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Sample records for acid efa deficiency

  1. Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice.

    PubMed

    Lukovac, S; Los, E L; Stellaard, F; Rings, E H H M; Verkade, H J

    2009-09-01

    Essential fatty acid (EFA) deficiency in mice has been associated with increased bile production, which is mainly determined by the enterohepatic circulation (EHC) of bile salts. To establish the mechanism underlying the increased bile production, we characterized in detail the EHC of bile salts in EFA-deficient mice using stable isotope technique, without interrupting the normal EHC. Farnesoid X receptor (FXR) has been proposed as an important regulator of bile salt synthesis and homeostasis. In Fxr(-/-) mice we additionally investigated to what extent alterations in bile production during EFA deficiency were FXR dependent. Furthermore, we tested in differentiating Caco-2 cells the effects of EFA deficiency on expression of FXR-target genes relevant for feedback regulation of bile salt synthesis. EFA deficiency-enhanced bile flow and biliary bile salt secretion were associated with elevated bile salt pool size and synthesis rate (+146 and +42%, respectively, P < 0.05), despite increased ileal bile salt reabsorption (+228%, P < 0.05). Cyp7a1 mRNA expression was unaffected in EFA-deficient mice. However, ileal mRNA expression of Fgf15 (inhibitor of bile salt synthesis) was significantly reduced, in agreement with absent inhibition of the hepatic bile salt synthesis. Bile flow and biliary secretion were enhanced to the same extent in EFA-deficient wild-type and Fxr(-/-) mice, indicating contribution of other factors besides FXR in regulation of EHC during EFA deficiency. In vitro experiments show reduced induction of mRNA expression of relevant genes upon chenodeoxycholic acid and a selective FXR agonist GW4064 stimulation in EFA-deficient Caco-2 cells. In conclusion, our data indicate that EFA deficiency is associated with interrupted negative feedback of bile salt synthesis, possibly because of reduced ileal Fgf15 expression.

  2. Essential fatty acid requirements of cats: pathology of essential fatty acid deficiency.

    PubMed

    MacDonald, M L; Anderson, B C; Rogers, Q R; Buffington, C A; Morris, J G

    1984-07-01

    The pathologic changes of essential fatty acid (EFA) deficiency were studied in specific-pathogen-free, domestic shorthair cats which were fed purified diets for 1.5 to 2.5 years. Cats fed an EFA-deficient diet exhibited signs of deficiency: severe fatty degeneration of the liver, excessive fat in the kidneys, dystrophic mineralization of the adrenal glands, degeneration of the testes, and hyperkeratosis of the skin. Minor clinical pathologic changes were consistent with liver damage. Fatty acid analyses of plasma lipids revealed low concentrations of linoleate and other n6-fatty acids, and high concentrations of n7- and n9-fatty acids, consistent with EFA deficiency. These signs of deficiency were prevented by including safflower seed oil in the diet at a concentration to supply linoleate at 6.7% of dietary energy. Therefore, linoleate is an EFA for the cat, despite negligible conversion of linoleate to arachidonate in cat liver. However, in cats fed a diet containing linoleate, but lacking arachidonate, there was mild mineralization of the kidneys, and the neutral fat content of the liver was slightly higher than that of cats fed a diet containing arachidonate and other long-chain polyunsaturated fatty acids. Also, 2 of the 19 cats fed arachidonate-deficient diets developed unusual inflammatory skin lesions. In cats fed a diet containing hydrogenated coconut oil, safflower seed oil, and chicken fat, fatty livers developed despite the presence of high levels of linoleate. The fatty livers appeared to result from a specific deleterious effect of the medium-chain triglycerides in hydrogenated coconut oil. Most of the organ pathologic changes of EFA deficiency in the cat can be prevented by feeding dietary linoleate. Linoleate meets the EFA requirement for functions which depend on proper membrane structure: growth, lipid transport, normal skin and coat condition, and maintenance of the epidermal permeability barrier. However, dietary arachidonate is required by the

  3. Fatty acid composition, eicosanoid production and permeability in skin tissues of rainbow trout (Oncorhynchus mykiss) fed a control or an essential fatty acid deficient diet.

    PubMed

    Ghioni, C; Bell, J G; Bell, M V; Sargent, J R

    1997-06-01

    Rainbow trout (Oncorhynchus mykiss) were fed either a control diet containing fish oil or an essential fatty acid (EFA) deficient diet containing only hydrogenated coconut oil and palmitic acid as lipid source (93.4% saturated fatty acids) for 14 weeks and the fatty acid compositions of individual phospholipid classes from skin and opercular membrane (OM) determined. The permeability of skin and OM to water and the production of eicosanoids in skin and gills challenged with the Ca2+ ionophore A23187 were also measured. Phospholipid (PL) fatty acid compositions were substantially modified in EFA-deficient fish, with increased saturated fatty acids and decreased polyunsaturated fatty acids (PUFA), especially arachidonic acid (AA) and eicosapentaenoic acid (EPA), while docosahexaenoic acid (DHA) was largely retained. The onset of EFA deficiency was shown by the appearance of n-9 PUFA, particularly 20:3n-9. The main effects of EFA deficiency on phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were to increase saturated fatty acids and monoenes, especially 16:1 and 18:1, and to decrease EPA and DHA. The content of DHA in phosphatidylserine (PS) was high in control animals (40% in skin and 35% in opercular membrane) and was mostly retained in EFA deficient animals. Arachidonic acid (AA) was the most abundant PUFA esterified to phosphatidylinositol (PI) and was significantly reduced in EFA deficient animals (from 31% to 13% in skin), where a large amount of 20:3n-9 (9% in skin) was also present. Influxes and effluxes of water through skin and opercular membrane were measured in vitro. No differences were detected between rainbow trout fed the control or the EFA deficient diet. 12-Hydroxyeicosatetraenoic acid (12-HETE), 12-hydroxyeicosapentaenoic acid (12-HEPE) and 14-hydroxydocosahexaenoic acid (14-HDHE) could not be detected in skin from control or EFA deficient fish. There was no difference between control and EFA deficient trout in the levels of leukotriene C

  4. Essential fatty acid deficiency delays the onset of puberty in the female rat.

    PubMed

    Smith, S S; Neuringer, M; Ojeda, S R

    1989-09-01

    This study assessed the effect of a dietary deficiency in the essential fatty acids (EFA) linoleic and linolenic acids on the onset of female puberty. EFA deficiency was produced in female rats by means of a semipurified diet and was biochemically documented by analyzing serum and erythrocyte fatty acid levels of more than 30 fatty acids, including all members of the n-6 and n-3 series. Levels of linoleic acid (18:2 n-6) and all n-6 derivatives, particularly arachidonic acid, were strikingly reduced. A less pronounced but clear-cut decrease in n-3 fatty acids, including docosahexaenoic acid (22:6 n-3) was also found. The times of puberty and first ovulation, as assessed by the ages at vaginal opening and first diestrus, were significantly delayed in EFA-deficient rats. The mechanisms underlying this delay appear to reside at both hypothalamic and ovarian sites. Simulation of preovulatory plasma estradiol (E2) levels via implantation of E2-containing Silastic capsules evoked a LH surge 30 h later in control juvenile rats, but not in EFA-deficient animals, indicating a delay in the development of the hypothalamic component of E2-positive feedback in the latter group. This delay appears to be due at least in part to reduced prostaglandin E2 (PGE2) synthesis, as the ability of the neurotransmitter norepinephrine to induce PGE2 release from median eminence nerve terminals was markedly reduced in EFA-deficient rats compared with that in controls. The decrease in hypothalamic PGE2 release was related to the EFA deficiency and not to reduced PG synthase activity, as determined by HPLC analysis of PG synthase products derived from exogenous [14C]arachidonic acid. Basal and hCG-stimulated PGE2 synthesis was also compromised in ovaries from EFA-deficient rats. Depressed gonadal function resulting from the EFA deficiency was further evidenced by a reduced gonadotropin receptor content, a blunted E2 response to hCG in vitro, and an increase in mean serum FSH levels. These

  5. Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes

    PubMed Central

    1990-01-01

    Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes

  6. [Pathology of placenta of rats induced by fatty acid deficiency].

    PubMed

    Glocker, T M

    2000-01-01

    Lipids are important cell components, both from the structural and the functional point of view. Besides, they intervene in transporting functions, cell recognition and immunity. Essential Fatty Acids (EFA) are important for the functional and structural maintenance of animal organisms. In our laboratory, it was demonstrated that one group of pregnant rats fed on an EFA deficient diet, and other group of rats fed on the same diet but with 5% of corn oil (rich in linoleic acid) showed alterations on the development of the metrial gland. In the present work, 57 female rats of a Wistar strain were fed since weaning with one of the following diets: EFAD: deficient in essential fatty acids, COD: EFAD + 5% corn oil (linoleic acid sufficient but alpha-linoleic acid deficient); SAD: EFAD + 5% soy oil (both EFA sufficient) and CD: commercial diet. After 3 months the animals were sacrificed on the 13 th. day of gestation. Uteru's horns were dissected and the implantation sities were fixed on formol and embebbed in parafin. The observations were carried out with H/E coloured cross-sections and the corialantoidea placenta, the cities of implantations and the sitios of reabsortions were studied. The metrial gland of DAGE and DAM rats presented structural modifications compared to DC rats. The most relevant findings were: indifferentiation of the granulated metrial gland cells and an increase in the amount of connective tissue. In DAS rats, on the contrary, the aspect of the metrial gland was similar to the observed in the DC group. In the DAGE and the DAM groups Labyrinthium was enlarged with vascular septum group. Mean while DAS was similar to group DC (thin and vascular). Differences in the cities of implantations and reabsortions were not detected. The present results suggest that alpha-linolenico acid is essential for the rat placenta to reach normal development.

  7. Dietary protein deficiency affects n-3 and n-6 polyunsaturated fatty acids hepatic storage and very low density lipoprotein transport in rats on different diets.

    PubMed

    Bouziane, M; Prost, J; Belleville, J

    1994-04-01

    Fatty livers and the similarity between the skin lesions in kwashiorkor and those described in experimental essential fatty acid (EFA) deficiency have led to the hypothesis that protein and EFA deficiencies may both occur in chronic malnutrition. The relationship between serum very low density lipoprotein (VLDL) and hepatic lipid composition was studied after 28 d of protein depletion to determine the interactions between dietary protein levels and EFA availability. Rats were fed purified diets containing 20 or 2% casein and 5% fat as either soybean oil rich in EFA, or salmon oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, or hydrogenated coconut oil poor in EFA. Animals were divided into six groups, SOC (20% casein + 5% soybean oil), SOd (2% casein + 5% soybean oil), COC (20% casein + 5% hydrogenated coconut oil), COd (2% casein + 5% hydrogenated coconut oil), SAC (20% casein + 5% salmon oil) and SAd (2% casein + 5% salmon oil). After 28 d, liver steatosis and reduced VLDL-phospholipid contents (P < 0.001) were observed in protein-deficient rats. In protein deficiency, triacylglycerol and phospholipid fatty acid compositions in both liver and VLDL showed a decreased polyunsaturated-to-saturated fatty acid ratio. This ratio was higher with the salmon oil diets and lower with the hydrogenated coconut oil diets. Furthermore, independent of the oil in the diet, protein deficiency decreased linoleic and arachidonic acids in VLDL phospholipids. Conversely, despite decreased proportions of EPA at low protein levels, DHA levels remained higher in rats fed salmon oil diets.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Dietary influences of evening primrose and fish oil on the skin of essential fatty acid-deficient guinea pigs.

    PubMed

    Chapkin, R S; Ziboh, V A; McCullough, J L

    1987-08-01

    There have been reports that certain dietary lipids are capable of regulating cellular inflammation and hyperproliferation. To investigate further the role of dietary manipulation involving gamma-linolenic acid (18:3n-6) and eicosapentaenoic acid (20:5n-3) on hyperproliferative cellular components, the effects of orally administered primrose oil (containing 18:3n-6) and menhaden fish oil (containing 20:5n-3) were tested in a cutaneous system using the essential fatty acid (EFA)-deficient guinea pig fed a hydrogenated coconut oil (HCO) diet. The effects of the dietary crossover regimen were determined on epidermal 1) morphology, 2) DNA synthesis, 3) delta 6- and delta 5-desaturase activities and 4) fatty acid composition of skin and liver lipids. Our results demonstrated that dietary fish oil lacked the capacity to reverse the signs of epidermal hyperproliferation, acanthosis and hypergranulosis that are characteristic of EFA deficiency. In contrast, primrose oil feeding reversed the histological and biochemical signs of hyperproliferation. These results suggest that dietary fish oil, which contains largely the 20:5n-3 fatty acid, lacks EFA-functional properties in the skin. In addition, substitution of HCO with primrose or fish oil after 6 wk revealed incorporation of 18:3n-6 and 20:5n-3 into epidermal lipids, respectively. The significance of these altered epidermal fatty acid profiles is discussed.

  9. Comparison of the clinical efficacy of two commercial fatty acid supplements (EfaVet and DVM Derm Caps), evening primrose oil, and cold water marine fish oil in the management of allergic pruritus in dogs: a double-blinded study.

    PubMed

    Scott, D W; Miller, W H; Decker, G A; Wellington, J R

    1992-07-01

    Twenty dogs with atopy or idiopathic pruritus were treated in a double-blinded clinical trial with computer-randomized and computer-generated sequences of 4 fatty acid-containing products: evening primrose oil, cold water marine fish oil, DVM Derm Caps, and EfaVet. Each dog received each product for a 2-week period. Five of 20 dogs (25%) had a good-to-excellent reduction in their level of pruritus with at least 1 of the products: evening primrose oil (2 dogs), DVM Derm Caps (1), EfaVet (1), DVM Derm Caps and cold water marine fish oil (1). Only 1 dog experienced a side effect (loose stools). Clinical response to fatty acid supplements appeared to be quite individualized, and independent of age, breed, sex, weight, duration of disease, specific diagnosis, or number of positive intradermal test reactions.

  10. Rapid effects of essential fatty acid deficiency on growth and development parameters and transcription of key fatty acid metabolism genes in juvenile barramundi (Lates calcarifer).

    PubMed

    Salini, Michael J; Turchini, Giovanni M; Wade, Nicholas M; Glencross, Brett D

    2015-12-14

    Barramundi (Lates calcarifer), a catadromous teleost of significant and growing commercial importance, are reported to have limited fatty acid bioconversion capability and therefore require preformed long-chain PUFA (LC-PUFA) as dietary essential fatty acid (EFA). In this study, the response of juvenile barramundi (47·0 g/fish initial weight) fed isolipidic and isoenergetic diets with 8·2% added oil was tested. The experimental test diets were either devoid of fish oil (FO), and thus with no n-3 LC-PUFA (FO FREE diet), or with a low inclusion of FO (FO LOW diet). These were compared against a control diet containing only FO (FO CTRL diet) as the added lipid source, over an 8-week period. Interim samples and measurements were taken fortnightly during the trial in order to define the aetiology of the onset and progression of EFA deficiency. After 2 weeks, the fish fed the FO FREE and FO LOW diets had significantly lower live-weights, and after 8 weeks significant differences were detected for all performance parameters. The fish fed the FO FREE diet also had a significantly higher incidence of external abnormalities. The transcription of several genes involved in fatty acid metabolism was affected after 2 weeks of feeding, showing a rapid nutritional regulation. This experiment documents the aetiology of the onset and the progression of EFA deficiency in juvenile barramundi and demonstrates that such deficiencies can be detected within 2 weeks in juvenile fish.

  11. Rapid effects of essential fatty acid deficiency on growth and development parameters and transcription of key fatty acid metabolism genes in juvenile barramundi (Lates calcarifer).

    PubMed

    Salini, Michael J; Turchini, Giovanni M; Wade, Nicholas M; Glencross, Brett D

    2015-12-14

    Barramundi (Lates calcarifer), a catadromous teleost of significant and growing commercial importance, are reported to have limited fatty acid bioconversion capability and therefore require preformed long-chain PUFA (LC-PUFA) as dietary essential fatty acid (EFA). In this study, the response of juvenile barramundi (47·0 g/fish initial weight) fed isolipidic and isoenergetic diets with 8·2% added oil was tested. The experimental test diets were either devoid of fish oil (FO), and thus with no n-3 LC-PUFA (FO FREE diet), or with a low inclusion of FO (FO LOW diet). These were compared against a control diet containing only FO (FO CTRL diet) as the added lipid source, over an 8-week period. Interim samples and measurements were taken fortnightly during the trial in order to define the aetiology of the onset and progression of EFA deficiency. After 2 weeks, the fish fed the FO FREE and FO LOW diets had significantly lower live-weights, and after 8 weeks significant differences were detected for all performance parameters. The fish fed the FO FREE diet also had a significantly higher incidence of external abnormalities. The transcription of several genes involved in fatty acid metabolism was affected after 2 weeks of feeding, showing a rapid nutritional regulation. This experiment documents the aetiology of the onset and the progression of EFA deficiency in juvenile barramundi and demonstrates that such deficiencies can be detected within 2 weeks in juvenile fish. PMID:26411329

  12. The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally.

    PubMed

    Wene, J D; Connor, W E; DenBesten, L

    1975-07-01

    The hypothesis that clinical and biochemical essential fatty acid deficiency (EFA) might occur from the feeding of eucaloric, fat-free diets was tested in two experiments in healthy men. In Study I, eight men were given fat-free, eucaloric diets containing 80% of calories as glucose and 20% as amino acid hydrolysates by a constant drip over a 24-h period. The diets were fed in succession for periods of 2 wk each, either through a superior vena cava catheter or via a nasogastric tube. EFA deficiency was detected by decreases in linoleic acid and by the appearance of 5, 8, 11-eicosatrienoic acid in lipid fractions of plasma. Linoleic acid decreased significantly during 2 wk of the fat-free diet given intravenously from 48.8 to 9.8% (percent of total fatty acids) in cholesterol esters, from 21.2 to 3.2% in phospholipids, from 9.6 to 2.0% in free fatty acids, and from 14.1 to 2.6% in triglycerides. Eicosatrienoic acid, normally undetectable, appeared 0.6% in cholesterol esters, 2.5% in phospholipids, 0.2% in free fatty acids, and 2.3% in triglycerides. EFA deficiency occurred similarly during the nasogastric feeding. In Study II a subject received the same diet continuously by the nasogastric route for 10 days followed by a 24-h fast. He was then given the fat-free diet intermittently in three meals per day for 3 days. Finally, he was repleted with a diet containing 2.6% linoleic acid. By the 3rd day of the continuous nasogastric feeding, linoleic acid had fallen significantly and eicosatrienoic acid had appeared in plasma lipid fractions as in Study I. These findings were accentuated by day 10. Adipose tissue fatty acid composition did not change. Free fatty acid outflow from adipose tissue was presumably suppressed during the 10 days of continuous feeding. With increased free fatty acid outflow during fasting and intermittent feeding, linoleic acid rose and eicosatrienoic acid decreased. After 13 days of repletion with dietary linoleic acid, the EFA deficiency

  13. Development of an in vitro model of essential fatty acid deficiency in fish cells.

    PubMed

    Tocher, D R; Dick, J R; Sargent, J R

    1995-11-01

    Levels of eicosapentaenoic acid (EPA; 20:5, n-3) greatly exceed those of arachidonic acid (AA; 20:4, n-6) in the tissue phospholipids of most fish species. Despite this, it is 20:4, n-6-derived eicosanoids that are produced predominantly in fish cells. The development of an essential fatty acid (EFA)-deficient fish cell line would greatly assist the study of this selectivity and so several fish cell lines were cultured in EFA-deficient (EFAD) media. All n-3 and n-6 polyunsaturated fatty acids (PUFA) and total PUFA were considerably reduced in all lines, except turbot fin (TF) in which total n-9 PUFA doubled from 13.8% to 27.5% of total fatty acids. In the topminnow hepatocarcinoma cell line (PLHC-1), there was almost complete depletion of both n-3 and n-6 PUFA and in TF cells, no n-3 PUFA were detected. In the carp epithelial papilloma cell line (EPC), both n-6 and n-3 PUFA were reduced by approximately 70%. The reduced PUFA in cells cultured in EFAD media was compensated to a large extent in most cell lines by significantly increased percentages of monounsaturated fatty acids, particularly 18:1, n-9. Total n-9 PUFA were significantly increased in all cell lines by culture in EFAD media, with 20:2, n-9 significantly increased in all cell lines. There were relatively small increases, but often significant, in 20:3, n-9 in all cell lines. Of the cell lines investigated, only EPC and PLHC-1 showed proliferation after four passages in EFAD medium, although the growth rates were reduced in comparison with media supplemented with serum, but EPC was the only cell line able to survive and proliferate in long-term culture on EFAD medium. The EFAD-EPC line is a potentially useful model system for the study of the effects of EFA deficiency on cell structure and function and eicosanoid metabolism in fish. PMID:8596777

  14. Genetics Home Reference: aromatic l-amino acid decarboxylase deficiency

    MedlinePlus

    ... aromatic l-amino acid decarboxylase deficiency aromatic l-amino acid decarboxylase deficiency Enable Javascript to view the expand/ ... PDF Open All Close All Description Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that ...

  15. Esterification of essential and non-essential fatty acids into distinct lipid classes in ruminant and non-ruminant tissues.

    PubMed

    Caldari-Torres, Cristina; McGilliard, Michael L; Corl, Benjamin A

    2016-10-01

    Extensive microbial biohydrogenation of polyunsaturated fatty acids (PUFA) in the rumen reduces the essential fatty acids (EFA) available for absorption in ruminant animals, but there is no published documentation of ruminants developing EFA deficiency. In ruminants, most circulating PUFA are found in the phospholipid (PL) and cholesteryl ester lipid classes that have slow turn-over compared to other lipid classes. The objective of this experiment was to measure fatty acid esterification patterns of the non-EFA palmitic (16:0) and oleic acid (18:1), and the EFA linoleic (18:2) and linolenic acid (18:3) in small intestine, liver, and muscle tissue of cows and pigs to identify tissues participating in sequestration of these FA in less metabolically active lipid classes in ruminants. Bovine and porcine small intestine, liver, and muscle explants were prepared and incubated in media containing radiolabeled 16:0, 18:1, 18:2, or 18:3 to measure esterification of fatty acids into PL and TG. Neither bovine nor porcine small intestine explants preferentially incorporated non-EFA compared to EFA into PL vs TG. Bovine liver explants esterified a larger proportion of EFA than non-EFA into PL compared to TG, while incorporation was similar among the FA tested in porcine liver explants. Bovine muscle explants showed preferential incorporation of EFA into PL rather than TG. Results show that bovine and porcine liver and muscle esterify EFA and non-EFA differently and that the conservation of EFA in ruminants is a result of preferential incorporation of EFA into PL mediated by bovine liver and muscle, but not the small intestine. PMID:27134010

  16. The Effect of varying ratios of docosahexaenoic Acid and arachidonic acid in the prevention and reversal of biochemical essential fatty acid deficiency in a murine model

    PubMed Central

    Le, Hau D.; Fallon, Erica M.; Kalish, Brian T.; de Meijer, Vincent E.; Meisel, Jonathan A.; Gura, Kathleen M.; Nose, Vania; Pan, Amy H.; Bistrian, Bruce R.; Puder, Mark

    2012-01-01

    Objective Essential fatty acids (EFA) are necessary for growth, development, and biological function, and must be acquired through the diet. While linoleic acid (LA) and alpha-linolenic acid (ALA) have been considered the true EFAs, we previously demonstrated that docosahexaenoic acid (DHA) and arachidonic acid (AA) taken together as the sole source of dietary fatty acids can prevent biochemical essential fatty acid deficiency (EFAD). This study evaluates the effect of varying dietary ratios of DHA:AA in the prevention and reversal of biochemical EFAD in a murine model. Methods Using a murine model of EFAD, we provided mice with 2.1% of daily caloric intake in varying DHA:AA ratios (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) for 19 days in association with a liquid high-carbohydrate fat-free diet to evaluate the effect on fatty acid profiles. In a second experiment, we evaluated the provision of varying DHA:AA ratios (20:1, 200:1, 100:0) on the reversal of biochemical EFAD. Results Mice provided with DHA and AA had no evidence of biochemical EFAD, regardless of the ratio (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) administered. Biochemical EFAD was reversed with DHA:AA ratios of 20:1, 200:1, and 100:0 following 3 and 5 weeks of dietary provision, although the 20:1 ratio was most effective in the reversal and stabilization of the triene:tetraene ratio. Conclusion Provision of DHA and AA, at 2.1% of daily caloric intake in varying ratios can prevent biochemical evidence of EFAD and hepatic steatosis over the short-term, with a ratio of 20:1 DHA:AA most effectively reversing EFAD. PMID:23151438

  17. Polyunsaturated fatty acids in the low-birth-weight infant.

    PubMed

    Friedman, Z

    1979-10-01

    The essentiality of certain PUFAs is related to their capability to be incorporated into lipids and to act as precursor in the formation of prostaglandins. Via phospholipids the EFA's influence the physico-chemical characteristics of biomembranes. EFAs are metabolized differently from nonessential PUFAs. While the nonessential fatty acids are metabolized rapidly, the organism tends to conserve the stores of EFAs. Inhibitions and competitions among the EFAs of the three series (oleic, linoleic, and alpha-linolenic) have been demonstrated. Apparently, for any given chain length the more unsaturated fatty acid has a greater affinity for the enzyme system responsible for further elongation and desaturation. EFAs are also necessary for the proper utilization of the saturated fatty acids. Vitamin E and pyridoxine seem to be involved in EFA metabolism. Normal growth of infants is dependent upon an adequate supply of EFA. The human fetus, like the adult, is unable to synthesize the EFAs, which must therefore be derived from the maternal circulation and pass through the placenta. In the fetus, increased concentration of the polyenoic fatty acids with advanced gestational age may result from increased activity of the fetomaternal unit by preferential transfer of these FAs. Enzymatic activity in the placenta or the fetus may also be responsible for desaturation and elongation of these EFAs. Several clinical manifestations have been ascribed in the human infant to prolonged EFA deficiency; however, none of these findings was noted in a group of sick newborn infants with very rapid onset of deficiency. Platelet dysfunction, decreased prostaglandin biosynthesis and turnover and altered pulmonary surfactant are among the effects of EFA deficiency on infants. Supplementation of the EFAs by the diet, parenterally or by the inunction of oil rich in linoleic acid, were reported to alleviate the symptoms of EFA deficiency. The minimal estimated requirement of linoleic acid is 1% of

  18. The neurology of folic acid deficiency.

    PubMed

    Reynolds, E H

    2014-01-01

    The metabolism of folic acid and the metabolism of vitamin B12 are intimately linked such that deficiency of either vitamin leads to an identical megaloblastic anemia. The neurologic manifestations of folate deficiency overlap with those of vitamin B12 deficiency and include cognitive impairment, dementia, depression, and, less commonly, peripheral neuropathy and subacute combined degeneration of the spinal cord. In both deficiency states there is often dissociation between the neuropsychiatric and the hematologic complications. There is a similar overlap and dissociation between neurologic and hematologic manifestations of inborn errors of folate and vitamin B12 metabolism. Low folate and raised homocysteine levels are risk factors for dementia, including Alzheimer's disease, and depression. Even when folate deficiency is secondary to psychiatric illness due to apathy or poor diet it may eventually aggravate the underlying disorder in a vicious circle effect. Clinical responses to treatment with folates are usually slow over weeks and months, probably due to the efficient blood-brain barrier mechanism for the vitamin, perhaps in turn related to the experimentally demonstrated excitatory properties of folate derivatives. The inappropriate administration of folic acid in the presence of vitamin B12 deficiency may lead to both neurologic and, later, hematologic relapse. Impaired maternal folate intake and status increases the risk of neural tube defects. Periconceptual prophylactic administration of the vitamin reduces, but does not eliminate the risk of neural tube defects even in the absence of folate deficiency. Folates and vitamin B12 have fundamental roles in central nervous system function at all ages, especially in purine, thymidine, neucleotide, and DNA synthesis, genomic and nongenomic methylation and, therefore, in tissue growth, differentiation and repair. There is interest in the potential role of both vitamins in the prevention of disorders of central

  19. EFA Mid-Decade Assessment Meeting Report. Annual EFA Coordinators Meeting/EFA Mid-Decade Assessment Planning Meeting (7th, Bangkok, Thailand, October 24-29, 2005)

    ERIC Educational Resources Information Center

    Tung, Ko-Chih

    2006-01-01

    Six Education For All (EFA) goals were agreed to in the World Education Forum in Dakar, Senegal in 2000. Since then, UNESCO Bangkok, UNICEF and the Regional Thematic Working Group on EFA have been jointly assisting countries in conducting assessment of progress and gaps towards the EFA goals and mid-term review of policies and reforms. In October…

  20. Therapeutic Response of Vitamin A, Vitamin B Complex, Essential Fatty Acids (EFA) and Vitamin E in the Treatment of Phrynoderma: A Randomized Controlled Study

    PubMed Central

    S., Ragunatha; Kumar V., Jagannath; S.B., Murugesh; M., Ramesh; G., Narendra; Kapoor, Meenakshi

    2014-01-01

    Background: In the treatment of phrynoderma, various nutrients have been tried in different dosages and routes with variable therapeutic outcomes. Aims: The present study was undertaken to compare the efficacy of various nutrients in the treatment of phrynoderma. Settings and Design: An open label randomized controlled study was conducted in the out-patient department of Dermatology in a tertiary care hospital. Material and Methods: The patients were divided into group of five and each patient received one of the five regimens [10 injections of Vitamin A 1 lakh units, intramuscularly (IM) on alternate day, 10 injections of Vitamin B complex, 2cc IM on alternate day, 2 table spoon of safflower oil, two times daily with meals, Tab Vitamin E 400mg once daily, and only topical keratolytic (salicylic acid 3% ointment) two times daily] respectively. The first four regimens also received topical keratolytic. The primary outcome measured was therapeutic response at the end of regimen. The response was graded based on the percentage of flattening and decrease in number of lesions. Less than 25% improvement was graded as poor, 26-50% improvement as moderate, 51-75% improvement as good, and more than 75% improvement as excellent response. In the statistical analysis, comparison was done using Chi-square and Fisher’s exact test. Results: A total of 125 patients were included in the study with 25 patients each in five regimen groups. There were 79 (63.2%) males and 46 (36.8%) females with a ratio of 1.72:1. The age of the patients ranged from 3 to 26 years with mean of 10.1±4.3 years. Out of 125 patients, 105 completed the study. In regimen 1 and 2, significant number of patients showed good to excellent response whereas significant number of patients in remaining regimen showed moderate to poor response with a p value of <0.05. The therapeutic response to Vitamin A and Vitamin B complex therapy was significantly better than other regimens. Conclusion: Intramuscular

  1. Essential fatty acid deficiency in malnourished children.

    PubMed

    Holman, R T; Johnson, S B; Mercuri, O; Itarte, H J; Rodrigo, M A; De Tomas, M E

    1981-08-01

    Fatty acid patterns of major classes of lipids of serum were measured in forty Argentine children ages 2 to 24 months admitted to the hospital with chronic malnutrition. A normal control group of 48 children from the same population was also examined. Serum lipids were extracted and separated into phospholipids, cholesteryl esters, triglycerides, and free fatty acids. These were converted to methyl esters which were analyzed by gas chromatography. In chronic malnutrition, the fatty acid patterns of phospholipids and cholesteryl esters indicated changes characteristic of essential fatty acid deficiency of moderate degree. The total omega 6 acids were found to be highly significantly diminished from normal, and the ratio of 20:3 omega 9/20:4 omega 6 was highly significantly increased. Decreased proportions of omega 6 metabolites suggested impaired desaturase activity, and elevated ratios of 22:4 omega 6/20:4 omega 6 and 20:2 omega 6/18:2 omega 6 suggested increased chain elongation in chronic malnutrition.

  2. Effects of an essential fatty acid deficiency, pair-feeding and level of dietary corn oil on the hypothalamic-pituitary-gonadal axis and other physiological parameters in the male chicken.

    PubMed

    Engster, H M; Carew, L B; Cunningham, F J

    1978-06-01

    Two studies were conducted to observe the effects of an essential fatty acid (EFA) deficiency, added dietary corn oil and pair-feeding on growth, reproduction and other physiological parameters in the mature cockerel. A purified, linoleic acid (LA)-deficient diet (0.01% LA), or additions of 5% (3.01% LA) or 15% (9.04% LA) corn oil, were fed ad libitum from hatching through 24 weeks of age. Reductions in growth, feed consumption, and comb, and testes size, incomplete spermatogenesis, increased tissue eicosatrienoic acid (20: 3 omega 9) and changes in weights of selected internal organs were observed in deficient cockerels. Total pituitary gonadotropic activity was measured by two bioassay procedures and blood luteinizing hormone was measured by radioimmunoassay. By maturity both of these parameters were significantly reduced in deficient chickens. When these chickens were fed diets with 5% or 15% corn oil under pair-feeding or ad libitum conditions from 20 to 24 weeks, the reduced growth, comb and testes size and gonadotropin metabolism appeared to be caused by depressions in appetite and energy intake rather than EFA per se. The degenerate testicular histology of the 20-week old deficient cockerels, while responding fully to the ad libitum intake of the diets containing corn oil, showed only partial rehabilitation of spermatogenesis when diets with either 5% or 15% corn oil were pair-fed. In general, increasing the level of dietary fat from 5% to 15% did not cause many physiological changes.

  3. Rats rapidly reject diets deficient in essential amino acids.

    PubMed

    Koehnle, Thomas J; Russell, Matthew C; Gietzen, Dorothy W

    2003-07-01

    Omnivores must obtain diets balanced with respect to amino acids to support growth and protein synthesis. The standard paradigm used to study behavioral responses to amino acid deficiency combines deficient diets with dietary novelty. The objective of this study was to examine the effects of amino acid deficiency on the first meal of rats without the confounding effects of novelty. We report on a series of five studies of feeding behavior in rats. Rats were fed low protein diets for 5-7 d and then exposed to diets with and without essential amino acids. Rats consistently demonstrated recognition of essential amino acid deficiency within the first meal by a significant reduction in first meal duration, rejecting the deficient diets after just 12-16 min exposure. This is the first report of a rapid effect of amino acid-deficient diets without the confounding effects of dietary novelty.

  4. Stimulation of proliferation of an essential fatty acid-deficient fish cell line by C20 and C22 polyunsaturated fatty acids and effects on fatty acid composition.

    PubMed

    Tocher, D R; Dick, J R; Sargent, J R

    1996-11-01

    Recently we reported the development of a fish cell line, EPC-EFAD, derived from the carp (Cyprinus carpio) epithelial papilloma line, EPC, that could survive and proliferate in essential fatty acid-deficient (EFAD) medium. The EPC-EFAD cell line may be a useful model system in which to study the cellular biochemical effects of EFA deficiency and has advantages in studies of polyunsaturated fatty acid (PUFA) and eicosanoid metabolism in fish in that the complications introduced by culture in relatively n-6 PUFA-rich mammalian sera are removed. In the present study, the effects on cell proliferation rate of supplementing EPC-EFAD cells with various n-3 and n-6 PUFA were investigated to determine the possible role(s) of PUFA in cell growth and division. The selectivity of incorporation of specific PUFA into individual glycerophospholipid classes and the feasibility of reproducing in vivo fatty acid compositions in vitro were also investigated. Proliferation of the EPC-EFAD cell line was stimulated by arachidonic (20:4 n-6), eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) fatty acids but not by 18:2 n-6 or 18:3 n-3. The differential effects of PUFA on cellular proliferation may be related to the lack of significant delta 5 desaturase activity in the cells at 22 degrees C and may implicate a role for eicosanoids in the mechanism of stimulation of proliferation. PUFA supplementation increased the cytotoxic effects of longer term culture, an effect that was partly alleviated by inclusion of vitamin E in the culture medium. The cells could generally be supplemented with PUFA to produce cellular fatty acid compositions in vitro that were similar to in vivo compositions. PMID:8981632

  5. Artificial rearing of infant mice leads to n-3 fatty acid deficiency in cardiac, neural and peripheral tissues.

    PubMed

    Hussein, Nahed; Fedorova, Irina; Moriguchi, Toru; Hamazaki, Kei; Kim, Hee-Yong; Hoshiba, Junji; Salem, Norman

    2009-08-01

    The ability to control the fatty acid content of the diet during early development is a crucial requirement for a one-generation model of docosahexaenoic acid (DHA; 22:6n3) deficiency. A hand feeding method using artificial rearing (AR) together with sterile, artificial milk was employed for feeding mice from postnatal day 2-15. The pups were fed an n-3 fatty acid adequate (3% alpha-linolenic acid (LNA; 18:3n3) + 1% 22:6n3) or a deficient diet (0.06% 18:3n3) with linoleic acid (LA; 18:2n6) as the only dietary source of essential fatty acids by AR along with a dam-reared control group (3.1% 18:3n3). The results indicate that restriction of n-3 fatty acid intake during postnatal development leads to markedly lower levels of brain, retinal, liver, plasma and heart 22:6n3 at 20 weeks of age with replacement by docosapentaenoic acid (DPAn6; 22:5n6), arachidonic acid (ARA; 20:4n6) and docosatetraenoic acid (DTA; 22:4n6). A detailed analysis of phospholipid classes of heart tissue indicated that phosphatidylethanolamine, phosphatidylcholine and cardiolipin were the major repositories of 22:6n3, reaching 40, 29 and 15%, respectively. A novel heart cardiolipin species containing four 22:6n3 moieties is described. This is the first report of the application of artificially rearing to mouse pup nutrition; this technique will facilitate dietary studies of knockout animals as well as the study of essential fatty acid (EFA) functions in the cardiovascular, neural and other organ systems.

  6. Biologic significance of polyunsaturated fatty acids in the skin.

    PubMed

    Ziboh, V A; Chapkin, R S

    1987-12-01

    Deficiency of essential fatty acid (EFA) containing linoleic acid (18:2n-6) in humans or animals induces morphologic changes characterized by severe scaly dermatosis, extensive percutaneous water loss, and hyperproliferation of the epidermis. Microscopically, the epidermis is characterized by hyperkeratosis and acanthosis. The refeeding of safflower oil containing linoleic acid or primrose oil (containing linoleic acid [18:2n-6] and gamma-linolenic acid [18:3n-6]) acids to EFA-deficient guinea pigs reverses the EFA-deficiency symptoms. In contrast, replacement of safflower oil with menhaden fish oil, (containing eicosapentaenoic acid [20:5n-3] and docosahexaenoic acid [22:6n-3]) did not reverse the symptoms of EFA deficiency. These results indicate: (1) that an understanding of the roles of vegetable or fish oil in skin must evolve from an understanding of the roles of each constituent n-6 or n-3 fatty acid, and (2) that the n-3 fatty acids may function to modulate the metabolism and function of the n-6 fatty acids in vivo.

  7. DOCOSAHEXAENOIC ACID AND ARACHIDONIC ACID PREVENT ESSENTIAL FATTY ACID DEFICIENCY AND HEPATIC STEATOSIS

    PubMed Central

    Le, Hau D.; Meisel, Jonathan A.; de Meijer, Vincent E.; Fallon, Erica M.; Gura, Kathleen M.; Nose, Vania; Bistrian, Bruce R.; Puder, Mark

    2012-01-01

    Objectives Essential fatty acids are important for growth, development, and physiologic function. Alpha-linolenic acid and linoleic acid are the precursors of docosahexaenoic and arachidonic acid, respectively, and have traditionally been considered the essential fatty acids. However, we hypothesized that docosahexaenoic acid and arachidonic acid can function as the essential fatty acids. Methods Using a murine model of essential fatty acid deficiency and consequent hepatic steatosis, we provided mice with varying amounts of docosahexaenoic and arachidonic acids to determine whether exclusive supplementation of docosahexaenoic and arachidonic acids could prevent essential fatty acid deficiency and inhibit or attenuate hepatic steatosis. Results Mice supplemented with docosahexaenoic and arachidonic acids at 2.1% or 4.2% of their calories for 19 days had normal liver histology and no biochemical evidence of essential fatty acid deficiency, which persisted when observed after 9 weeks. Conclusion Supplementation of sufficient amounts of docosahexaenoic and arachidonic acids alone without alpha-linolenic and linoleic acids meets essential fatty acid requirements and prevents hepatic steatosis in a murine model. PMID:22038210

  8. Clinical Features of Lysosomal Acid Lipase Deficiency

    PubMed Central

    Burton, Barbara K.; Deegan, Patrick B.; Enns, Gregory M.; Guardamagna, Ornella; Horslen, Simon; Hovingh, Gerard K.; Lobritto, Steve J.; Malinova, Vera; McLin, Valerie A.; Raiman, Julian; Di Rocco, Maja; Santra, Saikat; Sharma, Reena; Sykut-Cegielska, Jolanta; Whitley, Chester B.; Eckert, Stephen; Valayannopoulos, Vassili; Quinn, Anthony G.

    2015-01-01

    Abstract Objective: The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults. Methods: Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. Results: A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0–42); mean age at diagnosis was 15.2 years (range 1–46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9–43.5 years). Conclusion: This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation. PMID:26252914

  9. Cerebral folate deficiency: life-changing supplementation with folinic acid.

    PubMed

    Hansen, Flemming Juul; Blau, Nenad

    2005-04-01

    Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on folinic acid (15-30 mg/day) and her 5-methyltetrahydrofolate in CSF normalized. This report demonstrates the importance of CSF investigation in the diagnosis of cerebral folate deficiency and efficiency of folinic acid (5-formyltetrahydrofolate) supplementation. PMID:15781200

  10. Handbook for Decentralized Education Planning. Implementing National EFA Plans

    ERIC Educational Resources Information Center

    Online Submission, 2005

    2005-01-01

    The Dakar 2000 goal of Education For All (EFA) is at the center of UNESCO's education activities worldwide. The wide-ranging efforts to achieve EFA in many countries involve education reform, development strategies and plans. Decentralization, a major component in modernizing the public sector, is also applicable to the education sector. The…

  11. EFA, Civil Society and the Post-2015 Agenda

    ERIC Educational Resources Information Center

    Verger, Antoni; Sayed, Yusuf; Hiroshi, Ito; Croso, Camilla; Beardmore, Sarah

    2012-01-01

    The year 2015 is the deadline for most of the Education for All (EFA) goals. As this date gets closer, reviews about what has been done and reflection about future agendas will multiply. This Forum aims to contribute such a pressing debate, bringing together contributors from key international organisations within the EFA movement. They are…

  12. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  13. Maternal bile acid transporter deficiency promotes neonatal demise

    PubMed Central

    Zhang, Yuanyuan; Li, Fei; Wang, Yao; Pitre, Aaron; Fang, Zhong-ze; Frank, Matthew W.; Calabrese, Christopher; Krausz, Kristopher W.; Neale, Geoffrey; Frase, Sharon; Vogel, Peter; Rock, Charles O.; Gonzalez, Frank J.; Schuetz, John D.

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition. PMID:26416771

  14. Maternal bile acid transporter deficiency promotes neonatal demise.

    PubMed

    Zhang, Yuanyuan; Li, Fei; Wang, Yao; Pitre, Aaron; Fang, Zhong-Ze; Frank, Matthew W; Calabrese, Christopher; Krausz, Kristopher W; Neale, Geoffrey; Frase, Sharon; Vogel, Peter; Rock, Charles O; Gonzalez, Frank J; Schuetz, John D

    2015-09-29

    Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition.

  15. Developments of the European Flood Awareness System (EFAS)

    NASA Astrophysics Data System (ADS)

    Olav Skøien, Jon; Salamon, Peter; Pappenberger, Florian; Wetterhall, Fredrik; Holst, Bo; Asp, Sara-Sofia; Garcia Padilla, Mercedes; Garcia Sanchez, Rafael J.; Schweim, Christoph; Ziese, Markus

    2016-04-01

    EFAS (http://www.efas.eu) is an operational system for flood forecasting and flood warning for Europe which has become fully operational as part of the Copernicus Emergency Management Service in 2012. The aim of EFAS is to gain time for preparedness measures before major flood events strike particularly for trans-national river basins both at country as well as on European level. This is achieved by providing complementary, added value information to the national hydrological services. Using a coherent model for all of Europe forced with a range of deterministic and ensemble weather forecasts, the system can give a probabilistic flood forecast for a medium range lead time (up to 10 days) independent of country borders. The system is under continuous development, and we will present the basic set up, some prominent examples of recent and ongoing developments and the future challenges.

  16. True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase (QPRT) Knockout Mice.

    PubMed

    Shibata, Katsumi

    2015-01-01

    Pyridine nucleotide coenzymes (PNCs) are involved in over 500 enzyme reactions. PNCs are biosynthesized from the amino acid L-tryptophan (L-Trp), as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-) or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and the qprt(+/-) mice. On the other hand, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (p<0.01) and 70% (p<0.05) of the corresponding values for the qprt(-/-) mice fed the complete diet at day 23, respectively. The nutritional levels of niacin such as blood and liver NAD concentrations were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of quinolinic acid was greater in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice (p<0.01). These data suggest that we generated truly niacin-deficient mice. PMID:26598832

  17. True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase (QPRT) Knockout Mice.

    PubMed

    Shibata, Katsumi

    2015-01-01

    Pyridine nucleotide coenzymes (PNCs) are involved in over 500 enzyme reactions. PNCs are biosynthesized from the amino acid L-tryptophan (L-Trp), as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-) or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and the qprt(+/-) mice. On the other hand, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (p<0.01) and 70% (p<0.05) of the corresponding values for the qprt(-/-) mice fed the complete diet at day 23, respectively. The nutritional levels of niacin such as blood and liver NAD concentrations were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of quinolinic acid was greater in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice (p<0.01). These data suggest that we generated truly niacin-deficient mice.

  18. Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat.

    PubMed

    Ganguli, M; Tobian, L; Ferris, T; Johnson, M A

    1989-07-01

    Renal distribution of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, an 18% reduction (p less than .025). Second study: Male Sprague-Dawley rats were made prostaglandin deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin deficient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p less than .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.

  19. Retinoic acid deficiency alters second heart field formation.

    PubMed

    Ryckebusch, Lucile; Wang, Zengxin; Bertrand, Nicolas; Lin, Song-Chang; Chi, Xuan; Schwartz, Robert; Zaffran, Stéphane; Niederreither, Karen

    2008-02-26

    Retinoic acid (RA), the active derivative of vitamin A, has been implicated in various steps of cardiovascular development. The retinaldehyde dehydrogenase 2 (RALDH2) enzyme catalyzes the second oxidative step in RA biosynthesis and its loss of function creates a severe embryonic RA deficiency. Raldh2(-/-) knockout embryos fail to undergo heart looping and have impaired atrial and sinus venosus development. To understand the mechanism(s) producing these changes, we examined the contribution of the second heart field (SHF) to pharyngeal mesoderm, atria, and outflow tract in Raldh2(-/-) embryos. RA deficiency alters SHF gene expression in two ways. First, Raldh2(-/-) embryos exhibited a posterior expansion of anterior markers of the SHF, including Tbx1, Fgf8, and the Mlc1v-nlacZ-24/Fgf10 reporter transgene as well as of Islet1. This occurred at early somite stages, when cardiac defects became irreversible in an avian vitamin A-deficiency model, indicating that endogenous RA is required to restrict the SHF posteriorly. Explant studies showed that this expanded progenitor population cannot differentiate properly. Second, RA up-regulated cardiac Bmp expression levels at the looping stage. The contribution of the SHF to both inflow and outflow poles was perturbed under RA deficiency, creating a disorganization of the heart tube. We also investigated genetic cross-talk between Nkx2.5 and RA signaling by generating double mutant mice. Strikingly, Nkx2.5 deficiency was able to rescue molecular defects in the posterior region of the Raldh2(-/-) mutant heart, in a gene dosage-dependent manner. PMID:18287057

  20. Physical fatty acid deficiency signs in children with ADHD symptoms.

    PubMed

    Sinn, N

    2007-08-01

    Fatty acid deficiency symptoms (FADS) of dry hair and skin, frequent thirst and urination have been observed to be higher in children with attention deficit hyperactivity disorder (ADHD). Two studies investigated FADS in 7-12-year-old children; Study 1 in a general population (N=347) and Study 2 in children with ADHD symptoms (N=104). Correlations between FADS and ADHD-related symptoms were found at baseline in Study 1 but not Study 2. FADS did not improve after supplementation with omega-3 and omega-6 polyunsaturated fatty acids (PUFA) versus placebo after 15 weeks in Study 2, and were not related to improvements in ADHD symptoms in the PUFA groups. However, FADS did improve in all groups, possibly attributable to the linoleic acid present in both the PUFA and placebo (palm oil) supplements. FADS are not a reliable selection criterion for children with ADHD who might benefit from omega-3 PUFA supplementation.

  1. Inclusive Education: An EFA Strategy For All Children 31195

    ERIC Educational Resources Information Center

    Peters, Susan J.

    2004-01-01

    The fundamental principle of Education for All (EFA) is that all children should have the opportunity to learn. The fundamental principle of Inclusive Education (IE) is that all children should have the opportunity to learn?together. Diversity is a characteristic that all children and youth have in common?both within each individual child and…

  2. Guidelines for Preparing Gender Responsive EFA Plans. Education for All.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    These guidelines have been prepared to assist individuals and "teams" to produce EFA (Education for All) plans that are gender responsive. The guidelines aim to raise awareness about issues that need to be considered to produce plans leading to the achievement of gender equality in education. Further information and guidance regarding gender…

  3. Conceptualising Disability in Ghana: Implications for EFA and Inclusive Education

    ERIC Educational Resources Information Center

    Anthony, Jane

    2011-01-01

    The Ghanaian government has recently ratified its commitment to Education for All (EFA) and to reaching marginalised students through inclusive education. This article critically examines the often conflicting demands of internationally driven initiatives and their subsequent interpretation and implementation in a disparate culture. A…

  4. Aspirin-triggered metabolites of EFAs.

    PubMed

    Makriyannis, Alexandros; Nikas, Spyros P

    2011-10-28

    Aspirin triggers the biosynthesis of oxygenated metabolites from arachidonic, eicosapentaenoic, and docosahexaenoic (DHA) acids. In a preceding issue, Serhan et al. (2011) describe a novel aspirin-triggered DHA pathway for the biosynthesis of a potent anti-inflammatory and proresolving molecule. PMID:22035788

  5. Essential fatty acid nutrition of the American alligator (Alligator mississippiensis).

    PubMed

    Staton, M A; Edwards, H M; Brisbin, I L; Joanen, T; McNease, L

    1990-07-01

    The essential fatty acid (EFA) nutrition of young American alligators (Alligator mississippiensis) was examined by feeding a variety of fats/oils with potential EFA activity. Over a 12-wk period, alligators fed diets containing 2.5 or 5.0% chicken liver oil grew longer and heavier and converted feed to body mass more efficiently than alligators fed other fat/oil combinations that lacked or contained only trace amounts of arachidonic acid [20:4(n-6)]. Alligators fed an EFA-deficient diet (containing only coconut fat as the dietary fat) were the slowest-growing animals and converted feed to body mass least efficiently. However, over a 41-wk feeding period, alligators fed this diet showed no obvious external signs of deficiency other than being reduced in size and unthrifty. Fatty acid composition of heart, liver, muscle, skin and adipose tissue lipids was influenced markedly by dietary fat composition. Tissues varied significantly in response to dietary fat composition. Heart lipids contained the lowest levels of short- and medium-chain fatty acids and the highest levels of arachidonic acid. Arachidonic acid levels were less influenced by diet than were levels of other 20- and 22-carbon polyunsaturated fatty acids. Radiotracer studies indicated that linoleic acid was converted to arachidonic acid in the liver. Nevertheless, tissue arachidonic acid levels also appeared to be maintained by concentration from dietary sources and selective conservation. It appears that a dietary source of arachidonic acid may be required for a maximum rate of growth.

  6. Nickel deficiency disrupts metabolism of ureides, amino acids, and organic acids of young pecan foliage.

    PubMed

    Bai, Cheng; Reilly, Charles C; Wood, Bruce W

    2006-02-01

    The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan. PMID:16415214

  7. Prevalence of anaemia, deficiencies of iron and folic acid and their determinants in Ethiopian women.

    PubMed

    Haidar, Jemal

    2010-08-01

    A cross-sectional community-based study with analytic component was conducted among Ethiopian women during June-July 2005 to assess the magnitude of anaemia and deficiencies of iron and folic acid and to compare the factors responsible for anaemia among anaemic and non-anaemic cases. In total, 970 women, aged 15-19 years, were selected systematically for haematological and other important parameters. The overall prevalence of anaemia, iron deficiency, iron-deficiency anaemia, deficiency of folic acid, and parasitic infestations was 30.4%, 50.1%, 18.1%, 31.3%, and 13.7% respectively. Women who had more children aged less than five years but above two years, open-field toilet habits, chronic illnesses, and having intestinal parasites were positively associated with anaemia. Women who had no formal education and who did not use contraceptives were negatively associated with anaemia. The major determinants identified for anaemia were chronic illnesses [adjusted odds ratio (AOR) = 1.1, 95% confidence interval (CI) 1.15-1.55), deficiency of iron (AOR = 0.4, 95% CI 0.35-0.64), and deficiency of folic acid (AOR = 0.5, 95% CI 0.50-0.90). The odds for developing anaemia was 1.1 times more likely among women with chronic illnesses, 60% more likely in the iron-deficient and 40% more likely in the folic acid-deficient than their counterparts. One in every three women had anaemia and deficiency of folic acid while one in every two had iron deficiency, suggesting that deficiencies of both folic acid and iron constitute the major micronutrient deficiencies in Ethiopian women. The risk imposed by anaemia to the health of women ranging from impediment of daily activities and poor pregnancy outcome calls for effective public-health measures, such as improved nutrient supplementation, health education, and timely treatment of illnesses.

  8. Potential of essential fatty acid deficiency with extremely low fat diet in lipoprotein lipase deficiency during pregnancy: A case report

    PubMed Central

    Tsai, Elaine C; Brown, Judy A; Veldee, Megan Y; Anderson, Gregory J; Chait, Alan; Brunzell, John D

    2004-01-01

    Background Pregnancy in patients with lipoprotein lipase deficiency is associated with high risk of maternal pancreatitis and fetal death. A very low fat diet (< 10% of calories) is the primary treatment modality for the prevention of acute pancreatitis, a rare but potentially serious complication of severe hypertriglyceridemia. Since pregnancy can exacerbate hypertriglyceridemia in the genetic absence of lipoprotein lipase, a further reduction of dietary fat intake to < 1–2% of total caloric intake may be required during the pregnancy, along with the administration of a fibrate. It is uncertain if essential fatty acid deficiency will develop in the mother and fetus with this extremely low fat diet, or whether fibrates will cross the placenta and concentrate in the fetus. Case presentation A 23 year-old gravida 1 woman with primary lipoprotein lipase deficiency was seen at 7 weeks of gestation in the Lipid Clinic for management of severe hypertriglyceridemia that had worsened with pregnancy. While on her habitual fat intake of 10% of total calories, her pregnancy resulted in an exacerbation of the hypertriglyceridemia, which prompted further restriction of fat intake to < 2% of total calories, as well as administration of gemfibrozil at a lower than average dose. The level of gemfibrozil, as the active metabolite, in the venous and arterial fetal cord blood was within the expected therapeutic range for adults. The clinical signs and a biomarker of essential fatty acid deficiency, namely the ratio of 20:3 [n-9] to 20:4 [n-6] fatty acids, were closely monitored throughout her pregnancy. Despite her extremely low fat diet, the levels of essential fatty acids measured in the mother and in the fetal blood immediately postpartum were normal. Normal essential fatty acid levels may have been achieved by the topical application of sunflower oil. Conclusions An extremely low fat diet in combination with topical sunflower oil and gemfibrozil administration was safely

  9. [Lysosomal acid lipase deficiency. Overview of Czech patients].

    PubMed

    Elleder, M; Poupĕtová, H; Ledvinová, J; Hyánek, J; Zeman, J; Sýkora, J; Stozický, F; Chlumská, A; Lohse, P

    1999-11-29

    Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage of triacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediated LDL endocytosis are affected (liver, kidneys). There are two basic phenotypes. The fatal infantile phenotype (Wolman's disease) with generalized storage of both types of apolar lipids. This form was diagnosed in this country only once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterized by the storage of CE (which gave this entity the name of cholesteryl storage disease--CESD). Its main sign is affection of the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotic transformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increased VLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipids is a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases of CESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy with hepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patients with permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quite incidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis was established in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) and molecular genetic level (mutation in enzyme locus). In all instances mutation of G934A was found leading to reduction and loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations were heterozygous. In one instance for technical

  10. Pantothenic acid deficiency may increase the urinary excretion of 2-oxo acids and nicotinamide catabolites in rats.

    PubMed

    Shibata, Katsumi; Inomoto, Kasumi; Nakata, Chifumi; Fukuwatari, Tsutomu

    2013-01-01

    Pantothenic acid (PaA) is involved in the metabolism of amino acids as well as fatty acid. We investigated the systemic metabolism of amino acids in PaA-deficient rats. For this purpose, urine samples were collected and 2-oxo acids and L-tryptophan (L-Trp) and its metabolites including nicotinamide were measured. Group 1 was freely fed a conventional chemically-defined complete diet and used as an ad lib-fed control, which group was used for showing reference values. Group 2 was freely fed the complete diet without PaA (PaA-free diet) and used as a PaA-deficient group. Group 3 was fed the complete diet, but the daily food amount was equal to the amount of the PaA-deficient group and used as a pair-fed control group. All rats were orally administered 100 mg of L-Trp/kg body weight at 09:00 on day 34 of the experiment and the following 24-h urine samples were collected. The urinary excretion of the sum of pyruvic acid and oxaloacetic acid was higher in rats fed the PaA-free diets than in the rats fed pair-fed the complete diet. PaA deficiency elicited the increased urinary excretion of anthranilic acid and kynurenic acid, while the urinary excretion of xanthurenic acid decreased. The urinary excretion of L-Trp itself, 3-hydroxyanthranilic acid, and quinolinic acid revealed no differences between the rats fed the PaA-free and pair-fed the complete diets. PaA deficiency elicited the increased excretion of N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide. These findings suggest that PaA deficiency disturbs the amino acid catabolism.

  11. 27 CFR 24.182 - Use of acid to correct natural deficiencies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... citric acid may be added to citrus fruit, juice or wine, only malic acid may be added to apples, apple... (including berries) may be added within the limitations of § 24.246 to juice or wine in order to correct natural deficiencies; however, no acid may be added to juice or wine which is ameliorated to...

  12. 27 CFR 24.182 - Use of acid to correct natural deficiencies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... citric acid may be added to citrus fruit, juice or wine, only malic acid may be added to apples, apple... (including berries) may be added within the limitations of § 24.246 to juice or wine in order to correct natural deficiencies; however, no acid may be added to juice or wine which is ameliorated to...

  13. 27 CFR 24.182 - Use of acid to correct natural deficiencies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... citric acid may be added to citrus fruit, juice or wine, only malic acid may be added to apples, apple... (including berries) may be added within the limitations of § 24.246 to juice or wine in order to correct natural deficiencies; however, no acid may be added to juice or wine which is ameliorated to...

  14. 27 CFR 24.182 - Use of acid to correct natural deficiencies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... citric acid may be added to citrus fruit, juice or wine, only malic acid may be added to apples, apple... (including berries) may be added within the limitations of § 24.246 to juice or wine in order to correct natural deficiencies; however, no acid may be added to juice or wine which is ameliorated to...

  15. 27 CFR 24.182 - Use of acid to correct natural deficiencies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... citric acid may be added to citrus fruit, juice or wine, only malic acid may be added to apples, apple... (including berries) may be added within the limitations of § 24.246 to juice or wine in order to correct natural deficiencies; however, no acid may be added to juice or wine which is ameliorated to...

  16. Plasma Amino Acids Profiles in Children with Autism: Potential Risk of Nutritional Deficiencies.

    ERIC Educational Resources Information Center

    Arnold, Georgianne L.; Hyman, Susan L.; Mooney, Robert A.; Kirby, Russell S.

    2003-01-01

    The plasma amino acid profiles of 10 children with autism on gluten and casein restricted diets and 26 on unrestricted diets were reviewed. There was a trend for the children on restricted diets to have an increased prevalence of essential amino acid deficiencies and lower plasma levels of essential acids. (Contains references.) (Author/CR)

  17. Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy.

    PubMed

    Herbert, M A; Clayton, P T

    1994-01-01

    This report describes a patient with high serum phytanic acid concentration due to phytanic acid alpha-oxidase deficiency (classical Refsum disease). He presented unusually early, hypotonia and developmental delay being apparent by 7 months. A generalized peroxisomal disorder (so-called 'infantile Refsum disease') was excluded by analyses of pristanic acid, very long-chain fatty acids, bile acids and plasmalogen synthesis. The early presentation raises the possibility of in utero exposure to phytanate.

  18. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    SciTech Connect

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-03-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using /sup 14/C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD.

  19. Complete Genome Sequence of a New Enterococcus faecalis Bacteriophage, vB_EfaS_IME197

    PubMed Central

    Cheng, Shi; Xing, Shaozhen; Zhang, Xianglilan; Pei, Guangqian; An, Xiaoping; Mi, Zhiqiang; Huang, Yong

    2016-01-01

    We report here the whole-genome sequence of a new Enterococcus faecalis phage, vB_EfaS_IME197, which has a linear double-stranded DNA genome of 41,307 bp with 34% G+C content. We describe the main features of the genome of vB_EfaS_IME197. PMID:27634987

  20. Complete Genome Sequence of a New Enterococcus faecalis Bacteriophage, vB_EfaS_IME197.

    PubMed

    Cheng, Shi; Xing, Shaozhen; Zhang, Xianglilan; Pei, Guangqian; An, Xiaoping; Mi, Zhiqiang; Huang, Yong; Tong, Yigang

    2016-01-01

    We report here the whole-genome sequence of a new Enterococcus faecalis phage, vB_EfaS_IME197, which has a linear double-stranded DNA genome of 41,307 bp with 34% G+C content. We describe the main features of the genome of vB_EfaS_IME197. PMID:27634987

  1. Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures.

    PubMed Central

    Isaacs, H; Savage, N; Badenhorst, M; Whistler, T

    1986-01-01

    An adult patient with lysosomal acid alpha-glucosidase deficiency was fully investigated, and then placed on various forms of therapy with favourable response to a high protein, low carbohydrate diet. The rationale for the employment of this therapy, the problem of acid maltase deficiency and the relationship to weakness and glycogenosome formation with accumulation or otherwise of glycogen within the muscle fibres is discussed. Images PMID:3093639

  2. L-ascorbic acid metabolism in the ascorbate-deficient arabidopsis mutant vtc1.

    PubMed Central

    Conklin, P L; Pallanca, J E; Last, R L; Smirnoff, N

    1997-01-01

    The biosynthesis of L-ascorbic acid (vitamin C) is not well understood in plants. The ozone-sensitive Arabidopsis thaliana mutant vitamin c-1 (vtc1; formerly known as soz1) is deficient in ascorbic acid, accumulating approximately 30% of wild-type levels. This deficiency could result from elevated catabolism or decreased biosynthesis. No differences that could account for the deficiency were found in the activities of enzymes that catalyze the oxidation or reduction of ascorbic acid. The absolute rate of ascorbic acid turnover is actually less in vtc1 than in wild type; however, the turnover rate relative to the pool of ascorbic acid is not significantly different. The results from [U-14C]Glc labeling experiments suggest that the deficiency is the result of a biosynthetic defect: less L-[14C]ascorbic acid as a percentage of total soluble 14C accumulates in vtc1 than in wild type. The feeding of two putative biosynthetic intermediates, D-glucosone and L-sorbosone, had no positive effect on ascorbic acid levels in either genotype. The vtc1 defect does not appear to be the result of a deficiency in L-galactono-1,4-lactone dehydrogenase, an enzyme able to convert L-galactono-1,4-lactone to ascorbic acid. PMID:9390448

  3. URBANIZATION ALTERS FATTY ACID CONCENTRATIONS OF STREAM FOOD WEBS IN THE NARRAGANSETT BAY WATERSHED

    EPA Science Inventory

    Urbanization and associated human activities negatively affect stream algal and invertebrate assemblages, likely altering food webs. Our goal was to determine if urbanization affects food web essential fatty acids (EFAs) and if EFAs could be useful ecological indicators in monito...

  4. Education For All: A Committment and an Opportunity. National EFA Coordinators Meeting under the Sub-Regional EFA Forum for East and Southeast Asia Final Report (2nd, Bangkok, Thailand, December 10-12, 2001).

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Bangkok (Thailand). Regional Office for Education in Asia and the Pacific.

    The working group of Sub-Regional Forum (SRF) and the Thematic Working Group (TWG) on Education for All (EFA) organized the second meeting of the SRF for East and Southeast Asia and the National EFA Coordinators in Bangkok, Thailand December 10-12, 2001. The meeting offered an opportunity for EFA coordinators to reflect on the outcomes of the EFA…

  5. Essential Fatty Acids and Attention-Deficit-Hyperactivity Disorder: A Systematic Review

    ERIC Educational Resources Information Center

    Raz, Raanan; Gabis, Lidia

    2009-01-01

    Aim: Essential fatty acids (EFAs), also known as omega-3 and omega-6 fatty acids, have been claimed to have beneficial effects as a treatment for attention-deficit-hyperactivity disorder (ADHD). Animal experiments have provided information about the role of EFA in the brain, and several mechanisms of EFA activity are well known. The current review…

  6. Voluntary wheel running is beneficial to the amino acid profile of lysine-deficient rats.

    PubMed

    Nagao, Kenji; Bannai, Makoto; Seki, Shinobu; Kawai, Nobuhiro; Mori, Masato; Takahashi, Michio

    2010-06-01

    Rats voluntarily run up to a dozen kilometers per night when their cages are equipped with a running wheel. Daily voluntary running is generally thought to enhance protein turnover. Thus, we sought to determine whether running worsens or improves protein degradation caused by a lysine-deficient diet and whether it changes the utilization of free amino acids released by proteolysis. Rats were fed a lysine-deficient diet and were given free access to a running wheel or remained sedentary (control) for 4 wk. Amino acid levels in plasma, muscle, and liver were measured together with plasma insulin levels and tissue weight. The lysine-deficient diet induced anorexia, skeletal muscle loss, and serine and threonine aminoacidemia, and it depleted plasma insulin and essential amino acids in skeletal muscle. Allowing rats to run voluntarily improved these symptoms; thus, voluntary wheel running made the rats less susceptible to dietary lysine deficiency. Amelioration of the declines in muscular leucine and plasma insulin observed in running rats could contribute to protein synthesis together with the enhanced availability of lysine and other essential amino acids in skeletal muscle. These results indicate that voluntary wheel running under lysine-deficient conditions does not enhance protein catabolism; on the contrary, it accelerates protein synthesis and contributes to the maintenance of muscle mass. The intense nocturnal voluntary running that characterizes rodents might be an adaptation of lysine-deficient grain eaters that allows them to maximize opportunities for food acquisition. PMID:20233939

  7. USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly

    PubMed Central

    Théard, Delphine; Labarrade, Florian; Partisani, Mariagrazia; Milanini, Julie; Sakagami, Hiroyuki; Fon, Edward A; Wood, Stephen A; Franco, Michel; Luton, Frédéric

    2010-01-01

    In epithelial cells, the tight junction (TJ) functions as a permeability barrier and is involved in cellular differentiation and proliferation. Although many TJ proteins have been characterized, little is known about the sequence of events and temporal regulation of TJ assembly in response to adhesion cues. We report here that the deubiquitinating enzyme USP9x has a critical function in TJ biogenesis by controlling the levels of the exchange factor for Arf6 (EFA6), a protein shown to facilitate TJ formation, during a narrow temporal window preceding the establishment of cell polarity. At steady state, EFA6 is constitutively ubiquitinated and turned over by the proteasome. However, at newly forming contacts, USP9x-mediated deubiquitination protects EFA6 from proteasomal degradation, leading to a transient increase in EFA6 levels. Consistent with this model, USP9x and EFA6 transiently co-localize at primordial epithelial junctions. Furthermore, knockdown of either EFA6 or USP9x impairs TJ biogenesis and EFA6 overexpression rescues TJ biogenesis in USP9x-knockdown cells. As the loss of cell polarity is a critical event in the metastatic spread of cancer, these findings may help to understand the pathology of human carcinomas. PMID:20339350

  8. EFA6 controls Arf1 and Arf6 activation through a negative feedback loop.

    PubMed

    Padovani, Dominique; Folly-Klan, Marcia; Labarde, Audrey; Boulakirba, Sonia; Campanacci, Valérie; Franco, Michel; Zeghouf, Mahel; Cherfils, Jacqueline

    2014-08-26

    Guanine nucleotide exchange factors (GEFs) of the exchange factor for Arf6 (EFA6), brefeldin A-resistant Arf guanine nucleotide exchange factor (BRAG), and cytohesin subfamilies activate small GTPases of the Arf family in endocytic events. These ArfGEFs carry a pleckstrin homology (PH) domain in tandem with their catalytic Sec7 domain, which is autoinhibitory and supports a positive feedback loop in cytohesins but not in BRAGs, and has an as-yet unknown role in EFA6 regulation. In this study, we analyzed how EFA6A is regulated by its PH and C terminus (Ct) domains by reconstituting its GDP/GTP exchange activity on membranes. We found that EFA6 has a previously unappreciated high efficiency toward Arf1 on membranes and that, similar to BRAGs, its PH domain is not autoinhibitory and strongly potentiates nucleotide exchange on anionic liposomes. However, in striking contrast to both cytohesins and BRAGs, EFA6 is regulated by a negative feedback loop, which is mediated by an allosteric interaction of Arf6-GTP with the PH-Ct domain of EFA6 and monitors the activation of Arf1 and Arf6 differentially. These observations reveal that EFA6, BRAG, and cytohesins have unanticipated commonalities associated with divergent regulatory regimes. An important implication is that EFA6 and cytohesins may combine in a mixed negative-positive feedback loop. By allowing EFA6 to sustain a pool of dormant Arf6-GTP, such a circuit would fulfill the absolute requirement of cytohesins for activation by Arf-GTP before amplification of their GEF activity by their positive feedback loop.

  9. Baker's Yeast Deficient in Storage Lipid Synthesis Uses cis-Vaccenic Acid to Reduce Unsaturated Fatty Acid Toxicity.

    PubMed

    Sec, Peter; Garaiova, Martina; Gajdos, Peter; Certik, Milan; Griac, Peter; Hapala, Ivan; Holic, Roman

    2015-07-01

    The role of cis-vaccenic acid (18:1n-7) in the reduction of unsaturated fatty acids toxicity was investigated in baker's yeast Saccharomyces cerevisiae. The quadruple mutant (QM, dga1Δ lro1Δ are1Δ are2Δ) deficient in enzymes responsible for triacylglycerol and steryl ester synthesis has been previously shown to be highly sensitive to exogenous unsaturated fatty acids. We have found that cis-vaccenic acid accumulated during cultivation in the QM cells but not in the corresponding wild type strain. This accumulation was accompanied by a reduction in palmitoleic acid (16:1n-7) content in the QM cells that is consistent with the proposed formation of cis-vaccenic acid by elongation of palmitoleic acid. Fatty acid analysis of individual lipid classes from the QM strain revealed that cis-vaccenic acid was highly enriched in the free fatty acid pool. Furthermore, production of cis-vaccenic acid was arrested if the mechanism of fatty acids release to the medium was activated. We also showed that exogenous cis-vaccenic acid did not affect viability of the QM strain at concentrations toxic for palmitoleic or oleic acids. Moreover, addition of cis-vaccenic acid to the growth medium provided partial protection against the lipotoxic effects of exogenous oleic acid. Transformation of palmitoleic acid to cis-vaccenic acid is thus a rescue mechanism enabling S. cerevisiae cells to survive in the absence of triacylglycerol synthesis as the major mechanism for unsaturated fatty acid detoxification.

  10. Studies of the effects of essential fatty acid deficiency in the rat.

    PubMed

    Cox, J W; Rutecki, G W; Francisco, L L; Ferris, T F

    1982-12-01

    We report a model of prostaglandin depletion induced in rats by fasting for 11 days, followed by institution of an essential fatty acid-deficient diet. Urinary prostaglandin E, 2 weeks after this diet had been implemented, was 22 +/- 2 ng/24 hours compared to 113 +/- 8.5 ng/24 hours in controls (P less than 0.01). There was no difference in 24-hour urine volume or solute excretion in controls and essential fatty acid-deficient rats. Five hours after administration of NaCl, 10 mM/kg, essential fatty acid-deficient diet rats excreted 1.85 +/- 0.78 ml urine compared to 6.42 +/- 2.26 ml in control (p less than 0.01) with Na+ excretion 447 +/- 273 muEq in essential fatty acid-deficient rats vs 1483 +/- 366 muEq in control (P less than 0.01). Intravenous isotonic NaCl, 1.5% body weight, resulted in increased urine flow rate in control rats from 8.3 +/- 2 microliter/min to 28.7 +/- 8.8 microliter/min with sodium excretion increasing from 0.19 +/- 0.2 to 3.3 +/- 0.9 muEq/min. In the essential fatty acid-deficient diet animals, there was no significant change in flow rate, 6.07 +/- 2.43 to 9.85 +/- 4.29 microliter/min, or sodium excretion, 0.09 +/- 0.03 to 0.40 +/- 0.24 muEq, after saline infusion. There was no difference in the glomerular filtration rate of plasma aldosterone in the two groups after the salt load. When given a water load, 3 ml/100 g body weight, essential fatty acid-deficient diet rats excreted 2.5 +/- 0.7 ml in 5 hours compared to 6.3 +/- 1.4 ml in controls (P less than 0.01). The defect in water excretion was not due to increased sensitivity to antidiuretic hormone, since similar sensitivity to this hormone was demonstrated in the essential fatty acid-deficient diet and control rats during a water diuresis. When isotonic saline was substituted for drinking water, there was an increase in systolic blood pressure in essential fatty acid-deficient diet rats from 124 +/- 2 to 142 +/- 3 mm Hg over 9 days (P less than 0.01) compared to 122 +/- 2 before and 122

  11. Omega-3 fatty acid deficiency disrupts endocytosis, neuritogenesis, and mitochondrial protein pathways in the mouse hippocampus

    PubMed Central

    English, Jane A.; Harauma, Akiko; Föcking, Melanie; Wynne, Kieran; Scaife, Caitriona; Cagney, Gerard; Moriguchi, Toru; Cotter, David R.

    2013-01-01

    Omega-3 fatty acid (n-3 FA) deficiency is an environmental risk factor for schizophrenia, yet characterization of the consequences of deficiency at the protein level in the brain is limited. We aimed to identify the protein pathways disrupted as a consequence of chronic n-3 deficiency in the hippocampus of mice. Fatty acid analysis of the hippocampus following chronic dietary deficiency revealed a 3-fold decrease (p < 0.001) in n-3 FA levels. Label free LC-MS/MS analysis identified and profiled 1008 proteins, of which 114 were observed to be differentially expressed between n-3 deficient and control groups (n = 8 per group). The cellular processes that were most implicated were neuritogenesis, endocytosis, and exocytosis, while specific protein pathways that were most significantly dysregulated were mitochondrial dysfunction and clathrin mediated endocytosis (CME). In order to characterize whether these processes and pathways are ones influenced by antipsychotic medication, we used LC-MS/MS to test the differential expression of these 114 proteins in the hippocampus of mice chronically treated with the antipsychotic agent haloperidol. We observed 23 of the 114 proteins to be differentially expressed, 17 of which were altered in the opposite direction to that observed following n-3 deficiency. Overall, our findings point to disturbed synaptic function, neuritogenesis, and mitochondrial function as a consequence of dietary deficiency in n-3 FA. This study greatly aids our understanding of the molecular mechanism by which n-3 deficiency impairs normal brain function, and provides clues as to how n-3 FA exert their therapeutic effect in early psychosis. PMID:24194745

  12. Vitamin B(12) deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid.

    PubMed

    Vaes, Bart L T; Lute, Carolien; Blom, Henk J; Bravenboer, Nathalie; de Vries, Teun J; Everts, Vincent; Dhonukshe-Rutten, Rosalie A; Müller, Michael; de Groot, Lisette C P G M; Steegenga, Wilma T

    2009-05-01

    The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B(12) deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B(12), Hcy, and MMA on differentiation and activity of bone cells. B(12) deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B(12) deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B(12), Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B(12) did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B(12) deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.

  13. Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma.

    PubMed

    Atwal, Paldeep S; Donti, Taraka R; Cardon, Aaron L; Bacino, C A; Sun, Qin; Emrick, L; Reid Sutton, V; Elsea, Sarah H

    2015-01-01

    Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines. We report a case of AADC deficiency that was detected using the Global MAPS platform. This is a novel platform that allows for parallel clinical testing of hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art mass spectrometry platform, and the resulting spectra are compared against a library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen at 11 months of age for developmental delay and hypotonia. Multiple tests had not yielded a diagnosis until exome sequencing revealed compound heterozygous variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L) in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa). Metabolomic profiling was performed on plasma and revealed marked elevation in 3-methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency. These results demonstrate that the Global MAPS platform is able to diagnose AADC deficiency from plasma. In summary, we report a novel and less invasive approach to diagnose AADC deficiency using plasma metabolomic profiling.

  14. Anaerobic conditions improve germination of a gibberellic acid deficient rice

    NASA Technical Reports Server (NTRS)

    Frantz, Jonathan M.; Bugbee, Bruce

    2002-01-01

    Dwarf plants are useful in research because multiple plants can be grown in a small area. Rice (Oryza sativa L.) is especially important since its relatively simple genome has recently been sequenced. We are characterizing a gibberellic acid (GA) mutant of rice (japonica cv 'Shiokari,' line N-71) that is extremely dwarf (20 cm tall). Unfortunately, this GA mutation is associated with poor germination (70%) under aerobic conditions. Neither exogenous GA nor a dormancy-breaking heat treatment improved germination. However, 95% germination was achieved by germinating the seeds anaerobically, either in a pure N2 environment or submerged in unstirred tap water. The anaerobic conditions appear to break a mild post-harvest dormancy in this rice cultivar. Copyright 2002 Crop Science Society of America.

  15. Aberrant distribution of junctional complex components in retinoic acid receptor alpha-deficient mice

    PubMed Central

    Chung, Sanny S W; Choi, Cindy; Wang, Xiangyuan; Hallock, Loretta; Wolgemuth, Debra J

    2009-01-01

    Retinoic acid receptor alpha (RARα)-deficient mice are sterile, with abnormalities in the progression of spermatogenesis and spermiogenesis. In the present study, we investigated whether defective retinoid signaling involved at least in part, disrupted cell-cell interactions. Hypertonic fixation approaches revealed defects in the integrity of the Sertoli-cell barrier in the tubules of RARα-deficient testes. Dye transfer experiments further revealed that coupling between cells from the basal to adluminal compartments was aberrant. There were also differences in the expression of several known retinoic acid (RA)-responsive genes encoding structural components of tight junctions and gap junctions. Immunostaining demonstrated a delay in the incorporation of zonula occludens (ZO-1), a peripheral component protein of tight junctions, into the Sertoli cell tight junctions. Markedly reduced expression of connexin-40 in mutant pachytene spermatocytes and round spermatids was found by in situ hybridization. An ectopic distribution of vimentin and disrupted cyclic expression of vimentin, which is usually tightly regulated during spermiogenesis, was found in RARα-deficient testes at all ages examined. Thus, the specific defects in spermiogenesis in RARα-deficient testes may correlate with a disrupted cyclic expression of RA-responsive structural components, including vimentin, a down-regulation of connexin-40 in spermatogenic cells, and delayed assembly of ZO-1 into Sertoli cell tight junctions. Interestingly, bioinformatic analysis revealed that many genes that are components of tight junctions and gap junctions contained potential retinoic acid response element binding sites. PMID:19937743

  16. Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases.

    PubMed

    Ferraz, Maria J; Marques, André R A; Appelman, Monique D; Verhoek, Marri; Strijland, Anneke; Mirzaian, Mina; Scheij, Saskia; Ouairy, Cécile M; Lahav, Daniel; Wisse, Patrick; Overkleeft, Herman S; Boot, Rolf G; Aerts, Johannes M

    2016-03-01

    Glycosphingoid bases are elevated in inherited lysosomal storage disorders with deficient activity of glycosphingolipid catabolizing glycosidases. We investigated the molecular basis of the formation of glucosylsphingosine and globotriaosylsphingosine during deficiency of glucocerebrosidase (Gaucher disease) and α-galactosidase A (Fabry disease). Independent genetic and pharmacological evidence is presented pointing to an active role of acid ceramidase in both processes through deacylation of lysosomal glycosphingolipids. The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed.

  17. Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases.

    PubMed

    Ferraz, Maria J; Marques, André R A; Appelman, Monique D; Verhoek, Marri; Strijland, Anneke; Mirzaian, Mina; Scheij, Saskia; Ouairy, Cécile M; Lahav, Daniel; Wisse, Patrick; Overkleeft, Herman S; Boot, Rolf G; Aerts, Johannes M

    2016-03-01

    Glycosphingoid bases are elevated in inherited lysosomal storage disorders with deficient activity of glycosphingolipid catabolizing glycosidases. We investigated the molecular basis of the formation of glucosylsphingosine and globotriaosylsphingosine during deficiency of glucocerebrosidase (Gaucher disease) and α-galactosidase A (Fabry disease). Independent genetic and pharmacological evidence is presented pointing to an active role of acid ceramidase in both processes through deacylation of lysosomal glycosphingolipids. The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed. PMID:26898341

  18. N-Glycolylneuraminic acid deficiency worsens cardiac and skeletal muscle pathophysiology in α-sarcoglycan-deficient mice

    PubMed Central

    Martin, Paul T; Camboni, Marybeth; Xu, Rui; Golden, Bethannie; Chandrasekharan, Kumaran; Wang, Chiou-Miin; Varki, Ajit; Janssen, Paul M L

    2013-01-01

    Roughly 3 million years ago, an inactivating deletion occurred in CMAH, the human gene encoding CMP-Neu5Ac (cytidine-5′-monophospho-N-acetylneuraminic acid) hydroxylase (Chou HH, Takematsu H, Diaz S, Iber J, Nickerson E, Wright KL, Muchmore EA, Nelson DL, Warren ST, Varki A. 1998. A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc Natl Acad Sci USA. 95:11751–11756). This inactivating deletion is now homozygous in all humans, causing the loss of N-glycolylneuraminic acid (Neu5Gc) biosynthesis in all human cells and tissues. The CMAH enzyme is active in other mammals, including mice, where Neu5Gc is an abundant form of sialic acid on cellular membranes, including those in cardiac and skeletal muscle. We recently demonstrated that the deletion of mouse Cmah worsened the severity of pathophysiology measures related to muscular dystrophy in mdx mice, a model for Duchenne muscular dystrophy (Chandrasekharan K, Yoon JH, Xu Y, deVries S, Camboni M, Janssen PM, Varki A, Martin PT. 2010. A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med. 2:42–54). Here, we demonstrate similar changes in cardiac and skeletal muscle pathology and physiology resulting from Cmah deletion in α-sarcoglycan-deficient (Sgca−/−) mice, a model for limb girdle muscular dystrophy 2D. These experiments demonstrate that loss of mouse Cmah can worsen disease severity in more than one form of muscular dystrophy and suggest that Cmah may be a general genetic modifier of muscle disease. PMID:23514716

  19. A Study of the Prevalence of Serum Vitamin B12 and Folic Acid Deficiency in Western Maharashtra

    PubMed Central

    Mahajan, Sanket K.; Aundhakar, Swati C.

    2015-01-01

    Context: This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice. Aims and Objectives: 1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels. Materials and Methods: The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency. Results: Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency

  20. Contribution of Efa1/LifA to the adherence of enteropathogenic Escherichia coli to epithelial cells.

    PubMed

    Badea, Luminita; Doughty, Stephen; Nicholls, Larissa; Sloan, Joan; Robins-Browne, Roy M; Hartland, Elizabeth L

    2003-05-01

    Enteropathogenic E. coli(EPEC) is an important diarrhoeal pathogen that induces characteristic lesions on the host intestine termed attaching and effacing (A/E) lesions. In this study we have examined the contribution of a large gene, efa1, which is present in all A/E pathogens, to the adherence phenotype of EPEC. An efa- derivative of EPEC JPN15 was constructed and this mutant was significantly less adherent to epithelial cells than the parent strain. The JPN15 efa- derivative was FAS-positive, produced EspA filaments and showed comparable levels of EspA secretion to JPN15. In addition, polyclonal antibodies raised to Efa1 partially inhibited the adherence of JPN15 to cultured epithelial cells. In further work, we showed that human and rabbit hosts infected with an A/E pathogen produced antibodies to Efa1 and we observed that the truncated form of efa1 present in EHEC O157:H7 was specific to that serotype. Generally efa1 was present in its entirety in the genomes of other A/E pathogens. Overall our data suggest that Efa1 has host cell binding activity, at least in tissue culture, and that it is produced during infection. These findings suggest that Efa1 may play a direct role in the pathogenesis of infections caused by A/E pathogens.

  1. Erythrocyte Membrane Fatty Acid Composition in Premenopausal Patients with Iron Deficiency Anemia.

    PubMed

    Aktas, Mehmet; Elmastas, Mahfuz; Ozcicek, Fatih; Yilmaz, Necmettin

    2016-01-01

    Iron deficiency anemia (IDA) is one of the most common nutritional disorders in the world. In the present study, we evaluated erythrocyte membrane fatty acid composition in premenopausal patients with IDA. Blood samples of 102 premenopausal women and 88 healthy control subjects were collected. After the erythrocytes were separated from the blood samples, the membrane lipids were carefully extracted, and the various membrane fatty acids were measured by gas chromatography (GC). Statistical analyses were performed with the SPSS software program. We used blood ferritin concentration <15 ng/mL as cut-off for the diagnosis of IDA. The five most abundant individual fatty acids obtained were palmitic acid (16:0), oleic acid (18:1, n-9c), linoleic acid (18:2, n-6c), stearic acid (18:0), and erucic acid (C22:1, n-9c). These compounds constituted about 87% of the total membrane fatty acids in patients with IDA, and 79% of the total membrane fatty acids in the control group. Compared with control subjects, case patients had higher percentages of palmitic acid (29.9% case versus 25.3% control), oleic acid (16.8% case versus 15.1% control), and stearic acid (13.5% case versus 10.5% control), and lower percentages of erucic acid (11.5% case versus 13.6% control) and linoleic acid (15.2% case versus 15.4% control) in their erythrocyte membranes. In conclusion, the total-erythrocyte-membrane saturated fatty acid (SFA) composition in premenopausal women with IDA was found to be higher than that in the control group; however, the total-erythrocyte-membrane unsaturated fatty acid (UFA) composition in premenopausal women with IDA was found to be lower than that in the control group. The differences in these values were statistically significant.

  2. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  3. Effect of undernutrition and amino acid deficiency on the timing of puberty in rats.

    PubMed

    Glass, A R; Harrison, R; Swerdloff, R S

    1976-11-01

    Sexual maturation was examined in underfed or amino acid-deficient rats. We have demonstrated a highly significant negative linear relationship (r = -0.80, P less than 0.001) between the age at puberty and the growth rate in rats under conditions of food restriction. The weight at puberty in animals growing at different rates because of undernutrition was not constant but behaved as a quadratic function of growth rate, as predicted from the assumption that growth rate was an independent variable. Growth rate is therefore more important than arrival at a particular fixed weight in determining the timing of puberty. Feeding of low valine diets resulted in delayed sexual maturation. Both the weight at vaginal opening (182 +/- 5.9 g) and the weight at first estrus (187 +/- 6.1 g) were significantly greater in the valine-deficient group when compared with growth-matched control (139 +/- 10.7 g and 161 +/- 9.3 g, respectively, P less than 0.05). The valine-deficient group also had significantly later vaginal opening (98.8+/- 4.7 days) than growth-matched controls (76.6 +/- 6.6 days, P less than 0.02). Valine deficiency seemed to have a specific effect on the hypothalamic-pituitary-gonadal axis since puberty in valine-deficient animals was delayed more than could be accounted for by impairment of growth.

  4. Nutrition in brain development and aging: role of essential fatty acids.

    PubMed

    Uauy, Ricardo; Dangour, Alan D

    2006-05-01

    The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

  5. Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency

    PubMed Central

    Peretti, N; Marcil, V; Drouin, E; Levy, E

    2005-01-01

    Transport mechanisms, whereby alimentary lipids are digested and packaged into small emulsion particles that enter intestinal cells to be translocated to the plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose of this paper is to focus on defects that are related to intraluminal and intracellular events in this life-limiting genetic disorder. Specific evidence is presented to highlight the relationship between fat malabsorption and essential fatty acid deficiency commonly found in patients with cystic fibrosis that are often related to the genotype. Given the interdependency of pulmonary disease, pancreatic insufficiency and nutritional status, greater attention should be paid to the optimal correction of fat malabsorption and essential fatty acid deficiency in order to improve the quality of life and extend the life span of patients with cystic fibrosis. PMID:15869703

  6. Essential fatty acid deficiency while a patient receiving fat regimen total parenteral nutrition

    PubMed Central

    Roongpisuthipong, Wanjarus; Phanachet, Pariya; Roongpisuthipong, Chulaporn; Rajatanavin, Natta

    2012-01-01

    A 32-year-old man was diagnosed with lymphoma and underwent Billroth’s II operation because of upper gastrointestinal haemorrhage. Although the patient received fat regimen total parenteral nutrition (TPN), the patient developed typical skin rash of essential fatty acid deficiency after 2 weeks of starting TPN. The diagnosis was confirmed by biochemical and histological analyses. After increasing the lipid infusion, the rash was gradually improved with complete resolution after 19 days. PMID:22707694

  7. Adaptational modification of serine and threonine metabolism in the liver to essential amino acid deficiency in rats.

    PubMed

    Nagao, Kenji; Bannai, Makoto; Seki, Shinobu; Mori, Masato; Takahashi, Michio

    2009-03-01

    It is known that plasma serine and threonine concentrations are elevated in rats chronically fed an essential amino acid deficient diet, but the underlying mechanisms including related gene expressions or serine and threonine concentrations in liver remained to be elucidated. We fed rats lysine or valine deficient diet for 4 weeks and examined the mRNA expressions of serine synthesising (3-phosphoglycerate dehydrogenase, PHGDH) and serine/threonine degrading enzymes (serine dehydratase, SDS) in the liver. Dietary deficiency induced marked elevation of hepatic serine and threonine levels associated with enhancement of PHGDH mRNA expression and repression of SDS mRNA expression. Increases in plasma serine and threonine levels due to essential amino acid deficiency in diet were caused by marked increases in hepatic serine and threonine levels. Proteolytic responses to the amino acid deficiency may be lessened by storing amino radicals as serine and inducing anorexia through elevation of threonine. PMID:18584286

  8. Adolescent behavior and dopamine availability are uniquely sensitive to dietary omega-3 fatty acid deficiency

    PubMed Central

    Bondi, Corina O.; Taha, Ameer Y.; Tock, Jody L.; Totah, Nelson K.; Cheon, Yewon; Torres, Gonzalo E.; Rapoport, Stanley I.; Moghaddam, Bita

    2013-01-01

    Background Understanding the nature of environmental factors that contribute to behavioral health is critical for successful prevention strategies in individuals at-risk for psychiatric disorders. These factors are typically experiential in nature, such as stress and urbanicity, but nutrition, in particular dietary deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs), has increasingly been implicated in the symptomatic onset of schizophrenia and mood disorders, which typically occurs during adolescence to early adulthood. Thus, adolescence may be the critical age range for the negative impact of diet as an environmental insult. Methods A rat model involving consecutive generations of n-3 PUFA deficiency was developed based on the assumption that dietary trends toward decreased consumption of these fats began four-five decades ago when the parents of current adolescents were born. Behavioral performance in a wide range of tasks, as well as markers of dopamine-related neurotransmission was compared in adolescents and adults fed n-3 PUFA adequate and deficient diets. Results In adolescents, dietary n-3 PUFA deficiency across consecutive generations produced a modality-selective and task-dependent impairment in cognitive and motivated behavior distinct from the deficits observed in adults. While this dietary deficiency affected expression of dopamine-related proteins in both age groups, in adolescents, but not adults, there was an increase in tyrosine hydroxylase expression that was selective to the dorsal striatum. Conclusions These data support a nutritional contribution to optimal cognitive and affective functioning in adolescents. Furthermore, they suggest that n-3 PUFA deficiency disrupts adolescent behaviors through enhanced dorsal striatal dopamine availability. PMID:23890734

  9. Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress in rats.

    PubMed

    Ferreira, Charles Francisco; Bernardi, Juliana Rombaldi; Krolow, Rachel; Arcego, Danusa Mar; Fries, Gabriel Rodrigo; de Aguiar, Bianca Wollenhaupt; Senter, Gabrielle; Kapczinski, Flávio Pereira; Silveira, Patrícia Pelufo; Dalmaz, Carla

    2013-06-01

    The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.

  10. Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson's disease.

    PubMed

    dos Santos, Eliseu Felippe; Busanello, Estela Natacha Brandt; Miglioranza, Anelise; Zanatta, Angela; Barchak, Alethea Gatto; Vargas, Carmen Regla; Saute, Jonas; Rosa, Charles; Carrion, Maria Júlia; Camargo, Daiane; Dalbem, André; da Costa, Jaderson Costa; de Sousa Miguel, Sandro René Pinto; de Mello Rieder, Carlos Roberto; Wajner, Moacir

    2009-06-01

    In the present work we measured blood levels of total homocysteine ((t)Hcy), vitamin B(12) and folic acid in patients with Parkinson s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma (t)Hcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of (t)Hcy in PD patients was folic acid deficiency, whereas in controls (t)Hcy levels were mainly determined by plasma vitamin B(12) concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma (t)Hcy, folic acid and vitamin B(12) levels in parkinsonians. Furthermore, disease duration was positively associated with (t)Hcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.

  11. 41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... provided by any eFAS-approved SC. If the agency decides that there are more effective sales solutions than... this part as if it were an SC. (d) An executive agency must comply with all eFAS milestones approved by... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and...

  12. Some Partners Are More Equal than Others: EFA and Civil Society in Papua New Guinea and Vanuatu Education Policy Processes

    ERIC Educational Resources Information Center

    McCormick, Alexandra

    2011-01-01

    This article considers a parallel marginalisation of Education for All (EFA) as a holistic approach to education, and the civil society actors and coalitions who address sidelined Dakar goals of early childhood care and education, adult literacy, quality and non-formal education. I argue that in spite of over two decades of EFA rhetoric prizing…

  13. Long-chain omega-3 fatty acid deficiency in mood disorders: rationale for treatment and prevention.

    PubMed

    McNamara, Robert K

    2013-09-01

    Major recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder (BD) are associated with significant psychosocial morbidity and excess premature mortality primarily attributable to suicide and coronary heart disease. Limited efficacy and adverse side-effects associated with psychotropic medications used in the treatment of MDD and BD highlight the urgent need to develop safe and efficacious treatments or treatment adjuncts. A body of evidence now indicates that long-chain omega-3 (LCn-3) fatty acid deficiency is a feature associated with MDD and BD. The etiology of LCn-3 deficits in MDD and BD patients may be attributable to both genetic and environmental factors. Dietary LCn-3 supplementation is safe and well-tolerated with chronic administration and corrects LCn-3 deficiency in MDD and BD patients. LCn-3 supplementation has been found to augment the therapeutic efficacy of psychotropic medications in the treatment of mood symptoms and to reduce suicidality. Preliminary studies also suggest that LCn-3 supplementation is efficacious as monotherapy in the treatment and prevention of psychopathology in children and adolescents. LCn-3 supplementation is also associated with reduced risk for developing coronary heart disease. The overall cost-benefit ratio associated with LCn-3 supplementation provides a strong rationale to diagnose and treat LCn-3 deficiency in MDD and BD patients, and to prevent LCn-3 deficiency in subjects at high risk for developing these disorders.

  14. Effect of marginal ascorbic acid deficiency on saliva level of cortisol in the guinea pig.

    PubMed

    Enwonwu, C O; Sawiris, P; Chanaud, N

    1995-08-01

    Male guinea pigs subjected to prolonged marginal ascorbic acid deficiency developed moon facies and oedema, features of functional adrenal hypercorticism. Compared with age- and sex-matched controls fed an adequate diet for a similar period, ascorbate deficiency had no effect on submandibular gland weight but elicited a significant (p < 0.005) reduction in stimulated whole-saliva flow rate. Plasma cortisol concentration (nmol/L) was significantly increased (p < 0.005) in the deficient animals (998.21 +/- 57.19 compared to 254.66 +/- 15.62 for the controls). Associated with marked hypercortisolaemia in the deficient animals was a significant (p < 0.01) but less prominent increase in the whole-saliva cortisol level, resulting in a mean saliva/plasma cortisol ratio of 46% for this group compared to 72% for the controls. Increased corticosteroid levels suppress immunological and inflammatory responses, particularly neutrophil function, impair production of some cytokines, inhibit collagen synthesis, and impair wound healing and bone matrix formation. Numerous conditions such as ageing, stress, smoking, ionizing radiation, ingestion of drugs, protein malnutrition, diabetes, and several other pathological states, which are among the risk factors for xerostomia and periodontal/oral mucosal lesions, promote tissue depletion of ascorbate. This study suggests that increased salivary and blood levels of glucocorticoids in these conditions may be important in reducing the ability of the host to mount an effective immune response to oral pathogens. PMID:7487575

  15. Derepression of certain aromatic amino acid biosynthetic enzymes of Escherichia coli K-12 by growth in Fe3+-deficient medium.

    PubMed Central

    McCray, J W; Herrmann, K M

    1976-01-01

    3-Deoxy-arabino-heptulosonic acid 7-phosphate synthase, prephenate dehydratase, tryptophan synthase, and 2,3-dihydroxybenzoylserine synthase enzyme activities are derepressed in wild-type Escherichia coli K-12 cells grown on Fe3+-deficient medium. This derepression is reversed when FeSO4 is added to the growth medium. Addition of shikimic acid to the Fe3+-deficient growth medium caused repression of the first three enzyme activities but not of 2,3-dihydroxybenzoylserine synthase activity. Addition of 2,3-dihydroxybenzoic acid to the Fe3+-deficient growth medium has no effect on any of the above-mentioned enzyme activities. The Fe3+ deficiency-mediated derepression of 3-deoxyarabino-heptulosonic acid 7-phosphate synthase activity is due to an elevation of the tyrosine-sensitive isoenzyme; the phenylalanine-sensitive isoenzyme is not derepressed under these conditions. PMID:1383

  16. An Assessment of Children Literacy Development in Nigeria in the Context of EFA 2015 Policy Targets

    ERIC Educational Resources Information Center

    Ozohu-Suleiman, Yakubu

    2012-01-01

    The paper analyses the interface between Nigeria's anticipated failure in the Education for All (EFA) 2015 targets and her policy implementation strategies in relation to children literacy. The principal purpose is to locate evidences that may explain the expected failure. The paper relies largely on secondary data and existing literature to…

  17. Hard-Pressed to Achieve the EFA Goals by 2015 in the Philippines

    ERIC Educational Resources Information Center

    Caoli-Rodriguez, Rhona B.

    2008-01-01

    The Philippines has experienced a setback in its progress towards EFA 2015 Goals. In particular, a decline in primary and secondary education performance indicators and a widening gap between boys' and girls' performance were noted. While the present policy environment in the country has been conducive to education reforms, a lack of political…

  18. Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

    PubMed

    Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru

    2015-06-01

    In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function.

  19. [Effect of phosphorus deficiency on activity of acid phosphatase exuded by wheat roots].

    PubMed

    Sun, Haiguo; Zhang, Fusuo

    2002-03-01

    The activity of acid phosphatase exuded by roots, the tissue location of the enzyme, and the relationship between the enzyme activity and phosphorus efficiency of wheat were studied. The results showed that the activity of acid phosphatase exuded by wheat 81(85)5-3-3-3 and NC37 under P-sufficiency treat were lower than those under P-deficiency, and the enzyme activity of the former variety was significantly higher than that of the latter. There was a significant difference in the enzyme activity among 12 wheat genotypes grown under P-deficiency treat. Acid phosphatase was exuded by epidermis cell of root, especially by epidermal cell of root apex. Thus, there was a linear relationship between the enzyme activity and the surface area of root or the number of root apexes. It implied that the enzyme activity was markedly related to the size of root system. The linear relationship between relative grain yield and acid phosphatase activity was significant. It indicates that the enzyme activity could be used as an early indicator to select P-efficient wheat genotypes.

  20. Omega-3 fatty acids (image)

    MedlinePlus

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...

  1. Effects of iron deficiency on iron binding and internalization into acidic vacuoles in Dunaliella salina.

    PubMed

    Paz, Yakov; Shimoni, Eyal; Weiss, Meira; Pick, Uri

    2007-07-01

    Uptake of iron in the halotolerant alga Dunaliella salina is mediated by a transferrin-like protein (TTf), which binds and internalizes Fe(3+) ions. Recently, we found that iron deficiency induces a large enhancement of iron binding, which is associated with accumulation of three other plasma membrane proteins that associate with TTf. In this study, we characterized the kinetic properties of iron binding and internalization and identified the site of iron internalization. Iron deficiency induces a 4-fold increase in Fe binding, but only 50% enhancement in the rate of iron uptake and also increases the affinity for iron and bicarbonate, a coligand for iron binding. These results indicate that iron deprivation leads to accumulation and modification of iron-binding sites. Iron uptake in iron-sufficient cells is preceded by an apparent time lag, resulting from prebound iron, which can be eliminated by unloading iron-binding sites. Iron is tightly bound to surface-exposed sites and hardly exchanges with medium iron. All bound iron is subsequently internalized. Accumulation of iron inhibits further iron binding and internalization. The vacuolar inhibitor bafilomycin inhibits iron uptake and internalization. Internalized iron was localized by electron microscopy within vacuolar structures that were identified as acidic vacuoles. Iron internalization is accompanied by endocytosis of surface proteins into these acidic vacuoles. A novel kinetic mechanism for iron uptake is proposed, which includes two pools of bound/compartmentalized iron separated by a rate-limiting internalization stage. The major parameter that is modulated by iron deficiency is the iron-binding capacity. We propose that excessive iron binding in iron-deficient cells serves as a temporary reservoir for iron that is subsequently internalized. This mechanism is particularly suitable for organisms that are exposed to large fluctuations in iron availability. PMID:17513481

  2. A mutant of Arabidopsis deficient in desaturation of palmitic acid in leaf lipids

    SciTech Connect

    Kunst, L.; Somerville, C. ); Browse, J. )

    1989-07-01

    The overall fatty acid composition of leaf lipids in a mutant of Arabidopsis thaliana was characterized by elevated amounts of palmitic acid and a decreased amount of unsaturated 16-carbon fatty acids as a consequence of a single nuclear mutation. Quantitative analysis of the fatty acid composition of individual lipids suggested that the mutant is deficient in the activity of a chloroplast {omega}9 fatty acid desaturase which normally introduces a double bond in 16-carbon acyl chains esterified to monogalactosyldiacylglycerol (MGD). The mutant exhibited an increased ratio of 18- to 16-carbon fatty acids in MGD due to a change in the relative contribution of the prokaryotic and eukaryotic pathways of lipid biosynthesis. This appears to be a regulated response to the loss of chloroplast {omega}9 desaturase and presumably reflects a requirement for polyunsaturated fatty acids for the normal assembly of chloroplast membranes. The reduction in mass of prokaryotic MGD species involved both a reduction in synthesis of MGD by the prokaryotic pathway and increased turnover of MGD molecular species which contain 16:0.

  3. Elevated Fundus Autofluorescence in Monkeys Deficient in Lutein, Zeaxanthin, and Omega-3 Fatty Acids

    PubMed Central

    McGill, Trevor J.; Renner, Lauren M.; Neuringer, Martha

    2016-01-01

    Purpose We quantified fundus autofluorescence (FAF) in the nonhuman primate retina as a function of age and diets lacking lutein and zeaxanthin (L/Z) and omega-3 fatty acids. Methods Quantitative FAF was measured in a cross-sectional study of rhesus macaques fed a standard diet across the lifespan, and in aged rhesus macaques fed lifelong diets lacking L/Z and providing either adequate or deficient levels of omega-3 fatty acids. Macular FAF images were segmented into multiple regions of interest, and mean gray values for each region were calculated using ImageJ. The resulting FAF values were compared across ages within the standard diet animals, and among diet groups and regions. Results Fundus autofluorescence increased with age in the standard diet animals, and was highest in the perifovea. Monkeys fed L/Z-free diets with either adequate or deficient omega-3 fatty acids had significantly higher FAF overall than age-matched standard diet monkeys. Examined by region, those with adequate omega-3 fatty acids had higher FAF in the fovea and superior regions, while monkeys fed the diet lacking L/Z and omega-3 fatty acids had higher FAF in all regions. Conclusions Diets devoid of L/Z resulted in increased retinal autofluorescence, with the highest values in animals also lacking omega-3 fatty acids. The increase was equivalent to a 12- to 20-year acceleration in lipofuscin accumulation compared to animals fed a standard diet. Together these data add support for the role of these nutrients as important factors in lipofuscin accumulation, retinal aging, and progression of macular disease. PMID:27002296

  4. Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: Rationale and implementation.

    PubMed

    Messamore, Erik; McNamara, Robert K

    2016-02-10

    A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case-control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA + DHA biostatus can be treated with fish oil-based formulations containing preformed EPA + DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA + DHA levels at ≤ 4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice.

  5. Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: Rationale and implementation.

    PubMed

    Messamore, Erik; McNamara, Robert K

    2016-01-01

    A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case-control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA + DHA biostatus can be treated with fish oil-based formulations containing preformed EPA + DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA + DHA levels at ≤ 4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice. PMID:26860589

  6. Effect of folic acid deficiency on pregnant rats and their offspring.

    PubMed

    Tagbo, I F; Hill, D C

    1977-06-01

    Two groups of 63-day-old female Wistar rats were fed a folic acid deficient diet, based on 20% of vitamin-free casein and containing 1% of succinylsulfathiazole, for 5 weeks (group A) and 9 weeks (group B) before being bred, and the same diet was continued through pregnancy and lactation. Three out of eleven (21.3%) and three out of seven (42.9%) rats in groups A and B, respectively, resorbed completely, while no control rat resorbed. No pups from group B survived to weaning. Both groups (A and B) showed depressed feed consumption (although the effect in group A rats was small) and weight gains and increased formiminoglutamic acid excretion in the urine during gestation, and low serum folic acid by the end of lactation. A study of blood components in group A rats revealed leucopenia, granulocytopenia, and increased reticulocyte count. While no congenital deformities were observed in pups from deficient dams, group A and group B dams in contrast to controls produced smaller sized litters with lower birth weights and poor survival rate. Surviving pups from group A dams had decreased weaning weights with significantly lower brain weights and brain DNA per gram of tissue. PMID:884600

  7. Optimization of a histopathological biomarker for sphingomyelin accumulation in acid sphingomyelinase deficiency.

    PubMed

    Taksir, Tatyana V; Johnson, Jennifer; Maloney, Colleen L; Yandl, Emily; Griffiths, Denise; Thurberg, Beth L; Ryan, Susan

    2012-08-01

    Niemann-Pick disease (types A and B), or acid sphingomyelinase deficiency, is an inherited deficiency of acid sphingomyelinase, resulting in intralysosomal accumulation of sphingomyelin in cells throughout the body, particularly within those of the reticuloendothelial system. These cellular changes result in hepatosplenomegaly and pulmonary infiltrates in humans. A knockout mouse model mimics many elements of human ASMD and is useful for studying disease histopathology. However, traditional formalin-fixation and paraffin embedding of ASMD tissues dissolves sphingomyelin, resulting in tissues with a foamy cell appearance, making quantitative analysis of the substrate difficult. To optimize substrate fixation and staining, a modified osmium tetroxide and potassium dichromate postfixation method was developed to preserve sphingomyelin in epon-araldite embedded tissue and pulmonary cytology specimens. After processing, semi-thin sections were incubated with tannic acid solution followed by staining with toluidine blue/borax. This modified method provides excellent preservation and staining contrast of sphingomyelin with other cell structures. The resulting high-resolution light microscopy sections permit digital quantification of sphingomyelin in light microscopic fields. A lysenin affinity stain for sphingomyelin was also developed for use on these semi-thin epon sections. Finally, ultrathin serial sections can be cut from these same tissue blocks and stained for ultrastructural examination by electron microscopy. PMID:22614361

  8. Optimization of a histopathological biomarker for sphingomyelin accumulation in acid sphingomyelinase deficiency.

    PubMed

    Taksir, Tatyana V; Johnson, Jennifer; Maloney, Colleen L; Yandl, Emily; Griffiths, Denise; Thurberg, Beth L; Ryan, Susan

    2012-08-01

    Niemann-Pick disease (types A and B), or acid sphingomyelinase deficiency, is an inherited deficiency of acid sphingomyelinase, resulting in intralysosomal accumulation of sphingomyelin in cells throughout the body, particularly within those of the reticuloendothelial system. These cellular changes result in hepatosplenomegaly and pulmonary infiltrates in humans. A knockout mouse model mimics many elements of human ASMD and is useful for studying disease histopathology. However, traditional formalin-fixation and paraffin embedding of ASMD tissues dissolves sphingomyelin, resulting in tissues with a foamy cell appearance, making quantitative analysis of the substrate difficult. To optimize substrate fixation and staining, a modified osmium tetroxide and potassium dichromate postfixation method was developed to preserve sphingomyelin in epon-araldite embedded tissue and pulmonary cytology specimens. After processing, semi-thin sections were incubated with tannic acid solution followed by staining with toluidine blue/borax. This modified method provides excellent preservation and staining contrast of sphingomyelin with other cell structures. The resulting high-resolution light microscopy sections permit digital quantification of sphingomyelin in light microscopic fields. A lysenin affinity stain for sphingomyelin was also developed for use on these semi-thin epon sections. Finally, ultrathin serial sections can be cut from these same tissue blocks and stained for ultrastructural examination by electron microscopy.

  9. Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice.

    PubMed

    Terakata, Miki; Fukuwatari, Tsutomu; Sano, Mitsue; Nakao, Natsuki; Sasaki, Ryuzo; Fukuoka, Shin-Ichi; Shibata, Katsumi

    2012-12-01

    Pyridine nucleotide coenzymes are involved in >500 enzyme reactions and are biosynthesized from the amino acid L-tryptophan (L-Trp) as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid (QA) phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-), or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and qprt(+/-) mice. On the contrary, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (P < 0.01) and 70% (P < 0.05) of the corresponding values for the qprt(-/-) mice fed the complete diet at d 23, respectively. The nutritional levels of niacin, such as blood and liver NAD concentrations, were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of QA was greater in the qprt(-/-) mice than in the qprt(+/+) and qprt(+/-) mice (P < 0.01). These data suggest that we generated truly niacin-deficient mice.

  10. Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer

    PubMed Central

    Vashi, Pankaj; Edwin, Persis; Popiel, Brenten; Lammersfeld, Carolyn; Gupta, Digant

    2016-01-01

    Background/Aims Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer. Methods This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard". Results Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in

  11. Protective effect of myristic acid on renal necrosis occurring in rats fed a methyl-deficient diet.

    PubMed

    Monserrat, A J; Cutrin, J C; Coll, C

    2000-02-01

    Weanling rats fed a methyl-deficient diet develop acute renal failure, the morphological features of which vary from focal tubular necrosis to widespread cortical necrosis. We and others have shown that coconut oil, rich in saturated fatty acids, has a renal protective effect in this experimental model. In the experiment we are reporting now, we studied which fatty acid is involved in the protection afforded by coconut oil by feeding five groups of methyl-deficient rats a mixture of corn oil and hydrogenated vegetable oil, C6-C8-C10 fatty acids, C12 fatty acid, C14 fatty acid and C16-C18 fatty acids. Five groups of rats receiving the same diets supplemented with choline chloride were used as controls. The group of methyl-deficient rats fed C14 fatty acid (myristic acid) showed a greater percentage of surviving animals and lower renal damage than the other groups of methyl-deficient rats, indicating that the protective effect of coconut oil found in previous experiments is due to its high content of myristic acid.

  12. [Metabolism of pantothenic acid and its derivatives in animals deficient in this enzyme].

    PubMed

    Gurinovich, V A; Moiseenok, A G

    1987-01-01

    Distribution of [14C]labelled metabolites of pantothenic acid (PAA) has been studied in tissues of normal and PAA-deficient rats-weaners 6 h after single injection of the calcium pantothenate (PAA-Ca), calcium 4'-phosphopantothenate (PAA-Ca) or pantethine (PT) preparations. Essential differences in the intertissue distribution of vitamin derivatives to be injected are revealed against a background of a higher vitamin-retaining ability of the PAA-deficient tissues. A degree of radionuclides' biotransformation into CoA permits them to be arranged in the series: PPA-Ca greater than PAA-Ca greater than PT. In PAA-deficient animals which were injected labelled PPA-Ca up to 41% of the liver radioactivity is concentrated in the CoA fraction and the quantity of label in the composition of PAA-protein cytosolium complexes increases considerably. It is supposed that there is a special PAA-depositing system which provides the intracellular CoA biosynthesis. PMID:3686695

  13. Influence of a dietary n-3 fatty acid deficiency on the cerebral catecholamine contents, EEG and learning ability in rat.

    PubMed

    Takeuchi, Takashi; Fukumoto, Yutaka; Harada, Etsumori

    2002-04-01

    Female rats were fed on a diet deficient in (n-3) fatty acid or enriched in docosahexaenoic acid (DHA) diet from mating and throughout pregnancy and lactation. Pups fed on the same diet as their dams were used for experiments. The effects of dietary (n-3) fatty acid deficiency on cerebral catecholamine contents and electroencephalogram (EEG) in rat pups during the postnatal development were investigated. The (n-3) deficient rat pups showed significantly lower levels of noradrenaline (NA) in cerebral cortex, hippocampus and striatum, compared with those in the DHA adequate rats. Dopamine (DA) contents were significantly lower in the (n-3) deficient rats until the 7th day of age. These results were consistent with observations in the EEG analysis, relative powers of fast activities in the EEG recorded from the (n-3) deficient rats were significantly lower than those in the DHA adequate rats. The effect of supplementation with DHA in (n-3) deficient rats on learning ability was also studied in a model of learning, active avoidance test and three-panel run way test, after weaning. Although the percentages of avoidance in the (n-3) deficient rats (saline group) were constantly 20% or less until the 3rd session, the percentage of avoidance in the DHA supplemented rats rapidly increased to 53% following the first administration. While in the three-panel runway test, there were no significant differences between two groups. These results suggest that chronic consumption of a (n-3) fatty acid deficient diet could modify the biosynthesis of catecholamine in the brain, and might induce the behavioral disturbances. Furthermore, the decreased learning ability induced by (n-3) deficiency in the active avoidance test is a reversible following a supplementing DHA after the weaning.

  14. Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry.

    PubMed Central

    Stabler, S P; Marcell, P D; Podell, E R; Allen, R H; Lindenbaum, J

    1986-01-01

    To determine the incidence of elevated levels of serum methylmalonic acid in patients with cobalamin deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure methylmalonic acid in the serum of 73 patients with clinically confirmed cobalamin deficiency. Values ranged from 55 to 22,300 ng/ml, and 69 of the 73 patients had values above the normal range of 19-76 ng/ml as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum methylmalonic acid was significantly correlated with the serum folate level and the degree of neurologic involvement. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of methylmalonic acid while free of hematologic and neurologic abnormalities. A cobalamin-deficient patient is described with a normal serum cobalamin and an elevated serum methylmalonic acid. We conclude that the ability to measure methylmalonic acid in human serum will be useful in studies designed to determine the incidence of cobalamin deficiency in various patient populations. PMID:3700655

  15. SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES

    PubMed Central

    SILVA, Rafaella de Andrade; MALTA, Flávia Monteiro França; CORREIA, Maria Flora Ferreira Sampaio Carvalho; BURGOS, Maria Goretti Pessoa de Araújo

    2016-01-01

    ABSTRACT Background: Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Aim: Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. Methods: A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the São João Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (p<0.05). Results: Among 286 individuals evaluated, females accounted for 90.9% of the overall sample (both techniques). Gastric banding was performed more (68.9%), but greater nutrient deficiencies were found following gastric bypass. Iron was the most prevalent deficiency (21.3%), followed by vitamin B12 (16.9%) and folic acid (4.5%). Mild to moderate alcohol intake, adherence to the diet and the use of multivitamins reduced the frequency, but did not avoid micronutrient deficiency. Conclusion: Vitamin B12, iron and folic acid deficiencies were found in the first and second year following the two bariatric techniques analyzed and were more frequent among individuals submitted to gastric bypass. PMID:27683779

  16. Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency

    NASA Technical Reports Server (NTRS)

    Tawa, N. E. Jr; Goldberg, A. L.

    1992-01-01

    To define the adaptations that conserve amino acids and muscle protein when dietary protein intake is inadequate, rats (60-70 g final wt) were fed a normal or protein-deficient (PD) diet (18 or 1% lactalbumin), and their muscles were studied in vitro. After 7 days on the PD diet, both protein degradation and synthesis fell 30-40% in skeletal muscles and atria. This fall in proteolysis did not result from reduced amino acid supply to the muscle and preceded any clear decrease in plasma amino acids. Oxidation of branched-chain amino acids, glutamine and alanine synthesis, and uptake of alpha-aminoisobutyrate also fell by 30-50% in muscles and adipose tissue of PD rats. After 1 day on the PD diet, muscle protein synthesis and amino acid uptake decreased by 25-40%, and after 3 days proteolysis and leucine oxidation fell 30-45%. Upon refeeding with the normal diet, protein synthesis also rose more rapidly (+30% by 1 day) than proteolysis, which increased significantly after 3 days (+60%). These different time courses suggest distinct endocrine signals for these responses. The high rate of protein synthesis and low rate of proteolysis during the first 3 days of refeeding a normal diet to PD rats contributes to the rapid weight gain ("catch-up growth") of such animals.

  17. Adaptive transport of folic acid across renal epithelia in folate-deficient rats.

    PubMed

    Wani, Nissar Ahmad; Kaur, Jyotdeep

    2012-11-01

    Folate (vitamin B(9)) is an essential vitamin for a wide spectrum of biochemical reactions; however, unlike bacteria and plants, mammals are devoid of folate biosynthesis and thus must obtain this cofactor from exogenous sources. The activities of folate transporters on the kidneys play an important role in conserving folate excretion and reabsorption across the apical membrane of the renal proximal tubules. The different transport system activities may become identifiable in response to external stimuli, such as folate availability and exposure to chemotherapeutic agents. We have explored the effect of folate deficiency on the activity and expression of folate transporters in rat kidneys. Wistar rats were fed a folate-containing diet (2 mg folic acid kg(-1) diet) or a folic acid-free diet over a 3-month period, and mechanisms of folate transport were studied in renal brush border membrane vesicles and basolateral membrane vesicles. The renal folate uptake process is saturable and pH dependent, and it involves the folate receptor and reduced folate carrier (RFC) systems and possibly the proton coupled folate transporter (PCFT) system. We found that folate deficiency increased the renal brush border membrane and basolateral folate uptake by increasing the number of transporter molecules. The observed up-regulation of mRNA expression was also associated with a significant increase in RFC and PCFT expression at the protein level.

  18. Influence of dietary n-3 polyunsaturated fatty acids on plasma lipemic effect of vitamin B6 deficiency.

    PubMed

    Bergami, R; Maranesi, M; Marchetti, M; Sangiorgi, Z; Tolomelli, B

    1999-09-01

    Since many connections exist between vitamin B6 and lipid metabolism, we aim to investigate the lipemic effect of different dietary intakes of polyunsaturated fatty acids in rats fed a vitamin B6 deficient diet. Diets were either vitamin B6 deficient (-B6) or vitamin B6 sufficient, pair-fed to the deficient group (PF) and ad libitum (N). The diets were combined with normal lipid (LC: soya bean-coconut-palm oils) and fish oil (FO: soya bean-fish oil). The fish oil diet with sufficient vitamin B6 content caused an increase in n-3 long chain polyunsaturated fatty acids and a decrease in arachidonic acid. In the -B6 group fed a normal lipid diet, the arachidonic acid percentage decreased and the linoleic acid percentage increased; in the -B6 group fed fish oil these changes in fatty acid composition, already consequent upon dietary intake of n-3 long chain polyunsaturated fatty acids, did not show further variations. In the dietary condition of vitamin B6 deficiency, plasma cholesterol content increased in rats fed a lipid control diet, whereas no hypocholesterolemic effect was observed in those fed a fish oil diet. Plasma triglyceride contents were not influenced by dietary lipid quality because, in all conditions, the lower food intake of the PF groups caused a decrease and vitamin B6 deficiency caused an elevation in triglyceride contents which reached those of the ad libitum groups. The study highlights the interaction between vitamin B6 and polyunsaturated fatty acids and the opportunity of dietary intake of fish oil to counterbalance some effects of vitamin B6 deficiency.

  19. Isotope-dilution assay for urinary methylmalonic acid in the diagnosis of vitamin B12 deficiency. A prospective clinical evaluation

    SciTech Connect

    Matchar, D.B.; Feussner, J.R.; Millington, D.S.; Wilkinson, R.H. Jr.; Watson, D.J.; Gale, D.

    1987-05-01

    Vitamin B12 deficiency is a frequently considered diagnosis for which there is no single, commonly available and accurate test. A urinary methylmalonic acid assay using gas chromatography-mass spectrometry has been proposed as the preferred test. We reviewed vitamin B12 assays on 1599 consecutive patients and prospectively studied all patients with low serum B12 levels (n = 75) and a random sample of patients with normal levels (n = 68). Of 96 evaluable patients, 7 had clinical deficiency. All 7 deficient patients had urinary methylmalonic acid levels greater than 5 micrograms/mg creatine (sensitivity, 100%; confidence interval, 65% to 100%). Of the 89 patients who were not clinically deficient, 88 had urinary methylmalonic acid levels less than or equal to 5 micrograms/mg creatinine (specificity, 99%). The overall test accuracy in this population was 99%. If the high sensitivity and specificity of the gas chromatography-mass spectrometry assay for urinary methylmalonic acid is supported by other clinical studies, the methylmalonic acid assay may become the reference standard for the diagnosis of vitamin B12 deficiency.

  20. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

    PubMed

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.

  1. Bile acids override steatosis in farnesoid X receptor deficient mice in a model of non-alcoholic steatohepatitis

    SciTech Connect

    Wu, Weibin; Liu, Xijun; Peng, Xiaomin; Xue, Ruyi; Ji, Lingling; Shen, Xizhong; Chen, She; Gu, Jianxin; Zhang, Si

    2014-05-23

    Highlights: • FXR deficiency enhanced MCD diet-induced hepatic fibrosis. • FXR deficiency attenuated MCD diet-induced hepatic steatosis. • FXR deficiency repressed genes involved in fatty acid uptake and triglyceride accumulation. - Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and the pathogenesis is still not well known. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in maintaining bile acid and lipid homeostasis. In this study, we study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient (FXR{sup −/−}) mice fed methionine- and choline-deficient (MCD) diet had higher serum ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT) mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and fibrosis (α-SMA) was increased in FXR{sup −/−} mice fed MCD diet (FXR{sup −/−}/MCD) compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly induced hepatic fibrosis in terms of liver histology, FXR{sup −/−}/MCD mice showed less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency synergistically potentiated the elevation effects of MCD diet on serum and hepatic bile acids levels. The super-physiological concentrations of hepatic bile acids in FXR{sup −/−}/MCD mice inhibited the expression of genes involved in fatty acid uptake and triglyceride accumulation, which may be an explanation for less steatosis in FXR{sup −/−}/MCD mice in contrast to WT/MCD mice. These results suggest that hepatic bile acids accumulation could override simple steatosis in hepatic injury during the progression of NAFLD and further emphasize the role of FXR in maintaining hepatic bile acid homeostasis in liver disorders and in hepatic protection.

  2. Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation.

    PubMed

    Song, No-Joon; Yun, Ui Jeong; Yang, Sunghee; Wu, Chunyan; Seo, Cho-Rong; Gwon, A-Ryeong; Baik, Sang-Ha; Choi, Yuri; Choi, Bo Youn; Bahn, Gahee; Kim, Suji; Kwon, So-Mi; Park, Jin Su; Baek, Seung Hyun; Park, Tae Joo; Yoon, Keejung; Kim, Byung-Joon; Mattson, Mark P; Lee, Sung-Joon; Jo, Dong-Gyu; Park, Kye Won

    2016-01-01

    Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis. PMID:26786165

  3. Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

    PubMed Central

    Song, No-Joon; Yun, Ui Jeong; Yang, Sunghee; Wu, Chunyan; Seo, Cho-Rong; Gwon, A-Ryeong; Baik, Sang-Ha; Choi, Yuri; Choi, Bo Youn; Bahn, Gahee; Kim, Suji; Kwon, So-Mi; Park, Jin Su; Baek, Seung Hyun; Park, Tae Joo; Yoon, Keejung; Kim, Byung-Joon; Mattson, Mark P.; Lee, Sung-Joon; Jo, Dong-Gyu; Park, Kye Won

    2016-01-01

    Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis. PMID:26786165

  4. Lysosomal acid lipase deficiency in rats: Lipid analyses and lipase activities in liver and spleen

    SciTech Connect

    Kuriyama, M.; Yoshida, H.; Suzuki, M.; Fujiyama, J.; Igata, A. )

    1990-09-01

    We report the biological characterization of an animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected rats accumulated cholesteryl esters (13.3-fold), free cholesterol (2.8-fold), and triglycerides (5.4-fold) in the liver, as well as cholesteryl esters (2.5-fold) and free cholesterol (1.33-fold) in the spleen. Triglycerides did not accumulate, and the levels actually decreased in the spleen. Analysis of the fatty acid composition of the cholesteryl esters and triglycerides showed high percentages of linoleic acid (18:2) and arachidonic acid (20:4) in both organs, especially in the liver. No accumulation of phospholipids, neutral glycosphingolipids, or gangliosides was found in the affected rats. Acid lipase activity for (14C)triolein, (14C)cholesteryl oleate, and 4-methyl-umbelliferyl oleate was deficient in both the liver and spleen of affected rats. Lipase activity at neutral pH was normal in both liver and spleen. Heterozygous rats showed intermediate utilization of these substrates in both organs at levels between those for affected rats and those for normal controls, although they did not accumulate any lipids. These data suggest that these rats represent an animal counterpart of Wolman's disease in humans.

  5. Triglyceride accumulation and altered composition of triglyceride-associated fatty acids in the skin of tenascin-X-deficient mice.

    PubMed

    Matsumoto, Ken-ichi; Sato, Takashige; Oka, Seiko; Orba, Yasuko; Sawa, Hirofumi; Kabayama, Kazuya; Inokuchi, Jin-ichi; Ariga, Hiroyoshi

    2004-08-01

    Tenascin-X (TNX) is a member of the tenascin family of glycoproteins of the extracellular matrix. Here, we observed abnormalities in the skin of TNX-deficient mice in comparison with that of wild-type mice. Histological analysis with Oil Red O staining demonstrated that there was considerable accumulation of lipid in the skin of TNX-deficient (TNX-/-) mice. By thin-layer chromatography of total lipids, it was found that the level of triglyceride was significantly increased in TNX-/- mice. The mRNA levels of most of the lipogenic enzyme genes examined were remarkably increased in TNX-/- mice. By gas chromatography-mass spectrometry analysis of triglyceride-associated fatty acids in the skin, saturated fatty acid palmitoic acid was decreased, whereas unsaturated fatty acids palmitoleic acid and oleic acid were increased in TNX-/- mice compared with those in wild-type mice. Conversely, fibroblast cell lines transfected with TNX showed a significant decrease in the amount of triglyceride. An increase in the saturated fatty acid stearic acid and decreases in the unsaturated fatty acids palmitoleic acid, oleic acid and linoleic acid, compared to those in mock-transfected cells were also caused by over-expression of TNX. These results indicate that TNX is involved in the regulation of triglyceride synthesis and the regulation of composition of triglyceride-associated fatty acids.

  6. An Alternative Retinoic Acid-responsive Stra6 Promoter Regulated in Response to Retinol Deficiency*

    PubMed Central

    Laursen, Kristian B.; Kashyap, Vasundhra; Scandura, Joseph; Gudas, Lorraine J.

    2015-01-01

    Cellular uptake of vitamin A (retinol) is essential for many biological functions. The Stra6 protein binds the serum retinol-binding protein, RBP4, and acts in conjunction with the enzyme lecithin:retinol acyltransferase to facilitate retinol uptake in some cell types. We show that in embryonic stem (ES) cells and in some tissues, the Stra6 gene encodes two distinct mRNAs transcribed from two different promoters. Whereas both are all-trans-retinoic acid (RA)-responsive in ES cells, the downstream promoter contains a half-site RA response element (RARE) and drives an ∼13-fold, RA-associated increase in luciferase reporter activity. We employed CRISPR-Cas9 genome editing to show that the endogenous RARE is required for RA-induced transcription of both Stra6 isoforms. We further demonstrate that in ES cells, 1) both RARγ and RXRα are present at the Stra6 RARE; 2) RA increases co-activator p300 (KAT3B) binding and histone H3 Lys-27 acetylation at both promoters; 3) RA decreases Suz12 levels and histone H3 Lys-27 trimethylation epigenetic marks at both promoters; and 4) these epigenetic changes are diminished in the absence of RARγ. In the brains of WT mice, both the longer and the shorter Stra6 transcript (Stra6L and Stra6S, respectively) are highly expressed, whereas these transcripts are found only at low levels in RARγ−/− mice. In the brains of vitamin A-deficient mice, both Stra6L and Stra6S levels are decreased. In contrast, in the vitamin A-deficient kidneys, the Stra6L levels are greatly increased, whereas Stra6S levels are decreased. Our data show that kidneys respond to retinol deficiency by differential Stra6 promoter usage, which may play a role in the retention of retinol when vitamin A is low. PMID:25544292

  7. Morphological influence of ascorbic acid deficiency on endochondral ossification in osteogenic disorder Shionogi rat.

    PubMed

    Sakamoto, Yujiro; Takano, Yoshiro

    2002-10-01

    The influences of chronic deficiency of L-ascorbic acid (AsA) on the differentiation of osteo-chondrogenic cells and the process of endochondral ossification were examined in the mandibular condyle and the tibial epiphysis and metaphysis by using Osteogenic Disorder Shionogi (ODS) rats that bear an inborn deficiency of L-gulonolactone oxidase. Weanling male rats were kept on an AsA-free diet for up to 4 weeks, until the symptoms of scurvy became evident. The tibiae and condylar processes of scorbutic rats displayed undersized and distorted profiles with thin cortical and scanty cancellous bones. In these scorbutic bones, the osteoblasts showed characteristic expanded round profiles of rough endoplasmic reticulum, and lay on the bone surface where the osteoid layer was missing. Trabeculae formation was deadlocked, although calcification of the cartilage matrix proceeded in both types of bone. Scorbutic condylar cartilage showed severe disorganization of cell zones, such as unusual thickening of the calcification zone, whereas the tibial cartilage showed no particular alterations (except for a moderately decreased population of chondrocytes). In condylar cartilage, hypertrophic chondrocytes were encased in a thickened calcification zone, and groups of nonhypertrophic chondrocytes occasionally formed cell nests surrounded by a metachromatic matrix in the hypertrophic cell zone. These results indicate that during endochondral ossification, chronic AsA deficiency depresses osteoblast function and disturbs the differentiation pathway of chondrocytes. The influence of scurvy on mandibular condyle cartilage is different from that on articular and epiphyseal cartilage of the tibia, suggesting that AsA plays different roles in endochondral ossification in the mandibular condyle and long bones.

  8. Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa

    PubMed Central

    Su, Kim; Donaldson, Emma; Sharma, Reena

    2016-01-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with lipid-modifying agents does not ameliorate disease progression. Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications. Sebelipase alfa (Kanuma) is a recombinant human LAL protein and the first enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter. Sebelipase alfa has received marketing authorization in the United States and Europe as long-term therapy for all affected individuals. The availability of enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians. PMID:27799810

  9. Lysosomal acid lipase deficiency: diagnosis and treatment of Wolman and Cholesteryl Ester Storage Diseases.

    PubMed

    Porto, Anthony F

    2014-09-01

    Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesterol esters and triglycerides. LAL is coded by the LIPA gene on chromosome 10q23.31. Its deficiency leads to two autosomal recessive disorders, Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD). WD has an estimated incidence of 1 in 500,000 live births and is the result of a complete loss of LAL and presents in infancy with vomiting, diarrhea, poor weight gain and hepatomegaly subsequently leading to death. CESD is the result of partial loss of LAL and its presentation is more variable. Patients may be asymptomatic or present with nonspecific gastrointestinal symptoms, hepatomegaly, elevated transaminases and dystipidemia which may be confused with the diagnosis of Non-alcoholic Fatty Liver Disease. CESD is currently underdiagnosed and has an estimated prevalence as high as I in 40,000 individuals. Radiologic findings in WD is calcification of the adrenal glands. Hepatomegaly is noted on CT scan in both WD and CESD. MRI may demonstrate accumulation of cholesterol esters and may be useful to study effects of potential medical therapies. The diagnosis of WD and CESD is based on LIPA gene sequencing and the measurement of LAL levels in peripheral blood leukocytes. Treatment of LAL deficiency is currently limited to control of cholesterol levels and to prevent premature atherosclerosis. Use of enzyme replacement therapy with recombinant human LAL in short-term studies has shown to be safe and effective. PMID:25345094

  10. Physiological management of dietary deficiency in n-3 fatty acids by spawning Gulf killifish (Fundulus grandis).

    PubMed

    Patterson, Joshua T; Green, Christopher C

    2015-08-01

    Lipid dynamics of spawning fish are critical to the production of viable embryos and larvae. The present study utilized manipulation of dietary fatty acid (FA) profiles to examine the ability of spawning Gulf killifish (Fundulus grandis) to mobilize critical lipid components from somatic reserves or synthesize long-chain polyunsaturated FAs (LC-PUFAs) de novo from shorter-chain C18 precursors. An egg and multi-tissue evaluation of changes in FA concentrations across time after fish were switched from LC-PUFA-rich to LC-PUFA-deficient experimental diets was employed. The two experimental diets contained lipid sources which differed drastically in n-3 C18 FA content but had similar levels of n-6 C18 FAs. Discrete effects of dietary n-3 FAs can be analyzed because n-3 and n-6 represent distinct metabolic families which cannot be exchanged in vivo. Results indicate that a combination of mobilization and de novo synthesis is likely utilized to maintain physiologically required FA levels in critical tissues and embryos. Mobilization was supported by decreases in LC-PUFAs in somatic tissues and decreases in intraperitoneal fat content and liver mass. Evidence for biosynthesis was provided by a higher level of n-3 LC-PUFAs in the liver and ova of fish fed diets containing n-3 C18 precursors versus those fed diets with low levels of precursor FAs. The characteristic physiological plasticity of Gulf killifish is exemplified in the nutritional domain by its management of dietary FA deficiency. PMID:25939715

  11. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction.

    PubMed

    Reiner, Željko; Guardamagna, Ornella; Nair, Devaki; Soran, Handrean; Hovingh, Kees; Bertolini, Stefano; Jones, Simon; Ćorić, Marijana; Calandra, Sebastiano; Hamilton, John; Eagleton, Terence; Ros, Emilio

    2014-07-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme. PMID:24792990

  12. Enhanced thermal tolerance in a mutant of Arabidopsis deficient in palmitic acid unsaturation

    SciTech Connect

    Kunst, L.; Somerville, C. ); Browse, J. )

    1989-09-01

    A mutant of Arabidopsis thaliana, deficient in the activity of a chloroplast {omega}9 fatty acid desaturase, accumulates high amounts of palmitic acid (16:0), and exhibits an overall reduction in the level of unsaturation of chloroplast lipids. Under standard conditions the altered membrane lipid composition had only minor effects on growth rate of the mutant, net photosynthetic CO{sub 2} fixation, photosynthetic electron transport, or chloroplast ultrastructure. Similarly, fluorescence polarization measurements indicated that the fluidity of the membranes was not significantly different in the mutant and the wild type. However, at temperatures above 28{degree}C, the mutant grew more rapidly than the wild type suggesting that the altered fatty acid composition enhanced the thermal tolerance of the mutant. Similarly, the chloroplast membranes of the mutant were more resistant than wild type to thermal inactivation of photosynthetic electron transport. These observations lend support to previous suggestions that chloroplast membrane lipid composition may be an important component of the thermal acclimation response observed in many plant species which are photosynthetically active during periods of seasonally variable temperature extremes.

  13. Blood risk factor metabolites associated with heart disease and myocardial fatty acids in copper-deficient male and female rats

    SciTech Connect

    Fields, M.; Lewis, C.; Beal, T. ); Berlin, E.; Kliman, P.G.; Peters, R.C. )

    1989-07-01

    Intact and castrated males and intact and ovariectomized female rats were fed a copper-deficient diet in order to establish whether the protection provided in females against cardiovascular pathology and mortality is due to endogenous sex hormones, and different levels of blood lipids and/or myocardial fatty acids. Seventy-three male and female rats were assigned to a copper-deficient diet (0.6 {mu}g of copper/g diet) containing 62% fructose for 8 weeks. Twelve of the male rats underwent castration and 12 of the females were ovariectomized. All animals exhibited high levels of plasma cholesterol, triglycerides, and uric acid, which were neither affected by the sex of the rat nor by the surgical treatment. The composition of fatty acids of the myocardium was similar in males and females. Except for those animals that were sacrificed by us, all other male rats died of heart pathology. In contrast, none of the female rats exhibited heart pathology and none died of the deficiency. It is suggested that heart pathology and mortality in copper deficiency are sex related and not due to high levels of plasma cholesterol, triglycerides, and uric acid or to differences in myocardial fatty acid composition.

  14. Evaluation of the tolerance of acetic acid and 2-furaldehyde on the growth of Pichia stipitis and its respiratory deficient.

    PubMed

    Ortiz-Muñiz, B; Rasgado-Mellado, J; Solis-Pacheco, J; Nolasco-Hipólito, C; Domínguez-González, J M; Aguilar-Uscanga, M G

    2014-10-01

    The use of lignocellulosic residues for ethanol production is limited by toxic compounds in fermenting yeasts present in diluted acid hydrolysates like acetic acid and 2-furaldehyde. The respiratory deficient phenotype gives the cell the ability to resist several toxic compounds. So the aim of this work was to evaluate the tolerance to toxic compounds present in lignocellulosic hydrolysates like acetic acid and 2-furaldehyde in Pichia stipitis and its respiratory deficient strains. The respiratory deficient phenotype was induced by exposure to chemical agents such as acriflavine, acrylamide and rhodamine; 23 strains were obtained. The selection criterion was based on increasing specific ethanol yield (g ethanol g(-1) biomass) with acetic acid and furaldehyde tolerance. The screening showed that P. stipitis NRRL Y-7124 ACL 2-1RD (lacking cytochrome c), obtained using acrylamide, presented the highest specific ethanol production rate (1.82 g g(-1 )h(-1)). Meanwhile, the ACF8-3RD strain showed the highest acetic acid tolerance (7.80 g L(-1)) and the RHO2-3RD strain was able to tolerate up to 1.5 g L(-1) 2-furaldehyde with a growth and ethanol production inhibition of 23 and 22 %, respectively. The use of respiratory deficient yeast phenotype is a strategy for ethanol production improvement in a medium with toxic compounds such as hydrolysed sugarcane bagasse amongst others.

  15. Effects of protein deficiency and food restriction on lung ascorbic acid and glutathione in rats exposed to ozone

    SciTech Connect

    Dubick, M.A.; Heng, H.; Rucker, R.B.

    1985-08-01

    Weanling (52 +/- 4 g) or adult (259 +/- 16 g) male Sprague-Dawley rats were fed ad libitum casein-based diets containing 4 or 16% protein. A third group (food restricted) was fed daily the 16% protein diet, but at the food intake level of the 4% protein group. After 3 wk (weanling) or 5 wk (adults), half of the rats in each group were continuously exposed to 0.64 ppm ozone for 7 d. Ascorbic acid and reduced glutathione levels were then measured. In the heart and liver from weanling rats, ascorbic acid concentrations were lower in the protein-deficient group than in either control group. In the liver from weanling rats glutathione concentrations were also reduced in response to protein deficiency. Exposure to ozone produced no additional response. For adult rats the response for liver glutathione was similar to that of the weanlings. The liver ascorbate concentration, however, was consistently lower in adult rats compared to weanlings exposed to ozone. In lungs from adult rats, the ascorbic acid concentration was lower in the protein-deficient group than in either control group. On a whole-organ basis, both ascorbic acid and glutathione were usually higher in lungs from rats exposed to ozone than from those exposed to air. Interestingly, protein deficiency did not appear to compromise the lung's ability to maintain, in relative terms, the ascorbic acid or glutathione concentration in response to ozone.

  16. Aromatic amino Acid decarboxylase deficiency not responding to pyridoxine and bromocriptine therapy: case report and review of response to treatment.

    PubMed

    Alfadhel, Majid; Kattan, Rana

    2014-01-01

    Aromatic L-amino acid decarboxylase (AADC) deficiency (MIM #608643) is an autosomal recessive inborn error of monoamines. It is caused by a mutation in the DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of this condition include a combination of dopamine, noradrenaline, and serotonin deficiencies, and a patient may present with hypotonia, oculogyric crises, sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy with severe developmental delay. We report the case of an 8-month-old boy who presented with the abovementioned symptoms and who was diagnosed with AADC deficiency based on clinical, biochemical, and molecular investigations. Treatment with bromocriptine and pyridoxine showed no improvement. These data support the findings observed among previously reported cohorts that showed poor response of this disease to current regimens. Alternative therapies are needed to ameliorate the clinical complications associated with this disorder.

  17. Performance of calcium deficient hydroxyapatite-polyglycolic acid composites: an in vitro study.

    PubMed

    Dunne, Nicholas; Jack, Valerie; O'Hara, Rochelle; Farrar, David; Buchanan, Fraser

    2010-08-01

    The strategic incorporation of bioresorbable polymeric additives to calcium-deficient hydroxyapatite cement may provide short-term structural reinforcement and modify the modulus to closer match bone. The longer-term resorption properties may also be improved, creating pathways for bone in-growth. The aim of this study was to investigate the resorption process of a calcium phosphate cement system containing either in polyglycolic acid tri-methylene carbonate particles or polyglycolic acid fibres. This was achieved by in vitro aging in physiological conditions (phosphate buffered solution at 37 degrees C) over 12 weeks. The unreinforced CPC exhibited an increase in compressive strength at 12 weeks, however catastrophic failure was observed above a critical loading. The fracture behaviour of cement was improved by the incorporation of PGA fibres; the cement retained its cohesive structure after critical loading. Gravimetric analysis and scanning electron microscopy showed a large proportion of the fibres had resorbed after 12 weeks allowing for the increased cement porosity, which could facilitate cell infiltration and faster integration of natural bone. Incorporating the particulate additives in the cement did not provide any mechanism for mechanical property augmentation or did not demonstrate any appreciable level of resorption after 12 weeks.

  18. Neural regulation of acid maltase in an unusual adult onset deficiency.

    PubMed

    Meola, G; Sansone, V; Rotondo, G; Radice, S; Sterlicchio, M; Mauri, M; Bresolin, N; Moggio, M

    1994-01-01

    In a 48-year-old female, the first symptoms apparently manifested themselves 18 years before, with occasional tripping and weakness in both legs. During the next 18 years, weakness progressed and the patient developed a waddling gait; she became unable to rise from a lying or seated position unassisted and the shoulder girdle also became affected. Neurological examination revealed limb and shoulder girdle predominantly involving the lower extremities. We established cell cultures from muscle biopsy specimens obtained from our patient and carried out morphological analysis which, although aspecific, demonstrated clear signs of neurogenic suffering. This was confirmed in EMG studies performed. Biochemical analysis revealed very low acid maltase residual activity. We describe an unusual case of adult-onset acid maltase deficiency (AMD) with neurogenic atrophy and low residual activity. Innervated myofibres prepared by co-culturing the patient's myoblasts, with spinal cord foetal mouse explants were not associated with an abnormal in vitro maturation of the innervated myofibres as expected by the very low residual enzymatic activity found both in the muscle biopsy specimens and in the muscle cultures. There is strong suggestion that factors other than the amount of residual activity must be involved to determine the clinical manifestation of this disease.

  19. Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice.

    PubMed

    Han, Na-Ra; Kim, Hee-Yun; Yang, Woong Mo; Jeong, Hyun-Ja; Kim, Hyung-Min

    2015-09-01

    Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-β messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-β mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells.

  20. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    PubMed

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. PMID:25421565

  1. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    PubMed

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation.

  2. Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

    PubMed

    Saheki, T; Mori, K; Kobayashi, K; Horiuchi, M; Shige, T; Obara, T; Suzuki, S; Mori, M; Yamamura, K

    1995-01-25

    We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

  3. Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis.

    PubMed

    Kong, Bo; Zhu, Yan; Li, Guodong; Williams, Jessica A; Buckley, Kyle; Tawfik, Ossama; Luyendyk, James P; Guo, Grace L

    2016-03-01

    Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily with its endogenous ligands bile acids. Mice with whole body FXR deficiency develop liver tumors spontaneously, but the underlying mechanism is unclear. Moreover, it is unknown whether FXR deficiency in liver alone serves as a tumor initiator or promoter during liver carcinogenesis. This study aims to evaluate the effects of hepatocyte-specific FXR deficiency (FXR(hep-/-)) in liver tumor formation. The results showed that FXR(hep-/-) mice did not show spontaneous liver tumorigenesis with aging (up to 24 mo of age). Therefore FXR(hep-/-) mice were fed a bile acid (cholic acid)-containing diet alone or along with a liver tumor initiator, diethylnitrosamine (DEN). Thirty weeks later, no tumors were found in wild-type or FXR(hep-/-) mice without any treatment or with DEN only. However, with cholic acid, while only some wild-type mice developed tumors, all FXR(hep-/-) mice presented with severe liver injury and tumors. Interestingly, FXR(hep-/-) mouse livers increased basal expression of tumor suppressor p53 protein, apoptosis, and decreased basal cyclin D1 expression, which may prevent tumor development in FXR(hep-/-) mice. However, cholic acid feeding reversed these effects in FXR(hep-/-) mice, which is associated with an increased cyclin D1 and decreased cell cycle inhibitors. More in-depth analysis indicates that the increased in cell growth might result from disturbance of the MAPK and JAK/Stat3 signaling pathways. In conclusion, this study shows that hepatic FXR deficiency may only serve as a tumor initiator, and increased bile acids is required for tumor formation likely by promoting cell proliferation. PMID:26744468

  4. Acid-Labile Subunit Deficiency and Growth Failure: Description of Two Novel Cases

    PubMed Central

    David, A; Rose, S.J.; Miraki-Moud, F.; Metherell, L.A.; Savage, M.O.; Clark, A.J.L.; Camacho-Hübner, C.

    2010-01-01

    Background/Aims Mutations in the acid-labile subunit (ALS) gene (IGFALS) have been associated with circulating insulin-like growth factor I (IGF-I) deficiency and short stature. Whether severe pubertal delay is also part of the phenotype remains controversial due to the small number of cases reported. We report 2 children with a history of growth failure due to novel IGFALS mutations. Methods The growth hormone receptor gene (GHR) and IGFALS were analyzed by direct sequencing. Ternary complex formation was studied by size exclusion chromatography. Results Two boys of 13.3 and 10.6 years, with pubertal stages 2 and 1, had mild short stature (−3.2 and −2.8 SDS, respectively) and a biochemical profile suggestive of growth hormone resistance. No defects were identified in the GHR. Patient 1 was homozygous for the IGFALS missense mutation P73L. Patient 2 was a compound heterozygote for the missense mutation L134Q and a novel GGC to AG substitution at position 546–548 (546–548delGGCinsAG). The latter causes a frameshift and the appearance of a premature stop codon. Size exclusion chromatography showed no peaks corresponding to ternary and binary complexes in either patient. Conclusion Screening of the IGFALS is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS. PMID:20389102

  5. Accumulation of methyl-deficient rat liver messenger ribonucleic acid on ethionine administration

    SciTech Connect

    Goswami, B.B.; Sharma, O.K.

    1980-01-01

    Highly purified poly(adenylic acid)-containing RNA isolated from livers of rats fed 0.25% DL-etionine in the diet for 7 days accepted methyl groups from S-adenosyl(methyl-/sup 3/H)methionine, when incubated in vitro with mRNA methyltransferases from vaccinia virus or Ehrlich ascites cells, whereas RNA from control rats had no such activity. Nuclease digestion followed by chromatographic analyses of mRNA methylated in vitro revealed that the methyl groups were incorporated at the 5' end into cap 1 structures (m/sup 7/GpppNmp...) by the viral enzyme, whereas both cap 0 (m/sup 7/GpppNp...) and cap 1 (m/sup 7/Gpppm/sup 6/Am...) structures were formed by the Ehrlich ascites cell enzymes. the methyl-deficient mRNA isolated from the liver of ethionine-fed rats differed in its translational properties from mRNA isolated from control animals in an in vitro protein synthesizing system from wheat germ.

  6. Role of the plasma membrane H+-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency

    PubMed Central

    Yu, Wenqian; Kan, Qi; Zhang, Jiarong; Zeng, Bingjie; Chen, Qi

    2016-01-01

    Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H+-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H+-ATPase in organic acid exudation under Al toxicity and P deficiency conditions. PMID:26713714

  7. Intestinal absorption, liver uptake, and excretion of /sup 3/H-folic acid in folic acid-deficient, alcohol-consuming nonhuman primates

    SciTech Connect

    Blocker, D.E.; Thenen, S.W.

    1987-09-01

    Nonhuman primates fed folic acid-deficient diets +/- 30% kcal ethanol were used to determine alcohol effects on megaloblastic anemia development and folate bioavailability. Lower hemoglobin (Hb) and red blood cell (RBC) counts and higher mean corpuscular volume (MCV) occurred after 13 wk in alcohol-fed monkeys, later in controls. Plasma, RBC, and liver folate declined and urinary formiminoglutamic acid (FIGLU) was elevated in both groups with FIGLU increasing more among alcohol-fed monkeys at 38 wk. After 40 wk, the bioavailability of oral /sup 3/H-folic acid was investigated and showed increased fecal and reduced urinary tritium excretion in alcohol-fed monkeys compared with controls while plasma uptake and liver and whole body tritium retention were similar in both groups. These observations demonstrate that chronic alcohol consumption impairs folate coenzymes, accelerates appearance of hematologic indices of megaloblastic anemia, and causes possible malabsorption of enterohepatically circulated folates in folate deficiency even when other essential nutrients are provided.

  8. Dataset on inflammatory proteins expressions and sialic acid levels in apolipoprotein E-deficient mice with administration of N-acetylneuraminic acid and/or quercetin.

    PubMed

    Dong, Rongrong; Li, Fahui; Qin, Shucun; Wang, Yi; Si, Yanhong; Xu, Xuelian; Tian, Hua; Zhai, Lei; Zhang, Guangjie; Li, Yongjun; Zhou, Yawei; Zhang, Ying; Zhang, Nan; Guo, Shoudong

    2016-09-01

    The data presented in this article describe an effect of N-acetylneuraminic acid and/or quercetin on the inflammatory proteins expressions (TNF-α, ICAM-1, VCAM-1 and MOMA-2) and the N-acetylneuraminic acid (NANA) levels of apolipoprotein E-deficient mice that are given a high-fat diet. Protein expression was performed by immunohistochemical imaging and NANA was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or semi-quantified using Image-Pro Plus software after ligation with fluorescein-5-thiosemicarbazide (FTSC). Further interpretation and discussion could be found at our research article entitled "Exogenous supplement of N-acetylneuraminic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice" (Guo et al., 2016) [1]. PMID:27419199

  9. Effects of folic acid deficiency and MTHFRC677T polymorphisms on cytotoxicity in human peripheral blood lymphocytes

    SciTech Connect

    Wu Xiayu; Liang Ziqing; Zou Tianning; Wang Xu

    2009-02-13

    Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicity was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.

  10. Effect of selenium and vitamin E deficiencies on the fate of arachidonic acid in rat isolated lungs

    SciTech Connect

    Uotila, P.; Puustinen, T.

    1985-06-01

    The fate of exogenous /sup 14/C-arachidonic acid (/sup 14/C-AA) was investigated in the isolated lungs of rats fed selenium and vitamin E deficient diet or diets supplemented with selenium and/or vitamin E. When 80 nmol of /sup 14/C-AA was infused into the pulmonary circulation most of the infused /sup 14/C-AA was found in different phospholipid and neutral lipid fractions of the perfused lungs. Only less than ten percent of the infused radioactivity was recovered in the perfusion effluent. The amount of arachidonate metabolites in the perfusion effluent was negligible, and most of the radioactivity in the perfusion effluent consisted of unmetabolized arachidonate. Selenium deficiency had no significant effect on the distribution of /sup 14/C-AA in different lung lipid fractions. However, in the lungs of vitamin E deficient rats the amount of radioactivity was slightly increased in the neutral lipid fraction, which was due to the increased amount of /sup 14/C-AA in the diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of /sup 14/C-AA in the triacylglycerols and in different phospholipids was not significantly changed. The present study might indicate that selenium deficiency has no significant effect on the fate of exogenous arachidonic acid in isolated rat lungs, and that vitamin E deficiency would slightly increase the amount of arachidonic acid in the diacylglycerols.

  11. Lung, aorta, and platelet metabolism of /sup 14/C-arachidonic acid in vitamin E deficient rats

    SciTech Connect

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1982-08-01

    /sup 14/C-arachidonic acid metabolism was determined in aortas, platelets, and perfused lungs from rats pair fed a basal diet supplemented with 0 or 100 ppm vitamin E for 11 weeks. Spontaneous erythrocyte hemolysis tests showed 92% and 8% hemolysis for the 0 and 100 ppm vitamin E groups, respectively. Elevated lung homogenate levels of malonaldehyde in the 0 ppm group confirmed its deficient vitamin E status. Aortas from the vitamin E deficient group synthesized 54% less prostacyclin than aortas from the supplemented group (p less than 0.05). Although thromboxane generation by platelets from the vitamin E deficient group exhibited a 37% increase, this difference was not statistically significant compared to the supplemented animals. Greater amounts of PGE2, PGF2 alpha, TXB2, and 6-keto-PGF1 alpha were obtained in albumin buffer perfusates from lungs of vitamin E deficient rats than in those from supplemented rats. Significant differences (p less than 0.05) were noticed, however, only for PGE2 and PGF2 alpha. These studies indicate that vitamin E quantitatively alters arachidonic acid metabolism in aortic and lung tissue but its effect on thromboxane synthesis by platelets is less marked.

  12. Mefolinate (5-methyltetrahydrofolate), but not folic acid, decreases mortality in an animal model of severe methylenetetrahydrofolate reductase deficiency.

    PubMed

    Li, D; Karp, N; Wu, Q; Wang, X-L; Melnyk, S; James, S J; Rozen, R

    2008-06-01

    Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) results in homocystinuria, with a variety of neurological and vascular complications, and sometimes death in the first year of life. MTHFR (EC 1.5.1.20) catalyses the synthesis of 5-methyltetrahydrofolate (5-methylTHF) which is required for homocysteine remethylation to methionine. Mthfr (-/-) mice are a good animal model of severe MTHFR deficiency in humans. They have marked hyperhomocysteinaemia and a high rate of mortality in the neonatal period. We attempted to rescue Mthfr (-/-) mice from postnatal death by treating their Mthfr (+/-) mothers with mefolinate (a synthetic form of 5-methylTHF, dissolved in their drinking water) or with a folic acid-enriched diet throughout pregnancy and lactation. We monitored pups' vitality and body weights until 3 weeks of age. The majority of Mthfr (-/-) pups from the control groups died during the first week of life. Body weights of -/- pups from control groups were significantly less than those of their Mthfr (+/-) and Mthfr ( +/+ ) littermates. Mefolinate treatment significantly improved survival rates (64% survival) in the -/- pups and improved morphology of the cerebellum. Folic acid supplementation did not affect the survival rate or body weights of the -/- pups. Our study suggests that MTHFR is important for postnatal growth and vitality, and that 5-methylTHF deficiency contributes to the high postnatal mortality. Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency. PMID:18415702

  13. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

    PubMed

    Diekman, Eugene F; van Weeghel, Michel; Wanders, Ronald J A; Visser, Gepke; Houten, Sander M

    2014-07-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

  14. Effect of n-3 fatty acids on serum lipid levels and hepatic fatty acid metabolism in BALB/c.KOR-Apoeshl mice deficient in apolipoprotein E expression.

    PubMed

    Ide, Takashi; Takahashi, Yoko; Kushiro, Masayo; Tachibana, Masayoshi; Matsushima, Yoshibumi

    2004-03-01

    N-3 fatty acids exert a potent serum lipid-lowering effect in rodents mainly by affecting hepatic fatty acid oxidation and synthesis. However, it has been observed that fish oil and docosahexaenoic acid ethyl ester do not lower serum lipid levels in apolipoprotein E (apoE)-knockout (Apoetm1Unc) mice generated by gene targeting. To test the hypothesis that apoE expression is required for n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism, we examined the effect of fish oil and n-3 fatty acid ethyl esters on the activity and gene expression of hepatic enzymes involved in fatty acid oxidation and synthesis using an alternative apoE-deficient mouse model with the BALB/c genetic background (BALB/c.KOR-Apoeshl). ApoE-deficient mice were fed diets containing 9.4% palm oil, fish oil, or 5.4% palm oil and 1% EPA plus 3% DHA ethyl esters for 15 days. In contrast to the reported data on apoE-knockout mice, fish oil and n-3 fatty acid ethyl esters greatly decreased serum triacylglycerol, cholesterol, and phospholipid levels in the Apoeshl mice. The decreases were greater with fish oil than with ethyl esters. The alterations by dietary n-3 fatty acids of serum lipid levels were accompanied by parallel changes in the activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation and synthesis. The reason for the discrepancy between the results of the current study and previous studies is unknown. However, our study at least indicates that a lack of apoE expression does not necessarily accompany deficits in the n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism.

  15. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.

    PubMed

    Czeizel, Andrew E; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-11-21

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of prevention is better than a pound of care".

  16. A Mixed-Method Study to Determine the Benefits of Periconceptional Folic Acid Supplementation and Effects of Folic Acid Deficiency in Mothers on Birth Outcomes

    PubMed Central

    Murthy, Gudlavalleti Venkata S; Kolli, Sunanda Reddy; Neogi, Sutapa B; Singh, Samiksha; John, Neena; N., Srinivas; Ramani, Sudha; Shamanna, BR; Doyle, Pat; Kinra, Sanjay; Ness, Andy; Pallepogula, Dinesh Raj; Pant, Hira B; Babbar, Smiksha; Reddy, Raghunath; Singh, Rachna

    2016-01-01

    Background Evidence from high income countries shows mothers who are supplemented with folic acid in their periconceptional period and early pregnancy have significantly reduced adverse outcomes like birth defects. However, in India there is a paucity of data on association of birth defects and folic acid supplementation. We identified a few important questions to be answered using separate scientific methods and then planned to triangulate the information. Objective In this paper, we describe the protocol of our study that aims to determine the association of folic acid and pregnancy outcomes like neural tube defects (NTDs) and orofacial clefts (OFCs). We decided to fill the gaps in knowledge from India to determine public health consequences of folic acid deficiency and factors influencing dietary and periconceptional consumption of folic acid. Methods The proposed study will be carried out in five stages and will examine the questions related to folic acid deficiency across selected locations in South and North India. The study will be carried out over a period of 4 years through the hierarchical evidence-based approach. At first a systematic review was conducted to pool the current birth prevalence of NTDs and orofacial clefts OFCs in India. To investigate the population prevalence, we plan to use the key informant method to determine prevalence of NTDs and OFCs. To determine the normal serum estimates of folic acid, iron, and vitamin B12 among Indian women (15-35 years), we will conduct a population-based, cross-sectional study. We will further strengthen the evidence of association between OFCs and folic acid by conducting a hospital-based, case-control study across three locations of India. Lastly, using qualitative methods we will understand community and health workers perspective on factors that decide the intake of folic acid supplements. Results This study will provide evidence on the community prevalence of birth defects and prevalence folic acid and

  17. Effect of 1-naphthaleneacetic acid on organic acid exudation by the roots of white lupin plants grown under phosphorus-deficient conditions.

    PubMed

    Gómez, Diego A; Carpena, Ramón O

    2014-09-15

    The effect of NAA (1-naphthaleneacetic acid) on organic acid exudation in white lupin plants grown under phosphorus deficiency was investigated. Plants were sampled periodically for collecting of organic acids (citrate, malate, succinate), and also were used to study the effect on proton extrusion and release of Na(+), K(+), Ca(2+) and Mg(2+). The tissues were later processed to quantify the organic acids in tissues, the phosphorus content and the effects on plant biomass. The exogenous addition of NAA led to an increase in organic acid exudation, but this response was not proportional to the concentration of the dose applied, noticing the largest increments with NAA 10(-8)M. In contrast the increase in root weight was proportional to the dose applied, which shows that with higher doses the roots produced are not of proteoid type. Proton extrusion and the release of cations were related to the NAA dose, the first was proportional to the dose applied and the second inversely proportional. Regarding the analysis of tissues, the results of citrate and phosphorus content in shoots show that the overall status of these parts are the main responsible of the organic acids exuded. NAA served as an enhancer of the organic acid exudation that occurs under phosphorus deficient conditions, with a response that depends on the dose applied, not only in its magnitude, but also in the mechanism of action of the plant hormone. PMID:25046756

  18. Effect of 1-naphthaleneacetic acid on organic acid exudation by the roots of white lupin plants grown under phosphorus-deficient conditions.

    PubMed

    Gómez, Diego A; Carpena, Ramón O

    2014-09-15

    The effect of NAA (1-naphthaleneacetic acid) on organic acid exudation in white lupin plants grown under phosphorus deficiency was investigated. Plants were sampled periodically for collecting of organic acids (citrate, malate, succinate), and also were used to study the effect on proton extrusion and release of Na(+), K(+), Ca(2+) and Mg(2+). The tissues were later processed to quantify the organic acids in tissues, the phosphorus content and the effects on plant biomass. The exogenous addition of NAA led to an increase in organic acid exudation, but this response was not proportional to the concentration of the dose applied, noticing the largest increments with NAA 10(-8)M. In contrast the increase in root weight was proportional to the dose applied, which shows that with higher doses the roots produced are not of proteoid type. Proton extrusion and the release of cations were related to the NAA dose, the first was proportional to the dose applied and the second inversely proportional. Regarding the analysis of tissues, the results of citrate and phosphorus content in shoots show that the overall status of these parts are the main responsible of the organic acids exuded. NAA served as an enhancer of the organic acid exudation that occurs under phosphorus deficient conditions, with a response that depends on the dose applied, not only in its magnitude, but also in the mechanism of action of the plant hormone.

  19. Parenteral safflower oil emulsion (Liposyn 10%): safety and effectiveness in treating or preventing essential fatty acid deficiency in surgical patients.

    PubMed Central

    Bivins, B A; Rapp, R P; Record, K; Meng, H C; Griffen, W O

    1980-01-01

    The safety and effectiveness of a 10% safflower oil emulsion in treating or preventing essential fatty acid deficiency was tested in a prospective study of 15 surgical patients requiring total parenteral nutrition for two to four weeks. Three dosage regimens were evaluated including: Group I: 4% of calories as linoleate daily (five patients), Group II: 4% of calories as linoleate every other day (two patients), and Group III: 8% of calories every other day (eight patients). Patients were monitored for laboratory changes from baseline specifically in those areas where previous fat emulsions have caused serious deviations. No significant changes were noted in hematologic parameters, coagulation studies, cholesterol and triglyceride serum levels. Although there were sporadic mild deviations in liver function changes in several patients, no clinically significant adverse effects could be directly attributed to infusion of the fat emulsion. Three patients had baseline triene/tetraene ratios of 0.4 or greater, indicative of essential fatty/acid deficiency, and these ratios dropped to less than 0.4 within eight days of beginning therapy with the parenteral fat emulsion. The remaining 12 patients maintained a normal triene/tetraene ratio of less than 0.4 throughout the 28 day study period. All three dosage regimens were considered effective for treatment and prevention of essential fatty acid deficiency. Images Fig. 1. Fig. 2. Fig. 3. PMID:6767452

  20. Successful Within-patient Dose Escalation of Olipudase Alfa in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Soran, Handrean; Diaz, George A.; Lippa, Natalie; Thurberg, Beth L.; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F.; Puga, Ana Cristina

    2015-01-01

    Background Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Methods Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. Results All patients successfully reached 3.0 mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4 hours across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. Conclusions This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. PMID:26049896

  1. In vivo correction with recombinant adenovirus of 4-hydroxyphenylpyruvic acid dioxygenase deficiencies in strain III mice.

    PubMed

    Kubo, S; Kiwaki, K; Awata, H; Katoh, H; Kanegae, Y; Saito, I; Yamamoto, T; Miyazaki, J; Matsuda, I; Endo, F

    1997-01-01

    Tyrosinemia type 3, caused by a genetic deficiency of 4-hydroxyphenylpyruvic acid dioxygenase (HPD) in tyrosine catabolism, is characterized by convulsion, ataxia, and mental retardation. The III mouse is a model of tyrosinemia type 3. HPD activity and protein are defective in the liver and its blood tyrosine levels are elevated, the range being between 1,100 and 1,656 microM. We constructed a recombinant adenoviral vector bearing the human HPD cDNA (AdexCAGhHPD), which is expressed under the control of a potent CAG promoter. III mice were injected with 1.0 x 10(8) to 1.0 x 10(9) pfu of AdexCAGhHPD through the tail vein. When 3.0 x 10(8) - 1.0 x 10(9) pfu were injected, blood tyrosine levels decreased within 3 hr, reached a normal range (under 300 microM), and remained at a low level for 2-6 weeks. Hepatic HPD activities also increased as early as 3 hr after the injection of 5.0 x 10(8) pfu, reached the levels comparable to the control mice in 3-7 days, and then decreased, and correlated well to blood tyrosine. Hepatic HPD expression was confirmed by Northern blot and immunoblot analyses. Histology revealed no difference (gross or microscopic) between the liver injected with AdexCAGhHPD and the control. No significant changes in blood tyrosine levels were noted after the second injection of 5.0 x 10(8) pfu of AdexCAGhHPD. Thus, the intravenous administration of the adenoviral vector bearing a foreign gene seems suitable for transient, early gene transfer into the liver.

  2. Identification of genes and pathways involved in the synthesis of Mead acid (20:3n-9), an indicator of essential fatty acid deficiency.

    PubMed

    Ichi, Ikuyo; Kono, Nozomu; Arita, Yuka; Haga, Shizuka; Arisawa, Kotoko; Yamano, Misato; Nagase, Mana; Fujiwara, Yoko; Arai, Hiroyuki

    2014-01-01

    In mammals, 5,8,11-eicosatrienoic acid (Mead acid, 20:3n-9) is synthesized from oleic acid during a state of essential fatty acid deficiency (EFAD). Mead acid is thought to be produced by the same enzymes that synthesize arachidonic acid and eicosapentaenoic acid, but the genes and the pathways involved in the conversion of oleic acid to Mead acid have not been fully elucidated. The levels of polyunsaturated fatty acids in cultured cells are generally very low compared to those in mammalian tissues. In this study, we found that cultured cells, such as NIH3T3 and Hepa1-6 cells, have significant levels of Mead acid, indicating that cells in culture are in an EFAD state under normal culture conditions. We then examined the effect of siRNA-mediated knockdown of fatty acid desaturases and elongases on the level of Mead acid, and found that knockdown of Elovl5, Fads1, or Fads2 decreased the level of Mead acid. This and the measured levels of possible intermediate products for the synthesis of Mead acid such as 18:2n-9, 20:1n-9 and 20:2n-9 in the knocked down cells indicate two pathways for the synthesis of Mead acid: pathway 1) 18:1n-9→(Fads2)→18:2n-9→(Elovl5)→20:2n-9→(Fads1)→20:3n-9 and pathway 2) 18:1n-9→(Elovl5)→20:1n-9→(Fads2)→20:2n-9→(Fads1)→20:3n-9.

  3. Effects of essential fatty acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in young pigs.

    PubMed

    Melton, J L; Wertz, P W; Swartzendruber, D C; Downing, D T

    1987-09-25

    Linoleate-rich O-acylglucosylceramides and acylceramides are thought to be of major significance for the physical structure and function of the epidermal permeability barrier. In the present investigation, the effects of a linoleate-free diet on O-acylsphingolipids and their associated functions were investigated. Starting at 5 days of age, male pigs were fed diets containing 12% of either lard or hydrogenated coconut oil. Transepidermal water loss was measured with an electrolytic water analyzer at weekly intervals. Pigs were killed at intervals, and epidermal lipids were isolated and analyzed. Fatty acid compositions were determined by gas-liquid chromatography (GLC). Within 2-3 weeks, pigs on the diet containing coconut oil began to display biochemical and physiological symptoms of essential fatty acid deficiency. Within 2 months, this group had extremely scaly skin and transepidermal water loss was elevated to five times that of controls. The progressive increase in transepidermal water loss correlated with replacement of linoleate by oleate in both acylceramide and acylglucosylceramide. The formation of lamellar granules and intercellular lipid sheets in the stratum corneum was not impaired in essential fatty acid deficiency as judged by electron microscopy. These results suggest that the linoleic acid normally found in the O-acylsphingolipids is not essential for formation of the epidermal membrane system. Rather, it appears that the nature of the ester-linked fatty acid in the O-acylsphingolipids regulates the permeability of this membrane system.

  4. Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse*

    PubMed Central

    Bröer, Angelika; Juelich, Torsten; Vanslambrouck, Jessica M.; Tietze, Nadine; Solomon, Peter S.; Holst, Jeff; Bailey, Charles G.; Rasko, John E. J.; Bröer, Stefan

    2011-01-01

    Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B0AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na+-dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking B0AT1 showed a reduced body weight. When adapted to a standard 20% protein diet, B0AT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation. PMID:21636576

  5. Reflecting on the EFA Global Monitoring Report's Framework for Understanding Quality Education: A Teacher's Perspective in Eritrea

    ERIC Educational Resources Information Center

    Gordon, Charlie

    2010-01-01

    This paper considers issues concerning the quality of education in Eritrea using the Education for All (EFA) Global Monitoring Report's (GMR) framework for quality education. Drawing on 2 years school-based professional experience in the country, the multiple factors affecting quality in schooling are discussed. The applicability of the GMR…

  6. Membrane omega-3 Fatty Acid deficiency as a preventable risk factor for comorbid coronary heart disease in major depressive disorder.

    PubMed

    McNamara, Robert K

    2009-01-01

    Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  7. Massive excretion of 2-oxoglutaric acid and 3-hydroxyisovaleric acid in a patient with a deficiency of 3-methylcrotonyl-CoA carboxylase.

    PubMed

    Finnie, M D; Cottrall, K; Seakins, J W; Snedden, W

    1976-12-01

    A three-month old child, presenting with a history of feeding problems, suspected respiratory infection and failure to thrive, later developed fits and a profound irreversible metabolic acidosis. Chromatographic investigation of the urine revealed a gross excretion of 2-oxoglutaric and 3-hydroxyisovaleric acids. The identity of these two acids was confirmed by mass spectrometry. Enzyme studies on liver obtained at post-mortem demonstrated a deficiency of 3-methylcrotonyl-CoA:carbon dioxide ligase (ADP) (EC 6.4.1.4).

  8. Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice.

    PubMed

    Cheng, Jie; Fang, Zhong-Ze; Kim, Jung-Hwan; Krausz, Kristopher W; Tanaka, Naoki; Chiang, John Y L; Gonzalez, Frank J

    2014-03-01

    Vitamin D receptor (VDR) mediates vitamin D signaling involved in bone metabolism, cellular growth and differentiation, cardiovascular function, and bile acid regulation. Mice with an intestine-specific disruption of VDR (Vdr(ΔIEpC)) have abnormal body size, colon structure, and imbalance of bile acid metabolism. Lithocholic acid (LCA), a secondary bile acid that activates VDR, is among the most toxic of the bile acids that when overaccumulated in the liver causes hepatotoxicity. Because cytochrome P450 3A4 (CYP3A4) is a target gene of VDR-involved bile acid metabolism, the role of CYP3A4 in VDR biology and bile acid metabolism was investigated. The CYP3A4 gene was inserted into Vdr(ΔIEpC) mice to produce the Vdr(ΔIEpC)/3A4 line. LCA was administered to control, transgenic-CYP3A4, Vdr(ΔIEpC), and Vdr(ΔIEpC)/3A4 mice, and hepatic toxicity and bile acid levels in the liver, intestine, bile, and urine were measured. VDR deficiency in the intestine of the Vdr(ΔIEpC) mice exacerbates LCA-induced hepatotoxicity manifested by increased necrosis and inflammation, due in part to over-accumulation of hepatic bile acids including taurocholic acid and taurodeoxycholic acid. Intestinal expression of CYP3A4 in the Vdr(ΔIEpC)/3A4 mouse line reduces LCA-induced hepatotoxicity through elevation of LCA metabolism and detoxification, and suppression of bile acid transporter expression in the small intestine. This study reveals that intestinal CYP3A4 protects against LCA hepatotoxicity.

  9. Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression.

    PubMed

    Liu, Huan; Tian, Tian; Qin, Shanchun; Li, Wen; Zhang, Xumei; Wang, Xuan; Gao, Yuxia; Huang, Guowei

    2015-12-01

    Recent efforts have revealed the microRNA (miRNA) pathways in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have revealed an association between folic acid deficiency and AD risk. However, the effects of folic acid deficiency on miRNA expression in AD animals have not been observed. We aimed to find if folic acid deficiency may enhance amyloid-β (Aβ) peptide deposition and regulate amyloid-associated miRNAs and their target genes expression in APP/PS1 mice. APP/PS1 mice and N2a cells were treated with folic acid-deficient diet or medium. Cognitive function of mice was assessed using the Morris water maze. miRNA profile was tested by polymerase chain reaction (PCR) array. Different expressional miRNAs were validated by real-time PCR. The deposition of Aβ plaques was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. APP and BACE1 proteins in mice brain and N2a cells were determined by Western blot. Folic acid deficiency aggravated amyloid pathology in AD mice. The AD+FD group showed shorter time spent in the target zone during the probe test. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that were differentially modulated by folic acid deficiency. In APP/PS1 mice brains and N2a cells with folic acid-deficient treatment, miR-106a-5p, miR-200b-3p and miR-339-5p were down-regulated, and their target genes APP and BACE1 were up-regulated. In conclusion, folic acid deficiency can enhance Aβ accumulation in APP/PS1 mice brain and decrease amyloid-associated miRNAs expression.

  10. Heavy metal extraction from an artificially contaminated sandy soil under EDDS deficiency: significance of humic acid and chelant mixture.

    PubMed

    Yip, Theo C M; Yan, Dickson Y S; Yui, Matthew M T; Tsang, Daniel C W; Lo, Irene M C

    2010-06-01

    Biodegradable EDDS ([S,S]-ethylenediaminedisuccinic acid) has been suggested for enhancing heavy metal extraction from contaminated soils. Recent studies showed that Zn and Pb are less effectively extracted due to metal exchange and re-adsorption onto the soil surfaces, especially for EDDS-deficiency conditions. This study therefore investigated the influence of dissolved organic matter and the co-presence of EDTA (ethylene-diamine-tetraacetic acid) on metal extraction from an artificially contaminated sandy soil under deficient amount of chelants in batch kinetics experiments. The addition of 10 and 20mgL(-1) of humic acid as dissolved organic matter (DOC) suppressed metal extraction by EDDS, probably resulting from the competition of adsorbed humic acid for heavy metals and adsorption of metal-humate complexes onto the soil surfaces. The effects were most significant for Pb because of greater extent of metal exchange of PbEDDS and high affinity towards organic matter. Thus, one should be cautious when there is a high content of organic matter in soils or groundwater. On the other hand, compared to individual additions of EDDS or EDTA, the equimolar EDDS and EDTA mixture exhibited significantly higher Pb extraction without notable Pb re-adsorption. The synergistic performance of the EDDS and EDTA mixture probably resulted from the change of chemical speciation and thus less competition among Cu, Zn and Pb for each chelant. These findings suggest further investigation into an optimum chemistry of the chelant mixture taking into account the effectiveness and associated environmental impact.

  11. In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials

    PubMed Central

    Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

    2015-01-01

    Objective To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Methods Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. Results HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after

  12. Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

    PubMed

    Ranganath, Prajnya; Matta, Divya; Bhavani, Gandham SriLakshmi; Wangnekar, Savita; Jain, Jamal Mohammed Nurul; Verma, Ishwar C; Kabra, Madhulika; Puri, Ratna Dua; Danda, Sumita; Gupta, Neerja; Girisha, Katta M; Sankar, Vaikom H; Patil, Siddaramappa J; Ramadevi, Akella Radha; Bhat, Meenakshi; Gowrishankar, Kalpana; Mandal, Kausik; Aggarwal, Shagun; Tamhankar, Parag Mohan; Tilak, Preetha; Phadke, Shubha R; Dalal, Ashwin

    2016-10-01

    Acid sphingomyelinase (ASM)-deficient Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann-Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc. PMID:27338287

  13. Is hyperuricemia a risk factor for arteriosclerosis? Uric acid and arteriosclerosis in apolipoprotein e-deficient mice.

    PubMed

    Wakuda, Hirokazu; Uchida, Shinya; Ikeda, Masahiko; Tabuchi, Masaki; Akahoshi, Yasumitsu; Shinozuka, Kazumasa; Yamada, Shizuo

    2014-01-01

    Although hyperlipidemia, high blood pressure, and diabetes increase the risk of arteriosclerosis, it is not clear whether hyperuricemia increases the risk of arteriosclerosis or not. We examined the effects of uric acid and curative drugs for hyperuricemia on atherosclerosis-susceptible C57BL/6J apolipoprotein E-deficient (apoE(-/-)) mice. Male apoE(-/-) mice (age: 6 weeks) were fed a normal diet (normal diet group) or a uric acid-enriched diet. Mice fed the uric acid-enriched diet were divided into three groups and administered a drinking vehicle (high uric acid diet group), allopurinol (20 mg·kg(-1)·d(-1)), or benzbromarone (20 mg·kg(-1)·d(-1)) for 10 weeks. Serum uric acid concentrations were higher in the high uric acid diet group than in the normal diet group, and concentrations in the allopurinol and benzbromarone groups were lower than in the high uric acid diet group. Serum total cholesterol and triglyceride levels were lower in the allopurinol group than in the high uric acid diet group. Oxidative stress was lower in the benzbromarone group than in the high uric acid diet group. Atherosclerotic lesion areas were smaller in the allopurinol and benzbromarone groups than in the high uric acid diet group. Thus, hyperuricemia may not be an independent risk factor for arteriosclerosis; however, the administration of allopurinol and benzbromarone prevented the development of atherosclerosis in apoE(-/-) mice fed a uric acid-enriched diet. The anti-atherosclerotic effect was in part due to lower total cholesterol and oxidative stress in the serum. Other possible mechanisms underlying this effect should be investigated.

  14. Evaluation of ensemble streamflow predictions of the European Flood Awareness System (EFAS)

    NASA Astrophysics Data System (ADS)

    Alfieri, Lorenzo; Pappenberger, Florian; Wetterhall, Fredrik; Haiden, Thomas; Richardson, David; Salamon, Peter; Thielen, Jutta

    2014-05-01

    In operational hydrological forecasting systems, improvements are directly related to the continuous monitoring of the forecast performance. An efficient evaluation framework must be able to spot issues and limitations and provide feedback to the system developers. In regional systems, the expertise of analysts on duty is a major component of the daily evaluation. On the other hand, large scale systems need to be complemented with semi-automated tools to evaluate the quality of forecasts equitably in every part of their domain. This work presents the current status of the monitoring and evaluation framework of the European Flood Awareness System (EFAS). Twice per day, EFAS performs hydrological simulation of ensemble weather predictions over Europe and detects river sections where forecast streamflow is likely to exceed flood warning thresholds in the coming days. In each 5x5 km2 grid point of the European river network, 10-day ensemble streamflow predictions driven by ECMWF weather forecasts are evaluated against a reference simulation which uses observed meteorological fields as input to a calibrated hydrological model. Performance scores are displayed spatially on maps and plotted against their forecast lead time, basin size, as well as in time, considering average scores for 12-month moving windows of forecasts. Results indicate skillful predictions in medium to large river basins over the 10-day range. An evaluation of 12-month average scores over the past 5 years suggests a moderate improvement for all 12-month forecasts ending from the beginning of 2013 onwards. Such improvement occurred notwithstanding an increasing negative forecast bias in mountain regions. On average, performance drops significantly in river basins with upstream area smaller than 300 km2, due to resolution issues and to the underestimation of the runoff in mountain areas. On the other hand, performance in rivers with large upstream area (i.e., 10,000 km2 and above) shows highly positive

  15. Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow: a review.

    PubMed

    Rosero, David S; Boyd, R Dean; Odle, Jack; van Heugten, Eric

    2016-01-01

    pregnant: sows bred = 98 %). Collectively, we conclude that a minimum dietary intake of 10 g/d of α-linolenic acid, simultaneous with a minimum of 125 g/d of linoleic acid should be provided to ≥ 95 % of the sows; thereby, achieving a maximum sow reproductive efficiency through multiple mechanisms that include rapid return to estrus, high maintenance of pregnancy and large subsequent litter size in mature sows, that appear to be susceptible to EFA deficiency.

  16. Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow: a review.

    PubMed

    Rosero, David S; Boyd, R Dean; Odle, Jack; van Heugten, Eric

    2016-01-01

    pregnant: sows bred = 98 %). Collectively, we conclude that a minimum dietary intake of 10 g/d of α-linolenic acid, simultaneous with a minimum of 125 g/d of linoleic acid should be provided to ≥ 95 % of the sows; thereby, achieving a maximum sow reproductive efficiency through multiple mechanisms that include rapid return to estrus, high maintenance of pregnancy and large subsequent litter size in mature sows, that appear to be susceptible to EFA deficiency. PMID:27274395

  17. Aromatic L-amino acid decarboxylase deficiency with hyperdopaminuria. Clinical and laboratory findings in response to different therapies.

    PubMed

    Fiumara, A; Bräutigam, C; Hyland, K; Sharma, R; Lagae, L; Stoltenborg, B; Hoffmann, G F; Jaeken, J; Wevers, R A

    2002-08-01

    Aromatic L-amino acid decarboxylase (AADC - E.C. 4.1.1.28) converts L-dopa to dopamine and 5-hydroxytryptophan to serotonin. Inherited deficiency of this enzyme leads to decreased brain levels of these neurotransmitters. Clinically this results in the development of a progressive neurometabolic disorder characterized by severe hypotonia, dystonic and choreoathetoid movements, oculogyric crises, and hypothermia from infancy. Here we describe the clinical, biochemical and molecular details of two affected brothers, one of whom, despite the lack of AADC, presented with hyperdopaminuria. In addition, we detail his reactions to treatment with dopaminergic agonists, monoamine oxidase inhibitors and pyridoxine.

  18. Cholestane-3β,5α,6β-triol: high levels in Niemann-Pick type C, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency[S

    PubMed Central

    Pajares, Sonia; Arias, Angela; García-Villoria, Judit; Macías-Vidal, Judit; Ros, Emilio; de las Heras, Javier; Girós, Marisa; Coll, Maria J.; Ribes, Antonia

    2015-01-01

    Niemann-Pick type C (NPC) is a progressive neurodegenerative disease characterized by lysosomal/endosomal accumulation of unesterified cholesterol and glycolipids. Recent studies have shown that plasma cholestane-3β,5α,6β-triol (CT) and 7-ketocholesterol (7-KC) could be potential biomarkers for the diagnosis of NPC patients. We aimed to know the sensitivity and specificity of these biomarkers for the diagnosis of NPC compared with other diseases that can potentially lead to oxysterol alterations. We studied 107 controls and 122 patients including 16 with NPC, 3 with lysosomal acid lipase (LAL) deficiency, 8 with other lysosomal diseases, 5 with galactosemia, 11 with cerebrotendinous xanthomatosis (CTX), 3 with Smith-Lemli-Opitz, 14 with peroxisomal biogenesis disorders, 19 with unspecific hepatic diseases, 13 with familial hypercholesterolemia, and 30 with neurological involvement and no evidence of an inherited metabolic disease. CT and 7-KC were analyzed by HPLC-ESI-MS/MS as mono-dimethylglycine derivatives. Levels of 7-KC were high in most of the studied diseases, whereas those of CT were only high in NPC, LAL, and CTX patients. Consequently, although CT is a sensitive biomarker of NPC disease, including those cases with doubtful filipin staining, it is not specific. 7-KC is a very unspecific biomarker. PMID:26239048

  19. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice12345

    PubMed Central

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas DE

    2015-01-01

    Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Objective: Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Design: Folic acid–supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr+/+ and Mthfr+/− mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Results: Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr+/− livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr+/− mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. Conclusions: We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2

  20. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

    PubMed

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.

  1. Myeloid-derived suppressor cells are involved in lysosomal acid lipase deficiency-induced endothelial cell dysfunctions.

    PubMed

    Zhao, Ting; Ding, Xinchun; Du, Hong; Yan, Cong

    2014-08-15

    The underlying mechanisms that lysosomal acid lipase (LAL) deficiency causes infiltration of myeloid-derived suppressor cells (MDSCs) in multiple organs and subsequent inflammation remain incompletely understood. Endothelial cells (ECs), lining the inner layer of blood vessels, constitute barriers regulating leukocytes transmigration to the site of inflammation. Therefore, we hypothesized that ECs are dysfunctional in LAL-deficient (lal(-/-)) mice. We found that Ly6G(+) cells transmigrated more efficiently across lal(-/-) ECs than wild-type (lal(+/+)) ECs, which were associated with increased levels of PECAM-1 and MCP-1 in lal(-/-) ECs. In addition, lal(-/-) ECs showed enhanced migration and proliferation, decreased apoptosis, but impaired tube formation and angiogenesis. lal(-/-) ECs also suppressed T cell proliferation in vitro. Interestingly, lal(-/-) Ly6G(+) cells promoted in vivo angiogenesis (including a tumor model), EC tube formation, and proliferation. Finally, the mammalian target of rapamycin (mTOR) pathway was activated in lal(-/-) ECs, and inhibition of mTOR reversed EC dysfunctions, including decreasing Ly6G(+) cell transmigration, delaying migration, and relieving suppression of T cell proliferation, which was mediated by decreasing production of reactive oxygen species. Our results indicate that LAL regulates EC functions through interaction with MDSCs and modulation of the mTOR pathway, which may provide a mechanistic basis for targeting MDSCs or mTOR to rejuvenate EC functions in LAL deficiency-related diseases. PMID:25000979

  2. The effect of humic acids and their complexes with iron on the functional status of plants grown under iron deficiency

    NASA Astrophysics Data System (ADS)

    Abros'kin, D. P.; Fuentes, M.; Garcia-Mina, J. M.; Klyain, O. I.; Senik, S. V.; Volkov, D. S.; Perminova, I. V.; Kulikova, N. A.

    2016-10-01

    The effect of humic acids (HAs) and their iron complexes (Fe-HAs) on the input of the main mineral elements into wheat seedlings, as well as on the efficiency of photosynthesis and the lipid profile of plants, under iron deficiency has been studied. The input of iron from Fe-HA complexes and its predominant accumulation in roots are demonstrated. It is found that HAs increase the efficiency of photosynthesis due to enhanced electron transport in photosystem II. It is shown that the application of HAs and Fe-HAs is accompanied by an enhanced input of Zn into plants, which could increase the antioxidant status of plants under iron deficiency conditions. In addition, a pronounced increase in the content of lipids in plants is revealed, which is indicative of the effect of HAs on plant metabolism. The obtained results suggest that the positive effect of Fe-HAs and HAs on plants under iron deficiency conditions is due to a combination of factors, among which the effect of HAs on the antioxidant status of plants and the plant lipid metabolism predominates.

  3. Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed a vitamin A-deficient diet.

    PubMed

    Verma, A K; Shoemaker, A; Simsiman, R; Denning, M; Zachman, R D

    1992-11-01

    The effects of vitamin A nutritional status on the levels of expression of retinoic acid nuclear receptors (RAR), and the retinoic acid-responsive gene, tissue transglutaminase, were determined in rats. Weanling male Sprague-Dawley rats fed a vitamin A-deficient diet for approximately 7 wk developed vitamin A deficiency, as confirmed by the depletion of liver retinol and retinyl palmitate. Controls were fed the same diet supplemented with 24 mg/kg retinyl acetate. The levels of expression of RAR beta mRNA were approximately 80% lower in bladder, brain, liver, lung and trachea and those of RAR gamma mRNA were approximately 50% lower in bladder, lung and trachea of rats fed the vitamin A-deficient diet than in controls. The levels of expression of RAR alpha mRNA were approximately 90% lower in brain and approximately 30% greater in liver, kidney, intestine and lung of rats fed the vitamin A-deficient diet. Vitamin A deficiency also resulted in reduced expression of tissue transglutaminase in the bladder, lungs and trachea, which paralleled the effects observed for RAR beta and RAR gamma. When vitamin A-deficient rats were subsequently fed a retinol-deficient diet supplemented with retinoic acid for 4 wk, the expression of RAR (beta and gamma) and tissue transglutaminase returned to the control levels. These results indicate that vitamin A nutritional status in rats influences the expression of both RAR and tissue transglutaminase in certain tissues. PMID:1279143

  4. Effect of gestational age and retinol (vitamin A) deficiency on fetal rat lung nuclear retinoic acid receptors.

    PubMed

    McMenamy, K R; Zachman, R D

    1993-03-01

    Retinol, or one of its metabolites such as retinoic acid (RA), is an important factor in the differentiation and maintenance of integrity of lung epithelium. Retinol deficiency in rats induces morphologic changes in respiratory tract epithelial cells that are histologically similar to those found in human premature infants with bronchopulmonary dysplasia. The exact mechanism of retinoid action in cellular growth and differentiation is not understood, but recently investigators have focused on mechanisms mediated by nuclear RA receptors (RAR). The role of these RAR as regulators of retinoid function is being studied in adult animal tissues and malignant cell lines, but little is known about RAR in developing fetal lung tissue. The purpose of this study was to determine the effect of gestational age and vitamin A deficiency on fetal rat lung nuclear RAR. RAR were also assayed in vitamin A control and vitamin A-deficient adult rat lung. A competitive binding assay and size exclusion HPLC separation were used to quantitate total RAR-specific binding. Binding analysis revealed a single class of receptor binding sites with high affinity (kd approximately 10(-9) M) for RA and RAR saturation at 2-5 nM RA. Specific binding of lung RAR in rat fetuses at 18 d gestation was two to three times greater than in fetuses at 20-21 d gestation, newborn pups, or adults. Western blot analysis revealed a predominance of RAR-beta receptors in fetal lung. Lungs from vitamin A-deficient fetuses demonstrated up-regulation of nuclear RAR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8384711

  5. Long-term effects of perinatal essential fatty acid deficiency on anxiety-related behavior in mice.

    PubMed

    Palsdottir, Vilborg; Månsson, Jan-Eric; Blomqvist, Maria; Egecioglu, Emil; Olsson, Bob

    2012-04-01

    Dietary essential fatty acids have been shown to regulate behavioral and cognitive functions in rodents. However, the long-term effect on behavior, besides memory and learning, of essential fatty acid deficiency (EFAD), i.e., lack of n-3 and n-6 fatty acids, during the perinatal period has not been investigated. Therefore, pregnant C57Bl/6 mice were given either an EFAD or an isoenergetic control diet from gestational day 16 and throughout lactation. The female offspring were given standard chow from 3 weeks of age, and at 12 to 14 weeks of age, open-field, object recognition, light-dark transition, elevated plus maze, and social interaction tests were performed. The brain glycerophospholipid fatty acid composition was investigated in 3-week-old and adult offspring by gas chromatography. The differences observed in behavior were indicative of lower anxiety in the EFAD mice compared to controls illustrated by more time spent in the open arms of the elevated plus maze (+ 41%, p < .05) and in the light compartment in the light-dark transition test (+ 63%, p < .05). The proportion of total n-3 fatty acids, especially 22:6n-3 in the brain, was lower with a compensatory increase in the proportion of total n-6 fatty acids, foremost 22:5n-6, in the EFAD mice compared to controls at 3 weeks of age. In the adult brains the fatty acid composition was normalized. In conclusion, our data show that EFAD during the perinatal period results in short-term alterations of fatty acid composition in brain and decreased anxiety in adult life. PMID:22352789

  6. Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment.

    PubMed

    Burda, P; Kuster, A; Hjalmarson, O; Suormala, T; Bürer, C; Lutz, S; Roussey, G; Christa, L; Asin-Cayuela, J; Kollberg, G; Andersson, B A; Watkins, D; Rosenblatt, D S; Fowler, B; Holme, E; Froese, D S; Baumgartner, M R

    2015-09-01

    In the folate cycle MTHFD1, encoded by MTHFD1, is a trifunctional enzyme containing 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase activity. To date, only one patient with MTHFD1 deficiency, presenting with hyperhomocysteinemia, megaloblastic anaemia, hemolytic uremic syndrome (HUS) and severe combined immunodeficiency, has been identified (Watkins et al J Med Genet 48:590-2, 2011). We now describe four additional patients from two different families. The second patient presented with hyperhomocysteinemia, megaloblastic anaemia, HUS, microangiopathy and retinopathy; all except the retinopathy resolved after treatment with hydroxocobalamin, betaine and folinic acid. The third patient developed megaloblastic anaemia, infection, autoimmune disease and moderate liver fibrosis but not hyperhomocysteinemia, and was successfully treated with a regime that included and was eventually reduced to folic acid. The other two, elder siblings of the third patient, died at 9 weeks of age with megaloblastic anaemia, infection and severe acidosis and had MTFHD1 deficiency diagnosed retrospectively. We identified a missense mutation (c.806C > T, p.Thr296Ile) and a splice site mutation (c.1674G > A) leading to exon skipping in the second patient, while the other three harboured a missense mutation (c.146C > T, p.Ser49Phe) and a premature stop mutation (c.673G > T, p.Glu225*), all of which were novel. Patient fibroblast studies revealed severely reduced methionine formation from [(14)C]-formate, which did not increase in cobalamin supplemented culture medium but was responsive to folic and folinic acid. These additional cases increase the clinical spectrum of this intriguing defect, provide in vitro evidence of disturbed methionine synthesis and substantiate the effectiveness of folic or folinic acid treatment. PMID:25633902

  7. Influence of sex and gonadal hormones on rat-liver and carcass lipids during the development of an essential fatty acid deficiency

    PubMed Central

    Ostwald, Rosemarie; Bouchard, Pauline; Miljanich, P.; Lyman, R. L.

    1965-01-01

    1. Groups of intact male and female rats and castrated rats injected with oestradiol or testosterone were given a diet containing hydrogenated coconut oil for 9 weeks, and at intervals the amounts and fatty acid compositions of the carcass and liver lipids were determined. 2. Male rats grew faster and larger, and exhibited typical external essential fatty acid deficiency symptoms sooner than did females. Testosterone-treated castrated male rats were similar to males, and oestradiol-injected castrated male rats resembled females. 3. Intact females maintained a higher linoleic acid concentration in their carcass than did males. Total amounts of carcass linoleic acid remained similar for all groups, only 200mg. being removed in 9 weeks regardless of body size. 4. The amounts of total cholesteryl esters were independent of liver size. They were higher in males and testosterone-treated castrated male rats than in females and oestrogen-treated castrated male rats. 5. Phospholipids represented about 80% of the liver lipids. The total amounts of the phospholipid linoleic acid and arachidonic acid were similar for all groups regardless of liver size, and were not affected appreciably by the deficiency. Females and oestrogen-treated castrated male rats maintained a higher proportion of phospholipid arachidonic acid for longer periods than did their male counterparts. Both the total amounts and the proportions of eicosatrienoic acid and palmitic acid were higher in males than in females. 6. Supplementation of the essential fatty acid-deficient diet with linoleic acid caused a rapid loss of eicosatrienoic acid and palmitic acid with a concomitant increase in stearic acid and arachidonic acid. 7. There were no obvious differences in the way that the essential fatty acids were metabolized or mobilized from adipose tissue of male or female rats during essential fatty acid deficiency. 8. The results indicated that the greater growth rate of the male rats caused them to require and

  8. Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice.

    PubMed

    Merkel, M; Velez-Carrasco, W; Hudgins, L C; Breslow, J L

    2001-11-01

    Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway. PMID:11606787

  9. Research needs in allergy: an EAACI position paper, in collaboration with EFA.

    PubMed

    Papadopoulos, Nikolaos G; Agache, Ioana; Bavbek, Sevim; Bilo, Beatrice M; Braido, Fulvio; Cardona, Victoria; Custovic, Adnan; Demonchy, Jan; Demoly, Pascal; Eigenmann, Philippe; Gayraud, Jacques; Grattan, Clive; Heffler, Enrico; Hellings, Peter W; Jutel, Marek; Knol, Edward; Lötvall, Jan; Muraro, Antonella; Poulsen, Lars K; Roberts, Graham; Schmid-Grendelmeier, Peter; Skevaki, Chrysanthi; Triggiani, Massimo; Vanree, Ronald; Werfel, Thomas; Flood, Breda; Palkonen, Susanna; Savli, Roberta; Allegri, Pia; Annesi-Maesano, Isabella; Annunziato, Francesco; Antolin-Amerigo, Dario; Apfelbacher, Christian; Blanca, Miguel; Bogacka, Ewa; Bonadonna, Patrizia; Bonini, Matteo; Boyman, Onur; Brockow, Knut; Burney, Peter; Buters, Jeroen; Butiene, Indre; Calderon, Moises; Cardell, Lars Olaf; Caubet, Jean-Christoph; Celenk, Sevcan; Cichocka-Jarosz, Ewa; Cingi, Cemal; Couto, Mariana; Dejong, Nicolette; Del Giacco, Stefano; Douladiris, Nikolaos; Fassio, Filippo; Fauquert, Jean-Luc; Fernandez, Javier; Rivas, Montserrat Fernandez; Ferrer, Marta; Flohr, Carsten; Gardner, James; Genuneit, Jon; Gevaert, Philippe; Groblewska, Anna; Hamelmann, Eckard; Hoffmann, Hans Jürgen; Hoffmann-Sommergruber, Karin; Hovhannisyan, Lilit; Hox, Valérie; Jahnsen, Frode L; Kalayci, Omer; Kalpaklioglu, Ayse Füsun; Kleine-Tebbe, Jörg; Konstantinou, George; Kurowski, Marcin; Lau, Susanne; Lauener, Roger; Lauerma, Antti; Logan, Kirsty; Magnan, Antoine; Makowska, Joanna; Makrinioti, Heidi; Mangina, Paraskevi; Manole, Felicia; Mari, Adriano; Mazon, Angel; Mills, Clare; Mingomataj, Ervinç; Niggemann, Bodo; Nilsson, Gunnar; Ollert, Markus; O'Mahony, Liam; O'Neil, Serena; Pala, Gianni; Papi, Alberto; Passalacqua, Gianni; Perkin, Michael; Pfaar, Oliver; Pitsios, Constantinos; Quirce, Santiago; Raap, Ulrike; Raulf-Heimsoth, Monika; Rhyner, Claudio; Robson-Ansley, Paula; Alves, Rodrigo Rodrigues; Roje, Zeljka; Rondon, Carmen; Rudzeviciene, Odilija; Ruëff, Franziska; Rukhadze, Maia; Rumi, Gabriele; Sackesen, Cansin; Santos, Alexandra F; Santucci, Annalisa; Scharf, Christian; Schmidt-Weber, Carsten; Schnyder, Benno; Schwarze, Jürgen; Senna, Gianenrico; Sergejeva, Svetlana; Seys, Sven; Siracusa, Andrea; Skypala, Isabel; Sokolowska, Milena; Spertini, Francois; Spiewak, Radoslaw; Sprikkelman, Aline; Sturm, Gunter; Swoboda, Ines; Terreehorst, Ingrid; Toskala, Elina; Traidl-Hoffmann, Claudia; Venter, Carina; Vlieg-Boerstra, Berber; Whitacker, Paul; Worm, Margitta; Xepapadaki, Paraskevi; Akdis, Cezmi A

    2012-01-01

    In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and

  10. Research needs in allergy: an EAACI position paper, in collaboration with EFA

    PubMed Central

    2012-01-01

    In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients’ Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients’ organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform

  11. Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation.

    PubMed

    Mayr, Johannes A; Zimmermann, Franz A; Fauth, Christine; Bergheim, Christa; Meierhofer, David; Radmayr, Doris; Zschocke, Johannes; Koch, Johannes; Sperl, Wolfgang

    2011-12-01

    Lipoic acid is an essential prosthetic group of four mitochondrial enzymes involved in the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched chain amino acids and in the glycine cleavage. Lipoic acid is synthesized stepwise within mitochondria through a process that includes lipoic acid synthetase. We identified the homozygous mutation c.746G>A (p.Arg249His) in LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine. Investigation of the mitochondrial energy metabolism showed reduced oxidation of pyruvate and decreased pyruvate dehydrogenase complex activity. A pronounced reduction of the prosthetic group lipoamide was found in lipoylated proteins.

  12. Adult Medication-Free Schizophrenic Patients Exhibit Long-Chain Omega-3 Fatty Acid Deficiency: Implications for Cardiovascular Disease Risk

    PubMed Central

    McNamara, Robert K.; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Dwivedi, Yogesh; Pandey, Ghanshyam N.

    2013-01-01

    Deficiency in long-chain omega-3 (LCn − 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n − 3) and docosahexaenoic acid (DHA, 22:6n − 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n = 20) and age-matched healthy controls (n = 24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, −22%, P = 0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, P = 0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n − 6) (+9%, P = 0.02) and the AA:EPA + DHA ratio (+28%, P = 0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n − 6) was significantly lower (−12%, P = 0.009) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (−19%, P = 0.04) but not female (−13%, P = 0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, P = 0.008) and female (+22%, P = 0.04) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn − 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality. PMID:23533712

  13. Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo 1H-MRS study*s⃞

    PubMed Central

    McNamara, Robert K.; Able, Jessica; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lindquist, Diana M.

    2009-01-01

    To investigate the effects of omega-3 fatty acid deficiency on phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by in vivo proton magnetic resonance spectroscopy (1H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning α-linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a 1H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D1 receptors. Postmortem PFC fatty acid composition was determined by gas chromatography. Relative to controls, PFC DHA composition was significantly reduced in adult postweaning (−27%) and perinatal (−65%) ALA-deficiency groups. Basal PFC mI concentrations were significantly reduced in the perinatal deficiency group (−21%, P = 0.001), but not in the postweaning deficiency group (−1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly increased mI concentrations only in the perinatal deficiency group (+16%, P = 0.02). These data demonstrate that perinatal deficits in cortical DHA accrual significantly and selectively reduce mI concentrations and augment receptor-generated mI synthesis. PMID:18802197

  14. Histone Deacetylase Inhibitor Upregulates Peroxisomal Fatty Acid Oxidation and Inhibits Apoptotic Cell Death in Abcd1-Deficient Glial Cells

    PubMed Central

    Singh, Jaspreet; Khan, Mushfiquddin; Pujol, Aurora; Baarine, Mauhamad; Singh, Inderjit

    2013-01-01

    In X-ALD, mutation/deletion of ALD gene (ABCD1) and the resultant very long chain fatty acid (VLCFA) derangement has dramatically opposing effects in astrocytes and oligodendrocytes. While loss of Abcd1 in astrocytes produces a robust inflammatory response, the oligodendrocytes undergo cell death leading to demyelination in X-linked adrenoleukodystrophy (X-ALD). The mechanisms of these distinct pathways in the two cell types are not well understood. Here, we investigated the effects of Abcd1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oligodendrocytes. Loss of Abcd1 inhibited peroxisomal β-oxidation activity and increased expression of VLCFA synthesizing enzymes, elongase of very long chain fatty acids (ELOVLs) (1 and 3) in both cell types. However, higher induction of ELOVL's in Abcd1-deficient B12 oligodendrocytes than astrocytes suggests that ELOVL pathway may play a prominent role in oligodendrocytes in X-ALD. While astrocytes are able to maintain the cellular homeostasis of anti-apoptotic proteins, Abcd1-deletion in B12 oligodendrocytes downregulated the anti-apototic (Bcl-2 and Bcl-xL) and cell survival (phospho-Erk1/2) proteins, and upregulated the pro-apoptotic proteins (Bad, Bim, Bax and Bid) leading to cell loss. These observations provide insights into different cellular signaling mechanisms in response to Abcd1-deletion in two different cell types of CNS. The apoptotic responses were accompanied by activation of caspase-3 and caspase-9 suggesting the involvement of mitochondrial-caspase-9-dependent mechanism in Abcd1-deficient oligodendrocytes. Treatment with histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) corrected the VLCFA derangement both in vitro and in vivo, and inhibited the oligodendrocytes loss. These observations provide a proof-of principle that HDAC inhibitor SAHA may have a therapeutic potential for X-ALD. PMID:23923017

  15. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    PubMed

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant.

  16. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    PubMed

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant. PMID:26225744

  17. Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.

    PubMed

    Zito, Ester; Hansen, Henning Gram; Yeo, Giles S H; Fujii, Junichi; Ron, David

    2012-10-12

    Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1α, ERO1β, and PRDX4 compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly modest delay in disulfide bond formation in secreted proteins but a profound, 5-fold lower procollagen 4-hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice, and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H(2)O(2)-generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation, and a noncanonical form of scurvy.

  18. Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency.

    PubMed

    Veskovic, Milena; Mladenovic, Dusan; Jorgacevic, Bojan; Stevanovic, Ivana; de Luka, Silvio; Radosavljevic, Tatjana

    2015-04-01

    Deficiency in methionine or choline can induce oxidative stress in various organs such as liver, kidney, heart, and brain. This study was to examine the effects of alpha-lipoic acid (LA) on oxidative stress induced by methionine and choline deficiency (MCD) in several brain structures. Male mice C57BL/6 (n = 28) were divided into four groups: (1) control - continuously fed with standard chow; (2) LA - fed with standard chow and receiving LA; (3) MCD2 - fed with MCD diet for two weeks, and (4) MCD2+LA - fed with MCD diet for two weeks and receiving LA (100 mg/kg/day intraperitonealy [i.p.]). Brain tissue (cortex, hypothalamus, striatum and hippocampus) was taken for determination of oxidative stress parameters. MCD diet induced a significant increase in malondialdehyde and NOx concentration in all brain regions, while LA restored their content to normal values. Similar to this, in MCD2 group, activity of total SOD, MnSOD, and Cu/ZnSOD was reduced by MCD diet, while LA treatment improved their activities in all brain structures. Besides, in MCD2 group a decrease in catalase activity in cortex and GSH content in hypothalamus was evident, while LA treatment induced an increase in catalase activity in cortex and striatum and GSH content in hypothalamus. LA treatment can significantly reduce lipid peroxidation and nitrosative stress, caused by MCD diet, in all brain regions by restoring antioxidant enzymes activities, predominantly total SOD, MnSOD, and Cu/ZnSOD, and to a lesser extent by modulating catalase activity and GSH content. LA supplementation may be used in order to prevent brain oxidative injury induced by methionine and choline deficiency.

  19. Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency

    PubMed Central

    Veskovic, Milena; Mladenovic, Dusan; Jorgacevic, Bojan; Stevanovic, Ivana; de Luka, Silvio

    2015-01-01

    Deficiency in methionine or choline can induce oxidative stress in various organs such as liver, kidney, heart, and brain. This study was to examine the effects of alpha-lipoic acid (LA) on oxidative stress induced by methionine and choline deficiency (MCD) in several brain structures. Male mice C57BL/6 (n = 28) were divided into four groups: (1) control – continuously fed with standard chow; (2) LA – fed with standard chow and receiving LA; (3) MCD2 – fed with MCD diet for two weeks, and (4) MCD2+LA – fed with MCD diet for two weeks and receiving LA (100 mg/kg/day intraperitonealy [i.p.]). Brain tissue (cortex, hypothalamus, striatum and hippocampus) was taken for determination of oxidative stress parameters. MCD diet induced a significant increase in malondialdehyde and NOx concentration in all brain regions, while LA restored their content to normal values. Similar to this, in MCD2 group, activity of total SOD, MnSOD, and Cu/ZnSOD was reduced by MCD diet, while LA treatment improved their activities in all brain structures. Besides, in MCD2 group a decrease in catalase activity in cortex and GSH content in hypothalamus was evident, while LA treatment induced an increase in catalase activity in cortex and striatum and GSH content in hypothalamus. LA treatment can significantly reduce lipid peroxidation and nitrosative stress, caused by MCD diet, in all brain regions by restoring antioxidant enzymes activities, predominantly total SOD, MnSOD, and Cu/ZnSOD, and to a lesser extent by modulating catalase activity and GSH content. LA supplementation may be used in order to prevent brain oxidative injury induced by methionine and choline deficiency. PMID:25193852

  20. Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic acid.

    PubMed

    Look, J; Landwehr, J; Bauer, F; Hoffmann, A S; Bluethmann, H; LeMotte, P

    1995-07-01

    Excessive intake of retinol or of retinoic acid causes a syndrome of characteristic toxic effects known as hypervitaminosis A. To test the role of the nuclear retinoic acid receptor (RAR gamma) in this process we produced mice with a targeted disruption of the RAR gamma gene and examined toxic effects of repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold higher doses of retinoic acid than wild-type mice as well as to elevated doses of the synthetic retinoids, indicating that RAR gamma may have a major role in mediating retinoid toxicity, a finding that possibly has practical implications for reducing the toxicity of synthetic retinoids in clinical use.

  1. Whole Blood Levels of the n-6 Essential Fatty Acid Linoleic Acid Are Inversely Associated with Stunting in 2-to-6 Year Old Tanzanian Children: A Cross-Sectional Study

    PubMed Central

    Jumbe, Theresia; Comstock, Sarah S.; Hahn, Samantha L.; Harris, William S.; Kinabo, Joyce; Fenton, Jenifer I.

    2016-01-01

    Background In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described. Objective The objectives of this cross-sectional study were to assess 1) whole blood levels of essential fatty acids and 2) the association between whole blood FA levels and growth parameters in Tanzanian children 2–6 years of age. Methods A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression. Results Of the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ) was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T) ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured. Conclusions The EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2–6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population. PMID:27137223

  2. Absorption and metabolism of ( sup 3 H)arachidonic and ( sup 14 C)linoleic acid in essential fatty acid-deficient rats

    SciTech Connect

    Hjelte, L.; Melin, T.; Nilsson, A.; Strandvik, B. )

    1990-07-01

    ({sup 3}H)arachidonic acid (20:4) and ({sup 14}C)linoleic acid (18:2) were fed in a triolein emulsion to essential fatty acid-deficient (EFAD) rats and to age-matched controls. Tissues were analyzed for radioactivity of different lipid classes after 1, 2, and 4 h. As in earlier studies, control rats retained more ({sup 3}H)20:4 than ({sup 14}C)18:2 in all organs except adipose tissue. In EFAD rats, recovery of ({sup 14}C)18:2 was increased in small intestine, liver, heart, and kidneys. In comparison to controls, EFAD rats retained much more ({sup 14}C)18:2 in phospholipids of these organs. The increase in the incorporation of both {sup 3}H and {sup 14}C into phosphatidylethanolamine was particularly pronounced. Another striking feature was the drastic increase in the retention after 4 h of {sup 14}C in cardiolipin, which is specifically located in the inner mitochondrial membrane. In contrast, incorporation of both {sup 3}H and {sup 14}C into phosphatidylinositol was decreased or unchanged in EFAD rats. Although fecal fat excretion was increased there was no evidence for a malabsorption or an increased retention in intestinal triacyglycerol of the radioactive fatty acids in EFAD rats. The proportion of ({sup 14}C)18:2 that had been converted to ({sup 14}C)20:4 was generally low but increased significantly with time in the liver and intestine of EFAD rats.

  3. Dietary zinc deficiency affects blood linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus gallus).

    PubMed

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P; Tako, Elad

    2014-03-20

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn⁺ (zinc adequate control, 42.3 μg/g zinc), and Zn⁻ (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn⁺ control versus Zn⁻ group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn⁺ control group (p < 0.05), and hepatic Δ⁶ desaturase was significantly higher in the Zn⁺ group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn⁻ group compared to the Zn⁺ group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.

  4. Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

    PubMed Central

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P.; Tako, Elad

    2014-01-01

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn(+) (zinc adequate control, 42.3 μg/g zinc), and Zn(−) (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+) control versus Zn(−) group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+) control group (p < 0.05), and hepatic Δ6 desaturase was significantly higher in the Zn(+) group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn(−) group compared to the Zn(+) group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation. PMID:24658588

  5. Early development of essential fatty acid deficiency in rats: Fat-free vs. hydrogenated coconut oil diet

    PubMed Central

    Ling, Pei-Ra; De Leon, Charlotte E.; Le, Hau; Puder, Mark; Bistrian, Bruce R.

    2011-01-01

    This study examined the effects of feeding an essential fatty acid deficient (EFAD) diet either without fat or with added hydrogenated coconut oil (HCO) on fatty acid profiles in rats. Both diets induced equivalent biochemical evidence of EFAD reflected by the triene/tetraene ratio in plasma phospholipids within 2 weeks. However, the HCO diet led to larger increases of 16:1n7 and 18:1n9 in muscle but smaller increases in fat tissue and plasma triglycerides than the fat-free diet, suggesting greater increases in hepatic de novo lipogenesis with the latter. In addition, the HCO diet led to larger decreases of some 18:3n3 metabolites, particularly 22:6n3, in muscle, fat and brain tissues than the fat-free diet, presumably related to lesser stimulation of elongation and desaturation. Thus, these secondary effects of an EFAD diet on fatty acid metabolism can be modified by the saturated fat in the diet while the primary impact of both diets on development of EFAD is unaffected. PMID:20675109

  6. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

    PubMed

    Das, Undurti N

    2013-10-01

    Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process.

  7. Mitochondrial and Oxidative Stress Aspects in Hippocampus of Rats Submitted to Dietary n-3 Polyunsaturated Fatty Acid Deficiency After Exposure to Early Stress.

    PubMed

    Ferreira, Charles Francisco; Bernardi, Juliana Rombaldi; da Silva, Diego Carrilho; de Sá Couto-Pereira, Natividade; de Souza Mota, Carina; Krolow, Rachel; Weis, Simone Nardin; Pettenuzzo, Letícia; Kapczinski, Flávio; Silveira, Patrícia Pelufo; Dalmaz, Carla

    2015-09-01

    Chronic dietary long-chain polyunsaturated fatty acids (PUFAs) deficiency may lead to changes in cortex and hippocampus neuronal membrane phospholipids, and may be linked to impaired central nervous system function. Particularly docosahexaenoic acid deficiency appears to be involved in neuropsychiatric disorders. On the other hand, adverse events early in life may also profoundly affect brain development, leading to long-lasting effects on neurophysiology, neurobiology and behavior. This research assessed if neonatal stress and a dietary n-3 PUFAs deficiency could interact to produce hippocampal alterations related to mitochondrial functions in adult rats. There were no effects of diet, neonatal intervention or interactions on superoxide dismutase or catalase enzymatic activities, mitochondrial membrane potential and respiratory chain complexes. Rats fed n-3 PUFAs deficient diet displayed higher levels of glutathione peroxidase and catalase activity, higher free radicals production and higher thiol content compared to rats fed n-3 PUFAs adequate diet. There were interactions among diets and neonatal stress, since glutathione peroxidase, free radicals production and thiol content were increased in groups that were subjected to neonatal interventions fed n-3 PUFAs deficient diet. Additionally, reduced mitochondrial potential was observed in handled animals. Total thiol revealed a neonatal stress effect, since animals subjected to neonatal interventions displayed lower thiol content. In conclusion, we observed that a chronic treatment with deficient n-3 PUFAs diet, from the puberty period on, increased free radicals production and imbalanced antioxidant enzymes activities, and these increases were higher in animals subjected to neonatal interventions.

  8. Egg boons: central components of marine fatty acid food webs.

    PubMed

    Fuiman, Lee A; Connelly, Tara L; Lowerre-Barbieri, Susan K; McClelland, James W

    2015-02-01

    Food web relationships are traditionally defined in terms of the flow of key elements, such as carbon, nitrogen, and phosphorus, and their role in limiting production. There is growing recognition that availability of important biomolecules, such as fatty acids, may exert controls on secondary production that are not easily explained by traditional element-oriented models. Essential fatty acids (EFAs) are required by most organisms for proper physiological function but are manufactured almost entirely by primary producers. Therefore, the flow of EFAs, especially docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), through aquatic food webs is critical for ecosystem functioning. A meta-analysis of data on the EFA content of marine organisms reveals that individual eggs of marine animals have exceptionally high concentrations of EFAs, and that superabundances of eggs released in temporally and spatially discrete patches create rich, but temporary, nutritional resources for egg predators, called "egg boons." Mortality rates of fish eggs are disproportionately higher than animals of similar size, and those eggs are consumed by predators, both larger and smaller than the adults that produce the eggs. Thus, egg boons are a major trophic pathway through which EFAs are repackaged and redistributed, and they are among the few pathways that run counter to the main direction of trophic flow. Egg boons can transport EFAs across ecosystems through advection of patches of eggs and spawning migrations of adults. Recognizing the significance of egg boons to aquatic food webs reveals linkages and feedbacks between organisms and environments that have important implications for understanding how food webs vary in time and space. Examples are given of top-down, bottom-up, and lateral control mechanisms that could significantly alter food webs through their effects on eggs. Our results suggest that trophodynamic food web models should include EFAs

  9. Additive effects of clofibric acid and pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) deficiency on hepatic steatosis in mice fed a high-saturated fat diet

    PubMed Central

    Hwang, Byounghoon; Wu, Pengfei; Harris, Robert A.

    2012-01-01

    SUMMARY Although improving glucose metabolism by inhibition of pyruvate dehydrogenase kinase 4 (PDK4) might prove beneficial in the treatment of type 2 diabetes or diet-induced obesity, it might induce detrimental effects by inhibiting fatty acid oxidation. PPARα agonists are often used to treat dyslipidemia in patients, especially in type 2 diabetes. Combinational treatment with a PDK4 inhibitor and PPARα agonists may prove beneficial. However, PPARα agonists may be less effective in the presence of a PDK4 inhibitor because PPARα agonists induce PDK4 expression. In the present study, the effects of clofibric acid, a PPARα agonist, on blood and liver lipids were determined in wild type and PDK4 knockout mice fed a high fat diet. As expected, treatment of wild type mice with clofibric acid resulted in less body weight gain, smaller epididymal fat pads, greater insulin sensitivity, and lower levels of serum and liver triacylglycerol. Surprisingly, rather than decreasing the effectiveness of clofibric acid, PDK4 deficiency enhanced the beneficial effects of clofibric acid on hepatic steatosis, lowered blood glucose levels, and did not prevent the positive effects of clofibric acid on serum triacylglycerols and free fatty acids. The metabolic effects of clofibric acid are therefore independent of the induction of PDK4 expression. The additive beneficial effects on hepatic steatosis may be due to induction of increased capacity for fatty acid oxidation and partial uncoupling of oxidative phosphorylation by clofibric acid and a reduction in the capacity for fatty acid synthesis by PDK4 deficiency. PMID:22429297

  10. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency.

    PubMed

    Roy, Marc; Leclerc, Daniel; Wu, Qing; Gupta, Sapna; Kruger, Warren D; Rozen, Rima

    2008-10-01

    Valproate (VPA) treatment in pregnancy leads to congenital anomalies, possibly by disrupting folate or homocysteine metabolism. Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine metabolism, we addressed the possibility that VPA might have different teratogenicity in Mthfr(+/+) and Mthfr(+/-) mice and that VPA might interfere with folate metabolism through MTHFR modulation. Mthfr(+/+) and Mthfr(+/-) pregnant mice were injected with VPA on gestational day 8.5; resorption rates and occurrence of neural tube defects (NTDs) were examined on gestational day 14.5. We also examined the effects of VPA on MTHFR expression in HepG2 cells and on MTHFR activity and homocysteine levels in mice. Mthfr(+/+) mice had increased resorption rates (36%) after VPA treatment, compared to saline treatment (10%), whereas resorption rates were similar in Mthfr(+/-) mice with the two treatments (25-27%). NTDs were only observed in one group (VPA-treated Mthfr(+/+)). In HepG2 cells, VPA increased MTHFR promoter activity and MTHFR mRNA and protein (2.5- and 3.7-fold, respectively). Consistent with cellular MTHFR upregulation by VPA, brain MTHFR enzyme activity was increased and plasma homocysteine was decreased in VPA-treated pregnant mice compared to saline-treated animals. These results underscore the importance of folate interconversion in VPA-induced teratogenicity, since VPA increases MTHFR expression and has lower teratogenic potential in MTHFR deficiency. PMID:18615588

  11. Pharmacokinetic comparison of ferulic acid in normal and blood deficiency rats after oral administration of Angelica sinensis, Ligusticum chuanxiong and their combination.

    PubMed

    Li, Weixia; Guo, Jianming; Tang, Yuping; Wang, Huan; Huang, Meiyan; Qian, Dawei; Duan, Jin-Ao

    2012-01-01

    Radix Angelica Sinensis (RAS) and Rhizome Ligusticum (RLC) combination is a popular herb pair commonly used in clinics for treatment of blood deficiency syndrome in China. The aim of this study is to compare the pharmacokinetic properties of ferulic acid (FA), a main bioactive constituent in both RAS and RLC, between normal and blood deficiency syndrome animals, and to investigate the influence of compatibility of RAS and RLC on the pharmacokinetic of FA. The blood deficiency rats were induced by injecting 2% Acetyl phenylhydrazine (APH) on the first day, every other day, to a total of five times, at the dosage of 100, 50, 50, 30, 30 mg/kg body mass, respectively. Quantification of FA in rat plasma was achieved by using a simple and rapid HPLC method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time, and estimate pharmacokinetic parameters. Between normal and blood deficiency model groups, both AUC((0-) (t) ()) and C(max) of FA in blood deficiency rats after RAS-RLC extract administration increased significantly (P < 0.05), while clearance (CL) decreased significantly. Among three blood deficiency model groups, t(1/2α), V(d), AUC((0-) (t) ()) and AUC((0-∞)) all increased significantly in the RAS-RLC extract group compared with the RAS group. The results indicated that FA was absorbed better and eliminated slower in blood deficiency rats; RLC could significantly prolong the half-life of distribution, increase the volume of distribution and the absorption amount of FA of RAS in blood deficiency rats, which may be due to the synergic action when RAS and RLC were used together to treat blood deficiency syndrome. PMID:22489169

  12. Growth and graviresponsiveness of primary roots of Zea mays seedlings deficient in abscisic acid and gibberellic acid

    NASA Technical Reports Server (NTRS)

    Moore, R.; Dickey, K.

    1985-01-01

    The objective of this research was to determine if gibberellic acid (GA) and/or abscisic acid (ABA) are necessary for graviresponsiveness by primary roots of Zea mays. To accomplish this objective we measured the growth and graviresponsiveness of primary roots of seedlings in which the synthesis of ABA and GA was inhibited collectively and individually by genetic and chemical means. Roots of seedlings treated with Fluridone (an inhibitor of ABA biosynthesis) and Ancymidol (an inhibitor of GA biosynthesis) were characterized by slower growth rates but not significantly different gravicultures as compared to untreated controls. Gravicurvatures of primary roots of d-5 mutants (having undetectable levels of GA) and vp-9 mutants (having undectable levels of ABA) were not significantly different from those of wild-type seedlings. Roots of seedlings in which the biosynthesis of ABA and GA was collectively inhibited were characterized by gravicurvatures not significantly different for those of controls. These results (1) indicate that drastic reductions in the amount of ABA and GA in Z. mays seedlings do not significantly alter root graviresponsiveness, (2) suggest that neither ABA nor GA is necessary for root gravicurvature, and (3) indicate that root gravicurvature is not necessarily proportional to root elongation.

  13. Root Carbon Dioxide Fixation by Phosphorus-Deficient Lupinus albus (Contribution to Organic Acid Exudation by Proteoid Roots).

    PubMed Central

    Johnson, J. F.; Allan, D. L.; Vance, C. P.; Weiblen, G.

    1996-01-01

    When white lupin (Lupinus albus L.) is subjected to P deficiency lateral root development is altered and densely clustered, tertiary lateral roots (proteoid roots) are initiated. These proteoid roots exude large amounts of citrate, which increases P solubilization. In the current study plants were grown with either 1 mM P (+P-treated) or without P (-P-treated). Shoots or roots of intact plants from both P treatments were labeled independently with 14CO2 to compare the relative contribution of C fixed in each with the C exuded from roots as citrate and other organic acids. About 25-fold more acid-stable 14C, primarily in citrate and malate, was recovered in exudates from the roots of -P-treated plants compared with +P-treated plants. The rate of in vivo C fixation in roots was about 4-fold higher in -P-treated plants than in +P-treated plants. Evidence from labeling intact shoots or roots indicates that synthesis of citrate exuded by -P-treated roots is directly related to nonphotosynthetic C fixation in roots. C fixed in roots of -P-treated plants contributed about 25 and 34% of the C exuded as citrate and malate, respectively. Nonphotosynthetic C fixation in white lupin roots is an integral component in the exudation of large amounts of citrate and malate, thus increasing the P available to the plant. PMID:12226371

  14. Impact of physiological levels of chenodeoxycholic acid supplementation on intestinal and hepatic bile acid and cholesterol metabolism in Cyp7a1-deficient mice

    PubMed Central

    Jones, Ryan D.; Lopez, Adam M.; Tong, Ernest Y.; Posey, Kenneth S.; Chuang, Jen-Chieh; Repa, Joyce J.; Turley, Stephen D.

    2014-01-01

    Mice deficient in cholesterol 7α-hydroxylase (Cyp7a1) have a diminished bile acid pool (BAP) and therefore represent a useful model for investigating the metabolic effects of restoring the pool with a specific BA. Previously we carried out such studies in Cyp7a1−/−mice fed physiological levels of cholic acid (CA) and achieved BAP restoration, along with an increased CA enrichment, at a dietary level of just 0.03% (w/w). Here we demonstrate that in Cyp7a1−/− mice fed chenodeoxycholic acid (CDCA) at a level of 0.06 % (w/w), the BAP was restored to normal size and became substantially enriched with muricholic acid (MCA)(>70%), leaving the combined contribution of CA and CDCA to be <15%. This resulted in a partial to complete reversal of the main changes in cholesterol and BA metabolism associated with Cyp7a1 deficiency such as an elevated rate of intestinal sterol synthesis, an enhanced level of mRNA for Cyp8b1 in the liver, and depressed mRNA levels for Ibabp, Shp and Fgf15 in the distal small intestine. When Cyp7a1−/− and matching Cyp7a1+/+ mice were fed a diet with added cholesterol (0.2%) (w/w), either alone, or also containing CDCA (0.06%) (w/w) or CA (0.03%) (w/w) for 18 days, the hepatic total cholesterol concentrations (mg/g) in the Cyp7a1−/− mice were 26.9±3.7, 16.4±0.9 and 47.6±1.9, respectively, vs 4.9±0.4, 5.0±0.7 and 6.4±1.9, respectively in the corresponding Cyp7a1+/+ controls. These data affirm the importance of using moderate levels of dietary BA supplementation to elicit changes in hepatic cholesterol metabolism through shifts in BAP size and composition. PMID:25447797

  15. Comparative effects of wild type Stenotrophomonas maltophilia and its indole acetic acid-deficient mutants on wheat.

    PubMed

    Hassan, T U; Bano, A

    2016-09-01

    The present investigation evaluated the role of Stenotrophomonas maltophilia and its IAA-deficient mutant on soil health and plant growth under salinity stress in the presence of tryptophan. In the first phase, S. maltophilia isolated from roots of the halo- phytic herb, Cenchrus ciliaris was used as bio-inoculant on wheat grown in saline sodic soil. A field experiment was conducted at Soil Salinity Research Institute during 2010-2011. Treatments included seed inoculation with S. maltophilia with or without tryptophan; uninoculated untreated plants were taken as control. An aqueous solution of tryptophan was added to rhizosphere soil at 1 μg l(_1) after seed germination. Inoculation with S. maltophilia significantly increased soil organic matter, enhanced (20-30%) availability of P, K, Ca and NO3 -N and decreased Na content and electrical conductivity of rhizosphere soil. Plant height, fresh weight, proline and phytohormone content of leaves were increased 30-40% over the control. Activities of superoxide dismutase (SOD) and peroxidase (POD) were 40-50% higher than control. Addition of tryptophan further augmented (10-15%) growth parameters, whereas NO3 -N, P, K and Ca content, proline content and SOD and POD increased 20-30%. In a second phase, indoleacetic acid (IAA)-deficient mutants of S. maltophilia were constructed and evaluated for conversion of tryptophan to IAA at the University of Calgary, Canada, during 2013-2014. About 1800 trans-conjugants were constructed that were unable to produce IAA in the presence of tryptophan. The results suggest that tryptophan assisted S. maltophilia in the amelioration of salt stress, and that IAA played positive role in induction of salt tolerance. PMID:27263526

  16. The Effects of α-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine–Choline Deficient Diet-Induced NAFLD

    PubMed Central

    Stanković, Milena N.; Mladenović, Dušan; Ninković, Milica; Ðuričić, Ivana; Šobajić, Slađana; Jorgačević, Bojan; de Luka, Silvio; Vukicevic, Rada Jesic

    2014-01-01

    Abstract Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of α-lipoic acid (LA) on methionine–choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 group—fed with MCD diet for 2 weeks, and (3) MCD2+LA group—2 weeks on MCD receiving LA i.p. 100 mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD. PMID:24325457

  17. Effects of essential amino acid deficiency: down-regulation of KCC2 and the GABAA receptor; disinhibition in the anterior piriform cortex.

    PubMed

    Sharp, James W; Ross-Inta, Catherine M; Baccelli, Irène; Payne, John A; Rudell, John B; Gietzen, Dorothy W

    2013-11-01

    The anterior piriform cortex (APC) is activated by, and is the brain area most sensitive to, essential (indispensable) amino acid (IAA) deficiency. The APC is required for the rapid (20 min) behavioral rejection of IAA deficient diets and increased foraging, both crucial adaptive functions supporting IAA homeostasis in omnivores. The biochemical mechanisms signaling IAA deficiency in the APC block initiation of translation in protein synthesis via uncharged tRNA and the general amino acid control kinase, general control nonderepressing kinase 2. Yet, how inhibition of protein synthesis activates the APC is unknown. The neuronal K(+) Cl(-) cotransporter, neural potassium chloride co-transporter (KCC2), and GABAA receptors are essential inhibitory elements in the APC with short plasmalemmal half-lives that maintain control in this highly excitable circuitry. After a single IAA deficient meal both proteins were reduced (vs. basal diet controls) in western blots of APC (but not neocortex or cerebellum) and in immunohistochemistry of APC. Furthermore, electrophysiological analyses support loss of inhibitory elements such as the GABAA receptor in this model. As the crucial inhibitory function of the GABAA receptor depends on KCC2 and the Cl(-) transmembrane gradient it establishes, these results suggest that loss of such inhibitory elements contributes to disinhibition of the APC in IAA deficiency. The circuitry of the anterior piriform cortex (APC) is finely balanced between excitatory (glutamate, +) and inhibitory (GABA, -) transmission. GABAA receptors use Cl(-), requiring the neural potassium chloride co-transporter (KCC2). Both are rapidly turning-over proteins, dependent on protein synthesis for repletion. In IAA (indispensable amino acid) deficiency, within 20 min, blockade of protein synthesis prevents restoration of these inhibitors; they are diminished; disinhibition ensues. GCN2 = general control non-derepressing kinase 2, eIF2α = α-subunit of the eukaryotic

  18. Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency

    PubMed Central

    Schiff, Manuel; Haberberger, Birgit; Xia, Chuanwu; Mohsen, Al-Walid; Goetzman, Eric S.; Wang, Yudong; Uppala, Radha; Zhang, Yuxun; Karunanidhi, Anuradha; Prabhu, Dolly; Alharbi, Hana; Prochownik, Edward V.; Haack, Tobias; Häberle, Johannes; Munnich, Arnold; Rötig, Agnes; Taylor, Robert W.; Nicholls, Robert D.; Kim, Jung-Ja; Prokisch, Holger; Vockley, Jerry

    2015-01-01

    Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fatty acids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fatty acid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fatty acid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fatty acid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunctions. PMID:25721401

  19. Vanillic acid prevents the deregulation of lipid metabolism, endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats.

    PubMed

    Kumar, Subramanian; Prahalathan, Pichavaram; Saravanakumar, Murugesan; Raja, Boobalan

    2014-11-15

    Hypertension is one of the main factors causing cardiovascular diseases. The present study was designed to evaluate the protective effect of vanillic acid against nitric oxide deficient rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220g, by oral administration of N(ω)-nitro-l arginine methyl ester (l-NAME) 40mg/kg in drinking water for 4 weeks. Vanillic acid was administered orally at a dose of 50mg/kg b.w. Nitric oxide deficient rats showed increased levels of mean arterial pressure (MAP), heart rate (HR) and decreased heart nitric oxide metabolites (NOx). A significant increase in the levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase in the plasma, liver and kidney and decreased level of high density lipoprotein-cholesterol (HDL-C) are observed, whereas there is a decrease in the activities of plasma lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) in nitric oxide deficient rats. l-NAME rats also showed an increase in TC, TG, FFA and PL levels in the liver and kidney tissues. Vanillic acid treatment brought the above parameters towards near normal level. Moreover the down regulated endothelial nitric oxide synthase (eNOS) and up regulated expression of endothelin 1 (ET1) components was also attenuated by vanillic acid treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that vanillic acid has enough potential to attenuate hypertension, dyslipidemia and hepatic and renal damage in nitric oxide deficient rats. PMID:25239071

  20. Acid Sphingomyelinase Gene Deficiency Ameliorates the Hyperhomocysteinemia-Induced Glomerular Injury in Mice

    PubMed Central

    Boini, Krishna M.; Xia, Min; Li, Caixia; Zhang, Chun; Payne, Lori P.; Abais, Justine M.; Poklis, Justin L.; Hylemon, Philip B.; Li, Pin-Lan

    2011-01-01

    Hyperhomocysteinemia (hHcys) enhances ceramide production, leading to the activation of NADPH oxidase and consequent glomerular oxidative stress and sclerosis. The present study was performed to determine whether acid sphingomyelinase (Asm), a ceramide-producing enzyme, is implicated in the development of hHcys-induced glomerular oxidative stress and injury. Uninephrectomized Asm-knockout (Asm−/−) and wild-type (Asm+/+) mice, with or without Asm short hairpin RNA (shRNA) transfection, were fed a folate-free (FF) diet for 8 weeks, which significantly elevated the plasma Hcys level compared with mice fed normal chow. By using in vivo molecular imaging, we found that transfected shRNAs were expressed in the renal cortex starting on day 3 and continued for 24 days. The FF diet significantly increased renal ceramide production, Asm mRNA and activity, urinary total protein and albumin excretion, glomerular damage index, and NADPH-dependent superoxide production in the renal cortex from Asm+/+ mice compared with that from Asm−/− or Asm shRNA-transfected wild-type mice. Immunofluorescence analysis showed that the FF diet decreased the expression of podocin but increased desmin and ceramide levels in glomeruli from Asm+/+ mice but not in those from Asm−/− and Asm shRNA-transfected wild-type mice. In conclusion, our observations reveal that Asm plays a pivotal role in mediating podocyte injury and glomerular sclerosis associated with NADPH oxidase–associated local oxidative stress during hHcys. PMID:21893018

  1. Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives.

    PubMed

    Pritchard, J A; Scott, D E; Whalley, P J

    1971-02-01

    A group of studies on indigent hospital patients were conducted on the role of folate supplements, pregnancy and oral contraceptives in megaloblastic anemia. First 25 pregnant women, given 500 mg iron dextran and 30 mg folic acid for 2-3 months, had 12.4% hemoglogin at delivery, compared with 49 women given only iron who had 12.5% hemoglobin, and 49 untreated women who had 11.3% hemoglobin. Second, plasma folate levels in groups of pregnant women were compared: mean folate was 4.7 ng/ml in 82 normal women, 3.1 in 21 treated epileptics, and about 1.2 in 31 women with megaloblastic anemia. In 77 pregnancies in 43 epileptic women there were no reasons to blame low folate levels for pregnancy wastage since no abruptio placentae or bleeding occurred; and incidence of low birth weight, perinatal death, and prematurity was lower than in the general population. Third, the effect of oral contraceptives on folate levels was observed. Mean plasma folate levels were 8.1 ng/ml in 55 control women, 8.0 in 57 women using the pill, 4.7 in normal women in late pregnancy, and about 1.1 in pregnant women with megaloblastic anemia. Fourth, mean hemoglobin levels rose from 7.6 to 13.4 9m/100 ml within a few weeks in 5 women with gestational megaloblastic anemia after treatment with normal diet, without supplement, and oral contraceptives. One woman with puerperal megaloblastic anemia failed to respond to a regular diet while taking Ovulen, 6 tablets daily. The results suggest that plasma folate levels were neither lower in oral contracepting women nor did the pill prevent the increase in folate in megaloblastic anemia patients treated with diet. Thus the authors concluded that folate supplement is not needed for pill users. PMID:5549181

  2. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

    PubMed

    Konuma, Kuniha; Itoh, Michiko; Suganami, Takayoshi; Kanai, Sayaka; Nakagawa, Nobutaka; Sakai, Takeru; Kawano, Hiroyuki; Hara, Mitsuko; Kojima, Soichi; Izumi, Yuichi; Ogawa, Yoshihiro

    2015-01-01

    Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.

  3. The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome.

    PubMed

    Kanabus, Marta; Fassone, Elisa; Hughes, Sean David; Bilooei, Sara Farahi; Rutherford, Tricia; Donnell, Maura O'; Heales, Simon J R; Rahman, Shamima

    2016-05-01

    There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis. The effects of C10 were investigated in primary fibroblasts from a cohort of patients with Leigh syndrome (LS) caused by nuclear-encoded defects of respiratory chain complex I, using mitochondrial respiratory chain enzyme assays, gene expression microarray, qPCR and flow cytometry. Treatment with C10 increased citrate synthase activity, a marker of cellular mitochondrial content, in 50 % of fibroblasts obtained from individuals diagnosed with LS in a PPAR-γ-mediated manner. Gene expression analysis and qPCR studies suggested that treating cells with C10 supports fatty acid metabolism, through increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism (PDK3, PDK4). PCK2, involved in blocking glucose metabolism, was upregulated, as was CAT, encoding catalase. Moreover, treatment with C10 also decreased oxidative stress in complex I deficient (rotenone treated) cells. However, since not all cells from subjects with LS appeared to respond to C10, prior cellular testing in vitro could be employed as a means for selecting individuals for subsequent clinical studies involving C10 preparations. PMID:27080638

  4. Investigation of trimethylacetic acid adsorption on stoichiometric and oxygen-deficient CeO2(111) surfaces.

    PubMed

    Sanghavi, Shail; Wang, Weina; Nandasiri, Manjula I; Karakoti, Ajay S; Wang, Wenliang; Yang, Ping; Thevuthasan, S

    2016-06-21

    We studied the interactions between the carboxylate anchoring group from trimethylacetic acid (TMAA) and CeO2(111) surfaces as a function of oxygen stoichiometry using in situ X-ray photoelectron spectroscopy (XPS). The stoichiometric CeO2(111) surface was obtained by annealing the thin film under 2.0 × 10(-5) Torr of oxygen at ∼550 °C for 30 min. In order to reduce the CeO2(111) surface, the thin film was annealed under ∼5.0 × 10(-10) Torr vacuum conditions at 550 °C, 650 °C, 750 °C and 850 °C for 30 min to progressively increase the oxygen defect concentration on the surface. The saturated TMAA coverage on the CeO2(111) surface determined from XPS elemental composition is found to increase with increasing oxygen defect concentration. This is attributed to the increase of under-coordinated cerium sites on the surface with the increase in the oxygen defect concentrations. XPS results were in agreement with periodic density functional theory (DFT) calculations and indicate a stronger binding between the carboxylate group from TMAA and the oxygen deficient CeO2-δ(111) surface through dissociative adsorption.

  5. Melatonin enhances cold tolerance in drought-primed wild-type and abscisic acid-deficient mutant barley.

    PubMed

    Li, Xiangnan; Tan, Dun-Xian; Jiang, Dong; Liu, Fulai

    2016-10-01

    Melatonin is involved in multiple plant developmental processes and various stress responses. To explore the roles of melatonin played as well as its association with abscisic acid (ABA) in a process of drought priming-induced cold tolerance (DPICT), a wild-type barley and its ABA-deficient mutant Az34 counterpart were selected for comparison, in which the effects of melatonin application (either foliarly or rhizospherically) and/or drought priming on the cold tolerance of both types of barleys were systematically investigated. It was demonstrated that the early drought priming induced an increase of endogenous melatonin production, which is not ABA dependent. In addition, exogenously applied melatonin resulted in higher ABA concentration in the drought-primed plants than in the nonprimed plants when exposed to cold stress, indicating that ABA responded in a drought-dependent manner. The interplay of melatonin and ABA leads to plants maintaining better water status. Drought priming-induced melatonin accumulation enhanced the antioxidant capacity in both chloroplasts and mitochondria, which sustained the photosynthetic electron transport in photosynthetic apparatus of the plants under cold stress. These results suggest that the exogenous melatonin application enhances the DPICT by modulating subcellular antioxidant systems and ABA levels in barley. PMID:27299847

  6. Investigation of trimethylacetic acid adsorption on stoichiometric and oxygen-deficient CeO2 (111) surfaces

    DOE PAGES

    Sanghavi, Shail; Wang, Weina; Nandasiri, Manjula I.; Karakoti, Ajay S.; Wang, Wenliang; Yang, Ping; Thevuthasan, S.

    2016-05-12

    We studied the interactions between the carboxylate anchoring group from trimethylacetic acid (TMAA) and CeO2(111) surfaces as a function of oxygen stoichiometry using in situ X-ray photoelectron spectroscopy (XPS). The stoichiometric CeO2(111) surface was obtained by annealing the thin film under 2.0 × 10–5 Torr of oxygen at ~550 °C for 30 min. In order to reduce the CeO2(111) surface, the thin film was annealed under ~5.0 × 10–10 Torr vacuum conditions at 550 °C, 650 °C, 750 °C and 850 °C for 30 min to progressively increase the oxygen defect concentration on the surface. The saturated TMAA coverage onmore » the CeO2(111) surface determined from XPS elemental composition is found to increase with increasing oxygen defect concentration. This is attributed to the increase of under-coordinated cerium sites on the surface with the increase in the oxygen defect concentrations. Furthermore, XPS results were in agreement with periodic density functional theory (DFT) calculations and indicate a stronger binding between the carboxylate group from TMAA and the oxygen deficient CeO2–δ(111) surface through dissociative adsorption.« less

  7. Normalizing Microbiota-Induced Retinoic Acid Deficiency Stimulates Protective CD8(+) T Cell-Mediated Immunity in Colorectal Cancer.

    PubMed

    Bhattacharya, Nupur; Yuan, Robert; Prestwood, Tyler R; Penny, Hweixian Leong; DiMaio, Michael A; Reticker-Flynn, Nathan E; Krois, Charles R; Kenkel, Justin A; Pham, Tho D; Carmi, Yaron; Tolentino, Lorna; Choi, Okmi; Hulett, Reyna; Wang, Jinshan; Winer, Daniel A; Napoli, Joseph L; Engleman, Edgar G

    2016-09-20

    Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC.

  8. Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice.

    PubMed

    Reardon, Catherine A; Blachowicz, Lydia; Gupta, Gaorav; Lukens, John; Nissenbaum, Michael; Getz, Godfrey S

    2006-08-01

    Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.

  9. Normalizing Microbiota-Induced Retinoic Acid Deficiency Stimulates Protective CD8(+) T Cell-Mediated Immunity in Colorectal Cancer.

    PubMed

    Bhattacharya, Nupur; Yuan, Robert; Prestwood, Tyler R; Penny, Hweixian Leong; DiMaio, Michael A; Reticker-Flynn, Nathan E; Krois, Charles R; Kenkel, Justin A; Pham, Tho D; Carmi, Yaron; Tolentino, Lorna; Choi, Okmi; Hulett, Reyna; Wang, Jinshan; Winer, Daniel A; Napoli, Joseph L; Engleman, Edgar G

    2016-09-20

    Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC. PMID:27590114

  10. Graviresponsiveness and abscisic-acid content of roots of carotenoid-deficient mutants of Zea mays L

    NASA Technical Reports Server (NTRS)

    Moore, R.; Smith, J. D.

    1985-01-01

    The abscisic-acid (ABA) content of roots of the carotenoid-deficient w-3, vp-5, and vp-7 mutants of Z. mays was analyzed using gas chromatography-mass spectrometry with an analysis sensitivity of 6 ng ABA g-1 fresh weight (FW). Roots of normal seedlings of the same lines were characterized by the following amounts of ABA (as ng ABA g-1 FW, +/- standard deviation): w-3, 279 +/- 43; vp-5, 237 +/- 26; vp-7, 338 +/- 61. We did not detect any ABA in roots of any of the mutants. Thus, the lack of carotenoids in these mutants correlated positively with the apparent absence of ABA. Primary roots of normal and mutant seedlings were positively gravitropic, with no significant differences in the curvatures of roots of normal as compared with mutant seedlings. These results indicate that ABA 1) is synthesized in maize roots via the carotenoid pathway, and 2) is not necessary for positive gravitropism by primary roots of Z. mays.

  11. Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction.

    PubMed

    Zhou, Mi; Bao, Yuqian; Li, Haobo; Pan, Yong; Shu, Lingling; Xia, Zhengyuan; Wu, Donghai; Lam, Karen S L; Vanhoutte, Paul M; Xu, Aimin; Jia, Weiping; Hoo, Ruby L-C

    2015-10-01

    Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.

  12. Characterization of heme-deficient neuronal nitric-oxide synthase reveals a role for heme in subunit dimerization and binding of the amino acid substrate and tetrahydrobiopterin.

    PubMed

    Klatt, P; Pfeiffer, S; List, B M; Lehner, D; Glatter, O; Bächinger, H P; Werner, E R; Schmidt, K; Mayer, B

    1996-03-29

    Neuronal nitric-oxide (NO) synthase contains FAD, FMN, heme, and tetrahydrobiopterin as prosthetic groups and represents a multifunctional oxidoreductase catalyzing oxidation of L-arginine to L-citrulline and NO, reduction of molecular oxygen to superoxide, and electron transfer to cytochromes. To investigate how binding of the prosthetic heme moiety is related to enzyme activities, cofactor, and L-arginine binding, as well as to secondary and quaternary protein structure, we have purified and characterized heme-deficient neuronal NO synthase. The heme-deficient enzyme, which had preserved its cytochrome c reductase activity, contained FAD and FMN, but virtually no tetrahydrobiopterin, and exhibited only marginal NO synthase activity. By means of gel filtration and static light scattering, we demonstrate that the heme-deficient enzyme is a monomer and provide evidence that heme is the sole prosthetic group controlling the quaternary structure of neuronal NO synthase. CD spectroscopy showed that most of the structural elements found in the dimeric holoenzyme were conserved in heme-deficient monomeric NO synthase. However, in spite of being properly folded, the heme-deficient enzyme did bind neither tetrahydrobiopterin nor the substrate analog N(G)-nitro-L-arginine. Our results demonstrate that the prosthetic heme group of neuronal NO synthase is requisite for dimerization of enzyme subunits and for the binding of amino acid substrate and tetrahydrobiopterin.

  13. Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

    PubMed

    Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

    2016-02-01

    Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD.

  14. Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

    PubMed

    Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

    2016-02-01

    Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. PMID:26683372

  15. Effects of hardness and alkalinity on the removal of arsenic(V) from humic acid-deficient and humic acid-rich groundwater by zero-valent iron.

    PubMed

    Mak, Mark S H; Rao, Pinhua; Lo, Irene M C

    2009-09-01

    The effects of hardness (Ca(2+)) and alkalinity (HCO(3)(-)) on arsenic(V) removal from humic acid (HA)-deficient and HA-rich groundwater by zero-valent iron (Fe(0)) were investigated using batch experiments. Arsenic, in general, is removed from groundwater possibly by adsorption and co-precipitation with the iron corrosion products. However, in the co-presence of HCO(3)(-) and Ca(2+), the removal rate of arsenic increased with increasing concentrations of either Ca(2+) or HCO(3)(-). It was observed that the removal of arsenic was significantly enhanced by the formation of CaCO(3) as a nucleation seed for the growth of large iron (hydr)oxide particles. In the co-existence of Ca(2+), HCO(3)(-) and HA, the presence of HA diminished the positive role of Ca(2+) due to the formation of Fe-humate complexes in solution and delaying of the formation of CaCO(3). As a result, the formation of the large iron (hydr)oxide particles was inhibited in the earlier stage which, in turn, affected the removal of arsenic. However, after the formation of CaCO(3) and the subsequent growth of such particles, the presence of large iron (hydr)oxide particles resulted in the rapid removing of arsenic and Fe-humate by adsorption and/or co-precipitation.

  16. Mass Spectrometric Confirmation of γ-Linolenic Acid Ester-Linked Ceramide 1 in the Epidermis of Borage Oil Fed Guinea Pigs.

    PubMed

    Shin, Kyong-Oh; Kim, Kunpyo; Jeon, Sanghun; Seo, Cho-Hee; Lee, Yong-Moon; Cho, Yunhi

    2015-10-01

    Ceramide 1 (Cer1), a Cer species with eicosasphingenine (d20:1) amide-linked to two different ω-hydroxy fatty acids (C30wh:0:C32wh:1), which are, in turn, ester-linked to linoleic acid (LNA; 18:2n-6), plays a critical role in maintaining the structural integrity of the epidermal barrier. Prompted by the recovery of a disrupted epidermal barrier with dietary borage oil [BO: 36.5% LNA and 23.5% γ-linolenic acid (GLA; 18:3n-6)], in essential fatty acid (EFA)-deficient guinea pigs, we further investigated the effects of BO on the substitution of ester-linked GLA for LNA in these two epidermal Cer1 species by LC-MS in positive and negative modes. Dietary supplementation of BO for 2 weeks in EFA-deficient guinea pigs increased LNA ester-linked to C32wh:1/d20:1 and C30wh:0/d20:1 of Cer1. Moreover, GLA ester-linked to C32wh:1/d20:1, but not to C30wh:0/d20:1, of Cer1 was detected, which was further confirmed by the product ions of m/z 277.2 for ester-linked GLA and m/z 802.3 for the deprotonated C32wh:1/d20:1. C20-Metabolized fatty acids of LNA or GLA were not ester-linked to these Cer1 species. Dietary BO induced GLA ester-linked to C32wh:1/d20:1 of epidermal Cer1. PMID:26233818

  17. Mass Spectrometric Confirmation of γ-Linolenic Acid Ester-Linked Ceramide 1 in the Epidermis of Borage Oil Fed Guinea Pigs.

    PubMed

    Shin, Kyong-Oh; Kim, Kunpyo; Jeon, Sanghun; Seo, Cho-Hee; Lee, Yong-Moon; Cho, Yunhi

    2015-10-01

    Ceramide 1 (Cer1), a Cer species with eicosasphingenine (d20:1) amide-linked to two different ω-hydroxy fatty acids (C30wh:0:C32wh:1), which are, in turn, ester-linked to linoleic acid (LNA; 18:2n-6), plays a critical role in maintaining the structural integrity of the epidermal barrier. Prompted by the recovery of a disrupted epidermal barrier with dietary borage oil [BO: 36.5% LNA and 23.5% γ-linolenic acid (GLA; 18:3n-6)], in essential fatty acid (EFA)-deficient guinea pigs, we further investigated the effects of BO on the substitution of ester-linked GLA for LNA in these two epidermal Cer1 species by LC-MS in positive and negative modes. Dietary supplementation of BO for 2 weeks in EFA-deficient guinea pigs increased LNA ester-linked to C32wh:1/d20:1 and C30wh:0/d20:1 of Cer1. Moreover, GLA ester-linked to C32wh:1/d20:1, but not to C30wh:0/d20:1, of Cer1 was detected, which was further confirmed by the product ions of m/z 277.2 for ester-linked GLA and m/z 802.3 for the deprotonated C32wh:1/d20:1. C20-Metabolized fatty acids of LNA or GLA were not ester-linked to these Cer1 species. Dietary BO induced GLA ester-linked to C32wh:1/d20:1 of epidermal Cer1.

  18. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia.

  19. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids.

    PubMed

    Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana

    2014-01-01

    Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPARα and PPARγ but reduced (p<0.05) SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the

  20. Children, Education and War: Reaching Education for All (EFA) Objectives in Countries Affected by Conflict. Conflict Prevention and Reconstruction Unit Working Paper.

    ERIC Educational Resources Information Center

    Sommers, Marc

    Conflict's path of devastation and chaos has dramatically slowed the ability of war-torn countries to reach the Education for All (EFA) goals adopted in Dakar (April 2000). This paper describes the situation confronting children, their families, and governments in conflict countries and describes the challenges of reaching universal primary…

  1. Determining the Number of Factors to Retain in EFA: Using the SPSS R-Menu v2.0 to Make More Judicious Estimations

    ERIC Educational Resources Information Center

    Courtney, Matthew Gordon Ray

    2013-01-01

    Exploratory factor analysis (EFA) is a common technique utilized in the development of assessment instruments. The key question when performing this procedure is how to best estimate the number of factors to retain. This is especially important as under- or over-extraction may lead to erroneous conclusions. Although recent advancements have been…

  2. Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice.

    PubMed

    Fujii, Masanori; Nakashima, Hiroyuki; Tomozawa, Junko; Shimazaki, Yuki; Ohyanagi, Chie; Kawaguchi, Naomi; Ohya, Susumu; Kohno, Shigekatsu; Nabe, Takeshi

    2013-04-01

    Hairless mice fed a special diet, HR-AD, develop atopic dermatitis (AD)-like skin inflammation with skin barrier defects and itch-related scratching; however, the ingredient(s) causing the dermatitis remains unclear. In this study, we examined whether deficiency of certain polyunsaturated fatty acids (PUFAs) is involved in HR-AD-induced AD. High-purity PUFAs were given to HR-AD-fed mice by dietary supplementation or gavage. Fatty acid levels in the serum and skin were determined by using gas chromatography-mass spectrometry. In serum from HR-AD-fed mice, linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. When mice were fed HR-AD supplemented with LA or ALA in an amount equal to that contained in a normal diet, the development of AD-like symptoms was completely prevented by supplementation with LA but not with ALA. Relatively high dose of ALA slightly alleviated skin barrier defects, but did neither itch-related scratching nor skin inflammation. On the other hand, gavage administration of LA metabolites, such as γ-linolenic acid and arachidonic acid (AA), significantly ameliorated established dermatitis without increasing LA in the serum and skin. Moreover, AA-induced amelioration of dermatitis was not affected by pharmacological blockade of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX), suggesting no involvement of 5-LOX- or COX-mediated AA metabolites in the amelioration. In conclusion, our results indicate that deficiency of n-6 PUFAs is mainly responsible for AD-like symptoms by HR-AD feeding. Thus, this model could be useful for studying the pathomechanisms associated with deficiency of n-6 PUFAs in AD.

  3. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency.

    PubMed

    Thurberg, Beth L; Wasserstein, Melissa P; Jones, Simon A; Schiano, Thomas D; Cox, Gerald F; Puga, Ana Cristina

    2016-09-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  4. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Schiano, Thomas D.; Cox, Gerald F.; Puga, Ana Cristina

    2016-01-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  5. Iodine plus n-3 fatty acid supplementation augments rescue of postnatal neuronal abnormalities in iodine-deficient rat cerebellum.

    PubMed

    Pal, Amit; Mohan, Vishwa; Modi, Dinesh R; Sinha, Rohit A; Rastogi, Leena; Kumar, Praveen; Godbole, Madan M

    2013-08-01

    High prevalence of hypothyroxinaemia in iodine-deficient (ID) mothers has serious implications for mental health of the progeny. Independent supplementation of iodine and n-3 fatty acids (FA) markedly improves growth and cognitive performance of school children. Discerning effects of n-3 FA and iodine on the developing cerebellum have not been ascertained. The present study investigates effects of these two micronutrients separately as well as together in an ID rat model. We studied the effects of these micronutrients on progeny of ID dams by instituting the following supplementation diets: (1) low-iodine diet (LID), (2) LID+potassium iodide (KI), (3) LID+n-3 FA and (4) LID+KI+n-3 FA. Pups were investigated for morphological and biochemical parameters at the peak of cerebellar histogenesis on postnatal day (P) 16 and for neurobehavioural as well as motor coordination parameters at P40. Results indicate that n-3 FA alone, without improvement in circulating thyroid hormone (TH), significantly improves functional, morphological and biochemical indices of the developing cerebellum. Further, results show that co-supplementation with iodine and n-3 FA rescues not only the loss of neurotrophic support, but also salvages motor coordination, memory and learning. This additive effect results in significantly improving neurotrophic support and seems to be mediated by parallel significant increase in TH receptor (TR)α and normalisation of TRβ, retinoic orphan receptor α and p75 neurotrophin receptor, as well as noteworthy prevention of apoptotic cell death and strengthening of anti-oxidative defence. The overall results indicate important mitigating role that n-3 FA may play in enhancing TH nuclear receptor-mediated signalling in the developing cerebellum. PMID:23312094

  6. Occurrence of cleft-palate and alteration of Tgf-β(3) expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency.

    PubMed

    Maldonado, Estela; Murillo, Jorge; Barrio, Carmen; del Río, Aurora; Pérez-Miguelsanz, Juliana; López-Gordillo, Yamila; Partearroyo, Teresa; Paradas, Irene; Maestro, Carmen; Martínez-Sanz, Elena; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción

    2011-01-01

    Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2-8 weeks' induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks' maternal FA deficiency caused complete CP in the fetuses although a 2 weeks' maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor-β(3) (TGF-β(3)) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β(3)null mutant mice, we investigated the presence of TGF-β(3) mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β(3) expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β(3) expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of TGF-β(3) to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous TGF-β(3) compensates this deficit in vitro.

  7. Structure and lipid distribution of polyenoic very-long-chain fatty acids in the brain of peroxisome-deficient patients (Zellweger syndrome).

    PubMed Central

    Sharp, P; Poulos, A; Fellenberg, A; Johnson, D

    1987-01-01

    The polyenoic fatty acids with carbon chain lengths from 26 to 38 (very-long-chain fatty acids, VLCFA) previously detected in abnormal amounts in Zellweger syndrome brain have been shown to be n-6 derivatives and therefore probably derived by chain elongation of shorter-chain n-6 fatty acids such as linoleic acid and arachidonic acid. Polyenoic VLCFA are also present in Zellweger syndrome liver, but this tissue differs significantly from brain in that the saturated and mono-unsaturated derivatives are the major VLCFA. Zellweger syndrome brain polyenoic VLCFA are present in the neutral lipids predominantly in cholesterol esters, with smaller amounts in the non-esterified fatty acid and triacylglycerol fractions. These fatty acids are barely detectable in any of the major phospholipids, but are present in significant amounts in an unidentified minor phospholipid. The polyenoic VLCFA composition of this lipid differs markedly from that observed for all other lipids, as it contains high proportions of pentaenoic and hexaenoic fatty acids with 34, 36 and 38 carbon atoms. A polar lipid with the chromatographic properties in normal brain contains similar fatty acids. It is postulated that the polyenoic VLCFA may play an important role in normal brain and accumulate in Zellweger syndrome brain because of a deficiency in the peroxisomal beta-oxidation pathway, although a possible peroxisomal role in the control of carbon-chain elongation cannot be discounted. PMID:3435449

  8. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

    PubMed

    Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

    2015-11-01

    An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing.

  9. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

    PubMed

    Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

    2015-11-01

    An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. PMID:26284828

  10. Seed storage protein deficiency improves sulfur amino acid content in common bean (Phaseolus vulgaris L.): redirection of sulfur from gamma-glutamyl-S-methyl-cysteine.

    PubMed

    Taylor, Meghan; Chapman, Ralph; Beyaert, Ronald; Hernández-Sebastià, Cinta; Marsolais, Frédéric

    2008-07-23

    The contents of sulfur amino acids in seeds of common bean ( Phaseolus vulgaris L.) are suboptimal for nutrition. They accumulate large amounts of a gamma-glutamyl dipeptide of S-methyl-cysteine, a nonprotein amino acid that cannot substitute for methionine or cysteine in the diet. Protein accumulation and amino acid composition were characterized in three genetically related lines integrating a progressive deficiency in major seed storage proteins, phaseolin, phytohemagglutinin, and arcelin. Nitrogen, carbon, and sulfur contents were comparable among the three lines. The contents of S-methyl-cysteine and gamma-glutamyl-S-methyl-cysteine were progressively reduced in the mutants. Sulfur was shifted predominantly to the protein cysteine pool, while total methionine was only slightly elevated. Methionine and cystine contents (mg per g protein) were increased by up to ca. 40%, to levels slightly above FAO guidelines on amino acid requirements for human nutrition. These findings may be useful to improve the nutritional quality of common bean. PMID:18588315

  11. Effects of dietary deficiency of selective amino acids on the function of the cornea and lens in rats.

    PubMed

    Wegener, A; Golubnitschaja, O; Breipohl, W; Schild, H H; Vrensen, G F J M

    2002-01-01

    Effects of dietary deficiencies of tryptophan and methionin on the transparency of cornea and lens were investigated in young rats (Brown-Norway, BN; Sprague-Dawley, SD) over 3 months. Transparency of the cornea and lens were evaluated in weekly intervals using a photo-slitlamp microscope. After sacrifice and lens fresh weight determination the lenses were prepared for histopathology. Methionin deficiency had no effect on the parameters investigated. Tryptophan deficiency caused severe loss of body weight in both strains, with additional loss of hair in SD rats. These developed corneal neovascularisations and cataracts. BN rats showed an enhanced zone of discontinuity in the lens. Diet intermission arrested the pathological processes in the eye which restarted when feeding the diet again. This observation is supported by lens fresh weight data. DNA staining evidenced that tryptophan deficiency arrested lens fiber maturation in both strains but stimulated corneal neovascularisation only in SD rats.

  12. D-lactic acid production from cellooligosaccharides and beta-glucan using L-LDH gene-deficient and endoglucanase-secreting Lactobacillus plantarum.

    PubMed

    Okano, Kenji; Zhang, Qiao; Yoshida, Shogo; Tanaka, Tsutomu; Ogino, Chiaki; Fukuda, Hideki; Kondo, Akihiko

    2010-01-01

    In order to achieve direct fermentation of an optically pure D: -lactic acid from cellulosic materials, an endoglucanase from a Clostridium thermocellum (CelA)-secreting plasmid was introduced into an L: -lactate dehydrogenase gene (ldhL1)-deficient Lactobacillus plantarum (ldhL1) bacterial strain. CelA expression and its degradation of beta-glucan was confirmed by western blot analysis and enzyme assay, respectively. Although the CelA-secreting ldhL1 assimilated cellooligosaccharides up to cellohexaose (although not cellotetraose), the main end product was acetic acid, not lactic acid, due to the conversion of lactic acid to acetic acid. Cultivation under anaerobic conditions partially suppressed this conversion resulting in the production of 1.27 g/l of D: -lactic acid with a high optical purity of 99.5% from a medium containing 2 g/l of cellohexaose. Subsequently, D: -lactic acid fermentation from barley beta-glucan was carried out with the addition of Aspergillus aculeatus beta-glucosidase produced by recombinant Aspergillus oryzae and 1.47 g/l of D: -lactic was produced with a high optical purity of 99.7%. This is the first report of direct lactic acid fermentation from beta-glucan and a cellooligosaccharide that is a more highly polymerized sugar than cellotriose.

  13. Effects of phosphate deficiency and sugars on expression of rab18 in Arabidopsis: hexokinase-dependent and okadaic acid-sensitive transduction of the sugar signal.

    PubMed

    Ciereszko, Iwona; Kleczkowski, Leszek A

    2002-11-13

    The lack of phosphorus in the nutrient medium increased the expression of rab18, an abscisic acid (ABA)-responsive gene, in leaves of Arabidopsis thaliana. The expression of this gene was also upregulated after feeding the excised leaves with D-mannose and sucrose for both wild-type (wt) and aba1 (ABA-deficient) mutant plants. For aba1 mutants, both the phosphate deficiency and sugar effects on rab18 were weaker than in wt plants, suggesting possible involvement of both ABA-dependent and ABA-independent components in signalling. Transgenic Arabidopsis plants with increased hexokinase (HXK) expression had a much higher sucrose-dependent level of rab18 mRNA, implying the HXK involvement in sensing/transmitting the sugar signal. Sucrose-related induction of rab18 was completely inhibited by okadaic acid (OKA), suggesting the involvement of specific protein phosphatase(s) in transduction of the sugar signal. The results suggest that rab18 is regulated via interaction of a plethora of signals, including ABA, sugar and phosphate deficiency, and that the sugar effect is transmitted via a HXK-pathway, involving OKA-sensitive component(s). The findings prompt caution in linking the expression of rab18 solely to ABA signalling.

  14. Omega-3 fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism.

    PubMed

    Ross, Brian M

    2007-01-01

    Omega-3 fatty acids are a type of polyunsaturated fatty acid (PUFA). A growing body of evidence suggests that this form PUFA is a useful and well tolerated treatment for major depressive disorder, a common and serious mental illness. The efficacy of omega-3 PUFA is routinely explained as being due to a deficiency caused by inadequate dietary intake of this class of fatty acid. The hypothesis considered states that low omega-3 PUFA abundance in patients with major depressive and related disorders is due to an underlying genetically determined abnormality. The hypothesis can explain why although a specific and consistent deficit in omega-3, but not omega-6, PUFA occurs in major depressive and related disorders, the literature does not consistently support the notion that this is due to deficient dietary intake. Specifically it is hypothesized that having genetically determined low activity of fatty acid CoA ligase 4 and/or Type IV phospholipase A(2) combined with the low dietary availability of omega-3 PUFA results in reduced cellular uptake of omega-3 PUFA and constitutes a risk factor for depression. The hypothesis also has important consequences for the pharmacological treatment of depression in that it predicts that administering agents which enhance phospholipid synthesis, particularly those containing ethanolamine such as CDP-ethanolamine, should be effective antidepressants especially when co-administered with omega-3 PUFA.

  15. Altered mRNA editing and expression of ionotropic glutamate receptors after kainic acid exposure in cyclooxygenase-2 deficient mice.

    PubMed

    Caracciolo, Luca; Barbon, Alessandro; Palumbo, Sara; Mora, Cristina; Toscano, Christopher D; Bosetti, Francesca; Barlati, Sergio

    2011-01-01

    Kainic acid (KA) binds to the AMPA/KA receptors and induces seizures that result in inflammation, oxidative damage and neuronal death. We previously showed that cyclooxygenase-2 deficient (COX-2(-/-)) mice are more vulnerable to KA-induced excitotoxicity. Here, we investigated whether the increased susceptibility of COX-2(-/-) mice to KA is associated with altered mRNA expression and editing of glutamate receptors. The expression of AMPA GluR2, GluR3 and KA GluR6 was increased in vehicle-injected COX-2(-/-) mice compared to wild type (WT) mice in hippocampus and cortex, whereas gene expression of NMDA receptors was decreased. KA treatment decreased the expression of AMPA, KA and NMDA receptors in the hippocampus, with a significant effect in COX-2(-/-) mice. Furthermore, we analyzed RNA editing levels and found that the level of GluR3 R/G editing site was selectively increased in the hippocampus and decreased in the cortex in COX-2(-/-) compared with WT mice. After KA, GluR4 R/G editing site, flip form, was increased in the hippocampus of COX-2(-/-) mice. Treatment of WT mice with the COX-2 inhibitor celecoxib for two weeks decreased the expression of AMPA/KA and NMDAR subunits after KA, as observed in COX-2(-/-) mice. After KA exposure, COX-2(-/-) mice showed increased mRNA expression of markers of inflammation and oxidative stress, such as cytokines (TNF-α, IL-1β and IL-6), inducible nitric oxide synthase (iNOS), microglia (CD11b) and astrocyte (GFAP). Thus, COX-2 gene deletion can exacerbate the inflammatory response to KA. We suggest that COX-2 plays a role in attenuating glutamate excitotoxicity by modulating RNA editing of AMPA/KA and mRNA expression of all ionotropic glutamate receptor subunits and, in turn, neuronal excitability. These changes may contribute to the increased vulnerability of COX-2(-/-) mice to KA. The overstimulation of glutamate receptors as a consequence of COX-2 gene deletion suggests a functional coupling between COX-2 and the

  16. Effects of folic acid deficiency and MTHFR C677T polymorphism on spontaneous and radiation-induced micronuclei in human lymphocytes.

    PubMed

    Leopardi, Paola; Marcon, Francesca; Caiola, Stefania; Cafolla, Arturo; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo

    2006-09-01

    Folic acid plays a key role in the maintenance of genomic stability, providing methyl groups for the conversion of uracil to thymine and for DNA methylation. Besides dietary habits, folic acid metabolism is influenced by genetic polymorphism. The C677T polymorphism of the methylene-tetrahydrofolate reductase (MTHFR) gene is associated with a reduction of catalytic activity and is suggested to modify cancer risk differently depending on folate status. In this work the effect of folic acid deficiency on genome stability and radiosensitivity has been investigated in cultured lymphocytes of 12 subjects with different MTHFR genotype (four for each genotype). Cells were grown for 9 days with 12, 24 and 120 nM folic acid and analyzed in a comprehensive micronucleus test coupled with centromere characterization by CREST immunostaining. In other experiments, cells were grown with various folic acid concentrations, irradiated with 0.5 Gy of gamma rays and analyzed in the micronucleus test. The results obtained indicate that folic acid deficiency induces to a comparable extent chromosome loss and breakage, irrespective of the MTHFR genotype. The effect of folic acid was highly significant (P < 0.001) and explained >50% of variance of both types of micronuclei. Also nucleoplasmic bridges and buds were significantly increased under low folate supply; the increase in bridges was mainly observed in TT cells, highlighting a significant effect of the MTHFR genotype (P = 0.006) on this biomarker. Folic acid concentration significantly affected radiation-induced micronuclei (P < 0.001): the increased incidence of radiation-induced micronuclei with low folic acid was mainly accounted for by carriers of the variant MTHFR allele (both homozygotes and heterozygotes), but the overall effect of genotype did not attain statistical significance. Treatment with ionizing radiations also increased the frequency of nucleoplasmic bridges. The effect of folic acid level on this end-point was

  17. Folic acid deficiency impairs the gill health status associated with the NF-κB, MLCK and Nrf2 signaling pathways in the gills of young grass carp (Ctenopharyngodon idella).

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-11-01

    The aim of this study was to investigate the effect of dietary folic acid on fish growth, the immune and barrier functions of fish gills, and the potential mechanisms of these effects. Young grass carp (Ctenopharyngodon idella) were fed diets containing graded levels of folic acid at 0.10 (basal diet), 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results showed that acid phosphatase and lysozyme activities and the complement component 3 content in fish gills decreased with folic acid deficiency (P < 0.05). Folic acid deficiency up-regulated liver-expressed antimicrobial peptide 1, interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65, IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression. Folic acid deficiency down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in fish gills (P < 0.05). These results showed that limited folic acid decreased fish gill immune status. Furthermore, folic acid deficiency down-regulated claudin-b, claudin-c, claudin-3, occludin and zonula occludens 1 gene expression, whereas folic acid deficiency up-regulated claudin-12, claudin-15, myosin light chain kinase and p38 mitogen activated protein kinase gene expression in fish gills (P < 0.05). These results suggested that folic acid deficiency disrupted tight junction-mediated fish gill barrier function. Additionally, folic acid deficiency increased the content of reactive oxygen species, protein carbonyl and malondialdehyde (MDA); Mn superoxide dismutase activity and gene expression; and Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression (P < 0.05). Conversely, folic acid deficiency decreased Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase activities and gene expression as well as NF-E2-related factor 2 gene expression in fish gills (P < 0.05). All of these results indicated that folic acid

  18. Trace element status and fatty acids metabolism during healthy ageing: an example of a population from the Tunisian eastern coast.

    PubMed

    Sfar, Sonia; El Heni, Jihen; Laporte, François; Braham, Hamadi; Jawed, Abdelhafidh; Amor, Salah; Sfar, Mohamed Tahar; Kerkeni, Abdelhamid

    2012-03-01

    Micronutrients as well as essential fatty acids are indispensable for the correct functioning of the organism. The risk of disturbance in the associated nutrition and metabolism is expected to increase during ageing. In addition, it seems that trace elements are involved in the fatty acids metabolism. The aim of the present study was then to assess age-related changes in trace elements status and in plasma essential fatty acids composition with an emphasis on the desaturase activity estimation. Two hundred healthy Tunisian subjects (30-85 years old) were recruited and separated into two subgroups: elderly (65-85 years old) and middle-aged (30-60 years old). The findings revealed that plasma zinc and calcium concentrations significantly decreased according to age. The prevalence of zinc deficiency was therefore shown to increase in old age (over 60% of elderly subjects were deficient or at risk of deficiency). No age-related changes were obtained for copper or magnesium status. The Δ6 desaturase, involved in the EFAs conversion, was shown to decrease according to age and to be associated with the plasma zinc level. Since elderly subjects were at risk of nutritional imbalance, it would be interesting to set optimal dietary proportion. This will help to prevent age-associated alterations and diseases for a better and healthy ageing. PMID:22222317

  19. Early Life Stress Interacts with the Diet Deficiency of Omega-3 Fatty Acids during the Life Course Increasing the Metabolic Vulnerability in Adult Rats

    PubMed Central

    Bernardi, Juliana R.; Ferreira, Charles F.; Senter, Gabrielle; Krolow, Rachel; de Aguiar, Bianca W.; Portella, André K.; Kauer-Sant'Anna, Márcia; Kapczinski, Flávio; Dalmaz, Carla; Goldani, Marcelo Z.; Silveira, Patrícia P.

    2013-01-01

    Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32°C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animal's body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood. PMID:23614006

  20. Genetics Home Reference: arginase deficiency

    MedlinePlus

    ... deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia ... links) Encyclopedia: Hereditary urea cycle abnormality Health Topic: Amino Acid Metabolism Disorders Health Topic: Genetic Brain Disorders Health ...

  1. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

    PubMed Central

    Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B.; Enns, Gregory M.; Jones, Simon A.; Kane, John P.; Stock, Eveline O.; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S.; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A.; Sharma, Reena; Twelves, Chris; Whitley, Chester B.; Quinn, Anthony G.

    2014-01-01

    Background and aims Lysosomal Acid Lipase Deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results 216 infusions were administered to eight adult subjects through Week 52 during LAL-CL04. At Week 52, mean alanine aminotransferase and aspartate aminotransferase were normal with mean change from baseline of −58% and −40%. Mean change for low density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were −60%, −39%, −36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions Long-term dosing with sebelipase alfa in Lysosomal Acid Lipase-Deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). PMID:24993530

  2. Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism.

    PubMed

    Martínez-Vega, Raquel; Garrido, Francisco; Partearroyo, Teresa; Cediel, Rafael; Zeisel, Steven H; Martínez-Álvarez, Concepción; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel; Pajares, María A

    2015-02-01

    Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.

  3. Dermatan sulfate epimerase 1-deficient mice have reduced content and changed distribution of iduronic acids in dermatan sulfate and an altered collagen structure in skin.

    PubMed

    Maccarana, Marco; Kalamajski, Sebastian; Kongsgaard, Mads; Magnusson, S Peter; Oldberg, Ake; Malmström, Anders

    2009-10-01

    Dermatan sulfate epimerase 1 (DS-epi1) and DS-epi2 convert glucuronic acid to iduronic acid in chondroitin/dermatan sulfate biosynthesis. Here we report on the generation of DS-epi1-null mice and the resulting alterations in the chondroitin/dermatan polysaccharide chains. The numbers of long blocks of adjacent iduronic acids are greatly decreased in skin decorin and biglycan chondroitin/dermatan sulfate, along with a parallel decrease in iduronic-2-O-sulfated-galactosamine-4-O-sulfated structures. Both iduronic acid blocks and iduronic acids surrounded by glucuronic acids are also decreased in versican-derived chains. DS-epi1-deficient mice are smaller than their wild-type littermates but otherwise have no gross macroscopic alterations. The lack of DS-epi1 affects the chondroitin/dermatan sulfate in many proteoglycans, and the consequences for skin collagen structure were initially analyzed. We found that the skin collagen architecture was altered, and electron microscopy showed that the DS-epi1-null fibrils have a larger diameter than the wild-type fibrils. The altered chondroitin/dermatan sulfate chains carried by decorin in skin are likely to affect collagen fibril formation and reduce the tensile strength of DS-epi1-null skin.

  4. Nutritional stress effects under different nitrogen sources on the genes in microalga Isochrysis zhangjiangensis and the assistance of Alteromonas macleodii in releasing the stress of amino acid deficiency.

    PubMed

    Wu, Shuang; Zhou, Jiannan; Xin, Yanjuan; Xue, Song

    2015-10-01

    The expressions of nine nitrogen assimilation-associated genes, NRT2, NAR1, NIA2, NIR, GLN2, GLSF, GSN1, GDH, and AAT2, in the microalga Isochrysis zhangjiangensis were investigated to unveil the effects of limitations of various nitrogen sources (NaNO3 , NH4 Cl, NaNO2 , and an amino acid mixture) on the microalgae. The results demonstrated that the NRT2, NAR1, GLN2, GSN1, and AAT2 genes were highly expressed in lipid-rich microalgae under inorganic nitrogen-deficient conditions and they decreased after nitrogen resupply. Significant increases in the expressions of NAR1, GLN2, and GLSF were found in nitrate-depleted microalgae, whereas significant increases in the expressions of NRT2, NAR1, GLN2, and GSN1 were found in nitrite-depleted microalgae. Significant increases in the expressions of only NRT2 and GSN1 were found in ammonium-depleted microalgae (P < 0.05). Except for the NRT2, other genes were expressed at lower levels under amino acid-deficient conditions compared with amino acid-sufficient controls. The expression of the NIA2 gene decreased in nitrogen-depleted microalgae regardless of the initial nitrogen source. However, the results of fatty acid analyses showed that the features of fatty acid profiles followed a similar mode, in which the percentage compositions of C16:0 and C18:1Δ(9) increased in nitrogen-depleted cells and that of C16:1Δ(9) , C18:3Δ(9,12,15) , C18:4Δ(6,9,12,15) , and C18:5Δ(3,6,9,12,15) decreased, regardless of the type of nitrogen source applied. It was also found that the epiphytic bacterium Alteromonas macleodii played a particularly important role in releasing microalgae from the stress of amino acid deficiency. These findings also provide a foundation for regulating microalgal lipid production through manipulation of the nitrogen assimilation-associated genes.

  5. Assembly of D-alanyl-lipoteichoic acid in Lactobacillus casei: mutants deficient in the D-alanyl ester content of this amphiphile

    SciTech Connect

    Ntamere, A.S.; Taron, D.J.; Neuhaus, F.C.

    1987-04-01

    D-Alanyl-lipoteichoic acid (D-alanyl-LTA) from Lactobacillus casei ATCC 7469 contains a poly(glycerophosphate) moiety that is acylated with D-alanyl ester residues. The physiological function of these residues is not well understood. Five mutant strains of this organism that are deficient in the esters of this amphiphile were isolated and characterized. When compared with the parent, strains AN-1 and AN-4 incorporated less than 10% of D-(/sup 14/C)alanine into LTA, whereas AN-2, AN-3, and AN-5 incorporated 50%. The synthesis of D-(/sup 14/C)alanyl-lipophilic LTA was virtually absent in the first group and was approximately 30% in the second group. The mutant strains synthesized and selected the glycolipid anchor for LTA assembly. In addition, all of the strains synthesized the poly(glycerophosphate) moiety of LTA to the same extent as did the parent or to a greater extent. It was concluded that the membranes from the mutant strains AN-1 and AN-4 are defective for D-alanylation of LTA even though acceptor LTA is present. Mutant strains AN-2 and AN-3 appear to be partially deficient in the amount of the D-alanine-activating enzyme. Aberrant morphology and defective cell separation appear to result from this deficiency in D-alanyl ester content.

  6. Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance.

    PubMed

    Häberle, Johannes; Shahbeck, Noora; Ibrahim, Khalid; Schmitt, Bernhard; Scheer, Ianina; O'Gorman, Ruth; Chaudhry, Farrukh A; Ben-Omran, Tawfeg

    2012-07-25

    Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.

  7. Homo-D-lactic acid fermentation from arabinose by redirection of the phosphoketolase pathway to the pentose phosphate pathway in L-lactate dehydrogenase gene-deficient Lactobacillus plantarum.

    PubMed

    Okano, Kenji; Yoshida, Shogo; Tanaka, Tsutomu; Ogino, Chiaki; Fukuda, Hideki; Kondo, Akihiko

    2009-08-01

    Optically pure d-lactic acid fermentation from arabinose was achieved by using the Lactobacillus plantarum NCIMB 8826 strain whose l-lactate dehydrogenase gene was deficient and whose phosphoketolase gene was substituted with a heterologous transketolase gene. After 27 h of fermentation, 38.6 g/liter of d-lactic acid was produced from 50 g/liter of arabinose.

  8. Dietary zinc deficiency affects blood linoleic acid: dihomo-gamma-linolenic acid (LA:DGLA) ratio; a reactive physiological marker of zinc status in vivo (Gallus gallus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary Zinc (Zn) deficiency affects approximately 30% of the world’s population. Zinc is a vital micronutrient and is important for the body’s ability to function. To date, accurate biological markers of the Zn subject’s status are still needed. The aim of this study was to evaluate the chicken mod...

  9. In silico study of interaction between rice proteins enhanced disease susceptibility 1 and phytoalexin deficient 4, the regulators of salicylic acid signalling pathway.

    PubMed

    Singh, Indra; Shah, Kavita

    2012-07-01

    Enhanced disease susceptibility 1 (EDS1), a plant-specific protein has homology with the eukaryotic lipase in their N-terminal halves and a unique domain at its C-termini. EDS1 is known to be an important regulator of biotic stress and an essential component of basal immunity. EDS1 interacts with its positive co-regulator phytoalexin deficient 4 (PAD4), resulting in mobilization of the salicylic acid defence pathway. Limited information regarding this interaction in rice is available. To study this interaction, a model of EDS1 and PAD4 proteins from rice was generated and validated with Accelrys DS software version 3.1 using bioinformatics interface. The in silico docking between the two proteins showed a significant protein-protein interaction between rice EDS1 and PAD4, suggesting that they form a dimeric protein complex, which, similar to that in Arabidopsis, is perhaps also important for triggering the salicylic acid signalling pathway in plants.

  10. Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid composition in mice[S

    PubMed Central

    Wang, Qiong; Li, Shoufeng; Jiang, Lei; Zhou, Yunhua; Li, Zi; Shao, Mengle; Li, Wenjun; Liu, Yong

    2010-01-01

    ATP-citrate lyase (ACL) is a key lipogenic enzyme that converts citrate in the cytoplasm to acetyl-CoA, the initial precursor that yields malonyl-CoA for fatty acid biosynthesis. As cytosolic citrate is derived from the tricarboxylic acid cycle in the mitochondrion, ACL catalyzes a critical reaction linking cellular glucose catabolism and lipid synthesis. To investigate the metabolic action of ACL in lipid homeostasis, we specifically knocked down hepatic ACL expression by adenovirus-mediated RNA interference in mice maintained on a low-fat or high-fat diet. Hepatic ACL abrogation markedly reduced the liver abundance of both acetyl-CoA and malonyl-CoA regardless of dietary fat intake, which was paralleled with decreases in circulating levels of triglycerides and free fatty acids. Moreover, hepatic ACL knockdown resulted in diet-dependent changes in the expression of other lipogenic enzymes, accompanied by altered fatty acid compositions in the liver. Interestingly, ACL deficiency led to reduced serum VLDL-triglyceride levels but increased hepatic triglyceride content, resulting at least partially from decreased hepatic secretion of VLDL-containing apolipoprotein B-48. Together, these results demonstrate that hepatic ACL suppression exerts profound effects on triglyceride mobilization as well as fatty acid compositions in the liver, suggesting an important role for ACL in lipid metabolism. PMID:20488800

  11. Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training.

    PubMed

    Lavoie, Jean-Marc

    2016-08-18

    Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative. PMID:27621762

  12. Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

    PubMed Central

    Lavoie, Jean-Marc

    2016-01-01

    Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.

  13. Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

    PubMed Central

    Lavoie, Jean-Marc

    2016-01-01

    Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative. PMID:27621762

  14. Alloy B-10, a new nickel-based alloy for strong chloride-containing, highly acidic and oxygen-deficient environments

    SciTech Connect

    Kohler, M.; Kirchheiner, R.; Stenner, F.

    1998-12-31

    Alloy B-10 is a Ni-Mo-Cr alloy, recently developed for highly acidic but oxygen-deficient environments in the chemical process and environmental protection industries. The new nickel-based alloy with nominally (wt. %) 62 Ni, 24 MO, 8 Cr and 6 Fe, exhibits excellent corrosion resistance in intermediate concentrations of sulfuric acid, as well as in hydrochloric acid, even with additions of small amounts of oxidizing agents. In a simulated Flue Gas Desulfurization (FGD) environment of sulfuric acid of pH 1 with additions of 7% chloride and 0.01% fluoride, and also containing 15% gypsum the new alloy demonstrated high crevice corrosion resistance at 100 C, whereas a common Ni-Cr-Mo alloy of the C-type suffers crevice corrosion under the same conditions. This new alloy can easily be welded without filler or using matching filler. Good practical experience has been gained with Alloy B-10 in a district heating power station as a tube sheet and bottom wall liner for a glass tube heat exchanger working at 130 C with condensing 70% sulfuric acid.

  15. Stabilization of emulsion and butter like products containing essential fatty acids using kalonji seeds extract and curcuminoids.

    PubMed

    Rege, Sameera A; Momin, Shamim A; Bhowmick, Dipti N; Pratap, Amit A

    2012-01-01

    Owing to the tendency of essential fatty acids (EFAs) to undergo autoxidation, their storage becomes a key problem. Generally, they are stabilized by synthetic antioxidants like TBHQ that are toxic in nature. Recently many studies were reported where these EFAs are stabilized by natural antioxidants. In the present study, curcuminoids and kalonji seeds ethanol extract (KEE) were used to stabilize these EFAs in refined sunflower oil (RSFO), water-in-oil (w/o) emulsion and butter like products (BLPs). In RSFO, though curcuminoids alone exerted pro-oxidant effect, KEE and curcuminoids showed synergistic antioxidant activity that was comparable to TBHQ. KEE exhibited good antioxidant activity in emulsions and BLPs, providing fine physical properties like slipping point, dropping point and spreadability. EFAs increased the nutritional value of BLPs and antioxidants added for their stabilization provided their medicinal benefits. PMID:22188801

  16. Prevalence of anemia, iron, folic acid and vitamin B12 deficiency in two Bari Indian communities from western Venezuela.

    PubMed

    Diez-Ewald, M; Torres-Guerra, E; Layrisse, M; Leets, I; Vizcaíno, G; Arteaga-Vizcaíno, M

    1997-12-01

    The hematological status of 406 Bari indians from two communities was studied. One hundred and seventy nine individuals were from Campo Rosario a village located in a low arid plain south to the Perijá mountain range and 287 were from Saimadoyi, a fertile valley in the heart of the mountain. Anemia was found in 54% and 31% of the people from Campo Rosario and Saimadoyi respectively. Low serum iron was present in 28% of the population in both communities while low serum ferritin levels were encountered in 20% of the population from Campo Rosario and 5% of the people from Saimadoyi. A high prevalence of serum folate and vitamin B12 deficiency (91% and 64% respectively) was found in Campo Rosario, in contrast only 5% of the population from Saimadoyi had low folate and none were vitamin B12 deficient. While there was a positive significant correlation between hemoglobin and serum iron concentrations (r = 0.517, p < 0.001), no significative correlation was found between the other parameters studied. The high prevalence of anemia and nutrient deficiency among the Bari indians, can be attributed to inadequate diets and the varied diseases encountered in the population.

  17. Essential fatty acids and human brain.

    PubMed

    Chang, Chia-Yu; Ke, Der-Shin; Chen, Jen-Yin

    2009-12-01

    The human brain is nearly 60 percent fat. We've learned in recent years that fatty acids are among the most crucial molecules that determine your brain's integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain's integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain's critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.

  18. In-Depth Dissection of the P133R Mutation in Steroid 5β-Reductase (AKR1D1): A Molecular Basis of Bile Acid Deficiency.

    PubMed

    Chen, Mo; Jin, Yi; Penning, Trevor M

    2015-10-20

    Human steroid-5β-reductase (aldo-keto reductase 1D1, AKR1D1) stereospecifically reduces Δ(4)-3-ketosteroids to 5β-dihydrosteroids and is essential for steroid hormone metabolism and bile acid biosynthesis. Genetic defects in AKR1D1 cause bile acid deficiency that leads to life threatening neonatal hepatitis and cholestasis. The disease-associated P133R mutation caused significant decreases in catalytic efficiency with both the representative steroid (cortisone) and the bile acid precursor (7α-hydroxycholest-4-en-3-one) substrates. Pro133 is a second shell residue to the steroid binding channel and is distal to both the cofactor binding site and the catalytic center. Strikingly, the P133R mutation caused over a 40-fold increase in Kd values for the NADP(H) cofactors and increased the rate of release of NADP(+) from the enzyme by 2 orders of magnitude when compared to the wild type enzyme. By contrast the effect of the mutation on Kd values for steroids were 10-fold or less. The reduced affinity for the cofactor suggests that the mutant exists largely in the less stable cofactor-free form in the cell. Using stopped-flow spectroscopy, a significant reduction in the rate of the chemical step was observed in multiple turnover reactions catalyzed by the P133R mutant, possibly due to the altered position of NADPH. Thus, impaired NADPH binding and hydride transfer is the molecular basis for bile acid deficiency in patients with the P133R mutation. Results revealed that optimal cofactor binding is vulnerable to distant structural perturbation, which may apply to other disease-associated mutations in AKR1D1, all of which occur at conserved residues and are unstable.

  19. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

    PubMed Central

    Burgos-Morón, Estefanía; Calderón-Montaño, José Manuel; Orta, Manuel Luis; Guillén-Mancina, Emilio; Mateos, Santiago; López-Lázaro, Miguel

    2016-01-01

    Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee. PMID:27399778

  20. Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle.

    PubMed

    Cecatto, Cristiane; Godoy, Kálita Dos Santos; da Silva, Janaína Camacho; Amaral, Alexandre Umpierrez; Wajner, Moacir

    2016-10-01

    The pathogenesis of the muscular symptoms and recurrent rhabdomyolysis that are commonly manifested in patients with mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies is still unknown. In this study we investigated the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in these disorders, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria. 3HTA and 3HPA markedly increased resting (state 4) and decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration. 3HPA provoked similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. Furthermore, 3HTA and 3HPA markedly diminished mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlie these effects since they were totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA did not alter the tested parameters. Our data strongly indicate that 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. It is proposed that these pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic of MTP and LCHAD deficiencies.

  1. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid.

    PubMed

    Burgos-Morón, Estefanía; Calderón-Montaño, José Manuel; Orta, Manuel Luis; Guillén-Mancina, Emilio; Mateos, Santiago; López-Lázaro, Miguel

    2016-01-01

    Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee. PMID:27399778

  2. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  3. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  4. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  5. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  6. Tor-Sch9 deficiency activates catabolism of the ketone body-like acetic acid to promote trehalose accumulation and longevity.

    PubMed

    Hu, Jia; Wei, Min; Mirzaei, Hamed; Madia, Federica; Mirisola, Mario; Amparo, Camille; Chagoury, Shawna; Kennedy, Brian; Longo, Valter D

    2014-06-01

    In mammals, extended periods of fasting leads to the accumulation of blood ketone bodies including acetoacetate. Here we show that similar to the conversion of leucine to acetoacetate in fasting mammals, starvation conditions induced ketone body-like acetic acid generation from leucine in S. cerevisiae. Whereas wild-type and ras2Δ cells accumulated acetic acid, long-lived tor1Δ and sch9Δ mutants rapidly depleted it through a mitochondrial acetate CoA transferase-dependent mechanism, which was essential for lifespan extension. The sch9Δ-dependent utilization of acetic acid also required coenzyme Q biosynthetic genes and promoted the accumulation of intracellular trehalose. These results indicate that Tor-Sch9 deficiency extends longevity by switching cells to an alternative metabolic mode, in which acetic acid can be utilized for the storage of stress resistance carbon sources. These effects are reminiscent of those described for ketone bodies in fasting mammals and raise the possibility that the lifespan extension caused by Tor-S6K inhibition may also involve analogous metabolic changes in higher eukaryotes.

  7. [Blood deficiency values of polyunsaturated fatty acids of phospholipids, vitamin E and glutathione peroxidase as possible risk factors in the onset and development of acquired immunodeficiency syndrome].

    PubMed

    Passi, S; De Luca, C; Picardo, M; Morrone, A; Ippolito, F

    1990-04-01

    Plasma levels of vitamin E (vit E) and polyunsatured fatty acids of phospholipids (PUFA-PL) as well as erythrocyte glutathione peroxidase (GSH-Px) activity are significantly lower (p less than 0.001) in patients HIV sero-positive (AIDS and ARC cases) both affected and not affected with seborrheic dermatitis and in 32% of HIV sero-negative intravenous drug abusers (IVDA, A subgroup) than in controls. The deficiency of PUFA-PL (mainly C20:3 n-6, C20:4 n-6 and C22:6 n-3) which is associated with a significant increase (p less than 0.001) of saturated palmitic and stearic acids and monounsaturated oleic acid, cannot be correlated to an active lipoperoxidative process. In fact the levels of thiobarbituric acid-reactive materials (TBA-RM) are not increased in the plasma of HIV sero-positive patients and A subgroup of IVDA. It is likely that the reduction of PUFA-PL is due to an inhibition of hepatic microsomal desaturase enzymes (delta 6 desaturase, delta 5 desaturase, delta 4 desaturase) which are involved in both n-6 and n-3 pathways. Since IVDA represent, and not only in Italy, a major risk category for HIV infection, we suggest that reduced blood levels of vit E, GSH-Px and particularly PUFA-PL may be added to the list of risk factors favouring the onset and the development of AIDS.

  8. Glutaric acid and its metabolites cause apoptosis in immature oligodendrocytes: a novel mechanism of white matter degeneration in glutaryl-CoA dehydrogenase deficiency.

    PubMed

    Gerstner, Bettina; Gratopp, Alexander; Marcinkowski, Monika; Sifringer, Marco; Obladen, Michael; Bührer, Christoph

    2005-06-01

    Glutaryl-CoA dehydrogenase deficiency is an inherited metabolic disease characterized by elevated concentrations of glutaric acid (GA) and its metabolites glutaconic acid (GC) and 3-hydroxy-glutaric acid (3-OH-GA). Its hallmarks are striatal and cortical degeneration, which have been linked to excitotoxic neuronal cell death. However, magnetic resonance imaging studies have also revealed widespread white matter disease. Correspondingly, we decided to investigate the effects of GA, GC, and 3-OH-GA on the rat immature oligodendroglia cell line, OLN-93. For comparison, we also exposed the neuroblastoma line SH-SY5Y and the microglia line BV-2 to GA, GC, and 3-OH-GA. Cell viability was measured by metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium. Flow cytometry was used to assess apoptosis via annexin-V, anti-active caspase-3 antibody, and propidium iodide staining. GA, GC, and 3-OH-GA reduced OLN-93 oligodendroglia cell viability in a dose-dependent manner. Toxicity of GA, GC, and 3-OH-GA was abrogated by preincubation with the pan-caspase inhibitor z-VAD-fmk. Apoptosis but not necrosis was detected at various stages (early: annexin-V; effector: caspase-3) after 24-48 h of incubation with GA, GC, or 3-OH-GA in OLN-93 but not in neuroblastoma or microglia cells. OLN-93 lacked expression of N-methyl-d-aspartate receptors, making classical glutamatergic excitotoxicity an unlikely explanation for the selective toxicity of GA, GC, and 3-OH-GA for OLN-93 cells. GA, GC, and 3-OH-GA directly initiate the apoptotic cascade in oligodendroglia cells. This mechanism may contribute to the white matter damage observed in glutaryl-CoA dehydrogenase deficiency.

  9. The Effects of Supplemental Intra-Articular Lubricin and Hyaluronic Acid on the Progression of Post-Traumatic Arthritis in the Anterior Cruciate Ligament Deficient Rat Knee

    PubMed Central

    Teeple, Erin; Elsaid, Khaled A.; Jay, Gregory D.; Zhang, Ling; Badger, Gary J.; Akelman, Matthew; Bliss, Thomas F.; Fleming, Braden C.

    2010-01-01

    Background Lubricin and hyaluronic acid lubricate articular cartilage and prevent wear. Because lubricin loss occurs following ACL injury, intra-articular lubricin injections may reduce cartilage damage in the ACL deficient knee. Purpose To determine if lubricin and/or hyaluronic acid supplementation will reduce cartilage damage in the ACL deficient knee. Study Design Controlled laboratory study Methods 36 male rats, 3 months old, underwent unilateral ACL transection. They were randomized to four treatments: 1) saline (PBS), 2) hyaluronic acid (HA), 3) purified human lubricin (LUB), and 4) LUB and HA (LUB+HA). Intra-articular injections were given twice weekly for four weeks starting one week after surgery. Knees were harvested one week following final injection. Radiographs of each limb and synovial fluid lavages were obtained at harvest. Histology was performed to assess cartilage damage using Safranin O/Fast green staining. Radiographs were scored for the severity of joint degeneration using the modified Kellgren-Lawrence scale. Synovial fluid levels of sulfated glycosaminoglycan, collagen II breakdown, IL-1β, TNF-α and lubricin were measured using ELISA. Results Treatment with LUB or LUB+HA significantly decreased radiographic and histologic scores of cartilage damage (p=0.039, p=0.015, respectively) when compared to the PBS and HA conditions. There was no evidence of an effect of HA nor was the LUB effect HA dependent suggesting that the addition of HA did not further reduce damage. The synovial fluid of knees treated with LUB had significantly more lubricin in the synovial fluid at euthanasia, though there were no differences in the other cartilage metabolism biomarkers. Conclusions Supplemental intra-articular LUB reduced cartilage damage in the ACL transected rat knee 6 weeks after injury, while treatment with HA did not. Clinical Relevance Although longer-term studies are needed, intra-articular supplementation (tribosupplementation) with lubricin

  10. OsNIP3;1, a rice boric acid channel, regulates boron distribution and is essential for growth under boron-deficient conditions.

    PubMed

    Hanaoka, Hideki; Uraguchi, Shimpei; Takano, Junpei; Tanaka, Mayuki; Fujiwara, Toru

    2014-06-01

    Boron is an essential micronutrient for higher plants. Boron deficiency is an important agricultural issue because it results in loss of yield quality and/or quantity in cereals and other crops. To understand boron transport mechanisms in cereals, we characterized OsNIP3;1, a member of the major intrinsic protein family in rice (Oryza sativa L.), because OsNIP3;1 is the most similar rice gene to the Arabidopsis thaliana boric acid channel genes AtNIP5;1 and AtNIP6;1. Yeast cells expressing OsNIP3;1 imported more boric acid than control cells. GFP-tagged OsNIP3;1 expressed in tobacco BY2 cells was localized to the plasma membrane. The accumulation of OsNIP3;1 transcript increased fivefold in roots within 6 h of the onset of boron starvation, but not in shoots. Promoter-GUS analysis suggested that OsNIP3;1 is expressed mainly in exodermal cells and steles in roots, as well as in cells around the vascular bundles in leaf sheaths and pericycle cells around the xylem in leaf blades. The growth of OsNIP3;1 RNAi plants was impaired under boron limitation. These results indicate that OsNIP3;1 functions as a boric acid channel, and is required for acclimation to boron limitation. Boron distribution among shoot tissues was altered in OsNIP3;1 knockdown plants, especially under boron-deficient conditions. This result demonstrates that OsNIP3;1 regulates boron distribution among shoot tissues, and that the correct boron distribution is crucial for plant growth.

  11. Overexpression of Aspergillus tubingensis faeA in protease-deficient Aspergillus niger enables ferulic acid production from plant material.

    PubMed

    Zwane, Eunice N; Rose, Shaunita H; van Zyl, Willem H; Rumbold, Karl; Viljoen-Bloom, Marinda

    2014-06-01

    The production of ferulic acid esterase involved in the release of ferulic acid side groups from xylan was investigated in strains of Aspergillus tubingensis, Aspergillus carneus, Aspergillus niger and Rhizopus oryzae. The highest activity on triticale bran as sole carbon source was observed with the A. tubingensis T8.4 strain, which produced a type A ferulic acid esterase active against methyl p-coumarate, methyl ferulate and methyl sinapate. The activity of the A. tubingensis ferulic acid esterase (AtFAEA) was inhibited twofold by glucose and induced twofold in the presence of maize bran. An initial accumulation of endoglucanase was followed by the production of endoxylanase, suggesting a combined action with ferulic acid esterase on maize bran. A genomic copy of the A. tubingensis faeA gene was cloned and expressed in A. niger D15#26 under the control of the A. niger gpd promoter. The recombinant strain has reduced protease activity and does not acidify the media, therefore promoting high-level expression of recombinant enzymes. It produced 13.5 U/ml FAEA after 5 days on autoclaved maize bran as sole carbon source, which was threefold higher than for the A. tubingensis donor strain. The recombinant AtFAEA was able to extract 50 % of the available ferulic acid from non-pretreated maize bran, making this enzyme suitable for the biological production of ferulic acid from lignocellulosic plant material. PMID:24664515

  12. Overexpression of Aspergillus tubingensis faeA in protease-deficient Aspergillus niger enables ferulic acid production from plant material.

    PubMed

    Zwane, Eunice N; Rose, Shaunita H; van Zyl, Willem H; Rumbold, Karl; Viljoen-Bloom, Marinda

    2014-06-01

    The production of ferulic acid esterase involved in the release of ferulic acid side groups from xylan was investigated in strains of Aspergillus tubingensis, Aspergillus carneus, Aspergillus niger and Rhizopus oryzae. The highest activity on triticale bran as sole carbon source was observed with the A. tubingensis T8.4 strain, which produced a type A ferulic acid esterase active against methyl p-coumarate, methyl ferulate and methyl sinapate. The activity of the A. tubingensis ferulic acid esterase (AtFAEA) was inhibited twofold by glucose and induced twofold in the presence of maize bran. An initial accumulation of endoglucanase was followed by the production of endoxylanase, suggesting a combined action with ferulic acid esterase on maize bran. A genomic copy of the A. tubingensis faeA gene was cloned and expressed in A. niger D15#26 under the control of the A. niger gpd promoter. The recombinant strain has reduced protease activity and does not acidify the media, therefore promoting high-level expression of recombinant enzymes. It produced 13.5 U/ml FAEA after 5 days on autoclaved maize bran as sole carbon source, which was threefold higher than for the A. tubingensis donor strain. The recombinant AtFAEA was able to extract 50 % of the available ferulic acid from non-pretreated maize bran, making this enzyme suitable for the biological production of ferulic acid from lignocellulosic plant material.

  13. Immunity decreases, antioxidant system damages and tight junction changes in the intestine of grass carp (Ctenopharyngodon idella) during folic acid deficiency: Regulation of NF-κB, Nrf2 and MLCK mRNA levels.

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-04-01

    This investigation used the same growth trial as the previous study, which showed that folic acid deficiency retarded growth in young grass carp (the percent weight gain of Groups 1-6 were 102.32 ± 3.41%, 137.25 ± 10.48%, 179.78 ± 3.95%, 164.33 ± 3.21%, 143.35 ± 8.12% and 115.28 ± 2.66%) [1]. In the present study, we investigated the effects of dietary folic acid on the immune response, antioxidant status and tight junctions in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp were fed diets containing graded levels of folic acid at 0.10, 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results indicated that acid phosphatase and lysozyme activities, and the complement component 3 content in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) were decreased with folic acid deficiency (0.1 mg kg(-1)) (P < 0.05). Folic acid deficiency (0.1 mg kg(-1)) up-regulated interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65 (NF-κB p65), IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression, meanwhile down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in the PI, MI and DI (P < 0.05). These data suggested that folic acid deficiency decreased fish intestinal innate immune function may be partly contributed to the regulation of NF-κB p65 pathway. Moreover, the activities and corresponding gene expression of glutathione content, Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase in fish intestine were depressed by deficient folic acid diet (0.1 mg kg(-1)) (P < 0.05). Furthermore, folic acid deficiency (0.1 mg kg(-1)) down-regulated NF-E2-related factor 2 (Nrf2) gene expression, up-regulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression in fish intestine (P < 0.05). These data indicated

  14. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    PubMed

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver. PMID:25036135

  15. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    PubMed

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

  16. Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B₁₂ Deficiency.

    PubMed

    Merchant, Randall Edward; Phillips, Todd W; Udani, Jay

    2015-12-01

    Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P < .05) by an average ∼34%. Fifteen of the 17 (88%) subjects showed at least a 10% drop in MMA. At the same time, Hcy trended downward and serum vitamin B12 trended upward, while MCV, Hgb, and Hct appeared unchanged. The results of this work suggest that the vitamin B12 in chlorella is bioavailable and such dietary supplementation is a natural way for vegetarians and vegans to get the vitamin B12 they need.

  17. Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B₁₂ Deficiency.

    PubMed

    Merchant, Randall Edward; Phillips, Todd W; Udani, Jay

    2015-12-01

    Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P < .05) by an average ∼34%. Fifteen of the 17 (88%) subjects showed at least a 10% drop in MMA. At the same time, Hcy trended downward and serum vitamin B12 trended upward, while MCV, Hgb, and Hct appeared unchanged. The results of this work suggest that the vitamin B12 in chlorella is bioavailable and such dietary supplementation is a natural way for vegetarians and vegans to get the vitamin B12 they need. PMID:26485478

  18. Effects of essential fatty acid supplementation in dogs with idiopathic epilepsy: a clinical trial.

    PubMed

    Matthews, Helen; Granger, Nicolas; Wood, James; Skelly, Barbara

    2012-03-01

    The effects of essential fatty acid supplementation (EFA) on the control of idiopathic epilepsy in dogs were investigated in a blinded, placebo-controlled trial. Fifteen dogs were treated with triple purified Ω-3 oil containing 400 mg eicosapentaenoic acid, 250 mg docosahexaenoic acid and 22 mg vitamin E per 1.5 mL at a dose of 1.5 mL/10 kg once daily for 12 weeks, followed by a 12 week placebo period of supplementation with olive oil. Owners recorded seizure frequency and severity and any adverse events. EFA supplementation did not reduce seizure frequency or severity in dogs with idiopathic epilepsy.

  19. Novel acid-labile subunit ( IGFALS ) mutation p.T145K (c.434C>A) in a patient with ALS deficiency, normal stature and immunological dysfunction.

    PubMed

    Schreiner, Felix; Schoenberger, Stefan; Koester, Bernhard; Domené, Horacio M; Woelfle, Joachim

    2013-01-01

    We report a novel missense mutation p.T145K in the insulin-like growth factor (IGF) acid-labile subunit (IGFALS) gene identified in a Turkish patient with normal growth, transient pancytopenic episodes and signs of immunological dysfunction. Because of recurrent cutaneous mycoses and absence of pubertal development until the age of 14.75 years we determined several endocrine parameters in order to rule out autoimmune-polyendocrine syndromes. Despite a normal height between the 25th and 50th percentile we found severely decreased IGF-1 and undetectably low IGFBP-3 levels. Laboratory signs of immunological dysfunction included reduced total lymphocyte count with diminished B and T helper cell fractions, decreased serum concentrations of IgM and IgG subclass 4, and elevated antinuclear antibody and anti-dsDNA titers as well as persistently high interleukin-2-receptor levels. Further endocrine work-up revealed elevated fasting insulin and undetectably low ALS serum levels, leading to the diagnosis of ALS deficiency. Sequencing of the coding region of the IGFALS gene showed a novel homozygous missense mutation (c.434C>A; p.T145K). Since immunological abnormalities have not been reported in more than 20 ALS-deficient patients so far and our patient was born to consanguineous parents, a second autosomal recessive defect is likely to underlie the immunological phenotype, although a causative role of IGFALS p.T145K cannot be entirely ruled out. PMID:24296365

  20. The Brain’s Response to an Essential Amino Acid-Deficient Diet and the Circuitous Route to a Better Meal

    PubMed Central

    Gietzen, Dorothy W.; Aja, Susan M.

    2012-01-01

    The essential (indispensable) amino acids (IAA) are neither synthesized nor stored in metazoans, yet they are the building blocks of protein. Survival depends on availability of these protein precursors, which must be obtained in the diet; it follows that food selection is critical for IAA homeostasis. If even one of the IAA is depleted, its tRNA becomes quickly deacylated and the levels of charged tRNA fall, leading to disruption of global protein synthesis. As they have priority in the diet, second only to energy, the missing IAA must be restored promptly or protein catabolism ensues. Animals detect and reject an IAA-deficient meal in 20 min, but how? Here, we review the molecular basis for sensing IAA depletion and repletion in the brain’s IAA chemosensor, the anterior piriform cortex (APC). As animals stop eating an IAA-deficient meal, they display foraging and altered choice behaviors, to improve their chances of encountering a better food. Within 2 h, sensory cues are associated with IAA depletion or repletion, leading to learned aversions and preferences that support better food selection. We show neural projections from the APC to appetitive and consummatory motor control centers, and to hedonic, motivational brain areas that reinforce these adaptive behaviors. PMID:22674217

  1. Genetics Home Reference: pyruvate carboxylase deficiency

    MedlinePlus

    ... carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in ... features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in ...

  2. Providing a diet deficient in valine but with excess leucine results in a rapid decrease in feed intake and modifies the postprandial plasma amino acid and α-keto acid concentrations in pigs.

    PubMed

    Gloaguen, M; Le Floc'h, N; Corrent, E; Primot, Y; van Milgen, J

    2012-09-01

    Indispensable AA are involved in the control of feed intake. When a diet deficient in Val is offered to pigs, feed intake is typically reduced. This effect is aggravated when dietary Leu is supplied in excess of the requirement. If an unbalanced supply of branched-chain AA (BCAA) is harmful, an anorectic response may serve as a mechanism to prevent this situation. We verified this hypothesis by measuring the voluntary feed intake of a balanced diet offered during the 30-min period 1 h after ingestion of a test meal deficient or not in Val (Val- and Val+) with an excess of Leu. Twelve and four 6-wk-old crossbred female pigs were used in Exp. 1 and 2, respectively. Prior ingestion of the Val- test meal resulted in a 14% reduction in feed intake compared with that observed after ingestion of the Val+ test meal (P = 0.06) in Exp. 1, indicating that the signal to reduce feed intake occurred within 1 h. It is possible that the plasma concentration of the limiting AA serves as a signal for the dietary AA deficiency. We therefore determined the postprandial plasma concentrations of BCAA and their α-keto acids after ingestion of Val- and Val+ in 4 pigs in Exp. 2. After ingestion of the Val- diet, plasma concentrations of Val and its keto acid were reduced compared with values observed after ingestion of the Val+ diet. The peak concentration occurred earlier after ingestion of the Val- diet compared with that of the Val+ diet. Although the plasma concentration increased after the meal, it declined rapidly in pigs offered Val-, and the Val concentration 4 h after ingestion of the meal was even less than that observed in the fasted state. In conclusion, it appears that the pig is able to detect a deficient supply of Val within 1 h after ingestion. The plasma concentration of Val or its concentration relative to the other BCAA during the postprandial period may act as a signal indicating the AA deficiency.

  3. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease.

    PubMed

    Simopoulos, Artemis P

    2013-08-01

    Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

  4. A New Mouse Model of Mild Ornithine Transcarbamylase Deficiency (spf-j) Displays Cerebral Amino Acid Perturbations at Baseline and upon Systemic Immune Activation

    PubMed Central

    Tarasenko, Tatyana N.; Rosas, Odrick R.; Singh, Larry N.; Kristaponis, Kara; Vernon, Hilary; McGuire, Peter J.

    2015-01-01

    Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans. PMID:25647322

  5. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    SciTech Connect

    Jin Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

    2007-12-28

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

  6. Antepartum ornithine transcarbamylase deficiency.

    PubMed

    Nakajima, Hitoshi; Sasaki, Yosuke; Maeda, Tadashi; Takeda, Masako; Hara, Noriko; Nakanishi, Kazushige; Urita, Yoshihisa; Hattori, Risa; Miura, Ken; Taniguchi, Tomoko

    2014-01-01

    Ornithine transcarbamylase deficiency (OTCD) is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left. PMID:25759629

  7. Thioacidolysis Marker Compound for Ferulic Acid Incorporation into Angiosperm Lignins (and an Indicator for Cinnamoyl-coenzyme-A Reductase Deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A molecular marker compound, derived from lignin by the thioacidolysis degradative method, for structures produced when ferulic acid is incorporated into lignification in angiosperms (poplar, Arabidopsis, tobacco) has been structurally identified as 1,2,2-trithioethyl ethylguaiacol [1-(4-hydroxy-3-m...

  8. Intracellular distribution of amino acids in an slp1 vacuole-deficient mutant of the yeast Saccharomyces cerevisiae.

    PubMed

    Gent, D P; Slaughter, J C

    1998-05-01

    Amino acid pools were compared in a constructed diploid strain of Saccharomyces cerevisiae, SKD1, and a closely related strain, SKD2, carrying the slp1 mutation characterized by low pools of lysine and lacking a central vacuole. Cells of SKD2 grew more poorly than SKD1 but took up the same total amount of amino acids from the medium per cell although the profile differed between the two strains. Initially, the total pool was much higher in SKD1 than in SKD2 but the overall relative distribution between cytosol and vacuole was identical and mainly cytosolic even though the composition differed between the two strains. At the end of growth the amino acid concentration had increased and become predominantly vacuolar. Two days later the total pool in SKD1 had declined to the starting level but the intracellular distribution remained identical to that at the end of fermentation. The total concentration of amino acids in SKD2 continued to increase, particularly in the cytosol. PMID:9674128

  9. Control of Gastric Acid Secretion in Somatostatin Receptor 2 Deficient Mice: Shift from Endocrine/Paracrine to Neurocrine Pathways

    PubMed Central

    Zhao, Chun-Mei; Martinez, Vicente; Piqueras, Laura; Wang, Lixin; Taché, Yvette; Chen, Duan

    2008-01-01

    The gastrin-enterochromaffin-like (ECL) cell-parietal cell axis is known to play an important role in the regulation of gastric acid secretion. Somatostatin, acting on somatostatin receptor type 2 (SSTR2), interferes with this axis by suppressing the activity of the gastrin cells, ECL cells, and parietal cells. Surprisingly, however, freely fed SSTR2 knockout mice seem to display normal circulating gastrin concentration and unchanged acid output. In the present study, we compared the control of acid secretion in these mutant mice with that in wild-type mice. In SSTR2 knockout mice, the number of gastrin cells was unchanged; whereas the numbers of somatostatin cells were reduced in the antrum (−55%) and increased in the oxyntic mucosa (35%). The ECL cells displayed a reduced expression of histidine decarboxylase and vesicle monoamine transport type 2 (determined by immunohistochemistry), and an impaired transformation of the granules to secretory vesicles (determined by electron microscopic analysis), suggesting low activity of the ECL cells. These changes were accompanied by an increased expression of galanin receptor type 1 in the oxyntic mucosa. The parietal cells were found to respond to pentagastrin or to vagal stimulation (evoked by pylorus ligation) with increased acid production. In conclusion, the inhibitory galanin-galanin receptor type 1 pathway is up-regulated in the ECL cells, and the direct stimulatory action of gastrin and vagal excitation is enhanced on the parietal cells in SSTR2 knockout mice. We suggest that there is a remodeling of the neuroendocrine mechanisms that regulate acid secretion in these mutant mice. PMID:17974627

  10. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain.

    PubMed

    Craciunescu, Corneliu N; Brown, Elliott C; Mar, Mei-Heng; Albright, Craig D; Nadeau, Marie R; Zeisel, Steven H

    2004-01-01

    In mice and rats, maternal dietary choline intake during late pregnancy modulates mitosis and apoptosis in progenitor cells of the fetal hippocampus and septum. Because choline and folate are interrelated metabolically, we investigated the effects of maternal dietary folate availability on progenitor cells in fetal mouse telencephalon. Timed-pregnant mice were fed a folate-supplemented (FS), control (FCT) or folate-deficient (FD) AIN-76 diet from d 11-17 of pregnancy. FD decreased the number of progenitor cells undergoing cell replication in the ventricular zones of the developing mouse brain septum (46.6% of FCT), caudate putamen (43.5%), and neocortex (54.4%) as assessed using phosphorylated histone H3 (a specific marker of mitotic phase) and confirmed by bromodeoxyuridine (BrdU) labeling of the S phase. In addition, 106.2% more apoptotic cells were found in FD than in FCT fetal septum. We observed 46.8% more calretinin-positive cells in the medial septal-diagonal band region of FD compared with pups from control dams. FS mice did not differ significantly from FCT mice in any of these measures. These results suggest that progenitor cells in fetal forebrain are sensitive to maternal dietary folate during late gestation. PMID:14704311

  11. Comparative Study of Intravenous Iron Versus Intravenous Ascorbic Acid for Treatment of Functional Iron Deficiency in Patients Under Hemodialysis: A Randomized Clinical Trial

    PubMed Central

    Sedighi, Omid; Makhlough, Atieh; Janbabai, Ghasem; Neemi, Mohammad

    2013-01-01

    Background Functional iron deficiency (FID) may cause erythropoietin resistance in patients under hemodialysis (HD). Since the role of chronic inflammation or oxidative stress in its pathogenesis is unclear, controversy remains to whether intravenous iron or intravenous ascorbic acid (an antioxidant) can improve this anemia due to decreased iron availability. Objectives The current study compared the effect of intravenous iron versus intravenous ascorbic acid in the management of FID in HD patients. Patients and Methods Forty HD patients with hemoglobin (Hb) ≤ 11 g/dL, serum ferritin ≥ 500 ng/mL and transferrin saturation (TSAT) ≤ 25% were randomly divided into two groups. 20 patients received 100 mg of intravenous (IV) iron (group I), and 20 patients received 300 mg of IV ascorbic acid (group II) postdialysis, twice a week for 5 consecutive weeks. Hb and iron metabolism indices were measured before the onset of the study and after 12 weeks following therapy. Results Twenty one percent of all HD patients, exhibited high serum ferritin, low TSAT and sufficient data for analysis. Both Group I (n = 20) and Group II (n = 20) patients showed a significant increase in Hb, serum iron, and TSAT (P < 0.001). There were no significant differences between both groups in increasing Hb (P = 0.076), serum iron (P = 0.589), serum ferritin (0.725), and TSAT (P = 0.887). Conclusions This study showed that both IV iron and IV ascorbic acid can improve FID in HD patients. A larger randomized trial is warranted to determine the optimal management of FID in HD patients. PMID:24350091

  12. Improved production of homo-D-lactic acid via xylose fermentation by introduction of xylose assimilation genes and redirection of the phosphoketolase pathway to the pentose phosphate pathway in L-Lactate dehydrogenase gene-deficient Lactobacillus plantarum.

    PubMed

    Okano, Kenji; Yoshida, Shogo; Yamada, Ryosuke; Tanaka, Tsutomu; Ogino, Chiaki; Fukuda, Hideki; Kondo, Akihiko

    2009-12-01

    The production of optically pure d-lactic acid via xylose fermentation was achieved by using a Lactobacillus plantarum NCIMB 8826 strain whose l-lactate dehydrogenase gene was deficient and whose phosphoketolase genes were replaced with a heterologous transketolase gene. After 60 h of fermentation, 41.2 g/liter of d-lactic acid was produced from 50 g/liter of xylose.

  13. Disturbances in cholesterol, bile acid and glucose metabolism in peroxisomal 3-ketoacylCoA thiolase B deficient mice fed diets containing high or low fat contents.

    PubMed

    Nicolas-Francès, Valérie; Arnauld, Ségolène; Kaminski, Jacques; Ver Loren van Themaat, Emiel; Clémencet, Marie-Claude; Chamouton, Julie; Athias, Anne; Grober, Jacques; Gresti, Joseph; Degrace, Pascal; Lagrost, Laurent; Latruffe, Norbert; Mandard, Stéphane

    2014-03-01

    The peroxisomal 3-ketoacyl-CoA thiolase B (ThB) catalyzes the thiolytic cleavage of straight chain 3-ketoacyl-CoAs. Up to now, the ability of ThB to interfere with lipid metabolism was studied in mice fed a laboratory chow enriched or not with the synthetic agonist Wy14,643, a pharmacological activator of the nuclear hormone receptor PPARα. The aim of the present study was therefore to determine whether ThB could play a role in obesity and lipid metabolism when mice are chronically fed a synthetic High Fat Diet (HFD) or a Low Fat Diet (LFD) as a control diet. To investigate this possibility, wild-type (WT) mice and mice deficient for Thb (Thb(-/-)) were subjected to either a synthetic LFD or a HFD for 25 weeks, and their responses were compared. First, when fed a normal regulatory laboratory chow, Thb(-/-) mice displayed growth retardation as well as a severe reduction in the plasma level of Growth Hormone (GH) and Insulin Growth Factor-I (IGF-I), suggesting alterations in the GH/IGF-1 pathway. When fed the synthetic diets, the corrected energy intake to body mass was significantly higher in Thb(-/-) mice, yet those mice were protected from HFD-induced adiposity. Importantly, Thb(-/-) mice also suffered from hypoglycemia, exhibited reduction in liver glycogen stores and circulating insulin levels under the LFD and the HFD. Thb deficiency was also associated with higher levels of plasma HDL (High Density Lipoproteins) cholesterol and increased liver content of cholesterol under both the LFD and the HFD. As shown by the plasma lathosterol to cholesterol ratio, a surrogate marker for cholesterol biosynthesis, whole body cholesterol de novo synthesis was increased in Thb(-/-) mice. By comparing liver RNA from WT mice and Thb(-/-) mice using oligonucleotide microarray and RT-qPCR, a coordinated decrease in the expression of critical cholesterol synthesizing genes and an increased expression of genes involved in bile acid synthesis (Cyp7a1, Cyp17a1, Akr1d1) were

  14. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  15. Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

    PubMed Central

    Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

    2016-01-01

    Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371

  16. PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

    PubMed Central

    Gao, Qian; Jia, Yuzhi; Yang, Gongshe; Zhang, Xiaohong; Boddu, Prajwal C.; Petersen, Bryon; Narsingam, Saiprasad; Zhu, Yi-Jun; Thimmapaya, Bayar; Kanwar, Yashpal S.; Reddy, Janardan K.

    2016-01-01

    Obesity poses an increased risk of developing metabolic syndrome and closely associated nonalcoholic fatty liver disease, including liver cancer. Satiety hormone leptin-deficient (ob/ob) mice, considered paradigmatic of nutritional obesity, develop hepatic steatosis but are less prone to developing liver tumors. Sustained activation of peroxisome proliferator–activated receptor α (PPARα) in ob/ob mouse liver increases fatty acid oxidation (FAO), which contributes to attenuation of obesity but enhances liver cancer risk. To further evaluate the role of PPARα-regulated hepatic FAO and energy burning in the progression of fatty liver disease, we generated PPARα-deficient ob/ob (PPARαΔob/ob) mice. These mice become strikingly more obese compared to ob/ob littermates, with increased white and brown adipose tissue content and severe hepatic steatosis. Hepatic steatosis becomes more severe in fasted PPARαΔob/ob mice as they fail to up-regulate FAO systems. PPARαΔob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARαΔob/ob mice are severely obese, there was no significant increase in liver tumor incidence, even when maintained on a diet containing Wy-14,643. We conclude that sustained PPARα activation–related increase in FAO in fatty livers of obese ob/ob mice increases liver cancer risk, whereas deletion of PPARα in ob/ob mice aggravates obesity and hepatic steatosis. However, it does not lead to liver tumor development because of reduction in FAO and energy burning. PMID:25773177

  17. Iron deficiency.

    PubMed

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  18. Flaxseed Oil Containing α-Linolenic Acid Ester of Plant Sterol Improved Atherosclerosis in ApoE Deficient Mice

    PubMed Central

    Han, Hao; Yan, Peipei; Chen, Li; Luo, Cheng; Gao, Hui; Deng, Qianchun; Zheng, Mingming; Shi, Yong; Liu, Liegang

    2015-01-01

    Plant sterols (PS) have potential preventive function in atherosclerosis due to their cholesterol-lowering ability. Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties. This study was designed to evaluate the effects of flaxseed oil containing α-linolenic acid ester of PS (ALA-PS) on atherosclerosis and investigate the underlying mechanisms. C57BL/6 mice were administered a regular diet and apoE knockout (apoE-KO) mice were given a high fat diet alone or supplemented with 5% flaxseed oil with or without 3.3% ALA-PS for 18 weeks. Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress. These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase). PMID:26180602

  19. Nutritional modulation of guinea pig skin hyperproliferation by essential fatty acid deficiency is associated with selective down regulation of protein kinase C-beta.

    PubMed

    Cho, Y; Ziboh, V A

    1995-11-01

    In a previous study we demonstrated that 13-hydroxyoctadecadienoic acid (13-HODE), a 15-lipoxygenase metabolite of linoleic acid is incorporated into epidermal phosphatidyl 4,5-bisphosphate (PtdIns 4,5-P2) and released as 13-HODE-containing-diacylglycerol (13-HODE-DAG). In vitro, 13-HODE-DAG was shown to selectively inhibit epidermal total protein kinase C (PKC-beta) activity. To determine whether these observations are relevant in vivo, guinea pigs were made essential fatty acid deficient (EFAD) by feeding them a basal diet supplemented with 4% hydrogenated coconut oil for 8 wk. Tissue levels of putative 13-HODE-DAG, protein kinase C (PKC) isozymes and tissue hyperproliferation were determined in the epidermal preparations from skin of control safflower oil-fed guinea pigs, those fed EFAD diet and those fed EFAD diet followed by the control diet for 2 wk. Our data revealed that cutaneous 13-HODE and 13-HODE-DAG were significantly lower in EFAD animals than in safflower-fed controls. These reductions were associated with both elevated epidermal hyperproliferation and elevated expressions and activities of PKC-alpha and beta-isozymes. Refeeding the animals with safflower oil for 2 wk replenished tissue levels of 13-HODE-DAG, which inversely correlated with the selective down regulation of PKC-beta expression and activity and the reversal of hyperproliferation. In contrast, although, the expression and activity of PKC-alpha was elevated in the epidermis of the EFAD guinea pigs, this elevated PKC-alpha expression was not down regulated after refeeding the safflower oil diet to the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: current status, future directions, and dietary recommendations.

    PubMed

    McNamara, Robert K

    2009-01-01

    Major recurrent affective disorders, including major depressive disorder (MDD) and bipolar disorder, represent a growing public health crisis in the United States. Evidence from cross-national and cross-sectional epidemiological surveys, comparative peripheral and central composition studies, and placebo-controlled intervention trials suggest that n-3 fatty acid deficiency may contribute to the pathoaetiology of affective disorders. These data are reviewed with the objective of estimating a daily docosahexaenoic acid (DHA, 22:6n-3) intake value that is projected to be efficacious in mitigating vulnerability. It is proposed that daily DHA intake sufficient to increase erythrocyte DHA composition to a level found in healthy subjects from Japan (7%), where the lifetime prevalence rates of MDD and bipolar disorder are several fold lower than the US, represents an appropriate target. To achieve this target, preliminary DHA intervention trials indicate that a daily dose of 400-700 mg/d in children and 700-1000 mg/d in adults would be required. Based on the results of placebo-controlled intervention trials, a higher daily DHA dose in the order of 1000-1500 mg/d in a 2:1 eicosapentaenoic acid (EPA, 20:5n-3):DHA ratio may be optimal for the treatment of established affective disorders. These recommendations are intended to guide future dose-ranging placebo-controlled DHA intervention trials in patients with established affective disorders, as well as in asymptomatic subjects at elevated risk for developing affective disorders. Such early intervention studies are currently feasible and will ultimately be required to definitively evaluate whether DHA is a required nutrient for the prevention of affective disorders.

  1. Response to zinc deficiency of two rice lines with contrasting tolerance is determined by root growth maintenance and organic acid exudation rates, and not by zinc-transporter activity.

    PubMed

    Widodo, Basuki; Broadley, Martin R; Rose, Terry; Frei, Michael; Pariasca-Tanaka, Juan; Yoshihashi, Tadashi; Thomson, Michael; Hammond, John P; Aprile, Alessio; Close, Timothy J; Ismail, Abdelbagi M; Wissuwa, Matthias

    2010-04-01

    *Zinc (Zn)-deficient soils constrain rice (Oryza sativa) production and cause Zn malnutrition. The identification of Zn-deficiency-tolerant rice lines indicates that breeding might overcome these constraints. Here, we seek to identify processes underlying Zn-deficiency tolerance in rice at the physiological and transcriptional levels. *A Zn-deficiency-tolerant line RIL46 acquires Zn more efficiently and produces more biomass than its nontolerant maternal line (IR74) at low [Zn](ext) under field conditions. We tested if this was the result of increased expression of Zn(2+) transporters; increased root exudation of deoxymugineic acid (DMA) or low-molecular-weight organic acids (LMWOAs); and/or increased root production. Experiments were performed in field and controlled environment conditions. *There was little genotypic variation in transcript abundance of Zn-responsive root Zn(2+)-transporters between the RIL46 and IR74. However, root exudation of DMA and LMWOA was greater in RIL46, coinciding with increased root expression of putative ligand-efflux genes. Adventitious root production was maintained in RIL46 at low [Zn](ext), correlating with altered expression of root-specific auxin-responsive genes. *Zinc-deficiency tolerance in RIL46 is most likely the result of maintenance of root growth, increased efflux of Zn ligands, and increased uptake of Zn-ligand complexes at low [Zn](ext); these traits are potential breeding targets. PMID:20100202

  2. Essential fatty acid profiles differ across diets and browse of black rhinoceros.

    PubMed

    Grant, Jacqualine B; Brown, Dan L; Dierenfeld, Ellen S

    2002-01-01

    In captivity, black rhinoceros (Diceros bicornis) suffer from idiopathic skin lesions that may be linked to dietary deficiencies, in particular essential fatty acid deficiency (EFAD). Therefore, a study was undertaken from July 1995 to May 1997 to characterize the diet of captive D. bicornis in North American zoos and measure fat and fatty acid composition in zoo diet, and African and North American browses. Descriptions of all dietary items offered to black rhinos on a daily basis were compiled from 20 North American zoos; zoo diet contained (mean +/- SE) 61 +/- 2% hay, 28 +/- 2% grain pellets, 6 +/- 1% produce, and 5 +/- 1% fresh browse, with hay and grain pellets together comprising nearly 90% of items offered. Gas chromatography-mass spectrometry analysis (GC-MS) was used to measure triacylglycerol equivalent (TAG), total fatty acids (TFA), and essential fatty acids (EFA) in zoo diet, and African and North American browses. North American browse contained more TAG and TFA than did zoo diet or African browse. Zoo diet contained more linoleic acid (18:2n6) and less linolenic acid (18:3n3) than either African browse corrected for degradation losses or North American browse, whether measured as weight percentage of dry sample or as weight percentage of TFA. In addition, the ratio of 18:2n6 to 18:3n3 was significantly lower in both browses than in zoo diet. There are significant nutritional differences between the major dietary components of North American captive black rhinoceros diets and native African browses that warrant further exploration given the health problems associated with this animal in captivity. PMID:11838204

  3. Essential fatty acid profiles differ across diets and browse of black rhinoceros.

    PubMed

    Grant, Jacqualine B; Brown, Dan L; Dierenfeld, Ellen S

    2002-01-01

    In captivity, black rhinoceros (Diceros bicornis) suffer from idiopathic skin lesions that may be linked to dietary deficiencies, in particular essential fatty acid deficiency (EFAD). Therefore, a study was undertaken from July 1995 to May 1997 to characterize the diet of captive D. bicornis in North American zoos and measure fat and fatty acid composition in zoo diet, and African and North American browses. Descriptions of all dietary items offered to black rhinos on a daily basis were compiled from 20 North American zoos; zoo diet contained (mean +/- SE) 61 +/- 2% hay, 28 +/- 2% grain pellets, 6 +/- 1% produce, and 5 +/- 1% fresh browse, with hay and grain pellets together comprising nearly 90% of items offered. Gas chromatography-mass spectrometry analysis (GC-MS) was used to measure triacylglycerol equivalent (TAG), total fatty acids (TFA), and essential fatty acids (EFA) in zoo diet, and African and North American browses. North American browse contained more TAG and TFA than did zoo diet or African browse. Zoo diet contained more linoleic acid (18:2n6) and less linolenic acid (18:3n3) than either African browse corrected for degradation losses or North American browse, whether measured as weight percentage of dry sample or as weight percentage of TFA. In addition, the ratio of 18:2n6 to 18:3n3 was significantly lower in both browses than in zoo diet. There are significant nutritional differences between the major dietary components of North American captive black rhinoceros diets and native African browses that warrant further exploration given the health problems associated with this animal in captivity.

  4. Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats.

    PubMed

    McNamara, Robert K; Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W

    2013-12-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here, we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group was administered FLX (10mg/kg/day) for 30days (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-25%, p≤0.0001) and DEF+FLX (-28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  5. Omega-3 Fatty Acid Deficiency Does Not Alter the Effects of Chronic Fluoxetine Treatment on Central Serotonin Turnover or Behavior in the Forced Swim Test in Female Rats

    PubMed Central

    McNamara, Robert K.; Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W.

    2013-01-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group were administered FLX (10 mg/kg/d) for 30 d (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (−25%, p≤0.0001) and DEF+FLX (−28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  6. Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice.

    PubMed

    Aqul, Amal; Lopez, Adam M; Posey, Kenneth S; Taylor, Anna M; Repa, Joyce J; Burns, Dennis K; Turley, Stephen D

    2014-10-15

    Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal(-/-) and matching lal(+/+) mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal(-/-) mice sequestered cholesterol at an average rate of 3.2 mg·day(-1)·animal(-1). The proportion of the body sterol pool contained in the liver of the lal(-/-) mice was 64 vs. 6.3% in their lal(+/+) controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal(-/-) mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal(-/-) mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal(+/+) controls. The rate of cholesterol synthesis in the lal(-/-) mice exceeded that in the lal(+/+) controls by 3.7 mg·day(-1)·animal(-1). Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal(-/-) mice, but their rate of neutral sterol excretion was 59% higher than in their lal(+/+) controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal(-/-) mice was 355 days.

  7. [Nutritional deficiencies associated with bariatric surgery].

    PubMed

    Folope, Vanessa; Coëffier, Moïse; Déchelotte, Pierre

    2007-04-01

    Morbidly obese patients often have nutritional deficiencies, particularly in fat-soluble vitamins, folic acid and zinc. After bariatric surgery, these deficiencies may increase and others can appear, especially because of the limitation of food intake in gastric reduction surgery and of malabsorption in by-pass procedures. The latter result in more important weight loss but also increase the risk of more severe deficiencies. The protein deficiency associated with a decrease in the fat-free mass has been described in both procedures. It can sometimes require an enteral or parenteral support. Anemia can be secondary to iron deficiency, folic acid deficiency and even to vitamin B12 deficiency. Neurological disorders such as Gayet-Wernicke encephalopathy due to thiamine deficiency, or peripheral neuropathies may also be observed. Malabsorption of fat-soluble vitamins and other nutrients, especially if diagnosed after by-pass surgery, rarely cause clinical symptoms. However, some complications have been reported such as bone demineralization due to vitamin D deficiency, hair loss secondary to zinc deficiency or hemeralopia from vitamin A deficiency. A careful nutritional follow-up should be performed during pregnancy after obesity surgery, because possible deficiencies can affect the health of both the mother and child. In conclusion, increased awareness of the risk of deficiency and the systematic dosage of micronutrients are needed in the pre- and postoperative period in obese patients undergoing bariatric surgery. The case by case correction of these deficiencies is mandatory, and their systematic prevention should be evaluated.

  8. Nonclinical safety assessment of recombinant human acid sphingomyelinase (rhASM) for the treatment of acid sphingomyelinase deficiency:the utility of animal models of disease in the toxicological evaluation of potential therapeutics.

    PubMed

    Murray, James M; Thompson, Anne Marie; Vitsky, Allison; Hawes, Michael; Chuang, Wei-Lien; Pacheco, Joshua; Wilson, Stephen; McPherson, John M; Thurberg, Beth L; Karey, Kenneth P; Andrews, Laura

    2015-02-01

    Recombinant human acid sphingomyelinase (rhASM) is being developed as an enzyme replacement therapy for patients with acid sphingomyelinase deficiency (Niemann-Pick disease types A and B), which causes sphingomyelin to accumulate in lysosomes. In the acid sphingomyelinase knock-out (ASMKO) mouse, intravenously administered rhASM reduced tissue sphingomyelin levels in a dose-dependent manner. When rhASM was administered to normal rats, mice, and dogs, no toxicity was observed up to a dose of 30mg/kg. However, high doses of rhASM≥10mg/kg administered to ASMKO mice resulted in unexpected toxicity characterized by cardiovascular shock, hepatic inflammation, adrenal hemorrhage, elevations in ceramide and cytokines (especially IL-6, G-CSF, and keratinocyte chemoattractant [KC]), and death. The toxicity could be completely prevented by the administration of several low doses (3mg/kg) of rhASM prior to single or repeated high doses (≥20mg/kg). These results suggest that the observed toxicity involves the rapid breakdown of large amounts of sphingomyelin into ceramide and/or other toxic downstream metabolites, which are known signaling molecules with cardiovascular and pro-inflammatory effects. Our results suggest that the nonclinical safety assessment of novel therapeutics should include the use of specific animal models of disease whenever feasible.

  9. Perigestational dietary folic acid deficiency protects against medulloblastoma formation in a mouse model of nevoid basal cell carcinoma syndrome.

    PubMed

    Been, Raha A; Ross, Julie A; Nagel, Christian W; Hooten, Anthony J; Langer, Erica K; DeCoursin, Krista J; Marek, Courtney A; Janik, Callie L; Linden, Michael A; Reed, Robyn C; Schutten, Melissa M; Largaespada, David A; Johnson, Kimberly J

    2013-01-01

    Hereditary nevoid basal cell carcinoma syndrome (NBCCS) is caused by PTCH1 gene mutations that result in diverse neoplasms including medulloblastoma (MB). Epidemiological studies report reduced pediatric brain tumor risks associated with maternal intake of prenatal vitamins containing folic acid (FA) and FA supplements specifically. We hypothesized that low maternal FA intake during the perigestational period would increase MB incidence in a transgenic NBCCS mouse model, which carries an autosomal dominant mutation in the Ptch1 gene. Female wild-type C57BL/6 mice (n = 126) were randomized to 1 of 3 diets with differing FA amounts: 0.3 mg/kg (low), 2.0 mg/kg (control), and 8.0 mg/kg (high) 1 mo prior to mating with Ptch1 (+/-) C57BL/6 males. Females were maintained on the diet until pup weaning; the pups were then aged for tumor development. Compared to the control group, offspring MB incidence was significantly lower in the low FA group (Hazard Ratio = 0.47; 95% confidence interval 0.27-0.80) at 1 yr. No significant difference in incidence was observed between the control and high FA groups. Low maternal perigestational FA levels may decrease MB incidence in mice genetically predisposed to tumor development. Our results could have implications for prenatal FA intake recommendations in the presence of cancer syndromes. PMID:23909730

  10. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis.

    PubMed

    Lazic, Milos; Inzaugarat, Maria Eugenia; Povero, Davide; Zhao, Iris C; Chen, Mark; Nalbandian, Madlena; Miller, Yury I; Cherñavsky, Alejandra C; Feldstein, Ariel E; Sears, Dorothy D

    2014-01-01

    Obesity is associated with metabolic perturbations including liver and adipose tissue inflammation, insulin resistance, and type 2 diabetes. Omega-6 fatty acids (ω6) promote and omega-3 fatty acids (ω3) reduce inflammation as they can be metabolized to pro- and anti-inflammatory eicosanoids, respectively. 12/15-lipoxygenase (12/15-LO) enzymatically produces some of these metabolites and is induced by high fat (HF) diet. We investigated the effects of altering dietary ω6/ω3 ratio and 12/15-LO deficiency on HF diet-induced tissue inflammation and insulin resistance. We examined how these conditions affect circulating concentrations of oxidized metabolites of ω6 arachidonic and linoleic acids and innate and adaptive immune system activity in the liver. For 15 weeks, wild-type (WT) mice were fed either a soybean oil-enriched HF diet with high dietary ω6/ω3 ratio (11∶1, HFH), similar to Western-style diet, or a fat Kcal-matched, fish oil-enriched HF diet with a low dietary ω6/ω3 ratio of 2.7∶1 (HFL). Importantly, the total saturated, monounsaturated and polyunsaturated fat content was matched in the two HF diets, which is unlike most published fish oil studies in mice. Despite modestly increased food intake, WT mice fed HFL were protected from HFH-diet induced steatohepatitis, evidenced by decreased hepatic mRNA expression of pro-inflammatory genes and genes involved in lymphocyte homing, and reduced deposition of hepatic triglyceride. Furthermore, oxidized metabolites of ω6 arachidonic acid were decreased in the plasma of WT HFL compared to WT HFH-fed mice. 12/15-LO knockout (KO) mice were also protected from HFH-induced fatty liver and elevated mRNA markers of inflammation and lymphocyte homing. 12/15-LOKO mice were protected from HFH-induced insulin resistance but reducing dietary ω6/ω3 ratio in WT mice did not ameliorate insulin resistance or adipose tissue inflammation. In conclusion, lowering dietary ω6/ω3 ratio in HF diet significantly reduces

  11. Rapid Phosphoproteomic Effects of Abscisic Acid (ABA) on Wild-Type and ABA Receptor-Deficient A. thaliana Mutants*

    PubMed Central

    Minkoff, Benjamin B.; Stecker, Kelly E.; Sussman, Michael R.

    2015-01-01

    Abscisic acid (ABA)1 is a plant hormone that controls many aspects of plant growth, including seed germination, stomatal aperture size, and cellular drought response. ABA interacts with a unique family of 14 receptor proteins. This interaction leads to the activation of a family of protein kinases, SnRK2s, which in turn phosphorylate substrates involved in many cellular processes. The family of receptors appears functionally redundant. To observe a measurable phenotype, four of the fourteen receptors have to be mutated to create a multilocus loss-of-function quadruple receptor (QR) mutant, which is much less sensitive to ABA than wild-type (WT) plants. Given these phenotypes, we asked whether or not a difference in ABA response between the WT and QR backgrounds would manifest on a phosphorylation level as well. We tested WT and QR mutant ABA response using isotope-assisted quantitative phosphoproteomics to determine what ABA-induced phosphorylation changes occur in WT plants within 5 min of ABA treatment and how that phosphorylation pattern is altered in the QR mutant. We found multiple ABA-induced phosphorylation changes that occur within 5 min of treatment, including three SnRK2 autophosphorylation events and phosphorylation on SnRK2 substrates. The majority of robust ABA-dependent phosphorylation changes observed were partially diminished in the QR mutant, whereas many smaller ABA-dependent phosphorylation changes observed in the WT were not responsive to ABA in the mutant. A single phosphorylation event was increased in response to ABA treatment in both the WT and QR mutant. A portion of the discovery data was validated using selected reaction monitoring-based targeted measurements on a triple quadrupole mass spectrometer. These data suggest that different subsets of phosphorylation events depend upon different subsets of the ABA receptor family to occur. Altogether, these data expand our understanding of the model by which the family of ABA receptors directs

  12. Rice: Characterizing the Environmental Response of a Gibberellic Acid-Deficient Rice for Use as a Model Crop

    NASA Technical Reports Server (NTRS)

    Frantz, Jonathan M.; Pinnock, Derek; Klassen, Steve; Bugbee, Bruce

    2004-01-01

    Rice (Oryza sativa L.) is a useful model crop plant. Rice was the first crop plant to have its complete genome sequenced. Unfortunately, even semi-dwarf rice cultivars are 60 to 90 an tail, and large plant populations cannot be grown in the confined volumes of greenhouses and growth chambers. We recently identified an extremely short (20 em tall) rice line, which is an ideal model for larger rice cultivars. We called this line "Super Dwarf rice." Here we report the response of Super Dwarf to temperature, photoperiod, photosynthetic photon flux (PPF), and factors that can affect time to head emergence. Vegetative biomass increased 6% per degree Celsius, with increasing temperature from 27 to 31 C. Seed yield decreased by 2% per degree Celsius rise in temperature, and as a result, harvest index decreased from 60 to 54%. The time to heading increased by 2 d for every hour above a 12-h photoperiod. Yield increased with increasing PPF up to the highest level tested at 1800 micro-mol/sq m/s (12-h photoperiod; 77.8 mol/sq m/d). Yield efficiency (grams per mole of photons) increased to 900 micro-mol/sq m/s and then slightly decreased at 1800 micro-mol/sq m/s . Heading was delayed by addition of gibberellic acid 3 (GA,) to the root zone but was hastened under mild N stress. Overall, short stature, high yield, high harvest index, and no extraordinary environmental requirements make Super Dwarf rice an excellent model plant for yield studies in controlled environments.

  13. Rapid Phosphoproteomic Effects of Abscisic Acid (ABA) on Wild-Type and ABA Receptor-Deficient A. thaliana Mutants.

    PubMed

    Minkoff, Benjamin B; Stecker, Kelly E; Sussman, Michael R

    2015-05-01

    Abscisic acid (ABA)¹ is a plant hormone that controls many aspects of plant growth, including seed germination, stomatal aperture size, and cellular drought response. ABA interacts with a unique family of 14 receptor proteins. This interaction leads to the activation of a family of protein kinases, SnRK2s, which in turn phosphorylate substrates involved in many cellular processes. The family of receptors appears functionally redundant. To observe a measurable phenotype, four of the fourteen receptors have to be mutated to create a multilocus loss-of-function quadruple receptor (QR) mutant, which is much less sensitive to ABA than wild-type (WT) plants. Given these phenotypes, we asked whether or not a difference in ABA response between the WT and QR backgrounds would manifest on a phosphorylation level as well. We tested WT and QR mutant ABA response using isotope-assisted quantitative phosphoproteomics to determine what ABA-induced phosphorylation changes occur in WT plants within 5 min of ABA treatment and how that phosphorylation pattern is altered in the QR mutant. We found multiple ABA-induced phosphorylation changes that occur within 5 min of treatment, including three SnRK2 autophosphorylation events and phosphorylation on SnRK2 substrates. The majority of robust ABA-dependent phosphorylation changes observed were partially diminished in the QR mutant, whereas many smaller ABA-dependent phosphorylation changes observed in the WT were not responsive to ABA in the mutant. A single phosphorylation event was increased in response to ABA treatment in both the WT and QR mutant. A portion of the discovery data was validated using selected reaction monitoring-based targeted measurements on a triple quadrupole mass spectrometer. These data suggest that different subsets of phosphorylation events depend upon different subsets of the ABA receptor family to occur. Altogether, these data expand our understanding of the model by which the family of ABA receptors directs

  14. Deficiency in a Very-Long-Chain Fatty Acid β-Ketoacyl-Coenzyme A Synthase of Tomato Impairs Microgametogenesis and Causes Floral Organ Fusion1[W

    PubMed Central

    Smirnova, Anna; Leide, Jana; Riederer, Markus

    2013-01-01

    Previously, it was shown that β-ketoacyl-coenzyme A synthase ECERIFERUM6 (CER6) is necessary for the biosynthesis of very-long-chain fatty acids with chain lengths beyond C28 in tomato (Solanum lycopersicum) fruits and C26 in Arabidopsis (Arabidopsis thaliana) leaves and the pollen coat. CER6 loss of function in Arabidopsis resulted in conditional male sterility, since pollen coat lipids are responsible for contact-mediated pollen hydration. In tomato, on the contrary, pollen hydration does not rely on pollen coat lipids. Nevertheless, mutation in SlCER6 impairs fertility and floral morphology. Here, the contribution of SlCER6 to the sexual reproduction and flower development of tomato was addressed. Cytological analysis and cross-pollination experiments revealed that the slcer6 mutant has male sterility caused by (1) hampered pollen dispersal and (2) abnormal tapetum development. SlCER6 loss of function provokes a decrease of n- and iso-alkanes with chain lengths of C27 or greater and of anteiso-alkanes with chain lengths of C28 or greater in flower cuticular waxes, but it has no impact on flower cuticle ultrastructure and cutin content. Expression analysis confirmed high transcription levels of SlCER6 in the anther and the petal, preferentially in sites subject to epidermal fusion. Hence, wax deficiency was proposed to be the primary reason for the flower fusion phenomenon in tomato. The SlCER6 substrate specificity was revisited. It might be involved in elongation of not only linear but also branched very-long-chain fatty acids, leading to production of the corresponding alkanes. SlCER6 implements a function in the sexual reproduction of tomato that is different from the one in Arabidopsis: SlCER6 is essential for the regulation of timely tapetum degradation and, consequently, microgametogenesis. PMID:23144186

  15. Abscisic Acid Deficiency Causes Changes in Cuticle Permeability and Pectin Composition That Influence Tomato Resistance to Botrytis cinerea1[C][W][OA

    PubMed Central

    Curvers, Katrien; Seifi, Hamed; Mouille, Grégory; de Rycke, Riet; Asselbergh, Bob; Van Hecke, Annelies; Vanderschaeghe, Dieter; Höfte, Herman; Callewaert, Nico; Van Breusegem, Frank; Höfte, Monica

    2010-01-01

    A mutant of tomato (Solanum lycopersicum) with reduced abscisic acid (ABA) production (sitiens) exhibits increased resistance to the necrotrophic fungus Botrytis cinerea. This resistance is correlated with a rapid and strong hydrogen peroxide-driven cell wall fortification response in epidermis cells that is absent in tomato with normal ABA production. Moreover, basal expression of defense genes is higher in the mutant compared with the wild-type tomato. Given the importance of this fast response in sitiens resistance, we investigated cell wall and cuticle properties of the mutant at the chemical, histological, and ultrastructural levels. We demonstrate that ABA deficiency in the mutant leads to increased cuticle permeability, which is positively correlated with disease resistance. Furthermore, perturbation of ABA levels affects pectin composition. sitiens plants have a relatively higher degree of pectin methylesterification and release different oligosaccharides upon inoculation with B. cinerea. These results show that endogenous plant ABA levels affect the composition of the tomato cuticle and cell wall and demonstrate the importance of cuticle and cell wall chemistry in shaping the outcome of this plant-fungus interaction. PMID:20709830

  16. Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

    PubMed

    Cheng, Yung-Hsin; Lin, Feng-Huei; Wang, Chien-Ying; Hsiao, Chen-Yuan; Chen, Hung-Ching; Kuo, Hsin-Yu; Tsai, Ting-Fen; Chiou, Shih-Hwa

    2016-10-01

    Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD.

  17. Oral retinyl palmitate or retinoic acid corrects mucosal IgA responses toward an intranasal influenza virus vaccine in vitamin A deficient mice.

    PubMed

    Surman, S L; Jones, B G; Sealy, R E; Rudraraju, R; Hurwitz, J L

    2014-05-01

    Vitamin A deficiency (VAD) is a leading cause of pediatric morbidity and mortality due to infectious diseases. Recent pre-clinical studies have revealed that VAD impairs mucosal IgA-producing antibody forming cell (AFC) responses toward a paramyxovirus vaccine in the upper respiratory tract (URT), thus impeding a first line of defense at the pathogen's point-of-entry. The studies described here tested the hypothesis that VAD may also impair immune responses after FluMist vaccinations. Results show that (i) IgA-producing antibody forming cells (AFCs) are significantly reduced following FluMist vaccination in VAD mice, and (ii) oral doses of either retinyl palmitate or retinoic acid administered on days 0, 3, and 7 relative to vaccination rescue the response. Data encourage the conduct of clinical studies to determine if there are FluMist vaccine weaknesses in human VAD populations and to test corrective supplementation strategies. Improvements in vaccine efficacy may ultimately reduce the morbidity and mortality caused by influenza virus worldwide. PMID:24657715

  18. Extending the Mannose 6-Phosphate Glycoproteome by High Resolution/Accuracy Mass Spectrometry Analysis of Control and Acid Phosphatase 5-Deficient Mice*

    PubMed Central

    Sleat, David E.; Sun, Pengling; Wiseman, Jennifer A.; Huang, Ling; El-Banna, Mukarram; Zheng, Haiyan; Moore, Dirk F.; Lobel, Peter

    2013-01-01

    In mammals, most newly synthesized lumenal lysosomal proteins are delivered to the lysosome by the mannose 6-phosphate (Man6P) targeting pathway. Man6P -containing proteins can be affinity-purified and characterized using proteomic approaches, and such studies have led to the discovery of new lysosomal proteins and associated human disease genes. One limitation to this approach is that in most cell types the Man6P modification is rapidly removed by acid phosphatase 5 (ACP5) after proteins are targeted to the lysosome, and thus, some lysosomal proteins may escape detection. In this study, we have extended the analysis of the lysosomal proteome using high resolution/accuracy mass spectrometry to identify and quantify proteins in a combined analysis of control and ACP5-deficient mice. To identify Man6P glycoproteins with limited tissue distribution, we analyzed multiple tissues and used statistical approaches to identify proteins that are purified with high specificity. In addition to 68 known Man6P glycoproteins, 165 other murine proteins were identified that may contain Man6P and may thus represent novel lysosomal residents. For four of these lysosomal candidates, (lactoperoxidase, phospholipase D family member 3, ribonuclease 6, and serum amyloid P component), we demonstrate lysosomal residence based on the colocalization of fluorescent fusion proteins with a lysosomal marker. PMID:23478313

  19. Cholestane-3β,5α,6β-triol: high levels in Niemann-Pick type C, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency.

    PubMed

    Pajares, Sonia; Arias, Angela; García-Villoria, Judit; Macías-Vidal, Judit; Ros, Emilio; de las Heras, Javier; Girós, Marisa; Coll, Maria J; Ribes, Antonia

    2015-10-01

    Niemann-Pick type C (NPC) is a progressive neurodegenerative disease characterized by lysosomal/endosomal accumulation of unesterified cholesterol and glycolipids. Recent studies have shown that plasma cholestane-3β,5α,6β-triol (CT) and 7-ketocholesterol (7-KC) could be potential biomarkers for the diagnosis of NPC patients. We aimed to know the sensitivity and specificity of these biomarkers for the diagnosis of NPC compared with other diseases that can potentially lead to oxysterol alterations. We studied 107 controls and 122 patients including 16 with NPC, 3 with lysosomal acid lipase (LAL) deficiency, 8 with other lysosomal diseases, 5 with galactosemia, 11 with cerebrotendinous xanthomatosis (CTX), 3 with Smith-Lemli-Opitz, 14 with peroxisomal biogenesis disorders, 19 with unspecific hepatic diseases, 13 with familial hypercholesterolemia, and 30 with neurological involvement and no evidence of an inherited metabolic disease. CT and 7-KC were analyzed by HPLC-ESI-MS/MS as mono-dimethylglycine derivatives. Levels of 7-KC were high in most of the studied diseases, whereas those of CT were only high in NPC, LAL, and CTX patients. Consequently, although CT is a sensitive biomarker of NPC disease, including those cases with doubtful filipin staining, it is not specific. 7-KC is a very unspecific biomarker.

  20. Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage.

    PubMed

    Hamilton, B F; Gould, D H

    1987-01-01

    The clinical signs and morphological brain lesions associated with histotoxic hypoxia induced by subcutaneous injection of 3-nitropropionic acid (NPA) in rats are described, and compared to hypoxic brain damage from other causes including ischemia and hypoglycemia. The brains were perfusion-fixed with paraformaldehyde/glutaraldehyde fixative, and examined by light and electron microscopy. Intoxicated rats developed severe neurological disease characterized by somnolence, uncoordinated gait with stereotypical paddling movements, and ventral or lateral recumbency. Recumbent rats had a selective, bilaterally symmetrical pattern of severe morphological injury in the caudate-putamen, hippocampus, and thalamus. Recumbency was a consistent indicator of the development of morphological brain lesions. In contrast to reports describing rat models of ischemia and hypoglycemia, morphological injury was not seen in the cerebral and cerebellar cortices of NPA-intoxicated rats. Ultrastructurally, neuronal alterations ranged from chromatin clumping with increased cytoplasmic lucency to severe cellular shrinkage or swelling with marked mitochondrial swelling (high amplitude swelling). White matter alterations included axonal swelling and adaxonal splitting of myelin lamellae. Vascular changes included perivascular deposits of proteinaceous material presumably from leakage of serum proteins, variable electron lucency of endothelial cell cytoplasm, an apparent increase in pinocytotic vesicles, rare platelet thrombosis of capillaries, and rare intravascular blebs of luminal plasma membrane. As a model of brain damage following energy deficiency, NPA intoxication has the advantages of producing morphological brain injury in a highly predictable anatomical pattern, and at a time paralleling the onset of clinical recumbency.

  1. Salicylic acid induction-deficient mutants of Arabidopsis express PR-2 and PR-5 and accumulate high levels of camalexin after pathogen inoculation.

    PubMed Central

    Nawrath, C; Métraux, J P

    1999-01-01

    In Arabidopsis, systemic acquired resistance against pathogens has been associated with the accumulation of salicylic acid (SA) and the expression of the pathogenesis-related proteins PR-1, PR-2, and PR-5. We report here the isolation of two nonallelic mutants impaired in the pathway leading to SA biosynthesis. These SA induction-deficient (sid) mutants do not accumulate SA after pathogen inoculation and are more susceptible to both virulent and avirulent forms of Pseudomonas syringae and Peronospora parasitica. However, sid mutants are not as susceptible to these pathogens as are transgenic plants expressing the nahG gene encoding an SA hydroxylase that degrades SA to catechol. In contrast to NahG plants, only the expression of PR-1 is strongly reduced in sid mutants, whereas PR-2 and PR-5 are still expressed after pathogen attack. Furthermore, the accumulation of the phytoalexin camalexin is normal. These results indicate that SA-independent compensation pathways that do not operate in NahG plants are active in sid mutants. One of the mutants is allelic to eds5 (for enhanced disease susceptibility), whereas the other mutant has not been described previously. PMID:10449575

  2. Evaluation of biomechanical strength, stability, bioactivity, and in vivo biocompatibility of a novel calcium deficient hydroxyapatite/poly(amino acid) composite cervical vertebra cage.

    PubMed

    Xiong, Yi; Li, Hong; Zhou, Chunguang; Yang, Xi; Song, Yueming; Qing, Yan; Yan, Yonggang

    2014-01-01

    A new type of cervical vertebra cage was prepared using a novel composite, calcium deficient hydroxyapatite/poly(amino acid) (HA/PAA), and its mechanical properties, in vitro stability and bioactivity, and in vivo biocompatibility were characterized. The results showed that the axial compressive loads of the HA/PAA cage were in the range of 10058-10612 N and the lateral compressive loads were in the range of 1180-2363 N, and varied with the height of the cervical vertebra cages. After immersion in simulated body fluid (SBF) for 16 weeks, the axial compressive loads of the cage decreased from 10058 to 7131 N and the lateral compressive loads decreased from 1180 to 479 N. In addition, the weight loss decreased 6.01%, showing that HA/PAA composites had good stability during the incubation period. The pH value of SBF was also monitored during the whole soaking period; it fluctuated in the range of 6.9-7.4. Scanning electron microscope and energy dispersive spectrometer results showed the cage was bioactive with a new apatite layer attached on the surface. The histological evaluation revealed that new bone tissue bonded tightly with the surfaces of the implants, showing excellent biocompatibility. In conclusion, the HA/PAA cage showed sufficient strength, good stability, bioactivity, and biocompatibility, and has potential applications for clinical cervical vertebrae repair.

  3. Preparation of ferulic acid from agricultural wastes: its improved extraction and purification.

    PubMed

    Tilay, Ashwini; Bule, Mahesh; Kishenkumar, Jyoti; Annapure, Uday

    2008-09-10

    Ferulic acid (FA) is a phenolic antioxidant present in plants, which is widely used in the food and cosmetic industry. In the present study, various agricultural wastes such as maize bran, rice bran, wheat bran, wheat straw, sugar cane baggasse, pineapple peels, orange peels, and pomegranate peels were screened for the presence of esterified FA (EFA). Among the sources screened, maize bran was found to contain the highest amount of EFA. Pineapple peels, orange peels, and pomegranate peels were also found to contain traces of EFA. Alkaline extraction of EFA from maize bran was carried out using 2 M NaOH. Response surface methodology (RSM) was used for optimization of EFA extraction, which resulted in a 1.3-fold increase as compared to the unoptimized conventional extraction technique. FA was analyzed by means of high-performance liquid chromatography (HPLC). Purification was carried out by adsorption chromatography using Amberlite XAD-16 followed by preparative high-performance thin-layer chromatography (HPTLC). The recovery of Amberlite XAD-16 purified FA was up to 57.97% with HPLC purity 50.89%. The fold purity achieved was 1.35. After preparative HPTLC, the maximum HPLC purity obtained was 95.35% along with an increase in fold purity up to 2.53.

  4. Alpha-1 Antitrypsin Deficiency

    MedlinePlus

    ... Liver Disease Information > Alpha-1 Antitrypsin Deficiency Alpha-1 Antitrypsin Deficiency Explore this section to learn more about alpha-1 antitrypsin deficiency, including a description of the disorder ...

  5. [The use of essential fatty acids in the treatments of wounds].

    PubMed

    Manhezi, Andreza Cano; Bachion, Maria Márcia; Pereira, Angela Lima

    2008-01-01

    In spite of being widely spread throughout Brazil, the use of essential fatty acids (EFA) for wound healing is controversial. This study aimed at identifying and analyzing the available scientific evidence for EFA to be used in the treatment of wounds. This is a descriptive study, carried out through a systematic literature review, concerning the Biblioteca Virtual de Saúde (Health Online Library) and PubMed data bank, from 1970 to 2006. Initially, we identified 503 references. After the relevance tests I and II, 11 articles were included in the analysis, showing evidence of recommendation- level II and III for EFA to be used in burns, mediastinitis, among others situations. Most studies still refer to its use in animal. Relevant publications are still scarce.

  6. Effects of mechanical loading on the degradability and mechanical properties of the nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer composite membrane tube for guided bone regeneration

    PubMed Central

    Duan, Hong; Yang, Hongsheng; Xiong, Yan; Zhang, Bin; Ren, Cheng; Min, Li; Zhang, Wenli; Yan, Yonggang; Li, Hong; Pei, Fuxing; Tu, Chongqi

    2013-01-01

    Background and methods Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls. Results The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis. Conclusions n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for critical size defects of long bones in goats for animal experiments. PMID:23946651

  7. Antiatherosclerotic Effects of 1-Methylnicotinamide in Apolipoprotein E/Low-Density Lipoprotein Receptor-Deficient Mice: A Comparison with Nicotinic Acid.

    PubMed

    Mateuszuk, Lukasz; Jasztal, Agnieszka; Maslak, Edyta; Gasior-Glogowska, Marlena; Baranska, Malgorzata; Sitek, Barbara; Kostogrys, Renata; Zakrzewska, Agnieszka; Kij, Agnieszka; Walczak, Maria; Chlopicki, Stefan

    2016-02-01

    1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/LDLR(-/-) mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1 α and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR(-/-) mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA.

  8. Antiatherosclerotic Effects of 1-Methylnicotinamide in Apolipoprotein E/Low-Density Lipoprotein Receptor-Deficient Mice: A Comparison with Nicotinic Acid.

    PubMed

    Mateuszuk, Lukasz; Jasztal, Agnieszka; Maslak, Edyta; Gasior-Glogowska, Marlena; Baranska, Malgorzata; Sitek, Barbara; Kostogrys, Renata; Zakrzewska, Agnieszka; Kij, Agnieszka; Walczak, Maria; Chlopicki, Stefan

    2016-02-01

    1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/LDLR(-/-) mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1 α and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR(-/-) mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA. PMID:26631491

  9. The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency.

    PubMed

    Montioli, Riccardo; Paiardini, Alessandro; Kurian, Manju A; Dindo, Mirco; Rossignoli, Giada; Heales, Simon J R; Pope, Simon; Voltattorni, Carla Borri; Bertoldi, Mariarita

    2016-06-01

    We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339). Arg347 appears to interact with Phe103, as well as with both Leu333 and Asp345. We have then prepared and characterized the artificial F103L, R347K and D345A mutants. F103L, D345A and R347K exhibit about 13-, 97-, and 345-fold kcat decrease compared to the wild-type AADC, respectively. However, unlike F103L, the R347G, R347K and R347Q mutants as well as the D345A variant appear to be more defective in catalysis than in protein folding. Moreover, the latter mutants, unlike the wild-type protein and the F103L variant, share a peculiar binding mode of dopa methyl ester consisting of formation of a quinonoid intermediate. This finding strongly suggests that their catalytic defects are mainly due to a misplacement of the substrate at the active site. Taken together, our results highlight the importance of the Arg347-Leu333-Asp345 hydrogen-bonds network in the catalysis of AADC and reveal the molecular basis for the pathogenicity of the variants R347. Following the above results, a therapeutic treatment for patients bearing the mutation R347G is proposed.

  10. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients.

    PubMed

    Yoshimoto-Furuie, K; Yoshimoto, K; Tanaka, T; Saima, S; Kikuchi, Y; Shay, J; Horrobin, D F; Echizen, H

    1999-02-01

    Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n-6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either gamma-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.

  11. Safety, efficacy and physiological actions of a lysine-free, arginine-rich formula to treat glutaryl-CoA dehydrogenase deficiency: focus on cerebral amino acid influx.

    PubMed

    Strauss, Kevin A; Brumbaugh, Joan; Duffy, Alana; Wardley, Bridget; Robinson, Donna; Hendrickson, Christine; Tortorelli, Silvia; Moser, Ann B; Puffenberger, Erik G; Rider, Nicholas L; Morton, D Holmes

    2011-01-01

    Striatal degeneration from glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type 1, GA1) is associated with cerebral formation and entrapment of glutaryl-CoA and its derivatives that depend on cerebral lysine influx. In 2006 we designed a lysine-free study formula enriched with arginine to selectively block lysine transport across cerebral endothelia and thereby limit glutaryl-CoA production by brain. Between 2006 and present, we treated twelve consecutive children with study formula (LYSx group) while holding all other treatment practices constant. Clinical and biochemical outcomes were compared to 25 GA1 patients (PROx group) treated between 1995 and 2005 with natural protein restriction (dietary lysine/arginine ratio of 1.7±0.3 mg:mg). We used published kinetic parameters of the y+and LAT1 blood-brain barrier transporters to model the influx of amino acids into the brain. Arginine fortification to achieve a mean dietary lysine/arginine ratio of 0.7±0.2 mg:mg was neuroprotective. All 12 LYSx patients are physically and neurologically healthy after 28 aggregate patient-years of follow up (current ages 28±21 months) and there were no adverse events related to formula use. This represents a 36% reduction of neurological risk (95% confidence interval 14-52%, p=0.018) that we can directly attribute to altered amino acid intake. During the first year of life, 20% lower lysine intake and two-fold higher arginine intake by LYSx patients were associated with 50% lower plasma lysine, 3-fold lower plasma lysine/arginine concentration ratio, 42% lower mean calculated cerebral lysine influx, 54% higher calculated cerebral arginine influx, 15-26% higher calculated cerebral influx of several anaplerotic precursors (isoleucine, threonine, methionine, and leucine), 50% less 3-hydroxyglutarate excretion, and a 3-fold lower hospitalization rate (0.8 versus 2.3 hospitalizations per patient per year). The relationship between arginine fortification and plasma lysine

  12. A non-canonical caleosin from Arabidopsis efficiently epoxidizes physiological unsaturated fatty acids with complete stereoselectivity.

    PubMed

    Blée, Elizabeth; Flenet, Martine; Boachon, Benoît; Fauconnier, Marie-Laure

    2012-10-01

    In plants, epoxygenated fatty acids (EFAs) are constituents of oil seeds as well as defence molecules and components of biopolymers (cutin, suberin). While the pleiotropic biological activities of mammalian EFAs have been well documented, there is a paucity of information on the physiological relevance of plant EFAs and their biosynthesis. Potential candidates for EFA formation are caleosin-type peroxygenases which catalyze the epoxidation of unsaturated fatty acids in the presence of hydroperoxides as co-oxidants. However, the caleosins characterized so far, which are mostly localized in seeds, are poor epoxidases. In sharp contrast, quantitative RT-PCR analysis revealed that PXG4, a class II caleosin gene, is expressed in roots, stems, leaves and flowers of Arabidopsis. Expressed in yeast, PXG4 encodes a calcium-dependent membrane-associated hemoprotein able to catalyze typical peroxygenase reactions. Moreover, we show here that purified recombinant PXG4 is an efficient fatty acid epoxygenase, catalyzing the oxidation of cis double bonds of unsaturated fatty acids. Physiological linoleic and linolenic acids proved to be the preferred substrates for PXG4; they are oxidized into the different positional isomers of the monoepoxides and into diepoxides. An important regioselectivity was observed; the C-12,13 double bond of these unsaturated fatty acids being the least favored unsaturation epoxidized by PXG4, linolenic acid preferentially yielded the 9,10-15,16-diepoxide. Remarkably, PXG4 catalyzes exclusively the formation of (R),(S)-epoxide enantiomers, which is the absolute stereochemistry of the epoxides found in planta. These findings pave the way for the study of the functional role of EFAs and caleosins in plants. PMID:22913587

  13. Feeding long-chain n-3 polyunsaturated fatty acids to obese leptin receptor-deficient JCR:LA- cp rats modifies immune function and lipid-raft fatty acid composition.

    PubMed

    Ruth, Megan R; Proctor, Spencer D; Field, Catherine J

    2009-05-01

    Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P < 0.05). The lower n-6:n-3 PUFA ratio of splenocyte PL was consistent with the lower mitogen-stimulated interferon (IFN)-gamma and IL-1beta production by cells from obese rats (P < 0.05). Obese rats fed the FO diet had lower mitogen-stimulated Th1 (IFN-gamma) and Th2 (IL-4) cytokine responses, but IL-2 production (concanavalin A; ConA) did not differ (P < 0.05). The HFO diet was more effective in lowering IL-1beta and increasing IL-10 production (ConA, P < 0.05). This lower IL-1beta production was accompanied by a lower proportion of major histocompatability complex class II-positive cells and a higher incorporation of DHA into lipid rafts. This is the first study to demonstrate impaired responses to mitogen stimulation and altered fatty acid incorporation into the membrane PL of JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.

  14. PGK deficiency.

    PubMed

    Beutler, Ernest

    2007-01-01

    Phosphoglycerate kinase (PGK) deficiency is one of the relatively uncommon causes of hereditary non-spherocytic haemolytic anaemia (HNSHA). The gene encoding the erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations. Twenty-six families have been described and in 20 of these the mutations are known. The reason for different clinical manifestations of mutations of the same gene remains unknown. PMID:17222195

  15. Application of a fiber-optic NIR-EFA sensor system for in situ monitoring of aromatic hydrocarbons in contaminated groundwater.

    PubMed

    Buerck, J; Roth, S; Kraemer, K; Scholz, M; Klaas, N

    2001-05-01

    Interaction of analyte molecules with the evanescent wave of light guided in optical fibers is among the most promising novel sensing schemes that can be applied for environmental monitoring and on-line process analysis. By combining this measuring principle with the solid-phase extraction of analyte molecules into the polymer cladding of a fiber, it is possible to perform direct absorption measurements in the cladding, if the fiber is adapted to a conventional spectrometer/photometer. A big advantage of this arrangement is that the measurement is scarcely disturbed by matrix effects (background absorption of water in IR measurements, stray light due to turbidity in the sample). By using near-infrared (NIR) evanescent field absorption (EFA) measurements in quartz glass fibers coated with a hydrophobic silicone membrane it is possible to design and construct sensors for monitoring apolar hydrocarbons (HCs) in aqueous matrices.The paper presents a fiber-optic sensor system for the determination of aromatic HCs in groundwater or industrial wastewater. Generally, this instrument is suitable for quantitative in situ monitoring of pollutants such as aromatic solvents, fuels, mineral oils or chlorinated HCs with relatively low water saturation solubility (typically between 0.01 and 10 g l(-1)). The sensor probe is connected via all-silica fibers to a filter photometer developed at the IFIA, thus, allowing even remote analysis in a monitoring well. This portable instrument provides a total concentration signal of the organic compounds extracted into the fiber cladding by measuring the integral absorption at the 1st C--H overtone bands in the NIR spectral range. In situ measurements with the sensor system were performed in a groundwater circulation well at the VEGAS research facility of the University of Stuttgart (Germany). The NIR-EFA sensor system was tested within the frame of an experiment that was carried through in a tank containing sandy gravel with a groundwater

  16. Peroxisomal bifunctional enzyme deficiency.

    PubMed Central

    Watkins, P A; Chen, W W; Harris, C J; Hoefler, G; Hoefler, S; Blake, D C; Balfe, A; Kelley, R I; Moser, A B; Beard, M E

    1989-01-01

    Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone. Images PMID:2921319

  17. Essential fatty acid intake and serum fatty acid composition among adolescent girls in central Mozambique.

    PubMed

    Freese, Riitta; Korkalo, Liisa; Vessby, Bengt; Tengblad, Siv; Vaara, Elina M; Hauta-alus, Helena; Selvester, Kerry; Mutanen, Marja

    2015-04-14

    Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.

  18. Essential fatty acid intake and serum fatty acid composition among adolescent girls in central Mozambique.

    PubMed

    Freese, Riitta; Korkalo, Liisa; Vessby, Bengt; Tengblad, Siv; Vaara, Elina M; Hauta-alus, Helena; Selvester, Kerry; Mutanen, Marja

    2015-04-14

    Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated. PMID:25772191

  19. Impact of dietary lipids on sow milk composition and balance of essential fatty acids during lactation in prolific sows.

    PubMed

    Rosero, D S; Odle, J; Mendoza, S M; Boyd, R D; Fellner, V; van Heugten, E

    2015-06-01

    Two studies were designed to determine the effects of supplementing diets with lipid sources of EFA (linoleic and α-linolenic acid) on sow milk composition to estimate the balance of EFA for sows nursing large litters. In Exp. 1, 30 sows, equally balanced by parity (1 and 3 to 5) and nursing 12 pigs, were fed diets supplemented with 6% animal-vegetable blend (A-V), 6% choice white grease (CWG), or a control diet without added lipid. Diets were corn-soybean meal based with 8% corn distiller dried grains with solubles and 6% wheat middlings and contained 3.25 g standardized ileal digestible Lys/Mcal ME. Sows fed lipid-supplemented diets secreted greater amounts of fat (P = 0.082; 499 and 559 g/d for control and lipid-added diets, respectively) than sows fed the control diet. The balance of EFA was computed as apparent ileal digestible intake of EFA minus the outflow of EFA in milk. For sows fed the control diet, the amount of linoleic acid secreted in milk was greater than the amount consumed, throughout lactation. This resulted in a pronounced negative balance of linoleic acid (-22.4, -38.0, and -14.1 g/d for d 3, 10, and 17 of lactation, respectively). In Exp. 2, 50 sows, equally balanced by parity and nursing 12 pigs, were randomly assigned to a 2 × 2 factorial arrangement of diets plus a control diet without added lipids. Factors included linoleic acid (2.1% and 3.3%) and α-linolenic acid (0.15% and 0.45%). The different concentrations of EFA were obtained by adding 4% of different mixtures of canola, corn, and flaxseed oils to diets. The n-6 to n-3 fatty acid ratios in the diets ranged from 5 to 22. Increasing supplemental EFA increased (P < 0.001) milk concentrations of linoleic (16.7% and 20.8%, for 2.1% and 3.3% linoleic acid, respectively) and α-linolenic acid (P < 0.001; 1.1 and 1.9% for 0.15 and 0.45% α-linolenic acid, respectively). Increasing supplemental EFA increased the estimated balance of α-linolenic acid (P < 0.001; -0.2 and 5.3 g/d for 0

  20. Folate deficiency

    MedlinePlus

    ... the digestive system (such as Celiac disease or Crohn disease ) Drinking too much alcohol Eating overcooked fruits and ... women need to get enough folic acid. The vitamin is important to the growth of the fetus's ...

  1. Genetics Home Reference: isobutyryl-CoA dehydrogenase deficiency

    MedlinePlus

    ... from food are broken down into parts called amino acids . Amino acids can be further processed to provide energy for ... an enzyme that helps break down a particular amino acid called valine. Most people with IBD deficiency are ...

  2. Essential Fatty Acids as Transdermal Penetration Enhancers.

    PubMed

    van Zyl, Lindi; du Preez, Jan; Gerber, Minja; du Plessis, Jeanetta; Viljoen, Joe

    2016-01-01

    The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F > control > EPO > Pheroid. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum-epidermis and the epidermis-dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation. PMID:26852854

  3. Disialotransferrin developmental deficiency syndrome.

    PubMed Central

    Kristiansson, B; Andersson, M; Tonnby, B; Hagberg, B

    1989-01-01

    Seven mentally deficient children and adolescents (three pairs of siblings and one singleton) were studied. A peculiar external appearance, a characteristic neurohepatosubcutaneous tissue impairment syndrome and, as a biological marker, an abnormal sialic acid transferrin pattern were characteristic features. All seven seemed odd from birth and prone to acute cerebral dysfunction during catabolic states. Abnormal lower neurone, cerebellar, and retinal functions dominated from later childhood. The disialotransferrin pattern found in serum and cerebrospinal fluid is thought to be the biological marker of a newly discovered inborn error of glycoprotein metabolism with autosomal recessive inheritance. Images Fig 1 Fig 2 p74-b PMID:2466439

  4. Spatial Patterns and Temperature Predictions of Tuna Fatty Acids: Tracing Essential Nutrients and Changes in Primary Producers

    PubMed Central

    Pethybridge, Heidi R.; Parrish, Christopher C.; Morrongiello, John; Young, Jock W.; Farley, Jessica H.; Gunasekera, Rasanthi M.; Nichols, Peter D.

    2015-01-01

    Fatty acids are among the least understood nutrients in marine environments, despite their profile as key energy components of food webs and that they are essential to all life forms. Presented here is a novel approach to predict the spatial-temporal distributions of fatty acids in marine resources using generalized additive mixed models. Fatty acid tracers (FAT) of key primary producers, nutritional condition indices and concentrations of two essential long-chain (≥C20) omega-3 fatty acids (EFA) measured in muscle of albacore tuna, Thunnus alalunga, sampled in the south-west Pacific Ocean were response variables. Predictive variables were: location, time, sea surface temperature (SST) and chlorophyll-a (Chla), and phytoplankton biomass at time of catch and curved fork length. The best model fit for all fatty acid parameters included fish length and SST. The first oceanographic contour maps of EFA and FAT (FATscapes) were produced and demonstrated clear geographical gradients in the study region. Predicted changes in all fatty acid parameters reflected shifts in the size-structure of dominant primary producers. Model projections show that the supply and availability of EFA are likely to be negatively affected by increases in SST especially in temperate waters where a 12% reduction in both total fatty acid content and EFA proportions are predicted. Such changes will have large implications for the availability of energy and associated health benefits to high-order consumers. Results convey new concerns on impacts of projected climate change on fish-derived EFA in marine systems. PMID:26135308

  5. Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids.

    PubMed Central

    Purasiri, P; Mckechnie, A; Heys, S D; Eremin, O

    1997-01-01

    Essential fatty acids (EFA) have been shown in animal studies to have a differential effect on various aspects of immune reactivity. However, there have been few studies in humans. Therefore, we elected to investigate the effects of a variety of EFA [gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in vitro on human blood lymphocyte reactivity, cytokine secretion and natural cytotoxicity. The proliferative response to polyclonal mitogens (phytohaemagglutinin, pokeweed mitogen, concanavalin A), as measured by [3H]thymidine incorporation into newly synthesized lymphocytes, was inhibited (P < 0.05) by all EFAs tested, in a dose-dependent manner (3-15 micrograms/ml). The greatest inhibition of proliferation was caused by EPA and DHA. Similarly, EPA, DHA and GLA significantly reduced cytotoxic activity [expressed as lytic units, using 51 chromium-release assays natural killer (NK) (K562 cells) and lymphokine-activated (LAK) (Daudi cells) cells] (P < 0.05) in a concentration-dependent manner (5-50 micrograms/ml), without affecting cell viability. EPA and DHA exhibited greater suppression than GLA. Furthermore, the inhibition of cell proliferation and suppression of natural cytotoxicity was associated with marked decrease in cytokine [interleukin-1 (IL-1), IL-2, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] production in vitro. Our findings demonstrate that EFAs (GLA, EPA, DHA) have the potential to inhibit significantly various aspects of human lymphocyte cell-mediated and humoral immune reactivities. PMID:9415022

  6. Vaccination with DNA Encoding Truncated Enterohemorrhagic Escherichia coli (EHEC) Factor for Adherence-1 Gene (efa-1′) Confers Protective Immunity to Mice Infected with E. coli O157:H7

    PubMed Central

    Riquelme-Neira, Roberto; Rivera, Alejandra; Sáez, Darwin; Fernández, Pablo; Osorio, Gonzalo; del Canto, Felipe; Salazar, Juan C.; Vidal, Roberto M.; Oñate, Angel

    2016-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1′) in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1′ gene (pVAXefa-1′) into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1′, EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10, and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1′ have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle. PMID:26835434

  7. Vaccination with DNA Encoding Truncated Enterohemorrhagic Escherichia coli (EHEC) Factor for Adherence-1 Gene (efa-1') Confers Protective Immunity to Mice Infected with E. coli O157:H7.

    PubMed

    Riquelme-Neira, Roberto; Rivera, Alejandra; Sáez, Darwin; Fernández, Pablo; Osorio, Gonzalo; del Canto, Felipe; Salazar, Juan C; Vidal, Roberto M; Oñate, Angel

    2015-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1') in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1' gene (pVAXefa-1') into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1', EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10, and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1' have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle.

  8. Multiple Peroxisomal Enzymatic Deficiency Disorders

    PubMed Central

    Vamecq, Joseph; Draye, Jean-Pierre; Van Hoof, François; Misson, Jean-Paul; Evrard, Philippe; Verellen, Gaston; Eyssen, Hendrik J.; Van Eldere, Johan; Schutgens, Ruud B. H.; Wanders, Ronald J. A.; Roels, Frank; Goldfischer, Sidney L.

    1986-01-01

    Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:2879480

  9. Efficient production of optically pure D-lactic acid from raw corn starch by using a genetically modified L-lactate dehydrogenase gene-deficient and alpha-amylase-secreting Lactobacillus plantarum strain.

    PubMed

    Okano, Kenji; Zhang, Qiao; Shinkawa, Satoru; Yoshida, Shogo; Tanaka, Tsutomu; Fukuda, Hideki; Kondo, Akihiko

    2009-01-01

    In order to achieve direct and efficient fermentation of optically pure D-lactic acid from raw corn starch, we constructed L-lactate dehydrogenase gene (ldhL1)-deficient Lactobacillus plantarum and introduced a plasmid encoding Streptococcus bovis 148 alpha-amylase (AmyA). The resulting strain produced only D-lactic acid from glucose and successfully expressed amyA. With the aid of secreting AmyA, direct D-lactic acid fermentation from raw corn starch was accomplished. After 48 h of fermentation, 73.2 g/liter of lactic acid was produced with a high yield (0.85 g per g of consumed sugar) and an optical purity of 99.6%. Moreover, a strain replacing the ldhL1 gene with an amyA-secreting expression cassette was constructed. Using this strain, direct D-lactic acid fermentation from raw corn starch was accomplished in the absence of selective pressure by antibiotics. This is the first report of direct D-lactic acid fermentation from raw starch.

  10. Carnitine palmitoyltransferase II deficiency

    PubMed Central

    Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.

    2008-01-01

    Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = β-hydroxypentanoate; BKP = β-ketopentanoate; BKP-CoA = β-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT

  11. Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5.

    PubMed

    Kitanovic, Ana; Bonowski, Felix; Heigwer, Florian; Ruoff, Peter; Kitanovic, Igor; Ungewiss, Christin; Wölfl, Stefan

    2012-01-01

    Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK), and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation.

  12. Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5

    PubMed Central

    Kitanovic, Ana; Bonowski, Felix; Heigwer, Florian; Ruoff, Peter; Kitanovic, Igor; Ungewiss, Christin; Wölfl, Stefan

    2012-01-01

    Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK), and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation. PMID:23050242

  13. Effects of a blend of essential oil compounds and benzoic acid on performance of broiler chickens as revealed by a meta-analysis of 4 growth trials in various locations.

    PubMed

    Weber, G M; Michalczuk, M; Huyghebaert, G; Juin, H; Kwakernaak, C; Gracia, M I

    2012-11-01

    A series of growth trials with broiler chicks was conducted in various geographical locations to evaluate the efficacy of a novel eubiotic feed additive (EFA) at various dietary inclusion levels on performance of growing chicks. The EFA product consisted of a blend of essential oil compounds (thymol, eugenol, piperine) with benzoic acid, all belonging to the group of flavoring substances. Although variable in responses, the overall results indicated that 300 mg/kg of this EFA represented an optimum supplementation dose for generation of beneficial performance effects in broilers. A meta-analysis with all data from the 300 mg/kg EFA-supplemented treatments in comparison with the non-supplemented controls revealed that the eubiotic product significantly improved BW on d 21 (+2.0%; P = 0.0021) and on d 42 (+1.4%; P = 0.0151). Furthermore, the birds on the EFA 300 mg/kg treatment expressed a higher average daily gain in the starter phase (d 1-21; +2.1%; P = 0.0023) and over the entire experimental period (d 1-42; +1.5%; P = 0.0154). Feed conversion ratio was more favorable with dietary EFA supplementation (-0.6%; P = 0.0414), when compared with the control birds. Mortality was considered normal and was not affected by the dietary treatment (control = 3.09%; EFA 300 mg/kg = 3.26%). In conclusion, 300 mg/kg of this new eubiotic product demonstrated to effectively improve performance of broiler chicks under various husbandry conditions. PMID:23091138

  14. [Peculiar features of the effect of cobalamines on the metabolism of vitamin B 12 and pantothenic acid in B 12 deficiency].

    PubMed

    Bud'ko, T N; Moiseenok, A G

    1980-01-01

    A single parenteral administration to B12-deficient rats of cyan cobalamine (CN-Cbl), oxycobalamine (OH-Cbl), methyl cobalamine (CH3-Cbl) and adenosyl cobalamine (Ado-Cbl) at a dose of 100 microgram/kg body weight increased the lowered level of total cobalamines in the liver to reach or exceed the norm. The study of cobalamine-protein complexes (CPC) in the liver of B12-deficient rats showed that the content of free cobalamines and CPC was decreased, the level of CPC degrading at 80 degrees C being particularly low. An administration of OH-Cbl and CH3-Cbl raised significantly the content of CPC degrading at 80 degrees C and presumably containing Ado-Cbl. Under the influence of cobalamines the increased activity of alpha-ketoglutarate dehydrogenase in hepatocytes returned to the normal and the CoA level declined only after administration of CN-Cbl and CH3-Cbl. PMID:7433432

  15. Consequences of Essential Fatty Acids

    PubMed Central

    Lands, Bill

    2012-01-01

    Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy. PMID:23112921

  16. Meeting EFA: Afghanistan Community Schools

    ERIC Educational Resources Information Center

    Balwanz; David

    2007-01-01

    From 1979 to 2002, Afghanistan was in a near constant state of war and exhibited some of the lowest levels of development in the world. While local conflicts and Taliban remnants continue to challenge Afghanistan's reconstruction and stabilization, significant progress has been made since the 2001 U.S. led invasion and subsequent fall of the…

  17. Progress towards EFA in Tanzania

    ERIC Educational Resources Information Center

    Woods, Eric

    2008-01-01

    Positive developments are identified, notably a strong policy and planning environment linked to overall strategy for growth and poverty reduction, leading to vigorous commitment to achievement of the Millennium Development Goals. Abolition of school fees, and a measure of compulsion, resulted in significant gains in school enrolment, including…

  18. Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids.

    PubMed

    Cunnane, S C; Manku, M S; Horrobin, D F

    1985-05-01

    Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

  19. [Effects of low molecular organic acids on nitrogen accumulation, nodulation, and nitrogen fixation of soybean (Glycine max L.) under phosphorus deficiency stress].

    PubMed

    Wang, Shu-Qi; Han, Xiao-Zeng; Qiao, Yun-Fa; Yan, Jun; Li, Xiao-Hui

    2009-05-01

    A greenhouse sand culture experiment was conducted to study the effects of citric acid, oxalic acid, malic acid, and their mixture on the nitrogen accumulation, nodulation, and nitrogen fixation of soybean. After the application of test low molecular weight organic acids, the nitrogen accumulation in the aboveground part of soybean decreased by 17.6%-44.9% at seedling stage, 29.8%-88.4% at flowering stage, 9.18%-69.6% at podding stage, and 2.21%-41.7% at maturing stage). In the meanwhile, the nodule number, nitrogenase activity, and leghemoglobin content decreased by 11.4%-59.6%, 80.5%-91.7%, and 11.9%-59.9%, respectively, resulting in a significant decrease (9.71%-64.5%) of nitrogen fixation of soybean, compared with the control. The inhibitory effect of test low molecular weight organic acids increased with their increasing concentration. Oxalic acid had a higher inhibitory effect than citric acid and malic acid, and the mixture of the three organic acids had an enhanced inhibitory effect.

  20. Do polyunsaturated fatty acids behave like an endogenous "polypill"?

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function. PMID:17624683

  1. Acid Lipase Disease

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage ... Trials Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs ...

  2. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid ...

  3. Leaf Senescence by Magnesium Deficiency

    PubMed Central

    Tanoi, Keitaro; Kobayashi, Natsuko I.

    2015-01-01

    Magnesium ions (Mg2+) are the second most abundant cations in living plant cells, and they are involved in various functions, including photosynthesis, enzyme catalysis, and nucleic acid synthesis. Low availability of Mg2+ in an agricultural field leads to a decrease in yield, which follows the appearance of Mg-deficient symptoms such as chlorosis, necrotic spots on the leaves, and droop. During the last decade, a variety of physiological and molecular responses to Mg2+ deficiency that potentially link to leaf senescence have been recognized, allowing us to reconsider the mechanisms of Mg2+ deficiency. This review focuses on the current knowledge about the physiological responses to Mg2+ deficiency including a decline in transpiration, accumulation of sugars and starch in source leaves, change in redox states, increased oxidative stress, metabolite alterations, and a decline in photosynthetic activity. In addition, we refer to the molecular responses that are thought to be related to leaf senescence. With these current data, we give an overview of leaf senescence induced by Mg deficiency. PMID:27135350

  4. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    PubMed

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats.

  5. 3-Ketothiolase deficiency.

    PubMed

    Middleton, B; Bartlett, K; Romanos, A; Gomez Vazquez, J; Conde, C; Cannon, R A; Lipson, M; Sweetman, L; Nyhan, W L

    1986-04-01

    Two patients have been studied in whom the activity of the short chain-length-specific mitochondrial 3-ketothiolase was found to be deficient. Use of a range of 3-ketoacyl-CoA substrates showed that the other 3-ketothiolase isoenzymes were normal in each case. Both patients had episodic ketosis and metabolic acidosis. One patient had substantial evidence of damage to the central nervous system and two siblings who had died of the disease. The organic aciduria was characterized by the excretion of 2-methyl-3-hydroxybutyric acid and tiglyglycine. In one patient the organic aciduria was very subtle and was masked during the presence of ketosis, but it was clarified by an isoleucine load after recovery from ketosis.

  6. Genetics Home Reference: 3-methylcrotonyl-CoA carboxylase deficiency

    MedlinePlus

    ... break down proteins containing a particular building block (amino acid) called leucine. Infants with 3-MCC deficiency appear ... for the fourth step in processing leucine, an amino acid that is part of many proteins. Mutations in ...

  7. Partitioning the Relative Importance of Phylogeny and Environmental Conditions on Phytoplankton Fatty Acids.

    PubMed

    Galloway, Aaron W E; Winder, Monika

    2015-01-01

    Essential fatty acids (EFA), which are primarily generated by phytoplankton, limit growth and reproduction in diverse heterotrophs. The biochemical composition of phytoplankton is well-known to be governed both by phylogeny and environmental conditions. Nutrients, light, salinity, and temperature all affect both phytoplankton growth and fatty acid composition. However, the relative importance of taxonomy and environment on algal fatty acid content has yet to be comparatively quantified, thus inhibiting predictions of changes to phytoplankton food quality in response to global environmental change. We compiled 1145 published marine and freshwater phytoplankton fatty acid profiles, consisting of 208 species from six major taxonomic groups, cultured in a wide range of environmental conditions, and used a multivariate distance-based linear model to quantify the total variation explained by each variable. Our results show that taxonomic group accounts for 3-4 times more variation in phytoplankton fatty acids than the most important growth condition variables. The results underscore that environmental conditions clearly affect phytoplankton fatty acid profiles, but also show that conditions account for relatively low variation compared to phylogeny. This suggests that the underlying mechanism determining basal food quality in aquatic habitats is primarily phytoplankton community composition, and allows for prediction of environmental-scale EFA dynamics based on phytoplankton community data. We used the compiled dataset to calculate seasonal dynamics of long-chain EFA (LCEFA; ≥C20 ɷ-3 and ɷ-6 polyunsaturated fatty acid) concentrations and ɷ-3:ɷ-6 EFA ratios in Lake Washington using a multi-decadal phytoplankton community time series. These analyses quantify temporal dynamics of algal-derived LCEFA and food quality in a freshwater ecosystem that has undergone large community changes as a result of shifting resource management practices, highlighting diatoms

  8. Partitioning the Relative Importance of Phylogeny and Environmental Conditions on Phytoplankton Fatty Acids

    PubMed Central

    Galloway, Aaron W. E.; Winder, Monika

    2015-01-01

    Essential fatty acids (EFA), which are primarily generated by phytoplankton, limit growth and reproduction in diverse heterotrophs. The biochemical composition of phytoplankton is well-known to be governed both by phylogeny and environmental conditions. Nutrients, light, salinity, and temperature all affect both phytoplankton growth and fatty acid composition. However, the relative importance of taxonomy and environment on algal fatty acid content has yet to be comparatively quantified, thus inhibiting predictions of changes to phytoplankton food quality in response to global environmental change. We compiled 1145 published marine and freshwater phytoplankton fatty acid profiles, consisting of 208 species from six major taxonomic groups, cultured in a wide range of environmental conditions, and used a multivariate distance-based linear model to quantify the total variation explained by each variable. Our results show that taxonomic group accounts for 3-4 times more variation in phytoplankton fatty acids than the most important growth condition variables. The results underscore that environmental conditions clearly affect phytoplankton fatty acid profiles, but also show that conditions account for relatively low variation compared to phylogeny. This suggests that the underlying mechanism determining basal food quality in aquatic habitats is primarily phytoplankton community composition, and allows for prediction of environmental-scale EFA dynamics based on phytoplankton community data. We used the compiled dataset to calculate seasonal dynamics of long-chain EFA (LCEFA; ≥C20 ɷ-3 and ɷ-6 polyunsaturated fatty acid) concentrations and ɷ-3:ɷ-6 EFA ratios in Lake Washington using a multi-decadal phytoplankton community time series. These analyses quantify temporal dynamics of algal-derived LCEFA and food quality in a freshwater ecosystem that has undergone large community changes as a result of shifting resource management practices, highlighting diatoms

  9. Progression of lipid peroxidation measured as thiobarbituric acid reactive substances, damage to DNA and histopathological changes in the liver of rats subjected to a methionine-choline-deficient diet.

    PubMed

    Jordao, Alceu Afonso; Zanutto, Marcia Elena; Domenici, Fernanda Aparecida; Portari, Guilherme Vannucchi; Cecchi, Andréa Oliveira; Zucoloto, Sergio; Vannucchi, Helio

    2009-09-01

    Methionine-choline-deficient diet represents a model for the study of the pathogenesis of steatohepatitis. Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine-choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro- and macro-vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine-choline-deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non-alcoholic steatohepatitis rates in humans.

  10. Iron deficiency in the tropics.

    PubMed

    Fleming, A F

    1982-06-01

    Iron in food is classified as belonging to the haem pool, the nonhaem pool, and extraneous sources. Haem iron is derived from vegetable and animal sources with varying bioavailability. Hookworm infestation of the intestinal tract affects 450 million people in the tropics. Schistosoma mansoni caused blood loss in 7 Egyptian patients of 7.5- 25.9 ml/day which is equivalent to a daily loss of iron of .6-7.3 mg daily urinary loss of iron in 9 Egyptian patients. Trichuris trichiura infestation by whipworm is widespread in children with blood loss of 5 ml/day/worm. The etiology of anemia in children besides iron deficiency includes malaria, bacterial or viral infections, folate deficiency and sickle-cell disease. Severe infections cause profound iron-deficiency anemia in children in central American and Malaysia. Plasmodium falciparum malaria-induced anaemia in tropical Africa lowers the mean haemoglobin concentration in the population by 2 g/dI, causing profound anaemia in some. The increased risk of premature delivery, low birthweight, fetal abnormalities, and fetal death is directly related to the degree of maternal anemia. Perinatal mortality was reduced from 38 to 4% in treated anemic mothers. Mental performance was significantly lower in anemic school children and improved after they received iron. Supplements of iron, soy-protein, calcium, and vitamins given to villagers with widespread malnutrition, iron deficiency, and hookworm infestation in Colombia reduced enteric infections in children. Severe iron-deficiency anemia was treated in adults in northern Nigeria by daily in Ferastral 10 ml, which is equivalent to 500 mg of iron per day. Choloroquine, folic acid, rephenium hydroxynaphthoate, and tetrachlorethylene treat adults with severe iron deficiency from hookworm infestation in rural tropical Africa. Blood transfusion is indicated if the patient is dying of anaemia or is pregnant with a haemoglobin concentration 6 gm/dl. In South East Asia, mg per day

  11. Iron deficiency in the tropics.

    PubMed

    Fleming, A F

    1982-06-01

    Iron in food is classified as belonging to the haem pool, the nonhaem pool, and extraneous sources. Haem iron is derived from vegetable and animal sources with varying bioavailability. Hookworm infestation of the intestinal tract affects 450 million people in the tropics. Schistosoma mansoni caused blood loss in 7 Egyptian patients of 7.5- 25.9 ml/day which is equivalent to a daily loss of iron of .6-7.3 mg daily urinary loss of iron in 9 Egyptian patients. Trichuris trichiura infestation by whipworm is widespread in children with blood loss of 5 ml/day/worm. The etiology of anemia in children besides iron deficiency includes malaria, bacterial or viral infections, folate deficiency and sickle-cell disease. Severe infections cause profound iron-deficiency anemia in children in central American and Malaysia. Plasmodium falciparum malaria-induced anaemia in tropical Africa lowers the mean haemoglobin concentration in the population by 2 g/dI, causing profound anaemia in some. The increased risk of premature delivery, low birthweight, fetal abnormalities, and fetal death is directly related to the degree of maternal anemia. Perinatal mortality was reduced from 38 to 4% in treated anemic mothers. Mental performance was significantly lower in anemic school children and improved after they received iron. Supplements of iron, soy-protein, calcium, and vitamins given to villagers with widespread malnutrition, iron deficiency, and hookworm infestation in Colombia reduced enteric infections in children. Severe iron-deficiency anemia was treated in adults in northern Nigeria by daily in Ferastral 10 ml, which is equivalent to 500 mg of iron per day. Choloroquine, folic acid, rephenium hydroxynaphthoate, and tetrachlorethylene treat adults with severe iron deficiency from hookworm infestation in rural tropical Africa. Blood transfusion is indicated if the patient is dying of anaemia or is pregnant with a haemoglobin concentration 6 gm/dl. In South East Asia, mg per day

  12. Production of optically pure L-lactic acid from lignocellulosic hydrolysate by using a newly isolated and D-lactate dehydrogenase gene-deficient Lactobacillus paracasei strain.

    PubMed

    Kuo, Yang-Cheng; Yuan, Shuo-Fu; Wang, Chun-An; Huang, Yin-Jung; Guo, Gia-Luen; Hwang, Wen-Song

    2015-12-01

    The use of lignocellulosic feedstock for lactic acid production with a difficulty is that the release of inhibitory compounds during the pretreatment process which inhibit the growth of microorganism. Thus we report a novel lactic acid bacterium, Lactobacillus paracasei 7 BL, that has a high tolerance to inhibitors and produced optically pure l-lactic acid after the interruption of ldhD gene. The strain 7 BL fermented glucose efficiently and showed high titer of l-lactic acid (215 g/l) by fed-batch strategy. In addition, 99 g/l of l-lactic acid with high yield (0.96 g/g) and productivity (2.25-3.23 g/l/h) was obtained by using non-detoxified wood hydrolysate. Rice straw hydrolysate without detoxification was also tested and yielded a productivity rate as high as 5.27 g/l/h. Therefore, L. paracasei 7 BL represents a potential method of l-lactic acid production from lignocellulosic biomass and has attractive application for industries. PMID:26433790

  13. Genome-wide analyses of the transcriptomes of salicylic acid-deficient versus wild-type plants uncover Pathogen and Circadian Controlled 1 (PCC1) as a regulator of flowering time in Arabidopsis.

    PubMed

    Segarra, Silvia; Mir, Ricardo; Martínez, Cristina; León, José

    2010-01-01

    Salicylic acid (SA) has been characterized as an activator of pathogen-triggered resistance of plants. SA also regulates developmental processes such as thermogenesis in floral organs and stress-induced flowering. To deepen our knowledge of the mechanism underlying SA regulation of flowering time in Arabidopsis, we compared the transcriptomes of SA-deficient late flowering genotypes with wild-type plants. Down- or up-regulated genes in SA-deficient plants were screened for responsiveness to ultraviolet (UV)-C light, which accelerates flowering in Arabidopsis. Among them, only Pathogen and Circadian Controlled 1 (PCC1) was up-regulated by UV-C light through a SA-dependent process. Moreover, UV-C light-activated expression of PCC1 was also dependent on the flowering activator CONSTANS (CO). PCC1 gene has a circadian-regulated developmental pattern of expression with low transcript levels after germination that increased abruptly by day 10. RNAi plants with very low expression of PCC1 gene were late flowering, defective in UV-C light acceleration of flowering and contained FLOWERING LOCUS T (FT) transcript levels below 5% of that detected in wild-type plants. Although PCC1 seems to function between CO and FT in the photoperiod-dependent flowering pathway, transgenic plants overexpressing a Glucocorticoid Receptor (GR)-fused version of CO strongly activated FT but not PCC1 after dexamethasone treatment.

  14. 3-Hydroxy-3-methylglutaric and 3-methylglutaric acids impair redox status and energy production and transfer in rat heart: relevance for the pathophysiology of cardiac dysfunction in 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency.

    PubMed

    da Rosa, Mateus Struecker; Seminotti, Bianca; Ribeiro, César Augusto João; Parmeggiani, Belisa; Grings, Mateus; Wajner, Moacir; Leipnitz, Guilhian

    2016-09-01

    3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency is characterized by tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), and 3-methylglutaric (MGA) acids. Affected patients present cardiomyopathy, whose pathomechanisms are not yet established. We investigated the effects of HMG and MGA on energy and redox homeostasis in rat heart using in vivo and in vitro models. In vivo experiments showed that intraperitoneal administration of HMG and MGA decreased the activities of the respiratory chain complex II and creatine kinase (CK), whereas HMG also decreased the activity of complex II-III. Furthermore, HMG and MGA injection increased reactive species production and carbonyl formation, and decreased glutathione concentrations. Regarding the enzymatic antioxidant defenses, HMG and MGA increased glutathione peroxidase (GPx) and glutathione reductase (GR) activities, while only MGA diminished the activities of superoxide dismutase (SOD) and catalase, as well as the protein content of SOD1. Pre-treatment with melatonin (MEL) prevented MGA-induced decrease of CK activity and SOD1 levels. In vitro results demonstrated that HMG and MGA increased reactive species formation, induced lipid peroxidation and decreased glutathione. We also verified that reactive species overproduction and glutathione decrease provoked by HMG and MGA were abrogated by MEL and lipoic acid (LA), while only MEL prevented HMG- and MGA-induced lipoperoxidation. Allopurinol (ALP) also prevented reactive species overproduction caused by both metabolites. Our data provide solid evidence that bioenergetics dysfunction and oxidative stress are induced by HMG and MGA in heart, which may explain the cardiac dysfunction observed in HL deficiency, and also suggest that antioxidant supplementation could be considered as adjuvant therapy for affected patients.

  15. A Comparative Study of N-glycolylneuraminic Acid (Neu5Gc) and Cytotoxic T Cell (CT) Carbohydrate Expression in Normal and Dystrophin-Deficient Dog and Human Skeletal Muscle

    PubMed Central

    Martin, Paul T.; Golden, Bethannie; Okerblom, Jonathan; Camboni, Marybeth; Chandrasekharan, Kumaran; Xu, Rui; Varki, Ajit; Flanigan, Kevin M.; Kornegay, Joe N.

    2014-01-01

    The expression of N-glycolylneuraminic acid (Neu5Gc) and the cytotoxic T cell (CT) carbohydrate can impact the severity of muscular dystrophy arising from the loss of dystrophin in mdx mice. Here, we describe the expression of these two glycans in skeletal muscles of dogs and humans with or without dystrophin-deficiency. Neu5Gc expression was highly reduced (>95%) in muscle from normal golden retriever crosses (GR, n = 3) and from golden retriever with muscular dystrophy (GRMD, n = 5) dogs at multiple ages (3, 6 and 13 months) when compared to mouse muscle, however, overall sialic acid expression in GR and GRMD muscles remained high at all ages. Neu5Gc was expressed on only a minority of GRMD satellite cells, CD8+ T lymphocytes and macrophages. Human muscle from normal (no evident disease, n = 3), Becker (BMD, n = 3) and Duchenne (DMD, n = 3) muscular dystrophy individuals had absent to very low Neu5Gc staining, but some punctate intracellular muscle staining was present in BMD and DMD muscles. The CT carbohydrate was localized to the neuromuscular junction in GR muscle, while GRMD muscles had increased expression on a subset of myofibers and macrophages. In humans, the CT carbohydrate was ectopically expressed on the sarcolemmal membrane of some BMD muscles, but not normal human or DMD muscles. These data are consistent with the notion that altered Neu5Gc and CT carbohydrate expression may modify disease severity resulting from dystrophin deficiency in dogs and humans. PMID:24505439

  16. Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 deficient mice.

    PubMed

    Li, Wenmei; Sandhoff, Roger; Kono, Mari; Zerfas, Patricia; Hoffmann, Vickie; Ding, Bryan Char-Hoa; Proia, Richard L; Deng, Chu-Xia

    2007-02-06

    Very long chain fatty acids (VLCFA), either free or as components of glycerolipids and sphingolipids, are present in many organs. Elongation of very long chain fatty acids-4 (ELOVL4) belongs to a family of 6 members of putative fatty acid elongases that are involved in the formation of VLCFA. Mutations in ELOVL4 were found to be responsible for an autosomal dominant form of Stargardt's-like macular dystrophy (STGD3) in human. We have previously disrupted the mouse Elovl4 gene, and found that Elovl4+/- mice were developmentally normal, suggesting that haploinsufficiency of ELOVL4 is not a cause for the juvenile retinal degeneration in STGD3 patients. However, Elovl4-/- mice died within several hours of birth for unknown reason(s). To study functions of ELOVL4 further, we have explored the causes for the postnatal lethality in Elovl4-/- mice. Our data indicated that the mutant mice exhibited reduced thickness of the dermis, delayed differentiation of keratinocytes, and abnormal structure of the stratum corneum. We showed that all Elovl4-/- mice exhibited defective skin water permeability barrier function, leading to the early postnatal death. We further showed that the absence of ELOVL4 results in depletion in the epidermis of ceramides with omega-hydroxy very long chain fatty acids (> or = C28) and accumulation of ceramides with non omega-hydroxy fatty acids of C26, implicating C26 fatty acids as possible substrates of ELOVL4. These data demonstrate that ELOVL4 is required for VLCFA synthesis that is essential for water permeability barrier function of skin.

  17. Factor V deficiency

    MedlinePlus

    ... in blood plasma. These proteins are called blood coagulation factors. Factor V deficiency is caused by a ... Gailani D, Neff AT. Rare coagulation factor deficiencies. In: ... HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and ...

  18. Alpha-1 Antitrypsin Deficiency

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (an-tee-TRIP-sin) deficiency, or AAT ... as it relates to lung disease. Overview Alpha-1 antitrypsin, also called AAT, is a protein made ...

  19. DOCK8 Deficiency

    MedlinePlus

    ... on ClinicalTrials.gov . Related Links Primary Immune Deficiency Diseases (PIDDs) Immune System ​​​​​​​ Javascript Error Your browser JavaScript is turned ... Scientists Identify Genetic Cause of Previously Undefined Primary Immune Deficiency Disease Signs and Symptoms DOCK8 deficiency causes persistent skin ...

  20. Iron-Deficiency Anemia

    MedlinePlus

    ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  1. Nutrition and hair: deficiencies and supplements.

    PubMed

    Finner, Andreas M

    2013-01-01

    Hair follicle cells have a high turnover. A caloric deprivation or deficiency of several components, such as proteins, minerals, essential fatty acids, and vitamins, caused by inborn errors or reduced uptake, can lead to structural abnormalities, pigmentation changes, or hair loss, although exact data are often lacking. The diagnosis is established through a careful history, clinical examination of hair loss activity, and hair quality and confirmed through targeted laboratory tests. Examples of genetic hair disorders caused by reduced nutritional components are zinc deficiency in acrodermatitis enteropathica and copper deficiency in Menkes kinky hair syndrome.

  2. Neonatal hyperbilirubinemia caused by pyruvate kinase deficiency.

    PubMed

    Hammer, S G; Lewan, R B

    1988-01-01

    We report an infant with neonatal hyperbilirubinemia due to pyruvate kinase deficiency. The initial approach involved rapid evaluation, phototherapy, and close monitoring of serum bilirubin levels. Follow-up included maintenance on folic acid, monitoring blood counts, and educating the parents about the course of pyruvate kinase deficiency, especially aplastic crisis. We suggest that the informed family practitioner can manage neonatal hyperbilirubinemia and pyruvate kinase deficiency with referrals at critical times to pediatric or surgical specialists. The practitioner must be able to recognize quickly the need for exchange transfusion for severe jaundice and for blood transfusions or splenectomy when significant anemia or aplastic crisis occurs.

  3. Isolation and characterization of a transposon mutant of Pseudomonas fluorescens BM07 enhancing the production of polyhydroxyalkanoic acid but deficient in cold-induced exobiopolymer production.

    PubMed

    Xu, Ju; Zhao, Xu Ping; Choi, Mun Hwan; Yoon, Sung Chul

    2010-04-01

    Pseudomonas fluorescens BM07 is known to produce cold-induced exobiopolymer, which is mainly composed of water-insoluble hydrophobic polypeptides (up to 85%) and saccharides (8%), by decreasing the culture temperature down to as low as 10 degrees C. We screened for transposon insertion mutants of P. fluorescens BM07 that were unable to produce the exobiopolymer. Among the eight mutants that showed the deficiency of exobiopolymer and O-lipopolysaccharide, one mutant BM07-59 that had the highest polyhydroxyalkanoates (PHA) production was selected. The transposon inserted gene in BM07-59 was identified as galU. The disruption of the gene galU coded for the putative product, UDP-glucose pyrophosphorylase (GalU), resulted in 1.5-fold more accumulation of PHA compared with the wild-type strain from 70 mM fructose or galactose at 30 degrees C. Electrophoretic analysis of lipopolysaccharide showed that the mutant lacked the O-antigen lipopolysaccharide bands. The glycosyl composition of the lipopolysaccharide produced by the mutant strain was significantly different from that of the wild-type strain. We suggest that the deletion of galU could be a way to shift carbon flux efficiently from exobiopolymer toward PHA in P. fluorescens BM07.

  4. All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.

    PubMed

    Zhu, Xinfeng; Wang, Wenxue; Zhang, Xia; Bai, Jianhua; Chen, Gang; Li, Li; Li, Meizhang

    2015-01-01

    Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of β-catenin in vitro. ATRA also inhibited the function of PI3K-AKT and enhanced GSK-3β-dependent degradation of phosphorylated β-catenin. Furthermore, ATRA and β-catenin silencing both increased hCSC sensitivity to docetaxel treatment. Our results suggest that targeting β-catenin will provide extra benefits for ATRA-mediated treatment of hepatic cancer patients. PMID:26571119

  5. Simultaneous high-performance liquid chromatography determination of coenzyme A, dephospho-coenzyme A, and acetyl-coenzyme A in normal and pantothenic acid-deficient rats.

    PubMed

    Shibata, Katsumi; Nakai, Takumi; Fukuwatari, Tsutomu

    2012-11-15

    We describe here a simultaneous high-performance liquid chromatography method for practical and rapid determination of coenzyme A (CoA), dephospho-CoA, and acetyl-CoA in tissues. These coenzymes are biosynthesized from the vitamin pantothenic acid (PaA), which is involved in the metabolism of fatty acids, amino acid catabolism, and several other nutrients. The method employed a Tosoh TSK-GEL ODS-100 V column (250×4.6mm i.d., particle size 5μm) eluted with 100mmol/L NaH(2)PO(4) and 75mmol/L CH(3)COONa (pH was adjusted to 4.6 by the addition of concentrated H(3)PO(4))-acetonitrile (94:6, v/v) at a flow rate of 1.0ml/min. The ultraviolet detector was set at 259nm. The limits of detection for CoA, dephospho-CoA, and acetyl-CoA all were 10pmol. The method was applied to the analysis of several tissues of rats fed normal and PaA-free diets. The results clearly showed that the method was suitable for the simultaneous determination of CoA, dephospho-CoA, and acetyl-CoA in the liver, heart, kidney, spleen, testis, large colon, and muscle, but not for the small intestine, of rats.

  6. Nutritional Deficiencies and Phospholipid Metabolism

    PubMed Central

    Gimenez, María S.; Oliveros, Liliana B.; Gomez, Nidia N.

    2011-01-01

    Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the transcription activation. The components of the diet are determinant for cell functionality. In this review, the effects of macro and micronutrients deficiency on the quality, quantity and metabolism of different phospholipids and their distribution in cells of different organs is presented. Alterations in the amount of both saturated and polyunsaturated fatty acids, vitamins A, E and folate, and other micronutrients, such as zinc and magnesium, are discussed. In all cases we observe alterations in the pattern of phospholipids, the more affected ones being phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients, such as essential fatty acids, fat-soluble vitamins and some metals may contribute to a variety of diseases that can be irreversible even after replacement with normal amount of the nutrients. Usually, the sequelae are more important when the deficiency is present at an early age. PMID:21731449

  7. Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene.

    PubMed

    Alves, Mariana Q; Le Trionnaire, Emmanuelle; Ribeiro, Isaura; Carpentier, Stéphane; Harzer, Klaus; Levade, Thierry; Ribeiro, M Gil

    2013-07-01

    Farber disease, also known as Farber's lipogranulomatosis, is a clinically heterogeneous autosomal recessive disease caused by mutations in the ASAH1 gene. This gene codes for acid ceramidase, a lysosomal heterodimeric enzyme that hydrolyzes ceramide into sphingosine and fatty acid. To date, less than 25 distinct mutations have been identified in Farber patients, but no large deletions have yet been reported. In this work, cultured fibroblasts from a Farber patient with the rare neonatal form of Farber disease were studied to elucidate the molecular basis of this extremely severe phenotype. Direct sequencing of ASAH1 genomic DNA revealed the causative heterozygous mutation in the donor splice site consensus sequence of intron 11, g.24491A > G (c.917 + 4A > G), that resulted in the absence of detectable mRNA. Subsequent analysis of ASAH1 mRNA showed total skipping of exons 3 to 5. Long-range PCR and sequencing led to the identification of a gross deletion of ASAH1 gene, g.8728_18197del (c.126-3941_382 + 1358del) predicting the synthesis of a truncated polypeptide, p.Tyr42_Leu127delinsArgfs*10. Accordingly, no molecular forms corresponding to precursor or proteolytically processed mature protein were observed. These findings indicate that any functionally active acid ceramidase is absent in patient cells, underscoring the severity of the clinical phenotype. Molecular findings in the non-consanguineous parents confirmed the compound heterozygous ASAH1 genotype identified in this Farber case. This work unravels for the first time the mutations underlying the neonatal form of Farber disease and represents the first report of a large deletion identified in the ASAH1 gene. Screening for gross deletions in other patients in whom the mutation present in the second allele had not yet been identified is required to elucidate further its overall contribution for the molecular pathogenesis of this devastating disease.

  8. Development of a Nuclear Transformation System for Oleaginous Green Alga Lobosphaera (Parietochloris) incisa and Genetic Complementation of a Mutant Strain, Deficient in Arachidonic Acid Biosynthesis

    PubMed Central

    Khozin-Goldberg, Inna; Leu, Stefan; Shapira, Michal; Kaye, Yuval; Tourasse, Nicolas; Vallon, Olivier; Boussiba, Sammy

    2014-01-01

    Microalgae are considered a promising source for various high value products, such as carotenoids, ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The unicellular green alga Lobosphaera (Parietochloris) incisa is an outstanding candidate for the efficient phototrophic production of arachidonic acid (AA), an essential ω-6 PUFA for infant brain development and a widely used ingredient in the baby formula industry. Although phototrophic production of such algal products has not yet been established, estimated costs are considered to be 2–5 times higher than competing heterotrophic production costs. This alga accumulates unprecedented amounts of AA within triacylglycerols and the molecular pathway of AA biosynthesis in L. incisa has been previously elucidated. Thus, progress in transformation and metabolic engineering of this high value alga could be exploited for increasing the efficient production of AA at competitive prices. We describe here the first successful transformation of L. incisa using the ble gene as a selection marker, under the control of the endogenous RBCS promoter. Furthermore, we have succeeded in the functional complementation of the L. incisa mutant strain P127, containing a mutated, inactive version of the delta-5 (Δ5) fatty acid desaturase gene. A copy of the functional Δ5 desaturase gene, linked to the ble selection marker, was transformed into the P127 mutant. The resulting transformants selected for zeocine resistant, had AA biosynthesis partially restored, indicating the functional complementation of the mutant strain with the wild-type gene. The results of this study present a platform for the successful genetic engineering of L. incisa and its long-chain PUFA metabolism. PMID:25133787

  9. Iron deficiency anemia in pregnancy.

    PubMed

    Di Renzo, Gian Carlo; Spano, Filippo; Giardina, Irene; Brillo, Eleonora; Clerici, Graziano; Roura, Luis Cabero

    2015-11-01

    Anemia is the most frequent derailment of physiology in the world throughout the life of a woman. It is a serious condition in countries that are industrialized and in countries with poor resources. The main purpose of this manuscript is to give the right concern of anemia in pregnancy. The most common causes of anemia are poor nutrition, iron deficiencies, micronutrients deficiencies including folic acid, vitamin A and vitamin B12, diseases like malaria, hookworm infestation and schistosomiasis, HIV infection and genetically inherited hemoglobinopathies such as thalassemia. Depending on the severity and duration of anemia and the stage of gestation, there could be different adverse effects including low birth weight and preterm delivery. Treatment of mild anemia prevents more severe forms of anemia, strictly associated with increased risk of fetal-maternal mortality and morbidity.

  10. cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

    PubMed

    Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

    2016-09-01

    Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency.

  11. cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

    PubMed

    Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

    2016-09-01

    Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. PMID:27240720

  12. Relative nutritional deficiencies associated with centrally acting monoamines

    PubMed Central

    Hinz, Marty; Stein, Alvin; Uncini, Thomas

    2012-01-01

    Background Two primary categories of nutritional deficiency exist. An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone. The purpose of this paper is to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage. Materials and methods Monoamine transporter optimization results were investigated, reevaluated, and correlated with previous publications by the authors under the relative nutritional deficiency hypothesis. Most of those previous publications did not discuss the concept of a relative nutritional deficiency. It is the purpose of this paper to redefine the etiology expressed in these previous writings into the realm of relative nutritional deficiency, as demonstrated by monoamine transporter optimization. The novel and broad range of amino acid precursor dosing values required to address centrally acting monoamine relative nutritional deficiency properly is also discussed. Results Four primary etiologies are described for postsynaptic neuron damage leading to a centrally acting monoamine relative nutritional deficiency, all of which require monoamine transporter optimization to define the proper amino acid dosing values of serotonin and dopamine precursors. Conclusion Humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present

  13. Modelling linoleic acid and α-linolenic acid requirements for infants and young children in developing countries.

    PubMed

    Yang, Zhenyu; Huffman, Sandra L

    2013-01-01

    Essential fatty acids (EFAs), linoleic acid (LA) and α-linolenic acid (ALA), play a critical role in the growth and development of infants and young children. However, national guidelines for recommended intakes of EFAs are lacking in most developing countries. The objective of this study was to convert international EFA recommendations based on % of daily energy intake to recommended daily amounts for children aged 6-23 months in developing countries. The Food and Agriculture Organization (FAO) reports adequate intakes (AIs) for ALA as 0.4-0.6% of energy intake for children 6-23 months of age and as 3.0-4.5% of energy intake for LA. In order to estimate energy intakes, FAO daily energy requirements based on body weight were used. The daily AI amounts for these EFAs were calculated using the median body weight of the World Health Organization (WHO) Growth Standard population and median body weights with varying levels of malnutrition. The AI for ALA is equivalent to 0.3-0.4, 0.3-0.5 and 0.4-0.6 g day(-1), and the AI for LA is equivalent to 2.1-3.1, 2.4-3.5 and 2.8-4.3 g day(-1) for children aged 6-8, 9-11 and 12-23 months, respectively. While the lower median body weights of children in developing countries and associated reduced energy intake recommendations give lower estimated EFA requirements, recommendations based on median body weights in the WHO Reference Growth Standard is suggested. The upper levels of these calculated AIs are lower than or equal to those in North America (ALA: 0.5 and 0.7 g day(-1); LA: 4.6 and 7 g day(-1) for children aged 6-12 months and 1-3 years, respectively). The FAO AIs (g day(-1)) calculated here for ALA and LA can serve as a guideline for developing countries for setting national standards.

  14. Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

    NASA Astrophysics Data System (ADS)

    Menet, V.; Prieto, M.; Privat, A.; Giménez Y Ribotta, M.

    2003-07-01

    The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional disabilities. The inability of neurons to regenerate their axon is appreciably due to an inhospitable environment made of an astrocytic scar. We generated mice knock-out for glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, which are upregulated in reactive astrocytes. These animals, after a hemisection of the spinal cord, presented reduced astroglial reactivity associated with increased plastic sprouting of supraspinal axons, including the reconstruction of circuits leading to functional restoration. Therefore, improved anatomical and functional recovery in the absence of both proteins highlights the pivotal role of reactive astrocytes in axonal regenerative failure in adult CNS and could lead to new therapies of spinal cord lesions.

  15. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  16. Colour vision deficiency.

    PubMed

    Simunovic, M P

    2010-05-01

    Colour vision deficiency is one of the commonest disorders of vision and can be divided into congenital and acquired forms. Congenital colour vision deficiency affects as many as 8% of males and 0.5% of females--the difference in prevalence reflects the fact that the commonest forms of congenital colour vision deficiency are inherited in an X-linked recessive manner. Until relatively recently, our understanding of the pathophysiological basis of colour vision deficiency largely rested on behavioural data; however, modern molecular genetic techniques have helped to elucidate its mechanisms. The current management of congenital colour vision deficiency lies chiefly in appropriate counselling (including career counselling). Although visual aids may be of benefit to those with colour vision deficiency when performing certain tasks, the evidence suggests that they do not enable wearers to obtain normal colour discrimination. In the future, gene therapy remains a possibility, with animal models demonstrating amelioration following treatment.

  17. [Iodine deficiency during pregnancy ].

    PubMed

    de Luis, D A; Aller, R; Izaola, O

    2005-09-01

    Iodine is an essential micronutrient, it would be administered every day with our diet. The main role of this micronutrient is the synthesis of thyroid hormone. Thyroid hormones are related with brain development and metabolic regulation. Iodine deficit is related with goitre, and an important problem "diseases related with iodine deficiency", including high rate of neonatal mortality, decrease of intelligence, delayed of growth, high rate of aborts and congenital abnormalities.A risk group is pregnant women. Some authors have been demonstrated the utility of iodine supplementation during pregnancy. A systematic review of Cochrane group has shown that iodine supplementation during pregnancy decreased neonatal mortality RR 0.71 (0.56-0.9), and decrease the incidence of cretinism in children under 4 years RR 0.27 (0.12-0.6). As final recommendations, a program in pregnant women must be development to treat with iodine such as we make with folic acid. Pills with iron and iodine (1 mg iron and 25 ug iodine) have been demonstrated better results that pills with iodine. Tablets are the main presentation due to the role of the women in our Society and the work time. Programs of iodine enriched salt have been demonstrated a follow up of 50%. PMID:16386080

  18. Wall Teichoic Acid Deficiency in Staphylococcus aureus Confers Selective Resistance to Mammalian Group IIA Phospholipase A2 and Human β-Defensin 3▿

    PubMed Central

    Koprivnjak, Tomaz; Weidenmaier, Christopher; Peschel, Andreas; Weiss, Jerrold P.

    2008-01-01

    Wall teichoic acids (WTAs) and membrane lipoteichoic acids (LTAs) are the major polyanionic polymers in the envelope of Staphylococcus aureus. WTAs in S. aureus play an important role in bacteriophage attachment and bacterial adherence to certain host cells, suggesting that WTAs are exposed on the cell surface and could also provide necessary binding sites for cationic antimicrobial peptides and proteins (CAMPs). Highly cationic mammalian group IIA phospholipase A2 (gIIA PLA2) kills S. aureus at nanomolar concentrations by an action(s) that depends on initial electrostatic interactions, cell wall penetration, membrane phospholipid (PL) degradation, and activation of autolysins. A tagO mutant of S. aureus that lacks WTA is up to 100-fold more resistant to PL degradation and killing by gIIA PLA2 and CAMP human β-defensin 3 (HBD-3) but has the sensitivity of the wild type (wt) to other CAMPs, such as Magainin II amide, hNP1-3, LL-37, and lactoferrin. In contrast, there is little or no difference in either gIIA PLA2 activity toward cell wall-depleted protoplasts of the wt and tagO strains of S. aureus or in binding of gIIA PLA2 to wt and tagO strains. Scanning and transmission electron microscopy reveal increased surface protrusions in the S. aureus tagO mutant that might account for reduced activity of bound gIIA PLA2 and HBD-3 toward the tagO mutant. In summary, the absence of WTA in S. aureus causes a selective increase in bacterial resistance to gIIA PLA2 and HBD-3, the former apparently by reducing access and/or activity of bound antibacterial enzyme to the bacterial membrane. PMID:18347049

  19. ATF4-dependent Regulation of the JMJD3 Gene during Amino Acid Deprivation Can Be Rescued in Atf4-deficient Cells by Inhibition of Deacetylation*

    PubMed Central

    Shan, Jixiu; Fu, Lingchen; Balasubramanian, Mukundh N.; Anthony, Tracy; Kilberg, Michael S.

    2012-01-01

    Following amino acid deprivation, the amino acid response (AAR) induces transcription from specific genes through a collection of signaling mechanisms, including the GCN2-eIF2-ATF4 pathway. The present report documents that the histone demethylase JMJD3 is an activating transcription factor 4 (ATF4)-dependent target gene. The JMJD3 gene contains two AAR-induced promoter activities and chromatin immunoprecipitation (ChIP) analysis showed that the AAR leads to enhanced ATF4 recruitment to the C/EBP-ATF response element (CARE) upstream of Promoter-1. AAR-induced histone modifications across the JMJD3 gene locus occur upon ATF4 binding. Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA). The TSA rescue of AAR activation in the absence of Atf4 also occurred for the Atf3 and C/EBP homology protein (Chop) genes, but not for the asparagine synthetase gene. ChIP analysis of the Jmjd3, Atf3, and Chop genes in Atf4 knock-out cells documented that activation of the AAR in the presence of TSA led to specific changes in acetylation of histone H4. The results suggest that a primary function of ATF4 is to recruit histone acetyltransferase activity to a sub-set of AAR target genes. Thus, absolute binding of ATF4 to these particular genes is not required and no ATF4 interaction with the general transcription machinery is necessary. The data are consistent with the hypothesis that ATF4 functions as a pioneer factor to alter chromatin structure and thus, enhance transcription in a gene-specific manner. PMID:22955275

  20. α1-Antitrypsin Deficiency.

    PubMed

    Hatipoğlu, Umur; Stoller, James K

    2016-09-01

    α1-Antitrypsin deficiency is an autosomal codominant condition that predisposes to emphysema and cirrhosis. The condition is common but grossly under-recognized. Identifying patients' α1-antitrypsin deficiency has important management implications (ie, smoking cessation, genetic and occupational counseling, and specific treatment with the infusion of pooled human plasma α1-antitrypsin). The weight of evidence suggests that augmentation therapy slows the progression of emphysema in individuals with severe α1-antitrypsin deficiency. PMID:27514595

  1. A new phytase continuously hydrolyzes phytate and improves amino acid digestibility and mineral balance in growing pigs fed phosphorous-deficient diet.

    PubMed

    Zeng, Z K; Li, Q Y; Zhao, P F; Xu, X; Tian, Q Y; Wang, H L; Pan, L; Yu, S; Piao, X S

    2016-02-01

    Ten ileal T-cannulated pigs (19.26 ± 1.06 kg) were used to evaluate the effects of a novel phytase on apparent ileal digestibility (AID) of AA and apparent total tract digestibility (ATTD) and hindgut disappearance of DM, GE, CP, crude fiber, NDF, and ADF as well as minerals balance. Pigs were fed in a duplicated 5 × 4 incomplete Latin square design (5 diets with 4 periods). Each period consisted of a 5-d adjustment period followed by a 3-d total collection of feces and urine and then a 2-d collection of ileal digesta. The 5 diets included a P-deficient basal diet (0.43% Ca and 0.38% total P) that was supplemented with 0 (negative control [NC]), 500, 1,000, or 20,000 phytase units (FTU)/kg phytase and a positive control (PC) diet that was P adequate (0.64% Ca and 0.52% total P). The addition of phytase to the NC diet improved ( < 0.05) AID of phytate from 11.1 to 62.8, 70.6, and 90.5% at the inclusion rates of 500, 1,000, and 20,000 FTU/kg, respectively. In general, phytase supplementation at a dose of 20,000 FTU/kg further increased ( < 0.05) AID of Ca, total P, and phytate and reduced ( < 0.05) the ileal phytate concentration compared with diets with 500 or 1,000 FTU/kg phytase. Pigs fed the diet with 20,000 FTU/kg phytase but not diets with 500 and 1,000 FTU/kg phytase showed improved ( < 0.05) ATTD of CP and AID of DM, GE, CP, Leu, Lys, Thr, Val, Asp, and Ser compared with pigs fed the PC or NC diet. However, hindgut disappearance of crude fiber and NDF ( < 0.05) were reduced in pigs fed the diet with 20,000 FTU/kg phytase compared with pigs fed the PC or NC diet. Pigs fed diets with 500 or 1,000 FTU/kg phytase had greater ATTD and retention of Ca and P than pigs fed the NC diet but less compared with pigs fed the diet with 20,000 FTU/kg phytase. Supplementation of 20,000 FTU/kg phytase to the NC diet improved ( < 0.05) digestibility of Na, Mn, and Zn as well as retention (%) of Zn. Increasing phytase supplementation doses from 0 to 1,000 FTU/kg linearly

  2. [Vitamin B12 deficiency in geriatrics].

    PubMed

    Bopp-Kistler, I; Rüegger-Frey, B; Grob, D; Six, P

    1999-11-01

    Cobalamin deficiency increases with advancing age. The cut-off point of serum concentration should be raised, because many elderly people with "normal" serum vitamin B12 concentrations are metabolically deficient in cobalamin. The measurement of the metabolites homocysteine and/or methylmalonic acid is recommended. Cobalamin deficiency may result in a variety of atypical symptoms. Hematological changes typical of megaloblastic anemia are absent in a majority of patients with neuropsychiatric disorders. Generally underlying pernicious anemia is not the main cause of cobalamin deficiency in the elderly. Protein-bound cobalamin malabsorption due to atrophic gastritis with hypo- or achlorhydria is a common cause of cobalamin deficiency in elderly people. An important manifestation of cobalamin deficiency is cognitive impairment. Much controversy exists on the subject of the association of dementia of the Alzheimer type with cobalamin deficiency. In several studies dementia has been related to low serum cobalamin levels. Physicians should be liberal of cobalamin therapy. The window of opportunity for effective intervention may be as short as one year from the onset of medical symptoms. At last a compilation of recommendations is given.

  3. Essential fatty acids prevent slowed nerve conduction in streptozotocin diabetic rats.

    PubMed

    Julu, P O

    1988-01-01

    Rats were given streptozotocin to induce insulin-dependent diabetes or citrate buffer alone in two experiments. Initially, the effect of 5 wks of dietary gamma-linolenic acid (GLA) plus eicosapentaenoic acid (EPA) on cutaneous nerve conduction velocity (CV) was examined. CV was determined by direct stimulation and recording from saphenous nerve under urethane anesthesia. Secondly, a 5 weeks study of supplementing the diet with GLA, GLA and EPA, or hydrogenated coconut oil (HC) was done. In addition, motor nerve CV was determined by directly stimulating sciatic nerve and recording from gastrocnemius muscle. The acute diabetes led to weight loss, and elevated blood glucose and glycosylated hemoglobin levels. Essential fatty acid (EFA) supplementation had no effect on any of these measures of severity of diabetes. In diabetic rats without EFA supplementation, CV of the myelinated fibers fell by 19-21%, while those receiving both GLA and EPA had normal CV. In diabetic rats receiving GLA alone, CV fell by 5-7%, which was significantly less than those without EFA supplementation (p less than 0.01 for cutaneous, and p less than 0.001 for motor nerves).

  4. Effect of inositol and phytases on hematological indices and α-1 acid glycoprotein levels in laying hens fed phosphorus-deficient corn-soybean meal-based diets.

    PubMed

    Zyła, K; Grabacka, M; Pierzchalska, M; Duliński, R; Starzyńska-Janiszewska, A

    2013-01-01

    The effects of feeding low nonphytate phosphorus (NPP) corn-soybean meal-based diets supplemented with myo-inositol at 0.1%, or with phytase B at 1,300 acid phosphatase units/kg, or with phytase B enriched in 6-phytase A at 300 phytase units/kg on the hematological indices and the α-1 acid glycoprotein (AGP) concentrations in the blood of Bovans Brown laying hens were investigated. The experimental design comprised also a negative control diet and an internal control diet that had the NPP content adjusted by the addition of 0.304 g of monocalcium phosphate per kg to reach the NPP level similar to that resulting from the combined action of both phytases. A total of sixty 50-wk-old hens were randomly assigned to the dietary treatments with 12 cage replicates of 1 hen, and fed the experimental diets until wk 62, when the blood samples were taken and analyzed for basic hematological indices and for AGP concentrations in sera. The hematological indices from all the experimental groups remained in a normal range; nevertheless, the statistically significant effects of diet on hemoglobin concentration (P = 0.003), erythrocyte counts (P = 0.035), the percentage of lymphocytes (P = 0.020), heterophils (P = 0.002), eosinophils (P = 0.023), and basophils (P = 0.001) in the leucocyte population, as well as on the heterophil to lymphocyte ratio (P = 0.003), were observed. The highest erythrocyte counts were characteristic for hens fed the diet supplemented with both phytase A and phytase B. The highest heterophil to lymphocyte ratios were found in blood of hens fed the diet supplemented with phytase B, whereas the highest basophil percentages and the highest AGP concentrations occurred in birds fed the negative control diet. A highly significant correlation was observed between AGP concentrations in sera and BW losses determined previously. The results indicate that the low-NPP corn soybean meal-based diets increased acute phase protein level in laying hens. Phytase B alone

  5. Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants.

    PubMed

    Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Feussner, Ivo; Havaux, Michel; Riefler, Michael; Schmülling, Thomas

    2016-07-01

    The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress.

  6. Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells

    PubMed Central

    Reyes-Zurita, Fernando J.; Rufino-Palomares, Eva E.; García-Salguero, Leticia; Peragón, Juan; Medina, Pedro P.; Parra, Andrés; Cascante, Marta; Lupiáñez, José A.

    2016-01-01

    Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin. PMID:26751572

  7. Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants.

    PubMed

    Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Feussner, Ivo; Havaux, Michel; Riefler, Michael; Schmülling, Thomas

    2016-07-01

    The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

  8. Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

    PubMed Central

    Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

    2016-01-01

    The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

  9. Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4-Cre-mediated knockout of the tuberous sclerosis complex 1 gene.

    PubMed

    Xiang, Xinxin; Yuan, Fang; Zhao, Jing; Li, Ziru; Wang, Xian; Guan, Youfei; Tang, Chaoshu; Sun, Guang; Li, Yin; Zhang, Weizhen

    2013-03-01

    Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre (Fabp4-Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4-Tsc1cKO mouse revealed a much smaller phenotype relative to the wild-type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4-Tsc1cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of Fabp4-Tsc1cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the Fabp4-Tsc1cKO mice, which was rescued by maternal injection of rapamycin. Co-localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1-mTORC1 may be critical for the synthesis of surfactant proteins A and B.

  10. Purine metabolism in adenosine deaminase deficiency.

    PubMed Central

    Mills, G C; Schmalstieg, F C; Trimmer, K B; Goldman, A S; Goldblum, R M

    1976-01-01

    Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides. PMID:1066699

  11. Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

    SciTech Connect

    Takeuchi-Yorimoto, Ayano; Noto, Takahisa; Yamada, Atsushi; Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro

    2013-05-01

    Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

  12. The Combined Action of ENHANCED DISEASE SUSCEPTIBILITY1, PHYTOALEXIN DEFICIENT4, and SENESCENCE-ASSOCIATED101 Promotes Salicylic Acid-Mediated Defenses to Limit Fusarium graminearum Infection in Arabidopsis thaliana.

    PubMed

    Makandar, Ragiba; Nalam, Vamsi J; Chowdhury, Zulkarnain; Sarowar, Sujon; Klossner, Guy; Lee, Hyeonju; Burdan, Dehlia; Trick, Harold N; Gobbato, Enrico; Parker, Jane E; Shah, Jyoti

    2015-08-01

    Fusarium graminearum causes Fusarium head blight (FHB) disease in wheat and other cereals. F. graminearum also causes disease in Arabidopsis thaliana. In both Arabidopsis and wheat, F. graminearum infection is limited by salicylic acid (SA) signaling. Here, we show that, in Arabidopsis, the defense regulator EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) and its interacting partners, PAD4 (PHYTOALEXIN-DEFICIENT4) and SAG101 (SENESCENCE-ASSOCIATED GENE101), promote SA accumulation to curtail F. graminearum infection. Characterization of plants expressing the PAD4 noninteracting eds1(L262P) indicated that interaction between EDS1 and PAD4 is critical for limiting F. graminearum infection. A conserved serine in the predicted acyl hydrolase catalytic triad of PAD4, which is not required for defense against bacterial and oomycete pathogens, is necessary for limiting F. graminearum infection. These results suggest a molecular configuration of PAD4 in Arabidopsis defense against F. graminearum that is different from its defense contribution against other pathogens. We further show that constitutive expression of Arabidopsis PAD4 can enhance FHB resistance in Arabidopsis and wheat. Taken together with previous studies of wheat and Arabidopsis expressing salicylate hydroxylase or the SA-response regulator NPR1 (NON-EXPRESSER OF PR GENES1), our results show that exploring fundamental processes in a model plant provides important leads to manipulating crops for improved disease resistance.

  13. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

    PubMed

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda

    2016-01-01

    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

  14. Resistance to Botrytis cinerea in sitiens, an Abscisic Acid-Deficient Tomato Mutant, Involves Timely Production of Hydrogen Peroxide and Cell Wall Modifications in the Epidermis1[C][W][OA

    PubMed Central

    Asselbergh, Bob; Curvers, Katrien; França, Soraya C.; Audenaert, Kris; Vuylsteke, Marnik; Van Breusegem, Frank; Höfte, Monica

    2007-01-01

    Plant defense mechanisms against necrotrophic pathogens, such as Botrytis cinerea, are considered to be complex and to differ from those that are effective against biotrophs. In the abscisic acid-deficient sitiens tomato (Solanum lycopersicum) mutant, which is highly resistant to B. cinerea, accumulation of hydrogen peroxide (H2O2) was earlier and stronger than in the susceptible wild type at the site of infection. In sitiens, H2O2 accumulation was observed from 4 h postinoculation (hpi), specifically in the leaf epidermal cell walls, where it caused modification by protein cross-linking and incorporation of phenolic compounds. In wild-type tomato plants, H2O2 started to accumulate 24 hpi in the mesophyll layer and was associated with spreading cell death. Transcript-profiling analysis using TOM1 microarrays revealed that defense-related transcript accumulation prior to infection was higher in sitiens than in wild type. Moreover, further elevation of sitiens defense gene expression was stronger than in wild type 8 hpi both in number of genes and in their expression levels and confirmed a role for cell wall modification in the resistant reaction. Although, in general, plant defense-related reactive oxygen species formation facilitates necrotrophic colonization, these data indicate that timely hyperinduction of H2O2-dependent defenses in the epidermal cell wall can effectively block early development of B. cinerea. PMID:17573540

  15. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

    PubMed

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda

    2016-01-01

    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA. PMID:26077874

  16. Cerebral Folate Deficiency

    ERIC Educational Resources Information Center

    Gordon, Neil

    2009-01-01

    Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

  17. Iron induced nickel deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is increasingly apparent that economic loss due to nickel (Ni) deficiency likely occurs in horticultural and agronomic crops. While most soils contain sufficient Ni to meet crop requirements, situations of Ni deficiency can arise due to antagonistic interactions with other metals. This study asse...

  18. Iron deficiency: beyond anemia.

    PubMed

    Yadav, Dinesh; Chandra, Jagdish

    2011-01-01

    Iron deficiency is the most common nutritional disorder affecting at least one third of world's population. Though anemia is common manifestation of iron deficiency, other effects of iron deficiency on various tissues, organs and systems are usually under recognized. Impaired brain development and cognitive, behavioural and psychomotor impairment are most worrisome manifestations of iron deficiency. Studies have demonstrated that some of these changes occurring during period of brain growth spurt (<2 years age) may be irreversible. Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized. Impaired cell-mediated immunity and bactericidal function are generally noted in iron-deficient persons; however, the findings are inconsistent. Despite proven reversible functional immunological defects in vitro studies, a clinically important relationship between states of iron deficiency and susceptibility to infections remains controversial. Studies from malaria endemic regions have reported increased incidence of malaria in association with iron supplementation. These and some other aspects of iron deficiency are reviewed in this article.

  19. Iodine-deficiency disorders.

    PubMed

    Zimmermann, Michael B; Jooste, Pieter L; Pandav, Chandrakant S

    2008-10-01

    2 billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficiency disorders. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Assessment methods include urinary iodine concentration, goitre, newborn thyroid-stimulating hormone, and blood thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is iodisation of salt, which is one of the most cost-effective ways to contribute to economic and social development. When iodisation of salt is not possible, iodine supplements can be given to susceptible groups. Introduction of iodised salt to regions of chronic iodine-deficiency disorders might transiently increase the proportion of thyroid disorders, but overall the small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. International efforts to control iodine-deficiency disorders are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges. PMID:18676011

  20. MENTAL DEFICIENCY. SECOND EDITION.

    ERIC Educational Resources Information Center

    HILLIARD, L.T.; KIRMAN, BRIAN H.

    REVISED TO INCLUDE LEGISLATIVE AND ADMINISTRATIVE PROCEDURES NEW IN BRITAIN SINCE THE 1957 EDITION, THE TEXT INCLUDES RECENT ADVANCES IN ETIOLOGY, PATHOLOGY, AND TREATMENT OF MENTAL DEFICIENCY. CONSIDERATION OF THE BACKGROUND OF MENTAL DEFICIENCY INCLUDES HISTORICAL AND LEGAL ASPECTS, THE SOCIAL BACKGROUND OF MENTAL DEFECT, PRENATAL CAUSES OF…

  1. Iron deficiency anemia

    MedlinePlus

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  2. Multiple congenital coagulation deficiencies.

    PubMed

    BONNIN, J A; HICKS, N D; INNIS, M D; SIMPSON, D A

    1960-07-01

    A 6-week-old infant is presented who suffered from a congenital haemorrhagic disorder which caused death from subdural haemorrhage following mild trauma. Haematological investigation revealed deficiencies of factor VII and Christmas factor. Prower-Stuart factor was probably also deficient although investigation of this clotting factor was carried out only on serum obtained at necropsy.

  3. Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

    PubMed

    Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

    2011-04-01

    We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

  4. Recombination-deficient mutant of Streptococcus faecalis

    SciTech Connect

    Yagi, Y.; Clewell, D.B.

    1980-08-01

    An ultraviolet radiation-sensitive derivative of Streptococcus faecalis strain JH2-2 was isolated and found to be deficient in recombination, using a plasmid-plasmid recombination system. The strain was sensitive to chemical agents which interact with deoxyribonucleic acid and also underwent deoxyribonucleic acid degradation after ultraviolet irradiation. Thus, the mutant has properties similar to those of recA strains of Escherichia coli.

  5. Nature and nurture in vitamin B12 deficiency.

    PubMed

    Zschocke, J; Schindler, S; Hoffmann, G F; Albani, M

    2002-07-01

    We report on a child in whom severe nutritional vitamin B12 deficiency was exacerbated by a genetic impairment of the folate cycle, causing reduced CSF concentrations of the methyl group donor 5-methyltetrahydrofolate. Some patients with vitamin B12 deficiency may benefit from high dose folic acid supplementation, even if plasma concentrations are high.

  6. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    PubMed Central

    Werder, Steven F

    2010-01-01

    homocysteine, serum methylmalonic acid, antiparietal cell and anti-intrinsic factor antibodies, and serum gastrin level. In B12 deficiency dementia with versus without pernicious anemia, there appear to be different manifestations, need for further workup, and responses to treatment. Dementia of the Alzheimer’s type is a compatible diagnosis when B12 deficiency is found, unless it is caused by pernicious anemia. Patients with pernicious anemia generally respond favorably to supplemental B12 treatment, especially if pernicious anemia is diagnosed early in the course of the disease. Some patients without pernicious anemia, but with B12 deficiency and either mild cognitive impairment or mild to moderate dementia, might show some degree of cognitive improvement with supplemental B12 treatment. Evidence that supplemental B12 treatment is beneficial for patients without pernicious anemia, but with B12 deficiency and moderately-severe to severe dementia is scarce. Oral cyanocobalamin is generally favored over intramuscular cyanocobalamin. PMID:20505848

  7. Glucose-6-phosphate dehydrogenase deficiency

    MedlinePlus

    G6PD deficiency; Hemolytic anemia due to G6PD deficiency; Anemia - hemolytic due to G6PD deficiency ... Saunders; 2016:chap 161. Janz TG, Hamilton GC. Anemia, polycythemia, and white blood cell disorders. In: Marx ...

  8. Genetics Home Reference: X-linked creatine deficiency

    MedlinePlus

    ... gene mutations impair the ability of the transporter protein to bring creatine into cells, resulting in a creatine shortage ... E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. 2011 May;40( ...

  9. Genetics Home Reference: arginine:glycine amidinotransferase deficiency

    MedlinePlus

    ... links) Encyclopedia: Febrile Seizures Health Topic: Amino Acid Metabolism Disorders Health Topic: Developmental Disabilities Health Topic: Genetic ... amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Nov; ...

  10. [Approaches to vitamin B12 deficiency].

    PubMed

    Russcher, Henk; Heil, Sandra G; Slobbe, Lennert; Lindemans, Jan

    2012-01-01

    A 28-year-old female vegetarian was referred to a specialist in internal medicine with persistent iron deficiency. Laboratory analysis revealed microcytic anaemia with low ferritin levels but normal total vitamin B12 levels. The red blood cell distribution width, however, showed a very wide variation in red blood cell sizes, indicating a coexisting vitamin B12 deficiency, which was confirmed by the low concentration of active vitamin B12. Another patient, a 69-year-old woman with a history of previous gastric surgery and renal insufficiency as a complication of diabetes mellitus, was suspected to be deficient in vitamin B12, as she had low total vitamin B12 levels and an accumulation of methylmalonic acid and homocysteine in her blood. Testing the total concentration of vitamin B12 alone has insufficient diagnostic accuracy and no accepted gold standard is available for diagnosing vitamin B12 deficiency. With the development of newer tests, such as measuring holotranscobalamin II (concentration of active vitamin B12), atypical and subclinical deficiency states can be recognized. A new approach to diagnosing vitamin B12 deficiency is presented, based upon these 2 case descriptions.

  11. [Effects of nutrient deficiency on principal components of ginseng root exudates].

    PubMed

    Li, Yong; Huang, Xiao-fang; Ding, Wan-long

    2008-08-01

    By the method of solution culture, the effects of N, P, and K deficiency on the principol components in root exudates of ginseng at its early growth stage were studied. The results showed that in treatments N and K deficiency and control, no significant difference was observed in the principal components of ginseng root exudates, and 28, 29, and 27 principal chromatographic peaks were detected by GC-MS, respectively; while in treatment P deficiency, only 22 principal chromatographic peaks were detected. Furthermore compounds in the root exudates from treatments N, P, and K deficiency and control were identified, respectively. Compared with control, treatments N and K deficiency had more kinds of organic acids and phenolic acids in root exudates, while treatment P deficiency was in adverse, which suggested that at early growth stages, ginseng had more requirement to N and K than P, and N and K deficiency would accelerate the exudation of organic acids and phenolic acids by roots.

  12. Alpha-1 antitrypsin deficiency

    MedlinePlus

    ... liver from damage. The condition can lead to emphysema and liver disease . ... descent. Adults with severe AAT deficiency will develop emphysema , often before age 40. Smoking can increase the ...

  13. Growth hormone deficiency - children

    MedlinePlus

    ... the same age. The child will have normal intelligence in most cases. In older children, puberty may ... hormones cause the body to make. Tests can measure these growth factors. Accurate growth hormone deficiency testing ...

  14. Familial lipoprotein lipase deficiency

    MedlinePlus

    ... and white-colored blood vessels in the retinas Pancreatitis that keeps returning Yellowing of the eyes and ... discuss your diet needs with a registered dietitian. Pancreatitis that is related to lipoprotein lipase deficiency responds ...

  15. Vitamin D Deficiency

    MedlinePlus

    ... deficiency can lead to a loss of bone density (size and strength), broken bones (fractures), muscle weakness, ... get too much calcium in their blood or urine. Careful monitoring of blood vitamin D levels will ...

  16. Alpha-1 Antitrypsin Deficiency

    MedlinePlus

    ... the right shape, they get stuck in the liver cells and can't reach the lungs. Symptoms of AAT deficiency include Shortness of breath and wheezing Repeated lung ... or delay lung symptoms. NIH: National Heart, Lung, and Blood Institute

  17. Deletion of sterol O-acyltransferase 2 (SOAT2) function in mice deficient in lysosomal acid lipase (LAL) dramatically reduces esterified cholesterol sequestration in the small intestine and liver

    PubMed Central

    Lopez, Adam M.; Posey, Kenneth S.; Turley, Stephen D.

    2014-01-01

    Sterol O-acyltransferase 2 (SOAT2), also known as ACAT2, is the major cholesterol esterifying enzyme in the liver and small intestine (SI). Esterified cholesterol (EC) carried in certain classes of plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease (WD) or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to what effect the loss of SOAT2 function might have on tissue EC sequestration in LAL-deficient mice. When weaned at 21 days, Lal−/−:Soat2+/+ mice had a whole liver cholesterol content (mg/organ) of 24.7 mg vs. 1.9 mg in Lal+/+:Soat2+/+ littermates, with almost all the excess sterol being esterified. Over the next 31 days, liver cholesterol content in the Lal−/−:Soat2+/+ mice increased to 145 ± 2 mg but to only 29 ± 2 mg in their Lal−/−:Soat2−/− littermates. The level of EC accumulation in the SI of the Lal−/−:Soat2−/− mice was also much less than in their Lal−/−:Soat2+/+ littermates. In addition, there was a >70% reduction in plasma transaminase activities in the Lal−/−:Soat2−/− mice. These studies illustrate how the severity of disease in a mouse model for CESD can be substantially ameliorated by elimination of SOAT2 function. PMID:25450374

  18. AADC deficiency: occurring in humans, modeled in rodents.

    PubMed

    Hwu, Wuh-Liang; Lee, Ni-Chung; Chien, Yin-Hsiu; Muramatsu, Shin-ichi; Ichinose, Hiroshi

    2013-01-01

    Aromatic l-amino acid decarboxylase (AADC) is a homodimeric pyridoxal phosphate-dependent enzyme responsible for the syntheses of dopamine and serotonin. Defects in the AADC gene result in neurotransmitter deficiencies. Patients with AADC deficiency have severe motor and autonomic dysfunctions. A mouse model of AADC deficiency was recently established. These mice grow poorly and move awkwardly during infancy. They also show high anxiety when they grow up. Because drug therapy provides little or no benefit for many patients with AADC deficiency, a gene therapy has been attempted. The gene therapy employed an adeno-associated virus viral vector that can express the human AADC protein. The vector was injected to the brain of several children with AADC deficiency. The therapy was well tolerated, and all treated patients showed improvement. In the future, the mouse model will also help the development of treatments for AADC deficiency.

  19. Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity.

    PubMed

    Malik, Sushma; Paldiwal, Ashutosh Abhimanyu; Korday, Charusheela Sujit; Jadhav, Shruti Sudhir

    2015-10-01

    Carnitine palmitoyltransferase II (CPTII) deficiency is a rare disorder of mitochondrial fatty acid oxidation with autosomal recessive mode of inheritance. Three classic forms of CPT II deficiency have been described namely the lethal neonatal form, severe infantile hepatocardiomuscular form and the myopathic form. We present a three-day-old female child, admitted to us for lethargy, icterus, low sugars and convulsions. Persistent non ketotic hypoglycaemia, hyperammonemia, raised liver enzymes with hepatomegaly and cardiomyopathy led to the suspicion of fatty acid oxidation defect. Tandem mass spectrometry helped to clinch the diagnosis of CPT II Deficiency in the present case. PMID:26557586

  20. VERMILION-DEFICIENCY.

    PubMed

    Bridges, C B

    1919-07-20

    In May, 1916, a culture of Drosophila melanogaster showed that a new sex-linked lethal had arisen. The linkage relations indicated that the position of the lethal was in the neighborhood of the sex-linked recessive "vermilion," whose locus in the X chromosome is at 33.0. When females heterozygous for the lethal were outcrossed to vermilion males, all the daughters that received the lethal-bearing chromosome showed vermilion eye-color, though, from the pedigree, vermilion was known to be absent from the ancestry of the mother. The lethal action and the unexpected appearance of vermilion both suggested that this was another instance of the phenomenon called "deficiency;" that is, the loss or "inactivation" of the genes of a section of the X chromosome. The lethal action would then be due to the deficient region including one or more genes necessary for the life of the individual. The appearance of vermilion in females carrying only one vermilion gene would be explainable on the ground that the deficient-bearing females are virtually haploid for the region including the vermilion locus. Linkage tests showed that the amount of crossing over in the neighborhood of the deficiency was cut down by about five units. Part of this may be attributed to the actual length of the "deficient" region, within which it is probable that no crossing over occurs, and part (probably most) to an alteration in the synaptic relations in the regions immediately adjacent. In more remote regions there was no disturbance or perhaps a slight rise in the frequency of crossing over. Both the local fall and the possible rise in more distant regions would seem to argue that a "pucker" at synapsis had been caused by an actual shortening of the deficient chromosome. That the deficient region extends to the left of the locus of vermilion was indicated by a test in which it was observed that the presence of an extra piece of chromosome including the loci for vermilion and sable ("vermilion

  1. The Enteropathy of Prostaglandin Deficiency

    PubMed Central

    Adler, David H.; Phillips, John A.; Cogan, Joy D.; Iverson, Tina M.; Stein, Jeffrey A.; Brenner, David A.; Morrow, Jason D.; Boutaud, Olivier; Oates, John A.

    2009-01-01

    Purpose Small intestinal ulcers are frequent complications of therapy with non-steroidal anti-inflammatory drugs (NSAIDs). We present here a genetic deficiency of eicosanoid biosynthesis that illuminates the mechanism of NSAID-induced ulcers of the small intestine. Methods Eicosanoids and metabolites were measured by isotope-dilution with mass spectrometry. cDNA was obtained by reverse transcription and sequenced following amplification with RT-PCR. Results We investigated the cause of chronic recurrent small intestinal ulcers, small bowel perforations, and gastrointestinal blood loss in a 45 year old male who was not taking any cyclooxygenase inhibitor. Prostaglandin metabolites in urine were significantly depressed. Serum thromboxane B2 (TxB2) production was 4.6% of normal controls (p<0.006) and serum 12-HETE was 1.3% of controls (p<0.005). Optical platelet aggregation with simultaneous monitoring of ATP release demonstrated absent granule secretion in response to ADP and a blunted aggregation response to ADP and collagen, but normal response to arachidonic acid (AA). LTB4 biosynthesis by ionophore activated leukocytes was only 3% of controls and urinary LTE4 was undetectable. These findings suggested deficient AA release from membrane phospholipids by cytosolic phospholipase A2-α (cPLA2-α) which regulates cyclooxygenase and lipoxygenase mediated eicosanoid production by catalyzing the release of their substrate, AA. Sequencing of cPLA2-α cDNA demonstrated 2 heterozygous non-synonymous single base pair mutations: Ser111Pro (S111P) and Arg485His (R485H), as well as a known SNP: Lys651Arg (K651R). Conclusion Characterization of this cPLA2-α deficiency provides support for the importance of prostaglandins in protecting small intestinal integrity, and indicates that loss of prostaglandin biosynthesis is sufficient to produce small intestinal ulcers. PMID:19148786

  2. Deregulation of mitochondrial functions provoked by long-chain fatty acid accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial permeability transition deficiencies in rat heart--mitochondrial permeability transition pore opening as a potential contributing pathomechanism of cardiac alterations in these disorders.

    PubMed

    Cecatto, Cristiane; Hickmann, Fernanda H; Rodrigues, Marília D N; Amaral, Alexandre U; Wajner, Moacir

    2015-12-01

    Mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies are fatty acid oxidation disorders biochemically characterized by tissue accumulation of long-chain fatty acids and derivatives, including the monocarboxylic long-chain 3-hydroxy fatty acids (LCHFAs) 3-hydroxytetradecanoic acid (3HTA) and 3-hydroxypalmitic acid (3HPA). Patients commonly present severe cardiomyopathy for which the pathogenesis is still poorly established. We investigated the effects of 3HTA and 3HPA, the major metabolites accumulating in these disorders, on important parameters of mitochondrial homeostasis in Ca(2+) -loaded heart mitochondria. 3HTA and 3HPA significantly decreased mitochondrial membrane potential, the matrix NAD(P)H pool and Ca(2+) retention capacity, and also induced mitochondrial swelling. These fatty acids also provoked a marked decrease of ATP production reflecting severe energy dysfunction. Furthermore, 3HTA-induced mitochondrial alterations were completely prevented by the classical mitochondrial permeability transition (mPT) inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca(2+) uptake blocker, indicating that LCHFAs induced Ca(2+)-dependent mPT pore opening. Milder effects only achieved at higher doses of LCHFAs were observed in brain mitochondria, implying a higher vulnerability of heart to these fatty acids. By contrast, 3HTA and docosanoic acids did not change mitochondrial homeostasis, indicating selective effects for monocarboxylic LCHFAs. The present data indicate that the major LCHFAs accumulating in mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies induce mPT pore opening, compromising Ca(2+) homeostasis and oxidative phosphorylation more intensely in the heart. It is proposed that these pathomechanisms may contribute at least in part to the severe cardiac alterations characteristic of patients affected by these diseases.

  3. Comparison of gravimetric, creamatocrit and esterified fatty acid methods for determination of total fat content in human milk.

    PubMed

    Du, Jian; Gay, Melvin C L; Lai, Ching Tat; Trengove, Robert D; Hartmann, Peter E; Geddes, Donna T

    2017-02-15

    The gravimetric method is considered the gold standard for measuring the fat content of human milk. However, it is labor intensive and requires large volumes of human milk. Other methods, such as creamatocrit and esterified fatty acid assay (EFA), have also been used widely in fat analysis. However, these methods have not been compared concurrently with the gravimetric method. Comparison of the three methods was conducted with human milk of varying fat content. Correlations between these methods were high (r(2)=0.99). Statistical differences (P<0.001) were observed in the overall fat measurements and within each group (low, medium and high fat milk) using the three methods. Overall, stronger correlation with lower mean (4.73g/L) and percentage differences (5.16%) was observed with the creamatocrit than the EFA method when compared to the gravimetric method. Furthermore, the ease of operation and real-time analysis make the creamatocrit method preferable. PMID:27664665

  4. Comparison of gravimetric, creamatocrit and esterified fatty acid methods for determination of total fat content in human milk.

    PubMed

    Du, Jian; Gay, Melvin C L; Lai, Ching Tat; Trengove, Robert D; Hartmann, Peter E; Geddes, Donna T

    2017-02-15

    The gravimetric method is considered the gold standard for measuring the fat content of human milk. However, it is labor intensive and requires large volumes of human milk. Other methods, such as creamatocrit and esterified fatty acid assay (EFA), have also been used widely in fat analysis. However, these methods have not been compared concurrently with the gravimetric method. Comparison of the three methods was conducted with human milk of varying fat content. Correlations between these methods were high (r(2)=0.99). Statistical differences (P<0.001) were observed in the overall fat measurements and within each group (low, medium and high fat milk) using the three methods. Overall, stronger correlation with lower mean (4.73g/L) and percentage differences (5.16%) was observed with the creamatocrit than the EFA method when compared to the gravimetric method. Furthermore, the ease of operation and real-time analysis make the creamatocrit method preferable.

  5. Iron deficiency anaemia.

    PubMed

    Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent

    2016-02-27

    Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for