Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes.

Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.

French mothers' milk deficient in DHA contains phospholipid species of potential interest for infant development.

OBJECTIVES: An insufficient human milk docosahexaenoic acid (DHA) level was reported worldwide, which leads to the question of the sufficiency of the DHA supply for infant development in the French Mediterranean area. Also, among milk lipids, phospholipids may be of high potential interest for infant brain development, being a specific vector of DHA and providing plasmalogens. We aimed to estimate the consumption of such milk compounds by preterm and term infants. MATERIALS AND METHODS: Milk samples from 22 lactating French women living in a port city, Marseille, were collected in a neonatology department from a single full-breast expression using an electric pump. Amounts of triglycerides, total phospholipids and plasmalogens, and fatty acid profile were determined by gas chromatography, and cholesterol by enzymatic assay. RESULTS: Depending on the infant dietary guidelines we referred to, 46% or 82% of milk samples were below the recommended DHA level (0.4% or 0.7%), and a majority exhibited high linoleic acid/α-linolenic acid and n-6/n-3 ratios, probably resulting from high linoleic acid together with low fish and seafood products consumption. DHA carried by phospholipids in a majority of specimens met the requirements for brain development for term but not for premature infants. Milk plasmalogen levels ranged from 3.4 to 39.2  mg/L. CONCLUSIONS: Our results support the recommendation of DHA supplementation to French mothers living in a Mediterranean port city, and of decreased linoleic acid intake, to reach optimal milk composition for infant health. DHA-containing phospholipids including plasmalogen species may represent important bioactive human milk compounds.

Increased tissue arachidonic acid and reduced linoleic acid in a mouse model of cystic fibrosis are reversed by supplemental glycerophospholipids enriched in docosahexaenoic acid.

An imbalance in (n-6)/(n-3) PUFA has been reported in cystic fibrosis (CF) patients. Glycerophospholipids enriched in docosahexaenoic acid (GPL-DHA) have been shown to regulate the (n-6)/(n-3) fatty acid ratio in the elderly. Here, we tested the effect of GPL-DHA supplementation on PUFA status in F508del homozygous CF mice. GPL-DHA liposomes were administrated by gavage (60 mg DHA/kg daily, i.e. at maximum 1.4 mg DHA/d) to 1.5-mo-old CF mice (CF+DHA) and their corresponding wild-type (WT) homozygous littermates (WT+DHA) for 6 wk. The PUFA status of different tissues was determined by GC and compared with control groups (CF and WT). There was an alteration in the (n-6) PUFA pathway in several CF-target organs in CF compared with WT mice, as evidenced by a higher level of arachidonic acid (AA) in membrane phospholipids or whole tissue (21 and 39% in duodenum-jejunum, 32 and 38% in ileum, and 19 and 43% in pancreas). Elevated AA levels were associated with lower linoleic acid (LA) and higher dihomo-gamma-linolenic acid levels. No DHA deficiency was observed. GPL-DHA treatment resulted in different PUFA composition changes depending on the tissue (increase in LA, decrease in elevated AA, DHA increase, increase in (n-6)/(n-3) fatty acid ratio). However, the DHA/AA ratio consistently increased in all tissues in CF+DHA and WT+DHA mice. Our study demonstrates the effectiveness of an original oral DHA formulation in counter-balancing the abnormal (n-6) fatty acid metabolism in organs of CF mice when administrated at a low dose and highlights the potential of the use of GPL-DHA as nutritherapy for CF patients.

Influence of pancreatic status and sex on polyunsaturated fatty acid profiles in cystic fibrosis.

BACKGROUND: Some but not all studies have reported abnormal polyunsaturated fatty acid composition in cystic fibrosis (CF) patients. We investigated the influence of pancreatic status and sex on the fatty acid profile in plasma and erythrocyte membranes in patients with CF. METHODS: After a 1-step transesterification with acetyl chloride on plasma and washed erythrocyte membranes, we quantified fatty acid methyl esters by use of GC-MS in 124 CF patients and 80 age-matched healthy controls. In the CF group, mean (SD) age was 17.5 (11.3) years, and 51.6% were male. Pancreatic insufficiency was diagnosed in 78% of the CF population. RESULTS: A decrease in docosahexaenoic acid concentrations was observed in CF patients independently of pancreatic status. Pancreatic insufficient CF patients displayed lower concentrations of linoleic acid and arachidonic acid and higher concentrations of dihomo-gamma-linolenic acid and eicosatrienoic acid (mead acid) in plasma and erythrocyte membranes compared with healthy controls and pancreatic sufficient CF patients. Male CF patients had significantly lower docosahexaenoic acid and higher eicosatrienoic acid in plasma and erythrocyte membranes compared with female CF patients. CONCLUSIONS: These results support the concept that multiple abnormalities of polyunsaturated fatty acid composition participate in the CF disease phenotype and that pancreatic status plays a major role in such abnormalities. Moreover, patient sex influences the polyunsaturated fatty acid spectrum in CF, with more marked abnormalities in males.

An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis.

Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and omega3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of omega3 fatty acid supplementation in cystic fibrosis.

At low doses, a gamma-linolenic acid-lipoic acid conjugate is more effective than docosahexaenoic acid-enriched phospholipids in preventing neuropathy in diabetic rats.

A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of gamma-linolenic acid (GLA)-lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid (DHA)-enriched phospholipids (PL) supplementations on NCV and NBF. Streptozotocin-induced diabetic (D) and control (C) rats were supplemented for 8 wk with either DHA-enriched PL at a dose of 30 mg.kg-1.d-1 (DDHA and CDHA) or with corn oil enriched with GLA-LA at a dose of 30 mg.kg-1.d-1 (DGLA and CGLA). Moreover, a C and D group received no supplementation. After 8 wk, NCV (-30%) and NBF (-50%) were lower in the D group than in the C group. Supplementation with GLA-LA totally prevented the decrease in NCV and NBF in the DGLA group, in which values did not differ from group C. Supplementation with DHA only partially prevented the decrease in NCV in the DDHA group, in which value was different from groups C and D and did not affect NBF. We conclude that at the low doses used, supplementation with GLA-LA is more effective than supplementation with DHA in preventing experimental diabetic neuropathy. The difference could be due in part to an antioxidant protective effect of LA on GLA.

Time-resolved fluorescence allows selective monitoring of Trp30 environmental changes in the seven-Trp-containing human pancreatic lipase.

Human pancreatic lipase (HPL, triacylglycerol acylhydrolase, EC 3.1.1.3) is a carboxyl esterase which hydrolyzes insoluble emulsified triglycerides and is essential for the efficient digestion of dietary fats. Though the three-dimensional structure of this enzyme has been determined, monitoring the conformational changes that may accompany the binding of various substrates and inhibitors is still of interest. Because of its sensitivity and ease of use, fluorescence spectroscopy of the intrinsic Trp residues is ideally suited for this purpose. However, the presence of seven Trp residues spread all over the HPL structure renders the interpretation of the fluorescence changes difficult with respect to the identification and location of the conformational or environmental changes taking place at the various Trp residues. In this context, the aim of this work was to investigate the contribution of the individual Trp residues to the fluorescence properties of HPL. To this end, we analyzed the steady-state and time-resolved fluorescence parameters of five single-point mutants in which one Trp residue was substituted with a weakly fluorescent Phe residue. In addition to the Trp residues at positions 30, 86, and 252, strategically located with respect to the active site, we also mutated Trp residues at positions 17 and 402, as representative residues of the HPL N- and C-terminal domains, respectively. Taken together, our data suggested that the solvent-exposed Trp30 residue contributed to at least 44% of the overall fluorescence of wild-type HPL. Moreover, we found that the long-lived fluorescence lifetime (6.77 ns) of wild-type HPL could be specifically attributed to Trp30, a feature that enables selective monitoring of its environmental changes. Additionally, Trp residues at positions 17 and 402 strongly contributed to the 1.61 ns lifetime of HPL, while Trp residues at positions 86 and 252 contributed to the 0.29 ns lifetime.

Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy.

A deficiency in essential fatty acid metabolism has been widely reported in both human and animal diabetes. Fish oil supplementations (n-3 fatty acids), containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were less effective on diabetic neuropathy than (n-6) fatty acids. This partial effect of (n-3) fatty acids might be attributed to the presence of EPA, a competitor of arachidonic acid, which enhanced the diabetes-induced decrease of this fatty acid in serum and tissues. For determining whether a supplementation with DHA alone could prevent neuropathy in streptozotocin-induced diabetes, diabetic rats were given daily, by gavage, liposomes containing DHA phospholipids, at a dose of 60 mg/kg. Eight weeks of diabetes induced significant decreases in nerve conduction velocity (NCV), nerve blood flow (NBF), and sciatic nerve and erythrocyte (red blood cells [RBCs]) Na,K-ATPase activities. DHA phospholipids totally prevented the decrease in NCV and NBF observed during diabetes when compared with the nonsupplemented diabetic group. DHA phospholipids also prevented the Na,K-ATPase activity decrease in RBC but not in sciatic nerve. Moreover, DHA level in sciatic nerve membranes was correlated with NCV. These results demonstrate a protective effect of daily doses of DHA on experimental diabetic neuropathy. Thus, treatment with DHA phospholipids could be suitable for evaluation in clinical trials.

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.

BACKGROUND & AIMS: Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations. METHODS: We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy. RESULTS: Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001). CONCLUSIONS: Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.

[Inappropriateness of hospital days and causes of failure in a Gastroenterology and Internal Medicine ward]. / Etude de la pertinence des journées d'hospitalisation dans un service de Gastroentérologie et Médecine Interne et analyse des causes de non-pertinence.

OBJECTIVES: To analyse patients' features linked to hospital inappropriateness and to highlight causes of inappropriate days in a Gastroenterology and Internal Medicine ward of a teaching hospital. METHODS: Appropriateness of patients' hospital days (2 months activity) was assessed using the French version of criteria of the Appropriateness Evaluation Protocol. Reasons of inappropriate hospital days were identified through a questionnaire based on patients' need. RESULTS: Two hundred and twenty patients were studied. Among the 2151 hospital days assessed, 880 (41%) were inappropriate. Two different groups of inappropriate stays were brought up. In the first group, the inappropriate period duration was short (<=5 days) and patients were not different from those of the appropriate group. In the second group, the inappropriate period duration was long ( > 5 days) and 710 days (33%) were inappropriate. Patients were elderly, lived alone and their disease did not concern the gastrointestinal tract. During inappropriate days, they expected access to less technical facilities than the short stay medical ward. CONCLUSION: The socio-demographic and medical features of the patients from the long duration inappropriateness group should help to limit inappropriate hospital days: a significant economic and organizational stake for patients, hospital and public interest.