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Sample records for cd36 deficiency protects

  1. CD36 deficiency blunts effects of diet on regulatory T cells in murine gonadal adipose tissue and mesenteric lymph nodes.

    Science.gov (United States)

    Geys, Lotte; Vranckx, Christine; Lijnen, Henri Roger; Scroyen, Ilse

    2015-01-01

    The effect of cluster of differentiation (CD)36 on regulatory T cells (Treg) was investigated in gonadal (GN) adipose tissues and mesenteric lymph nodes (MLN) of wild-type (WT) and CD36 deficient (CD36(-/-)) mice kept on standard fat (SFD, lean) or on high fat diet (HFD, obese). GN adipose tissue mass was smaller, but MLN size larger for obese CD36(-/-) versus obese WT mice. Overall, the reduction of Treg cells in GN adipose tissue and MLN after a HFD is much more prominent in WT than CD36(-/-) mice. Moreover, CD36(-/-) mice may be protected against obesity-related chronic inflammation. PMID:26344897

  2. CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance

    NARCIS (Netherlands)

    Goudriaan, [No Value; den Boer, MAM; Rensen, PCN; Febbraio, M; Kuipers, F; Romijn, JA; Havekes, LM; Voshol, PJ

    2005-01-01

    CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36(-/-)) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36(-/-) mice. cd36(-/-) mice showed no differences in hep

  3. CD36 deficiency protects against malarial anaemia in children by reducing Plasmodium falciparum-infected red blood cell adherence to vascular endothelium

    NARCIS (Netherlands)

    Chilongola, J.; Balthazary, S.T.; Mpina, M.; Mhando, M.; Mbugi, E.V.

    2009-01-01

    Objective CD36 is a receptor that occurs on the surface of activated immune cells, vascular endothelial cells and participates in phagocytosis and lipid metabolism. CD36 is known to be the major endothelial receptor molecule for field isolates of Plasmodium falciparum. A T1264G mutation in exon X of

  4. Cluster Differentiating 36 (CD36 Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

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    Mohamed Gharib

    Full Text Available Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36 protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear.The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity.Studies were conducted in control (Lean, obese leptin-deficient (Lepob/ob and leptin-CD36 double null (Lepob/obCD36-/- mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity.CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

  5. CD36 is important for adipocyte recruitment and affects lipolysis

    NARCIS (Netherlands)

    Vroegrijk, I.O.; Klinken, J.B. van; Diepen, J.A. van; Berg, S.A. van den; Febbraio, M.; Steinbusch, L.K.; Glatz, J.F.C.; Havekes, L.M.; Voshol, P.J.; Rensen, P.C.; Dijk, K.W. van; Harmelen, V. van

    2013-01-01

    OBJECTIVE: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. DESIGN A

  6. CD36 is important for adipocyte recruitment and affects lipolysis

    NARCIS (Netherlands)

    Vroegrijk, I.O.; Klinken, J.B. van; Diepen, J.A. van; Berg, S.A. van den; Febbraio, M.; Steinbusch, L.K.; Glatz, J.F.; Havekes, L.M.; Voshol, P.J.; Rensen, P.C.; Dijk, K.W. van; Harmelen, V. van

    2013-01-01

    Objective: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design a

  7. CD36 is important for adipocyte recruitment and affects lipolysis

    OpenAIRE

    Vroegrijk, I.O.; Klinken, J.B. van; Diepen, J.A. van; Berg, S.A. van den; Febbraio, M.; Steinbusch, L.K.; Glatz, J.F.; Havekes, L M; Voshol, P.J.; Rensen, P. C.; Dijk, K.W. van; Harmelen, V. van

    2013-01-01

    Objective: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and methods: Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36(-/-) and WT mice after 6 weeks on HFD. Basal lipolysis and insulin-inhibited lipol...

  8. Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions.

    Science.gov (United States)

    Krupková, Michaela; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Kren, Vladimír; Seda, Ondrej

    2010-04-16

    Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

  9. Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36

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    Roger S. Holmes

    2012-09-01

    Full Text Available Platelet glycoprotein 4 (CD36 (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3] is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA contributing to a high gene expression level (6.6 times average. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate

  10. Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

    OpenAIRE

    Rac, Monika; Kurzawski, Grzegorz; Safranow, Krzysztof; Rac, Michal; Sagasz-Tysiewicz, Dagmara; Krzystolik, Andrzej; Poncyljusz, Wojciech; Olszewska, Maria; Dawid, Grażyna; Chlubek, Dariusz

    2012-01-01

    Introduction CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy. Material and methods The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic...

  11. Soluble CD36- a marker of the (pathophysiological) role of CD36 in the metabolic syndrome?

    DEFF Research Database (Denmark)

    Koonen, Debby P Y; Jensen, Majken K; Handberg, Aase

    2011-01-01

    CD36 is a class B scavenger receptor observed in many cell types and tissues throughout the body. Recent literature has implicated CD36 in the pathogenesis of metabolic dysregulation such as found in obesity, insulin resistance, and atherosclerosis. Genetic variation at the CD36 loci have been as...... steatosis may contribute to elevated levels of sCD36....

  12. Leishmania amazonensis Engages CD36 to Drive Parasitophorous Vacuole Maturation.

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    Kendi Okuda

    2016-06-01

    Full Text Available Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi-expressing flies for anti-Leishmania defense factors. Notably, we found three CD36-like scavenger receptors that were important for defending against Leishmania infection. Mechanistic studies in mouse macrophages showed that CD36 accumulates specifically at sites where the parasite contacts the parasitophorous vacuole membrane. Furthermore, CD36-deficient macrophages were defective in the formation of the large parasitophorous vacuole typical of L. amazonensis infection, a phenotype caused by inefficient fusion with late endosomes and/or lysosomes. These data identify an unprecedented role for CD36 in the biogenesis of the parasitophorous vacuole and further highlight the utility of Drosophila as a model system for dissecting innate immune responses to infection.

  13. Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity

    OpenAIRE

    Lei Cai; Zhen Wang; Ailing Ji; Meyer, Jason M.; Deneys R. van der Westhuyzen

    2012-01-01

    OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) fo...

  14. Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.

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    Pin Yue

    Full Text Available CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/- mice. Feeding CD36(-/- mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/- mice and cholesterol uptake from HDL or LDL by isolated CD36(-/- hepatocytes was unaltered. However, CD36(-/- hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/- macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/- cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.

  15. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity.

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    Lei Cai

    Full Text Available OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO mice and wild type (WT mice fed a high fat diet (60% kcal fat for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice. RESULTS: Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS. Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects. CONCLUSIONS: CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.

  16. CD36 is indispensable for thermogenesis under conditions of fasting and cold stress

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    Putri, Mirasari [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Syamsunarno, Mas Rizky A.A. [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Biochemistry, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Jatinangor, West Java 45363 (Indonesia); Iso, Tatsuya, E-mail: isot@gunma-u.ac.jp [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamaguchi, Aiko; Hanaoka, Hirofumi [Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Sunaga, Hiroaki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Koitabashi, Norimichi [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Matsui, Hiroki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamazaki, Chiho; Kameo, Satomi [Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Tsushima, Yoshito [Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); and others

    2015-02-20

    Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36{sup −/−} mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36{sup −/−} mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue {sup 125}I-BMIPP and the glucose analogue {sup 18}F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36{sup −/−} mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36{sup −/−} mice after cold exposure. These findings strongly suggest that CD36{sup −/−} mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation. - Highlights: • We examined the role of CD36 in thermogenesis during cold exposure. • CD36{sup −/−} mice exhibit rapid hypothermia after cold exposure during fasting. • Uptake of fatty acid and glucose is impaired in thermogenic tissues during fasting. • Storage of energy substrates is

  17. Molecular Basis of Human CD36 Gene Mutations

    OpenAIRE

    Rać, Monika Ewa; Safranow, Krzysztof; Poncyljusz, Wojciech

    2007-01-01

    CD36 is a transmembrane glycoprotein of the class B scavenger receptor family. The CD36 gene is located on chromosome 7 q11.2 and is encoded by 15 exons. Defective CD36 is a likely candidate gene for impaired fatty acid metabolism, glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer disease, and modification of the clinical course of malaria. Contradictory data concerning the effects of antiatherosclerotic drugs on CD36 expression indicate that fur...

  18. Activation of Peroxisome Proliferator-activated Receptor γ (PPARγ) and CD36 Protein Expression: THE DUAL PATHOPHYSIOLOGICAL ROLES OF PROGESTERONE.

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    Yang, Xiaoxiao; Zhang, Wenwen; Chen, Yuanli; Li, Yan; Sun, Lei; Liu, Ying; Liu, Mengyang; Yu, Miao; Li, Xiaoju; Han, Jihong; Duan, Yajun

    2016-07-15

    Progesterone or its analog, one of components of hormone replacement therapy, may attenuate the cardioprotective effects of estrogen. However, the underlying mechanisms have not been fully elucidated. Expression of CD36, a receptor for oxidized LDL (oxLDL) that enhances macrophage/foam cell formation, is activated by the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). CD36 also functions as a fatty acid transporter to influence fatty acid metabolism and the pathophysiological status of several diseases. In this study, we determined that progesterone induced macrophage CD36 expression, which is related to progesterone receptor (PR) activity. Progesterone enhanced cellular oxLDL uptake in a CD36-dependent manner. Mechanistically, progesterone increased PPARγ expression and PPARγ promoter activity in a PR-dependent manner and the binding of PR with the progesterone response element in the PPARγ promoter. Specific deletion of macrophage PPARγ (MφPPARγ KO) expression in mice abolished progesterone-induced macrophage CD36 expression and cellular oxLDL accumulation. We also determined that, associated with gestation and increased serum progesterone levels, CD36 and PPARγ expression in mouse adipose tissue, skeletal muscle, and peritoneal macrophages were substantially activated. Taken together, our study demonstrates that progesterone can play dual pathophysiological roles by activating PPARγ expression, in which progesterone increases macrophage CD36 expression and oxLDL accumulation, a negative effect on atherosclerosis, and enhances the PPARγ-CD36 pathway in adipose tissue and skeletal muscle, a protective effect on pregnancy. PMID:27226602

  19. CD36 is required for myoblast fusion during myogenic differentiation

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    Park, Seung-Yoon [Department of Biochemistry, College of Medicine, Dongguk University and Medical Institute of Dongguk University, Gyeongju 780-714 (Korea, Republic of); Yun, Youngeun [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, In-San, E-mail: iskim@knu.ac.kr [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Biomedical Research Institute, Korea Institute Science and Technology, Seoul (Korea, Republic of)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer CD36 expression was induced during myogenic differentiation. Black-Right-Pointing-Pointer CD36 expression was localized in multinucleated myotubes. Black-Right-Pointing-Pointer The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. Black-Right-Pointing-Pointer Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

  20. Molecular basis of human CD36 gene mutations.

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    Rać, Monika Ewa; Safranow, Krzysztof; Poncyljusz, Wojciech

    2007-01-01

    CD36 is a transmembrane glycoprotein of the class B scavenger receptor family. The CD36 gene is located on chromosome 7 q11.2 and is encoded by 15 exons. Defective CD36 is a likely candidate gene for impaired fatty acid metabolism, glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer disease, and modification of the clinical course of malaria. Contradictory data concerning the effects of antiatherosclerotic drugs on CD36 expression indicate that further investigation of the role of CD36 in the development of atherosclerosis may be important for the prevention and treatment of this disease. This review summarizes current knowledge of CD36 gene structure, splicing, and mutations and the molecular, metabolic, and clinical consequences of these phenomena. PMID:17673938

  1. Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36)

    OpenAIRE

    Holmes, Roger S.

    2012-01-01

    Platelet glycoprotein 4 (CD36) (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3]) is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs) and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, mal...

  2. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

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    Tang Bing

    2011-04-01

    Full Text Available Abstract Background Elevated plasma free fatty acid (FFA levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36 is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs treated with oleic acid (OA. We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L became foam cells based on morphological (Oil Red O staining and biochemical (5 times increase in cellular triglyceride criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC, OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p 5 μm2 vs. OA plus acipimox: 2.60 ± 0.10 ×105 μm2, p p Conclusions These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.

  3. CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

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    Ifeanyi U Anidi

    Full Text Available Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS. To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our

  4. Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen: A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)γ-DEPENDENT MECHANISM.

    Science.gov (United States)

    Yu, Miao; Jiang, Meixiu; Chen, Yuanli; Zhang, Shuang; Zhang, Wenwen; Yang, Xiaoxiao; Li, Xiaoju; Li, Yan; Duan, Shengzhong; Han, Jihong; Duan, Yajun

    2016-08-12

    Macrophage CD36 binds and internalizes oxidized low density lipoprotein (oxLDL) to facilitate foam cell formation. CD36 expression is activated by peroxisome proliferator-activated receptor γ (PPARγ). Tamoxifen, an anti-breast cancer medicine, has demonstrated pleiotropic functions including cardioprotection with unfully elucidated mechanisms. In this study, we determined that treatment of ApoE-deficient mice with tamoxifen reduced atherosclerosis, which was associated with decreased CD36 and PPARγ expression in lesion areas. At the cellular level, we observed that tamoxifen inhibited CD36 protein expression in human THP-1 monocytes, THP-1/PMA macrophages, and human blood monocyte-derived macrophages. Associated with decreased CD36 protein expression, tamoxifen reduced cellular oxLDL accumulation in a CD36-dependent manner. At the transcriptional level, tamoxifen decreased CD36 mRNA expression, promoter activity, and the binding of the PPARγ response element in CD36 promoter to PPARγ protein. Tamoxifen blocked ligand-induced PPARγ nuclear translocation and CD36 expression, but it increased PPARγ phosphorylation, which was due to that tamoxifen-activated ERK1/2. Furthermore, deficiency of PPARγ expression in macrophages abolished the inhibitory effect of tamoxifen on CD36 expression or cellular oxLDL accumulation both in vitro and in vivo Taken together, our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen. PMID:27358406

  5. Alternative promoter usage of the membrane glycoprotein CD36

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    Whatling Carl

    2006-03-01

    Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  6. Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

    Directory of Open Access Journals (Sweden)

    Courtney M. Anderson

    2015-02-01

    Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

  7. A novel ELISA for measuring CD36 protein in human adipose tissue

    OpenAIRE

    Allred, Carolyn C.; Krennmayr, Thomas; Koutsari, Christina; Zhou, Lianzhen; Ali, Asem H.; Jensen, Michael D.

    2011-01-01

    CD36 is a transmembrane protein present in many tissues that is believed to facilitate inward fatty acid transport. Western blotting is the most widely used method to measure tissue CD36 protein content, but it is time consuming, technically demanding, and semiquantitative. To more precisely measure adipose tissue CD36 content we developed an enzyme linked immunosorbent assay (ELISA) after establishing that: 1) the anti-CD36 antibodies gave a single distinct band on traditional Western blots,...

  8. 血小板CD36新等位基因1142T>G序列分析及确认%Analysis and identification of a novel CD36 allele, 1142 T>G

    Institute of Scientific and Technical Information of China (English)

    林凤秋; 李晓丰; 邵超鹏; 李剑平

    2015-01-01

    BACKGROUND:As a main antigen of platelet, CD36 antigen is also known as platelet glycoprotein IV (GPIV). The mutation of CD36 gene may result in deficiency of the antigen. OBJECTIVE:To identify a novel CD36 alele. METHODS: DNA was isolated from peripheral blood sample, and 12 coding regions of CD36 gene were amplified by PCR. Sequencing-based typing was used to analyze the sequence of the target regions. The derived sequences were aligned with the standard sequence of NG_008192 in GenBank to identify the novel alele. RESULTS AND CONCLUSION: 1142 T>G mutation was detected in exon 12 of CD36 gene of the proband, and the other regions were consistent with the standard sequence. No data or report about 1142 T>G was found in GenBank or National Center for Biotechnology Information (NCBI), and thus it was reported to GenBank and received by number KM275213. 1142 T>G results in amino acid 381 Leu>Ser of the CD36 protein. There is a big difference in hydrophilia and polarity of the two amino acids. Also the 381 amino acid locates in highly conserved region. Thus it is speculated that 1142 T>G may reduce or vanish the activity of the protein.%背景:作为血小板上的主要抗原之一,CD36抗原又被称为血小板糖蛋白Ⅳ,其基因变异会导致 CD36抗原缺失。  目的:序列分析并确认1例CD36抗原新等位基因。  方法:提取外周血样本DNA,应用聚合酶链式反应扩增CD36基因的12个编码区序列片段,应用直接测序法对目的片段的序列进行检测。所得序列与基因库中编号为 NG_008192的标准序列进行比对分析,以确定新的基因突变。  结果与结论:被检样本在第12外显子的1142位发生T>G的碱基突变,其他外显子序列与标准序列一致。检索国际基因数据库GenBank和美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI),均未发现关于1142 T>G突变的数据和报道,因此为国际上首次确认

  9. The structural basis for CD36 binding by the malaria parasite

    DEFF Research Database (Denmark)

    Hsieh, Fu-Lien; Turner, Louise; Bolla, Jani Reddy;

    2016-01-01

    allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1...

  10. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Albers, Peter Hjorth; Rose, Adam John;

    2011-01-01

    FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions associated with...

  11. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma

    DEFF Research Database (Denmark)

    Handberg, Aase; Levin, Klaus; Højlund, Kurt;

    2006-01-01

    BACKGROUND: Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature...... was demonstrated by immunopurification and Western blotting. We established ELISA assays to determine sCD36 in plasma and measured sCD36 in obese type 2 diabetic patients, obese nondiabetic relatives, and obese and lean control subjects. sCD36 was markedly elevated in type 2 diabetic patients compared with both...

  12. CD36 mediates proximal tubular binding and uptake of albumin and is upregulated in proteinuric nephropathies.

    Science.gov (United States)

    Baines, Richard J; Chana, Ravinder S; Hall, Matthew; Febbraio, Maria; Kennedy, David; Brunskill, Nigel J

    2012-10-01

    Dysregulation of renal tubular protein handling in proteinuria contributes to the development of chronic kidney disease. We investigated the role of CD36 as a novel candidate mediator of albumin binding and endocytosis in the kidney proximal tubule using both in vitro and in vivo approaches, and in nephrotic patient renal biopsy samples. In CD36-transfected opossum kidney proximal tubular cells, both binding and uptake of albumin were substantially enhanced. A specific CD36 inhibitor abrogated this effect, but receptor-associated protein, which blocks megalin-mediated endocytosis of albumin, did not. Mouse proximal tubular cells expressed CD36 and this was absent in CD36 null animals, whereas expression of megalin was equal in these animals. Compared with wild-type mice, CD36 null mice demonstrated a significantly increased urinary protein-to-creatinine ratio and albumin-to-creatinine ratio. Proximal tubular cells expressed increased CD36 when exposed to elevated albumin concentrations in culture medium. Expression of CD36 was studied in renal biopsy tissue obtained from adult patients with heavy proteinuria due to minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. Proximal tubular CD36 expression was markedly increased in proteinuric individuals. We conclude that CD36 is a novel mediator influencing binding and uptake of albumin in the proximal tubule that is upregulated in proteinuric renal diseases. CD36 may represent a potential therapeutic target in proteinuric nephropathy. PMID:22791331

  13. A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection.

    Directory of Open Access Journals (Sweden)

    Dongqing Li

    Full Text Available Staphylococcus epidermidis (S.epidermidis plays important protective roles by directly producing or by stimulating hosts to produce antimicrobial peptides (AMPs against pathogenic infections. Although several AMPs from S.epidermidis have been identified, molecules that stimulate hosts to produce AMPs remain largly unknown. Here we demonstrate that a new lipopeptide (named LP01 purified from S.epidermidis culture media has a unique structure with heneicosanoic acid (21 carbons binding to lysine(11 of a peptide chain. In vitro LP01 increased the expression of β-defensin 2(hBD2 and hBD3 in neonatal human epidermal keratinocytes(NHEK, leading to increased capacity of cell lysates to inhibit the growth of S.aureus. In vivo LP01 induced the expression of mouse β-defensin 4(mBD4 to decrease the survival of local S.aureus in skin and systemic S.aureus survival in liver. The induction of beta-defensins by LP01 was dependent on TLR2 as Tlr2-deficient mice had decreased mBD4. Furthermore, knockdown of CD36 decreased the expression of hBD2 and hBD3, and p38 MAPK inhibitor significantly inhibited the expression of hBDs induced by LP01.Taken together, these findings demonstrate that lipopeptide LP01 from normal commensal S.epidermidis increases antimicrobial peptide hBD2 and hBD3 expression via the activation of TLR2/CD36-p38 MAPK, thus enhancing antimicrobial defense against pathogenic infections.

  14. Opposite Regulation of CD36 Ubiquitination by Fatty Acids and Insulin: EFFECTS ON FATTY ACID UPTAKE*

    OpenAIRE

    Smith, Jill; Su, Xiong; El-Maghrabi, Raafat; Stahl, Philip D.; Abumrad, Nada A.

    2008-01-01

    FAT/CD36 is a membrane scavenger receptor that facilitates long chain fatty acid uptake by muscle. Acute increases in membrane CD36 and fatty acid uptake have been reported in response to insulin and contraction. In this study we have explored protein ubiquitination as one potential mechanism for the regulation of CD36 level. CD36 expressed in Chinese hamster ovary (CHO) or HEK 293 cells was found to be polyubiquitinated via a process involving both lysines 48 and 63 of ubiquitin. Using CHO c...

  15. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

    Science.gov (United States)

    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  16. Rapamycin-mediated CD36 translational suppression contributes to alleviation of hepatic steatosis.

    Science.gov (United States)

    Wang, Chuan; Yan, Yong; Hu, Lin; Zhao, Lei; Yang, Ping; Moorhead, John F; Varghese, Zac; Chen, Yaxi; Ruan, Xiong Z

    2014-04-25

    Rapamycin, a mammalian target of rapamycin (mTOR)-specific inhibitor, has the effect of anti-lipid deposition on non-alcoholic fatty liver disease (NAFLD), but the mechanisms with which rapamycin alleviates hepatic steatosis are not fully disclosed. CD36 is known to facilitate long-chain fatty acid uptake and contribute to NAFLD progression. Hepatic CD36 expression is closely associated with hepatic steatosis, while mTOR pathway is involved in CD36 translational control. This study was undertaken to investigate whether rapamycin alleviates hepatic steatosis via the inhibition of mTOR pathway-dependent CD36 translation. Human hepatoblastoma HepG2 cells were treated with palmitate and C57BL/6J mice were fed with high fat diet (HFD) to induce hepatic steatosis. Hepatic CD36 protein expression was significantly increased with lipid accumulation in palmitate-treated HepG2 cells or HFD-fed C57BL/6J mice. Rapamycin reduced hepatic steatosis and CD36 protein expression, but it had no influence on CD36 mRNA expression. Rapamycin had no effect on CD36 protein stability, but it significantly decreased CD36 translational efficiency. We further confirmed that rapamycin inhibited the phosphorylation of mTOR and its downstream translational regulators including p70 ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic initiation factor 4E (eIF4E). This study demonstrates that rapamycin inhibits hepatic CD36 translational efficiency through the mTOR pathway, resulting in reduction of CD36 protein expression and alleviation of hepatic steatosis. PMID:24685479

  17. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN...... not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect ß-cells......Fatty acid-induced damage in pancreatic ß-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve ß-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of...

  18. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN...... not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells......Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of...

  19. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity

    Science.gov (United States)

    Castro-Albarran, Jorge; Sandoval-García, Flavio; Flores-Alvarado, Luis-Javier

    2016-01-01

    Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity. PMID:27525284

  20. CD36, but not GPR120, is required for efficient fatty acid utilization during endurance exercise.

    Science.gov (United States)

    Fujitani, Mina; Matsumura, Shigenobu; Masuda, Daisaku; Yamashita, Shizuya; Fushiki, Tohru; Inoue, Kazuo

    2014-01-01

    Fatty acids (FA) are an important energy source during exercise. In addition to its role as an energy supply for skeletal muscle, FA may activate signaling pathways that regulate gene expression. FA translocase/cluster of differentiation 36 (CD36) and G protein-coupled receptor GPR120 are long-chain FA receptors. In this study, we investigated the impact of CD36 or GPR120 deletion on energy metabolism during exercise. CD36 has been reported to facilitate cellular transport and oxidation of FA during endurance exercise. We show that CD36 deletion decreased exogenous FA oxidation during exercise, using a combination of (13)C-labeled FA oxidation measurement and indirect calorimetry. In contrast, GPR120 deletion had no observable effect on energy metabolism during exercise. Our results further substantiate that CD36-mediated FA transport plays an essential role in efficient FA oxidation during exercise. PMID:25070011

  1. Association of CD36 expression and polymorphism with serum biochemical indices in Cherry Valley duck.

    Science.gov (United States)

    Wang, D D; Li, W G; Zhang, Y Y

    2016-01-01

    Cluster of differentiation 36 (CD36) plays a crucial role in lipid sensing, innate immunity, atherogenesis, and glycolipid metabolism. This aims of this study were to delineate the CD36 mRNA expression profile in 16 duck tissues using relative quantitative real-time PCR and to screen single nucleotide polymorphisms (SNPs) in the duck CD36 gene by PCR-single strand conformation polymorphism and DNA direct sequencing. In addition, this study investigated CD36 gene expression, genetic variation, and their effect on serum biochemical indices in duck. The results showed that CD36 mRNA was expressed in all tissues, and was highly specific to the pituitary and large intestine, and to subcutaneous and abdominal fat. Furthermore, three genotypes of the SNP g.476593 T > C in exon 9 of the duck CD36 gene were identified: MM, MN, and NN. The dominant genotype and allele were MM and M, with frequencies of 0.453 and 0.643, respectively. The genotype distributions deviated from Hardy-Weinberg equilibrium (P NN genotype were significantly higher than those in birds with the MM genotype. These findings demonstrated that CD36 might be an important genetic marker for the selection of lipid metabolism and meat quality traits in ducks. PMID:27323079

  2. The structural basis for CD36 binding by the malaria parasite

    DEFF Research Database (Denmark)

    Hsieh, Fu-Lien; Turner, Louise; Bolla, Jani Reddy;

    2016-01-01

    CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum......, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket...

  3. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    OpenAIRE

    Jeppesen, J; Albers, P. H.; Rose, A. J.; Birk, J. B.; Schjerling, P; Dzamko, N.; Steinberg, G. R.; Kiens, B

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat ...

  4. Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet.

    OpenAIRE

    Greenwalt, D E; Scheck, S H; Rhinehart-Jones, T

    1995-01-01

    High levels of CD36 expression are found in triglyceride storing and secreting cells such as differentiated adipocytes and mammary secretory epithelial cells and in some capillary endothelial cells. We have found high levels of CD36 in the capillary endothelium of murine adipose tissue and in cardiac and skeletal muscles. Muscle cells themselves were CD36 negative. No CD36 was found in brain endothelium. Cardiac and skeletal muscle tissues are highly oxidative and catabolize long-chain fatty ...

  5. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

    OpenAIRE

    Tang Bing; Li; Yang Dachun; Ma Shuangtao; Yang Yongjian

    2011-01-01

    Abstract Background Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accum...

  6. Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension.

    Science.gov (United States)

    Pravenec, M; Zidek, V; Simakova, M; Kren, V; Krenova, D; Horky, K; Jachymova, M; Mikova, B; Kazdova, L; Aitman, T J; Churchill, P C; Webb, R C; Hingarh, N H; Yang, Y; Wang, J M; Lezin, E M; Kurtz, T W

    1999-06-01

    Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.

  7. The role of CD36 in the regulation of myocardial lipid metabolism.

    Science.gov (United States)

    Kim, Ty T; Dyck, Jason R B

    2016-10-01

    Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50-70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26995462

  8. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

    Science.gov (United States)

    Buttet, Marjorie; Poirier, Hélène; Traynard, Véronique; Gaire, Kévin; Tran, Thi Thu Trang; Sundaresan, Sinju; Besnard, Philippe; Abumrad, Nada A; Niot, Isabelle

    2016-01-01

    The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP) and blood clearance (ApoC2). These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG), while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the reported

  9. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

    Directory of Open Access Journals (Sweden)

    Marjorie Buttet

    Full Text Available The metabolic syndrome (MetS greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD. By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP and blood clearance (ApoC2. These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG, while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the

  10. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model

    Science.gov (United States)

    Buttet, Marjorie; Poirier, Hélène; Traynard, Véronique; Gaire, Kévin; Tran, Thi Thu Trang; Sundaresan, Sinju; Besnard, Philippe; Abumrad, Nada A.; Niot, Isabelle

    2016-01-01

    The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP) and blood clearance (ApoC2). These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG), while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the reported

  11. Circulating CD36 is reduced in HNF1A-MODY carriers.

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    Siobhan Bacon

    Full Text Available INTRODUCTION: Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36 are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus. METHODS: We recruited 37 participants with HNF1A-MODY diabetes and compared levels of sCD36 with BMI-matched participants with type 2 diabetes mellitus and normoglycaemic HNF1A-MODY negative family controls. Levels of sCD36 were correlated with phenotypic and biochemical parameters. RESULTS: HNF1A-MODY participants were lean, normotensive, with higher HDL and lower triglyceride levels when compared to controls and participants with type 2 diabetes mellitus. sCD36 was also significantly lower in HNF1A-MODY participants when compared to both the normoglycaemic family controls and to lean participants with type 2 diabetes mellitus. CONCLUSION: In conclusion, sCD36 is significantly lower in lean participants with HNF1A-MODY diabetes when compared to weight-matched normoglycaemic familial HNF1A-MODY negative controls and to lean participants with type 2 diabetes mellitus. Lower levels of this pro-atherogenic marker may

  12. Circulating CD36 Is Reduced in HNF1A-MODY Carriers.

    LENUS (Irish Health Repository)

    Bacon, Siobhan

    2013-01-01

    Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY) accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A) accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36) are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus.

  13. Mechanism linking atherosclerosis and type 2 diabetes: increased expression of scavenger receptor CD36 in monocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-mei; ZHANG Xiao-lian; ZHOU Xin; LI Dong; GU Jin-gang; WU Juan-juan

    2005-01-01

    Background We investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.Methods According to the criteria by WHO, diabetic patients were classified into two groups: well controlled diabetic patients (WCP) and poorly controlled diabetic patients (PCP). The expression of CD36 protein and mRNA were evaluated by flow cytometry and reversal transcription polymerase chain reaction (RT-PCR). Plasma levels of accumulution of oxidized LDL (oxLDL) were directly measured by sandwich enzyme-linked immunosorbent assay (ELISA) method.Results Flow cytometry and RT-PCR showed that the mean fluorescence intensity (MFI) of CD36 in monocyte and CD36 mRNA were significantly higher in the PCP and WCP in comparison with healthy controls (P0.05). The concentrations of plasma oxLDL were higher in the PCP group compared to WCP and control group (P0.05). In the WCP and PCP groups, oxLDL levels were higher in patients with diabetic atherosclerosis than those without diabetic atherosclerosis (P<0.05).Conclusions The increased expression of scavenger receptor CD36 may be one of the mechanism of accelerated atherosclerosis in diabetic. The poorly controlled diabetes patients are at higher risk for the vascular complications than the well controlled diabetic patients.

  14. Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population

    DEFF Research Database (Denmark)

    Handberg, A; Højlund, K; Gastaldelli, A;

    2012-01-01

    Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid...

  15. Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats.

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    Valentine S Moullé

    Full Text Available Variations in plasma fatty acid (FA concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36. The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, IL(H, respectively or saline/heparin (SH were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1 Rats previously injected in ventromedian nucleus (VMN with shRNA against CD36 or scrambled RNA; 2 Etomoxir (CPT1 inhibitor or saline co-infused with IL(H/S(H; and 3 Triacsin C (acylCoA synthase inhibitor or saline co-infused with IL(H/S(H. IL(H significantly lowered food intake during refeeding compared to S(H (p<0.001. Five hours after refeeding, etomoxir did not affect this inhibitory effect of IL(H on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented IL(H effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation.

  16. Formulation, characteristics and antiatherogenic bioactivities of CD36-targeted epigallocatechin gallate (EGCG)-loaded nanoparticles.

    Science.gov (United States)

    Zhang, Jia; Nie, Shufang; Martinez-Zaguilan, Raul; Sennoune, Souad R; Wang, Shu

    2016-04-01

    Intimal macrophages are determinant cells for atherosclerotic lesion formation by releasing inflammatory factors and taking up oxidized low-density lipoprotein (oxLDL) via scavenger receptors, primarily the CD36 receptor. (-)-Epigallocatechin-3-gallate (EGCG) has a potential to decrease cholesterol accumulation and inflammatory responses in macrophages. We made EGCG-loaded nanoparticles (Enano) using phosphatidylcholine, kolliphor HS15, alpha-tocopherol acetate and EGCG. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a CD36-targeted ligand found on oxLDL, was incorporated on the surface of Enano to make ligand-Enano (L-Enano). The objectives of this study are to deliver EGCG to macrophages via CD36-targeted L-Enano and to determine its antiatherogenic bioactivities. The optimized nanoparticles obtained in our study were spherical and around 108 nm in diameter, and had about 10% of EGCG loading capacity and 96% of EGCG encapsulation efficiency. Compared to Enano, CD36-targeted L-Enano had significantly higher binding affinity to and uptake by macrophages at the same pattern as oxLDL. CD36-targeted L-Enano dramatically improved EGCG stability, increased macrophage EGCG content, delivered EGCG to macrophage cytosol and avoided lysosomes. L-Enano significantly decreased macrophage mRNA levels and protein secretion of monocyte chemoattractant protein 1, but did not significantly change macrophage cholesterol content. The innovative CD36-targeted nanoparticles may facilitate targeted delivery of diagnostic, preventive and therapeutic compounds to intimal macrophages for the diagnosis, prevention and treatment of atherosclerosis with enhanced efficacy and decreased side effects. PMID:27012617

  17. Platelet CD36 mediates interactions with endothelial cell–derived microparticles and contributes to thrombosis in mice

    Science.gov (United States)

    Ghosh, Arunima; Li, Wei; Febbraio, Maria; Espinola, Ricardo G.; McCrae, Keith R.; Cockrell, Erin; Silverstein, Roy L.

    2008-01-01

    CD36 is a scavenger receptor that binds multiple ligands, including phosphatidyl serine (PS). Although CD36– mice do not have a bleeding diathesis, we show here that they do have significantly prolonged thrombotic occlusion times in response to FeCl3-induced vascular injury. Because cell-derived microparticles (MPs) are generated in response to vascular injury and circulate in patients with prothrombotic diseases, we hypothesized that PS exposed on their surfaces could be an endogenous CD36 ligand that transmits an activating signal to platelets. We found that MPs prepared from human ECs, monocytes, or platelets or isolated from blood of normal subjects bound to platelets. Binding was not observed with platelets from CD36– donors and was inhibited by an anti-CD36 antibody or by blockade of exposed PS by annexin V or anti-PS IgM. Preincubation of platelets with MPs led to CD36-dependent augmentation of platelet activation in response to low doses of ADP, as assessed by measuring α2bβ3 activation, P-selectin expression, and aggregation. Immunofluorescence confocal microscopy of murine carotid thrombi from CD36– mice showed a significant decrement in endothelial antigen accumulation, which suggests that CD36 plays a role in MP recruitment into thrombi. These results provide what we believe to be a novel role for CD36 in thrombosis. PMID:18431509

  18. Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers.

    Science.gov (United States)

    Daoudi, Hadjer; Plesník, Jiří; Sayed, Amira; Šerý, Omar; Rouabah, Abdelkader; Rouabah, Leila; Khan, Naim Akhtar

    2015-11-04

    Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

  19. Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers

    Directory of Open Access Journals (Sweden)

    Hadjer Daoudi

    2015-11-01

    Full Text Available Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36, plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165. The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29 exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001. We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

  20. CD36 Is Essential for Regulation of the Host Innate Response to Staphylococcus aureus α-Toxin-Mediated Dermonecrosis.

    Science.gov (United States)

    Castleman, Moriah J; Febbraio, Maria; Hall, Pamela R

    2015-09-01

    Staphylococcus aureus is the primary cause of skin and skin structure infections (SSSIs) in the United States. α-Hemolysin (Hla), a pore-forming toxin secreted by S. aureus and a major contributor to tissue necrosis, prompts recruitment of neutrophils critical for host defense against S. aureus infections. However, the failure to clear apoptotic neutrophils can result in damage to host tissues, suggesting that mechanisms of neutrophil clearance are essential to limiting Hla-mediated dermonecrosis. We hypothesized that CD36, a scavenger receptor which facilitates recognition of apoptosing cells, would play a significant role in regulating Hla-mediated inflammation and tissue injury during S. aureus SSSI. In this study, we show that CD36 on macrophages negatively regulates dermonecrosis caused by Hla-producing S. aureus. This regulation is independent of bacterial burden, as CD36 also limits dermonecrosis caused by intoxication with sterile bacterial supernatant or purified Hla. Dermonecrotic lesions of supernatant intoxicated CD36(-/-) mice are significantly larger, with increased neutrophil accumulation and IL-1β expression, compared with CD36(+/+) (wild-type) mice. Neutrophil depletion of CD36(-/-) mice prevents this phenotype, demonstrating the contribution of neutrophils to tissue injury in this model. Furthermore, administration of CD36(+/+) but not CD36(-/-) macrophages near the site of intoxication reduces dermonecrosis, IL-1β production and neutrophil accumulation to levels seen in wild-type mice. This therapeutic effect is reversed by inhibiting actin polymerization in the CD36(+/+) macrophages, supporting a mechanism of action whereby CD36-dependent macrophage phagocytosis of apoptotic neutrophils regulates Hla-mediated dermonecrosis. Taken together, these data demonstrate that CD36 is essential for controlling the host innate response to S. aureus skin infection.

  1. CD36 expression and lipid metabolism following an oralglucose challenge in South Asians

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To investigate lipid metabolism and the relationshipwith monocyte expression of the fatty acid translocaseCD36 in South Asians.METHODS: An observational study of South Asianswhom as an ethnic group have - a higher risk ofdeveloping diabetes. The susceptibility to diabetes iscoupled with an earlier and more rapid progressionof micro-, and macro-vascular complications. Twentyninehealthy South Asian participants [mean age 34.6(8.9) years, 76.2% male, mean body-mass index 25.0(5.2) kg/m2] were recruited from an urban residentialarea of central Birmingham (United Kingdom). Themain outcomes measured were post prandial (30 min)and post absorptive (120 min) changes from fasting (0min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 goral glucose challenge. The inducements of variations ofmonocyte CD36 expression were analysed.RESULTS: Our results showed evident changes inmonocyte CD36 expression following the glucosechallenge (P 〈 0.001). Non-esterified fatty acids (NEFA)levels decreased progressively during the challenge(P 〈 0.001), in contrast to increased cholesterol(but not triglyceride) concentrations within very lowdensity lipoprotein (VLDL) and low density lipoproteinsubfractions (P 〈 0.01). Levels of, glucose, serumtriglycerides and high density lipoprotein cholesterolremained largely unchanged. Variations of monocyteCD36 were negatively (r = -0.47, P = 0.04) associatedto fat from the diet and positively to carbohydrate fromthe diet (r = 0.65, P 〈 0.001).CONCLUSION: These data suggest that the initiationof VLDL genesis follows the consumption of glucosewithin this population, inferring that the sequestrationof NEFA from these particles happens due to theincreased availability of CD36 receptors. While theseare preliminary results, it would appear that lifestyleexposures have a role in moderating the expression ofCD36.

  2. CD36 genetic variation, fat intake and liver fibrosis in chronic hepatitis C virus infection

    Science.gov (United States)

    Ramos-Lopez, Omar; Roman, Sonia; Martinez-Lopez, Erika; Fierro, Nora A; Gonzalez-Aldaco, Karina; Jose-Abrego, Alexis; Panduro, Arturo

    2016-01-01

    AIM To analyze the association of the CD36 polymorphism (rs1761667) with dietary intake and liver fibrosis (LF) in chronic hepatitis C (CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype (G > A) was determined by a TaqMan real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography (Fibroscan®) and APRI score was classified as mild LF (F1-F2) and advanced LF (F3-F4). RESULTS Overall, the CD36 genotypic frequencies were AA (30.1%), AG (54.8%), and GG (15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase (AST) serum values were higher in AA genotype carriers compared to non-AA carriers (91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST (β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG (OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes (OR = 3.52, 95%CI: 1.18-10.45, P = 0.02). CONCLUSION This study suggests that the CD36 (rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients. PMID:27660673

  3. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q. [Department of Cardiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2014-08-08

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

  4. Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.

    Directory of Open Access Journals (Sweden)

    Fiona E Lovegrove

    2008-05-01

    Full Text Available Although acute lung injury (ALI is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM; however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL, histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA. BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar-capillary membrane barrier-the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36(-/- mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.

  5. Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

    Directory of Open Access Journals (Sweden)

    Chuan Wang

    Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

  6. Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation.

    Science.gov (United States)

    Kang, Lin-Lin; Zhang, Dong-Mei; Ma, Chun-Hua; Zhang, Jian-Hua; Jia, Ke-Ke; Liu, Jia-Hui; Wang, Rong; Kong, Ling-Dong

    2016-01-01

    Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor, and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis. PMID:27270216

  7. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation

    Science.gov (United States)

    Boehm, Olaf; El Aissati, Sakina; Foltz, Fabian; Goelz, Lina; Goertz, David; Kebir, Sied; Weisheit, Christina; Wolf, Michael; Meyer, Rainer; Baumgarten, Georg

    2015-01-01

    Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR)-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15mg/g bodyweight) or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization) signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced hyperinflammatory

  8. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation.

    Directory of Open Access Journals (Sweden)

    Heidi Ehrentraut

    Full Text Available Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15 mg/g bodyweight or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced

  9. Skeletal Muscle and Liver Lipidomics and the Regulation of FAT/CD36

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting

    that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver......; amongst these is fatty acid transport across the plasma membrane. Data suggest that the transmembrane transport of fatty acid into cells involves a protein mediated transport, involving the fatty acid transporter FAT/CD36. Herein we show that FAT/CD36 is important for fatty acid uptake and oxidation......Increased caloric intake and physical inactivity can lead to the development of insulin resistance and puts a large burden on the Western society. Often increased caloric intake is associated with elevated plasma fatty acid concentrations and decreased insulin sensitivity and it is now recognized...

  10. Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport.

    OpenAIRE

    Ibrahimi, A.; Sfeir, Z; Magharaie, H; Amri, E Z; Grimaldi, P.; Abumrad, N A

    1996-01-01

    An adipocyte membrane glycoprotein, (FAT), homologous to human CD36, has been previously implicated in the binding/transport of long-chain fatty acids. It bound reactive derivatives of long-chain fatty acids and binding was specific and associated with significant inhibition of fatty acid uptake. Tissue distribution of the protein and regulation of its expression were also consistent with its postulated role. In this report, we have examined the effects of FAT expression on rates and properti...

  11. The Functional Role of CD36 Involved in Fatty Acid Transduction

    OpenAIRE

    Xu, Han

    2014-01-01

    The multifunctional fatty acid (FA) binding protein, Cluster of Differentiation 36 (CD36), has been found to be expressed in a variety of tissues where it is involved in multiple fat-related biological processes, such as lipid metabolism in mammals and the detection of lipid-like pheromones in insects. As identified in the apical membranes of taste cells, along with functional evidence in behavioral and cellular level, its involvement in the gustatory FAs detection is suggested. Nonetheless, ...

  12. miRNA-133a attenuates lipid accumulation via TR4-CD36 pathway in macrophages.

    Science.gov (United States)

    Peng, Xiao-Ping; Huang, Lei; Liu, Zhi-Hong

    2016-08-01

    lipid metabolism is the major causes of atherosclerosis. There is increasing evidence that miR-133a plays an important role in atherosclerosis. However, the regulatory mechanism of miR-133a in macrophages is still unclear. Several lines of evidence indicate that loss of TR4 leads to reduce lipid accumulation in liver and adipose tissues, etc, and lesional macrophages-derived TR4 can greatly increase the foam cell formation through increasing the CD36-mediated the uptake of ox-LDL. Interestingly, computational analysis suggests that TR4 may be a target gene of miR-133a. Here, we examined whether miR-133a regulates TR4 expression in ox-LDL-induced mouse RAW 264.7 macrophages, thereby affecting lipid accumulation. Using ox-LDL-treatment RAW 264.7 macrophages transfected with miR-133a mimics or inhibitors, we have showed that miR-133a can directly regulate the expression of TR4 in RAW 264.7 cells, thereby attenuates CD36-medide lipid accumulation. Furthermore, our studies suggest an additional explanation for the regulatory mechanism of miR-133a regulation to its functional target, TR4 in RAW 264.7 macrophages. Thus, our findings suggest that miR-133a may regulate lipid accumulation in ox-LDL-stimulated RAW 264.7 macrophages via TR4-CD36 pathway.

  13. A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism

    Science.gov (United States)

    Gomez-Diaz, Carolina; Bargeton, Benoîte; Abuin, Liliane; Bukar, Natalia; Reina, Jaime H.; Bartoi, Tudor; Graf, Marion; Ong, Huy; Ulbrich, Maximilian H.; Masson, Jean-Francois; Benton, Richard

    2016-01-01

    CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure–activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors. PMID:27302750

  14. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Katalin Susztak

    2005-02-01

    Full Text Available BACKGROUND: Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood. METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis. CONCLUSION: Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  15. Increased FAT/CD36 cycling and lipid accumulation in myotubes derived from obese type 2 diabetic patients.

    Directory of Open Access Journals (Sweden)

    Celine Aguer

    Full Text Available BACKGROUND: Permanent fatty acid translocase (FAT/CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Primary muscle cells derived from obese type 2 diabetic patients (OBT2D and from healthy subjects (Control were used to examine the regulation of FAT/CD36. We showed that compared to Control myotubes, FAT/CD36 was continuously cycling between intracellular compartments and the cell surface in OBT2D myotubes, independently of lipid raft association, leading to increased cell surface FAT/CD36 localization and lipid accumulation. Moreover, we showed that FAT/CD36 cycling and lipid accumulation were specific to myotubes and were not observed in reserve cells. However, in Control myotubes, the induction of FAT/CD36 membrane translocation by the activation of (AMP-activated protein kinase (AMPK pathway did not increase lipid accumulation. This result can be explained by the fact that pharmacological activation of AMPK leads to increased mitochondrial beta-oxidation in Control cells. CONCLUSION/SIGNIFICANCE: Lipid accumulation in myotubes derived from obese type 2 diabetic patients arises from abnormal FAT/CD36 cycling while lipid accumulation in Control cells results from an equilibrium between lipid uptake and oxidation. As such, inhibiting FAT/CD36 cycling in the skeletal muscle of obese type 2 diabetic patients should be sufficient to diminish lipid accumulation.

  16. Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

    DEFF Research Database (Denmark)

    Knøsgaard, L; Thomsen, S B; Støckel, M;

    2014-01-01

    BACKGROUND: The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to s......-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model...

  17. Oxidised LDL up-regulate CD36 expression by the Nrf2 pathway in 3T3-L1 preadipocytes.

    Science.gov (United States)

    D'Archivio, Massimo; Scazzocchio, Beatrice; Filesi, Carmela; Varì, Rosaria; Maggiorella, Maria Teresa; Sernicola, Leonardo; Santangelo, Carmela; Giovannini, Claudio; Masella, Roberta

    2008-06-25

    The effect of oxLDL on CD36 expression has been assessed in preadipocytes induced to differentiate. Novel evidence is provided that oxLDL induce a peroxisome proliferator-activated receptor gamma-independent CD36 overexpression, by up-regulating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2). The nuclear translocation of Nrf2 appeared to depend on PKC pathway activation. In adipocytes, the CD36 up-regulation may indicate a compensation mechanism to meet the demand of excess oxLDL and oxidised lipids in blood, reducing the risk of atherogenesis. Besides strengthening the hypothesis that oxLDL can contribute to the onset of insulin-resistance, data herein presented highlight the significance of oxLDL-induced CD36 overexpression within the cellular defence response. PMID:18514070

  18. Increased FAT/CD36 Cycling and Lipid Accumulation in Myotubes Derived from Obese Type 2 Diabetic Patients

    OpenAIRE

    Celine Aguer; Marc Foretz; Louise Lantier; Sophie Hebrard; Benoit Viollet; Jacques Mercier; Magali Kitzmann

    2011-01-01

    BACKGROUND: Permanent fatty acid translocase (FAT/)CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Primary muscle cells derived from obese type 2 diabetic patients (OBT2D) and from healthy subjects (Control) were used to examine th...

  19. CD36 and Na/K-ATPase-α1 Form a Pro-inflammatory Signaling Loop in Kidney

    OpenAIRE

    Kennedy, David J.; Chen, Yiliang; Huang, Wenxin; Viterna, Jamie; Liu, Jiang; Westfall, Kristen; Tian, Jian; Bartlett, David J.; Wilson Tang, W. H.; Xie, Zi-jian; Shapiro, Joseph I; Silverstein, Roy L.

    2012-01-01

    Pro-atherogenic, hyperlipidemic states demonstrate increases in circulating ligands for scavenger receptor CD36 (e.g. oxidized LDL (oxLDL)) and the Na/K-ATPase (e.g. cardiotonic steroids). These factors increase inflammation, oxidative stress, and progression of chronic kidney disease. We hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/ Na/K-ATPase -dependent inflammatory paracrine loop between proximal tubule cells (PTC) and their associated macrophages and thereb...

  20. Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  1. Role of FAT/CD36 in high-fat diet-induced adipose tissue inflammation%FAT/CD36在高脂喂养小鼠脂肪组织炎症中的作用

    Institute of Scientific and Technical Information of China (English)

    张艳艳; 赵蕾; 谢云霞; 陈压西; 阮雄中

    2015-01-01

    AIM: To investigate the role of fatty acid translocase/CD36 (FAT/CD36) in adipose tissue in-flammation induced by a high-fat diet.METHODS:C57BL/6J mice were fed with a normal-chow diet ( NCD) or a high-fat diet ( HFD) for 14 weeks.The content of free fatty acid ( FFA) in the serum was measured by ELISA.The expression of CD36, cytokines and chemokines at mRNA and protein levels in the adipose tissues was determined by real-time poly-merase chain reaction and Western blotting.Immunohistochemical staining was used to examine the macrophages infiltration in the adipose tissues.The inflammatory responses in CD36 knockout mice and wild type mice with high-fat diet were ana-lyzed.RESULTS:The levels of FAT/CD36 were higher in HFD group than that in NCD group.HFD feeding enhanced the mRNA and protein expression of IL-1β, IL-6, TNF-α, MCP-1 and MIP-1, as well as promoted macrophage infiltration in the adipose tissues.Interestingly, as fed with HFD, the expression of cytokines/chemokines and macrophage infiltration were significantly reduced in adipose tissues of the CD36 knockout mice, compared with the wild type mice.CONCLU-SION:High-fat diet promotes adipose tissue inflammation in the mice in a FAT/CD36-dependent manner.%目的:探讨脂肪酸转运酶/白细胞分化抗原36(fatty acid translocase/CD36,FAT/CD36)在高脂饮食诱导的小鼠脂肪组织炎症中的作用。方法:将6周龄雄性C57BL/6J小鼠分别随机分为普通饮食组和高脂饮食组,喂养14周后,ELISA测定血清游离脂肪酸( FFA)含量,应用荧光实时定量 PCR和Western blotting检测脂肪组织中FAT/CD36及炎症/趋化因子( IL-1β、IL-6、TNF-α、MCP-1、MIP-1) mRNA和蛋白的表达,免疫组织化学染色检测脂肪组织巨噬细胞浸润,比较高脂喂养14周的野生型小鼠和CD36基因敲除小鼠的脂肪组织炎症反应情况。结果:与普通饮食组相比,高脂饮食能增强C57BL/6J小鼠脂肪组织的FAT/CD

  2. Dietary Lipids Inform the Gut and Brain about Meal Arrival via CD36-Mediated Signal Transduction.

    Science.gov (United States)

    Sundaresan, Sinju; Abumrad, Nada A

    2015-10-01

    Sensing mechanisms for nutrients, in particular dietary fat, operate in the mouth, brain, and gastrointestinal tract and play a key role in regulating feeding behavior and energy balance. Critical to these regulatory mechanisms are the specialized receptors present on taste buds on the tongue, on neurons in specialized centers in the brain, and on epithelial and enteroendocrine cells in the intestinal mucosa. These receptors recognize nutrients and respond by inducing intracellular signals that trigger release of bioactive compounds that influence other organs and help coordinate the response to the meal. Components of dietary fat that are recognized by these receptors are the long-chain fatty acids that act as ligands for 2 G protein-coupled receptors, GPR40 and GPR120, and the fatty acid (FA) translocase/CD36. Recent evidence that emphasizes the important role of CD36 in orosensory, intestinal, and neuronal sensing of FAs under physiologic conditions is highlighted in the review. How this role intersects with that of GPR120 and GPR40 in the regulation of food preference and energy balance is briefly discussed. PMID:26269236

  3. Inflammatory cytokines up-regulate FAT/CD36 expression in renal cells loaded by fatty acids%炎症对脂肪酸负荷的肾细胞FAT/CD36表达的影响

    Institute of Scientific and Technical Information of China (English)

    万克强; 廖俊蕾; 赵蕾; 李青; 陈压西; 阮雄中

    2012-01-01

    目的:观察炎症是否干扰脂肪酸负荷的肾细胞[人系膜细胞(HMCs)和肾小管上皮细胞HK-2]脂肪酸转运蛋白(FAT/CD36)的表达.方法:分别给予不同浓度软脂酸(0 mmol/L、0.02 mmol/L、0.04 mmol/L、0.08 mmol/L、0.16 mmol/L、0.32 mmol/L)处理HMCs和HK-2细胞24 h.采用实时定量PCR和Western blotting方法检测细胞FAT/CD36的mRNA及蛋白的表达.进一步选取0.04 mmol/L软脂酸联合炎症因子(25 μg/L TNF-α或20 μg/L IL-6)处理肾细胞24 h后,观察炎症因子对肾细胞FAT/CD36 mRNA及蛋白表达的影响;油红O染色及酶比色法检测细胞甘油三酯(TG)水平;ELISA检测细胞游离脂肪酸(FFA)含量.结果:软脂酸呈浓度依赖性上调HMCs和HK-2细胞FAT/CD36 mRNA和蛋白表达.炎症因子明显刺激脂肪酸负荷的肾细胞FAT/CD36 mRNA和蛋白表达进一步增加.油红O染色及胞内TG和FFA含量测定显示炎症因子促进肾细胞脂质积聚.结论:炎症上调脂肪酸负荷的肾细胞FAT/CD36表达,加重胞内脂质积聚.%AIM: To investigate the effects of inflammatory cytokines on the expression of fatty acid transporter ( FAT/CD36 ) in renal cells loaded by fatty acids. METHODS: Human mesangial cells ( HMCs ) and renal tubular epithelial HK -2 cells were treated with palmitate at concentrations of 0 mmol/L, 0. 02 mmol/L, 0. 04 mmol/L, 0. 08 mmol/L, 0. 16 mmol/L and 0. 32 mmol/L for 24 h. The expression of FAT/CD36 at mRNA and protein levels was detected by real - time PCR and Western blotting, respectively. The renal cells were treated with palmitate at concentration of 0. 04 mmol/L combined with TNF - a ( 25 μg/L ) or IL - 6 ( 20 μg/L ) for 24 h. The effect of inflammatory cytokines on the mRNA and protein levels of FAT/CD36 in the renal cells was also investigated. Oil red 0 staining was used to determine the intracellular lipid droplet formation. The intracellular triglyceride ( TG ) and free fatty acid ( FFA ) were measured by enzymic assay and ELISA, respectively

  4. Hematopoietic Cell–Restricted Deletion of CD36 Reduces High-Fat Diet–Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue

    OpenAIRE

    Nicholls, Hayley T.; Kowalski, Greg; Kennedy, David J.; Risis, Steve; Zaffino, Lee A.; Watson, Nadine; Kanellakis, Peter; Watt, Matthew J.; Bobik, Alex; Bonen, Arend; Febbraio, Maria; Lancaster, Graeme I.; Febbraio, Mark A.

    2011-01-01

    OBJECTIVE The fatty acid translocase and scavenger receptor CD36 is important in the recognition and uptake of lipids. Accordingly, we hypothesized that it plays a role in saturated fatty acid–induced macrophage lipid accumulation and proinflammatory activation. RESEARCH DESIGN AND METHODS In vitro, the effect of CD36 inhibition and deletion in lipid-induced macrophage inflammation was assessed using the putative CD36 inhibitor, sulfosuccinimidyl oleate (SSO), and bone marrow–derived macropha...

  5. Effect of high glucose on the expression of CD36 and lipid accumulation in THP-1 macrophages

    Institute of Scientific and Technical Information of China (English)

    谭玉林

    2014-01-01

    Objective To investigate the effect of high glucose on regulating the expression of CD36 and lipid accumulation in THP-1 macrophages.Methods THP-1 macrophages were incubated with different concentrations of D-glucose(5.6,11,20,30 and 35 mmol/L),50 mg/L oxidized low density lipoprotein(ox-LDL),50 mg/L oxLDL+20 mmol/L D-glucose for 24 h.Total cholesterol content in THP-1 macrophages was determined by high performance liquid chromatography,the lipid accumulation was detected by oil red O stain.CD36 mRNA and

  6. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease

    NARCIS (Netherlands)

    Sheedfar, Fareeba; Sung, Miranda My; Aparicio-Vergara, Marcela; Kloosterhuis, Niels J; Miquilena-Colina, Maria Eugenia; Vargas-Castrillón, Javier; Febbraio, Maria; Jacobs, René L; de Bruin, Alain; Vinciguerra, Manlio; García-Monzón, Carmelo; Hofker, Marten H; Dyck, Jason Rb; Koonen, Debby P Y

    2014-01-01

    CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with si

  7. FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Mogensen, Martin; Prats, Clara;

    2010-01-01

    was performed on single muscle fibers dissected from soleus muscle of lean and obese Zucker rats and from the vastus lateralis muscle from humans. Co-staining against FAT/CD36 and MitoNEET clearly show that FAT/CD36 is highly present in sarcolemma and it also associates with some vesicle-like intracellular...

  8. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.

    Science.gov (United States)

    Luz, Paola Rosa; Miyazaki, Márcia I; Chiminacio Neto, Nelson; Padeski, Marcela C; Barros, Ana Cláudia M; Boldt, Angelica B W; Messias-Reason, Iara J

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.

  9. CD36- and GPR120-mediated Ca2+ Signaling in Human Taste Bud Cells Mediates Differential Responses to Fatty Acids and is Altered in Obese Mice

    Science.gov (United States)

    Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A.; Khan, Naim Akhtar

    2014-01-01

    Background & Aims It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca2+ signaling in fungiform taste bud cells (TBC). Methods We measured Ca2+ signaling in human TBC, transfected with small interfering RNAs (siRNAs) against mRNAs encoding CD36 and GPR120 (or control siRNAs). We also studied Ca2+ signaling in TBC from CD36−/− mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and GLP-1 from human and mice TBC in response to CD36 and GPR120 activation. Results High concentrations of linoleic acid induced Ca2+ signaling via CD36 and GPR120 in human and mice TBC as well as in STC-1 cells, whereas low concentrations induced Ca2+ signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid downregulated CD36 and upregulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca2+ and serotonin responses but increased release of GLP1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. Conclusions CD36 and GPR120 have non-overlapping roles in TBC signaling during oro-gustatory perception of dietary lipids; these are differentially regulated by obesity. PMID:24412488

  10. Association between rs1761667 polymorphism of CD36 gene and risk of coronary atherosclerosis in Egyptian population

    Science.gov (United States)

    Arafa, Usama Ahmed; Sabet, Eman A.; Salama, Eman; El Sharawy, Ahmed; Elbadry, Mahmoud I.

    2016-01-01

    Background Recent studies have demonstrated that CD36 is involved in the progression of atherosclerosis. Associations between rs1761667 polymorphisms of the CD36 gene and susceptibility to coronary artery disease (CAD) are not obvious. Methods We studied the relationship between single nucleotide polymorphisms (SNPs), rs1761667 of CD36 gene and the risk of coronary atherosclerosis in a case-control study composed of 71 CAD patients and 76 healthy controls by assessment of allele frequencies and genotype distributions using real-time polymerase chain reaction (PCR) and the allele discrimination technique. Additionally, we detected CD36 expression by flow cytometry. Results The distribution of rs1761667 genotypes between the two groups was significantly different (P<0.001), with the frequency of the AG genotype being significantly higher in the CAD group than in the control group (P<0.001). The expression level of CD36 in the CAD group was significantly higher than that in the control group (P<0.001), with significant differences in the CAD patients with an AG genotype compared with those with an AA and GG genotype (P<0.001). The plasma levels (mg/dL) of low-density lipoprotein (LDL) in the CAD group were much higher than that in the control group (P<0.001). On the other hand, the plasma LDL levels in CAD patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.046) and AG genotype was significantly more prevalent among type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) patients (P<0.05). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CAD (OR=17.97, 95% CI, 3.19–87.85, P=0.001). Conclusions The AG genotype of the rs1761667 polymorphism in the CD36 gene may be involved in CAD pathogenesis as well as increased body mass index (BMI), T2DM and MetS in the Sohag population of Egypt. PMID:27054101

  11. Clearance of Apoptotic Cells by Macrophages Induces Regulatory Phenotype and Involves Stimulation of CD36 and Platelet-Activating Factor Receptor

    Directory of Open Access Journals (Sweden)

    Matheus Ferracini

    2013-01-01

    Full Text Available Phagocytosis of apoptotic cells (efferocytosis induces macrophage differentiation towards a regulatory phenotype (IL-10high/IL-12p40low. CD36 is involved in the recognition of apoptotic cells (AC, and we have shown that the platelet-activating factor receptor (PAFR is also involved. Here, we investigated the contribution of PAFR and CD36 to efferocytosis and to the establishment of a regulatory macrophage phenotype. Mice bone marrow-derived macrophages were cocultured with apoptotic thymocytes, and the phagocytic index was determined. Blockage of PAFR with antagonists or CD36 with specific antibodies inhibited the phagocytosis of AC (~70–80%. Using immunoprecipitation and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR colocalisation in the macrophage plasma membrane; PAFR and CD36 coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and disruption of these membrane microdomains by methyl-β-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10high/IL-12p40low, that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and this was prevented by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype.

  12. Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes.

    Science.gov (United States)

    Mentese, Ahmet; Alver, Ahmet; Sumer, Aysegul; Demir, Selim

    2016-03-01

    The aim of this study was to investigate the effects of homocysteine (Hcy), a risk factor for cardiovascular diseases, hypertension, stroke and obesity, on expression of CD36 that regulates uptake of oxidized low-density lipoprotein (Ox-LDL) by adipocytes and differentiation of 3T3-L1 cells to adipocytes. Cell viability was determined using MTT assay, and density of triglycerides were measured with Oil Red O staining. The expression levels of CD36 were analyzed using SYBR green assay by quantitative RT-PCR. Our results showed that the addition of Hcy inhibited differentiation of 3T3-L1 preadipocytes in a dose-dependent manner without a significant cell toxicity (p  0.05) compared to differentiated adipocytes. Hcy reduced adipocyte differentiation, but had no effect on the expression level of CD36 in vitro conditions. The effect of Hcy on uptake and clearance of Ox-LDL by adipose tissue now needs to be investigated in vivo. PMID:26691520

  13. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36[S

    Science.gov (United States)

    Chevrot, Michael; Bernard, Arnaud; Ancel, Déborah; Buttet, Marjorie; Martin, Céline; Abdoul-Azize, Souleymane; Merlin, Jean-François; Poirier, Hélène; Niot, Isabelle; Khan, Naim Akhtar; Passilly-Degrace, Patricia; Besnard, Philippe

    2013-01-01

    A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca2+]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior. PMID:23840049

  14. Chemokine Signaling Enhances CD36 Responsiveness toward Oxidized Low-Density Lipoproteins and Accelerates Foam Cell Formation

    Directory of Open Access Journals (Sweden)

    Harikesh S. Wong

    2016-03-01

    Full Text Available Excessive uptake of oxidized low-density lipoproteins (oxLDL by macrophages is a fundamental characteristic of atherosclerosis. However, signals regulating the engagement of these ligands remain elusive. Using single-molecule imaging, we discovered a mechanism whereby chemokine signaling enhanced binding of oxLDL to the scavenger receptor, CD36. By activating the Rap1-GTPase, chemokines promoted integrin-mediated adhesion of macrophages to the substratum. As a result, cells exhibited pronounced remodeling of the cortical actin cytoskeleton that increased CD36 clustering. Remarkably, CD36 clusters formed predominantly within actin-poor regions of the cortex, and these regions were primed to engage oxLDL. In accordance with enhanced ligand engagement, prolonged exposure of macrophages to chemokines amplified the accumulation of esterified cholesterol, thereby accentuating the foam cell phenotype. These findings imply that the activation of integrins by chemokine signaling exerts feedforward control over receptor clustering and effectively alters the threshold for cells to engage ligands.

  15. The Protective Effect of Soybean and Thyme on Iron Deficiency Anemia in Rats

    Directory of Open Access Journals (Sweden)

    Nora M. El-Sheikh

    2008-12-01

    Full Text Available Objective: The present study is carried out to investigate the protective effect and antioxidant activity of soybean and thyme on iron deficiency anemia. Material and Methods: Thirty five male albino rats were divided into five groups (7rats each. The first group fed on basal diet, iron sufficient (35 mg Fe / kg, and served as control. Rats of other groups (second - fifth were induced anemic by placing them on diet containing 3mg Fe / kg for 21 days, then divided to four dietary groups. The second group (anemic stayed on basal diet with Fe-deficiency. The third group fed on basal diet with sufficient iron in the form of ferrous sulphate. The fourth group fed modified basal diet free from iron and supplemented with soybean. The fifth group fed basal diet free from iron and supplemented with thyme. All three iron sources provide 35 mg iron/kg diet. At the end of experiment (49 days, rats were anesthetized, whole blood was used for determination of hemoglobin (Hb, hematocrit (HCt and reduced glutathione (GSH levels. Serum was used for determination of iron and lipid profile as well as lipid peroxidation as malondialdehyde (MDA. The liver was used for determination of iron and copper concentrations. Results: The present results indicated that Fe-deficiency caused many adverse effects reflected the significant decrease of Hb, HCt, serum iron, liver iron, GSH and high density lipoprotein-cholesterol (HDL-C. Fe-deficiency also caused significant increase in total iron binding capacity (TIBC, liver copper, MDA, triacylglycerols (TG and total cholesterol (TC. In contrary, administration of ferrous sulphate (FeSO4, soybean or thyme induced a significant increase of serum and liver iron profile. Conclusion: Soybean and thyme could able to provide iron to correct dietary iron-deficiency anemia and powerful antioxidant effect of soybean or thyme was reflected on marked decrease of MDA and increase of GSH and HDL-C.

  16. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue;

    2015-01-01

    Purpose. We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. Methods. Double-blinded, placebo-controlled study in 54 men aged 60-78 years....... units] vs. TT and vs. placebo (p body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta...

  17. FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria

    OpenAIRE

    Jeppesen, Jacob; Mogensen, Martin; Prats, Clara; Sahlin, Kent; Madsen, Klavs; Kiens, Bente

    2010-01-01

    The primary aim of the present study was to investigate in which cellular compartments fatty acid trans­locase CD36 (FAT/CD36) is localized. Intact and fully functional skeletal muscle mitochondria were isolated from lean and obese female Zucker rats and from 10 healthy male individuals. FAT/CD36 could not be detected in the isolated mitochondria, whereas the mitochondrial marker F1ATPase-β was clearly detected using immunoblotting. Lack of markers for other membrane structures indicated that...

  18. Aquaporin-1 Deficiency Protects Against Myocardial Infarction by Reducing Both Edema and Apoptosis in Mice.

    Science.gov (United States)

    Li, Lihua; Weng, Zhiyong; Yao, Chenjuan; Song, Yuanlin; Ma, Tonghui

    2015-01-01

    Many studies have determined that AQP1 plays an important role in edema formation and resolution in various tissues via water transport across the cell membrane. The aim of this research was to determine both if and how AQP1 is associated with cardiac ischemic injury, particularly the development of edema following myocardial infarction (MI). AQP1+/+ and AQP1-/- mice were used to create the MI model. Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis. Cardiac ischemia caused by hypoxia secondary to AQP1 deficiency stabilized the expression of HIF-1α in endothelial cells and subsequently decreased microvascular permeability, resulting in the development of edema. The AQP1-dependent myocardial edema and apoptosis contributed to the development of MI. AQP1 deficiency protected cardiac function from ischemic injury following MI. Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI. PMID:26348407

  19. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference.

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    Céline Martin

    Full Text Available BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s played by these gustatory lipid-sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36(+/-and CD36(-/- mice, it was found that: 1° CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2° this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3° CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4° this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression. CONCLUSIONS/SIGNIFICANCE: In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

  20. Salvianolic acid B inhibits macrophage uptake of modified low density lipoprotein (mLDL) in a scavenger receptor CD36-dependent manner

    OpenAIRE

    Bao, Yi; Wang, Li; Xu, Yanni; Yang, Yuan; Wang, Lifei; Si, Shuyi; Cho, Sunghee; Hong, Bin

    2012-01-01

    CD36, a class B scavenger receptor, has been implicated in the pathogenesis of a host of vascular inflammatory diseases. Through a high-throughput screening (HTS) assay for CD36 antagonist, we previously identified salvianolic acid B (SAB), a hydrophilic component derived from the herb Danshen, as a potential candidate. Danshen, the dried roots of Salvia miltiorrhiza, has been widely used in China for the prevention and treatment of atherosclerosis-related disorders. Previous studies showed t...

  1. CD36/SR-B2-TLR2 Dependent Pathways Enhance Porphyromonas gingivalis Mediated Atherosclerosis in the Ldlr KO Mouse Model.

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    Paul M Brown

    Full Text Available There is strong epidemiological association between periodontal disease and cardiovascular disease but underlying mechanisms remain ill-defined. Because the human periodontal disease pathogen, Porphyromonas gingivalis (Pg, interacts with innate immune receptors Toll-like Receptor (TLR 2 and CD36/scavenger receptor-B2 (SR-B2, we studied how CD36/SR-B2 and TLR pathways promote Pg-mediated atherosclerosis. Western diet fed low density lipoprotein receptor knockout (Ldlr° mice infected orally with Pg had a significant increase in lesion burden compared with uninfected controls.This increase was entirely CD36/SR-B2-dependent, as there was no significant change in lesion burden between infected and uninfected Cd36o/Ldlro mice [corrected]. Western diet feeding promoted enhanced CD36/SR-B2-dependent IL1β generation and foam cell formation as a result of Pg lipopolysaccharide (PgLPS exposure. CD36/SR-B2 and TLR2 were necessary for inflammasome activation and optimal IL1ß generation, but also resulted in LPS induced lethality (pyroptosis. Modified forms of LDL inhibited Pg-mediated IL1ß generation in a CD36/SR-B2-dependent manner and prevented pyroptosis, but promoted foam cell formation. Our data show that Pg infection in the oral cavity can lead to significant TLR2-CD36/SR-B2 dependent IL1ß release. In the vessel wall, macrophages encountering systemic release of IL1ß, PgLPS and modified LDL have increased lipid uptake, foam cell formation, and release of IL1ß, but because pyroptosis is inhibited, this enables macrophage survival and promotes increased plaque development. These studies may explain increased lesion burden as a result of periodontal disease, and suggest strategies for development of therapeutics.

  2. CD36 is not involved in scavenger receptor-mediated endocytic uptake of glycolaldehyde- and methylglyoxal-modified proteins by liver endothelial cells.

    Science.gov (United States)

    Nakajou, Keisuke; Horiuchi, Seikoh; Sakai, Masakazu; Hirata, Kenshiro; Tanaka, Makiko; Takeya, Motohiro; Kai, Toshiya; Otagiri, Masaki

    2005-05-01

    Circulating proteins modified by advanced glycation end-products (AGE) are mainly taken up by liver endothelial cells (LECs) via scavenger receptor-mediated endocytosis. Endocytic uptake of chemically modified proteins by macrophages and macrophage-derived cells is mediated by class A scavenger receptor (SR-A) and CD36. In a previous study using SR-A knockout mice, we demonstrated that SR-A is not involved in endocytic uptake of AGE proteins by LECs [Matsumoto et al. (2000) Biochem. J. 352, 233-240]. The present study was conducted to determine the contribution of CD36 to this process. Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were used as AGE proteins. 125I-GA-BSA and 125I-MG-BSA underwent endocytic degradation by these cells at 37 degrees C, and this process was inhibited by several ligands for the scavenger receptors. However, this endocytic uptake of 125I-GA-BSA by LECs was not inhibited by a neutralizing anti-CD36 antibody. Similarly, hepatic uptake of (111)In-GA-BSA after its intravenous injection was not significantly attenuated by co-administration of the anti-CD36 antibody. These results clarify that CD36 does not play a significant role in elimination of GA-BSA and MG-BSA from the circulation, suggesting that the receptor involved in endocytic uptake of circulating AGE proteins by LEC is not SR-A or CD36.

  3. The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses.

    Science.gov (United States)

    Sanjurjo, Lucía; Amézaga, Núria; Aran, Gemma; Naranjo-Gómez, Mar; Arias, Lilibeth; Armengol, Carolina; Borràs, Francesc E; Sarrias, Maria-Rosa

    2015-01-01

    CD5L (CD5 molecule-like) is a secreted glycoprotein that participates in host response to bacterial infection. CD5L influences the monocyte inflammatory response to the bacterial surface molecules lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by inhibiting TNF secretion. Here we studied the intracellular events that lead to macrophage TNF inhibition by human CD5L. To accomplish this goal, we performed functional analyses with human monocytic THP1 macrophages, as well as with peripheral blood monocytes. Inhibition of phosphatidylinositol 3-kinase (PtdIns3K) reversed the inhibitory effect of CD5L on TNF secretion. Among the various PtdIns3K isoforms, our results indicated that CD5L activates PtdIns3K (whose catalytic subunit is termed PIK3C3), a key modulator involved in autophagy. Further analysis revealed a concomitant enhancement of autophagy markers such as cellular LC3-II content, increased LC3 puncta, as well as LC3-LysoTracker Red colocalization. Moreover, electron microscopy showed an increased presence of cytosolic autophagosomes in THP1 macrophages overexpressing CD5L. Besides preventing TNF secretion, CD5L also inhibited IL1B and enhanced IL10 secretion. This macrophage anti-inflammatory pattern of CD5L was reverted upon silencing of autophagy protein ATG7 by siRNA transfection. Additional siRNA experiments in THP1 macrophages indicated that the induction of autophagy mechanisms by CD5L was achieved through cell-surface scavenger receptor CD36, a multiligand receptor expressed in a wide variety of cell types. Our data represent the first evidence that CD36 is involved in autophagy and point to a significant contribution of the CD5L-CD36 axis to the induction of macrophage autophagy.

  4. FAT/CD36-mediated Long-Chain Fatty Acid Uptake in Adipocytes Requires Plasma Membrane Rafts

    OpenAIRE

    Pohl, Jürgen; Ring, Axel; Korkmaz, Ümine; Ehehalt, Robert; Stremmel, Wolfgang

    2005-01-01

    We previously reported that lipid rafts are involved in long-chain fatty acid (LCFA) uptake in 3T3-L1 adipocytes. The present data show that LCFA uptake does not depend on caveolae endocytosis because expression of a dominant negative mutant of dynamin had no effect on uptake of [3H]oleic acid, whereas it effectively prevented endocytosis of cholera toxin. Isolation of detergent-resistant membranes (DRMs) from 3T3-L1 cell homogenates revealed that FAT/CD36 was expressed in both DRMs and deter...

  5. Uptake of long chain fatty acids is regulated by dynamic interaction of FAT/CD36 with cholesterol/sphingolipid enriched microdomains (lipid rafts

    Directory of Open Access Journals (Sweden)

    Herrmann Thomas

    2008-08-01

    Full Text Available Abstract Background Mechanisms of long chain fatty acid uptake across the plasma membrane are important targets in treatment of many human diseases like obesity or hepatic steatosis. Long chain fatty acid translocation is achieved by a concert of co-existing mechanisms. These lipids can passively diffuse, but certain membrane proteins can also accelerate the transport. However, we now can provide further evidence that not only proteins but also lipid microdomains play an important part in the regulation of the facilitated uptake process. Methods Dynamic association of FAT/CD36 a candidate fatty acid transporter with lipid rafts was analysed by isolation of detergent resistant membranes (DRMs and by clustering of lipid rafts with antibodies on living cells. Lipid raft integrity was modulated by cholesterol depletion using methyl-β-cyclodextrin and sphingolipid depletion using myriocin and sphingomyelinase. Functional analyses were performed using an [3H]-oleate uptake assay. Results Overexpression of FAT/CD36 and FATP4 increased long chain fatty acid uptake. The uptake of long chain fatty acids was cholesterol and sphingolipid dependent. Floating experiments showed that there are two pools of FAT/CD36, one found in DRMs and another outside of these domains. FAT/CD36 co-localized with the lipid raft marker PLAP in antibody-clustered domains at the plasma membrane and segregated away from the non-raft marker GFP-TMD. Antibody cross-linking increased DRM association of FAT/CD36 and accelerated the overall fatty acid uptake in a cholesterol dependent manner. Another candidate transporter, FATP4, was neither present in DRMs nor co-localized with FAT/CD36 at the plasma membrane. Conclusion Our observations suggest the existence of two pools of FAT/CD36 within cellular membranes. As increased raft association of FAT/CD36 leads to an increased fatty acid uptake, dynamic association of FAT/CD36 with lipid rafts might regulate the process. There is no

  6. Coronary artery calcification in hemophilia A: No evidence for a protective effect of factor VIII deficiency on atherosclerosis

    NARCIS (Netherlands)

    Tuinenburg, A.; Rutten, A.; Kavousi, M.; Leebeek, F.W.G.; Ypma, P.F.; Laros-Van Gorkom, B.A.P.; Nijziel, M.R.; Kamphuisen, P.W.; Mauser-Bunschoten, E.P.; Roosendaal, G.; Biesma, D.H.; Van Der Lugt A., [No Value; Hofman, A.; Witteman, J.C.M.; Bots, M.L.; Schutgens, R.E.G.

    2011-01-01

    Mortality due to ischemic heart disease is lower in hemophilia patients when compared to the general male population. As coagulation plays a role in the inflammatory pathways involved in atherogenesis, we investigated whether the clotting factor deficiency protects hemophilia patients from developin

  7. Oily Fish Consumption Modifies the Association between CD36 rs6969989 Polymorphism and Lipid Profiles in Korean Women

    Science.gov (United States)

    Shin, Yoonjin; Kim, Yangha

    2016-01-01

    The aim of this study was to investigate the association of CD36, a class B scavenger receptor, rs6969989 polymorphism with the serum lipid profiles in Korean women, together with their modulation by oily fish consumption. Subjects were participants from the Korean Genome Epidemiology Study (KoGES), which was initiated in 2001 as a large-scale. A total of 4,210 women aged 39 to 70 were included in this study. Data were collected using self-administered questionnaires, anthropometric measurements, and blood chemical analysis. Dietary intake was analyzed using a semi-quantitative food frequency questionnaire. The minor allele frequency for rs6969989 was found in 12% of this population. Homozygotes minor G allele at the rs6868989 exhibited significantly higher high density lipoprotein cholesterol (HDL-C) concentrations (P-trend=0.043) and lower fasting glucose (P-trend=0.013) than major allele A carriers. The risk of low HDL-C was significantly lower in homozygotes for the G allele than the A allele carriers (P-trend=0.032). Gene-diet interaction effects between rs6969989 and oily fish intake were significantly associated with the risk of dyslipidemia (P-interaction= 0.004). Subjects with homozygotes minor G allele and high oily fish intake generally had a lower risk of dyslipidemia than did those with major allele homozygotes and low oily fish intake. These findings supported that oily fish consumption may modulate the contributions of CD36 rs6969989 on genetic predisposition to the risk of dyslipidemia. PMID:27752496

  8. Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis.

    Science.gov (United States)

    Berger, E; Héraud, S; Mojallal, A; Lequeux, C; Weiss-Gayet, M; Damour, O; Géloën, A

    2015-01-01

    Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesion (fibronectin FN1, collagens COL1A1, COL1A3, metalloprotein MMP9, or both (scavenger receptor FAT/CD36). Using real-time analysis of cell surface occupancy on xCELLigence system we developed a new method to study lipid uptake and differentiation of mouse 3T3L1 fibroblasts and human adipose stem cells. Both processes are regulated by insulin and fatty acids such as oleic acid. We showed that fatty acid addition to culture media increased the differentiation rate and was required for full differentiation into unilocular adipocytes. Significant activation of lipogenesis, i.e. lipid accumulation, by either insulin or oleic acid was monitored in times ranging from 1 to 24 h, depending on differentiation state, whereas significant effects on adipogenesis, i.e., surperimposed lipid accumulation and gene transcriptional regulations were measured after 3 to 4 d. Combination of selected times for analysis of lipid contents, cell counts, size fractionations, and gene transcriptional regulations showed that FAT/CD36 specific inhibitor AP5258 significantly increased cell survival of oleic acid-treated mouse and human adipocytes, and partially restored the transcriptional response to oleic acid in the presence of insulin through JNK pathway. Taken together, these data open new perspectives to study the molecular mechanisms commonly dysregulated in mouse and human obesity at the level of lipogenesis linked to hypertrophy and adipogenesis linked to hyperplasia. PMID:26257990

  9. The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

    International Nuclear Information System (INIS)

    Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA+FA) or depleted of them (HSA−FA). Receptor-mediated endocytosis of FITC-HSA+FA over 60 min was 5 times greater than that of FITC-HSA−FA. 24 h exposure of podocytes to albumin up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA−FA. Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes

  10. Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle.

    Science.gov (United States)

    Zhou, Liang; Pan, Yongquan; Chonan, Ritsu; Batey, Robert; Rong, Xianglu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2016-01-01

    Mangiferin is one of the prominent active components responsible for the antidiabetic property of many traditional herbs, but its underlying mechanisms of action remain unclear. CD36 in skeletal muscle is known to contribute to the etiology of insulin resistance by facilitating fatty acid uptake. This study investigated the effect of mangiferin on insulin resistance. The results showed that treatment of Wistar-Kyoto rats with mangiferin (15 mg/kg, once daily, by oral gavage) for 7 weeks inhibited chronic liquid fructose consumption-induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test (OGTT), and the homeostasis model assessment of insulin resistance index. It also suppressed the increases in fasted plasma nonesterified fatty acid (NEFA) concentration and the adipose tissue insulin resistance index. Mechanistically, mangiferin neither affected intakes of fructose and chow, and the increase in epididymal and perirenal fat, nor attenuated fructose-induced hypertension. In contrast, mangiferin attenuated fructose-induced acceleration of plasma NEFA clearance during OGTT, and tended to decrease excessive triglyceride accumulation in gastrocnemius. Immunofluorescence staining and subsequent rating of CD36-expressing fibers in gastrocnemius revealed that mangiferin restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution. In addition, the effects of mangiferin on the parameters associated with insulin resistance and abnormal fatty acid metabolism were absent in the spontaneously hypertensive rats carrying numerous nonfunctional mutations in the CD36 gene. Thus, these results suggest that mangiferin treatment mitigates insulin resistance in a rat model of fructose-induced metabolic syndrome by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle.

  11. The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

    Energy Technology Data Exchange (ETDEWEB)

    Pawluczyk, I.Z.A., E-mail: izap1@le.ac.uk [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); John Walls Renal Unit, Leicester General Hospital Leicester (United Kingdom); Pervez, A.; Ghaderi Najafabadi, M. [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); Saleem, M.A. [Academic and Children' s Renal Unit, University of Bristol, Southmead Hospital, Bristol (United Kingdom); Topham, P.S. [Department of Infection, Immunity and inflammation, University of Leicester, Leicester (United Kingdom); John Walls Renal Unit, Leicester General Hospital Leicester (United Kingdom)

    2014-08-15

    Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA{sub +FA}) or depleted of them (HSA{sub −FA}). Receptor-mediated endocytosis of FITC-HSA{sub +FA} over 60 min was 5 times greater than that of FITC-HSA{sub −FA}. 24 h exposure of podocytes to albumin up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA{sub −FA.} Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes.

  12. The anti-TNF-α antibody infliximab inhibits the expression of fat-transporter-protein FAT/CD36 in a selective hepatic-radiation mouse model.

    Science.gov (United States)

    Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens F; Wolff, Hendrik A; Malik, Ihtzaz A

    2015-01-01

    Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1-3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6-12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6-12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. PMID:25739082

  13. Comparative study of Zn deficiency in L. sativa and B. oleracea plants: NH4(+) assimilation and nitrogen derived protective compounds.

    Science.gov (United States)

    Navarro-León, Eloy; Barrameda-Medina, Yurena; Lentini, Marco; Esposito, Sergio; Ruiz, Juan M; Blasco, Begoña

    2016-07-01

    Zinc (Zn) deficiency is a major problem in agricultural crops of many world regions. N metabolism plays an essential role in plants and changes in their availability and their metabolism could seriously affect crop productivity. The main objective of the present work was to perform a comparative analysis of different strategies against Zn deficiency between two plant species of great agronomic interest such as Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco. For this, both species were grown in hydroponic culture with different Zn doses: 10μM Zn as control and 0.01μM Zn as deficiency treatment. Zn deficiency treatment decreased foliar Zn concentration, although in greater extent in B. oleracea plants, and caused similar biomass reduction in both species. Zn deficiency negatively affected NO3(-) reduction and NH4(+) assimilation and enhanced photorespiration in both species. Pro and GB concentrations were reduced in L. sativa but they were increased in B. oleracea. Finally, the AAs profile changed in both species, highlighting a great increase in glycine (Gly) concentration in L. sativa plants. We conclude that L. sativa would be more suitable than B. oleracea for growing in soils with low availability of Zn since it is able to accumulate a higher Zn concentration in leaves with similar biomass reduction. However, B. oleracea is able to accumulate N derived protective compounds to cope with Zn deficiency stress. PMID:27181942

  14. Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Andreas Billich

    Full Text Available BACKGROUND: Sphingosine-1-phosphate (S1P regulates the egress of T cells from lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase (Sgpl1. Hence, Sgpl1 offers a target to block T cell-dependent inflammatory processes. However, the involvement of Sgpl1 in models of disease has not been fully elucidated yet, since Sgpl1 KO mice have a short life-span. METHODOLOGY: We generated inducible Sgpl1 KO mice featuring partial reduction of Sgpl1 activity and analyzed them with respect to sphingolipid levels, T-cell distribution, and response in models of inflammation. PRINCIPAL FINDINGS: The partially Sgpl1 deficient mice are viable but feature profound reduction of peripheral T cells, similar to the constitutive KO mice. While thymic T cell development in these mice appears normal, mature T cells are retained in thymus and lymph nodes, leading to reduced T cell numbers in spleen and blood, with a skewing towards increased proportions of memory T cells and T regulatory cells. The therapeutic relevance of Sgpl1 is demonstrated by the fact that the inducible KO mice are protected in experimental autoimmune encephalomyelitis (EAE. T cell immigration into the CNS was found to be profoundly reduced. Since S1P levels in the brain of the animals are unchanged, we conclude that protection in EAE is due to the peripheral effect on T cells, leading to reduced CNS immigration, rather than on local effects in the CNS. SIGNIFICANCE: The data suggest Sgpl1 as a novel therapeutic target for the treatment of multiple sclerosis.

  15. A20 (Tnfaip3 deficiency in myeloid cells protects against influenza A virus infection.

    Directory of Open Access Journals (Sweden)

    Jonathan Maelfait

    Full Text Available The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.

  16. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne;

    2008-01-01

    for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. RESULTS......: sCD36 (2.87 relative units [0.88-9.36] vs. 1.67 relative units [0.72-3.89]), oxLDL (44.9 units/l [26.9-75.1] vs. 36.1 units/l [23.4-55.5]), and hsCRP (0.26 mg/dl [0.03-2.41] vs. 0.12 mg/dl [0.02-0.81]) were significantly increased in PCOS patients versus control subjects (geometric mean +/- 2 SD...... during insulin stimulation in PCOS patients and control subjects (n = 44). sCD36 and oxLDL were significant independent predictors of glucose and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3...

  17. CD34(+)/CD36(-) cells from myelodysplasia patients have a limited capacity to proliferate but can differentiate in response to Epo and MGF stimulation

    NARCIS (Netherlands)

    Brada, SJL; de Wolf, JTW; Smit, JW; Vellenga, E

    1998-01-01

    Myelodysplasia (MDS) is mostly characterized by a normal or increased number of normoblasts in the bone marrow and an impaired in vitro colony formation. In the present study we analyzed whether this might he due to a disconnection between proliferation and differentiation. CD34(+)/CD36(-) sorted bo

  18. Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes

    DEFF Research Database (Denmark)

    Habets, Daphna D. J.; Coumans, Will A.; El Hasnaoui, Mohammed;

    2009-01-01

    Enhanced contractile activity increases cardiac long-chain fatty acid (LCFA) uptake via translocation of CD36 to the sarcolemma, similarly to increase in glucose uptake via GLUT4 translocation. AMP-activated protein kinase (AMPK) is assumed to mediate contraction-induced LCFA utilization. However...

  19. Changes of Protective Enzymes and Accumulation of Polyamines Induced by Boron Deficiency in Roots of Rape Seedlings

    Institute of Scientific and Technical Information of China (English)

    XIAOFENGHUI

    1998-01-01

    The effects of boron deficiency on the membrane permeability,the lipid peroxidation of membrane ,the activities of the protective enzymes and the accumulation of polyamines in the roots of rape (Brassica napus L.cv Zhongyou 821)plants were examined using solution culture experiment .Compared to the 20 mmol B m-3 treatment ,boron-deficient treatment( 2 mmol B m-3) decreased root dry weight and increased the rate of solute leakage and malondialdehyde (MDA) concentration in the roots of rape.Similar patterns of change were observed in the level of lipid peroxidation (MDA concentration) and the rate of solute leakage under boron deficiency.Results suggested that a signifcant alteration of membrane composition had occurred under B deficiency.The concentration of putrescin and the ration of putrescine to spermidine +spermine in the roots of rape increaed significantly,and the activities of superoxide dismutase and catalase decreased in the roots of rape during B deficiency,But peroxidase activity in root of B-defcient plant was higher than that of control plant.

  20. Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.

    Science.gov (United States)

    Boddu, Ravindra; Hull, Travis D; Bolisetty, Subhashini; Hu, Xianzhen; Moehle, Mark S; Daher, João Paulo Lima; Kamal, Ahmed Ibrahim; Joseph, Reny; George, James F; Agarwal, Anupam; Curtis, Lisa M; West, Andrew B

    2015-07-15

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease. LRRK2 is expressed in many organs in mammals but is particularly abundant in the kidney. We find that LRRK2 protein is predominantly localized to collecting duct cells in the rat kidney, with much lower expression in other kidney cells. While genetic knockout (KO) of LRRK2 expression is well-tolerated in mice and rats, a unique age-dependent pathology develops in the kidney. The cortex and medulla of LRRK2 KO rat kidneys become darkly pigmented in early adulthood, yet aged animals display no overt signs of kidney failure. Accompanying the dark pigment we find substantial macrophage infiltration in LRRK2 KO kidneys, suggesting the presence of chronic inflammation that may predispose to kidney disease. Unexpectedly, the dark kidneys of the LRRK2 KO rats are highly resistant to rhabdomyolysis-induced acute kidney injury compared with wild-type rats. Biochemical profiling of the LRRK2 KO kidneys using immunohistochemistry, proteomic and lipidomic analyses show a massive accumulation of hemoglobin and lipofuscin in renal tubules that account for the pigmentation. The proximal tubules demonstrate a corresponding up-regulation of the cytoprotective protein heme oxygenase-1 (HO-1) which is capable of mitigating acute kidney injury. The unusual kidney pathology of LRRK2 KO rats highlights several novel physiological roles for LRRK2 and provides indirect evidence for HO-1 expression as a protective mechanism in acute kidney injury in LRRK2 deficiency. PMID:25904107

  1. The Deterioration Seen in Myelin Related Morphophysiology in Vanadium Exposed Rats is Partially Protected by Concurrent Iron Deficiency.

    Science.gov (United States)

    Usende, Ifukibot Levi; Leitner, Dominque F; Neely, Elizabeth; Connor, James R; Olopade, James O

    2016-01-01

    Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental exposure to vanadium, a transition metal can disrupt this iron homeostasis. We investigated the interaction of iron deficiency and vanadium exposure on the myelination infrastructure and its related neurobehavioural phenotypes, and neurocellular profiles in developing rat brains. Control group (C) dams were fed normal diet while Group 2 (V) dams were fed normal diet and pups were injected with 3mg/kg body weight of sodium metavanadate daily from postnatal day (PND) 1-21. Group 3 (I+V) dams were fed iron deficient diet after delivery and pups injected with 3mg/kg body weight sodium metavanadate from PND1-21. Body and brain weights deteriorated in I+V relative to C and V while neurobehavioral deficit occurred more in V. Whereas immunohistochemical staining shows more astrogliosis and microgliosis indicative of neuroinflammation in I+V, more intense OPCs depletion and hypomyelination were seen in the V, and this was partially protected in I+V. In in vitro studies, vanadium induced glial cells toxicity was partially protected only at the LD 50 dose with the iron chelator, desferroxamine. The data indicate that vanadium promotes myelin damage and iron deficiency in combination with vanadium partially protects this neurotoxicological effects of vanadium. PMID:27574759

  2. 血浆sCD36与2型糖尿病非酒精性脂肪肝的关系%Relationship between Plasma sCD36 and Type 2 Diabetes Mellitus Combined with Nonalcoholic Fatty Liver Disease

    Institute of Scientific and Technical Information of China (English)

    杨玲; 贾国瑜; 王璐; 李强; 张洁; 谢春晓; 邸阜生

    2014-01-01

    目的:研究血浆可溶性CD36(sCD36)与2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)的关系。方法检测正常对照组(A组,39例)、T2DM未合并NAFLD组(B组,39例)和T2DM合并NAFLD组(C组,59例)患者的血浆sCD36水平,计算C组的肝脏脂肪含量(LFC)及NAFLD纤维化评分(NFS),测定上述3组糖脂代谢指标、肝功能指标及炎症指标。方差分析法比较上述指标在3组中的差异;相关分析法分析C组患者上述各项指标与sCD36的相关性;多元逐步回归法分析C组sCD36的影响因素。结果血浆sCD36(μg/L)水平在B组(3.87±1.16)、C组(5.72±1.79)均高于A组(2.57±0.93),且C组高于B组(均P<0.01);相关分析示C组的sCD36水平与体质量指数(BMI)、腰围、内脏脂肪面积、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、游离脂肪酸(FFA)、丙氨酸转氨酶(ALT)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、LFC、NFS呈正相关(均P<0.05),多元逐步回归分析示FFA、LFC、TNF-α、IL-6是sCD36的影响因素。结论血浆sCD36与脂肪肝严重程度、肝脏损伤以及脂肪性肝纤维化有关,可能成为T2DM合并NAFLD的血浆标志物,CD36可能通过炎症机制参与T2DM合并NAFLD的发生发展。%Objective To investigate the relationship between plasma soluble CD36 (sCD36) and nonalcoholic fatty liver disease (NAFLD) in patients combined with type 2 diabetes mellitus (T2DM). Methods Plasma levels of sCD36 were determined in normal control group (group A, n=39), patients of T2DM without NAFLD group (group B, n=39) and T2DM with NAFLD group (group C, n=59). Liver fat content (LFC) and nonalcoholic fatty liver fibrosis score (NFS) were calculated in group C. Glucose and lipid metabolic parameters, liver function parameters and inflammatory parameters were also detect⁃ed in all three groups. Variance analysis was applied to

  3. TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver.

    Directory of Open Access Journals (Sweden)

    Susanne Nicole Weber

    depends on pre-existing fibrosis and genetic background. The generation of ABCB4-/: TLR4-/- double-deficient mice illustrates that TLR4-deficiency protects against hepatic injury in a preclinical mouse model of chronic liver disease.

  4. B-vitamin deficiency is protective against DSS-induced colitis in mice

    Science.gov (United States)

    Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met) and its increase in IBD patients indicates a disruption of Met metabolism, yet the role of Hcys and Met metabolism in IBD is not well und...

  5. Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function.

    Science.gov (United States)

    Zhu, Sen-Zhi; Huang, Wei-Ping; Huang, Lin-Qiang; Han, Yong-Li; Han, Qian-Peng; Zhu, Gao-Feng; Wen, Miao-Yun; Deng, Yi-Yu; Zeng, Hong-Ke

    2016-09-19

    Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.

  6. Analysis of human CD36 gene sequence alterations in the oxidized low-density lipoprotein-binding region using denaturing high-performance liquid chromatography.

    Science.gov (United States)

    Rać, Monika Ewa; Suchy, Janina; Kurzawski, Grzegorz; Safranow, Krzysztof; Jakubowska, Katarzyna; Olszewska, Maria; Garanty-Bogacka, Barbara; Rać, Michał; Poncyljusz, Wojciech; Chlubek, Dariusz

    2010-08-01

    Denaturing high-performance liquid chromatography (DHPLC) has been employed as a prescreening tool to reduce the amount of DNA sequencing. It could be a simple and cost-effective screening method for mutations and polymorphisms in exons 4, 5, and 6 of the CD36 gene, which encode the protein region responsible for the removal of oxidized low-density lipoprotein. Genomic DNA was isolated from 306 Caucasian infants of Polish origin. Six single-nucleotide substitutions were detected by DHPLC and confirmed by direct sequencing. The A591T, G550A, and C572T alterations have not been described so far. Each of two nonsynonymous substitutions (Asp184Asn, Pro191Leu) was found in one subject (0.2% minor allele frequency). The results suggest that nonsynonymous alterations in the analyzed CD36 region are rare in Caucasians. DHPLC is a specific and cost-effective technique that may prove to be particularly useful for the identification of polymorphisms and mutations in the CD36 gene. PMID:20722468

  7. Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.

    Directory of Open Access Journals (Sweden)

    Christopher B Guest

    Full Text Available Type 2 diabetes (T2D is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db mice are given cholesteryl ester intraperitoneally (IP, peritoneal macrophages (PerMPhis recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMPhis from heterozygote control (db/+ mice. Notably, PerMPhi fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to determine if these scavenger receptors (SRs were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression.

  8. NOX2 Deficiency Protects Against Streptozotocin-Induced β-Cell Destruction and Development of Diabetes in Mice

    OpenAIRE

    Xiang, Fu-Li; Lu, Xiangru; Strutt, Brenda; Hill, David J.; Feng, Qingping

    2010-01-01

    OBJECTIVE The role of NOX2-containing NADPH oxidase in the development of diabetes is not fully understood. We hypothesized that NOX2 deficiency decreases reactive oxygen species (ROS) production and immune response and protects against streptozotocin (STZ)-induced β-cell destruction and development of diabetes in mice. RESEARCH DESIGN AND METHODS Five groups of mice—wild-type (WT), NOX2−/−, WT treated with apocynin, and WT adoptively transferred with NOX2−/− or WT splenocytes—were treated wi...

  9. Deficiency of TDAG51 Protects Against Atherosclerosis by Modulating Apoptosis, Cholesterol Efflux, and Peroxiredoxin‐1 Expression

    OpenAIRE

    Hossain, Gazi S.; Lynn, Edward G.; Maclean, Kenneth N.; Zhou, Ji; Dickhout, Jeffrey G.; Lhoták, Šárka; Trigatti, Bernardo; Capone, John; Rho, Jaerang; Tang, Damu; McCulloch, Christopher A.; Al‐Bondokji, Imtisal; Malloy, Mary J.; Pullinger, Clive R.; Kane, John P.

    2013-01-01

    Background Apoptosis caused by endoplasmic reticulum (ER) stress contributes to atherothrombosis, the underlying cause of cardiovascular disease (CVD). T‐cell death‐associated gene 51 (TDAG51), a member of the pleckstrin homology‐like domain gene family, is induced by ER stress, causes apoptosis when overexpressed, and is present in lesion‐resident macrophages and endothelial cells. Methods and Results To study the role of TDAG51 in atherosclerosis, male mice deficient in TDAG51 and apolipopr...

  10. Impact of anti-OX-LDL antibodies on CD36 mRNA expression in monocytes%氧化型低密度脂蛋白抗体对单个核细胞CD36 mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    王磊; 宫剑滨; 王璟; 张启高; 王立军

    2012-01-01

    目的:通过观察氧化型低密度脂蛋白(OX-LDL)抗体对单个核细胞CD36 mRNA表达的影响,探讨OX-LDL抗体影响泡沫细胞形成的可能机制.方法:U937细胞和新西兰兔外周血单个核细胞分别被分成4组:空白对照组(普通培养基孵育)、OX-LDL刺激组(培养基中添加50μg/L的兔抗人OX-LDL多克隆抗体)、抗体干预组(培养基中添加50 μg/L的兔抗人OX-LDL多克隆抗体及100 μg/L的纯化人OX-LDL)及单纯抗体组(培养基中添加100 μg/L的纯化人OX-LDL),经培养24 h后,利用半定量RT-PCR技术分析CD36的mRNA表达水平.结果:无论在U937细胞或兔单个核细胞中,OX-LDL刺激组及抗体干预组CD36 mRNA的表达量均显著高于对照组,而经抗体干预后,CD36 mRNA表达量在U937细胞和在兔单个核细胞分别降低了约64.80%和35.18%,种属间差异有统计学意义.结论:抗OX-LDL抗体可以抑制单个核细胞CD36抗原的表达,从而抑制泡沫细胞形成过程中OX-LDL向细胞内的聚集.%AIM: To investigate the impact of antibodies to oxidized low-density lipoprotein ( OX-LDL) on CD36 mRNA expression in monocytes and explore the mechanism underlying the impact on the formation of foam cells. METHODS; U937 cells and the monocytes of New Zealand rabbit were respectively cultured in vitro and divided into 4 groups: the control group (cultured in nutrient medium of RPMI1640), the OX-LDL group (with additional OX-LDL of 50 uc/L in nutrient medium), the OX-LDL + Ab-OX-LDL group (with additional OX-LDL of 50 ug/L and Ab-OX-LDL of 100 yg/L in nutrient medium) and the Ab-OX-LDL group (with additional Ab-OX-LDL of 100 ug/L in nutrient medium). After 24-hour culture, the expression of CD36 mRNA was detected by semi-quantitative RT-PCR. RESULTS; The expression of CD36 mRNA, either in the OX-LDL group or in the OX-LDL + Ab-OX-LDL group, was higher than that in the control group. After intervened by Ab-OX-LDL, the expression was respectively down-regulated by 64

  11. 孕期炎症刺激对子代小鼠脂质代谢及 FAT/CD36表达的影响%Prenatal exposure to lipopolysaccharide results in lipid metabolism and FAT/CD36 expression in mice offspring

    Institute of Scientific and Technical Information of China (English)

    秦书刚; 陈新; 贾乙; 周见至; 苏敏; 李晓辉

    2016-01-01

    Aim To explore the effect of prenatal expo-sure to lipopolysaccharide ( LPS ) on lipid metabolism in mice offspring from the starting point of FAT/CD36 expression.Methods 8-week old C57 mice mated 2∶1, then they were caged separately , marked as preg-nancy 0 d.The pregnant mice were given single intrap-eritoneal injection of 75 μg・ kg -1 LPS, and the con-trol received injections of 0.2 mL saline .The perirenal adipose of female mice and epididymis adipose of male mice were collected in 4 w,8 w,12 w,respectively. The weight of visceral adipose tissue and the free fatty acid( FFA) and triglyceride ( TG) of adipose tissue and FAT/CD36 of offspring mice were quantitated .Results The body weight of offspring of LPS group was also significantly higher than that of NS group , and LPS group offspring displayed increased adipose tissue wet weights , the expression of TG and FFA was increased in LPS group compared with NS .Especially , prenatal exposure to inflammatory stimulation resulted in marked increase of FAT/CD36 and abnormal adipocyte development .Conclusions Inflammation induced by prenatal exposure to LPS results in increased body weight , adipose coefficient and FAT/CD36 that might develop into obesity in adult mice .These results are relevant in that anomalous local adipose tissue and FAT/CD36 regulation may be an important mechanism underlying obesity .%目的:以FAT/CD36为切入点,研究母体孕期炎症刺激对子代脂质代谢的影响。方法8周龄C57小鼠,♀♂2∶1合笼配种,d 2♀鼠分笼饲养记为在孕0 d,在孕11 d给予孕鼠一次性腹腔注射脂多糖(LPS)(75μg・ kg-1),对照组注射0.2 mL的生理盐水。分别于子鼠4、8、12周取材(♀鼠取肾周脂肪、♂鼠取附睾周围脂肪),对子代小鼠体重、内脏脂肪重量、脂肪组织和细胞中游离脂肪酸( FFA)、甘油三酯( TG)、FAT/CD36表达量进行检测。结果与NS组相比, LPS组小鼠体重、内

  12. Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis

    OpenAIRE

    Singh, Anjana; Rajasekaran, Narendiran; Hartenstein, Bettina; Szabowski, Sibylle; Gajda, Mieczyslaw; Angel, Peter; Bräuer, Rolf; Illges, Harald

    2013-01-01

    Introduction Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis. Methods For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13 –/– ) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacri...

  13. Intestinal GATA4 deficiency protects from diet-induced hepatic steatosis

    OpenAIRE

    Patankar, Jay V.; Obrowsky, Sascha; Doddapattar, Prakash; Hoefler, Gerald; Battle, Michele; Levak-Frank, Sanja; Kratky, Dagmar

    2012-01-01

    Background & Aims GATA4, a zinc finger domain transcription factor, is critical for jejunal identity. Mice with an intestine-specific GATA4 deficiency (GATA4iKO) are resistant to diet-induced obesity and insulin resistance. Although they have decreased intestinal lipid absorption, hepatic de novo lipogenesis is inhibited. Here, we investigated dietary lipid-dependent and independent effects on the development of steatosis and fibrosis in GATA4iKO mice. Methods GATA4iKO and control mice were f...

  14. B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.

    Directory of Open Access Journals (Sweden)

    Amy G Feldman

    Full Text Available A leading theory regarding the pathogenesis of biliary atresia (BA is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this study was to determine the role of B cells in the development of biliary obstruction in the Rhesus rotavirus (RRV-induced mouse model of BA. Wild-type (WT and B cell-deficient (Ig-α(-/- mice received RRV shortly after birth. Ig-α(-/- RRV-infected mice had significantly increased disease-free survival rate compared to WT RRV-infected BA mice (76.8% vs. 17.5%. In stark contrast to the RRV-infected BA mice, the RRV-infected Ig-α(-/- mice did not have hyperbilirubinemia or bile duct obstruction. The RRV-infected Ig-α(-/- mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-α(-/- mice had significantly increased numbers of regulatory T cells (Tregs at baseline and after RRV infection compared to WT mice. However, depletion of Tregs in Ig-α(-/- mice did not induce biliary obstruction, indicating that the expanded Tregs in the Ig-α(-/- mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-α(-/- mice are protected from biliary obstruction in the RRV-induced mouse model of BA, indicating a primary role of B cells in mediating disease pathology. The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA.

  15. Prokaryotic Expression of FAT/CD36 Fusion Protein and the Specific Effects on the Deposition of Visceral Fat in Cockerel Chicks%FAT/CD36融合蛋白的表达及其对鸡腹脂沉积的特异性调控

    Institute of Scientific and Technical Information of China (English)

    束刚; 张永亮; 江青艳; 冯嘉颖; 余凯凡; 徐平稳; 朱晓彤; 高萍; 王松波; 习欠云; 王修启

    2009-01-01

    [目的]脂肪酸转位酶(fatty acid trans locase,FAT/C036)是介导脂肪酸跨膜转运和脂肪细胞聚脂的重要载体蛋白.本试验采用主动免疫法研究FAT/CD36在鸡脂肪沉积调控中的作用.[方法]将FAT/CD36膜外区抗原表位基因片段克隆入表达载体pET-32a(+),并转化在大肠杆菌BL21(DE3),构建FAT/CD36融合蛋白表达载体.主动免疫试验选取22日龄黄羽肉鸡60只,按公、母各随机分为2组,共4组.公鸡和母鸡的试验组分别在第34、49、和63天肌肉注射1 mg重组鸡FAT/CD36融合蛋白,以牛血清白蛋白(boyine serum albumin,BSA)为对照.[结果]重组菌表达分子量约为29 kD的鸡FAT/CD36融合蛋白,在0.1 mmol·L-1 IPTG诱导6 h后,目的蛋白表达量占菌体总蛋白的32%.表达产物主要以包涵体的形式存在,经纯化并透析复性后得到高纯度的FAT/CD36融合蛋白.主动免疫后,公鸡和母鸡试验组的血清抗FAT/CD36抗体水平逐渐升高,并在首次免疫后显著高于各自对照组.主动免疫FAT/CD36能特异性降低公鸡的腹脂率,但对母鸡无显著性影响.试验组与对照组皮下脂肪厚度差异不显著.[结论]FAT/CD36对鸡脂肪调控具有典型的性别特异性和部位差异.试验结果为进一步阐明禽类脂肪组织特异性沉积的分子机制提供理论依据.

  16. APS improves free fatty acid metabolism by activating AMPK and promoting translocation of FAT/CD36 in C2C12 myoblasts%黄芪多糖通过活化AMPK和促进骨骼肌FAT/CD36转位改善成肌细胞FFAs代谢

    Institute of Scientific and Technical Information of China (English)

    胡阳黔; 李静; 刘坚; 欧阳静萍; 宋杰

    2013-01-01

    AIM: To investigate the effect of Astragalus polysaccharides (APS) on the metabolism of free fatty acids (FFAs) in C2C12 myoblasts. METHODS: Cultured C2C12 myoblasts were used in the study. The viability of C2C12 myoblasts treated with FFAs at different concentrations for different time was observed by MTT assay. The concentrations of FFAs in the medium were detected by acetyl-CoA synthase (ACS) -acetyl-CoA oxidase (ACOD) method. The expression of fatty acid translocase (FAT/CD36), AMPK and p-AMPK protein was examined by Western blotting. RESULTS; FFAs decreased the viability of C2C12 myoblasts in a time- and concentration-dependent manner. Compared with FFAs group, the expression of cellular membrane FAT/CD36 and p-AMPK proteins increased in FFAs + APS group, but total AMPK and FAT/CD36 protein expression was not significantly changed. Meanwhile, the concentration of FFAs in the medium decreased and the cell viability increased in FFAs + APS group as compared with the group. CONCLUSION: APS improves the metabolism of FFAs by activating AMPK and promoting translocation of FAT/CD36 in C2C12 myoblasts.%目的:探讨黄芪多糖(Astragalus polysaccharides,APS)对骨骼肌游离脂肪酸(free fatty acids,FFAs)代谢的影响及其机制.方法:培养小鼠C2C12成肌细胞;MTT法检测不同浓度FFAs作用不同时间对细胞活性的影响.根据MTT结果选取FFAs最适浓度和时间处理细胞并用APS干预,采用乙酰辅酶A合成酶-乙酰辅酶A氧化酶法检测APS干预前后培养液FFAs浓度;Western blotting测APS干预前后细胞膜脂肪酸转位酶(FAT/CD36)、总FAT/CD36、磷酸化腺苷酸活化蛋白激酶(phosphorylated AMP-activated protein kinase,p-AMPK)和总AMPK蛋白表达.结果:FFAs对细胞的毒性呈浓度和时间依赖性.与FFAs组比较,FFAs+ APS组细胞膜FAT/CD36及p-AMPK蛋白表达增加(P<0.05),而总FAT/CD36及总AMPK蛋白表达无明显差异(P>0.05),同时培养液FFAs浓度降低,细胞活性增加(P<0.05).

  17. Matrix-mediated canal formation in primmorphs from the sponge Suberites domuncula involves the expression of a CD36 receptor-ligand system.

    Science.gov (United States)

    Müller, Werner E G; Thakur, Narsinh L; Ushijima, Hiroshi; Thakur, Archana N; Krasko, Anatoli; Le Pennec, Gaël; Indap, Madhavi M; Perovic-Ottstadt, Sanja; Schröder, Heinz C; Lang, Gerhard; Bringmann, Gerhard

    2004-05-15

    Sponges (Porifera), represent the phylogenetically oldest metazoan phylum still extant today. Recently, molecular biological studies provided compelling evidence that these animals share basic receptor/ligand systems, especially those involved in bodyplan formation and in immune recognition, with the higher metazoan phyla. An in vitro cell/organ-like culture system, the primmorphs, has been established that consists of proliferating and differentiating cells, but no canals of the aquiferous system. We show that after the transfer of primmorphs from the demosponge Suberites domuncula to a homologous matrix (galectin), canal-like structures are formed in these 3D-cell aggregates. In parallel with the formation of these structures a gene is expressed whose deduced protein falls into the CD36/LIMPII receptor family. The receptor was cloned and found to be strongly expressed after adhesion to the galectin matrix. This process was suppressed if primmorphs were co-incubated with a homologous polypeptide containing the CSVTCG domain, as found in thrombospondin-1 (and related) molecules of vertebrates. In situ hybridization studies revealed that the S. domuncula CD36/LIMPII receptor is localized in the pinacocytes that surround the canals of the sponge. Furthermore, a secondary metabolite from a sponge-associated bacterium was isolated and characterized, the 2-methylthio-1,4-naphthoquinone (MTN). MTN causes inhibition of cell proliferation of vertebrate tumor cells at concentrations of >80 ng/ml. However, doses of only 2 ng are required to potently inhibit angiogenesis in the chick chorio-allantoic membrane assay. At concentrations of 10 ng/ml this compound was also found to suppress the expression of the S. domuncula CD36/LIMPII; this result is a first indication that this secondary metabolite has a conserved functional activity: the suppression of the formation of the circulation system, from sponges to vertebrates.

  18. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Nylen, Susanne; Duncan, Robert; Sacks, David; Nakhasi, Hira L

    2009-08-01

    No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

  19. Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age

    OpenAIRE

    Rać, Monika Ewa; Suchy, Janina; Kurzawski, Grzegorz; Kurlapska, Agnieszka; Safranow, Krzysztof; Rać, Michał; Sagasz-Tysiewicz, Dagmara; Krzystolik, Andrzej; Poncyljusz, Wojciech; Jakubowska, Katarzyna; Olszewska, Maria; Krupa, Beata; Chlubek, Dariusz

    2011-01-01

    This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≤ 50 years old and the women were ≤ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism w...

  20. Aldose reductase deficiency in mice protects from ragweed pollen extract (RWE-induced allergic asthma

    Directory of Open Access Journals (Sweden)

    Yadav Umesh CS

    2011-11-01

    Full Text Available Abstract Background Childhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR, a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR-/- mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat. Methods The wild type (WT and AR-/- mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL were determined using mouse anti-Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS-staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4+CD25+ T cells population. Results Deficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper-responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR-/- mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4+CD25+FoxP3+ cells as compared to RWE-sensitized and challenged mice not treated with fidarestat. Conclusion Our results using AR-/- mice strongly suggest the role

  1. Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

    Directory of Open Access Journals (Sweden)

    Sali Arpana

    2011-05-01

    Full Text Available Abstract Background Cardiomyopathy in Duchenne muscular dystrophy (DMD is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. Methods Three month old female mdx mice were exposed to the β1 receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188 (460 mg/kg/dose i.p. daily. Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD and picrosirius red staining. Results BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p Conclusions This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.

  2. Palmitate exacerbates intracellular lipid accumulation via up-regulating CD36 in HepG2 cells%棕榈酸上调FAT/CD36表达致HepG2细胞脂质积聚的机制研究

    Institute of Scientific and Technical Information of China (English)

    谢云霞; 赵蕾; 张艳艳; 陈压西; 阮雄中

    2015-01-01

    目的 观察脂肪酸转位酶FAT/CD36在棕榈酸诱导的HepG2细胞内脂质积聚中的作用,并探讨其分子机制.方法 HepG2细胞分对照组和棕榈酸组,用Western blot、双荧光素酶报告基因、荧光定量PCR、多聚核糖体分析检测棕榈酸对CD36表达、启动子活性和蛋白翻译效率的影响;油红O染色和FFA定量测定反映细胞内脂质含量;荧光显微镜实时观察细胞对FFA的动态摄入.然后将小干扰RNA转染到HepG2细胞,构建低表达CD36的HepG2细胞和阴性对照HepG2.用油红O染色,FFA定量和荧光显微镜观测棕榈酸负荷的转染细胞内脂质积聚和FFA摄取.结果 棕榈酸能促进HepG2细胞CD36的表达,增强其启动子活性,增加蛋白翻译效率;棕榈酸组细胞内脂滴增多,FFA含量(240.17±19.83) ng/mg明显高于对照组(144.60±53.52) ng/mg(P<0.05),脂肪酸摄取速度也明显快于对照组;低表达CD36的HepG2细胞中CD36的mRNA和蛋白含量仅为阴性对照细胞的58%和50%.低表达CD36的HepG2细胞内脂滴明显少于阴性对照,FFA水平(98.38±14.18) ng/mg较阴性对照组(240.17 ±21.12) ng/mg明显减低(P<0.05),细胞对FFA的摄取也减慢.结论 棕榈酸在转录和翻译水平促进HepG2的CD36表达,导致细胞内脂质积聚.

  3. Effects of inflammation on FAT/CD36 expressions in HepG2 cells loaded with fatty acids%炎症对脂肪酸负荷的HepG2细胞FAT/CD36表达的影响

    Institute of Scientific and Technical Information of China (English)

    殷鹭; 赵蕾; 李青; 黄爱龙; 陈压西; 阮雄中

    2013-01-01

    目的:观察炎症是否干扰脂肪酸负荷的人肝癌细胞系HepG2细胞脂肪酸转运蛋白/CD36(fatty acid transporter/CD36,FAT/CD36)的表达及脂质代谢.方法:分别给予不同浓度软脂酸(0.00、0.04、0.08、0.16、0.32 mmol/L)处理HepG2细胞24h.采用Western blot和real-time PCR的方法检测HepG2细胞FAT/CD36的蛋白及mRNA的表达水平,再用油红O的方法观察细胞的脂质积聚情况.然后进一步选取0.04 mmol/L的软脂酸联合炎症因子[25 ng/ml的肿瘤坏死因子-α(tumor necrosis factor,TNF-α)或20 ng/ml的白细胞介素-6(interleukin-6,IL-6)]处理HepG2细胞24h后,观察细胞FAT/CD36的蛋白表达情况,再用油红O和酶法检测细胞内的甘油三酯(triglyceride,TG)水平,ELISA检测细胞内游离脂肪酸(free fatty acid,FFA)含量.结果:软脂酸呈浓度依赖性上调HepG2细胞FAT/CD36的蛋白(r=0.873,P=0.000)和mRNA表达(r=0.884,P=0.000)及细胞内脂质积聚.炎症因子TNF-α和IL-6能明显刺激脂肪酸负荷的HepG2细胞FAT/CD36的蛋白表达进一步增加(P值分别为0.001和0.000).油红O染色显示炎症因子TNF-α和IL-6能明显促进HepG2细胞的脂质积聚,胞内TG定量检测也显示炎症因子能促进HepG2细胞的脂质积聚,其中软脂酸联合TNF-α组与对照组及软脂酸组相比,P值分别为0.009和0.037,软脂酸联合IL-6组与对照组及软脂酸组相比,P值均为0.000.胞内FFA定量检测结果与油红O染色和TG检测结果一致,也显示炎症因子能促进HepG2细胞的脂质积聚,其中软脂酸联合TNF-α组与对照组及软脂酸组相比,P值分别为0.001和0.002,软脂酸联合IL-6组与对照组及软脂酸组相比,P值均为0.000.结论:炎症因子可以上调HepG2细胞FAT/CD36的表达并加重细胞内的脂质积聚.

  4. Fatty acid binding protein 4 deficiency protects against oxygen-induced retinopathy in mice.

    Science.gov (United States)

    Saint-Geniez, Magali; Ghelfi, Elisa; Liang, Xiaoliang; Yu, Chenwei; Spencer, Carrie; Abend, Stephanie; Hotamisligil, Gokhan; Cataltepe, Sule

    2014-01-01

    Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF) expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR). We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4-/- mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4-/- OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies. PMID:24802082

  5. Fatty acid binding protein 4 deficiency protects against oxygen-induced retinopathy in mice.

    Directory of Open Access Journals (Sweden)

    Magali Saint-Geniez

    Full Text Available Retinopathy of prematurity (ROP is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4 is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR. We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4-/- mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4-/- OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies.

  6. Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age.

    Science.gov (United States)

    Rać, Monika Ewa; Suchy, Janina; Kurzawski, Grzegorz; Kurlapska, Agnieszka; Safranow, Krzysztof; Rać, Michał; Sagasz-Tysiewicz, Dagmara; Krzystolik, Andrzej; Poncyljusz, Wojciech; Jakubowska, Katarzyna; Olszewska, Maria; Krupa, Beata; Chlubek, Dariusz

    2012-02-01

    This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≤ 50 years old and the women were ≤ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism was associated with higher prevalence of obesity and diabetes, higher hsCRP, lower Lp(a) serum concentrations, and younger age at myocardial infarction. The A allele of the IVS4-10 G/A polymorphism was associated with older age of myocardial infarction and higher white blood cell count. The functional role of CD36 polymorphisms in CAD development needs further research. PMID:22113854

  7. Diabetes mellitus tipo 2: qual o papel da insulina na expressão de NF-kappaB, PPARγ e CD36?

    Directory of Open Access Journals (Sweden)

    Cristina de Oliveira SILVA

    2014-12-01

    Full Text Available No diabetes mellitus tipo 2 (DM2 e na síndrome de resistência à insulina, as complicações cardiovasculares resultam de um conjunto de processos aterogênicos envolvendo hiperglicemia crônica, excessiva glicação de proteínas (AGEs, ativação do fator nuclear kappa B (NKκB associada com o aumento da expressão de citocinas inflamatórias e estresse oxidativo, observando-se ainda alteração de LDL e expressão do receptor de scavenger CD36. A contribuição da hiperinsulinemia nesta sequência não é completamente elucidada. Nesta revisão, relata-se como a insulina pode modular a expressão proteica de NFκB, PPAR gama (PPARγ e CD36 em células da musculatura lisa vascular (CMLV da aorta de ratos estimuladas pelos AGE.

  8. Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model

    Directory of Open Access Journals (Sweden)

    Caballero-Hidalgo A

    2008-02-01

    Full Text Available Abstract Background Thiazolidinediones exert anti-inflammatory and anti-oxidative roles and attenuate atherosclerosis by mechanisms partially independent of their metabolizing actions. High doses of angiotensin type 1 receptor (AT1R blocker losartan (LST seem to promote fat cell formation by preserving PPARγ activity. Methods C57BL/6J diet-induced atherosclerotic susceptible mice randomly received a normal or a high-fat high-cholesterol (HFHC diet and were treated with rosiglitazone (RG, LST or a vehicle for 12 weeks. Results HFHC was associated with increased PPARγ gene expression without an over regulation of PPARγ responsive genes, whereas RG and LST treatments were found to maintain PPARγ activity without resulting in increased PPARγ gene expression. A better anti-inflammatory and antioxidant profile in mice treated with RG regarding LST was observed in spite of a similar PPARγ preserved activity. Chromatin immunoprecipitation (ChIP assays revealed that animals under HFHC diet treated with RG showed a significant nuclear factor erythroid 2-like 2 (Nrf2-dependent down-regulation of the expression of the CD36 gene. Conclusion The PPARγ agonist RG exerts antioxidant properties that significantly reduced Nrf-2-dependent CD-36 up-regulation in mice under HFHC diet. Because LST treatment was also associated with a preserved PPARγ activity, our data suggests that these RG antioxidant effects are partially independent of its PPARγ metabolizing properties.

  9. Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC zeta-GLUT4-glucose pathway in cardiomyoblasts.

    Science.gov (United States)

    Chen, Yeh-Peng; Tsai, Chia-Wen; Shen, Chia-Yao; Day, Cecilia-Hsuan; Yeh, Yu-Lan; Chen, Ray-Jade; Ho, Tsung-Jung; Padma, V Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2016-05-01

    Metabolic regulation is inextricably linked with cardiac function. Fatty acid metabolism is a significant mechanism for creating energy for the heart. However, cardiomyocytes are able to switch the fatty acids or glucose, depending on different situations, such as ischemia or anoxia. Lipotoxicity in obesity causes impairments in energy metabolism and apoptosis in cardiomyocytes. We utilized the treatment of H9c2 cardiomyoblast cells palmitic acid (PA) as a model for hyperlipidemia to investigate the signaling mechanisms involved in these processes. Our results show PA induces time- and dose-dependent lipotoxicity in H9c2 cells. Moreover, PA enhances cluster of differentiation 36 (CD36) and reduces glucose transporter type 4 (GLUT4) pathway protein levels following a short period of treatment, but cells switch from CD36 back to the GLUT4 pathway after during long-term exposure to PA. As sirtuin 1 (SIRT1) and protein kinase Cζ (PKCζ) play important roles in CD36 and GLUT4 translocation, we used the SIRT1 activator resveratrol and si-PKCζ to identify the switches in metabolism. Although PA reduced CD36 and increased GLUT4 metabolic pathway proteins, when we pretreated cells with resveratrol to activate SIRT1 or transfected si-PKCζ, both were able to significantly increase CD36 metabolic pathway proteins and reduce GLUT4 pathway proteins. High-fat diets affect energy metabolism pathways in both normal and aging rats and involve switching the energy source from the CD36 pathway to GLUT4. In conclusion, PA and high-fat diets cause lipotoxicity in vivo and in vitro and adversely switch the energy source from the CD36 pathway to the GLUT4 pathway. PMID:27133433

  10. CD38 Deficiency Protects the Heart from Ischemia/Reperfusion Injury through Activating SIRT1/FOXOs-Mediated Antioxidative Stress Pathway

    Science.gov (United States)

    Guan, Xiao-Hui; Liu, Xiao-Hong; Hong, Xuan; Zhao, Ning; Xiao, Yun-Fei; Wang, Ling-Fang; Qian, Yi-Song; Deng, Ke-Yu; Ji, Guangju; Fu, Mingui

    2016-01-01

    Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac muscle. We previously observed that CD38 deficiency remarkably protects mouse embryonic fibroblasts (MEFs) from oxidative stress-induced injury. However, whether CD38 deficiency protects from I/R injury in the heart is not explored. Here, we showed that the hearts of CD38 deficient mice or wild type mice supplied with exogenous NAD were significantly protected from ischemia/reperfusion injury, seen as reduction of the myocardial infarct sizes when the mice were subjected to 30 min ischemia followed by 24 hours of reperfusion. Consistently, the protection of CD38 deficiency on hypoxia/reoxygenation (H/R) injury was confirmed with a CD38 knockdown H9c2 stable cell line. Furthermore, we observed that knockdown of CD38 remarkably inhibited ROS generation and intracellular Ca2+ overloading induced by H/R in H9c2 cells. The FOXO1 and FOXO3 expressions were significantly elevated by H/R injury in CD38 knockdown cells compared with normal H9c2 cells. The cell immunofluorescence assay showed that FOXO1 nuclear translocation was significantly increased in CD38 knockdown H9c2 cells. In addition, we demonstrated that the increase of FOXO1 nuclear translocation was associated with the increased expressions of antioxidant catalase and SOD2 and the attenuated expression of the ROS generation enzyme NOX4. In conclusion, our results provide new evidence that CD38 deficiency protects the heart from I/R injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. PMID:27547294

  11. Deficiency in type 1 insulin-like growth factor receptor in mice protects against oxygen-induced lung injury

    Directory of Open Access Journals (Sweden)

    Flejou Jean-François

    2005-04-01

    Full Text Available Abstract Background Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R. Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent deleterious effects of oxygen exposure. Methods Since IGF-1R null mutant mice die at birth from respiratory failure, we generated compound heterozygous mice harboring a hypomorphic (Igf-1rneo and a knockout (Igf-1r- receptor allele. These IGF-1Rneo/- mice, strongly deficient in IGF-1R, were subjected to hyperoxia and analyzed for survival time, ventilatory control, pulmonary histopathology, morphometry, lung edema and vascular permeability. Results Strikingly, after 72 h of exposure to 90% O2, IGF-1Rneo/- mice had a significantly better survival rate during recovery than IGF-1R+/+ mice (77% versus 53%, P neo/- mice which developed conspicuously less edema and vascular extravasation than controls. Also, hyperoxia-induced abnormal pattern of breathing which precipitated respiratory failure was elicited less frequently in the IGF-1Rneo/- mice. Conclusion Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury.

  12. LXRs激动剂T0901317对成人骨骼肌细胞FAT/CD36基因mRNA表达的影响%EFFECT OF LIVER X RECEPTORS AGONISTS T0901317 ON EXPRESSION OF FAT/CD36 GENE mRNA IN ADULT HUMAN SKELETAL MUSCLE CELL

    Institute of Scientific and Technical Information of China (English)

    曾蓉; 撒亚莲; 严新民

    2009-01-01

    目的:探讨肝核受体LXRs激动剂T0901317对正常人骨骼肌细胞中FAT/CD36基因mRNA表达的影响.方法:将原代培养的5例成人骨骼肌细胞分为用肝核受体LXRs激动剂T0901317(1 μmol/L)作用组、T0901317(0.5μmol/L)作用组和阴性对照组,作用24 h后采用SYBR Green Ⅰ实时荧光定量PCR法检测各组成人骨骼肌细胞FAT/CD36基因mRNA表达水平,并用2-△△Ct方法进行比较分析.结果:①以浓度为1 μmol/L的T0901317作用组和0.5μmol/L的T090131作用组和对照组样本的均数进行方差分析,差别有统计学意义(P<0.01).②浓度为1μmol/L的T0901317作用组和0.5 μmol/L的T090131作用组成人骨骼肌细胞中FAT/CD36基因的mRNA表达分别是对照组的3.03倍和2.91倍.结论:肝核受体LXRs激动剂T0901317能够提高成人骨骼肌细胞中FAT/CD36基因mRNA的表达水平,提示T0901317有加快骨骼肌细胞内脂肪酸的堆积作用,推测LXRs激动剂T0901317可能会增加糖尿病患者骨骼肌胰岛素抵抗的风险.

  13. The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation.

    Science.gov (United States)

    Holmes, Amie L; Joyce, Kellie; Xie, Hong; Falank, Carolyne; Hinz, John M; Wise, John Pierce

    2014-04-01

    Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation. PMID:24561002

  14. Associations between Orosensory Perception of Oleic Acid, the Common Single Nucleotide Polymorphisms (rs1761667 and rs1527483 in the CD36 Gene, and 6-n-Propylthiouracil (PROP Tasting

    Directory of Open Access Journals (Sweden)

    Melania Melis

    2015-03-01

    Full Text Available Orosensory perception of dietary fat varies in individuals, thus influencing nutritional status. Several studies associated fat detection and preference with CD36 or 6-n-propylthiouracil (PROP sensitivity. Other studies have not confirmed the latter association. We analyzed the relationship between orosensory perception of oleic acid, two CD36 variants, and PROP tasting. Thresholds of oleic acid perception were assessed in 64 subjects using a modification of the three-alternative forced-choice procedure. Subjects were classified for PROP taster status and genotyped for TAS2R38 and CD36 (SNPs: rs1761667 and rs1527483. Subjects homozygous for GG of the rs1761667 polymorphism showed higher sensitivity to oleic acid than AA subjects. The capability to detect oleic acid was directly associated with TAS2R38 or PROP responsiveness. PROP non-tasters had a lower papilla density than tasters, and those with genotype GG of the rs1761667 polymorphism had lower oleic acid thresholds than PROP non-tasters with genotype AA. In conclusion, results showed a direct association between orosensory perception of oleic acid and PROP tasting or rs1761667 polymorphism of CD36, which play a significant role in PROP non-tasters, given their low number of taste papillae. Characterization of individual capability to detect fatty acids may have important nutritional implications by explaining variations in human fat preferences.

  15. A MATE-family efflux pump rescues the Escherichia coli 8-oxoguanine-repair-deficient mutator phenotype and protects against H(2O(2 killing.

    Directory of Open Access Journals (Sweden)

    Javier R Guelfo

    2010-05-01

    Full Text Available Hypermutation may accelerate bacterial evolution in the short-term. In the long-term, however, hypermutators (cells with an increased rate of mutation can be expected to be at a disadvantage due to the accumulation of deleterious mutations. Therefore, in theory, hypermutators are doomed to extinction unless they compensate the elevated mutational burden (deleterious load. Different mechanisms capable of restoring a low mutation rate to hypermutators have been proposed. By choosing an 8-oxoguanine-repair-deficient (GO-deficient Escherichia coli strain as a hypermutator model, we investigated the existence of genes able to rescue the hypermutable phenotype by multicopy suppression. Using an in vivo-generated mini-MudII4042 genomic library and a mutator screen, we obtained chromosomal fragments that decrease the rate of mutation in a mutT-deficient strain. Analysis of a selected clone showed that the expression of NorM is responsible for the decreased mutation rate in 8-oxoguanine-repair-deficient (mutT, mutY, and mutM mutY strains. NorM is a member of the multidrug and toxin extrusion (MATE family of efflux pumps whose role in E. coli cell physiology remains unknown. Our results indicate that NorM may act as a GO-system backup decreasing AT to CG and GC to TA transversions. In addition, the ability of NorM to reduce the level of intracellular reactive oxygen species (ROS in a GO-deficient strain and protect the cell from oxidative stress, including protein carbonylation, suggests that it can extrude specific molecules-byproducts of bacterial metabolism-that oxidize the guanine present in both DNA and nucleotide pools. Altogether, our results indicate that NorM protects the cell from specific ROS when the GO system cannot cope with the damage.

  16. P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation

    OpenAIRE

    Rosenkranz, Alexander R.; Donna L. Mendrick; Cotran, Ramzi S.; Mayadas, Tanya N.

    1999-01-01

    P-selectin is a leukocyte adhesion receptor present in endothelial cells and platelets. We examined the role of P-selectin in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis using P-selectin–deficient mice and chimeric mice expressing P-selectin only in platelets or endothelial cells. P-selectin–deficient mice exhibited more severe glomerular damage with increased interstitial mononuclear leukocytic infiltrates, and had significantly ...

  17. Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge

    Science.gov (United States)

    Liu, Qiong; Liu, Qing; Yi, Jie; Liang, Kang; Hu, Bo; Zhang, Xiangmin; Curtiss, Roy; Kong, Qingke

    2016-01-01

    Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine. PMID:27698383

  18. Genetic variation in CD36, HBA, NOS3 and VCAM1 is associated with chronic haemolysis level in sickle cell anaemia: a longitudinal study.

    Science.gov (United States)

    Coelho, Andreia; Dias, Alexandra; Morais, Anabela; Nunes, Baltazar; Ferreira, Emanuel; Picanço, Isabel; Faustino, Paula; Lavinha, João

    2014-03-01

    Chronic haemolysis stands out as one of the hallmarks of sickle cell anaemia, a clinically heterogeneous autosomal recessive monogenic anaemia. However, the genetic architecture of this sub-phenotype is still poorly understood. Here, we report the results of an association study between haemolysis biomarkers (serum LDH, total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants of ten candidate genes in a series of 99 paediatric SS patients (median current age of 9.9 yr) followed up in two general hospitals in Greater Lisboa area (median follow-up per patient of 5.0 yr). Although in a large number of tests a seemingly significant (i.e. P haplotype 7 within VCAM1 gene; (ii) a lower total bilirubin was associated with the 3.7-kb deletion at HBA gene, rs2070744_T allele at NOS3 gene, and haplotype 9 within VCAM1 promoter; and (iii) a diminished reticulocyte count was associated with the 3.7-kb deletion at HBA, whereas an increased count was associated with rs1984112_G allele at CD36 gene. On the whole, our findings suggest a complex genetic architecture for the sickle cell anaemia haemolysis process involving multiple pathways, namely control of vascular cell adhesion, NO synthesis and erythrocyte volume and haemoglobinisation. PMID:24168396

  19. CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

    DEFF Research Database (Denmark)

    Magistrado, Pamela; Staalsoe, Trine; Theander, Thor;

    2008-01-01

    phenotype of the 3D7SM parasites was determined by flow cytometry using malaria semi-immune and immune plasma and transcription of the 59 var genes in 3D7 were analysed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using var-specific primers. RESULTS: A selection......ABSTRACT: BACKGROUND: A subset of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1SM) is involved in the cytoadherence of P. falciparum-infected red blood cells (iRBC) contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1SM...... - a major cytoadhesion phenotype of P. falciparum isolates. METHODS: A 3D7 PfEMP1SM sub-line (3D7SM) expressing VAR4 (PFD1235w/MAL8P1.207) was selected for binding to CD36. The protein expression of this parasite line was monitored by surface staining of iRBC using VAR4-specific antibodies. The serological...

  20. Plasmodium chabaudi-Infected Erythrocytes Adhere to CD36 and Bind to Microvascular Endothelial Cells in an Organ-Specific Way

    Science.gov (United States)

    Mota, Maria M.; Jarra, William; Hirst, Elizabeth; Patnaik, Pradeep K.; Holder, Anthony A.

    2000-01-01

    Adherence of erythrocytes infected with Plasmodium falciparum to microvascular endothelial cells (sequestration) is considered to play an important role in parasite virulence and pathogenesis. However, the real importance of sequestration for infection and disease has never been fully assessed. The absence of an appropriate in vivo model for sequestration has been a major barrier. We have examined the rodent malaria parasite Plasmodium chabaudi chabaudi AS in mice as a potential model. Erythrocytes infected with this parasite adhere in vitro to purified CD36, a critical endothelium receptor for binding P. falciparum-infected erythrocytes. P. c. chabaudi-infected erythrocytes adhere in vitro to endothelial cells in a gamma interferon-dependent manner, suggesting the involvement of additional adhesion molecules in the binding process, as is also the case with P. falciparum-infected cells. Furthermore, plasma or sera from infected and hyperimmune mice, respectively, have the ability to block binding of infected erythrocytes to endothelial cells. In vivo, erythrocytes containing mature P. c. chabaudi parasites are sequestered from the peripheral circulation. Sequestration is organ specific, occurring primarily in the liver, although intimate contact between infected erythrocytes and endothelial cells is also observed in the spleen and brain. The results are discussed in the context of the use of this model to study (i) the relationship between endothelial cell activation and the level of sequestration and (ii) the primary function of sequestration in malaria infection. PMID:10858230

  1. Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders.

    Science.gov (United States)

    Schaevitz, Laura R; Picker, Jonathan D; Rana, Jasmine; Kolodny, Nancy H; Shane, Barry; Berger-Sweeney, Joanne E; Coyle, Joseph T

    2012-06-01

    Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidase II (GCPII) and dietary folic acid deficiency. In addition to serving as a neuropeptidase, GCPII catalyzes the absorption of folate. GCPII and folate depletion interact within the one-carbon metabolic pathway and/or of modulate the glutamatergic system. Four groups of mice were tested: wild-type, GCPII hypomorphs, and wild-types and GCPII hypomorphs both fed a folate deficient diet. Due to sex differences in the prevalence of SZ and AD, both male and female mice were assessed on a number of behavioral tasks including locomotor activity, rotorod, social interaction, prepulse inhibition, and spatial memory. Wild-type mice of both sexes fed a folic acid deficient diet showed motor coordination impairments and cognitive deficits, while social interactions were decreased only in males. GCPII mutant mice of both sexes also exhibited reduced social propensities. In contrast, all folate-depleted GCPII hypomorphs performed similarly to untreated wild-type mice, suggesting that reduced GCPII expression and folate deficiency are mutually protective. Analyses of folate and neurometabolite levels associated with glutamatergic function suggest several potential mechanisms through which GCPII and folate may be interacting to create this protective effect.

  2. DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function.

    Science.gov (United States)

    Zhao, Jie; Shi, Peiliang; Sun, Ye; Sun, Jing; Dong, Jian-Ning; Wang, Hong-Gang; Zuo, Lu-Gen; Gong, Jian-Feng; Li, Yi; Gu, Li-Li; Li, Ning; Li, Jie-Shou; Zhu, Wei-Ming

    2015-07-01

    A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.

  3. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    Osama El-Assal; Feng Hong; Won-Ho Kim; Svetlana Radaeva; Bin Gao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes via induction of metallothionein protein expression, which may account for the protective role of IL-6 in alcoholic liver disease.

  4. IRS1 deficiency protects β-cells against ER stress-induced apoptosis by modulating sXBP-1 stability and protein translation.

    Science.gov (United States)

    Takatani, Tomozumi; Shirakawa, Jun; Roe, Michael W; Leech, Colin A; Maier, Bernhard F; Mirmira, Raghavendra G; Kulkarni, Rohit N

    2016-01-01

    Endoplasmic reticulum (ER) stress is among several pathological features that underlie β-cell failure in the development of type 1 and type 2 diabetes. Adaptor proteins in the insulin/insulin-like-growth factor-1 signaling pathways, such as insulin receptor substrate-1 (IRS1) and IRS2, differentially impact β-cell survival but the underlying mechanisms remain unclear. Here we report that β-cells deficient in IRS1 (IRS1KO) are resistant, while IRS2 deficiency (IRS2KO) makes them susceptible to ER stress-mediated apoptosis. IRS1KOs exhibited low nuclear accumulation of spliced XBP-1 due to its poor stability, in contrast to elevated accumulation in IRS2KO. The reduced nuclear accumulation in IRS1KO was due to protein instability of Xbp1 secondary to proteasomal degradation. IRS1KO also demonstrated an attenuation in their general translation status in response to ER stress revealed by polyribosomal profiling. Phosphorylation of eEF2 was dramatically increased in IRS1KO enabling the β-cells to adapt to ER stress by blocking translation. Furthermore, significantly high ER calcium (Ca(2+)) was detected in IRS1KO β-cells even upon induction of ER stress. These observations suggest that IRS1 could be a therapeutic target for β-cell protection against ER stress-mediated cell death by modulating XBP-1 stability, protein synthesis, and Ca(2+) storage in the ER. PMID:27378176

  5. Genetically Engineered Ascorbic acid-deficient Live Mutants of Leishmania donovani induce long lasting Protective Immunity against Visceral Leishmaniasis.

    Science.gov (United States)

    Anand, Sneha; Madhubala, Rentala

    2015-06-02

    Visceral leishmaniasis caused by Leishmania donovani is the most severe systemic form of the disease. There are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. Recently, we reported functional importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from L. donovani involved in ascorbate biosynthesis pathway. In this study, we have shown that ΔALO parasites do not affect the ability of null mutants to invade visceral organs but severely impair parasite persistence beyond 16 week in BALB/c mice and hence are safe as an immunogen. Both short term (5 week) and long term (20 week) immunization with ΔALO parasites conferred sustained protection against virulent challenge in BALB/c mice, activated splenocytes and resulted in induction of pro-inflammatory cytokine response. Protection in immunized mice after challenge correlated with the stimulation of IFN-γ producing CD4(+) and CD8(+) T cells. Antigen-mediated cell immunity correlated with robust nitrite and superoxide generation, macrophage-derived oxidants critical in controlling Leishmania infection. Our data shows that live attenuated ΔALO parasites are safe, induce protective immunity and can provide sustained protection against Leishmania donovani. We further conclude that the parasites attenuated in their anti-oxidative defence mechanism can be exploited as vaccine candidates.

  6. Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice.

    Directory of Open Access Journals (Sweden)

    Nicolas Bréchot

    Full Text Available BACKGROUND: Macrophages, key regulators of healing/regeneration processes, strongly infiltrate ischemic tissues from patients suffering from critical limb ischemia (CLI. However pro-inflammatory markers correlate with disease progression and risk of amputation, suggesting that modulating macrophage activation state might be beneficial. We previously reported that thrombospondin-1 (TSP-1 is highly expressed in ischemic tissues during CLI in humans. TSP-1 is a matricellular protein that displays well-known angiostatic properties in cancer, and regulates inflammation in vivo and macrophages properties in vitro. We therefore sought to investigate its function in a mouse model of CLI. METHODS AND FINDINGS: Using a genetic model of tsp-1(-/- mice subjected to femoral artery excision, we report that tsp-1(-/- mice were clinically and histologically protected from necrosis compared to controls. Tissue protection was associated with increased postischemic angiogenesis and muscle regeneration. We next showed that macrophages present in ischemic tissues exhibited distinct phenotypes in tsp-1(-/- and wt mice. A strong reduction of necrotic myofibers phagocytosis was observed in tsp-1(-/- mice. We next demonstrated that phagocytosis of muscle cell debris is a potent pro-inflammatory signal for macrophages in vitro. Consistently with these findings, macrophages that infiltrated ischemic tissues exhibited a reduced postischemic pro-inflammatory activation state in tsp-1(-/- mice, characterized by a reduced Ly-6C expression and a less pro-inflammatory cytokine expression profile. Finally, we showed that monocyte depletion reversed clinical and histological protection from necrosis observed in tsp-1(-/- mice, thereby demonstrating that macrophages mediated tissue protection in these mice. CONCLUSION: This study defines targeting postischemic macrophage activation state as a new potential therapeutic approach to protect tissues from necrosis and promote tissue

  7. p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation

    Science.gov (United States)

    Ammon-Treiber, Susanne; Schwab, Matthias; Piekorz, Roland P.; Hirsch, Emilio; Nürnberg, Bernd; Beer-Hammer, Sandra

    2016-01-01

    The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γKOδD910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation. PMID:27442134

  8. Perilipin1 deficiency in whole body or bone marrow-derived cells attenuates lesions in atherosclerosis-prone mice.

    Directory of Open Access Journals (Sweden)

    Xiaojing Zhao

    Full Text Available The objective of this study is to determine the role of perilipin 1 (Plin1 in whole body or bone marrow-derived cells on atherogenesis.Accumulated evidence have indicated the role of Plin1 in atherosclerosis, however, these findings are controversial. In this study, we showed that Plin1 was assembled and colocalized with CD68 in macrophages in atherosclerotic plaques of ApoE-/- mice. We further found 39% reduction of plaque size in the aortic roots of Plin1 and ApoE double knockout (Plin1-/-ApoE-/- females compared with ApoE-/- female littermates. In order to verify whether this reduction was macrophage-specific, the bone marrow cells from wild-type or Plin1 deficient mice (Plin1-/- were transplanted into LDL receptor deficient mice (LDLR-/-. Mice receiving Plin1-/- bone marrow cells showed also 49% reduction in aortic atherosclerotic lesions compared with LDLR-/- mice received wild-type bone marrow cells. In vitro experiments showed that Plin1-/- macrophages had decreased protein expression of CD36 translocase and an enhanced cholesterol ester hydrolysis upon aggregated-LDL loading, with unaltered expression of many other regulators of cholesterol metabolism, such as cellular lipases, and Plin2 and 3. Given the fundamental role of Plin1 in protecting LD lipids from lipase hydrolysis, it is reasonably speculated that the assembly of Plin1 in microphages might function to reduce lipolysis and hence increase lipid retention in ApoE-/- plaques, but this pro-atherosclerotic property would be abrogated on inactivation of Plin1.Plin1 deficiency in bone marrow-derived cells may be responsible for reduced atherosclerotic lesions in the mice.

  9. Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation

    OpenAIRE

    Langhauser, Friederike; Göb, Eva; Kraft, Peter; Geis, Christian; Schmitt, Joachim; Brede, Marc; Göbel, Kerstin; Helluy, Xavier; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Stoll, Guido; Meuth, Sven G.; Nieswandt, Bernhard; McCrae, Keith R.

    2012-01-01

    Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng−/− mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG defic...

  10. S-Propargyl-cysteine Exerts a Novel Protective Effect on Methionine and Choline Deficient Diet-Induced Fatty Liver via Akt/Nrf2/HO-1 Pathway

    Directory of Open Access Journals (Sweden)

    Wenwen Li

    2016-01-01

    Full Text Available This study investigated the antioxidative effect of S-propargyl-cysteine (SPRC on nonalcoholic fatty liver (NAFLD by treating mice fed a methionine and choline deficient (MCD diet with SPRC for four weeks. We found that SPRC significantly reduced hepatic reactive oxygen species (ROS and methane dicarboxylic aldehyde (MDA levels. Moreover, SPRC also increased the superoxide dismutase (SOD activity. By Western blot, we found that this protective effect of SPRC was importantly attributed to the regulated hepatic antioxidant-related proteins, including protein kinase B (Akt, heme oxygenase-1 (HO-1, nuclear factor erythroid 2-related factor 2 (Nrf2, and cystathionine γ-lyase (CSE, an enzyme that synthesizes hydrogen sulfide. Next, we examined the detailed molecular mechanism of the SPRC protective effect using oleic acid- (OA- induced HepG2 cells. The results showed that SPRC significantly decreased intracellular ROS and MDA levels in OA-induced HepG2 cells by upregulating the phosphorylation of Akt, the expression of HO-1 and CSE, and the translocation of Nrf2. SPRC-induced HO-1 expression and Nrf2 translocation were abolished by the phosphoinositide 3-kinase (PI3K inhibitor LY294002. Moreover, the antioxidative effect of SPRC was abolished by CSE inhibitor DL-propargylglycine (PAG and HO-1 siRNA. Therefore, these results proved that SPRC produced an antioxidative effect on NAFLD through the PI3K/Akt/Nrf2/HO-1 signaling pathway.

  11. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    OsamaEl-Assal; FengHong; Won-HoKim; SvetlanaRadaeva; BinGao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however,the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes v/a induction of metallothionein protein expression, which mav account for the nrotective role of IL-6 in alcoholic liver disease.

  12. Liver-protecting and fibrosis-resisting effect of Ganxianning on rats withspleen deficiency and stagnation of Liver-qi

    Institute of Scientific and Technical Information of China (English)

    Zhen Qiu Guo; Xiao Wei Zhao; Xin Yu Chen

    2000-01-01

    AIM To study the liver-protecting and fibrosis-resisting effect of Ganxianning (GXN) and its mechanism.METHODS Model of carbon tetrachloride hepatic injury fibrosis rats was reproduced. In the experimentthere were six groups, the treatment groups with GXN's large, moderate and small dose (GXNb, GXNm andGXNs), the treatment group with colchicine, the blank model group and normal control group. The course of treatment was 30 days, then the rats were killed with their blood and liver tested.RESULTS In treatment groups, alanine aminotransferase (ALT) was lower than that in the model group(P<0.01), and albumin (Alb) higher than that in the model (P<0.01). Hydroxylproline (Hyp) and redcell membrane C3B receptor garland in GXNb's and GXNm's groups were lower and circulation complex(CIC) was slightly higher. Fibrinogen (Fb) in both colchicine and model groups was higher than that innormal group and the difference was significant (P<0.05, P<0.01). Compared with model group, acid-α-naphthyl acetate esterase (ANAE) increased in GXNb's and GXNm's groups (P<0.05, P<0.01). Underlight and electron microscopes, level of hepatic fibrosis of GXN groups was much lower than that of themodel group, P<0.01, and their difference was very significant. In GXNms group, liver cell was normal onthe whole and its chromatin was more than the model group and its nucleolus was evident.CONCLUSION GXN has rather good functions of protecting liver and resisting fibrosis, and thesefunctions are related to the increase of ANAE and C3b, decrease of CIC and Fb. and improvement of bodyimmunity function.

  13. Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya

    2016-05-01

    Full Text Available Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which in C. neoformans is predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA genes have to be deleted to generate a chitosan-deficient C. neoformans strain. This cda1Δ2Δ3Δ strain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of the cda1Δ2Δ3Δ strain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in the cda1Δ2Δ3Δ strain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-type C. neoformans strain. Moreover, protective immunity was also induced in mice vaccinated with heat-killed cda1Δ2Δ3Δ cells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop the cda1Δ2Δ3Δ strain as a potential vaccine candidate for C. neoformans infection.

  14. Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans

    Science.gov (United States)

    Upadhya, Rajendra; Lam, Woei C.; Maybruck, Brian; Specht, Charles A.; Levitz, Stuart M.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which in C. neoformans is predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA) genes have to be deleted to generate a chitosan-deficient C. neoformans strain. This cda1Δ2Δ3Δ strain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of the cda1Δ2Δ3Δ strain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in the cda1Δ2Δ3Δ strain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-type C. neoformans strain. Moreover, protective immunity was also induced in mice vaccinated with heat-killed cda1Δ2Δ3Δ cells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop the cda1Δ2Δ3Δ strain as a potential vaccine candidate for C. neoformans infection. PMID:27165801

  15. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression

    Science.gov (United States)

    Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramírez, Cristina M.; He, Shun; Chousterman, Benjamin G.; Fenn, Ashley M.; Wanschel, Amarylis; Madrigal-Matute, Julio; Warrier, Nikhil; Martín-Ventura, Jose L.; Swirski, Filip K.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2016-07-01

    Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

  16. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS.

    Science.gov (United States)

    Zhao, Linjing; Wu, Hongbing; Qiu, Mingfeng; Sun, Wei; Wei, Runmin; Zheng, Xiaojiao; Yang, Yiting; Xin, Xue; Zou, Haimiao; Chen, Tianlu; Liu, Jiajian; Lu, Lina; Su, Jing; Ma, Chungwah; Zhao, Aihua; Jia, Wei

    2013-01-01

    Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine), lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol), gut microbiota metabolism (indole-3-propionic acid), biosynthesis of catecholamine (norepinephrine), and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH), and urine 17-hydroxycorticosteroids (17-OHCS). PMID:24159348

  17. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

    Directory of Open Access Journals (Sweden)

    Linjing Zhao

    2013-01-01

    Full Text Available Kidney Yang Deficiency Syndrome (KDS-Yang, a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine, lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol, gut microbiota metabolism (indole-3-propionic acid, biosynthesis of catecholamine (norepinephrine, and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH, and urine 17-hydroxycorticosteroids (17-OHCS.

  18. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Milos Lazic

    Full Text Available 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

  19. Caracterización del papel de la ácido graso translocasa CD36 en la enfermedad hepática grasa no alcohólica y en la hepatitis crónica por virus C

    OpenAIRE

    Fernández Bermejo, Miguel

    2014-01-01

    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 04-12-2014 Introducción: La ácido graso translocasa CD36 facilita la captación y el transporte intracelular de los ácidos grasos de cadena larga en diversos tipos celulares. En modelos animales de esteatosis hepática, su expresión está aumentada en los hepatocitos, acompañándose su translocación a la membrana plasmática de un incremento en la incorporación he...

  20. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor.

    Science.gov (United States)

    Zhang, Chongben; Cooper, Daniel E; Grevengoed, Trisha J; Li, Lei O; Klett, Eric L; Eaton, James M; Harris, Thurl E; Coleman, Rosalind A

    2014-08-01

    Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4(-/-) mice were more glucose tolerant and were protected from insulin resistance. Overexpression of GPAT4 in mouse hepatocytes impaired insulin-suppressed gluconeogenesis and insulin-stimulated glycogen synthesis. Impaired glucose homeostasis was coupled to inhibited insulin-stimulated phosphorylation of Akt(Ser⁴⁷³) and Akt(Thr³⁰⁸). GPAT4 overexpression inhibited rictor's association with the mammalian target of rapamycin (mTOR), and mTOR complex 2 (mTORC2) activity. Compared with overexpressed GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4(-/-) hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4(-/-) hepatocytes was lower than in controls, with the greatest decrease in 16:0-PA species. Compared with controls, liver and skeletal muscle from Gpat4(-/-)-deficient mice fed a high-fat diet were more insulin sensitive and had a lower hepatic content of di16:0-PA. Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely di16:0-PA, impairs insulin signaling in mouse liver and contributes to hepatic insulin resistance. PMID:24939733

  1. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor.

    Science.gov (United States)

    Zhang, Chongben; Cooper, Daniel E; Grevengoed, Trisha J; Li, Lei O; Klett, Eric L; Eaton, James M; Harris, Thurl E; Coleman, Rosalind A

    2014-08-01

    Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4(-/-) mice were more glucose tolerant and were protected from insulin resistance. Overexpression of GPAT4 in mouse hepatocytes impaired insulin-suppressed gluconeogenesis and insulin-stimulated glycogen synthesis. Impaired glucose homeostasis was coupled to inhibited insulin-stimulated phosphorylation of Akt(Ser⁴⁷³) and Akt(Thr³⁰⁸). GPAT4 overexpression inhibited rictor's association with the mammalian target of rapamycin (mTOR), and mTOR complex 2 (mTORC2) activity. Compared with overexpressed GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4(-/-) hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4(-/-) hepatocytes was lower than in controls, with the greatest decrease in 16:0-PA species. Compared with controls, liver and skeletal muscle from Gpat4(-/-)-deficient mice fed a high-fat diet were more insulin sensitive and had a lower hepatic content of di16:0-PA. Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely di16:0-PA, impairs insulin signaling in mouse liver and contributes to hepatic insulin resistance.

  2. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. Howeve

  3. Iron deficiency.

    Science.gov (United States)

    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.

  4. Vitamin B12 status in older adults living in Ontario long-term care homes: prevalence and incidence of deficiency with supplementation as a protective factor.

    Science.gov (United States)

    Pfisterer, Kaylen J; Sharratt, Mike T; Heckman, George G; Keller, Heather H

    2016-02-01

    Vitamin B12 (B12) deficiency, although treatable, impacts up to 43% of community-living older adults; long-term care (LTC) residents may be at greater risk. Recommendations for screening require further evidence on prevalence and incidence in LTC. Small, ungeneralizable samples provide a limited perspective on these issues. The purposes of this study were to report prevalence of B12 deficiency at admission to LTC, incidence 1 year post-admission, and identify subgroups with differential risk. This multi-site (8), retrospective prevalence study used random proportionate sampling of resident charts (n = 412). Data at admission extracted included demographics, B12 status, B12 supplementation, medications, diagnoses, functional independence, cognitive performance, and nutrition. Prevalence at admission of B12 deficiency (300 pmol/L). One year post-admission incidence was 4%. Better B12 status was significantly associated with supplementation use prior to LTC admission. Other characteristics were not associated with status. This work provides a better estimate of B12 deficiency prevalence than previously available for LTC, upon which to base protocols and policy. Prospective studies are needed to establish treatment efficacy and effect on health related outcomes. PMID:26781161

  5. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

    OpenAIRE

    Linjing Zhao; Hongbing Wu; Mingfeng Qiu; Wei Sun; Runmin Wei; Xiaojiao Zheng; Yiting Yang; Xue Xin; Haimiao Zou; Tianlu Chen; Jiajian Liu; Lina Lu; Jing Su; Chungwah Ma; Aihua Zhao

    2013-01-01

    Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrome...

  6. Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Esther K. Wolthuis

    2012-01-01

    Full Text Available Preventing tissue-factor-(TF- mediated systemic coagulopathy improves outcome in models of sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate ventilator-induced lung injury (VILI. We investigated the effect of relative TF deficiency on pulmonary coagulopathy and inflammation in a murine model of VILI. Heterozygous TF knockout (TF+/− mice and their wild-type (TF+/+ littermates were sedated (controls or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours. Mechanical ventilation resulted in pulmonary coagulopathy and inflammation, with more injury after mechanical ventilation with higher tidal volumes. Compared with TF+/+ mice, TF+/− mice demonstrated significantly lower pulmonary thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in lung wet-to-dry ratio, BALF total protein levels, neutrophil influx, and lung histopathology scores between TF+/− and TF+/+ mice. Notably, pulmonary levels of cytokines were significantly higher in TF+/− as compared to TF+/+ mice. Systemic levels of cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.

  7. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    DEFF Research Database (Denmark)

    Zhang, Chongben; Cooper, Daniel E; Grevengoed, Trisha J;

    2014-01-01

    GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4(-/-) hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4(-/-) hepatocytes was lower than in controls, with the greatest...... decrease in 16:0-PA species. Compared with controls, liver and skeletal muscle from Gpat4(-/-)-deficient mice fed a high-fat diet were more insulin sensitive and had a lower hepatic content of di16:0-PA. Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely di16:0-PA, impairs...

  8. 高糖高棕榈酸培养对β细胞脂质含量及脂肪酸转位酶表达的影响%Effects of supraphysiologic glucose and palmitate on the content of intracellular triglyceride and expression of FAT/CD36 in β-cells

    Institute of Scientific and Technical Information of China (English)

    李燕; 陈璐璐; 黎慧清; 王咏波; 田源

    2008-01-01

    目的 研究高糖高棕榈酸(PA)培养对β细胞脂质含量及脂肪酸转位酶(FAT/CD36)表达的影响.方法 NIT-1细胞分别以5mmol/L葡萄糖(NC组)、25mmol/L葡萄糖(HG组)、0.25mmol/L PA+5mmol/L葡萄糖(HP组)及0.25mmol/L PA+25mmol/L葡萄糖(GP组)培养24h后,测定细胞内甘油三酯(TG)含量、胰岛素分泌以及FAT/CD36 mRNA与蛋白的表达.结果 (1)与NC组比较,各处理组细胞内TG含量增加,而葡萄糖刺激的胰岛素分泌下降,以GP组变化最明显.(2)在高糖孵育下, HG组和GP组FAT/CD36mRNA与蛋白表达均较NC组显著增加(P<0.01),但HP和GP组与相应的葡萄糖组比较,FAT/CD36表达无明显变化.结论 在高棕榈酸的环境下,高糖可进一步促进β细胞脂质沉积,抑制葡萄糖刺激的胰岛素分泌;其中高糖上调脂肪酸转位酶表达可能是其重要机制之一.

  9. Experimental study of effect of liver X receptors agonists T0901317 on expression of FAT/CD36 gene mRNA in SD rat skeletal muscle cell%肝核受体激动剂T0901317对大鼠骨骼肌细胞脂肪酸转运酶基因表达影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    曾蓉; 严新民; 高建梅

    2009-01-01

    目的 探讨肝核受体(LXRs)激动剂T0901317对正常SD大鼠骨骼肌细胞中脂肪酸较运酶(FAT/CD36)基因mRNA表述的影响.方法 将原代培养的5只SD大鼠骨骼肌细胞分为T0901317 1μmol/L作用组、0.5μmol/L作用组和未作用(阴性对照)组,采用SYBR Green I实时荧光定量聚合酶链反应(PCR)法检测各组SD大鼠骨骼肌细胞FAT/CD36基因mRNA表达水平,并进行比较分析.结果 1μmol/L、0.5μmol/L作用组与阴性对照组比较,差异无显著性意义(P=0.116).结论 LXRs激动剂39901317对SD大鼠骨骼肌细胞中FAT/CD36基因mRNA的表达水平没有明显作用,提示T0901317在促进SD大鼠骨骼肌细胞内脂肪酸的堆积作用尚无确切的证据.

  10. Iron deficiency and iron deficiency anemia in women.

    Science.gov (United States)

    Coad, Jane; Pedley, Kevin

    2014-01-01

    Iron deficiency is one of the most common nutritional problems in the world and disproportionately affects women and children. Stages of iron deficiency can be characterized as mild deficiency where iron stores become depleted, marginal deficiency where the production of many iron-dependent proteins is compromised but hemoglobin levels are normal and iron deficiency anemia where synthesis of hemoglobin is decreased and oxygen transport to the tissues is reduced. Iron deficiency anemia is usually assessed by measuring hemoglobin levels but this approach lacks both specificity and sensitivity. Failure to identify and treat earlier stages of iron deficiency is concerning given the neurocognitive implications of iron deficiency without anemia. Most of the daily iron requirement is derived from recycling of senescent erythrocytes by macrophages; only 5-10 % comes from the diet. Iron absorption is affected by inhibitors and enhancers of iron absorption and by the physiological state. Inflammatory conditions, including obesity, can result in iron being retained in the enterocytes and macrophages causing hypoferremia as a strategic defense mechanism to restrict iron availability to pathogens. Premenopausal women usually have low iron status because of iron loss in menstrual blood. Conditions which further increase iron loss, compromise absorption or increase demand, such as frequent blood donation, gastrointestinal lesions, athletic activity and pregnancy, can exceed the capacity of the gastrointestinal tract to upregulate iron absorption. Women of reproductive age are at particularly high risk of iron deficiency and its consequences however there is a controversial argument that evolutionary pressures have resulted in an iron deficient phenotype which protects against infection.

  11. Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response.

    Science.gov (United States)

    Uzonna, Jude E; Späth, Gerald F; Beverley, Stephen M; Scott, Phillip

    2004-03-15

    Long-term immunity to Leishmania may require the continued presence of parasites, but previous attempts to create attenuated parasites that persist without causing disease have had limited success. Since Leishmania major mutants that lack lipophosphoglycan and other secreted phosphoglycans, termed lpg2-, persist indefinitely in infected mice without inducing any disease, we tested their ability to provide protection to virulent L. major challenge. In response to leishmanial Ag stimulation, cells from lpg2--infected mice produced minimal levels of IL-4 and IL-10, as well as very low levels of IFN-gamma. Nevertheless, when BALB/c mice infected with lpg2- parasites were challenged with virulent L. major they were protected from disease. Thus, these findings report on attenuated parasites that may be used to induce long-term protection against leishmaniasis and indicate that the immunity induced can be maintained in the absence of a strong Th1 response. PMID:15004184

  12. Hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by oxidized LDL

    Directory of Open Access Journals (Sweden)

    Sandra Garoby-Salom

    2015-04-01

    The protective mechanism of HAS2 involves an increased expression of the heat-shock protein Hsp72, a chaperone with antiapoptotic activity. Taken together, these results highlight the role of nSMase2 in apoptosis evoked by nutrient starvation that could contribute to the delayed apoptosis of hypertrophic chondrocytes in the growth plate, and emphasize the antiapoptotic properties of HAS2.

  13. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja;

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  14. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    OpenAIRE

    Zhang, Chongben; Cooper, Daniel E.; Grevengoed, Trisha J.; Li, Lei O.; Klett, Eric L.; Eaton, James M.; Harris, Thurl E.; Coleman, Rosalind A.

    2014-01-01

    Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4−/− mice were more glucose tolerant and were protected from insulin resistance. Overexpres...

  15. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... deficiency dwarfism, pituitary growth hormone deficiency dwarfism isolated GH deficiency isolated HGH deficiency isolated human growth hormone deficiency isolated somatotropin deficiency isolated somatotropin deficiency disorder ...

  16. VLCAD deficiency

    DEFF Research Database (Denmark)

    Boneh, A; Andresen, B S; Gregersen, N;

    2006-01-01

    -negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.......We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood...... samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false...

  17. Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome.

    Science.gov (United States)

    Russell, A L

    1999-04-01

    Ulcerative colitis, Crohn's disease and interstitial cystitis share many common features, the most important of which is a defect in the glycoaminoglycan (GAG) defensive barrier. This defect allows penetration of toxins causing localized inflammatory response, followed by fibrosis and distant pathological changes, together with a myriad of biochemical and immunological changes. The latter has caused confusion as to etiology of the aforementioned disorders. This hypothesis is somewhat supported by the fact that agents such as glucosamine and pentosan polysulphate (Elmiron) that replace the GAG layer, improve the conditions. The potential for extrapolation of this hypothesis to atherosclerosis and arthropathies exists. There is a great danger in modern medical research that if one misses the wood for the trees, one becomes hopelessly lost in the minutiae of research. At present, it is embarrassing that ulcerative colitis (UC), Crohn's (CR) and interstitial cystitis (IC) are the cause of a great deal of morbidity and occasionally mortality, yet after intensive research, the etiology and effective treatment eludes us. The research in the past has focused extensively on inflammatory response in the mucosal lining, and biochemical, infective and immunological changes in the serum. This has led to a vast array of research pathways that seem at the present time to be totally lost and, might I say, aimless in direction, as a cause for these conditions, that remain amongst the most imperically treated in modern medicine. Another possible syndrome in this class would be Reiter's, which has many features in common with the above. The basic tenet of a GAG deficiency hypothesis is that, as shown in Figure 1A, an intact GAG layer provides, firstly, a mechanical and electrostatic defence against penetration of infective agents, toxins, antigenic protein moieties, etc. and, secondly, the prevention of extravasation of body fluid components. A degraded GAG layer is the start of the

  18. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  19. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  20. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  1. B7 costimulation molecules encoded by replication-defective, vhs-deficient HSV-1 improve vaccine-induced protection against corneal disease.

    Directory of Open Access Journals (Sweden)

    Jane E Schrimpf

    Full Text Available Herpes simplex virus 1 (HSV-1 causes herpes stromal keratitis (HSK, a sight-threatening disease of the cornea for which no vaccine exists. A replication-defective, HSV-1 prototype vaccine bearing deletions in the genes encoding ICP8 and the virion host shutoff (vhs protein reduces HSV-1 replication and disease in a mouse model of HSK. Here we demonstrate that combining deletion of ICP8 and vhs with virus-based expression of B7 costimulation molecules created a vaccine strain that enhanced T cell responses to HSV-1 compared with the ICP8⁻vhs⁻ parental strain, and reduced the incidence of keratitis and acute infection of the nervous system after corneal challenge. Post-challenge T cell infiltration of the trigeminal ganglia and antigen-specific recall responses in local lymph nodes correlated with protection. Thus, B7 costimulation molecules expressed from the genome of a replication-defective, ICP8⁻vhs⁻ virus enhance vaccine efficacy by further reducing HSK.

  2. PROTECTION OF RESVERATROL ON HEPATOCYTES AGAINST METHIONINE-CHOLINE-DEFICIENCY-INDUCED INJURIES%白藜芦醇对蛋氨酸胆碱缺乏培养基诱导肝细胞损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    王宇琦; 纪桂元; 邓颖勋; 蒋卓勤

    2015-01-01

    Objective To investigate the effects of resveratrol on methionine-choline-deficiency-induced injuries in alpha mouse liver 12 ( AML12 ) hepatocytes. Methods The mouse liver cell line AML12 was cultured and the methionine-choline-deficiency-induced injury model was set up. Cell viability, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase( LDH) activities in culture supernatants and contents of triglyceride (TG) and malondialdehyde (MDA)in cell lysates were measured in hepatocytes incubated with resveratrol (25, 50, 100μmol/l) for 24h. The contents of IL-1β, IL-6 and TNF-αwere detected by ELISA methods, and the mRNA levels were determined by RT-PCR. Expression of microtubule-associated protein 1 light chain 3 (MAP1-LC3) was measured by Western blot method. Results Compared with the methionine-choline-deficiency-induced injury group, resveratrol treatment increased the survival of hepatocytes, lowered activities of ALT, AST and LDH in culture supernatants, reduced the contents of MDA and TG and the levels of inflammatory factors IL-1β, IL-6 and TNF-α, increased MAP1-LC3 expression. Conclusion Resveratrol can significantly protect AML12 hepatocytes against the damages induced by methionine-choline-deficiency, and the underlying mechanism is possibly associated with the autophagy induced by resveratrol.%目的研究白藜芦醇对蛋氨酸胆碱缺乏(methionine-choline-deficient,MCD)培养基诱导的小鼠正常肝细胞(alpha monse liver 12,AML12)损伤的保护作用。方法体外培养小鼠正常肝细胞AML12,建立蛋氨酸胆碱缺乏培养基诱导的肝细胞损伤模型,用不同浓度白藜芦醇(25、50、100μmol/L)进行干预24h,检测细胞的增值活性,以及细胞培养基上清液中谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱基酶(LDH)活性和细胞中丙二醛(MDA)水平、甘油三酯(TG)含量,检测细胞中炎性细胞因子 IL-1β、IL-6

  3. Clinical management of salivary deficiency: A review article

    International Nuclear Information System (INIS)

    The physical, chemical and antibacterial properties of saliva provide protection to human dentition against dental diseases, Therefore, salivary deficiency has to be managed carefully. The causes of saliva deficiency are many and varied. It is worth mentioning that saliva flow rate is normally affected by physiologic condition, such as eating, resting, sleeping, cold or hot season etc. In this paper the protective role of saliva, etiologiy of saliva deficiency and its clinical management are discussed. (author

  4. Protect Your Fertility

    Science.gov (United States)

    ... and deficiency of body fat can lead to infertility. To protect your chances of conceiving, maintain a healthy weight through proper nutrition and exercise. For more information about nutrition, visit ...

  5. Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism.

    Science.gov (United States)

    Kabir, Inamul; Li, Zhiqiang; Bui, Hai H; Kuo, Ming-Shang; Gao, Guangping; Jiang, Xian-Cheng

    2016-04-01

    Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specificLpcat3gene knock-out mice. We producedLpcat3-Flox/villin-Cre-ER(T2)mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to deleteLpcat3specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP-binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB-dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to depleteLpcat3in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia.

  6. 超声引导下乙醇硬化治疗卵巢子宫内膜样囊肿前后血清中差异表达因子%Expression difference of factors CD36, NR4A1 and HES1 which were before and after the ethanol sclerotherapy for ovarian endometrial cyst detected by gene chips

    Institute of Scientific and Technical Information of China (English)

    赵宁; 董晓秋; 王璐璐; 王思明; 邵小慧; 张立维

    2015-01-01

    ObjectiveTo explore changes of immune factors in serum before and after ultrasound-guided (US-guided ) interventional treatment of ovarian endometrial cyst.MethodsNine patients with ovarian endometrial cyst were selected between December 2011 and December 2013 in the fourth affiliated hospital of Harbin Medical University. All patients performed US-guided interventional treatment, the serum specimens were collected before and after three months of treatment respectively. NimbleGen genome microarray of serum specimens were performed to analysis the gene function and gene pathways of related factors of ovarian endometrial cyst and to find out factors with significant expression differences before and after treatment. The relevance between factors with significant expression differences and the pathogenesis of ovarian endometrial cyst were analyzed.ResultsThe expression of CD36, NR4A1and HES1 were found to be down-regulated after US-guided interventional treatment of ovarian endometrial cyst by NimbleGen genome microarray. The gene function of CD36, NR4A1 and HES1participating in angiogenesis, chemotaxis, cell adhesion was relevant to the pathogenesis of the ovarian endometrial cyst, and played roles through Adipocytokine signaling pathway, MAPK signalig pathway, Maturity onset diabetes of the young signaling pathways.ConclusionSerum CD36, NR4A1 and HES1of ovarian endometrial cyst were down-regulated after US-guided ethanol sclerotherapy , and involved in the pathogenesis of ovarian endometrial cyst .%目的:探讨超声引导介入治疗卵巢子宫内膜样囊肿前、后患者血清中的差异表达因子。方法选取2011年12月至2013年12月在哈尔滨医科大学附属第四医院治疗的9例卵巢子宫内膜样囊肿患者,全部患者均在超声引导下介入治疗,治疗前及治疗后3个月分别采集患者血清标本,行NimbleGen全基因组表达谱芯片检测,分析治疗前、后血清中卵巢子宫内膜样囊肿相关因子的

  7. Leukocyte Adhesion Deficiency (LAD)

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area Leukocyte Adhesion Deficiency (LAD) LAD is an immune deficiency in ... are slow to heal also may have LAD. Treatment and Research Doctors prescribe antibiotics to prevent and ...

  8. Factor VII deficiency

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  9. Folate-deficiency anemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL ... and women are the two groups at highest risk for iron-deficiency anemia. Outlook Doctors usually can ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ... treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics ...

  12. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic disorders ...

  13. Iron deficiency and cognition

    OpenAIRE

    Hulthén, Lena

    2003-01-01

    Iron deficiency is the most prevalent nutritional disorder in the world. One of the most worrying consequences of iron deficiency in children is the alteration of behaviour and cognitive performance. In iron-deficient children, striking behavioural changes are observed, such as reduced attention span, reduced emotional responsiveness and low scores on tests of intelligence. Animal studies on nutritional iron deficiency show effects on learning ability that parallel the human studies. Despite ...

  14. Iron-Deficiency Anemia

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, ... Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... 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 ...

  16. CYP1B1 deficiency ameliorates obesity and glucose intolerance induced by high fat diet in adult C57BL/6J mice.

    Science.gov (United States)

    Liu, Xiaocong; Huang, Tingting; Li, Lu; Tang, Yumeng; Tian, Yatao; Wang, Suqing; Fan, Cuifang

    2015-01-01

    Cytochrome P450 1B1 (CYP1B1) expression increases in multi-potential mesenchymal stromal cells C3H10T1/2 during adipogenesis, which parallel with PPARγ, a critical transcriptional factor in adipogenic process. To assess the role of CYP1B1 in fatty acid metabolism, adult C57BL/6J wild-type and CYP1B1 deficiency mice were fed with high fat diets (HFD) for 6 weeks. CYP1B1 deficiency attenuated HFD-induced obesity when compared with their wild type counterparts, and improve glucose tolerance. The reduction in body weight gain and white adipose tissue in CYP1B1 deficient mice exhibited coordinate decreases in fatty acid synthesis (PPARγ, CD36, FAS, SCD-1) and increases in fatty acid oxidation (UCP-2, CPT-1a) when compared with wild type ones. Lower hepatocyte TG contents were consistent with hepatic Oil-Red-O staining in the CYP1B1 deficiency mice. AMPK, a nutrient sensors for energy homeostasis, was activated in both fat pad and liver by CYP1B1 deficiency. However, in vitro system, knock down CYP1B1 in C3H10T1/2 cells does not abolish adipogenesis induced by adipogenic agents IDM (Insulin, Dexamethasone, Methylisobutylxanthine). Our in vivo and in vitro findings of CYP1B1 deficiency in fat metabolism suggest a complex regulation network between CYP1B1 and energy homeostasis. PMID:26064443

  17. Acquired color vision deficiency.

    Science.gov (United States)

    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.

  18. On the Modification of the"Three Guarantees"---Comment on the Deficiencies of Article 24 of Consumer Protection L aw%论我国“三包”规定的完善--兼评《消费者权益保护法》第24条之不足

    Institute of Scientific and Technical Information of China (English)

    何宗泽

    2015-01-01

    The"Three Guarantees"generates in the period of planned economy .After the modification of Consumer Protection L aw ,the"T hree Guarantees"must be modified in order to better protect the legitimate interests of consumers .Meanwhile ,the deficiencies of the Article 24 of the new Consumer Protection Law should be inproved .%我国“三包”规定产生于计划经济时期,《消费者权益保护法》修订后,“三包”规定亟须修改以做到明确统一。与此同时,《消费者权益保护法》第24条也应做相应完善。

  19. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  20. Lipoprotein lipase deficiency.

    OpenAIRE

    Shankar K; Bava H; Shetty J; Joshi M

    1997-01-01

    A rare case of a 3 month old child with lipoprotein lipase deficiency who presented with bronchopneumonia is reported. After noticing lipaemic serum and lipaemia retinalis, a diagnosis of hyperlipoproteinaemia was considered. Lipoprotein lipase deficiency was confirmed with post heparin lipoprotein lipase enzyme activity estimation.

  1. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  2. Iron deficiency in childhood

    NARCIS (Netherlands)

    L. Uijterschout

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  3. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A;

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  4. Vitamin deficiencies and excesses

    Science.gov (United States)

    Vitamins are essential nutrients that must be supplied exogenously either as part of a well balanced diet or as supplements. Deficiency states are uncommon in developed countries except, perhaps, among some food insecure families. In contrast, deficiency states are quite common in many developing ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Tests Blood Transfusion Restless Legs Syndrome Send a link to NHLBI to someone by E-MAIL | ... Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you ...

  6. Deficiently Extremal Gorenstein Algebras

    Indian Academy of Sciences (India)

    Pavinder Singh

    2011-08-01

    The aim of this article is to study the homological properties of deficiently extremal Gorenstein algebras. We prove that if / is an odd deficiently extremal Gorenstein algebra with pure minimal free resolution, then the codimension of / must be odd. As an application, the structure of pure minimal free resolution of a nearly extremal Gorenstein algebra is obtained.

  7. Mipu1 overexpression protects macrophages from oxLDL-induced foam cell formation and cell apoptosis.

    Science.gov (United States)

    Qu, Shun-Lin; Fan, Wen-Jing; Zhang, Chi; Guo, Fang; Han, Dan; Pan, Wen-Jun; Li, Wei; Feng, Da-Ming; Jiang, Zhi-Sheng

    2014-12-01

    Mipu1 (myocardial ischemic preconditioning upregulated protein 1) is a novel N-terminal Kruppel-associated box (KRAB)/C2H2 zinc finger superfamily protein, that displays a powerful effect in protecting H9c2 cells from oxidative stress-induced cell apoptosis. The present study aims to investigate the effect of Mipu1 overexpression on oxidized low-density lipoprotein (oxLDL)-induced foam cell formation, cell apoptosis, and its possible mechanisms. New Zealand healthy rabbits were used to establish atherosclerosis model, and serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were detected by an automatic biochemical analyzer. Sudan IV staining was used to detect atherosclerotic lesions. The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining, high-performance liquid chromatography, and Dil-labeled lipoprotein were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to determine cell apoptosis. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as ABCA1, ABCG1, SR-BI, and CD36. Western blot analysis was used to detect the protein expression of Mipu1. There were atherosclerotic lesions in the high-fat diet group with Sudan IV staining. High-fat diet decreased Mipu1 expression and increased CD36 expression significantly at the 10th week compared with standard-diet rabbits. Mipu1 overexpression decreased oxLDL-induced cholesterol accumulation, oxLDL uptake, cell apoptosis, and cleaved caspase-3. Mipu1 overexpression inhibited the oxLDL-induced CD36 mRNA and protein expression, but it did not significantly inhibit the mRNA expression of ABCA1, ABCG1, and SR-BI. Mipu1 overexpression inhibits oxLDL-induced foam cell formation and cell apoptosis. Mipu1 overexpression reduces the

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in ... 18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Entire Site Health Topics News & Resources Intramural Research Public Health Topics Education & Awareness Resources Contact The Health ... Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, ...

  11. Sleep Deprivation and Deficiency

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Sleep Deprivation and Deficiency? Sleep deprivation (DEP-rih-VA- ... Rate This Content: NEXT >> Updated: February 22, 2012 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Health Topics Education & Awareness Resources Contact The Health Information Center Health Professionals Systematic Evidence Reviews & Clinical Practice ... and see the benefits of treatment. For more information about living with and managing iron-deficiency anemia, ...

  13. Manganese deficiency in plants

    DEFF Research Database (Denmark)

    Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren

    2016-01-01

    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Digg. Share this page from the NHLBI on Facebook. Add this link to the NHLBI to my ... such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ... 2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National Institutes ...

  17. Adult growth hormone deficiency

    OpenAIRE

    Vishal Gupta

    2011-01-01

    Adult growth hormone deficiency (AGHD) is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD) has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth...

  18. Clinical significance of complement deficiencies.

    Science.gov (United States)

    Pettigrew, H David; Teuber, Suzanne S; Gershwin, M Eric

    2009-09-01

    The complement system is composed of more than 30 serum and membrane-bound proteins, all of which are needed for normal function of complement in innate and adaptive immunity. Historically, deficiencies within the complement system have been suspected when young children have had recurrent and difficult-to-control infections. As our understanding of the complement system has increased, many other diseases have been attributed to deficiencies within the complement system. Generally, complement deficiencies within the classical pathway lead to increased susceptibility to encapsulated bacterial infections as well as a syndrome resembling systemic lupus erythematosus. Complement deficiencies within the mannose-binding lectin pathway generally lead to increased bacterial infections, and deficiencies within the alternative pathway usually lead to an increased frequency of Neisseria infections. However, factor H deficiency can lead to membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally, deficiencies within the terminal complement pathway lead to an increased incidence of Neisseria infections. Two other notable complement-associated deficiencies are complement receptor 3 and 4 deficiency, which result from a deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited deficiencies of the complement system are autosomal recessive, but properidin deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal dominant, and mannose-binding lectin and factor I deficiencies are autosomal co-dominant. The diversity of clinical manifestations of complement deficiencies reflects the complexity of the complement system. PMID:19758139

  19. CD36 expression contributes to age induced cardiomyopathy in mice

    Science.gov (United States)

    Cardiac remodeling and impaired cardiac performance in the elderly significantly increase the risk of developing heart disease. Although vascular abnormalities associated with aging contribute to the age-related decline in cardiac function, myocardium-specific events may also be involved. We show th...

  20. Iron deficiency anaemia.

    Science.gov (United States)

    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 and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

  1. Antepartum ornithine transcarbamylase deficiency.

    Science.gov (United States)

    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

  2. Iodine Deficiency and Human Development

    Directory of Open Access Journals (Sweden)

    M A Sviridonova

    2014-03-01

    Full Text Available Iodine is а vital microelements that are essential for the normal human development and functions. Iodine deficiency is a global problem: about 2 billion individuals worldwide suffer from a lack of iodine. Despite goiter is the most visually noticeable manifestation of iodine deficiency, the most significant consequence of the iodine deficiency is impaired neurodevelopment, particularly early in life. Moreover, moderate to severe iodine deficiency increases the risk of spontaneous abortion, low birth weight and infant mortality. Babies in utero affected by iodine deficiency are at increased risk of mental developmental disorders, cretinism is their extreme degree. In addition, moderate to severe iodine deficiency in childhood negatively affects somatic growth. Iodine deficiency compensation improves cognitive and motor function in children. Iodine prophylaxis of deficient populations is an extremely effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.

  3. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    biennially to exchange views and research findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2-3 June 2005. This review covers the wide range of AAT deficiency-related topics that were addressed encompassing advances in genetic characterization, risk factor identification, clinical...... epidemiology, inflammatory and signalling processes, therapeutic advances, and lung imaging techniques....

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ... Institutes of Health—shows how Susan, a full-time worker and student, has coped with having iron- ...

  5. Iodine-deficiency disorders

    NARCIS (Netherlands)

    Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.

    2008-01-01

    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-deficien

  6. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben;

    2007-01-01

    OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into chil...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... body. Low iron levels usually are due to blood loss, poor diet, or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ...

  8. Folate deficiency affects histone methylation.

    Science.gov (United States)

    Garcia, Benjamin A; Luka, Zigmund; Loukachevitch, Lioudmila V; Bhanu, Natarajan V; Wagner, Conrad

    2016-03-01

    that the bound THF serves to protect the FAD class of histone demethylases from the destructive effects of formaldehyde generation by formation of 5,10-methylene-THF. We present pilot data showing that decreased folate in livers as a result of dietary folate deficiency is associated with increased levels of methylated lysine 4 of histone 3. This can be a result of decreased LSD1 activity resulting from the decreased folate available to scavenge the formaldehyde produced at the active site caused by the folate deficiency. Because LSD1 can regulate gene expression this suggests that folate may play a more important role than simply serving as a carrier of one-carbon units and be a factor in other diseases associated with low folate. PMID:26880641

  9. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition ...

  10. Transient partial growth hormone deficiency due to zinc deficiency.

    Science.gov (United States)

    Nishi, Y; Hatano, S; Aihara, K; Fujie, A; Kihara, M

    1989-04-01

    We present here a 13-year-old boy with partial growth hormone deficiency due to chronic mild zinc deficiency. When zinc administration was started, his growth rate, growth hormone levels, and plasma zinc concentrations increased significantly. His poor dietary intake resulted in chronic mild zinc deficiency, which in turn could be the cause of a further loss of appetite and growth retardation. There was also a possibility of renal zinc wasting which may have contributed to zinc deficiency. Zinc deficiency should be carefully ruled out in patients with growth retardation. PMID:2708733

  11. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  12. Proximal Focal Femoral Deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Kalia, Vibhuti

    2008-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a developmental disorder of the proximal segment of thefemur and of acetabulum resulting in shortening of the affected limb and impairment of the function. It isa spectrum of congenital osseous anomalies characterized by a deficiency in the structure of the proximalfemur. The diagnosis is often made by radiological evaluation which includes identification and descriptionof PFFD and evaluation of associated limb anomalies by plain radiographs. Contrast arthrography orMagnetic Resonance Imaging is indicated when radiological features are questionable and to disclose thepresence and location of the femoral head and any cartilagenous anlage. The disorder is more commonlyunilateral and is apparent at birth. However, bilateral involvement is rarely seen. Therapy of the disorder isdirected towards satisfactory ambulation and specific treatment depending on the severity of dysplasia.

  13. Micronutrient deficiency in children.

    Science.gov (United States)

    Bhan, M K; Sommerfelt, H; Strand, T

    2001-05-01

    Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to

  14. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Things to Know About Zika & Pregnancy Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia Print A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  15. Treatment of carnitine deficiency.

    Science.gov (United States)

    Winter, S C

    2003-01-01

    Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose-response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these

  16. Environmetal protection within the law relating to regional policy. Anchoring the climatic protection und the protection of biodiversity within the law relating to regional policy; Umweltschutz im Planungsrecht. Die Verankerung des Klimaschutzes und des Schutzes der biologischen Vielfalt im raumbezogenen Planungsrecht

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, Gerold; Albrecht, Juliane [Leibniz-Institut fuer oekologische Raumentwicklung e.V., Dresden (Germany)

    2008-03-15

    The report is concerned with the anchoring of the climate protection within the law relating to regional policy. The report covers the following topics: (1) Fundamentals of planning policy: the regional planning legislation, municipal planning authority, constitutional provisos, environmental protection as constitutional principle; (2) climate protection laws: legal instruments; legal planning relevance of climate protection instruments deficiencies and protective effect; (3) biodiversity protection: laws concerning biodiversity, legal planning relevance of biodiversity protection instruments: deficiencies and protective effects.

  17. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M;

    2003-01-01

    , oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  18. Phosphorus Deficiency in Ducklins

    Institute of Scientific and Technical Information of China (English)

    CuiHengmin; LuoLingping

    1995-01-01

    20 one-day-old Tianfu ducklings were fed on a natural diet deficient in phosphorus(Ca 0.80%,P 0.366%)for three weeks and examined for signs and lesions.Signs began to appear at the age of one week,and became serous at two weeks.13 ducklings died during the experiment.Morbidity was 100% and mortality was 65%.The affected ducklings mainly showed leg weakness,severe lamencess,deprssion,lack of appetite and stunted growth,The serum alkaline phosphatase activities increased markedly.The serum phosphorus concentration,tibial ash,ash calcium and phosphorus content decreased obviously.At necropsy,maxillae and ribe were soft,and the latter was crooked.Long ones were soft and broke easily.The hypertrophic zone of the growth-plate in the epiphysis of long ones was lengthened and osteoid tissue increased in the metaphyseal spongiosa histopathologically.The above mentioned symptoms and lesions could be prevented by adding phosphorus to the natural deficient diet(up to 0.65%),The relationship between lesions and signs,pathomorphological characterisation and pathogensis were also discussed in this paper.

  19. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  20. [Iron deficiency and digestive disorders].

    Science.gov (United States)

    Cozon, G J N

    2014-11-01

    Iron deficiency anemia still remains problematic worldwide. Iron deficiency without anemia is often undiagnosed. We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. Hepcidin and ferroportin are the main proteins of iron regulation. Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption.

  1. Iatrogenic limbal stem cell deficiency.

    OpenAIRE

    Holland, E J; Schwartz, G S

    1997-01-01

    PURPOSE: To describe a group of patients with limbal stem cell (SC) deficiency without prior diagnosis of a specific disease entity known to be causative of SC deficiency. METHODS: We performed a retrospective review of the records of all patients with ocular surface disease presenting to the University of Minnesota between 1987 and 1996. Patients were categorized according to etiology of limbal deficiency. Patients who did not have a specific diagnosis previously described as being causative...

  2. Zinc deficiency and eating disorders.

    Science.gov (United States)

    Humphries, L; Vivian, B; Stuart, M; McClain, C J

    1989-12-01

    Decreased food intake, a cyclic pattern of eating, and weight loss are major manifestations of zinc deficiency. In this study, zinc status was evaluated in 62 patients with bulimia and 24 patients with anorexia nervosa. Forty percent of patients with bulimia and 54% of those with anorexia nervosa had biochemical evidence of zinc deficiency. The authors suggest that for a variety of reasons, such as lower dietary intake of zinc, impaired zinc absorption, vomiting, diarrhea, and binging on low-zinc foods, patients with eating disorders may develop zinc deficiency. This acquired zinc deficiency could then add to the chronicity of altered eating behavior in those patients. PMID:2600063

  3. Iron deficiency and cardiovascular disease

    NARCIS (Netherlands)

    von Haehling, Stephan; Jankowska, Ewa A.; van Veldhuisen, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2015-01-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of card

  4. Iron deficiency anemia in children.

    Science.gov (United States)

    Subramaniam, Girish; Girish, Meenakshi

    2015-06-01

    Iron deficiency is not just anemia; it can be responsible for a long list of other manifestations. This topic is of great importance, especially in infancy and early childhood, for a variety of reasons. Firstly, iron need is maximum in this period. Secondly, diet in infancy is usually deficient in iron. Thirdly and most importantly, iron deficiency at this age can result in neurodevelopmental and cognitive deficits, which may not be reversible. Hypochromia and microcytosis in a complete blood count (CBC) makes iron deficiency anemia (IDA) most likely diagnosis. Absence of response to iron should make us look for other differential diagnosis like β thalassemia trait and anemia of chronic disease. Celiac disease is the most important cause of true IDA not responding to oral iron therapy. While oral ferrous sulphate is the cheapest and most effective therapy for IDA, simple nonpharmacological and pharmacological measures can go a long way in prevention of iron deficiency. PMID:25636824

  5. C5a receptor deficiency alters energy utilization and fat storage.

    Directory of Open Access Journals (Sweden)

    Christian Roy

    Full Text Available OBJECTIVE: To investigate the impact of whole body C5a receptor (C5aR deficiency on energy metabolism and fat storage. DESIGN: Male wildtype (WT and C5aR knockout (C5aRKO mice were fed a low fat (CHOW or a high fat high sucrose diet-induced obesity (DIO diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR. RESULTS: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO as well as smaller gonadal (-38% CHOW, -36% DIO and inguinal (-29% CHOW, -30% DIO fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW and liver (CHOW and DIO and PPARγ was increased in muscle and liver. CONCLUSION: These observations point towards a role (either direct or indirect for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

  6. Glucose-6-Phosphate Dehydrogenase Deficiency Overview

    Science.gov (United States)

    ... Drugs GARD Information Navigator FAQs About Rare Diseases Glucose-6-phosphate dehydrogenase deficiency Title Other Names: G6PD ... G6PD deficiency Categories: Newborn Screening Summary Summary Listen Glucose 6 phosphate dehydrogenase (G6PD) deficiency is a hereditary ...

  7. Genetics Home Reference: factor V deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions factor V deficiency factor V deficiency Enable Javascript to view the expand/collapse ... Print All Open All Close All Description Factor V deficiency is a rare bleeding disorder. The signs ...

  8. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  9. Genetics Home Reference: leptin receptor deficiency

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions leptin receptor deficiency leptin receptor deficiency Enable Javascript to view the expand/ ... boxes. Print All Open All Close All Description Leptin receptor deficiency is a condition that causes severe ...

  10. Genetics Home Reference: congenital leptin deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions congenital leptin deficiency congenital leptin deficiency Enable Javascript to view the expand/collapse ... Print All Open All Close All Description Congenital leptin deficiency is a condition that causes severe obesity ...

  11. Genetics Home Reference: factor XIII deficiency

    Science.gov (United States)

    ... InfoSearch: Factor XIII deficiency Factor XIII Registry Database: Introduction to Factor XIII Deficiency MalaCards: factor xiii deficiency ... Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA ...

  12. Genetics Home Reference: combined pituitary hormone deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions combined pituitary hormone deficiency combined pituitary hormone deficiency Enable Javascript to view the ... boxes. Print All Open All Close All Description Combined pituitary hormone deficiency is a condition that causes ...

  13. [Iodine deficiency during pregnancy ].

    Science.gov (United States)

    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

  14. Iodine deficiency disorders.

    Science.gov (United States)

    Elliott, T C

    1987-01-01

    Iodine deficiency disorder (IDD) affects 800 million people in the world, yet iodine supplementation is one of the most cost-effective nutritional interventions known. Iodine is incorporated into thyroid hormones, necessary for regulating metabolic rate, growth, and development of the brain and nervous system. IDD may appear as goiter in adults, usually not a serious problem, or in cretinism in children, which is marked by severe mental and physical retardation, with irreversible hearing and speech defects and either deaf-mutism, squint and paralysis, or stunting and edema. Children supplemented by age 1 or 2 can sometimes be helped. Foods contain variable amounts of iodine dependent on the soil where they are grown, hence mountainous and some inland regions have high goiter and IDD incidence. There are also goitrogenic foods, typically those of the cabbage family. Diagnosis is clinical or by blood tests for thyroid hormone levels and ratios. Finger-stick methods are available. Prevention of IDD is simple with either iodized salt or flour, iodinated central water supplies, injectable or oral iodine-containing oil. All cost about $.04 per person per year, except injections, which cost about $1 per person, but have the advantage that they could be combined with immunizations. Local problems with supplements are loss of iodine in salt with storage in tropics, and local production of cheaper uniodinated salt. Emphasis should be given to pregnant women and young children. There is no harm in giving pregnant women iodine injections in 2nd or 3rd trimester. PMID:12343033

  15. Differential diagnosis of tetrahydrobiopterin deficiency.

    Science.gov (United States)

    Niederwieser, A; Ponzone, A; Curtius, H C

    1985-01-01

    Six hundred and seventy-three children (483 newborns and 190 older selected children) were screened for tetrahydrobiopterin (BH4) deficiency by HPLC of urine pterins and BH4 load test. One patient with GTP cyclohydrolase I deficiency, 36 patients with dihydrobiopterin synthetase (DHBS) deficiency (of which six were in the newborn and 30 in the older children) and 14 with dihydropteridine reductase deficiency (DHPR) were found. All 37 patients with defective BH4 biosynthesis responded to a BH4 load by lowering of the elevated serum phenylalanine concentration but four of 14 patients with DHPR deficiency did not. Measurement of DHPR activity in blood spots on Guthrie cards is recommended. Since subvariants of patients with BH4 deficiency exist, homovanillic acid, 5-hydroxyindole acetic acid, pterins, phenylalanine, and tyrosine in cerebrospinal fluid should be measured for diagnosis and the control of therapy. The activity of the phosphate-eliminating enzyme (a key enzyme in BH4 biosynthesis and part of "DHBS") was measured in human liver and activities of approx. 1 n U (mg protein)-1 were found. In the liver biopsy of a patient with DHBS deficiency no activity (less than 3% of controls) was demonstrated. PMID:3930839

  16. Iron Deficiency Anemia in Pregnancy.

    Science.gov (United States)

    Breymann, Christian

    2015-10-01

    Anemia is a common problem in obstetrics and perinatal care. Any hemoglobin below 10.5 g/dL can be regarded as true anemia regardless of gestational age. Reasons for anemia in pregnancy are mainly nutritional deficiencies, parasitic and bacterial diseases, and inborn red blood cell disorders such as thalassemias. The main cause of anemia in obstetrics is iron deficiency, which has a worldwide prevalence between estimated 20%-80% and consists of a primarily female population. Stages of iron deficiency are depletion of iron stores, iron-deficient erythropoiesis without anemia, and iron deficiency anemia, the most pronounced form of iron deficiency. Pregnancy anemia can be aggravated by various conditions such as uterine or placental bleedings, gastrointestinal bleedings, and peripartum blood loss. In addition to the general consequences of anemia, there are specific risks during pregnancy for the mother and the fetus such as intrauterine growth retardation, prematurity, feto-placental miss ratio, and higher risk for peripartum blood transfusion. Besides the importance of prophylaxis of iron deficiency, the main therapy options for the treatment of pregnancy anemia are oral iron and intravenous iron preparations.

  17. JNK deficiency enhances fatty acid utilization and diverts glucose from oxidation to glycogen storage in cultured myotubes.

    Science.gov (United States)

    Vijayvargia, Ravi; Mann, Kara; Weiss, Harvey R; Pownall, Henry J; Ruan, Hong

    2010-09-01

    Although germ-line deletion of c-Jun NH(2)-terminal kinase (JNK) improves overall insulin sensitivity in mice, those studies could not reveal the underlying molecular mechanism and the tissue site(s) in which reduced JNK activity elicits the observed phenotype. Given its importance in nonesterified fatty acids (NEFA) and glucose utilization, we hypothesized that the insulin-sensitive phenotype associated with Jnk deletion originates from loss of JNK function in skeletal muscle. Short hairpin RNA (shRNA)-mediated gene silencing was used to identify the functions of JNK subtypes in regulating energy metabolism and metabolic responses to elevated concentrations of NEFA in C2C12 myotubes, a cellular model of skeletal muscle. We show for the first time that cellular JNK2- and JNK1/JNK2-deficiency divert glucose from oxidation to glycogenesis due to increased glycogen synthase (GS) activity and induction of Pdk4. We further show that JNK2- and JNK1/JNK2-deficiency profoundly increase cellular NEFA oxidation, and their conversion to phospholipids and triglyceride. The increased NEFA utilization was coupled to increased expressions of selective NEFA handling genes including Cd36, Acsl4, and Chka, and enhanced palmitic acid (PA)-dependent suppression of acetyl-CoA carboxylase (Acc). In JNK-intact cells, PA inhibited insulin signaling and glycogenesis. Although silencing Jnk1 and/or Jnk2 prevented PA-induced inhibition of insulin signaling, it did not completely block decreased insulin-mediated glycogenesis, thus indicating JNK-independent pathways in the suppression of glycogenesis by PA. Muscle-specific inhibition of JNK2 (or total JNK) improves the capacity of NEFA utilization and glycogenesis, and is a potential therapeutic target for improving systemic insulin sensitivity in type 2 diabetes (T2D). PMID:20094041

  18. Clinical manifestations of zinc deficiency.

    Science.gov (United States)

    Prasad, A S

    1985-01-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present

  19. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    Science.gov (United States)

    ... links) CLIMB: Children Living with Inherited Metabolic Diseases Muscular Dystrophy Association: Myoadenylate Deaminase Deficiency Genetic Testing Registry (1 link) Muscle AMP deaminase deficiency ...

  20. Sun Protection

    Science.gov (United States)

    ... Emitting Products Radiation-Emitting Products and Procedures Tanning Sun Protection Share Tweet Linkedin Pin it More sharing ... for integrating sun protection into your daily routine. Sun Protection Tips Avoid overexposure to UV rays from ...

  1. Genetic deficiency of adiponectin protects against acute kidney injury

    OpenAIRE

    Jin, Xiaogao; Chen, Jiyuan; Hu, Zhaoyong; Chan, Lawrence; Wang, Yanlin

    2013-01-01

    Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. Here we determined if adiponectin modulates ischemic acute kidney injury. Compared with wild-type mice, adiponectin knockout mice were found to have lower serum creatinine and less tubular damage or apoptosis following ischemia/reperfusion injury. This latter process was associated with decreased Bax and reduced activation of p53 and caspase-3. Targeted disruption of adiponectin was also found to inhibit the...

  2. Mechanisms associated with Fe-deficiency tolerance and signaling in shoots of Pisum sativum.

    Science.gov (United States)

    Kabir, Ahmad H; Paltridge, Nicholas G; Roessner, Ute; Stangoulis, James C R

    2013-03-01

    Mechanisms of Fe-deficiency tolerance and signaling were investigated in shoots of Santi (deficiency tolerant) and Parafield (deficiency intolerant) pea genotypes using metabolomic and physiological approaches. From metabolomic studies, Fe deficiency induced significant increases in N-, S- and tricarboxylic acid cycle metabolites in Santi but not in Parafield. Elevated N metabolites reflect an increase in N-recycling processes. Increased glutathione and S-metabolites suggest better protection of pea plants from Fe-deficiency-induced oxidative stress. Furthermore, Fe-deficiency induced increases in citrate and malate in leaves of Santi suggests long-distance transport of Fe is promoted by better xylem unloading. Supporting a role of citrate in the deficiency tolerance mechanism, physiological experiments showed higher Fe and citrate in the xylem of Santi. Reciprocal-grafting experiments confirm that the Fe-deficiency signal driving root Fe reductase and proton extrusion activity is generated in the shoot. Finally, our studies show that auxin can induce increased Fe-reductase activity and proton extrusion in roots. This article identifies several mechanisms in shoots associated with the differential Fe-deficiency tolerance of genotypes within a species, and provides essential background for future efforts to improve the Fe content and deficiency tolerance in peas. PMID:22913816

  3. Evolutionary Processes and Mental Deficiency

    Science.gov (United States)

    Spitz, Herman H.

    1973-01-01

    The author hypothesizes that central nervous system damage of deficiency associated with mental retardation affects primarily those cortical processes which developed at a late stage in man's evolutionary history. (Author)

  4. [Niacin deficiency and cutaneous immunity].

    Science.gov (United States)

    Ikenouchi-Sugita, Atsuko; Sugita, Kazunari

    2015-01-01

    Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E₂-EP4 (PGE₂-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity. PMID:25765687

  5. Cutaneous findings of nutritional deficiencies in children.

    Science.gov (United States)

    Goskowicz, M; Eichenfield, L F

    1993-08-01

    Nutritional deficiencies may be associated with a variety of cutaneous findings in children. This review emphasizes new developments relating to cutaneous findings of nutritional deficiencies. Zinc deficiency, acrodermatitis enteropathica, and acrodermatitis enteropathica-like eruptions are seen with a variety of conditions including cystic fibrosis, anorexia nervosa, and breastfeeding. Similar cutaneous findings not related to zinc deficiency may also occur with such metabolic disorders as methylmalonic aciduria, multiple carboxylase deficiency, essential fatty acid deficiency and other amino acid deficiencies. Vitamin K deficiency is associated with hemorrhagic disease of the newborn and coagulopathy. Vitamin A deficiency presents with a variety of systemic findings and distinctive dermatologic findings. Acute vitamin A deficiency may be seen in children infected with measles and is associated with more severe disease. The systemic and cutaneous findings of vitamin C deficiency, scurvy, are discussed. PMID:8374671

  6. Sickle cell protection from malaria: a review

    Directory of Open Access Journals (Sweden)

    Sandro Eridani

    2011-11-01

    Full Text Available A linkage between presence of Sickle Haemoglobin (HbS and protection from malaria infection and clinical manifestations in certain areas was suspected from early observations and progressively elucidated by more recent studies. Research has confirmed the abovementioned connection, but also clarified how such protection may be abolished by coexistence of sickle cell trait (HbS trait and alpha thalassemia, which may explain the relatively low incidence of HbS trait in the Mediterranean. The mechanisms of such protective effect are now being investigated: factors of genetic, molecular and immunological nature are prominent. As for genetic factors attention is given to the role of the red blood cell (RBC membrane complement regulatory proteins as polymorphisms of these components seem to be associated with resistance to severe malaria; genetic ligands like the Duffy group blood antigen, necessary for erythrocytic invasion, and human protein CD36, a major receptor for P. falciparum-infected RBC‘s, are also under scrutiny: attention is focused also on plasmodium erythrocyte-binding antigens, which bind to RBC surface components. Genome-wide linkage and association studies are now carried out too, in order to identify genes associated with malaria resistance. Only a minor role is attributed to intravascular sickling, phagocytosis and haemolysis, while specific molecular mechanisms are the object of intensive research: among these a decisive role is played by a biochemical sequence, involving activation of haeme oxygenase (HMO-1, whose effect appears mediated by carbon monoxide (CO. A central role in protection from malaria is also played by immunological factors, which may stimulate antibody production to plasmodium antigens in the early years of life; the role of agents like pathogenic CD8 T-cells has been suggested while the effects of molecular actions on the immunity mechanism are presently investigated. It thus appears that protection from

  7. Zinc and its deficiency diseases.

    Science.gov (United States)

    Evans, G W

    1986-01-01

    The pervasive role of zinc in the metabolic function of the body results from its function as a cofactor of a multitude of enzymes. Zinc is found in every tissue in the body, and because zinc metalloenzymes are found in every known class of enzymes, the metal has a function in every conceivable type of biochemical pathway. Symptoms resulting from zinc deficiency are as diverse as the enzymes with which the metal is associated. If chronic, severe, and untreated, zinc deficiency can be fatal. Less drastic symptoms include infections, hypogonadism, weight loss, emotional disturbance, dermatitis, alopecia, impaired taste acuity, night blindness, poor appetite, delayed wound healing, and elevated blood ammonia levels. Many symptoms of zinc deficiency result from poor diet consumption, but often the most severe symptoms result from other factors including excessive alcohol use, liver diseases, malabsorption syndromes, renal disease, enteral or parenteral alimentation, administration of sulfhydryl-containing drugs, and sickle cell disease. The most severe symptoms of zinc deficiency occur in young children affected with the autosomal-recessive trait, acrodermatitis enteropathica. This disease results in decreased synthesis of picolinic acid which causes an impaired ability to utilize zinc from common food. Because simple laboratory analyses are often not reliable in determining zinc nutriture of a patient, those symptoms caused by suspected zinc deficiency are best verified by the oral administration of zinc dipicolinate. This zinc compound is efficacious and safe and would provide an accurate means of identifying symptoms that do result from zinc deficiency. PMID:3514057

  8. [Iron deficiency and iron deficiency anemia are global health problems].

    Science.gov (United States)

    Dahlerup, Jens; Lindgren, Stefan; Moum, Björn

    2015-03-10

    Iron deficiency and iron deficiency anemia are global health problems leading to deterioration in patients' quality of life and more serious prognosis in patients with chronic diseases. The cause of iron deficiency and anemia is usually a combination of increased loss and decreased intestinal absorption and delivery from iron stores due to inflammation. Oral iron is first line treatment, but often hampered by intolerance. Intravenous iron is safe, and the preferred treatment in patients with chronic inflammation and bowel diseases. The goal of treatment is normalisation of hemoglobin concentration and recovery of iron stores. It is important to follow up treatment to ensure that these objectives are met and also long-term in patients with chronic iron loss and/or inflammation to avoid recurrence of anemia.

  9. The bile acid sensor FXR protects against dyslipidemia and aortic plaques development induced by the HIV protease inhibitor ritonavir in mice.

    Directory of Open Access Journals (Sweden)

    Andrea Mencarelli

    Full Text Available BACKGROUND: Although human immunodeficiency virus (HIV-related morbidity and mortality rates in patients treated with a combination of high active antiretroviral therapy (HAART have declined, significant metabolic/vascular adverse effects associated with the long term use of HIV protease inhibitors (PIs have emerged as a significant side effect. Here we illustrate that targeting the bile acid sensor farnesoid X receptor (FXR protects against dyslipidemia and vascular injury induced HIV-PIs in rodents. METHODOLOGY/PRINCIPAL FINDINGS: Administration of the HIV PI ritonavir to wild type mice increased plasma triacylglycerols and cholesterol levels and this effect was exacerbated by dosing ritonavir to mice harbouring a disrupted FXR. Dyslipidemia induced by ritonavir associated with a shift in the liver expression of signature genes, Sterol Regulatory Element-Binding Protein (SREBP-1 and fatty acid synthase. Treating wild type mice with the FXR agonist (chenodeoxycholic acid, CDCA protected against development of dyslipidemia induced by ritonavir. Administration of ritonavir to ApoE(-/- mice, a strain that develop spontaneously atherosclerosis, increased the extent of aortic plaques without worsening the dyslipidemia. Treating these mice with CDCA reduced the extent of aortic plaques by 70% without changing plasma lipoproteins or the liver expression of signature genes. A beneficial effect on aortic plaques was also obtained by treating ApoE(-/- mice with gemfibrozil, a PPARα agonist. FXR activation counter-regulated induction of expression/activity of CD36 caused by HIV-PIs in circulating monocytes and aortic plaques. In macrophages cell lines, CDCA attenuated CD36 induction and uptake of acetylated LDL caused by ritonavir. Natural and synthetic FXR ligands reduced the nuclear translocation of SREBP1c caused by ritonavir. CONCLUSIONS/SIGNIFICANCE: Activation of the bile acid sensor FXR protects against dyslipidemia and atherosclerotic caused by

  10. Iron deficiency and cardiovascular disease.

    Science.gov (United States)

    von Haehling, Stephan; Jankowska, Ewa A; van Veldhuisen, Dirk J; Ponikowski, Piotr; Anker, Stefan D

    2015-11-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of cardiovascular medicine. Data indicate that iron deficiency has detrimental effects in patients with coronary artery disease, heart failure (HF), and pulmonary hypertension, and possibly in patients undergoing cardiac surgery. Around one-third of all patients with HF, and more than one-half of patients with pulmonary hypertension, are affected by iron deficiency. Patients with HF and iron deficiency have shown symptomatic improvements from intravenous iron administration, and some evidence suggests that these improvements occur irrespective of the presence of anaemia. Improved exercise capacity has been demonstrated after iron administration in patients with pulmonary hypertension. However, to avoid iron overload and T-cell activation, it seems that recipients of cardiac transplantations should not be treated with intravenous iron preparations.

  11. Folate Deficiency in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Gopalakrishna Rajesh

    2010-07-01

    Full Text Available Dear Sir, While there has been a spurt of interest in genetic alterations associated with pancreatitis in the past few years, interest in the role of environmental factors has largely focused on alcoholism and smoking with insufficient attention being paid to the contributions of nutritional deficiency, and the role of environmental toxins in the pathogenesis of pancreatitis. Braganza and Dormandy [1] argue convincingly about the role played by cytochrome P450 monooxygenases (especially CYP1A enzyme induction by xenobiotics and the resultant oxidative stress, as also the now increasingly recognized reductive stress posed by the metabolites in initiating pancreatic injury. Their article underlines the important part played by the deficiency of methyl and thiol molecules in different stages of the progression of pancreatic damage. Furthermore, they attempt to establish a link between environmental and genetic factors and bring in a holistic view on the etiopathogenesis of chronic pancreatitis. We have recently demonstrated lower plasma methionine levels in two cohorts of chronic pancreatitis patients; one of tropical chronic pancreatitis and the other, of alcoholic chronic pancreatitis as compared to healthy controls [2] which suggests that deficiency of methyl groups may be a factor in various forms of pancreatitis. Similarly, we have shown lower red cell glutathione levels in chronic pancreatitis patients with tropical chronic pancreatitis and alcoholic chronic pancreatitis, indicating deficiency of thiol molecules. In addition, we have demonstrated significantly higher levels of plasma total homocysteine in chronic pancreatitis patients than in healthy controls. Moreover, our study has shown that there is a deficiency of red cell folate in the majority of chronic pancreatitis patients, more so in tropical chronic pancreatitis; and that folate deficiency appeared to be the key factor in hyperhomocysteinemia in chronic pancreatitis patients

  12. Iron deficiency in the tropics.

    Science.gov (United States)

    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

  13. [Phosphate metabolism and iron deficiency].

    Science.gov (United States)

    Yokoyama, Keitaro

    2016-02-01

    Autosomal dominant hypophosphatemic rickets(ADHR)is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage. Fibroblast growth factor 23(FGF23)is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. Low iron status plays a role in the pathophysiology of ADHR. Iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. It was reported that FGF23 elevation in patients with CKD, who are often iron deficient. In patients with nondialysis-dependent CKD, treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and FGF23.

  14. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  15. Epigenetic Deficiencies and Replicative Stress

    DEFF Research Database (Denmark)

    Shoaib, Muhammad; Sørensen, Claus Storgaard

    2015-01-01

    Cancer cell-specific synthetic lethal interactions entail promising therapeutic possibilities. In this issue of Cancer Cell, Pfister et al. describe a synthetic lethal interaction where cancer cells deficient in H3K36me3 owing to SETD2 loss-of-function mutation are strongly sensitized to inhibiti...

  16. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  17. Congenital β-lipoprotein deficiency

    NARCIS (Netherlands)

    Buchem, F.S.P. van; Pol, G.; Gier, J. de; Böttcher, C.J.F.; Pries, C.

    1966-01-01

    There are several degrees of β-lipoprotein deficiency. If there is no β-lipoprotein present, or if there are only traces of it, the Bassen-Kornzweig syndrome develops. A constant feature of this syndrome is disturbed fat absorption with accumulation of fat in the epithelium of intestinal mucosa and

  18. Iron deficiency and iron overload: effects of diet and genes.

    Science.gov (United States)

    Burke, W; Imperatore, G; Reyes, M

    2001-02-01

    Like most essential nutrients, Fe needs to be maintained in the body at a defined level for optimal health, with appropriate adaptation to varying Fe needs and supply. The primary mechanism for controlling Fe level is the regulation of Fe absorption. Several different proteins have been identified as contributors to the process. Despite a complex regulatory system, Fe disorders (both Fe deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide, resulting from inadequate dietary Fe and blood loss. Complications include pre-term labour, developmental delay, and impaired work efficiency. No specific genetic syndromes causing isolated Fe deficiency have been described, but animal studies and clinical observations suggest that such a relationship may be a possibility. Conversely, the known causes of Fe overload are genetic. Fe overload is less common than Fe deficiency, but can result in serious medical complications, including cirrhosis, primary liver cancer, diabetes, cardiomyopathy and arthritis. The most common and best characterized syndrome of Fe overload is hereditary haemochromatosis (HHC), an autosomal recessive disorder. Mutations in the HFE protein cause HHC, but the clinical presentation is variable. Of particular interest is the factor that some FIFE genotypes appear to be associated with protection from Fe deficiency. Other genetic variants in the regulatory pathway may influence the likelihood of Fe deficiency and Fe overload. Studies of genetic variants in HFE and other regulatory proteins provide important tools for studying the biological processes in Fe regulation. This work is likely to lead to new insights into Fe disorders and potentially to new therapeutic approaches. It will not be complete, however, until coordinated study of both genetic and nutritional factors is undertaken. PMID:11310426

  19. Qualitative study on the protective factors of resilience among children in rural areas in acquired immune deficiency syndrome(HIV/AIDS)-Affected families%我国部分农村地区受艾滋病影响儿童心理弹性的保护性因素研究

    Institute of Scientific and Technical Information of China (English)

    史从戎; 张曼华; 王宇; 来源; 高保兴; 乔晓春

    2011-01-01

    [目的]调查山西省某艾滋病比较集中的地区,探讨该区受艾滋病影响儿童心理弹性的保护性因素.[方法]采用儿童焦虑性情绪障碍筛查表和儿童抑郁障碍自评量表,将受艾滋病影响儿童筛分为心理弹性组与非弹性组,再采用半结构访谈的方法,对弹性组的儿童进行调查. [结果]受艾滋病影响儿童心理弹性的保护性因素可划分为四个因素.家庭因素包括父母的关心和支持、民主的教育方式、父母的榜样力量;学校包括老师的关心、同伴的支持;认知包括对父母的评价、相信自己、对未来的期望;行为包括倾诉、寻求帮助、感恩与回报. [结论]在对受艾滋病影响儿童进行心理干预时,应综合考虑家庭、学校、认知、行为等因素.促进其心理弹性的发展,增进其心理健康.%[Objective] To explore the protective factors of resilience among children in acquired immune deficiency syndrome(HIV/AIDS)-Affected families in Shanxi. [Methods] Children in HIV/AIDS families were allocated into resilience group and non-resilience group by The Screen for Child Anxiety Related Emotional Disorders and Depression Self-rating Scale for Children. Then semi-structured interviews were conducted among the resilience group. [Results] The protective factors of resilience among children include four factors. The factor of family consists of care of parents, democratic family education and a good example of parents. Care of teachers and support of peers were included in the factor of school.Estimate of parents, belief in themselves and expectation for the future were organized into the factors of cognition. Pouring out, searching for help and thanksgiving were packed in the factors of behaviors. [Conclusion] Family, school, cognition and behavior should be considered comprehensively in the psychological intervention for the children in HIV/AIDS family to make them more resilient and more healthy.

  20. Effect of Fe Deficiency on Antioxidant System in Leaves of Three Flax Cultivars

    Directory of Open Access Journals (Sweden)

    Zeinab Abd El-Rahman SALAMA

    2009-06-01

    Full Text Available The potential role of antioxidant enzymes as well as antioxidant compounds in protecting plant from the deleterious effect of iron deficiency was examined in different flax Linum usitassimum L. cultivars. Three flax cultivars (Sakha 1, Sakha 2 and Giza 8 were grown in water culture with (Fe-sufficient plants, +Fe or without (Fe-deficient plants,-Fe iron supply for 40 days. The obtained results showed that, iron deficiency severely decreased dry weight and concentration of iron in all cultivars leaf tissue. Besides this, to verify whether iron deficiency could induce alteration in reactive oxygen species, high concentration of lipid peroxidation (TBARS and H2O2 content in leaves of flax cultivars were detected under (-Fe compared to (+Fe treatments. Iron deficiency can also modulate the content of glutathione (GSH level, which were significantly increased in Fe deficient treatment compared to Fe-sufficient treatment among cultivars. Activity of superoxide dismutase (SOD was increased under deficient treatment. In contrast, significant differences were observed between cultivars in the activity of Fe containing enzymes such as ascorbate peroxidase (APX, peroxidase (POD and catalase (CAT that was greater under Fe sufficient treatment, suggesting higher amounts of physiological iron in leaf tissue of all cultivars. In addition, some changes in POD isoenzyme profile was detected under iron stress.These results suggested that, these antioxidant compounds are the key compounds to protect cell from oxidative injury.

  1. Present status of understanding on the G6PD deficiency and natural selection

    Directory of Open Access Journals (Sweden)

    Tripathy V

    2007-01-01

    Full Text Available G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

  2. 脂肪组织炎症在CYP1B1基因敲除抑制小鼠营养性肥胖及其胰岛素抵抗中的作用%Function of WAT Inflammation in Protecting CYPlBl Deficient Mice from Obesity and Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    吴连希; 邱高坤; Jefcoate CR; 王素青

    2011-01-01

    also performed to detect the infiltration of macrophages into adipose tissue and the activation of protein NFκB. Results KO mice exhibited reduced serum glucose and insulin level and improve insulin sensitivity after 11 weeks HFD feeding. HFD increased macrophage infiltration in epididymis adipose tissue,while CYPlBl deletion induced low level macrophage infiltration but inhibited inflammation induced by HFD a step further in adipose tissue. Compared with WT mice,the expression levels of macrophage markers Emrl and CD68, inflammatary factors and their receptors MCP-1 ,TNFα, IL-6, CCR2 and CSFR1 in KO mice increased,as well as InsR and lRS expressions under low-fat diet. NFκB,which was critical in the inllanmation pathway,was also activated. Conclusion CYPlBl deficiency protects high-fat fed mice from obesity and insulin resistance. And through activating adipose tissue inflammation, CYPlBl deficiency can regulate the expressions of key factors in insulin signaling pathway, which may constitute the major mechanism of this effect.

  3. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    Directory of Open Access Journals (Sweden)

    Steven F Werder

    2010-04-01

    Full Text Available Steven F Werder1,21Kansas University School of Medicine – Wichita, Wichita, KS, USA; 2Community Health Center of Southeast Kansas, Pittsburg, KS, USAIntroduction: Although consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1 Which patients should be tested? (2 What test should be ordered? (3 How are inferences made from such testing? (4 In addition to serum B12, should other tests be ordered? (5 Is B12 deficiency compatible with dementia of the Alzheimer’s type? (6 What is to be expected from treatment? (7 How is B12 deficiency treated?Methods: On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia. After limiting the search terms, all abstracts and/or articles and other references were categorized into six major groups (general, biochemistry, manifestations, associations and risks, evaluation, and treatment and then reviewed in answering the above questions.Results: The six major groups above are described in detail. Seventy-five key studies, series, and clinical trials were identified. Evidence-based suggestions for patient management were developed.Discussion: Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia. In the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia. B12 deficiency manifestations are variable and include abnormal psychiatric, neurological, gastrointestinal, and hematological findings. Radiological images of individuals with hyperhomocysteinemia frequently demonstrate leukoaraiosis. Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia. The serum B12 level is the standard initial test

  4. Diagnosis of vitamin B12 deficiency.

    OpenAIRE

    HU, Rehman

    1984-01-01

    Vitamin B12 (cobalamin) deficiency occurs primarily as a result  of insufficient dietary intake or poor absorp-tion. There is widespread global prevalence of vitamin B12 deficiency, resulting in considerable morbidity.

  5. Genetics Home Reference: tyrosine hydroxylase deficiency

    Science.gov (United States)

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions TH deficiency tyrosine hydroxylase deficiency ...

  6. Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients

    Institute of Scientific and Technical Information of China (English)

    Manas Kotepui; Kwuntida Uthaisar; Bhukdee PhunPhuech; Nuoil Phiwklam

    2016-01-01

    Background:This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency,in the western region of Thailand,an endemic region for malaria.Methods:Data about patients with malaria hospitalized between 2013 and 2015 were collected.Clinical and sociodemographic characteristics such as age and gender,diagnosis on admission,and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province,Thailand.Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination.Other data such as complete blood count and parasite density were also collected and analyzed.Results:Among the 245 malaria cases,28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P.vivax infections.Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1%) patients did not have a G6PD deficiency.Prevalence of male patients with G6PD deficiency was higher than that of female patients (P < 0.05,OR =5.167).Among the patients with a G6PD deficiency,two (11.8 %) were infected with P.falciparum,while the remaining were infected with P.vivax.Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 103/μL) than those without a G6PD deficiency (0.33 × 103/μL) (P< 0.05,OR=5.167).Univariate and multivariate analyses also confirmed that malaria patients with a G6PD deficiency have high monocyte counts.The association between G6PD status and monocyte counts was independent of age,gender,nationality,Plasmodium species,and parasite density (P < 0.005).Conclusion:This study showed a prevalence of G6PD deficiency in a malaria-endemic area.This study also supported the assertion that patients with G6PD-deficient red blood cells had no protection

  7. Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice

    Science.gov (United States)

    Consuming curcumin may benefit health by modulating lipid metabolism and suppressing atherogenesis. Fatty acid binding proteins (FABP-4/aP2) and CD36 expression are key factors in lipid accumulation in macrophages and foam cell formation in atherogenesis. Our earlier observations suggest that curcum...

  8. HSF1-deficiency affects gait coordination and cerebellar calbindin levels.

    Science.gov (United States)

    Ingenwerth, Marc; Estrada, Veronica; Stahr, Anna; Müller, Hans Werner; von Gall, Charlotte

    2016-09-01

    Heat shock proteins (HSPs) play an important role in cell homeostasis and protect against cell damage. They were previously identified as key players in different ataxia models. HSF1 is the main transcription factor for HSP activation. HSF1-deficient mice (HSF1-/-) are known to have deficiencies in motor control test. However, little is known about effects of HSF1-deficiency on locomotor, especially gait, coordination. Therefore, we compared HSF-deficient (HSF1-/-) mice and wildtype littermates using an automated gait analysis system for objective assessment of gait coordination. We found significant changes in gait parameters of HSF1-/- mice reminiscent of cerebellar ataxia. Immunohistochemical analyses of a cerebellum revealed co-localization of HSF1 and calbindin in Purkinje cells. Therefore, we tested the hypothesis of a potential interconnection between HSF1 and calbindin in Purkinje cells. Calbindin levels were analyzed qualitatively and quantitatively by immunohistochemistry and immunoblotting, respectively. While quantitative PCR revealed no differences in calbindin mRNA levels between HSF1+/+ and HSF1-/- mice, calbindin protein levels, however, were significantly decreased in a cerebellum of HSF1-/- mice. A pathway analysis supports the hypothesis of an interconnection between HSF1 and calbindin. In summary, the targeted deletion of HSF1 results in changes of locomotor function associated with changes in cerebellar calbindin protein levels. These findings suggest a role of HSF1 in regular Purkinje cell calcium homeostasis. PMID:27173427

  9. Metabolic Adaptations of White Lupin Roots and Shoots under Phosphorus Deficiency

    Science.gov (United States)

    Müller, Julia; Gödde, Victoria; Niehaus, Karsten; Zörb, Christian

    2015-01-01

    White lupin (Lupinus albus L.) is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography–mass spectrometry (GC-MS) for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose, and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil. PMID:26635840

  10. Cobalamin deficiency in children: A literature review

    OpenAIRE

    Moen, Synne Helland

    2013-01-01

    Objective: The aim of this review is to present cobalamin deficiency in children with a specific focus on infants. Background: Cobalamin deficiency is caused by inadequate intake, malabsorption or inborn errors of vitamin B12 metabolism. Cobalamin deficiency in infants is usually caused by deficiency in the mother. There is often a diagnostic delay among infants because the most frequent symptoms are unspecific, e.g., developmental delay, apathy, hypotonia, anorexia and failure to thrive. Chi...

  11. Iron Deficiency in Autism and Asperger Syndrome.

    Science.gov (United States)

    Latif, A.; Heinz, P.; Cook, R.

    2002-01-01

    Retrospective analysis of the full blood count and, when available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) found six autistic children had iron deficiency and 12 of the 23 autistic children with serum ferritin measures were iron deficient. Far fewer Asperger children were iron deficient. Results…

  12. Vitamin D deficiency in Europe

    DEFF Research Database (Denmark)

    Cashman, Kevin D.; Dowling, Kirsten G; Škrabáková, Zuzana;

    2016-01-01

    BACKGROUND: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing...... 25(OH)D values from national health/nutrition surveys. OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D...... sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. RESULTS: An overall pooled...

  13. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  14. Newborn screening for MCAD deficiency

    DEFF Research Database (Denmark)

    Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G;

    2008-01-01

    BACKGROUND: Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis...... of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. OBJECTIVES: To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). METHODS AND RESULTS: Medium chain...... is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD....

  15. Vitamin D deficiency in Fibromyalgia

    International Nuclear Information System (INIS)

    Objective: To check the Vitamin D levels in patients diagnosed as fibromyagia in our population. Methods: Study was done at Medical OPD of Civil Hospital Karachi, from January to March 2009. Female patients diagnosed as Fibromyalgia according to American College of Rheumatology (ACR) criteria and exclusion of systemic illness on examination, and normal reports of blood CP, ESR, serum calcium, phosphate and Alkaline Phosphatase, were asked to get Vitamin D levels in their serum. Vitamin D deficiency is defined as 30 ng/ml. Result: Forty female patients were included in the study. The mean age was 37.65 +- 11.5 years. Mean Vitamin D level was 17.41 +- 5.497 ng/ml. Thirty two (80%) of patients had Vitamin D deficiency, mean levels of 15.855 +- 4.918 ng/ml and 8(20%) had Vitamin D insufficiency, mean levels of 23.64 +- 2.39 ng/ml. Patients with vitamin D deficiency and age less than 45 years were 22 (68.75%), had mean vitamin D level 16.87 +- 4.48 ng/ml whereas in age ranging from 46-75 years were 10 (31.25%) had mean vitamin D level 16.09 +- 6.45 ng/ml. Conclusion: Vitamin D deficiency is frequently seen in patients diagnosed as fibromyalgia and nonspecific musculoskeletal pain in our population. Although the sample size of the study is small, but the figures are so alarming that it is an eye opener towards the need of a population based study, including normal population as well as those presenting with musculoskeletal pain. (author)

  16. [Iodine deficiency in cardiovascular diseases].

    Science.gov (United States)

    Molnár, I; Magyari, M; Stief, L

    1998-08-30

    The thyroid hormone deficiency on cardiovascular function can be characterized with decreased myocardial contractility and increased peripheral vascular resistance as well as with the changes in lipid metabolism. 42 patients with cardiovascular disease (mean age 65 +/- 13 yr, 16 males) were investigated if iodine insufficiency can play a role as a risk factor for the cardiovascular diseases. The patients were divided in 5 subgroups on the ground of the presence of hypertension, congestive heart failure, cardiomyopathy, coronary disfunction and arrhythmia. Urine iodine concentration (5.29 +/- 4.52 micrograms/dl) was detected with Sandell-Kolthoff colorimetric reaction. The most decreased urine iodine concentration was detected in the subgroups with arrhythmia and congestive heart failure (4.7 +/- 4.94 micrograms/dl and 4.9 +/- 4.81 micrograms/dl, respectively). An elevated TSH level was found by 3 patients (5.3 +/- 1.4 mlU/l). An elevation in lipid metabolism (cholesterol, triglyceride) associated with all subgroups without arrhythmia. In conclusion, the occurrence of iodine deficiency in cardiovascular disease is frequent. Iodine supplementation might prevent the worsing effect of iodine deficiency on cardiovascular disease.

  17. Environmental protection

    International Nuclear Information System (INIS)

    The question of environment protection related to the use of nuclear energy aiming to power generation, based on the harmonic concept of economic and industrial development, preserving the environment, is discussed. A brief study of environmental impacts for some energy sources, including nuclear energy, to present the systems of a nuclear power plant which aim at environmental protection, is done. (M.C.K.)

  18. Zinc Deficiency in Humans and its Amelioration

    OpenAIRE

    Yashbir Singh Shivay

    2015-01-01

    Zinc (Zn) deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in ...

  19. Deficiencies in the Management of Iron Deficiency Anemia During Childhood.

    Science.gov (United States)

    Powers, Jacquelyn M; Daniel, Catherine L; McCavit, Timothy L; Buchanan, George R

    2016-04-01

    Limited high-quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid-2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11- to 18-year-old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost-to-follow-up were common. Substantial improvements are required in the management of IDA.

  20. Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.

    Science.gov (United States)

    Li, Jau-Yi; Chassaing, Benoit; Tyagi, Abdul Malik; Vaccaro, Chiara; Luo, Tao; Adams, Jonathan; Darby, Trevor M; Weitzmann, M Neale; Mulle, Jennifer G; Gewirtz, Andrew T; Jones, Rheinallt M; Pacifici, Roberto

    2016-06-01

    A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis. PMID:27111232

  1. Radiation protection

    International Nuclear Information System (INIS)

    A NRPB leaflet in the 'At-a-Glance' series explains in a simple but scientifically accurate way what radiation is, the biological effects and the relative sensitivity of different parts of the human body. The leaflet then discusses radiation protection principles, radiation protection in the UK and finally the effectiveness of this radiation protection as judged by a breakdown of the total dose received by an average person in the UK, a heavy consumer of Cumbrian seafood, an average nuclear industry worker and an average person in Cornwall. (UK)

  2. Negotiating Protection

    DEFF Research Database (Denmark)

    Bille, Mikkel

    This thesis examines protection against risks as material and social phenomena among the Ammarin tribe in Petra - a settled Bedouin community in southern Jordan. By examining the active role of material culture that is often disregarded in risk studies, the thesis discusses how protective...... of architecture, the social use of luminosity, prophylactic items, saint veneration, Qur'anic items, and heritage production. The thesis challenges the preoccupation with "meaning" in material culture studies, by focusing on conceptualizations of "presence" and "absence" as equally important to protective...... strategies are confirming their efficacy, and act as material anchors for negotiating Bedouin identities in response to a rapid transformation from nomadic pastoralists to sedentary wageworkers. The tensions surrounding the materiality of protection, along with the role of the past in the present is further...

  3. Radiation protection

    International Nuclear Information System (INIS)

    This work define procedures and controls about ionizing radiations. Between some definitions it found the following topics: radiation dose, risk, biological effects, international radioprotection bodies, workers exposure, accidental exposure, emergencies and radiation protection

  4. Muscle phosphoglycerate mutase deficiency revisited

    DEFF Research Database (Denmark)

    Naini, Ali; Toscano, Antonio; Musumeci, Olimpia;

    2009-01-01

    storage disease type X and novel mutations in the gene encoding the muscle subunit of PGAM (PGAM2). DESIGN: Clinical, pathological, biochemical, and molecular analyses. SETTING: Tertiary care university hospitals and academic institutions. Patients A 37-year-old Danish man of Pakistani origin who had...... PGAM deficiency, and molecular studies revealed 2 novel homozygous mutations, a nonsense mutation and a single nucleotide deletion. Pathological studies of muscle showed mild glycogen accumulation but prominent tubular aggregates in both patients. CONCLUSIONS: We found that glycogen storage disease...

  5. Environmental Protection

    OpenAIRE

    Berger, Regina; Diewald, Martin

    2003-01-01

    Nature protection and conservation are fundamental elements of environmental protection as this is an important part of the human existence; it is a vital component of the present and future harmonious socio economic development. The ecosystems and the organisms, like the marine and atmospheric terrestrial resources used by humankind, must be administrated in such a way that their optimum and continuous productivity may be assured and maintained. It is necessary to take rigorous measures agai...

  6. Corrosion protection

    Science.gov (United States)

    Brown, Donald W.; Wagh, Arun S.

    2003-05-27

    There has been invented a chemically bonded phosphate corrosion protection material and process for application of the corrosion protection material for corrosion prevention. A slurry of iron oxide and phosphoric acid is used to contact a warm surface of iron, steel or other metal to be treated. In the presence of ferrous ions from the iron, steel or other metal, the slurry reacts to form iron phosphates which form grains chemically bonded onto the surface of the steel.

  7. Vitamin D deficiency and stroke

    Directory of Open Access Journals (Sweden)

    2012-12-01

    Full Text Available Vitamin D comprises a group of fat-soluble pro-hormones, obtained from sun exposure, food, and supplements, and it must undergo two hydroxylation reactions to be activated in the body. Several studies have shown the role of vitamin D in mineral metabolism regulation, especially calcium, phosphorus, and bone metabolism. Some factors such as inadequate vitamin intake and liver or kidney disorders can lead to vitamin D deficiency. Furthermore, vitamin D malnutrition may also be linked to susceptibility to chronic diseases such as heart failure, peripheral artery disease, high blood pressure, cognitive impairment including foggy brain and memory loss, and autoimmune diseases including diabetes type I. Recent research has revealed that low levels of vitamin D increase the risk of cardiovascular-related morbidity (Sato et al., 2004 and mortality (Pilz et al., 2008. Also, hypertension contributes to a reduction in bone mineral density and increase in the incidence of stroke and death. This article reviews the function and physiology of vitamin D and examines the effects of vitamin D deficiency on susceptibility to stroke, as a cardiovascular event, and its morbidity and subsequent mortality.

  8. Protected Areas - Protected Federal Lands

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — The Federal Lands data consists of land areas that are run and maintained by U.S. Governmental authorities and are considered protected.The Department of Natural...

  9. Multispectral Analysis of Color Vision Deficiency Tests

    OpenAIRE

    Sergejs FOMINS; Ozolinsh, Maris

    2011-01-01

    Color deficiency tests are usually produced by means of polygraphy technologies and help to diagnose the type and severity of the color deficiencies. Due to different factors, as lighting conditions or age of the test, standard characteristics of these tests fail, thus not allowing diagnosing unambiguously the degree of different color deficiency. Multispectral camera was used to acquire the spectral images of the Ishihara and Rabkin pseudoisochromatic plates in the visible spectrum. Spectral...

  10. Prevalence of Color Vision Deficiency in Qazvin

    OpenAIRE

    Mohammad khalaj; Ameneh Barikani; Mozhgan Mohammadi

    2014-01-01

    Background: Color vision deficiency (CVD) is an X chromosome-linked recessive autosomal dominant. Determine the prevalence of color blindness in Qazvin population. Materials and Methods: In a cross sectional study color vision deficiency examined in 1853 individuals with age 10-25 years old who participated in private clinics and eye clinic of Bu-Ali hospital in Qazvin in 2010. The screening of color vision deficiency was performed using Ishihara test. Data were analyzed by SPSS-16 with χP...

  11. Vitamin B12 deficiency and depression

    OpenAIRE

    Milanlıoğlu, Aysel

    2011-01-01

    Vitamin B12 deficiency may cause psychiatric manifestations preceding the hematological and neurological symptoms. Despite a variety of symptoms, data on the role of vitamin B12 deficiency in depression are sparse. We report a case with B12 deficiency that is diagnosed with psychotic depression and treated successively with vitamin B12 replacement instead of using conventional therapy. Future investigations should focus on the role of vitamin B12 status in depression and other neurops...

  12. Atypical B12 Deficiency with Nonresolving Paraesthesia

    OpenAIRE

    Haider, S.; Ahmad, N; Anaissie, E J; Abdel Karim, N.

    2013-01-01

    Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS). This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of P...

  13. Vitamin D Deficiency in Early Pregnancy

    OpenAIRE

    Flood-Nichols, Shannon K.; Tinnemore, Deborah; Huang, Raywin R.; Napolitano, Peter G.; Ippolito, Danielle L.

    2015-01-01

    Objective Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes. Study Design This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singlet...

  14. Vitamin D Deficiency in Children and Adolescents

    OpenAIRE

    Andıran, Nesibe; Çelik, Nurullah; AKÇA, Halise; Doğan, Güzide

    2012-01-01

    Objective Vitamin D deficiency is an important health problem in both developed and developing countries. Recent reports on the extraskeletal effects of vitamin D have led to increased interest in prevalence studies on states of deficiency/insufficiency of vitamin D. The aim of this study was to determine the frequency of vitamin D deficiency and insufficiency in children and adolescents residing in Ankara, Turkey and to investigate the factors associated with low vitamin D status. Methods: A...

  15. Machine Protection

    CERN Document Server

    Schmidt, R

    2014-01-01

    The protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent. It is related to the increasing beam power of high-power proton accelerators such as ISIS, SNS, ESS and the PSI cyclotron, to the emission of synchrotron light by electron–positron accelerators and FELs, and to the increase of energy stored in the beam (in particular for hadron colliders such as LHC). Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping the beam at low energy) and an ...

  16. Vitamin C deficiency in weanling guinea pigs

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E.;

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during...

  17. Genetics Home Reference: common variable immune deficiency

    Science.gov (United States)

    ... 2 links) National Institute of Allergy and Infectious Diseases: Immune System National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (8 links) Boston Children's ...

  18. Machine Protection

    CERN Document Server

    Zerlauth, Markus; Wenninger, Jörg

    2012-01-01

    The present architecture of the machine protection system is being recalled and the performance of the associated systems during the 2011 run will be briefly summarized. An analysis of the causes of beam dumps as well as an assessment of the dependability of the machine protection systems (MPS) itself is being presented. Emphasis will be given to events that risked exposing parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems will be evaluated along with their impact on the 2012 run. The role of rMPP during the various operational phases (commissioning, intensity ramp up, MDs...) will be discussed along with a proposal for the intensity ramp up for the start of beam operation in 2012.

  19. Physical protection

    Energy Technology Data Exchange (ETDEWEB)

    Myre, W.C.; DeMontmollin, J.M. (Sandia National Labs., Albuquerque, NM (USA))

    1989-07-01

    Serious concern about physical protection of nuclear facilities began around 1972. R and D was initiated at Sandia National Laboratories which had developed techniques to protect weapons for many years. Special vehicles, convoy procedures, and a communications system previously developed for weapons shipments were improved and extended for shipments of other sensitive materials. Barriers, perimeter alarms, portal and internal control systems were developed, tested, and published in handbooks and presented at symposia. Training programs were initiated for U.S. and foreign personnel. Containment and surveillance techniques were developed for the IAEA. Presently emphasis is on computer security, active barriers, and techniques to prevent theft or sabotage by insiders .

  20. Deficient approaches to human neuroimaging

    DEFF Research Database (Denmark)

    Stelzer, Johannes; Lohmann, Gabriele; Mueller, Karsten;

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is the workhorse of imaging-based human cognitive neuroscience. The use of fMRI is ever-increasing; within the last 4 years more fMRI studies have been published than in the previous 17 years. This large body of research has mainly focused...... of the major conceptual and practical deficiencies in widely used brain-mapping approaches, and exemplify some of these issues by the use of imaging data and simulations. In particular, we discuss the inherent pitfalls and shortcomings of methodologies for statistical parametric mapping. Our critique...... emphasizes recent reports of excessively high numbers of both false positive and false negative findings in fMRI brain mapping. We outline our view regarding the broader scientific implications of these methodological considerations and briefly discuss possible solutions....

  1. B12 Deficiency with Children

    Directory of Open Access Journals (Sweden)

    Selahattin Katar

    2007-01-01

    Full Text Available Aim of the study: to rewieved the clinical and laboratory properties of seven cases with megaloblastic anemia. Clinical and laboratory findings of seven cases with megaloblastic anemia are described. İt is determined that all of the patients received little or no animal products by nutritional history. Clinically apatite, malasia, headeche, otism, and parestheia in the lower extremities and foods were present in patients. On physical examination; four patients had glossit, four had hyporeflexia, one had ataxia. Folat level was normal and B12 vitamin level was low in all patients. The MCV (mean corpuscular volume was normal in three patients. Hypersegmentation of neutrophil was observed in all patients, leukopenia in two, and trombocytopenia was observed in one patient.Conclusion: it is suggested B12 vitamin deficiency in the patients that received little or no animal products by nutritional history. However, hypersegmentation of neutrophil in peripheral blood sample is an important finding for diagnosis of megaloblastic anemia.

  2. [Iron deficiency in the elderly].

    Science.gov (United States)

    Helsen, Tuur; Joosten, Etienne

    2016-06-01

    Anemia is a common diagnosis in the geriatric population, especially in institutionalized and hospitalized elderly. Most common etiologies for anemia in elderly people admitted to a geriatric ward are iron-deficiency anemia and anemia associated with chronic disease.Determination of serum ferritin is the most used assay in the differential diagnosis, despite low sensitivity and moderate specificity. New insights into iron homeostasis lead to new diagnostic assays such as serum hepcidin, serum transferrin receptor and reticulocyte hemoglobin equivalent.Importance of proper diagnosis and treatment for this population is large since there is a correlation between anemia and morbidity - mortality. Anemia is usually defined as hemoglobin less than 12 g/dl for women and less than 13 g/dl for men. There is no consensus for which hemoglobinvalue an investigation into underlying pathology is obligatory. This needs to be evaluated depending on functional condition of the patient. PMID:27106490

  3. [delta-Aminolevulinate dehydratase deficiency].

    Science.gov (United States)

    Fujita, H; Ishida, N; Akagi, R

    1995-06-01

    delta-Aminolevulinate dehydratase (ALAD: E. C. 4.2.1.24), the second enzyme in the heme biosynthetic pathway, condenses two moles of delta-aminolevulinic acid to form porphobilinogen. ALAD deficiency is well known to develop signs and symptoms of typical hepatic porphyria, and classified into three categories as follows: (i) ALAD porphyria, a genetic defect of the enzyme, (ii) tyrosinemia type I, a genetic defect of fumarylacetoacetase in the tyrosine catabolic pathway, producing succinylacetone (a potent inhibitor of ALAD), and (iii) ALAD inhibition by environmental hazards, such as lead, trichloroethylene, and styrene. In the present article, we will describe molecular and biochemical mechanisms to cause the enzyme defect to discuss the significance of ALAD defect on human health.

  4. The impact of phenotypic and genotypic G6PD deficiency on risk of plasmodium vivax infection: a case-control study amongst Afghan refugees in Pakistan.

    Directory of Open Access Journals (Sweden)

    Toby Leslie

    2010-05-01

    Full Text Available BACKGROUND: The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A- G6PD (glucose-6-phosphate dehydrogenase deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine. If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. METHODS AND FINDINGS: A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI 0.06-0.52], p = 0.001. Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041. The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037. CONCLUSIONS: G6PD deficiency (Mediterranean type conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human

  5. Protection Myopia

    DEFF Research Database (Denmark)

    Laursen, Keld; Salter, Ammon; Li, Cher

    from having an orientation towards legal appropriability, we conjecture that protection myopia may lead some firms to allocate too much attention to legal appropriability, in particular when the behavioral and structural contingencies are unfavorable. Examining a panel of three successive waves...

  6. Overexpression of Vesicle-associated Membrane Protein (VAMP) 3, but Not VAMP2, Protects Glucose Transporter (GLUT) 4 Protein Translocation in an in Vitro Model of Cardiac Insulin Resistance*

    Science.gov (United States)

    Schwenk, Robert W.; Angin, Yeliz; Steinbusch, Laura K. M.; Dirkx, Ellen; Hoebers, Nicole; Coumans, Will A.; Bonen, Arend; Broers, Jos L. V.; van Eys, Guillaume J. J. M.; Glatz, Jan F. C.; Luiken, Joost J. F. P.

    2012-01-01

    Cardiac glucose utilization is regulated by reversible translocation of the glucose transporter GLUT4 from intracellular stores to the plasma membrane. During the onset of diet-induced insulin resistance, elevated lipid levels in the circulation interfere with insulin-stimulated GLUT4 translocation, leading to impaired glucose utilization. Recently, we identified vesicle-associated membrane protein (VAMP) 2 and 3 to be required for insulin- and contraction-stimulated GLUT4 translocation, respectively, in cardiomyocytes. Here, we investigated whether overexpression of VAMP2 and/or VAMP3 could protect insulin-stimulated GLUT4 translocation under conditions of insulin resistance. HL-1 atrial cardiomyocytes transiently overexpressing either VAMP2 or VAMP3 were cultured for 16 h with elevated concentrations of palmitate and insulin. Upon subsequent acute stimulation with insulin, we measured GLUT4 translocation, plasmalemmal presence of the fatty acid transporter CD36, and myocellular lipid accumulation. Overexpression of VAMP3, but not VAMP2, completely prevented lipid-induced inhibition of insulin-stimulated GLUT4 translocation. Furthermore, the plasmalemmal presence of CD36 and intracellular lipid levels remained normal in cells overexpressing VAMP3. However, insulin signaling was not retained, indicating an effect of VAMP3 overexpression downstream of PKB/Akt. Furthermore, we revealed that endogenous VAMP3 is bound by the contraction-activated protein kinase D (PKD), and contraction and VAMP3 overexpression protect insulin-stimulated GLUT4 translocation via a common mechanism. These observations indicate that PKD activates GLUT4 translocation via a VAMP3-dependent trafficking step, which pathway might be valuable to rescue constrained glucose utilization in the insulin-resistant heart. PMID:22936810

  7. Overexpression of vesicle-associated membrane protein (VAMP) 3, but not VAMP2, protects glucose transporter (GLUT) 4 protein translocation in an in vitro model of cardiac insulin resistance.

    Science.gov (United States)

    Schwenk, Robert W; Angin, Yeliz; Steinbusch, Laura K M; Dirkx, Ellen; Hoebers, Nicole; Coumans, Will A; Bonen, Arend; Broers, Jos L V; van Eys, Guillaume J J M; Glatz, Jan F C; Luiken, Joost J F P

    2012-10-26

    Cardiac glucose utilization is regulated by reversible translocation of the glucose transporter GLUT4 from intracellular stores to the plasma membrane. During the onset of diet-induced insulin resistance, elevated lipid levels in the circulation interfere with insulin-stimulated GLUT4 translocation, leading to impaired glucose utilization. Recently, we identified vesicle-associated membrane protein (VAMP) 2 and 3 to be required for insulin- and contraction-stimulated GLUT4 translocation, respectively, in cardiomyocytes. Here, we investigated whether overexpression of VAMP2 and/or VAMP3 could protect insulin-stimulated GLUT4 translocation under conditions of insulin resistance. HL-1 atrial cardiomyocytes transiently overexpressing either VAMP2 or VAMP3 were cultured for 16 h with elevated concentrations of palmitate and insulin. Upon subsequent acute stimulation with insulin, we measured GLUT4 translocation, plasmalemmal presence of the fatty acid transporter CD36, and myocellular lipid accumulation. Overexpression of VAMP3, but not VAMP2, completely prevented lipid-induced inhibition of insulin-stimulated GLUT4 translocation. Furthermore, the plasmalemmal presence of CD36 and intracellular lipid levels remained normal in cells overexpressing VAMP3. However, insulin signaling was not retained, indicating an effect of VAMP3 overexpression downstream of PKB/Akt. Furthermore, we revealed that endogenous VAMP3 is bound by the contraction-activated protein kinase D (PKD), and contraction and VAMP3 overexpression protect insulin-stimulated GLUT4 translocation via a common mechanism. These observations indicate that PKD activates GLUT4 translocation via a VAMP3-dependent trafficking step, which pathway might be valuable to rescue constrained glucose utilization in the insulin-resistant heart.

  8. Genetics Home Reference: pyruvate kinase deficiency

    Science.gov (United States)

    ... National (UK) Information Centre for Metabolic Diseases National Organization for Rare Disorders (NORD): Pyruvate Kinase Deficiency Genetic Testing Registry (1 link) Pyruvate kinase deficiency of red cells Scientific articles on PubMed (1 link) PubMed OMIM (1 link) ...

  9. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif;

    1995-01-01

    Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency ...

  10. 30 CFR 57.5015 - Oxygen deficiency.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Oxygen deficiency. 57.5015 Section 57.5015..., Physical Agents, and Diesel Particulate Matter Air Quality-Underground Only § 57.5015 Oxygen deficiency. Air in all active workings shall contain at least 19.5 volume percent oxygen....

  11. Acquired Zinc Deficiency in an Adult Female

    OpenAIRE

    Mohanan Saritha; Divya Gupta; Laxmisha Chandrashekar; Devinder M Thappa; Nachiappa G Rajesh

    2012-01-01

    Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. Acquired cases are reported occasionally in patients with eating disorders or Crohn′s disease. We report a 24-year-old housewife with acquired isolated severe zinc deficiency with no other comorbidities to highlight the rare occurrence of isolated nutritional zinc deficiency in an otherwise normal patient.

  12. Academic Deficiency: Student Experiences of Institutional Labeling

    Science.gov (United States)

    Barouch-Gilbert, Abraham

    2015-01-01

    Limited existing research examines how undergraduate students in the United States experience the process of being identified as deficient due to their academic performance. The purpose of this phenomenological study was to explore the lived experiences of college students on academic probation who were labeled academically deficient. Students…

  13. Short Stature and Growth Hormone Deficiency

    OpenAIRE

    Matemi, Sezer

    1994-01-01

    This paper summarizes the importance of measurements of height and weight in normal children and emphasizes the role of growth increments for the diagnosis of short stature Causes of short stature methods for diagnosis of GH hormone deficiency actions of growth hormone treatment of growth hormone deficiency and doses for biosynthetic GH treatment are described Key words: Short Stature Growth Hormone

  14. Growth Hormone Deficiency, Brain Development, and Intelligence

    Science.gov (United States)

    Meyer-Bahlburg, Heino F. L.; And Others

    1978-01-01

    Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

  15. Genetics Home Reference: complement factor I deficiency

    Science.gov (United States)

    ... the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. ... in my area? Other Names for This Condition C3 inactivator deficiency complement component 3 inactivator deficiency Related Information How are ...

  16. Breath hydrogen test and sucrase isomaltase deficiency.

    OpenAIRE

    Ford, R P; Barnes, G L

    1983-01-01

    Sucrose breath hydrogen tests were performed on 7 children with proved sucrase isomaltase deficiency. All children had raised breath hydrogen excretion. The amount of hydrogen produced and symptoms experienced increased with increasing sucrose loads. The sucrose breath hydrogen test appears to be a reliable indicator of sucrose malabsorption in sucrase isomaltase deficiency.

  17. How Best To Utilize a Deficiency.

    Science.gov (United States)

    Miller, Patricia H.

    2000-01-01

    Focuses on the importance and meaning of the degree of spontaneity in memory strategy production. Situates the concept of utilization deficiency within current work on memory strategy heterogeneity, contextual support, and situation-specific skills. Concludes that work on utilization deficiencies helps balance the focus on early emergence of…

  18. Protection of DNA damage by radiation exposure

    International Nuclear Information System (INIS)

    The SOS response of Escherichia coli is positively regulated by RecA. To examine the effects of polyamines on The SOS response of E. Coli, we investigated the expression of recA gene in polyamine-deficient mutant and wild type carrying recA'::lacZ fusion gene. As a result, recA expression by mitomycin C is higher in wild type than that of polyamine-deficient mutant, but recA expression by UV radiation is higher in wild type than of mutant. We also found that exogenous polyamines restored the recA expression in the polyamine-deficient mutant to the wild type level. These results proposed that polyamines play an important role in mechanism of intracellular DNA protection by DNA damaging agents

  19. Protection of DNA damage by radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Ho; Kim, In Gyu; Lee, Kang Suk; Kim, Kug Chan; Oh, Tae Jung

    1998-12-01

    The SOS response of Escherichia coli is positively regulated by RecA. To examine the effects of polyamines on The SOS response of E. Coli, we investigated the expression of recA gene in polyamine-deficient mutant and wild type carrying recA'::lacZ fusion gene. As a result, recA expression by mitomycin C is higher in wild type than that of polyamine-deficient mutant, but recA expression by UV radiation is higher in wild type than of mutant. We also found that exogenous polyamines restored the recA expression in the polyamine-deficient mutant to the wild type level. These results proposed that polyamines play an important role in mechanism of intracellular DNA protection by DNA damaging agents.

  20. Generic physical protection logic trees

    International Nuclear Information System (INIS)

    Generic physical protection logic trees, designed for application to nuclear facilities and materials, are presented together with a method of qualitative evaluation of the trees for design and analysis of physical protection systems. One or more defense zones are defined where adversaries interact with the physical protection system. Logic trees that are needed to describe the possible scenarios within a defense zone are selected. Elements of a postulated or existing physical protection system are tagged to the primary events of the logic tree. The likelihood of adversary success in overcoming these elements is evaluated on a binary, yes/no basis. The effect of these evaluations is propagated through the logic of each tree to determine whether the adversary is likely to accomplish the end event of the tree. The physical protection system must be highly likely to overcome the adversary before he accomplishes his objective. The evaluation must be conducted for all significant states of the site. Deficiencies uncovered become inputs to redesign and further analysis, closing the loop on the design/analysis cycle

  1. Generic physical protection logic trees

    Energy Technology Data Exchange (ETDEWEB)

    Paulus, W.K.

    1981-10-01

    Generic physical protection logic trees, designed for application to nuclear facilities and materials, are presented together with a method of qualitative evaluation of the trees for design and analysis of physical protection systems. One or more defense zones are defined where adversaries interact with the physical protection system. Logic trees that are needed to describe the possible scenarios within a defense zone are selected. Elements of a postulated or existing physical protection system are tagged to the primary events of the logic tree. The likelihood of adversary success in overcoming these elements is evaluated on a binary, yes/no basis. The effect of these evaluations is propagated through the logic of each tree to determine whether the adversary is likely to accomplish the end event of the tree. The physical protection system must be highly likely to overcome the adversary before he accomplishes his objective. The evaluation must be conducted for all significant states of the site. Deficiencies uncovered become inputs to redesign and further analysis, closing the loop on the design/analysis cycle.

  2. Prevalence of Color Vision Deficiency in Qazvin

    Directory of Open Access Journals (Sweden)

    Mohammad khalaj

    2014-01-01

    Full Text Available Background: Color vision deficiency (CVD is an X chromosome-linked recessive autosomal dominant. Determine the prevalence of color blindness in Qazvin population. Materials and Methods: In a cross sectional study color vision deficiency examined in 1853 individuals with age 10-25 years old who participated in private clinics and eye clinic of Bu-Ali hospital in Qazvin in 2010. The screening of color vision deficiency was performed using Ishihara test. Data were analyzed by SPSS-16 with χP2P test with p<0.05. Results: Mean age of participant was 17.86±4.48 years. 59.5% of them were female. 3.49% of the total population had color vision deficiency that 0.93% and 2.56% were female and male respectively. Conclusion: color vision deficiency must be noticed by decision makers in health field for screen planning.

  3. [Vitamin B12 deficiency in the elderly].

    Science.gov (United States)

    Leischker, A H; Kolb, G F

    2015-01-01

    The prevalence of vitamin B12 deficiency increases with age. Patients with dementia and spouses of patients with dementia are at special risk for the development of vitamin B12 deficiency. In a normal diet this vitamin is present only in animal source foods; therefore, vegans frequently develop vitamin B12 deficiency if not using supplements or foods fortified with cobalamin. Apart from dementia, most of these manifestations are completely reversible under correct therapy; therefore it is crucial to identify and to treat even atypical presentations of vitamin B12 deficiency as early as possible. This article deals with the physiology and pathophysiology of vitamin B12 metabolism. A practice-oriented algorithm which also considers health economic aspects for a rational laboratory diagnosis of vitamin B12 deficiency is presented. In cases with severe neurological symptoms, therapy should be parenteral, especially initially. For parenteral treatment, hydroxocobalamin is the drug of choice. PMID:25586321

  4. [Vitamin B12 deficiency in the elderly].

    Science.gov (United States)

    Leischker, A H; Kolb, G F

    2015-01-01

    The prevalence of vitamin B12 deficiency increases with age. Patients with dementia and spouses of patients with dementia are at special risk for the development of vitamin B12 deficiency. In a normal diet this vitamin is present only in animal source foods; therefore, vegans frequently develop vitamin B12 deficiency if not using supplements or foods fortified with cobalamin. Apart from dementia, most of these manifestations are completely reversible under correct therapy; therefore it is crucial to identify and to treat even atypical presentations of vitamin B12 deficiency as early as possible. This article deals with the physiology and pathophysiology of vitamin B12 metabolism. A practice-oriented algorithm which also considers health economic aspects for a rational laboratory diagnosis of vitamin B12 deficiency is presented. In cases with severe neurological symptoms, therapy should be parenteral, especially initially. For parenteral treatment, hydroxocobalamin is the drug of choice.

  5. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    OpenAIRE

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T.; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M.

    2009-01-01

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (Ay/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficien...

  6. The Constitutional Deficiencies of the German 'Rechtsgutslehre'

    Directory of Open Access Journals (Sweden)

    Carl-Friedrich Stuckenberg

    2013-01-01

    Full Text Available This paper questions the theoretical merits and constitutional validity of the “Rechtsgutslehre” (doctrine of the protection of legal goods, a widely held doctrine about the limits of legitimate criminalization in Germany and some other jurisdictions. The immediate cause for this reassessment is a recent decision of the German constitutional court which upheld the German incest prohibition and simultaneously rejected the traditional “Rechtsgutslehre” as constitutionally irrelevant, thereby stirring up considerable controversy among academic criminal lawyers. The paper tries to show why the court’s view is correct by pointing out the main deficiencies of the doctrine and what criteria a better theory must fulfil. Este artículo cuestiona los méritos teóricos y la validez constitucional de la "Rechtsgutslehre" (doctrina de la protección de los bienes jurídicos, una doctrina muy extendida acerca de los límites de la criminalización legítima en Alemania y algunas otras jurisdicciones. La causa inmediata de esta nueva valoración es una decisión reciente del Tribunal Constitucional alemán que ratificó la prohibición del incesto en Alemania y al mismo tiempo rechazó el tradicional "Rechtsgutslehre" por ser constitucionalmente irrelevante, lo que provocó una considerable controversia entre la comunidad académica de abogados criminalistas. El artículo trata de mostrar por qué la decisión de la corte es correcta, señalando las deficiencias principales de la doctrina y los criterios que una teoría más adecuada debe cumplir. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2200870

  7. Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.

    Science.gov (United States)

    Barber, T; Borrás, E; Torres, L; García, C; Cabezuelo, F; Lloret, A; Pallardó, F V; Viña, J R

    2000-07-01

    Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored in re-fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was significantly lower than in control rats and returned to normal levels in restored vitamin A rats. Two populations of mitochondria were found in vitamin A-deficient rats according to the composition of membrane lipids. One population showed a similar pattern to the control mitochondria and the second population had a higher membrane lipid content. This report emphasizes the protective role of vitamin A in liver mitochondria under physiological circumstances.

  8. Historical role of alpha-1-antitrypsin deficiency in respiratory and hepatic complications.

    Science.gov (United States)

    Zuo, Li; Pannell, Benjamin K; Zhou, Tingyang; Chuang, Chia-Chen

    2016-09-10

    Alpha-1-antitrypsin (AAT) deficiency is a heritable disease that is commonly associated with complications in the respiratory and hepatic systems. AAT acts as a regulatory enzyme that primarily inhibits neutrophil elastase activity thus protecting tissues from proteolytic damage after inflammation. This paper provides a historical review of the discovery, classification, phenotypic expression, and treatment of AAT deficiency. While its pattern of inheritance has been long understood, the underlying mechanism between AAT deficiency and related diseases remains to be elucidated. Most commonly, AAT deficiency is associated with the development of emphysema in the lungs as well as various liver injuries. Cigarette smoke has been shown to be particularly detrimental in AAT deficient individuals during the development of lung disease. Therefore, understanding familial history may be beneficial when educating patients regarding lifestyle choices. While numerous AAT deficient phenotypes exist in the human populations, only specific variants have been proven to markedly predispose individuals to lung and liver disorders. The exact relationship between AAT levels and the aforementioned diseases is an essential area of further research. It is imperative that clinicians and researchers alike strive to standardize diagnostic criteria and develop safe and effective therapies for this genetic disease. PMID:26768576

  9. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

    Science.gov (United States)

    Pawlak, Roman

    2015-06-01

    The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. PMID:25998928

  10. Radiation protection

    CERN Multimedia

    Radioactive Shipping Service

    2005-01-01

    The section of the radiation protection group in charge of shipping radioactive material would like to remind users that all radioactive material leaving CERN must be checked for radioactivity and must be shipped according to the procedure given at http://cern.ch/service-rp-shipping Do not hesitate to contact us for any question or control. Radioactive Shipping Service: service-rp-shipping@cern.ch Tél. 73171

  11. Radiation protection

    CERN Multimedia

    2005-01-01

    The section of the Radiation Protection Group in charge of shipping radioactive material would like to remind users that all radioactive material leaving CERN must be checked for radioactivity and must be shipped according to the procedure given at http://cern.ch/service-rp-shipping Do not hesitate to contact us for any question or control. Radioactive Shipping Service: service-rp-shipping@cern.ch Tél. 73171

  12. Radiation protection

    CERN Multimedia

    2005-01-01

    The section of the Radiation Protection Group in charge of shipping radioactive material would like to remind users that all radioactive material leaving CERN must be checked for radioactivity and must be shipped according to the procedure given at http://cern.ch/service-rp-shipping Do not hesitate to contact us for any question or control. Radioactive Shipping Service: service-rp-shipping@cern.ch Tel. 73171

  13. Corrosion protection

    International Nuclear Information System (INIS)

    This invention describes a corrosion protection device for long-term storage containers of radioactive matter, in particular of irradiated fuel elements stored in geological formations apt for the purpose. This device prevents corrosion of the containers even if water emerges unexpectedly, or, in any case, inhibits and minimizes corrosion. The device comprehends reactive anodes that are connected to the containers by means of conductive connections. (orig.)

  14. Vitamin D deficiency in adolescents

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2014-01-01

    Full Text Available The prevalence of severe vitamin D deficiency (VDD in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical presentations may be subtle and go unnoticed, thus making true prevalence studies difficult. Adolescents with severe VDD may present with vague manifestations including pain in weight-bearing joints, back, thighs and/or calves, difficulty in walking and/or climbing stairs, or running and muscle cramps. Adaptation includes increased parathormone (PTH and deceased insulin-like growth factor-I (IGF-I secretion. PTH enhances the tubular reabsorption of Ca and stimulates the kidneys to produce 1, 25-(OH 2D3 that increases intestinal calcium absorption and dissolves the mineralized collagen matrix in bone, causing osteopenia and osteoporosis to provide enough Ca to prevent hypocalcaemia. Decreased insulin like growth factor-I (IGF-I delays bone growth to economize calcium consumption. Radiological changes are not uncommon and include osteoporosis/osteopenia affecting long bones as well as vertebrae and ribs, bone cysts, decalcification of the metaphysis of the long bones and pseudo fractures. In severe cases pathological fractures and deformities may occur. Vitamin D treatment of adolescents with VDD differs considerably in different studies and proved to be effective in treating all clinical, biochemical, and radiological manifestations. Different treatment regiments for VDD have been discussed and presented in this mini-review for practical use. Adequate vitamin D replacement after treating VDD, improving calcium intake (milk and dairy products, encouraging

  15. Protecting Democracy

    DEFF Research Database (Denmark)

    Galster, Kjeld

    2007-01-01

    ABSTRACT Galster, Kjeld Hald. Doctoral Student (History). Saxo Institute. May 2007. Protecting Democracy: Danish Defence Debate in Times of Change. Supervisor: Professor, Dr. Gunner Lind. Democratic debate on defence and democratic organisation of the forces are as central to the life of a democr......ABSTRACT Galster, Kjeld Hald. Doctoral Student (History). Saxo Institute. May 2007. Protecting Democracy: Danish Defence Debate in Times of Change. Supervisor: Professor, Dr. Gunner Lind. Democratic debate on defence and democratic organisation of the forces are as central to the life....... The dissertation addresses two essential problems of the correlation of democracy, the debate, and the current defence policy. Firstly, is democratic society capable of pursuing constantly a defence policy reflecting the classic, realist logic, or does this happen only sporadically, because the debate is being.......d.-studerende (historie). Saxo-Instituttet, maj 2007. Protecting Democracy: Danish Defence Debate in Times of Change. Vejleder: Professor, dr. phil. Gunner Lind. En forsvarsdebat hvilende på demokratisk debat og en demokratisk indretning af forsvaret er lige så selvfølgeligt for den demokratiske stat som forsvar i det...

  16. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

  17. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID:26564715

  18. On the worrying fate of Data Deficient amphibians.

    Science.gov (United States)

    Nori, Javier; Loyola, Rafael

    2015-01-01

    The 'Data Deficient' (DD) category of the IUCN Red List assembles species that cannot be placed in another category due to insufficient information. This process generates uncertainty about whether these species are safe or actually in danger. Here, we give a global overview on the current situation of DD amphibian species (almost a quarter of living amphibians) considering land-use change through habitat modification, the degree of protection of each species and the socio-political context of each country harboring DD species. We found that DD amphibians have, on average, 81% of their ranges totally outside protected areas. Worryingly, more than half of DD species have less than 1% of their distribution represented in protected areas. Furthermore, the percentage of overlap between species' range and human-modified landscapes is high, at approximately 58%. Many countries harboring a large number of DD species show a worrying socio-political trend illustrated by substantial, recent incremental increases in the Human Development Index and lower incremental increases in the establishment of protected areas. Most of these are African countries, which are located mainly in the central and southern regions of the continent. Other countries with similar socio-political trends are in southeastern Asia, Central America, and in the northern region of South America. This situation is concerning, but it also creates a huge opportunity for considering DD amphibians in future conservation assessments, planning, and policy at different levels of government administration.

  19. Effect of ADH II Deficiency on the Intracellular Redox Homeostasis in Zymomonas mobilis

    Directory of Open Access Journals (Sweden)

    Nina Galinina

    2012-01-01

    Full Text Available Mutant strain of the facultatively anaerobic, ethanol-producing bacterium Zymomonas mobilis, deficient in the Fe-containing alcohol dehydrogenase isoenzyme (ADH II, showed impaired homeostasis of the intracellular NAD(PH during transition from anaerobic to aerobic conditions, and also in steady-state continuous cultures at various oxygen supplies. At the same time, ADH II deficiency in aerobically grown cells was accompanied by a threefold increase of catalase activity and by about 50% increase of hydrogen peroxide excretion. It is concluded that ADH II under aerobic conditions functions to maintain intracellular redox homeostasis and to protect the cells from endogenous hydrogen peroxide.

  20. Effect of ADH II deficiency on the intracellular redox homeostasis in Zymomonas mobilis.

    Science.gov (United States)

    Galinina, Nina; Lasa, Zane; Strazdina, Inese; Rutkis, Reinis; Kalnenieks, Uldis

    2012-01-01

    Mutant strain of the facultatively anaerobic, ethanol-producing bacterium Zymomonas mobilis, deficient in the Fe-containing alcohol dehydrogenase isoenzyme (ADH II), showed impaired homeostasis of the intracellular NAD(P)H during transition from anaerobic to aerobic conditions, and also in steady-state continuous cultures at various oxygen supplies. At the same time, ADH II deficiency in aerobically grown cells was accompanied by a threefold increase of catalase activity and by about 50% increase of hydrogen peroxide excretion. It is concluded that ADH II under aerobic conditions functions to maintain intracellular redox homeostasis and to protect the cells from endogenous hydrogen peroxide.

  1. JNK1 Deficiency Does Not Enhance Muscle Glucose Metabolism in Lean Mice*

    OpenAIRE

    Witczak, CA; Hirshman, MF; Jessen, N.; Fujii, N; Seifert, M.; Brandauer, J; Hotamisligil, GS; Goodyear, LJ

    2006-01-01

    Mice deficient in c‐jun‐NH2‐terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity‐induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction‐induced muscle [³H]‐2‐deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct a...

  2. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia iron-refractory iron deficiency anemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  3. Genetics Home Reference: mannose-binding lectin deficiency

    Science.gov (United States)

    ... Health Conditions mannose-binding lectin deficiency mannose-binding lectin deficiency Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mannose-binding lectin deficiency is a condition that affects the immune ...

  4. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Home Health Conditions ataxia with vitamin E deficiency ataxia with vitamin E deficiency Enable Javascript to view ... boxes. Download PDF Open All Close All Description Ataxia with vitamin E deficiency is a disorder that ...

  5. Flu Vaccine Guidance for Patients with Immune Deficiency

    Science.gov (United States)

    ... Vaccine Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This ... is the best tool for prevention of the flu, should patients with immune deficiency be given the ...

  6. Testosterone deficiency and cardiovascular mortality

    Institute of Scientific and Technical Information of China (English)

    Abraham Morgentaler

    2015-01-01

    New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T‑treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T‑deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.

  7. Primary Immuno-deficiencies (PID

    Directory of Open Access Journals (Sweden)

    Javad Ghaffari1

    2009-01-01

    Full Text Available (Received 6 June, 2009 ; Accepted 22 July, 2009AbstractBackground and purpose: Primary immune-deficiencies (PID are associated with a wide range of clinical disorders along with variable symptoms. The aim of this study was to evaluate and improve our knowledge regarding PID from patients that were referred to Booali Sina Hospital.Materials and methods: We evaluated all of PID`s that were referred to Booali Sina Hospital from their data records. Demography, clinical and laboratory data were recorded and then analyzed.Results: In the duration of 3 years, we had 10 patients with PID (7 males and 3 females. Of these cases, 5 had hum oral (50%, 1case had phagocytic (10%, 3 cases had cellular (30% and 1 case had hyper IgE syndrome (10%. Many of them had respiratory and otitis media infections, while a few patients had adenitis, gastroenteritis, liver abscesses, bleedings and malignancy.Conclusion: PID is a diverse disorder that involves different immune systems. Knowledge from patient’s clinical symptoms and consideration in their differential diagnosis can be helpful in early diagnosis and an effective treatment.J Mazand Univ Med Sci 2009; 19(70: 76-80 (Persian

  8. Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity

    Directory of Open Access Journals (Sweden)

    Palmiter Richard D

    2005-12-01

    Full Text Available Abstract Background Autosomal recessive juvenile parkinsonism (AR-JP is caused by mutations in the parkin gene which encodes an E3 ubiquitin-protein ligase. Parkin is thought to be critical for protecting dopaminergic neurons from toxic insults by targeting misfolded or oxidatively damaged proteins for proteasomal degradation. Surprisingly, mice with targeted deletions of parkin do not recapitulate robust behavioral or pathological signs of parkinsonism. Since Parkin is thought to protect against neurotoxic insults, we hypothesized that the reason Parkin-deficient mice do not develop parkinsonism is because they are not exposed to appropriate environmental triggers. To test this possibility, we challenged Parkin-deficient mice with neurotoxic regimens of either methamphetamine (METH or 6-hydroxydopamine (6-OHDA. Because Parkin function has been linked to many of the pathways involved in METH and 6-OHDA toxicity, we predicted that Parkin-deficient mice would be more sensitive to the neurotoxic effects of these agents. Results We found no signs consistent with oxidative stress, ubiquitin dysfunction, or degeneration of striatal dopamine neuron terminals in aged Parkin-deficient mice. Moreover, results from behavioral, neurochemical, and immunoblot analyses indicate that Parkin-deficient mice are not more sensitive to dopaminergic neurotoxicity following treatment with METH or 6-OHDA. Conclusion Our results suggest that the absence of a robust parkinsonian phenotype in Parkin-deficient mice is not due to the lack of exposure to environmental triggers with mechanisms of action similar to METH or 6-OHDA. Nevertheless, Parkin-deficient mice could be more sensitive to other neurotoxins, such as rotenone or MPTP, which have different mechanisms of action; therefore, identifying conditions that precipitate parkinsonism specifically in Parkin-deficient mice would increase the utility of this model and could provide insight into the mechanism of AR

  9. Features and outcomes of malaria infection in glucose-6-phosphatedehydrogenase normal and deficient Nigerian children

    Directory of Open Access Journals (Sweden)

    Adebola Emmanuel Orimadegun

    2014-01-01

    Full Text Available Background & objectives: Malaria and G6PD deficiency-related haemolyses are known causes of hospital admissions in Nigeria and pose great danger to child survival but data on interactions of these two pathologies are scarce. This study was carried out to determine the association between features of Plasmodium falciparum infection and G6PD status. Methods: G6PD and haemoglobin were typed by fluorescent spot test and electrophoresis respectively, in 1120 children with microscopically-proven falciparum malaria. Clinical features of malaria were compared between G6PD normal and deficient children. Results: There were 558 males and 562 females with median age of 35 months (range, 6 months-12 yr. In males, prevalence of G6PD-deficiency in patients with uncomplicated malaria (UM, severe malarial anaemia (SMA and cerebral malaria (CM was 23.4, 7 and 16.7%, respectively compared with 11.1, 7.3 and 4.4%, respectively among females. In both males and females, convulsion and rectal temperature above 38°C were less likely presentations among G6PD-deficient compared with G6PD-normal children (p <0.05. The proportions of children with pallor, convulsion and impaired consciousness were significantly lower among G6PD-deficient than normal males (p <0.05 but these features were not different between deficient and normal females (p >0.05. Interpretation & conclusion: Convulsions, pallor and elevated temperature were more frequent features of malaria in G6PD normal than deficient children. G6PD-deficient male children are protected against impaired consciousness. These differences may offer useful hints in malaria treatment and researches in endemic regions.

  10. Vitamin D Deficiency in BALB/c Mouse Pregnancy Increases Placental Transfer of Glucocorticoids.

    Science.gov (United States)

    Tesic, Dijana; Hawes, Jazmin E; Zosky, Graeme R; Wyrwoll, Caitlin S

    2015-10-01

    The prevalence of vitamin D deficiency in pregnancy is increasing and implicated in adverse consequences for the health of offspring in later life. The aim of this study was to determine whether vitamin D deficiency increases fetal exposure to glucocorticoids, which are known to alter fetal development and result in adverse adult health outcomes. Female BALB/c mice were placed on either a vitamin D control (2195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks before and during pregnancy. Maternal serum, placentas and fetal brains were collected at embryonic day 14.5 or 17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy increased maternal corticosterone concentrations and reduced placental weight. Maternal vitamin D deficiency decreased placental expression of 11β-hydroxysteroid dehydrogenase type II, which inactivates glucocorticoids thereby protecting the fetus from inappropriate glucocorticoid exposure. There was a corresponding increase in placental and fetal expression of the highly glucocorticoid-sensitive factor glucocorticoid-induced leucine zipper. Furthermore, placental expression of the angiogenic factor vascular endothelial growth factor-A was reduced in vitamin D-deficient pregnancies, with a corresponding decline in fetal capillary volume within the placenta. Overall, we show that prenatal vitamin D deficiency leads to an increase in maternal corticosterone, alterations in genes indicative of increased fetal glucocorticoid exposure and impairment in placental vascular development. Thus, the long-term adverse health consequences of vitamin D deficiency during early development may not just be due to alteration in direct vitamin D-related pathways but also altered fetal glucocorticoid exposure. PMID:26252062

  11. Antibiotic prophylaxis in primary immune deficiency disorders.

    Science.gov (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  12. Reticulocyte maturity indices in iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Muriel Wollmann

    2014-01-01

    Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

  13. Treatment of zinc deficiency without zinc fortification

    Institute of Scientific and Technical Information of China (English)

    Donald OBERLEAS; Barbara F. HARLAND

    2008-01-01

    Zinc (Zn) deficiency in animals became of interest until the 1950s. In this paper, progresses in researches on physi-ology of Zn deficiency in animals, phytate effect on bioavailability of Zn, and role of phytase in healing Zn deficiency of animals were reviewed. Several studies demonstrated that Zn is recycled via the pancreas; the problem of Zn deficiency was controlled by Zn homeostasis. The endogenous secretion of Zn is considered as an important factor influencing Zn deficiency, and the critical molar ratio is 10. Phytate (inositol hexaphosphate) constituted up to 90% of the organically bound phosphorus in seeds. Great improvement has been made in recent years on isolating and measuring phytate, and its structure is clear. Phytate is considered to reduce Zn bioavailability in animal. Phytase is the enzyme that hydrolyzes phytate and is present in yeast, rye bran, wheat bran, barley, triticale, and many bacteria and fungi. Zinc nutrition and bioavailability can be enhanced by addition of phytase to animal feeds. Therefore, using phytase as supplements, the most prevalent Zn deficiency in animals may be effectively corrected without the mining and smelting of several tons of zinc daily needed to correct this deficiency by fortification worldwide.

  14. Perinatal iron deficiency and neurocognitive development

    Directory of Open Access Journals (Sweden)

    Emily Clare Radlowski

    2013-09-01

    Full Text Available Iron deficiency is the most common form of nutrient deficiency worldwide. It is highly prevalent due to the limited availability of high quality food in developing countries, and poor dietary habits in industrialized countries. According to the World Health Organization, it affects nearly 2 billion people and up to 50% of women who are pregnant. Maternal anemia during pregnancy is especially burdensome to healthy neurodevelopment in the fetus because iron is needed for proper neurogenesis, development, and myelination. Maternal anemia also increases the risk of low birth weight, either due to premature birth or fetal growth restriction, which is associated with delayed neurocognitive development and even psychiatric illness. As rapid neurodevelopment continues after birth infants that received sufficient iron in utero, but that receive a low iron diet after 6 months of age, also show deficits in neurocognitive development, including impairments in learning and memory. Unfortunately, the neurocognitive complications of iron deficiency during critical pre- and postnatal periods of brain development are difficult to remedy, persisting into adulthood. Thus, preventing iron deficiency in the pre- and postnatal periods is critical as is devising new means to recapture cognitive function in individuals who experienced early iron deficiency. This review will discuss the prevalence of pre- and postnatal iron deficiency, the mechanism, and effects of iron deficiency on brain and cognitive development.

  15. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif;

    1995-01-01

    Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency ......Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH...

  16. C3 Deficiency – A Case Report

    OpenAIRE

    Carreiro-Martins, P; Gaspar, A.; Rosado-Pinto, J.

    2006-01-01

    O sistema do complemento é um componente essencial do sistema imunitário inato, pelo que as deficiências de proteínas da sua complexa cascata podem ter consequências mais ou menos graves, de acordo com a importância do factor afectado. As complicações mais usuais das deficiências do complemento são infecções recorrentes a bactérias encapsuladas e distúrbios autoimunes. Os autores apresentam um caso clínico de deficiência do factor C3, situação extremamente rara, discutindo a fisiopatolo...

  17. Nutrition and hair: deficiencies and supplements.

    Science.gov (United States)

    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.

  18. The clinical spectrum of hexosaminidase deficiency diseases.

    Science.gov (United States)

    Johnson, W G

    1981-11-01

    Hexosaminidase deficiency diseases or GM2-gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.

  19. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    Science.gov (United States)

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  20. Severe Vitamin D Deficiency Causing Kyphoscoliosis.

    Science.gov (United States)

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been misdiagnosed as musculoskeletal disorders, including fibromyalgia, polymyalgia rheumatica and ankylosing spondylitis. Here, we report two cases presented with kyphoscoliosis, diagnosed to have severe vitamin D deficiency. PMID:26664847

  1. Protecting Antarctica

    Science.gov (United States)

    Carlowicz, Michael

    House Science Committee Chairman Robert Walker (R-Pa.) has introduced a bill into Congress to give the United States the legislative authority to implement the 1991 Environmental Protocol to the Antarctic Treaty. That protocol established rules and principles to shield the Antarctic environment from human spoilage—placing limits on the discharge of pollutants, protecting plant and animal life, and requiring environmental impact assessments before new activities and programs are launched. The protocol also forbids prospecting or developing of mineral resources except for scientific research.

  2. Environmental protection

    International Nuclear Information System (INIS)

    Environmental Studies and Internal Dosimetry projects include: Environmental Protection; 1977 Environmental Monitoring Report; Sewage Sludge Disposal on the Sanitary Landfill; Radiological Analyses of Marshall Islands Environmental Samples, 1974 to 1976; External Radiation Survey and Dose Predictions for Rongelap, Utirik, Rongerik, Ailuk, and Wotje Atolls; Marshall Islands - Diet and Life Style Study; Dose Reassessment for Populations on Rongelap and Utirik Following Exposure to Fallout from BRAVO Incident (March 1, 1954); Whole Body Counting Results from 1974 to 1979 for Bikini Island Residents; Dietary Radioactivity Intake from Bioassay Data, a Model Applied to 137Cs Intake by Bikini Island Residents; and External Exposure Measurements at Bikini Atoll

  3. Investigation of suspected growth hormone deficiency

    OpenAIRE

    Milner, R. D. G.; Burns, E C

    1982-01-01

    This paper describes views of the Health Services Human Growth Hormone Committee on how a child suspected of growth hormone deficiency should be investigated in a district general hospital or in a regional growth centre.

  4. Genetics Home Reference: GLUT1 deficiency syndrome

    Science.gov (United States)

    ... genetic conditions treated or managed? What is genetic testing? How can I find a genetics professional in my area? Other Names for This Condition De Vivo disease encephalopathy due to GLUT1 deficiency G1D glucose ...

  5. FastStats: Anemia or Iron Deficiency

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Anemia or Iron Deficiency Recommend on Facebook Tweet Share ... visits Number of visits to emergency departments with anemia as the primary hospital discharge diagnosis: 237,000 ...

  6. Sepiapterin Reductase Deficiency: Mimic of Cerebral Palsy

    OpenAIRE

    J Gordon Millichap

    2012-01-01

    Researchers at University of California at San Diego, and 22 other US national and international centers studied the clinical, biochemical, and molecular findings in a cohort of 38 patients with sepiapterin reductase deficiency (SRD).

  7. Somatomedin C deficiency in Asian sisters.

    OpenAIRE

    McGraw, M E; Price, D A; D. J. Hill

    1986-01-01

    Two sisters of Asian origin showed typical clinical and biochemical features of primary somatomedin C (SM-C) deficiency (Laron dwarfism). Abnormalities of SM-C binding proteins were observed, one sister lacking the high molecular weight (150 Kd) protein.

  8. Genetics Home Reference: deoxyguanosine kinase deficiency

    Science.gov (United States)

    ... or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the ... DNA (known as mitochondrial DNA depletion) impairs mitochondrial function ... deficiency . Learn more about the gene associated ...

  9. Vitamin D Deficiency (Beyond the Basics)

    Science.gov (United States)

    ... of Use ©2016 UpToDate, Inc. Patient education: Vitamin D deficiency (Beyond the Basics) Author Marc K Drezner, ... topic last updated: Jun 09, 2015. INTRODUCTION — Vitamin D plays an important role in many places throughout ...

  10. Genetics Home Reference: glutathione synthetase deficiency

    Science.gov (United States)

    ... elevated acidity in the blood and tissues (metabolic acidosis). In addition to the features present in moderate ... Kaabachi N, Hachicha M. Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency. Fetal Pediatr Pathol. ...

  11. Genetics Home Reference: phosphoglycerate kinase deficiency

    Science.gov (United States)

    ... Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Muscular Dystrophy Association National Organization for Rare Disorders (NORD) Resource list from the University of Kansas Medical Center: Metabolic Conditions Genetic Testing Registry (2 links) Deficiency of phosphoglycerate kinase ...

  12. Genetics Home Reference: sepiapterin reductase deficiency

    Science.gov (United States)

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions sepiapterin reductase deficiency sepiapterin reductase ...

  13. Genetics Home Reference: dopamine transporter deficiency syndrome

    Science.gov (United States)

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions dopamine transporter deficiency syndrome dopamine ...

  14. Genetics Home Reference: familial glucocorticoid deficiency

    Science.gov (United States)

    ... Clark AJ, Metherell LA. ACTH resistance: genes and mechanisms. Endocr Dev. 2013;24:57-66. doi: 10. ... Metherell LA. Familial glucocorticoid deficiency: New genes and mechanisms. Mol Cell Endocrinol. 2013 May 22;371(1- ...

  15. Vitamin K deficiency bleeding of the newborn

    Science.gov (United States)

    Vitamin K deficiency bleeding of the newborn (VKDB) is a bleeding disorder in babies. It most often ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often ...

  16. Iron Deficiency, Zinc, Magnesium, Vitamin Deficiencies in Crohn's Disease: Substitute or Not?

    Science.gov (United States)

    Kruis, Wolfgang; Phuong Nguyen, G

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by inflammatory reactions, complications, extraintestinal manifestations and a loss of intestinal functions, for example, failures of absorption and secretion. According to intestinal dysfunction, a wide array of pathogenetic pathways is existing leading to iron deficiency and numerous vitamins as well as trace element deficiencies. Complications, symptoms and signs of those deficiencies are common in IBD with varying degrees of clinical significance. This review focuses on selected micronutrients including iron, zinc, magnesium and some vitamins. Epidemiology with respect to IBD, pathophysiology, diagnosis and clinical aspects are addressed. Finally, some suggestions for treatment of deficient situations are discussed. In conclusion, some micronutrients have significant impact on complications and quality of life in IBD. Deficiencies may even influence the course of the disease. Those deficiencies should be thoroughly supplemented.

  17. Androgen deficiency and aging in men.

    OpenAIRE

    Swerdloff, R S; Wang, C

    1993-01-01

    Androgen levels decrease with age in men. Androgen deficiency in men older than 65 years leads to asthenia, a decrease in muscle mass, osteoporosis, and a decrease in sexual activity. Androgen deficiency has been reported to cause changes in mood and cognitive function. The combination of these factors results in impaired quality of life in older men. Androgen replacement therapy in hypogonadal men increases bone and muscle mass, enhances muscle and cardiovascular function, and improves sexua...

  18. Deficiently Extremal Cohen-Macaulay Algebras

    Indian Academy of Sciences (India)

    Chanchal Kumar; Pavinder Singh

    2010-04-01

    The aim of this paper is to study homological properties of deficiently extremal Cohen–Macaulay algebras. Eagon–Reiner showed that the Stanley–Reisner ring of a simplicial complex has a linear resolution if and only if the Alexander dual of the simplicial complex is Cohen–Macaulay. An extension of a special case of Eagon–Reiner theorem is obtained for deficiently extremal Cohen–Macaulay Stanley–Reisner rings.

  19. Cobalamin Deficiency: Clinical Picture and Radiological Findings

    OpenAIRE

    Chiara Briani; Chiara Dalla Torre; Valentina Citton; Renzo Manara; Sara Pompanin; Gianni Binotto; Fausto Adami

    2013-01-01

    Vitamin B12 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological disorders. Hematological presentation of cobalamin deficiency ranges from the incidental increase of mean corpuscular volume and neutrophil hypersegmentation to symptoms due to severe anemia, such as angor, dyspnea on exertion, fatigue or symptoms related to congestive heart failure, such as ankle edema, orthopnea and nocturia. Neuropsychiatric symptoms may precede hematologic signs and...

  20. Congenital leptin deficiency and thyroid function

    OpenAIRE

    Paz-Filho Gilberto; Delibasi Tuncay; Erol Halil K; Wong Ma-Li; Licinio Julio

    2009-01-01

    Abstract Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four l...

  1. Study of neutron-deficient Sn isotopes

    International Nuclear Information System (INIS)

    The formation of neutron deficient nuclei by heavy ion reactions is investigated. The experimental technique is presented, and the results obtained concerning Sn et In isotopes reported: first excited states of 106Sn, high spin states in 107Sn and 107In; Yrast levels of 106Sn, 107Sn, 108Sn; study of neutron deficient Sn and In isotopes formed by the desintegration of the compound nucleus 112Xe. All these results are discussed

  2. Severe Vitamin D Deficiency Causing Kyphoscoliosis

    OpenAIRE

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been ...

  3. Vitamin D Deficiency: Time for Inaction?

    OpenAIRE

    Plotnikoff, Gregory

    2013-01-01

    In 1998, the British Medical Journal boldly stated in an editorial headline, “Vitamin D Deficiency: Time for Action.” 1 The urgency was clear: vitamin D deficiency was going undiagnosed and untreated in large numbers of people. Patients were at risk and suffering needlessly. A simple, extremely low-cost, low-toxicity intervention was readily available. All that was required was vitamin D advocacy.

  4. TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed;

    2006-01-01

    in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate...... this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...... deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells...

  5. Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

    Science.gov (United States)

    von Bernuth, Horst; Picard, Capucine; Jin, Zhongbo; Pankla, Rungnapa; Xiao, Hui; Ku, Cheng-Lung; Chrabieh, Maya; Mustapha, Imen Ben; Ghandil, Pegah; Camcioglu, Yildiz; Vasconcelos, Júlia; Sirvent, Nicolas; Guedes, Margarida; Vitor, Artur Bonito; Herrero-Mata, María José; Aróstegui, Juan Ignacio; Rodrigo, Carlos; Alsina, Laia; Ruiz-Ortiz, Estibaliz; Juan, Manel; Fortuny, Claudia; Yagüe, Jordi; Antón, Jordi; Pascal, Mariona; Chang, Huey-Hsuan; Janniere, Lucile; Rose, Yoann; Garty, Ben-Zion; Chapel, Helen; Issekutz, Andrew; Maródi, László; Rodriguez-Gallego, Carlos; Banchereau, Jacques; Abel, Laurent; Li, Xiaoxia; Chaussabel, Damien; Puel, Anne; Casanova1, Jean-Laurent

    2009-01-01

    MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections. PMID:18669862

  6. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

    Science.gov (United States)

    The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid tran...

  7. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

    Science.gov (United States)

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

  8. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model

    OpenAIRE

    Marjorie Buttet; Hélène Poirier; Véronique Traynard; Kévin Gaire; Thi Thu Trang Tran; Sinju Sundaresan; Philippe Besnard; Abumrad, Nada A.; Isabelle Niot

    2016-01-01

    The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of ...

  9. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation.

    OpenAIRE

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot ana...

  10. [Approaches to vitamin B12 deficiency].

    Science.gov (United States)

    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. Divorced Women's Property Protection from Social Gender Perspective --On the Deficiency and Perfection of Divorced Women's Property Protection in Judicial Explanation in Marriage Law%基于社会性别分析下的离婚妇女财产权保护——兼议《〈婚姻法〉司法解释(三)》对离婚妇女财产权保护的不足与完善

    Institute of Scientific and Technical Information of China (English)

    冯博

    2012-01-01

    This paper discusses the law' s inadequate protection of divorced women' s property rights because its ignorance of social gender theory from the view of this theory. Thus we should put social gender theory into marriage law and define the proportion of prenuptial property division when divorcing to realize the special protection for women s rights.%从社会性别理论的视角来看,我国现行婚姻法律制度由于忽视了社会性别理论,而导致了对离婚妇女财产权保护力度不足的现状。因此,建议在婚姻法律制度中植入社会性别理论,并建议在离婚时对婚前财产应考虑增值部分和损耗部分,按比例处分,以实现对女性权利的特殊保护。

  12. Offspring Protection

    Directory of Open Access Journals (Sweden)

    Eric T. Steiner

    2016-08-01

    Full Text Available Parental aggression, that is, offspring protection aggression, can be viewed as a type of parental investment. Most mammalian males do not exhibit parental investment and therefore exhibit little, if any, parental aggression. Men demonstrate parental investment, and are typically more physically aggressive than women, but parental physical aggression in humans has been largely unexplored. The current study examined potential sex differences in estimates of parental physical aggression involving hypothetical situations, while controlling for general physical aggression. A self-report measure was administered to 217 students from a western U.S. university (55 male nonparents, 50 female nonparents, 54 fathers, and 58 mothers. Male nonparents reported higher parental physical aggression than female nonparents, but there was no difference between mothers and fathers. The results are interpreted in light of ancestral effects of sexual selection and proximal effects of sex differences in testosterone, risk taking, and fear aversion.

  13. Protective clothing

    International Nuclear Information System (INIS)

    A protective suit used for isolating its wearer from radioactively contaminated areas is described in three parts. The first part includes the covering for the wearer's head, arms and upper body and at the waist is releasably fitted around an opening into the contaminated area. The second part includes the legs of the suit and is releasably connectible to the first part of the suit to enclose the wearer who is then supplied with air through an umbilical pipe. A further part surrounds the second part and is releasably connectible to it, enclosing a space between the parts. This further part is also releasably connectible to the opening at the waist to prevent egress from the contaminated area. The releasable connections between the parts may be bayonet type fittings or may be rotating T-shaped projections which engage in T-shaped grooves. (author)

  14. 低磷对小麦代换系幼苗根系保护酶活性和丙二醛含量的影响及染色体效应%Effects of Phosphorus Deficiency Stress on Protective Enzyme Activities,MDA Content and Chromosome of Wheat Substitution Lines Seedling Roots

    Institute of Scientific and Technical Information of China (English)

    米少艳; 靖姣姣; 白志英; 李存东

    2013-01-01

      以中国春-Synthetic 6x染色体代换系及其亲本为材料,通过测定不同磷处理条件下根系抗氧化酶SOD、POD活性和丙二醛(MDA)含量,研究低磷胁迫对小麦代换系酶活性的影响,并对耐低磷胁迫特性的基因进行染色体定位。结果表明,低磷胁迫下,小麦代换系苗期根系SOD和POD活性显著升高,丙二醛含量降低。 Synthetic 6x的3A、4A、5A和7A染色体上可能存在诱导根系SOD活性增强的基因,5A、1D和2D染色体上可能存在诱导根系POD活性增强的基因,1A、2A、4B、6B和7D染色体上可能存在抑制根系MDA含量增高的基因。%The effects of phosphorus deficiency stress on enzyme activity in wheat was studied by determining antioxidant enzymes SOD,POD activities and MDA content and locating the gene controlling antioxidant enzymes SOD,POD activities and MDA content at the roots of the seedling stage using wheat substitution lines between Chi -nese Spring(CS)and Synthetic 6x.The results showed that SOD and POD activities increased ,MDA content reduced under phosphorus deficiency stress .This explains that the increased of antioxidant enzyme activity might reduce MDA content and lower membrane lipid peroxidation level ,to improve their resistance.The genes promoting SOD activity might be located on 3A,4A,5A and 7A chromosome of Synthetic 6x;and the genes promoting POD activity might be located on 5A,1D and 2D chromosome,while the genes inhibiting content might be located on 5A,2D,5D and 7D chromosome of Synthetic 6x.

  15. Lower limb deficient children in the Netherlands : epidemiological aspects

    NARCIS (Netherlands)

    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH

    2000-01-01

    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency o

  16. Immune response against Sporothrix schenckii in TLR-4-deficient mice.

    Science.gov (United States)

    Sassá, Micheli Fernanda; Ferreira, Lucas Souza; Ribeiro, Livia Carolina de Abreu; Carlos, Iracilda Zeppone

    2012-07-01

    For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.

  17. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    Science.gov (United States)

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

  18. Sensitivity of antioxidant-deficient yeast to hypochlorite and chlorite.

    Science.gov (United States)

    Kwolek-Mirek, Magdalena; Bartosz, Grzegorz; Spickett, Corinne M

    2011-08-01

    Sodium hypochlorite and sodium chlorite are commonly used as disinfectants, and understanding the mechanisms of microbial resistance to these compounds is of considerable importance. In this study, the role of oxidative stress and antioxidant enzymes in the sensitivity of the yeast Saccharomyces cerevisiae to hypochlorite and chlorite was studied. Yeast mutants lacking Cu-Zn superoxide dismutase, but not mutants deficient in cytoplasmic and peroxisomal catalase, were hypersensitive to the action of both hypochlorite and chlorite. Both compounds depleted cellular glutathione, induced the production of reactive oxygen species and decreased the viability of the cells. The toxicity of hypochlorite and chlorite was abolished by hypoxic and anoxic conditions and ameliorated by thiol antioxidants and ascorbate. The results demonstrated that the action of hypochlorite and chlorite involves the formation of superoxide and peroxide and that SOD1 is protective, probably by limiting the formation of hydroxyl radicals and damage to proteins. PMID:21761455

  19. [Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-].

    Science.gov (United States)

    Ozono, Keiichi

    2016-02-01

    Vitamin D deficiency causes rickets or osteomalacia, which is associated with hypomineralization of bone and chondrocytes, and/or hypocalcemia. Accumulating evidence indicates increase in frequency of vitamin D deficiency due to insufficient intake of vitamin D and calcium and decrease in sunshine. It is necessary for clinician to diagnose vitamin D deficiency accurately and treat patients with vitamin D deficiency adequately. For the purpose, clinical guideline or expert opinion on vitamin D deficiency has been reported. PMID:26813501

  20. [Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-].

    Science.gov (United States)

    Ozono, Keiichi

    2016-02-01

    Vitamin D deficiency causes rickets or osteomalacia, which is associated with hypomineralization of bone and chondrocytes, and/or hypocalcemia. Accumulating evidence indicates increase in frequency of vitamin D deficiency due to insufficient intake of vitamin D and calcium and decrease in sunshine. It is necessary for clinician to diagnose vitamin D deficiency accurately and treat patients with vitamin D deficiency adequately. For the purpose, clinical guideline or expert opinion on vitamin D deficiency has been reported.

  1. Iron deficiency anemia from diagnosis to treatment in children

    OpenAIRE

    Özdemir, Nihal

    2015-01-01

    Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms “iron deficiency” and “iron deficiency anemia” are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake toge...

  2. Vitamin D Deficiency Among Professional Basketball Players

    Science.gov (United States)

    Fishman, Matthew P.; Lombardo, Stephen J.; Kharrazi, F. Daniel

    2016-01-01

    Background: Vitamin D plays an important role in several systems of the human body. Various studies have linked vitamin D deficiency to stress and insufficiency fractures, muscle recovery and function, and athletic performance. The prevalence of vitamin D deficiency in the elite athletic population has not been extensively studied, and very few reports exist among professional athletes. Hypothesis: There is a high prevalence of vitamin D deficiency or insufficiency among players attending the National Basketball Association (NBA) Combine. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This is a retrospective review of data previously collected as part of the routine medical evaluation of players in the NBA Combines from 2009 through 2013. Player parameters evaluated were height, weight, body mass index (BMI), and vitamin D level. Statistical analysis using t tests and analysis of variance was used to detect any correlation between the player parameters and vitamin D level. Vitamin D levels were categorized as deficient (32 ng/mL). Results: After institutional review board approval was submitted to the NBA, the NBA released deidentified data on 279 players who participated in the combines from 2009 through 2013. There were 90 players (32.3%) who were deficient, 131 players (47.0%) who were insufficient, and 58 players (20.8%) who were sufficient. A total of 221 players (79.3%) were either vitamin D deficient or insufficient. Among all players included, the average vitamin D level was 25.6 ± 10.2 ng/mL. Among the players who were deficient, insufficient, and sufficient, the average vitamin D levels were 16.1 ± 2.1 ng/mL, 25.0 ± 3.4 ng/mL, and 41.6 ± 8.6 ng/mL, respectively. Player height and weight were significantly increased in vitamin D–sufficient players compared with players who were not sufficient (P = .0008 and .009, respectively). Player age and BMI did not significantly differ depending on vitamin D status (P = .15 and .77

  3. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  4. Vitamin D Deficiency in Medical Inpatients: A Retrospective Study of Implications of Untreated Versus Treated Deficiency

    Science.gov (United States)

    Zaidi, Syed Asher Hussain; Singh, Gurjit; Owojori, Olukolade; Kela, Ram; Spoors, Shirley; Abbas, Mohamed; Barton, Florence; Rogers, Caroline

    2016-01-01

    Vitamin D deficiency and insufficiency may further increase fracture risk in patients with decreased bone mineral density. A cross-sectional study on serum vitamin D concentrations in medical inpatients was conducted at Bassetlaw District General Hospital between April 2014 and January 2015 (10 months), and the relationship of serum vitamin D concentrations with calcium and alkaline phosphatase was evaluated. 25-Hydroxyvitamin D immunoassays were used and analyzed in the local laboratory. The total number of patients analyzed was 200, age range 18–99 years, with mean age of 76 years. The most common presentation was found to be fall/collapse. The following cutoff points for serum vitamin D were used: levels ≤30 nmol/L for severe deficiency, >30–50 nmol/L for moderate deficiency, >50–75 nmol/L for mild deficiency, and anything above 75 nmol/L as normal. Of the 209 participants examined, 78 (37.3%) participants had mild vitamin D deficiency, 54 (25.8%) participants had moderate vitamin D deficiency, 68 (32.5%) participants had severe vitamin D deficiency, and 9 (4.3%) participants with low vitamin D levels died during their admission. Of the 122 moderate/severe patients, 70 (57.4%) patients had their vitamin D deficiency treated, according to local Trust guidelines. The study found no relationship between serum calcium levels and vitamin D deficiency, whereas patients’ alkaline phosphatase levels were found to be higher with increased severity of vitamin D deficiency. The study examined the implications of untreated severe/moderate vitamin D deficiency compared to treated deficiency, in terms of the frequency of readmission with similar complaints. It was found that the rate of readmission within one year in patients who were not treated was 57%, compared to 48% in patients whose vitamin D deficiency was treated. Presenting after falls was a recurring theme. It was concluded that even if moderate vitamin D deficiency can be asymptomatic, it is important to

  5. Vitamin D Deficiency in Medical Inpatients: A Retrospective Study of Implications of Untreated Versus Treated Deficiency

    Science.gov (United States)

    Zaidi, Syed Asher Hussain; Singh, Gurjit; Owojori, Olukolade; Kela, Ram; Spoors, Shirley; Abbas, Mohamed; Barton, Florence; Rogers, Caroline

    2016-01-01

    Vitamin D deficiency and insufficiency may further increase fracture risk in patients with decreased bone mineral density. A cross-sectional study on serum vitamin D concentrations in medical inpatients was conducted at Bassetlaw District General Hospital between April 2014 and January 2015 (10 months), and the relationship of serum vitamin D concentrations with calcium and alkaline phosphatase was evaluated. 25-Hydroxyvitamin D immunoassays were used and analyzed in the local laboratory. The total number of patients analyzed was 200, age range 18–99 years, with mean age of 76 years. The most common presentation was found to be fall/collapse. The following cutoff points for serum vitamin D were used: levels ≤30 nmol/L for severe deficiency, >30–50 nmol/L for moderate deficiency, >50–75 nmol/L for mild deficiency, and anything above 75 nmol/L as normal. Of the 209 participants examined, 78 (37.3%) participants had mild vitamin D deficiency, 54 (25.8%) participants had moderate vitamin D deficiency, 68 (32.5%) participants had severe vitamin D deficiency, and 9 (4.3%) participants with low vitamin D levels died during their admission. Of the 122 moderate/severe patients, 70 (57.4%) patients had their vitamin D deficiency treated, according to local Trust guidelines. The study found no relationship between serum calcium levels and vitamin D deficiency, whereas patients’ alkaline phosphatase levels were found to be higher with increased severity of vitamin D deficiency. The study examined the implications of untreated severe/moderate vitamin D deficiency compared to treated deficiency, in terms of the frequency of readmission with similar complaints. It was found that the rate of readmission within one year in patients who were not treated was 57%, compared to 48% in patients whose vitamin D deficiency was treated. Presenting after falls was a recurring theme. It was concluded that even if moderate vitamin D deficiency can be asymptomatic, it is important to

  6. Vitamin D Deficiency in Medical Inpatients: A Retrospective Study of Implications of Untreated Versus Treated Deficiency.

    Science.gov (United States)

    Zaidi, Syed Asher Hussain; Singh, Gurjit; Owojori, Olukolade; Kela, Ram; Spoors, Shirley; Abbas, Mohamed; Barton, Florence; Rogers, Caroline

    2016-01-01

    Vitamin D deficiency and insufficiency may further increase fracture risk in patients with decreased bone mineral density. A cross-sectional study on serum vitamin D concentrations in medical inpatients was conducted at Bassetlaw District General Hospital between April 2014 and January 2015 (10 months), and the relationship of serum vitamin D concentrations with calcium and alkaline phosphatase was evaluated. 25-Hydroxyvitamin D immunoassays were used and analyzed in the local laboratory. The total number of patients analyzed was 200, age range 18-99 years, with mean age of 76 years. The most common presentation was found to be fall/collapse. The following cutoff points for serum vitamin D were used: levels ≤30 nmol/L for severe deficiency, >30-50 nmol/L for moderate deficiency, >50-75 nmol/L for mild deficiency, and anything above 75 nmol/L as normal. Of the 209 participants examined, 78 (37.3%) participants had mild vitamin D deficiency, 54 (25.8%) participants had moderate vitamin D deficiency, 68 (32.5%) participants had severe vitamin D deficiency, and 9 (4.3%) participants with low vitamin D levels died during their admission. Of the 122 moderate/severe patients, 70 (57.4%) patients had their vitamin D deficiency treated, according to local Trust guidelines. The study found no relationship between serum calcium levels and vitamin D deficiency, whereas patients' alkaline phosphatase levels were found to be higher with increased severity of vitamin D deficiency. The study examined the implications of untreated severe/moderate vitamin D deficiency compared to treated deficiency, in terms of the frequency of readmission with similar complaints. It was found that the rate of readmission within one year in patients who were not treated was 57%, compared to 48% in patients whose vitamin D deficiency was treated. Presenting after falls was a recurring theme. It was concluded that even if moderate vitamin D deficiency can be asymptomatic, it is important to correct

  7. The epidemiology of global micronutrient deficiencies.

    Science.gov (United States)

    Bailey, Regan L; West, Keith P; Black, Robert E

    2015-01-01

    Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

  8. Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

    DEFF Research Database (Denmark)

    Frøssing, Signe; Rønø, Birgitte; Hald, Andreas;

    2010-01-01

    During healing of incisional skin wounds, migrating keratinocytes dissect their way under the crust to re-epithelialize the wounded area. The efficiency of this tissue remodelling process depends on the concomitant activity of several extracellular proteases, including members of the plasminogen...... activation (PA) system and the matrix metalloproteinase (MMP) family. Treatment with the broad spectrum MMP inhibitor, galardin, delays wound healing in wildtype mice and completely arrest wound healing in plasminogen (Plg)-deficient mice, indicating a functional overlap between plasmin- and galardin......-sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue...

  9. Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure

    OpenAIRE

    Nagasubramanian, Ramamoorthy; Hansen, Ryan J.; Delaney, Shannon M.; Cherian, Mathew M.; Samson, Leona D.; Kogan, Scott C.; Dolan, M. Eileen

    2008-01-01

    O6-methylguanine DNA methyltransferase (MGMT) deficiency is associated with an increased susceptibility to alkylating agent toxicity. To understand the contribution of MGMT in protecting against cyclophosphamide (CP)-induced toxicity, mutagenesis and tumorigenesis, we compared the biological effects of this agent in transgenic Mgmt knockout and wild-type mice. In addition, neurofibromin (Nf1)+/− background was used to increase the likelihood of CP-induced tumorigenesis. Cohorts of Mgmt-profic...

  10. Gender Differences in Adiponectin Modulation of Cardiac Remodeling in Mice Deficient in Endothelial Nitric Oxide Synthase

    OpenAIRE

    Durand, Jorge L.; Nawrocki, Andrea R.; Scherer, Philipp E.; Jelicks, Linda A.

    2012-01-01

    Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels...

  11. Prevalence of micronutrient deficiency in popular diet plans

    Directory of Open Access Journals (Sweden)

    Calton Jayson B

    2010-06-01

    Full Text Available Abstract Background Research has shown micronutrient deficiency to be scientifically linked to a higher risk of overweight/obesity and other dangerous and debilitating diseases. With more than two-thirds of the U.S. population overweight or obese, and research showing that one-third are on a diet at any given time, a need existed to determine whether current popular diet plans could protect followers from micronutrient deficiency by providing the minimum levels of 27 micronutrients, as determined by the U.S. Food and Drug Administrations (FDA Reference Daily Intake (RDI guidelines. Methods Suggested daily menus from four popular diet plans (Atkins for Life diet, The South Beach Diet, the DASH diet, the DASH diet were evaluated. Calorie and micronutrient content of each ingredient, in each meal, were determined by using food composition data from the U.S. Department of Agriculture Nutrient Database for Standard Reference. The results were evaluated for sufficiency and total calories and deficient micronutrients were identified. The diet plans that did not meet 100% sufficiency by RDI guidelines for each of the 27 micronutrients were re-analyzed; (1 to identify a micronutrient sufficient calorie intake for all 27 micronutrients, and (2 to identify a second micronutrient sufficient calorie intake when consistently low or nonexistent micronutrients were removed from the sufficiency requirement. Results Analysis determined that each of the four popular diet plans failed to provide minimum RDI sufficiency for all 27 micronutrients analyzed. The four diet plans, on average, were found to be RDI sufficient in (11.75 ± 2.02; mean ± SEM of the analyzed 27 micronutrients and contain (1748.25 ± 209.57 kcal. Further analysis of the four diets found that an average calorie intake of (27,575 ± 4660.72 would be required to achieve sufficiency in all 27 micronutrients. Six micronutrients (vitamin B7, vitamin D, vitamin E, chromium, iodine and molybdenum were

  12. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  13. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice

    DEFF Research Database (Denmark)

    Carrasco, J; Penkowa, M; Hadberg, H;

    2000-01-01

    Metallothioneins (MTs) are major zinc binding proteins in the CNS that could be involved in the control of zinc metabolism as well as in protection against oxidative stress. Mice lacking MT-I and MT-II (MT-I + II deficient) because of targeted gene inactivation were injected with kainic acid (KA)...

  14. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 8, 0.08 Mechanical, Book 1

    Energy Technology Data Exchange (ETDEWEB)

    1993-05-01

    System information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet too & material listing; testing methods; inspection frequency; standard system design life tables; and system work breakdown structure. Deficiency standards are given for plumbing, fire protection, heating, cooling, and special (drinking water cooling systems).

  15. Multispectral Analysis of Color Vision Deficiency Tests

    Directory of Open Access Journals (Sweden)

    Sergejs FOMINS

    2011-03-01

    Full Text Available Color deficiency tests are usually produced by means of polygraphy technologies and help to diagnose the type and severity of the color deficiencies. Due to different factors, as lighting conditions or age of the test, standard characteristics of these tests fail, thus not allowing diagnosing unambiguously the degree of different color deficiency. Multispectral camera was used to acquire the spectral images of the Ishihara and Rabkin pseudoisochromatic plates in the visible spectrum. Spectral data was converted to cone signals, and successive mathematics applied to provide a simple simulation of the test performance. Colorimetric data of the each pixel of the test image can be calculated and distribution of color coordinates is presented.http://dx.doi.org/10.5755/j01.ms.17.1.259

  16. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    Science.gov (United States)

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters. PMID:26433309

  17. Ornithine Transcarbamylase Deficiency in Iranian Children

    Directory of Open Access Journals (Sweden)

    HR Joshaghani

    2003-08-01

    Full Text Available Ammonia is a toxic material for mammalians. It is detoxificated and converted to urea in the urea cycle in liver. Each defect in the urea cycle cause increase in blood ammonia level. Ornithine transcarbamylase enzyme (OTC is the second enzyme in the urea cycle that exists in mitochondria. OTC deficiency is the most common hereditary disorder in the urea cycle. In this study, 45 hyper ammonia patients were selected (2-13 years old and assayed for serum OTC, serum aspartate aminotransferase (AST, serum alanine aminotransferase (ALT. Four patients (n=45, 8.9% suffered from OTC deficiency. One patient was male (n=29, 3.4% and the others were female (n=16, 18.8%. About half of children (53.3 with hyper ammonia have liver disease. Further studies on OTC deficiency and OTC gene mutations in Iran are recommended.

  18. Vaccination against lymphocytic choriomeningitis virus infection in MHC class II-deficient mice

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...

  19. Cited1 deficiency suppresses intestinal tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Valérie Méniel

    Full Text Available Conditional deletion of Apc in the murine intestine alters crypt-villus architecture and function. This process is accompanied by multiple changes in gene expression, including upregulation of Cited1, whose role in colorectal carcinogenesis is unknown. Here we explore the relevance of Cited1 to intestinal tumorigenesis. We crossed Cited1 null mice with Apc(Min/+ and AhCre(+Apc(fl/fl mice and determined the impact of Cited1 deficiency on tumour growth/initiation including tumour multiplicity, cell proliferation, apoptosis and the transcriptome. We show that Cited1 is up-regulated in both human and murine tumours, and that constitutive deficiency of Cited1 increases survival in Apc(Min/+ mice from 230.5 to 515 days. However, paradoxically, Cited1 deficiency accentuated nearly all aspects of the immediate phenotype 4 days after conditional deletion of Apc, including an increase in cell death and enhanced perturbation of differentiation, including of the stem cell compartment. Transcriptome analysis revealed multiple pathway changes, including p53, PI3K and Wnt. The activation of Wnt through Cited1 deficiency correlated with increased transcription of β-catenin and increased levels of dephosphorylated β-catenin. Hence, immediately following deletion of Apc, Cited1 normally restrains the Wnt pathway at the level of β-catenin. Thus deficiency of Cited1 leads to hyper-activation of Wnt signaling and an exaggerated Wnt phenotype including elevated cell death. Cited1 deficiency decreases intestinal tumourigenesis in Apc(Min/+ mice and impacts upon a number of oncogenic signaling pathways, including Wnt. This restraint imposed by Cited1 is consistent with a requirement for Cited1 to constrain Wnt activity to a level commensurate with optimal adenoma formation and maintenance, and provides one mechanism for tumour repression in the absence of Cited1.

  20. Vitamin D Deficiency in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

  1. Vitamin D deficiency in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Shannon K Flood-Nichols

    Full Text Available Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years. Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL. Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057.Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

  2. Nutrition intervention strategies to combat zinc deficiency in developing countries.

    Science.gov (United States)

    Gibson, R S; Ferguson, E L

    1998-06-01

    Widespread zinc deficiency is likely to exist in developing countries where staple diets are predominantly plant based and intakes of animal tissues are low. The severe negative consequences of zinc deficiency on human health in developing countries, however, have only recently been recognized. An integrated approach employing targeted supplementation, fortification and dietary strategies must be used to maximize the likelihood of eliminating zinc deficiency at a national level in developing countries. Supplementation is appropriate only for populations whose zinc status must be improved over a relatively short time period, and when requirements cannot be met from habitual dietary sources. As well, the health system must be capable of providing consistent supply, distribution, delivery and consumption of the zinc supplement to the targeted groups. Uncertainties still exist about the type, frequency, and level of supplemental zinc required for prevention and treatment of zinc deficiency. Salts that are readily absorbed and at levels that will not induce antagonistic nutrient interactions must be used. At a national level, fortification with multiple micronutrients could be a cost effective method for improving micronutrient status, including zinc, provided that a suitable food vehicle which is centrally processed is available. Alternatively, fortification could be targeted for certain high risk groups (e.g. complementary foods for infants). Efforts should be made to develop protected fortificants for zinc, so that potent inhibitors of zinc absorption (e.g. phytate) present either in the food vehicle and/or indigenous meals do not compromise zinc absorption. Fortification does not require any changes in the existing food beliefs and practices for the consumer and, unlike supplementation, does not impose a burden on the health sector. A quality assurance programme is required, however, to ensure the quality of the fortified food product from production to consumption

  3. Phenylalanine hydroxylase deficiency: diagnosis and management guideline.

    Science.gov (United States)

    Vockley, Jerry; Andersson, Hans C; Antshel, Kevin M; Braverman, Nancy E; Burton, Barbara K; Frazier, Dianne M; Mitchell, John; Smith, Wendy E; Thompson, Barry H; Berry, Susan A

    2014-02-01

    Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder. Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120-360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine

  4. Serum thymulin in human zinc deficiency.

    OpenAIRE

    Prasad, A S; Meftah, S; J. Abdallah; Kaplan, J.; Brewer, G J; Bach, J F; Dardenne, M

    1988-01-01

    The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no over...

  5. Rickets-vitamin D deficiency and dependency

    Directory of Open Access Journals (Sweden)

    Manisha Sahay

    2012-01-01

    Full Text Available Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal.

  6. Phenylalanine hydroxylase deficiency: diagnosis and management guideline.

    Science.gov (United States)

    Vockley, Jerry; Andersson, Hans C; Antshel, Kevin M; Braverman, Nancy E; Burton, Barbara K; Frazier, Dianne M; Mitchell, John; Smith, Wendy E; Thompson, Barry H; Berry, Susan A

    2014-02-01

    Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder. Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120-360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine

  7. Tumoral calcinosis with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Kannan Subramanian

    2008-01-01

    Full Text Available A 50-year-old woman presented with recurrent calcified mass in the left gluteal region. The clinical, radiological, and biochemical profile confirmed the diagnosis of tumoral calcinosis. She also had associated vitamin D deficiency. The patient underwent surgical removal of the mass to relieve the sciatic nerve compression and was managed with acetazolamide, calcium carbonate, and aluminium hydroxide gel with which she showed significant improve-ment. The management implications and effect of vitamin D deficiency on phosphate metabolism in the setting of tumoral calcinosis is discussed.

  8. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders;

    2012-01-01

    on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light......-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night....

  9. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    DEFF Research Database (Denmark)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....

  10. Erythrocytic Iron Deficiency Enhances Susceptibility to Plasmodium chabaudi Infection in Mice Carrying a Missense Mutation in Transferrin Receptor 1.

    Science.gov (United States)

    Lelliott, Patrick M; McMorran, Brendan J; Foote, Simon J; Burgio, Gaetan

    2015-11-01

    The treatment of iron deficiency in areas of high malaria transmission is complicated by evidence which suggests that iron deficiency anemia protects against malaria, while iron supplementation increases malaria risk. Iron deficiency anemia results in an array of pathologies, including reduced systemic iron bioavailability and abnormal erythrocyte physiology; however, the mechanisms by which these pathologies influence malaria infection are not well defined. In the present study, the response to malaria infection was examined in a mutant mouse line, Tfrc(MRI24910), identified during an N-ethyl-N-nitrosourea (ENU) screen. This line carries a missense mutation in the gene for transferrin receptor 1 (TFR1). Heterozygous mice exhibited reduced erythrocyte volume and density, a phenotype consistent with dietary iron deficiency anemia. However, unlike the case in dietary deficiency, the erythrocyte half-life, mean corpuscular hemoglobin concentration, and intraerythrocytic ferritin content were unchanged. Systemic iron bioavailability was also unchanged, indicating that this mutation results in erythrocytic iron deficiency without significantly altering overall iron homeostasis. When infected with the rodent malaria parasite Plasmodium chabaudi adami, mice displayed increased parasitemia and succumbed to infection more quickly than their wild-type littermates. Transfusion of fluorescently labeled erythrocytes into malaria parasite-infected mice demonstrated an erythrocyte-autonomous enhanced survival of parasites within mutant erythrocytes. Together, these results indicate that TFR1 deficiency alters erythrocyte physiology in a way that is similar to dietary iron deficiency anemia, albeit to a lesser degree, and that this promotes intraerythrocytic parasite survival and an increased susceptibility to malaria in mice. These findings may have implications for the management of iron deficiency in the context of malaria.

  11. 7 CFR 1427.16 - Movement and protection of warehouse-stored cotton.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Movement and protection of warehouse-stored cotton... Cotton Loan and Loan Deficiency Payments § 1427.16 Movement and protection of warehouse-stored cotton. (a... to the following conditions: (1) The cotton is represented by an electronic warehouse receipt;...

  12. Iron Deficiency in Adolescents and Young Adults.

    Science.gov (United States)

    Risser, William L.; Risser, Jan M. H.

    1990-01-01

    Reviews the prevalence, natural history, causes, impact on performance, diagnosis, and treatment of iron deficiency in adolescent and young adult athletes. All athletes should be screened and treated. The best diagnosis involves determining serum ferritin and hemoglobin levels. Treatment requires therapeutic doses of oral ferrous iron for several…

  13. Iron and Folate-Deficiency Anaemias.

    Science.gov (United States)

    Hercberg, Serge

    1990-01-01

    Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

  14. Treatment of Vitamin D deficient states

    Science.gov (United States)

    UpToDate performs a continuous review of over 330 journals and other resources to synthesize and provide the latest medical information for clinicians. Updates are added as important new information is published. This document reviews the prevalence and treatment of vitamin D deficient states. Sever...

  15. Circadian behaviour in neuroglobin deficient mice.

    Directory of Open Access Journals (Sweden)

    Christian A Hundahl

    Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  16. Circadian behaviour in neuroglobin deficient mice.

    Science.gov (United States)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders; Georg, Birgitte; Faltoft, Birgitte; Hannibal, Jens

    2012-01-01

    Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  17. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)

    2014-01-01

    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SC

  18. Sequential growth hormone deficiency and acromegaly.

    OpenAIRE

    Heffernan, A.

    1988-01-01

    This is the case of a patient with a pituitary tumour presenting initially with growth hormone deficiency and requiring treatment with human growth hormone. Eight years later he represented with acromegaly. This sequence of events has not to my knowledge been reported previously.

  19. Color Vision Deficiencies in Children. United States.

    Science.gov (United States)

    National Center for Health Statistics (DHEW/PHS), Hyattsville, MD.

    Presented are prevalence data on color vision deficiencies (color blindness) in noninstitutionalized children, aged 6-11, in the United States, as estimated from the Health Examination Survey findings on a representative sample of over 7,400 children. Described are the two color vision tests used in the survey, the Ishihara Test for Color…

  20. Cobalamin Deficiency: Clinical Picture and Radiological Findings

    Directory of Open Access Journals (Sweden)

    Chiara Briani

    2013-11-01

    Full Text Available Vitamin B12 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological disorders. Hematological presentation of cobalamin deficiency ranges from the incidental increase of mean corpuscular volume and neutrophil hypersegmentation to symptoms due to severe anemia, such as angor, dyspnea on exertion, fatigue or symptoms related to congestive heart failure, such as ankle edema, orthopnea and nocturia. Neuropsychiatric symptoms may precede hematologic signs and are represented by myelopathy, neuropathy, dementia and, less often, optic nerve atrophy. The spinal cord manifestation, subacute combined degeneration (SCD, is characterized by symmetric dysesthesia, disturbance of position sense and spastic paraparesis or tetraparesis. The most consistent MRI finding is a symmetrical abnormally increased T2 signal intensity confined to posterior or posterior and lateral columns in the cervical and thoracic spinal cord. Isolated peripheral neuropathy is less frequent, but likely overlooked. Vitamin B12 deficiency has been correlated negatively with cognitive functioning in healthy elderly subjects. Symptoms include slow mentation, memory impairment, attention deficits and dementia. Optic neuropathy occurs occasionally in adult patient. It is characterized by symmetric, painless and progressive visual loss. Parenteral replacement therapy should be started soon after the vitamin deficiency has been established.

  1. Periodic fever and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Frenkel, Joost

    2002-01-01

    Mevalonate kinase (MK) deficiency is an autosomal recessive disorder, caused by mutations in the MVK-gene on chromosome 12q24. The affected enzyme catalyzes an early step in isoprenoid biosynthesis, the pathway that produces cholesterol and several non-sterol isoprenoids. The clinical spectrum inclu

  2. Iron deficiency anaemia in Sri Lanka

    International Nuclear Information System (INIS)

    The commonest cause of nutritional anaemia in the Sri Lankan population is iron deficiency. The diets of the population belonging to the lower socio-economic groups contain little food of animal origin. Thus, their diets are deficient in easily absorbable (haem) iron; and are also heavily cereal-based. Therefore interference in the absorption of dietary iron also occurs. Iron-deficiency anaemia is not restricted to the so-called ''vulnerable groups'' in Sri Lanka, however, their greater demands make the problem not only commoner but also more severe. Among pregnant and lactating women anaemia is often associated with folate deficiency. It must also be noted that the low availability of dietary iron is compounded in large population groups. Malaria, presently raging on an epidemic scale is also a major contributory factor to the incidence of anaemia. The purpose of this study was to examine the iron status of pre-school children and pregnant women; to establish normal levels of biochemical indices at different trimesters; to record the effect of iron supplementation during pregnancy; and to record the bioavailability of iron from weaning foods and common adult diets. 6 figs, 14 tabs

  3. Vitamin D deficiency and heart disease

    NARCIS (Netherlands)

    Pilz, Stefan; Tomaschitz, Andreas; Drechsler, Christiane; de Boer, Rudolf A.

    2011-01-01

    Vitamin D deficiency is present in the vast majority of patients with chronic kidney disease (CKD), and correcting a poor vitamin D status is recommended as a treatment of CKD-mineral and bone disorders. In this review, we summarize the molecular and clinical data on the role of vitamin D status for

  4. DEFICIENT FUNCTIONS OF RANDOM DIRICHLET SERIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this article, the uniqueness theorem of Dirichlet series is proved. Then the random Dirichlet series in the right half plane is studied, and the result that the random Dirichlet series of finite order has almost surely(a.s.) no deficient functions is proved.

  5. Farber's disease (lysosomal acid ceramidase deficiency).

    OpenAIRE

    Jameson, R. A.; Holt, P.J.; Keen, J H

    1987-01-01

    The patient presented with progressive joint deformity, a hoarse voice, subsequent cachexia, and myoclonic seizures. She was first seen aged 22 months and died aged 6 years. A diagnosis of Farber's disease was made by demonstrating a deficiency of acid ceramidase both in leucocytes and fibroblasts.

  6. Patient reported outcome in posttraumatic pituitary deficiency

    DEFF Research Database (Denmark)

    Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita;

    2015-01-01

    with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment. DESIGN AND METHODS: We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439...

  7. Colour Vision Deficiency and Physics Teaching

    Science.gov (United States)

    Maule, Louise; Featonby, David

    2016-01-01

    1 in 12 males suffer from some form of colour vision deficiency (CVD) which in the present colour dominated world of education presentation can be a severe disadvantage. Although aware of "colourblindness" most teachers make little or no adjustment for these pupils for whom tasks may be more difficult. This article examines colour vision…

  8. Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation.

    Directory of Open Access Journals (Sweden)

    Karolina Benesova

    Full Text Available Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe(-/- mice affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe(-/- and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe(-/- mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe(-/- and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis.

  9. Diagnosis and treatment of vitamin D deficiency.

    Science.gov (United States)

    Cannell, J J; Hollis, B W; Zasloff, M; Heaney, R P

    2008-01-01

    The recent discovery--in a randomised, controlled trial--that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician--or responsibility--to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, < or = 5000 IU (125 microg) of vitamin D/day may be required in obese, aged and/or dark-skinned patients to maintain adequate levels during the winter, a dose that makes many physicians uncomfortable. PMID

  10. From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum - a KIMS analysis

    DEFF Research Database (Denmark)

    Klose, M.; Jonsson, B.; Abs, R.;

    2009-01-01

    OBJECTIVE: To describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD. DESIGN: Observational prospective study. METHODS: Baseline characteristics were recorded in 4110 patients...... with organic AO-GHD, who were GH naive prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those...... with available data on concomitant medication (165 IGHD, 3006 MPHD). RESULTS: IGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed...

  11. [The frequency and development of tissue iron deficiency in 6 iron deficiency anemia patients with plummer-vinson syndrome].

    Science.gov (United States)

    Uchida, T; Matsuno, M; Ide, M; Kawachi, Y

    1998-11-01

    The physical signs of tissue iron deficiency include smooth and red tongue, angular stomatitis, koilonychia, and pica. The incidence of these conditions is unknown in Japan. We evaluated the frequency and development of tissue iron deficiency in 353 patients with iron deficiency anemia. The frequency of tissue iron deficiency was 6.8%; papillary atrophy of the tongue, 5.4%; abnormal nails, 5.4%; angular stomatitis, 1.1%; Plummer-Vinson syndrome, 1.7%; and pica, 0.06%. These findings were compared with the date collected by Wintrobe and Beveridge. The development and incidence of tissue iron deficiency correlated significantly with the severity of iron deficiency anemia.

  12. The Alleviation of Nutrient Deficiency Symptoms in Changbai Larch (Larix olgensis Seedlings by the Application of Exogenous Organic Acids

    Directory of Open Access Journals (Sweden)

    Jinfeng Song

    2016-09-01

    Full Text Available Exogenous organic acids are beneficial in protecting plants from the stress of heavy metal toxins (e.g., Pb in soils. This work focuses on the potential role of organic acids in protecting Changbai larch (Larix olgensis seedlings from the stress of growing in nutrient deficient soil. The seedlings were planted in a nutrient rich or deficient soil (A1 horizon of a Haplic Cambisol without organic acid as the nutrient rich control, or fully-mixed A1 + B horizons in a proportion of 1:2 as deficient in pots in a greenhouse. In A1 + B horizons the seedlings were treated daily with concentrations of oxalic or citric acid (OA or CA at a rate approximately equivalent to 0, 0.04, 0.2, 1.0, or 2.0 mmol·kg−1 of soil for 10, 20, and 30 days. Nutrient deficiency stressed the seedlings as indicated by lipid peroxidation and malondialdehyde (MDA content in leaves significantly increasing, and superoxide dismutase (SOD activities, proline, photosynthetic pigment contents, and chlorophyll fluorescence (Fv/Fm decreasing. The stress increased in controls over the application periods. When nutrient deficient plants were exposed to an organic acid (especially 5.0 or 10.0 mmol·L−1 for 20 days, the stress as indicated by the physiological parameters was reversed, and survival rate of seedlings, and biomass of root, stem, and leaf significantly increased; CA was more effective than OA. The results demonstrate that exogenous organic acids alleviate nutrient deficiency-induced oxidative injuries and improve the tolerance of L. olgensis seedlings to nutrient deficiency.

  13. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Abdoul Karim Ouattara; Cyrille Bisseye; Birama Diarra; Tegwind Rebeca Compaore; Florencia Djigma; Virginio Pietra; Remy Moret; Jacques Simpore

    2014-01-01

    Objective: To investigate 4 combinations of mutations responsible for glucose-6-phosphate dehydrogenase (G6PD) deficiency in a rural community of Burkina Faso, a malaria endemic country. Methods: Two hundred individuals in a rural community were genotyped for the mutations A376G, G202A, A542T, G680T and T968C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism. Results: The prevalence of the G6PD deficiency was 9.5% in the study population. It was significantly higher in men compared to women (14.3%vs 6.0%, P=0.049). The 202A/376G G6PD A-was the only deficient variant detected. Plasmodium falciparum asymptomatic parasitaemia was significantly higher among the G6PD-non-deficient persons compared to the G6PD-deficient (P Conclusions:This study showed that the G6PD A-variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.

  14. Diagnóstico diferencial da deficiência de ferro Differential diagnosis of iron deficiency

    Directory of Open Access Journals (Sweden)

    Perla Vicari

    2010-06-01

    Full Text Available A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

  15. High Prevalence of Vitamin D Deficiency in Cambodian Women: A Common Deficiency in a Sunny Country.

    Science.gov (United States)

    Smith, Geoffry; Wimalawansa, Sunil J; Laillou, Arnaud; Sophonneary, Prak; Un, Samoeurn; Hong, Rathavuth; Poirot, Etienne; Kuong, Khov; Chamnan, Chhoun; De Los Reyes, Francisco N; Wieringa, Frank T

    2016-01-01

    Recent studies have shown that in spite of being generally close to the equator; vitamin D deficiency is common in South East Asian countries. In order to quantify micronutrient status for women and children in Cambodia; a nationally-representative survey was conducted in 2014 linked to the Cambodian Demographic Health Survey. The countrywide median of 25(OH)D was, respectively, 64.9 and 91.1 nmol/L for mothers and children. Based on The Endocrine Society cutoffs (>50children had plasma vitamin D concentrations indicating insufficiency or deficiency. For deficiency alone, 29% of the mothers were found to be vitamin D deficient, but only 13.4% of children. Children who live in urban areas had a 43% higher rate of vitamin D insufficiency versus those who live in rural areas (OR; 1.434; 95% CI: 1.007; 2.041). However, such differences were not observed in their mothers. The high prevalence of vitamin D deficiency is likely in part due to lifestyle choices, including sun avoidance, increasingly predominant indoor work, and covered transport. These survey findings support the need for a broader national Cambodian study incorporating testing of adult men, adolescents and the elderly, and encompassing other parameters such as skeletal health. However, the data presented in this study already show significant deficiencies which need to be addressed and we discuss the benefit of establishing nationally-mandated food fortification programs to enhance the intake of vitamin D. PMID:27187456

  16. Vitamin D deficiency in postmenopausal women with pelvic floor disorders

    Directory of Open Access Journals (Sweden)

    Preethi Raja Navaneethan

    2015-01-01

    Conclusion: Findings suggest association of vitamin D deficiency and PFD in postmenopausal women. In addition, postmenopausal women have a high prevalence of vitamin D deficiency indicating a need to evaluate vitamin D levels in these women.

  17. Allergic disease as an association of steroid sulphatase deficiency.

    Science.gov (United States)

    Sakura, N; Nishimura, S; Matsumoto, T; Ohsaki, M; Ogata, T

    1997-11-01

    Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.

  18. Absorption of plutonium in the iron-deficient rat

    International Nuclear Information System (INIS)

    Iron deficiency did not enhance absorption of plutonium following intragastric gavage of rats. Absorption of plutonium citrate in both control and iron-deficient rats was about 0.03% of the administered dose

  19. Primary Immune Deficiency Diseases: Talking to Your Doctor

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area Primary Immune Deficiency Diseases Talking to Your Doctor Take Action: When Your ... repeat infections in the future. People with primary immune deficiency diseases (PIDDs), however, have defects in one or more ...

  20. What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

    Science.gov (United States)

    ... Pool Deficiencies Home About Bleeding Disorders What is combined deficiency of vitamin K-dependent clotting factors? Inherited combined deficiency of the vitamin K-dependent clotting factors ( ...