meeting in Geneva.

Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): Captivating Witness Reports of a Success Story.

Since the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan-European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.

Antinociceptive fatty acid patterns differ in children with psychosomatic recurrent abdominal pain and healthy controls.

AIM: Stress is considered to trigger psychosomatic recurrent abdominal pain (RAP), but the mechanism behind the pain is unclear. Because the essential fatty acids, omega-6 and omega-3, are involved in pain, by regulating lipid mediators, we analysed the fatty acid patterns in children with RAP compared to healthy children. METHODS: This was a cross-sectional study of plasma phospholipid fatty acids in 22 consecutively included children with RAP, aged six to 16 years, at an outpatient clinic specialising in RAP. The controls were 100 healthy children previously reported on and analysed in the same laboratory. RESULTS: The children with psychosomatic RAP showed higher mean concentrations of saturated fatty acids than the controls (49.0 mol% versus 47.4 mol%) but lower mean levels of polyunsaturated fatty acids (38.6 mol% versus 39.9 mol%). Omega-3 fatty acids were lower in children with psychosomatic RAP, resulting in higher ratios of linoleic to alpha-linolenic acids (p < 0.001) and arachidonic to eicosapentaenoic acids (p = 0.01), despite a lower concentration of arachidonic acid in children with RAP (p < 0.01). CONCLUSION: The results suggested an imbalance between nociceptive omega-6 fatty acids and antinociceptive omega-3 fatty acids in psychosomatic RAP. Further studies, including lipid mediators and oxidative products, are necessary to confirm an association.

Lipid Quality in Infant Nutrition: Current Knowledge and Future Opportunities.

Dietary lipids are key for infants to not only meet their high energy needs but also fulfill numerous metabolic and physiological functions critical to their growth, development, and health. The lipid composition of breast milk varies during lactation and according to the mother's diet, whereas the lipid composition of infant formulae varies according to the blend of different fat sources. This report compares the compositions of lipids in breast milk and infant formulae, and highlights the roles of dietary lipids in term and preterm infants and their potential biological and health effects. The major differences between breast milk and formulae lie in a variety of saturated fatty acids (such as palmitic acid, including its structural position) and unsaturated fatty acids (including arachidonic acid and docosahexaenoic acid), cholesterol, and complex lipids. The functional outcomes of these differences during infancy and for later child and adult life are still largely unknown, and some of them are discussed, but there is consensus that opportunities exist for improvements in the qualitative lipid supply to infants through the mother's diet or infant formulae. Furthermore, research is required in several areas, including the needs of term and preterm infants for long-chain polyunsaturated fatty acids, the sites of action and clinical effects of lipid mediators on immunity and inflammation, the role of lipids on metabolic, neurological, and immunological outcomes, and the mechanisms by which lipids act on short- and long-term health.

IL-1ß expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice.

Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1ß in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1ß under the control of the surfactant protein (SP)-C promoter. IL-1ß-expressing pups suffered respiratory failure and died shortly after birth. IL-1ß caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1ß decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1ß inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1ß-expressing fetal mice. IL-1ß suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1ß prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1ß. In conclusion, expression of IL-1ß in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth.

Serum phospholipid fatty acids are associated with bone mass in healthy 4-years-old children.

BACKGROUND: Fatty acids are involved in bone development but knowledge in children is limited. The aim of this study was to investigate bone mass and mineral density in healthy preschool children in relation to fatty acids. MATERIAL AND METHODS: In 111 healthy 4-yrs-old children (20 % overweight) bone was analysed by dual X-ray absorptiometry and serum phospholipid fatty acid by gas chromatography. Fat intake was calculated from 7 days self-reported dietary records and food frequency questionnaire. RESULTS: Total bone mass content (BMC) and mineral density (BMD) differed by sex in normal weight, but not in overweight children showing generally higher bone mass density than children with normal weight. Linoleic acid intake was strongly correlated to BMC and femoral BMD in normal weight children. Serum concentration of docosahexaenoic acid correlated positively to BMD in all children (p = 0.01), but linoleic and arachidonic acids, and monounsaturated fatty acids showed diverging associations with bone in normal weight and overweight children. CONCLUSION: Serum phospholipid DHA was associated with bone density. Other fatty acids associations to bone sites differed in overweight children, analogue to the pattern in healthy 8-yrs-old.The finding need to be confirmed longitudinally and in a larger group of overweight individuals.

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation.

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.

Relation between dietary fat intake type and serum fatty acid status in children with cystic fibrosis.

BACKGROUND AND OBJECTIVE: Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk for fatty acid (FA) abnormalities and essential FA deficiency, with low linoleic acid (LA) and docosahexaenoic acid (DHA) concentrations and abnormal triene:tetraene (T:T) and arachidonic acid (AA):DHA ratios. The aim of the article was to determine whether type of dietary fat predicted serum LA, DHA, T:T, and AA:DHA ratios in subjects with CF and PI as compared to an unaffected comparison group. METHODS: Serum FA concentrations were assessed by capillary gas-liquid chromatography (mol%) and dietary intake by 7-day weighed food records; the 3-day coefficient of fat absorption was calculated. Total energy intake was expressed in kilocalories. RESULTS: A total of 65 subjects with CF and PI (8.4 ±â€Š1.0 years, 32 girls) and 22 controls (8.5 ±â€Š1.1 years, 13 girls) were included. Despite greater energy, saturated fat, and LA intake, the subjects with CF had lower serum LA and DHA and higher T:T and AA:DHA than those in the comparison group. Dietary total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), LA, total ω 6 polyunsaturated fatty acid (Tω6PUFA), and α-linolenic acid (ALA) intake positively predicted serum LA concentration. MUFA, total ω 3 polyunsaturated fatty acid (Tω3PUFA), and ALA intake positively predicted serum DHA concentration. Total dietary fat, MUFA, PUFA, Tω3PUFA, LA, and ALA intake negatively predicted serum T:T. ALA and Tω3PUFA intake negatively predicted serum AA:DHA. CONCLUSIONS: Dietary fat patterns influenced serum LA, DHA, T:T, and AA:DHA in children with CF and PI. These data suggest that changes in dietary practices may result in FA profiles associated with improved clinical outcomes.

Nutrition in Cystic Fibrosis-Some Notes on the Fat Recommendations.

Nutrition is important in cystic fibrosis (CF) because the disease is associated with a higher energy consumption, special nutritional deficiencies, and malabsorption mainly related to pancreatic insufficiency. The clinical course with deterioration of lung function has been shown to relate to nutrition. Despite general recommendation of high energy intake, the clinical deterioration is difficult to restrain suggesting that special needs have not been identified and specified. It is well-known that the CF phenotype is associated with lipid abnormalities, especially in the essential or conditionally essential fatty acids. This review will concentrate on the qualitative aspects of fat metabolism, which has mainly been neglected in dietary fat recommendations focusing on fat quantity. For more than 60 years it has been known and confirmed that the patients have a deficiency of linoleic acid, an n-6 essential fatty acid of importance for membrane structure and function. The ratio between arachidonic acid and docosahexaenoic acid, conditionally essential fatty acids of the n-6 and n-3 series, respectively, is often increased. The recently discovered relations between the CFTR modulators and lipid metabolism raise new interests in this field and together with new technology provide possibilities to specify further specify personalized therapy.

Geographical distribution of cystic fibrosis carriers as population genetic determinant of COVID-19 spread and fatality in 37 countries.

COVID-19 has shown a relevant heterogeneity in spread and fatality among countries together with a significant variability in its clinical presentation, indicating that host genetic factors may influence COVID-19 pathogenicity. Indeed, subjects carrying single pathogenic variants of the Cystic Fibrosis (CF) Transmembrane Conductance Regulator (CFTR) gene - i.e. CF carriers - are more susceptible to respiratory tract infections and are more likely to undergo severe COVID-19 with higher risk of 14-day mortality. Given that CF carrier prevalence varies among ethnicities and nations, an ecological study in 37 countries was conducted, in order to determine to what extent the diverse CF carrier geographical distribution may have affected COVID-19 spread and fatality during the first pandemic wave. The CF prevalence in countries, as indicator of the geographical distribution of CF carriers, significantly correlated in a direct manner with both COVID-19 prevalence and its Case Fatality Rate (CFR). In a regression study weighted for the number of tests performed, COVID-19 prevalence positively correlated with CF prevalence, while CFR correlated with population percentage older than 65-year, cancer and CF prevalence. Multivariate regression model also confirmed COVID-19 CFR to be associated with CF prevalence, after adjusting for elderly, cancer prevalence, and weighting for the number of tests performed. This study suggests a putative contribution of population genetics of CFTR in understanding the spatial distribution of COVID-19 spread and fatality.

Ursodeoxycholic acid and liver disease associated with cystic fibrosis: A multicenter cohort study.

BACKGROUND: The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA. METHODS: We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model. RESULTS: Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12). CONCLUSIONS: CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF.

Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E2 and suppress tumor growth in medulloblastoma.

AIMS: Medulloblastoma (MB) is one of the most common malignant central nervous system tumors of childhood. Despite intensive treatments that often leads to severe neurological sequelae, the risk for resistant relapses remains significant. In this study we have evaluated the effects of the ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on MB cell lines and in a MB xenograft model. MAIN METHODS: Effects of ω3-LCPUFA treatment of MB cells were assessed using the following: WST-1 assay, cell death probes, clonogenic assay, ELISA and western blot. MB cells were implanted into nude mice and the mice were randomized to DHA, or a combination of DHA and EPA treatment, or to control group. Treatment effects in tumor tissues were evaluated with: LC-MS/MS, RNA-sequencing and immunohistochemistry, and tumors, erythrocytes and brain tissues were analyzed with gas chromatography. KEY FINDINGS: ω3-LCPUFA decreased prostaglandin E2 (PGE2) secretion from MB cells, and impaired MB cell viability and colony forming ability and increased apoptosis in a dose-dependent manner. DHA reduced tumor growth in vivo, and both PGE2 and prostacyclin were significantly decreased in tumor tissue from treated mice compared to control animals. All ω3-LCPUFA and dihomo-γ-linolenic acid increased in tumors from treated mice. RNA-sequencing revealed 10 downregulated genes in common among ω3-LCPUFA treated tumors. CRYAB was the most significantly altered gene and the downregulation was confirmed by immunohistochemistry. SIGNIFICANCE: Our findings suggest that addition of DHA and EPA to the standard MB treatment regimen might be a novel approach to target inflammation in the tumor microenvironment.

The skinny on tuna fat: health implications.

OBJECTIVE: Dietary n-3 (omega-3) and n-6 (omega-6) PUFA have significant implications in health and disease prevention. Marine life is rich in long-chain n-3 PUFA. Children and adults in North America are reluctant fish eaters; canned tuna is a common fish in children's diets. Although a multitude of tuna products are available, their respective PUFA contents have not been well described. The aim of the present study was to compare the fatty acid (FA) profiles of different commercially available US tuna products. DESIGN: Fat and FA composition of eight products randomly selected from two US suppliers were analysed with capillary GC after lipid extraction. SETTING: Large north-eastern US grocery store chain. SUBJECTS: Canned tuna. RESULTS: Energy from fat varied from 3 to 33 % and the essential FA (EFA) linoleic acid (18 : 2n-6) and α-linolenic acid (18 : 3n-3) varied tenfold. DHA varied between 90 and 770 mg/serving. The n-6:n-3 ratio was 3:1-4:1 in oil-packaged products, 2:1-7:1 in packaged tuna salads and 1:3-1:7 in water-packaged products. A similar magnitude of differences was seen in the ratio between arachidonic acid (20 : 4n-6) and DHA. CONCLUSIONS: Light tuna canned in water may be a better choice of providing n-3 PUFA to individuals in a healthy population, whereas oil-packaged products may be preferable for those individuals with a need for increased EFA, such as for patients with cystic fibrosis. Awareness regarding PUFA content may aid in consumer product choices and health-care provider advice.

Optimal vitamin A and suboptimal vitamin D status are common in Iranian infants.

AIM: Investigation of serum concentrations of vitamins A and D in Iranian infants. METHODS: A descriptive cross-sectional study, investigating 7112 infants (15-23 months of age) from all regions of Iran, who attended health care centres from May 25 to June 2, 2001. Unequal clusters with unequal household sizes were sampled. Vitamin A and D levels were analysed with high-performance liquid chromatography. RESULTS: The mean (SD) concentration of vitamin A was 2.09 (0.83) µmol/L. At a national level, 0.7% of the infants had a level indicating deficiency, and 0.5% of the infants had insufficient concentrations of vitamin A, defined as serum concentrations <0.35 and <0.7 µmol/L retinol, respectively. A total of 88% of infants had optimal concentrations (>1.4 µmol/L). The mean (SD) concentration of vitamin D was 61.3 (31.4) nmol/L. Deficiency was found in 2.8% of infants (<25 nmol/L), and insufficiency in 32.9% (<50 nmol/L). Suboptimal and optimal concentrations were found in 44% and 20%, representing 50-75 and >75 nmol/L, respectively. Girls had lower vitamin D concentrations than boys (p = 0.006). CONCLUSION: As in developed countries, vitamin A deficiency was rare in Iranian infants. Vitamin D deficiency was also rare, but 33% of infants had insufficient levels; this was more common in girls than boys.

Ezrin-radixin-moesin-binding phosphoprotein (EBP50), an estrogen-inducible scaffold protein, contributes to biliary epithelial cell proliferation.

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ie, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats and Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent up-regulation and intracellular redistribution in response to 17beta-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells.