WorldWideScience

Sample records for ameliorates neuronal cholesterol

  1. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression.

    Directory of Open Access Journals (Sweden)

    Cristin D Davidson

    2009-09-01

    Full Text Available Niemann-Pick type C (NPC disease is a fatal neurodegenerative disorder caused most commonly by a defect in the NPC1 protein and characterized by widespread intracellular accumulation of unesterified cholesterol and glycosphingolipids (GSLs. While current treatment therapies are limited, a few drugs tested in Npc1(-/- mice have shown partial benefit. During a combination treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ and allopregnanolone, we noted increased lifespan for Npc1(-/- mice receiving only 2-hydroxypropyl-beta-cyclodextrin (CD, the vehicle for allopregnanolone. This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit.Administration of CD to Npc1(-/- mice beginning at either P7 or P21 and continuing every other day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as well as free sphingosine accumulation, reduced markers of neurodegeneration, and led to longer survival than any previous treatment regime. We reasoned that other lysosomal diseases characterized by cholesterol and GSL accumulation, including NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis (MPS type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/- mice showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or MPS IIIA failed to show reduction in storage.Treatment with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1(-/- and Npc2(-/- mice. In contrast, CD failed to ameliorate cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA disease. Understanding the mechanism(s by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis.

  2. Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yongming Pan

    2018-03-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia characterized by aggregation of amyloid β (Aβ and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ, a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC and low density lipoprotein-cholesterol (LDL-C, and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1 and receptor for advanced glycation end products (RAGE, and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1 and insulin degrading enzyme (IDE. In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.

  3. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington's disease.

    Science.gov (United States)

    Valenza, M; Marullo, M; Di Paolo, E; Cesana, E; Zuccato, C; Biella, G; Cattaneo, E

    2015-04-01

    In the adult brain, neurons require local cholesterol production, which is supplied by astrocytes through apoE-containing lipoproteins. In Huntington's disease (HD), such cholesterol biosynthesis in the brain is severely reduced. Here we show that this defect, occurring in astrocytes, is detrimental for HD neurons. Astrocytes bearing the huntingtin protein containing increasing CAG repeats secreted less apoE-lipoprotein-bound cholesterol in the medium. Conditioned media from HD astrocytes and lipoprotein-depleted conditioned media from wild-type (wt) astrocytes were equally detrimental in a neurite outgrowth assay and did not support synaptic activity in HD neurons, compared with conditions of cholesterol supplementation or conditioned media from wt astrocytes. Molecular perturbation of cholesterol biosynthesis and efflux in astrocytes caused similarly altered astrocyte-neuron cross talk, whereas enhancement of glial SREBP2 and ABCA1 function reversed the aspects of neuronal dysfunction in HD. These findings indicate that astrocyte-mediated cholesterol homeostasis could be a potential therapeutic target to ameliorate neuronal dysfunction in HD.

  4. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  5. Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

    Science.gov (United States)

    Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

    2012-05-30

    Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

  6. Survival of adult neurons lacking cholesterol synthesis in vivo.

    Science.gov (United States)

    Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

    2007-01-02

    Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  7. Survival of adult neurons lacking cholesterol synthesis in vivo

    Directory of Open Access Journals (Sweden)

    Möbius Wiebke

    2007-01-01

    Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  8. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  9. The mevalonate pathway in neurons: It's not just about cholesterol.

    Science.gov (United States)

    Moutinho, Miguel; Nunes, Maria João; Rodrigues, Elsa

    2017-11-01

    Cholesterol homeostasis greatly impacts neuronal function due to the essential role of this sterol in the brain. The mevalonate (MVA) pathway leads to the synthesis of cholesterol, but also supplies cells with many other intermediary molecules crucial for neuronal function. Compelling evidence point to a model in which neurons shutdown cholesterol synthesis, and rely on a shuttle derived from astrocytes to meet their cholesterol needs. Nevertheless, several reports suggest that neurons maintain the MVA pathway active, even with sustained cholesterol supply by astrocytes. Hence, in this review we focus not on cholesterol production, but rather on the role of the MVA pathway in the synthesis of particular intermediaries, namely isoprenoids, and on their role on neuronal function. Isoprenoids act as anchors for membrane association, after being covalently bound to proteins, such as most of the small guanosine triphosphate-binding proteins, which are critical to neuronal cell function. Based on literature, on our own results, and on the analysis of public transcriptomics databases, we raise the idea that in neurons there is a shift of the MVA pathway towards the non-sterol branch, responsible for isoprenoid synthesis, in detriment to post-squalene branch, and that this is ultimately essential for synaptic activity. Nevertheless new tools that facilitate imaging and the biochemical characterization and quantification of the prenylome in neurons and astrocytes are needed to understand the regulation of isoprenoid production and protein prenylation in the brain, and to analyze its differences on diverse physiological or pathological conditions, such as aging and neurodegenerative states. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Regulation of neuronal APL-1 expression by cholesterol starvation.

    Directory of Open Access Journals (Sweden)

    Mary Wiese

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP. While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD, sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1, and lrp-1 (lipoprotein receptor-related protein 1, suggesting a potential interaction between apl-1 and cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. CONCLUSIONS: Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

  11. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  12. GPNMB ameliorates mutant TDP-43-induced motor neuron cell death.

    Science.gov (United States)

    Nagahara, Yuki; Shimazawa, Masamitsu; Ohuchi, Kazuki; Ito, Junko; Takahashi, Hitoshi; Tsuruma, Kazuhiro; Kakita, Akiyoshi; Hara, Hideaki

    2017-08-01

    Glycoprotein nonmetastatic melanoma protein B (GPNMB) aggregates are observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, but the detailed localization is still unclear. Mutations of transactive response DNA binding protein 43kDa (TDP-43) are associated with neurodegenerative diseases including ALS. In this study, we evaluated the localization of GPNMB aggregates in the spinal cord of ALS patients and the effect of GPNMB against mutant TDP-43 induced motor neuron cell death. GPNMB aggregates were not localized in the glial fibrillary acidic protein (GFAP)-positive astrocyte and ionized calcium binding adaptor molecule-1 (Iba1)-positive microglia. GPNMB aggregates were localized in the microtubule-associated protein 2 (MAP-2)-positive neuron and neurofilament H non-phosphorylated (SMI-32)-positive neuron, and these were co-localized with TDP-43 aggregates in the spinal cord of ALS patients. Mock or TDP-43 (WT, M337V, and A315T) plasmids were transfected into mouse motor neuron cells (NSC34). The expression level of GPNMB was increased by transfection of mutant TDP-43 plasmids. Recombinant GPNMB ameliorated motor neuron cell death induced by transfection of mutant TDP-43 plasmids and serum-free stress. Furthermore, the expression of phosphorylated ERK1/2 and phosphorylated Akt were decreased by this stress, and these expressions were increased by recombinant GPNMB. These results indicate that GPNMB has protective effects against mutant TDP-43 stress via activating the ERK1/2 and Akt pathways, and GPNMB may be a therapeutic target for TDP-43 proteinopathy in familial and sporadic ALS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

    Science.gov (United States)

    El-Awady, Mohammed S; Suddek, Ghada M

    2014-06-01

    The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

  14. Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.

    Science.gov (United States)

    Karten, Barbara; Vance, Dennis E; Campenot, Robert B; Vance, Jean E

    2003-02-07

    Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease.

  15. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets.

    Science.gov (United States)

    Lee, Yun Jung; Choi, Deok Ho; Cho, Guk Hyun; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-08-06

    Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD). EAL-I (100 mg·kg-1/day), EAL-II (200 mg·kg-1/day), and fluvastatin (3 mg·kg-1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

  16. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

    Directory of Open Access Journals (Sweden)

    Lee Yun

    2012-08-01

    Full Text Available Abstract Background Arctium lappa L. (Asteraceae, burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD. Method EAL-I (100 mg·kg−1/day, EAL-II (200 mg·kg−1/day, and fluvastatin (3 mg·kg−1/day groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Results Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM-1, vascular cell adhesion molecule (VCAM-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. Conclusion The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

  17. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

    Science.gov (United States)

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-01-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA (shRNA) to suppress expression of the enzyme CYP46A1. This protein hydroxylates cholesterol and so facilitates trans-membrane extrusion. A sh-RNA CYP46A1construction coupled to an adeno-associated virus (AAV5) was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the CA3a region. Cytoplasmic and membrane cholesterol increased, neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, inter-ictal EEG events occurred during exploration and non-REM sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low amplitude, high-frequency oscillations of peak power at ~300Hz and a range of 250-350 Hz. While episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behavior PMID:25847620

  18. The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: quantitative changes to the cortical neuron proteome.

    Science.gov (United States)

    Wang, Yuqin; Muneton, Sabina; Sjövall, Jan; Jovanovic, Jasmina N; Griffiths, William J

    2008-04-01

    In humans, the brain represents only about 2% of the body's mass but contains about one-quarter of the body's free cholesterol. Cholesterol is synthesized de novo in brain and removed by metabolism to oxysterols. 24S-Hydoxycholesterol represents the major metabolic product of cholesterol in brain, being formed via the cytochrome P450 (CYP) enzyme CYP46A1. CYP46A1 is expressed exclusively in brain, normally by neurons. In this study, we investigated the effect of 24S-hydroxycholesterol on the proteome of rat cortical neurons. With the use of two-dimensional liquid chromatography linked to nanoelectrospray tandem mass spectrometry, over 1040 proteins were identified including members of the cholesterol, isoprenoid and fatty acid synthesis pathways. With the use of stable isotope labeling technology, the protein expression patterns of enzymes in these pathways were investigated. 24S-Hydroxycholesterol was found to down-regulate the expression of members of the cholesterol/isoprenoid synthesis pathways including 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (EC 2.3.3.10), diphosphomevalonate decarboxylase (EC 4.1.1.33), isopentenyl-diphosphate delta isomerase (EC 5.3.3.2), farnesyl-diphosphate synthase (Geranyl trans transferase, EC 2.5.1.10), and dedicated sterol synthesis enzymes, farnesyl-diphosphate farnesyltransferase 1 (squalene synthase, EC 2.5.1.21) and methylsterol monooxygenase (EC 1.14.13.72). The expression of many enzymes in the cholesterol/isoprenoid and fatty acid synthesis pathways are regulated by the membrane-bound transcription factors named sterol regulatory element-binding proteins (SREBPs), which themselves are both transcriptionally and post-transcriptionally regulated. The current proteomic data indicates that 24S-hydroxycholesterol down-regulates cholesterol synthesis in neurons, possibly, in a post-transcriptional manner through SREBP-2. In contrast to cholesterol metabolism, enzymes responsible for the synthesis of fatty acids were not

  19. Freshwater Clam Extract Ameliorates Triglyceride and Cholesterol Metabolism through the Expression of Genes Involved in Hepatic Lipogenesis and Cholesterol Degradation in Rats

    Directory of Open Access Journals (Sweden)

    Thomas Laurent

    2013-01-01

    Full Text Available The freshwater clam (Corbicula spp. is a popular edible bivalve and has been used as a folk remedy for liver disease in Asia. As a Chinese traditional medicine, it is said that freshwater clam ameliorates alcoholic intoxication and cholestasis. In this study, to estimate the practical benefit of freshwater clam extract (FCE, we compared the effects of FCE and soy protein isolate (SPI on triglyceride and cholesterol metabolism in rats. FCE and SPI lowered serum cholesterol, and FCE tended to reduce serum triglycerides. FCE enhanced fecal sterol excretion and hepatic mRNA levels of CYP7A1 and ABCG5 more substantially than SPI; however, both diets reduced hepatic cholesterol. Both of the diets similarly suppressed liver lipids improved Δ9-desaturated fatty acid profile, and FCE was associated with a reduction in FAS and SCD1 mRNA levels. Hepatic transcriptome analysis revealed that inhibition of lipogenesis-related gene expression may contribute to downregulation of hepatic triglycerides by FCE. FCE would have better potential benefits for preventing metabolic disorders, through greater improvement of metabolism of triglycerides and cholesterol, likely through a mechanism similar to SPI.

  20. The Effect of 24S-Hydroxycholesterol on Cholesterol Homeostasis in Neurons: Quantitative Changes to the Cortical Neuron Proteome

    OpenAIRE

    Wang, Yuqin; Muneton, Sabina; Sjövall, Jan; Jovanovic, Jasmina N.; Griffiths, William J.

    2008-01-01

    In human the brain represents only about 2% of the body’s mass but contains about one quarter of the body’s free cholesterol. Cholesterol is synthesised de novo in brain, and removed by metabolism to oxysterols. 24S-Hydoxycholesterol represents the major metabolic product of cholesterol in brain, being formed via the cytochrome P450 (CYP) enzyme CYP46A1. CYP46A1 is expressed exclusively in brain, normally by neurons. In this study we investigated the effect of 24S-hydroxycholesterol on the pr...

  1. Super-resolution microscopy reveals functional organization of dopamine transporters into cholesterol and neuronal activity-dependent nanodomains

    DEFF Research Database (Denmark)

    Rahbek-Clemmensen, Troels; Lycas, Matthew D.; Erlendsson, Simon

    2017-01-01

    is dynamically sequestrated into cholesterol-dependent nanodomains in the plasma membrane of presynaptic varicosities and neuronal projections of dopaminergic neurons. Stochastic optical reconstruction microscopy reveals irregular dopamine transporter nanodomains (∼70 nm mean diameter) that were highly sensitive...... to cholesterol depletion. Live photoactivated localization microscopy shows a similar dopamine transporter membrane organization in live heterologous cells. In neurons, dual-color dSTORM shows that tyrosine hydroxylase and vesicular monoamine transporter-2 are distinctively localized adjacent to...

  2. Cholesterol up-regulates neuronal G protein-gated inwardly rectifying potassium (GIRK) channel activity in the hippocampus.

    Science.gov (United States)

    Bukiya, Anna N; Durdagi, Serdar; Noskov, Sergei; Rosenhouse-Dantsker, Avia

    2017-04-14

    Hypercholesterolemia is a well known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters. As a result, loss of GIRK function can enhance neuron excitability, whereas gain of GIRK function can reduce neuronal activity. Here we show that in rats on a high-cholesterol diet, cholesterol levels in hippocampal neurons are increased. We also demonstrate that cholesterol plays a critical role in modulating neuronal GIRK currents. Specifically, cholesterol enrichment of rat hippocampal neurons resulted in enhanced channel activity. In accordance, elevated currents upon cholesterol enrichment were also observed in Xenopus oocytes expressing GIRK2 channels, the primary GIRK subunit expressed in the brain. Furthermore, using planar lipid bilayers, we show that although cholesterol did not affect the unitary conductance of GIRK2, it significantly enhanced the frequency of channel openings. Last, combining computational and functional approaches, we identified two putative cholesterol-binding sites in the transmembrane domain of GIRK2. These findings establish that cholesterol plays a critical role in modulating GIRK activity in the brain. Because up-regulation of GIRK function can reduce neuronal activity, our findings may lead to novel approaches for prevention and therapy of cholesterol-driven neurodegenerative disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    OpenAIRE

    Khalil, Md. Ibrahim; Tanvir, E. M.; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

    2015-01-01

    The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey...

  4. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels.

    Science.gov (United States)

    Khalil, Md Ibrahim; Tanvir, E M; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

    2015-01-01

    The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  5. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    Directory of Open Access Journals (Sweden)

    Md. Ibrahim Khalil

    2015-01-01

    Full Text Available The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO- induced myocardial infarction (MI in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI, triglycerides (TG, total cholesterol (TC, lipid peroxidation (LPO products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40 were pretreated orally with Tualang honey (3 g/kg/day for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB, lactate dehydrogenase (LDH, and aspartate transaminase (AST, cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO products (TBARS and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST. Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  6. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

    Science.gov (United States)

    Cui, Qunli; Li, Xin; Zhu, Hongcan

    2016-02-01

    Parkinson's disease (PD) is an age-related complex neurodegenerative disease that affects ≤ 80% of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has previously been suggested that mitochondrial dysfunction, oxidative stress and oxidative damage underlie the pathogenesis of PD. Curcumin, which is a major active polyphenol component extracted from the rhizomes of Curcuma longa (Zingiberaceae), has been reported to exert neuroprotective effects on an experimental model of PD. The present study conducted a series of in vivo experiments, in order to investigate the effects of curcumin on behavioral deficits, oxidative damage and related mechanisms. The results demonstrated that curcumin was able to significantly alleviate motor dysfunction and increase suppressed tyrosine hydroxylase (TH) activity in the SNpc of rotenone (ROT)-injured rats. Biochemical measurements indicated that rats pretreated with curcumin exhibited increased glutathione (GSH) levels, and reduced reactive oxygen species activity and malondialdehyde content. Mechanistic studies demonstrated that curcumin significantly restored the expression levels of heme oxygenase-1 and quinone oxidoreductase 1, thus ameliorating ROT-induced damage in vivo, via the phosphorylation of Akt and nuclear factor erythroid 2-related factor 2 (Nrf2). Further studies indicated that the Akt/Nrf2 signaling pathway was associated with the protective role of curcumin in ROT-treated rats. Inhibiting the Akt/Nrf2 pathway using a lentiviral vector containing Nrf2-specific short hairpin RNA, or the phosphoinositide 3-kinase inhibitor LY294002, markedly reduced the expression levels of TH and GSH, ultimately attenuating the neuroprotective effects of curcumin against oxidative damage. These results indicated that curcumin was able to significantly ameliorate ROT-induced dopaminergic neuronal oxidative damage in the SNpc of rats via activation of the Akt/Nrf2 signaling pathway.

  7. Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2016-01-01

    Full Text Available Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD. The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD supplement with perilla oil (POH for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.

  8. Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling.

    Science.gov (United States)

    Song, Juhyun; Lee, Byeori; Kang, Somang; Oh, Yumi; Kim, Eosu; Kim, Chul-Hoon; Song, Ho-Taek; Lee, Jong Eun

    2016-02-01

    Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-β-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

  9. Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups.

    Science.gov (United States)

    Cho, Jung-Wan; Jung, Sun-Young; Lee, Sang-Won; Lee, Sam-Jun; Seo, Tae-Beom; Kim, Young-Pyo; Kim, Dae-Young

    2017-12-01

    Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe using immunofluorescence. The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The present results demonstrated that social isolation increased resting time and decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and expression of BDNF and TrkB in the hippocampus were decreased by social isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was suppressed by social isolation. Treadmill exercise decreased resting time and increased mobility in the social isolated rat pups. Expression of 5-HT, TPH, BDNF, and TrkB was increased by treadmill exercise. The present results suggested that treadmill exercise may ameliorates social isolation-induced depression through increasing neuronal generation.

  10. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress.

    Science.gov (United States)

    Shukitt-Hale, Barbara; Galli, Rachel L; Meterko, Vanessa; Carey, Amanda; Bielinski, Donna F; McGhie, Tony; Joseph, James A

    2005-03-01

    Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphenolics, 19-month-old male Fischer rats were fed a well-balanced control diet, or the diet supplemented with 2% extract from either blueberry, cranberry, blackcurrant, or Boysenberry fruit for eight weeks before testing began. The blackcurrant and cranberry diets enhanced neuronal signal transduction as measured by striatal dopamine release, while the blueberry and cranberry diets were effective in ameliorating deficits in motor performance and hippocampal HSP70 neuroprotection; these changes in HSP70 were positively correlated with performance on the inclined screen. It appears that the polyphenols in blueberries and cranberries have the ability to improve muscle tone, strength and balance in aging rats, whereas polyphenols in blueberries, cranberries and blackcurrants have the ability to enhance neuronal functioning and restore the brain's ability to generate a neuroprotective response to stress.

  11. Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis.

    Science.gov (United States)

    Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B

    2009-05-19

    Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.

  12. Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Teppei Noda

    2018-02-01

    Full Text Available Primary auditory neurons (PANs play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs, comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs. The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

  13. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

  14. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  15. Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

    Science.gov (United States)

    Husain, I; Akhtar, M; Abdin, M Zainul; Islamuddin, M; Shaharyar, M; Najmi, A K

    2018-04-01

    Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ 1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ 1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ 1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ 1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

  16. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

    Directory of Open Access Journals (Sweden)

    Lu Mei

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC together with cholesterol-lowering probiotics (P to improve high-fat diet (HFD-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1, low density lipoprotein receptor (LDL-R and farnesoid X receptor (FXR were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR was reduced. The expression of peroxisome proliferator activated receptor (PPAR-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1 were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the

  17. Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

    Science.gov (United States)

    Cheng, Shanshan; Hou, Jinxing; Zhang, Chen; Xu, Congyu; Wang, Long; Zou, Xiaoxia; Yu, Huahong; Shi, Yun; Yin, Zhenyu; Chen, Guiquan

    2015-01-01

    Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis. PMID:26000566

  19. TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin

    Science.gov (United States)

    Moruno Manchon, Jose Felix; Uzor, Ndidi-Ese; Kesler, Shelli R.; Wefel, Jeffrey S.; Townley, Debra M.; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S.; Sood, Anil K.; Tsvetkov, Andrey S.

    2016-01-01

    Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated liposomal doxorubicin exhibited autophagosomes, often with mitochondria, lipofuscin, and lipid droplets. Interestingly, lysosomes were less acidic in doxorubicin-treated neurons. Overexpression of the transcription factor EB (TFEB), which controls the autophagy-lysosome axis, increased survival of doxorubicin-treated neurons. 2-Hydroxypropyl-β-cyclodextrin (HPβCD), an activator of TFEB, also promoted neuronal survival, decreased the levels of p62, and lowered the pH in lysosomes. Taken together, substantial changes induced by doxorubicin contribute to neurotoxicity, cognitive disturbances in cancer patients and survivors, and accelerated brain aging. The TFEB pathway might be a new approach for mitigating damage of neuronal autophagy caused by doxorubicin. PMID:27992857

  20. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer's Disease.

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer's disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD.

  1. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  2. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  3. Curcumin ameliorates hippocampal neuron damage induced by human immunodeficiency virus-1★

    OpenAIRE

    Tang, Hongmei; Pan, Rui; Fang, Wenli; Xing, Yanyan; Chen, Dexi; Chen, Xiaobao; Yu, Yuanyuan; Wang, Junbing; Gong, Zheng; Xiong, Guoyin; Dong, Jun

    2013-01-01

    Our previous studies have shown that infection with the gp120 V3 loop can cause human immunodeficiency virus-1 associated neurocognitive disorders. Curcumin has been shown to improve these effects to some degree, but the precise mechanisms remain unknown. The present study analyzed the neuroprotective effect and mechanism of curcumin in relation to hippocampal neurons. Results showed that 1 nmol/L gp120 V3 loop suppressed the growth of synapses. After administration of 1 μmol/L curcumin, syna...

  4. Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Yazhou Li

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1, facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4 is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells and in vivo (SOD1 G93A mutant mice models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS.

  5. Neuroprotective and Ameliorating Impacts of Omega-3 Against Aspartame-induced Neuronal and Astrocytic Degeneration.

    Science.gov (United States)

    Ali, Eyad M T; Sonpol, Hany M A

    2017-07-01

    Aspartame (ASP) is one of the commonest artificial sweetener used all over the world and considered as an extremely risky compound and raises a lot of controversy. Therefore, this study was designed to investigate cellular damage of the anterior horn cells in the spinal cord of albino male rats and the possibility of hindering these changes by using omega-3 (OM3).Thirty seven adult male albino rats were divided into three groups: Control, ASP-treated and ASP + OM3-treated groups. Spinal cord sections were prepared and stained with Hx&E, caspase-3 and GFAP immunostaining. All data were morphometrically and statistically analyzed. In ASP-treated group, the cell body of some degenerated neurons was swollen and its cytoplasm was vacuolated. Their nuclei were eccentric and pyknotic. Moreover, other neurons were of a heterogeneous pattern in the form of cell body shrinkage, loss of Nissl substance, intensely stained eosinophilic cytoplasm and a small darkly stained nucleus that may eventually fragment. However, the cells were apparently normal in ASP+ OM3-treated group. Strong +ve caspase-3 stained neurons were detected in ASP-treated group. Furthermore, the immunoreaction was faint on treating the rats with both ASP and OM3. Few number of +ve GFAP- stained astrocytes were observed in ASP-treated rats. On the other hand, the immunoreactivity for GFAP was found to be intense in the ASP + OM3-treated group. Additionally, there was a significant decrease in the surface area percentage of the +ve GFAP-stained astrocytes of the ASP-treated group compared to the control and the ASP + OM3-treated groups. Anat Rec, 300:1290-1298, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol.

    Science.gov (United States)

    Teppola, Heidi; Sarkanen, Jertta-Riina; Jalonen, Tuula O; Linne, Marja-Leena

    2016-04-01

    Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was to examine in the RA and CHOL treated SH-SY5Y cells the additive impacts of estradiol (E2) and brain-derived neurotrophic factor (BDNF) on cell morphology, cell population growth, synaptic vesicle recycling and presence of neurofilaments. The above features indicate a higher level of neuronal differentiation. Our data show that treatment for 10 days in vitro (DIV) with RA alone or when combined with E2 (RE) or CHOL (RC), but not when combined with BDNF (RB), significantly (p differentiation.

  7. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  8. Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability.

    Science.gov (United States)

    Pontikis, Charles C; Davidson, Cristin D; Walkley, Steven U; Platt, Frances M; Begley, David J

    2013-05-01

    Niemann-Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments. It has been observed that the administration of hydroxypropyl-β-cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal/lysosomal compartment. Here, we present evidence that refutes this hypothesis. We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain. The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi-time-point regression analysis. Neither study demonstrates significant, time-dependent uptake of HPBCD in either adult or neonatal mice. However, the volume of distribution available to HPBCD (0.113 ± 0.010 ml/g) exceeds the accepted values for plasma and vascular volume of the brain. In fact, it is nearly three times larger than that for sucrose (0.039 ± 0.006 ml/g). We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.

  9. Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy in Drosophila

    Directory of Open Access Journals (Sweden)

    Dick R. Nässel

    2017-04-01

    Full Text Available The lifespan of Drosophilamelanogaster can be extended substantially by inducing reproductive dormancy (also known as diapause by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy. To study this we kept flies for seven or more weeks in normal rearing conditions or in diapause conditions and compared to 1-week-old flies in different behavioral assays of sleep, negative geotaxis and exploratory walking. We found that the senescence of geotaxis and locomotor behavior seen under normal rearing conditions was negligible in flies kept in dormancy. The normal senescence of rhythmic activity and sleep patterns during the daytime was also reduced by adult dormancy. Investigating the morphology of specific neuromuscular junctions (NMJs, we found that changes normally seen with aging do not take place in dormant flies. To monitor age-associated changes in neuronal circuits regulating activity rhythms, sleep and walking behavior we applied antisera to tyrosine hydroxylase (TH, serotonin and several neuropeptides to examine changes in expression levels and neuron morphology. In most neuron types the levels of stored neuromodulators decreased during normal aging, but not in diapause treated flies. No signs of neurodegeneration were seen in either condition. Our data suggest that age-related changes in motor neurons could be the cause of part of the behavioral senescence and that this is ameliorated by reproductive diapause. Earlier studies established a link between age-associated decreases in neuromodulator levels and behavioral decline that could be rescued by overexpression of neuromodulator. Thus, it is likely that the retained levels of neuromodulators in dormant flies alleviate behavioral senescence.

  10. 17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal autophagic death induced by transient global cerebral ischemia.

    Science.gov (United States)

    Li, Jianxiong; Yang, Fei; Guo, Jia; Zhang, Rongrong; Xing, Xiangfeng; Qin, Xinyue

    2015-06-12

    Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Amelioration of oxidative and inflammatory status in hearts of cholesterol-fed rats supplemented with oils or oil-products with extra virgin olive oil components.

    Science.gov (United States)

    Katsarou, Ageliki I; Kaliora, Andriana C; Chiou, Antonia; Kalogeropoulos, Nick; Papalois, Apostolos; Agrogiannis, George; Andrikopoulos, Nikolaos K

    2016-04-01

    The contribution of extra virgin olive oil (EVOO) macro- and micro-constituents in heart oxidative and inflammatory status in a hypercholesterolemic rat model was evaluated. Fatty acid profile as well as α-tocopherol, sterol, and squalene content was identified directly in rat hearts to distinguish the effect of individual components or to enlighten the potential synergisms. Oils and oil-products with discernible lipid and polar phenolic content were used. Wistar rats were fed a high-cholesterol diet solely, or supplemented with one of the following oils, i.e., EVOO, sunflower oil (SO), and high-oleic sunflower oil (HOSO) or oil-products, i.e., phenolics-deprived EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], and HOSO enriched with the EVOO phenolics [HOSO(+)]. Dietary treatment lasted 9 weeks; at the end of the intervention blood and heart samples were collected. High-cholesterol-diet-induced dyslipidemia was shown by increase in serum total cholesterol, low-density lipoprotein cholesterol, and triacylglycerols. Dyslipidemia resulted in increased malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels, while glutathione and interleukin 6 levels remained unaffected in all intervention groups. Augmentation observed in MDA and TNF-α was attenuated in EVOO, SO(+), and HOSO(+) groups. Heart squalene and cholesterol content remained unaffected among all groups studied. Heart α-tocopherol was determined by oil α-tocopherol content. Variations were observed for heart β-sitosterol, while heterogeneity was reported with respect to heart fatty acid profile in all intervention groups. Overall, we suggest that the EVOO-polar phenolic compounds decreased MDA and TNF-α in hearts of cholesterol-fed rats.

  12. Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

    Science.gov (United States)

    He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

    2014-05-01

    Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

  13. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    Science.gov (United States)

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.

  14. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer’s Disease

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer’s disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD. PMID:29636677

  15. 1,2-Dilinoleoyl-sn-glycero-3-phosphoethanolamine ameliorates age-related spatial memory deterioration by preventing neuronal cell death

    Directory of Open Access Journals (Sweden)

    Yaguchi Takahiro

    2010-09-01

    Full Text Available Abstract Background Accumulating evidence has pointed that a variety of lipids could exert their beneficial actions against dementia including Alzheimer disease and age-related cognitive decline via diverse signaling pathways. Endoplasmic reticulum (ER stress-induced neuronal apoptosis, on the other hand, is a critical factor for pathogenesis of neurodegenerative diseases such as Alzheimer disease and Parkinson disease, senile dementia, and ischemic neuronal damage. The present study examined the effects of 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPhtEtn, a phospholipid, on ER stress-induced neuronal death and age-related cognitive disorders. Methods PC-12 cell viability was assayed before and after treatment with amyloid-β1-40 peptide or thapsigargin in the presence and absence of DLPhtEtn. A series of behavioral tests were performed for senescence-accelerated mouse-prone 8 (SAMP8 mice after 7-month oral administration with polyethylene glycol (PEG or DLPhtEtn and then, the number of hippocampal neurons was counted. Results Amyloid-β1-40 peptide or thapsigargin is capable of causing ER stress-induced apoptosis. DLPhtEtn (30 μM significantly inhibited PC-12 cell death induced by amyloid-β1-40 peptide or thapsigargin. In the water maze test, oral administration with DLPhtEtn (1 mg/kg for 7 months (three times a week significantly shortened the prolonged retention latency for SAMP8 mice. In contrast, DLPhtEtn had no effect on the acquisition and retention latencies in both the open field test and the passive avoidance test for SAMP8 mice. Oral administration with DLPhtEtn (1 mg/kg for 7 months prevented a decrease in the number of hippocampal neurons for SAMP8 mice. Conclusion The results of the present study show that DLPhtEtn ameliorates age-related spatial memory decline without affecting motor activities or fear memory, possibly by protecting hippocampal neuronal death. DLPhtEtn, thus, might exert its beneficial action against

  16. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors.

    Science.gov (United States)

    Wang, Z; Liu, Q; Zhang, R; Liu, S; Xia, Z; Hu, Y

    2009-11-10

    The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. Furthermore, the brain-derived neurotrophic factor (BDNF) content in brain was significantly decreased in the model mice and catalpol elevated it to normal level (83%+/-3% and 102%+/-2% of normal respectively). There is a significant positive correlation between BDNF content and memory. Primary culture of forebrain neurons revealed that aggregated Abeta(25-35) induced significant decrease of ChAT positive neuron number, neurite outgrowth length, and M receptor density, while catalpol added to the culture medium 2 h prior to Abeta addition showed significant dose dependent protective effect. Notably, 24 h and 48 h after the addition of Abeta to the cultured cells, the BDNF mRNA level in the neurons decreased to 76%+/-7% and 66%+/-3% of control without catalpol treatment, but became 128%+/-17% and 131%+/-23% of control with catalpol treatment. When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already

  17. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

    Science.gov (United States)

    Sun, Kai; Fan, Jingyu; Han, Jingyan

    2015-01-01

    Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

  18. P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus

    Directory of Open Access Journals (Sweden)

    Ryu Hea Jin

    2011-06-01

    Full Text Available Abstract Background The release of tumor necrosis factor-α (TNF-α appears depend on the P2X7 receptor, a purinergic receptor. In the present study, we addressed the question of whether P2X7 receptor-mediated TNF-α regulation is involved in pathogenesis and outcome of status epilepticus (SE. Methods SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl-adenosine 5'-triphosphate (BzATP, adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP, A-438079, or A-740003 prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunit phosphorylations. Results Following SE, P2X7 receptor agonist (BzATP infusion increased TNF-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. In addition, TNF-α immunoreactivity was readily apparent in the mossy fibers, while TNF-α immunoreactivity in CA1-3 pyramidal cells was unaltered. However, P2X7 receptor antagonist (OxATP-, A-438079, and A-740003 infusion reduced SE-induced TNF-α expression in dentate granule cells. In the CA3 region, BzATP infusion attenuated SE-induced neuronal damage, accompanied by enhancement of p65-Ser276 and p65-Ser311 NF-κB subunit phosphorylations. In contrast, OxATP-, A-438079, and A-740003 infusions increased SE-induced neuronal death. Soluble TNF p55 receptor (sTNFp55R, and cotreatment with BzATP and sTNFp55R infusion also increased SE-induced neuronal damage in CA3 region. However, OxATP-, sTNFp55R or BzATP+sTNFp55R infusions could not exacerbate SE-induced neuronal damages in the dentate gyrus and the CA1 region, as compared to BzATP infusion. Conclusions These findings suggest that TNF-α induction by P2X7 receptor activation may ameliorate SE-induced CA3 neuronal damage via enhancing NF-κB p65-Ser276 and p65-Ser311 phosphorylations.

  19. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  20. Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

    Science.gov (United States)

    Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

    2018-06-02

    Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

  1. Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

    Directory of Open Access Journals (Sweden)

    Ramalingayya GV

    2017-03-01

    Full Text Available Grandhi Venkata Ramalingayya, Sri Pragnya Cheruku, Pawan G Nayak, Anoop Kishore, Rekha Shenoy, Chamallamudi Mallikarjuna Rao, Nandakumar Krishnadas Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Doxorubicin (DOX is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors’ quality of life. The study objective was to evaluate rutin (RUT for its neuroprotective effect against DOX in human neuroblastoma (IMR32 cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay (3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide, neurite growth assay, detection of apoptosis by (acridine orange/ethidium bromide staining, intracellular reactive oxygen species (ROS assay, and flowcytometric analysis were carried out to assess neuroprotective potential against DOX. An in vivo study was conducted for assessing protective effect of RUT against memory deficit associated with DOX-induced chemobrain using object recognition task (ORT. Locomotion was assessed using open field test. Serum biochemistry, acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex were assessed. Histopathological analysis of major organ systems was also carried out. Prior exposure to RUT at 100 µM protected IMR32 cells from DOX (1 µM neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and intracellular ROS generation with inhibition of neurite growth in differentiated IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intraperitoneal, once in 5 days, as we observed

  2. PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

    DEFF Research Database (Denmark)

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

    2017-01-01

    during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude...... depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling...

  3. ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer’s Disease in Mouse Models

    Directory of Open Access Journals (Sweden)

    Wei Yue

    2015-11-01

    Full Text Available Degeneration of basal forebrain cholinergic neurons (BFCNs is associated with cognitive impairments of Alzheimer’s disease (AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.

  4. Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol

    OpenAIRE

    Teppola, Heidi; Sarkanen, Jertta-Riina; Jalonen, Tuula O.; Linne, Marja-Leena

    2015-01-01

    Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was...

  5. Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol

    OpenAIRE

    Teppola, Heidi; Sarkanen, Jertta-Riina; Jalonen, Tuula; Linne, Marja-Leena

    2016-01-01

    Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was...

  6. Total Lignans of Schisandra chinensis Ameliorates Aβ1-42-Induced Neurodegeneration with Cognitive Impairment in Mice and Primary Mouse Neuronal Cells.

    Directory of Open Access Journals (Sweden)

    Xu Zhao

    Full Text Available Lignan compounds extracted from Schisandra chinensis (Turcz. Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC, as well as the level of malondialdehyde (MDA both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP, change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway. Moreover, TLS also decreased the activity of β-secretase 1 (BACE1, crucial protease contributes to the hydrolysis of amyloid precursor protein (APP, and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.

  7. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  8. Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice.

    Science.gov (United States)

    Wang, Jun; Chen, Fu; Zheng, Peng; Deng, Weijuan; Yuan, Jia; Peng, Bo; Wang, Ruochen; Liu, Wenjun; Zhao, Hui; Wang, Yanqing; Wu, Gencheng

    2012-07-01

    Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-γ and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-γ and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Directory of Open Access Journals (Sweden)

    Yong Sun Choi

    Full Text Available Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM. However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum.Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10 or a bariatric surgery group (gastric bypass surgery, n = 15. Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT. The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS, neuronal nitric oxide synthase (nNOS, Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG levels in the corpus cavernosum were assayed by using western blot and ELISA.The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002. The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014, and this was lower than the preoperative value (p = 0.037. The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021, and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025. Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively. Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032.In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  10. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Science.gov (United States)

    Choi, Yong Sun; Lee, Sang Kuon; Bae, Woong Jin; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Kim, Sae Woong

    2014-01-01

    Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum. Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA. The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032). In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  11. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  12. Cholesterol Test

    Science.gov (United States)

    ... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

  13. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  14. Cholesterol testing and results

    Science.gov (United States)

    ... your cholesterol is in this normal range. LDL (Bad) Cholesterol LDL cholesterol is sometimes called "bad" cholesterol. ... to 3.3 mmol/l) are desired. VLDL (Bad) Cholesterol VLDL contains the highest amount of triglycerides. ...

  15. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  16. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Managing High Cholesterol Cholesterol-lowering Medicine High Cholesterol Statistics and Maps High Cholesterol Facts High Cholesterol Maps ... Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart ...

  17. Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Rajib Paul

    Full Text Available Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

  18. Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

    Science.gov (United States)

    Paul, Rajib; Choudhury, Amarendranath; Kumar, Sanjeev; Giri, Anirudha; Sandhir, Rajat; Borah, Anupom

    2017-01-01

    Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

  19. DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.

    Science.gov (United States)

    He, Zhi; Lu, Qing; Xu, Xulin; Huang, Lin; Chen, Jianguo; Guo, Lianjun

    2009-01-28

    Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.

  20. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  1. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  2. LDL: The "Bad" Cholesterol

    Science.gov (United States)

    ... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

  3. 1,8-Cineole ameliorates oxygen-glucose deprivation/reoxygenation-induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia.

    Science.gov (United States)

    Ryu, Sangwoo; Park, Hyeon; Seol, Geun Hee; Choi, In-Young

    2014-12-01

    1,8-Cineole, the main monoterpene in many essential oils, has been used as an ingredient in flavourings and medicine. 1,8-Cineole has been shown to possess pharmacological properties, including anti-oxidative, anti-inflammatory and anti-nociceptive actions. However, to date, no studies have examined the potential of 1,8-cineole to protect against cerebral ischaemic injury. In this study, we investigated the neuroprotective effects of 1,8-cineole against cortical neuronal/glial cell injury caused by oxygen-glucose deprivation/reoxygenation (OGD/R) in an in-vitro model of ischaemia. 1,8-Cineole significantly attenuated OGD/R-induced cortical cell injury, as well as reduced n-methyl-d-aspartate (NMDA)-induced cell injury. However, it did not inhibit NMDA-induced cytosolic calcium overload. Nevertheless, 1,8-cineole significantly reduced the OGD/R- and NMDA-induced overproduction of reactive oxygen species (ROS). These results indicate that 1,8-cineole exerts neuroprotection through its anti-oxidative rather than its anti-excitotoxic, properties. The decrease in OGD/R-induced intracellular superoxide in 1,8-cineole-treated cortical cells was associated with the upregulation of superoxide dismutase activity. Moreover, 1,8-cineole showed direct ROS scavenging activity in an assay of oxygen radical absorbance capacity. Collectively, these results suggest 1,8-cineole as a potentially effective neuroprotective and anti-oxidative candidate for the treatment of patients with ischaemic stroke. © 2014 Royal Pharmaceutical Society.

  4. Cholesterol IQ Quiz

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Jul 5,2017 Begin the quiz ... What Your Cholesterol Levels Mean Common Misconceptions Cholesterol IQ Quiz • HDL, LDL, and Triglycerides • Causes of High ...

  5. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

  6. Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3).

    Science.gov (United States)

    Zarrouk, Amira; Nury, Thomas; Samadi, Mohammad; O'Callaghan, Yvonne; Hammami, Mohamed; O'Brien, Nora M; Lizard, Gérard; Mackrill, John J

    2015-07-01

    Some oxysterols are associated with neurodegenerative diseases. Their lipotoxicity is characterized by an oxidative stress and induction of apoptosis. To evaluate the capacity of these molecules to trigger cellular modifications involved in neurodegeneration, human neuronal cells SK-N-BE were treated with 7-ketocholesterol, 7α- and 7β-hydroxycholesterol, 6α- and 6β-hydroxycholesterol, 4α- and 4β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol (50-100μM, 24h) without or with docosahexaenoic acid (50μM). The effects of these compounds on mitochondrial activity, cell growth, production of reactive oxygen species (ROS) and superoxide anions (O2(-)), catalase and superoxide dismutase activities were determined. The ability of the oxysterols to induce increases in Ca(2+) was measured after 10min and 24h of treatment using fura-2 videomicroscopy and Von Kossa staining, respectively. Cholesterol, 7-ketocholesterol, 7β-hydroxycholesterol, and 24(S)-hydroxycholesterol (100μM) induced mitochondrial dysfunction, cell growth inhibition, ROS overproduction and cell death. A slight increase in the percentage of cells with condensed and/or fragmented nuclei, characteristic of apoptotic cells, was detected. With 27-hydroxycholesterol, a marked increase of O2(-) was observed. Increases in intracellular Ca(2+) were only found with 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Pre-treatment with docosahexaenoic acid showed some protective effects depending on the oxysterol considered. According to the present data, 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol could favor neurodegeneration by their abilities to induce mitochondrial dysfunctions, oxidative stress and/or cell death associated or not with increases in cytosolic calcium levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... This study was designed to evaluate the ameliorative effect of ... The group fed with 20% C. aconitifolius in place of 20% soya protein also ... to cholesterol enrichment of the erythrocytes membrane, ... rabbit and horse erythrocytes membrane with 1,2- .... various substances such as iron, vitamins and protein.

  8. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  9. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  10. Black ginseng extract ameliorates hypercholesterolemia in rats.

    Science.gov (United States)

    Saba, Evelyn; Jeon, Bo Ra; Jeong, Da-Hye; Lee, Kija; Goo, Youn-Kyoung; Kim, Seung-Hyung; Sung, Chang-Keun; Roh, Seong-Soo; Kim, Sung Dae; Kim, Hyun-Kyoung; Rhee, Man-Hee

    2016-04-01

    Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  11. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  12. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Science.gov (United States)

    Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

  13. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samia Hannaoui

    2014-11-01

    Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

  14. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  15. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

  16. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  17. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  18. Ameliorative percutaneous lumbar discectomy

    International Nuclear Information System (INIS)

    Xiao Chengjiang; Su Huanbin; He Xiaofeng; Li Yanhao

    2005-01-01

    Objective: To ameliorate the percutaneous lumbar discectomy (APLD) for improving the effectiveness and amplifying the indicative range of PLD. Methods: To ameliorate percutaneous punctured route based on classic PLD and discectomy of extracting pulp out of the herniated disc with special pulpforceps. The statistical analysis of the therapeutic results on 750 disc protrusions of 655 cases undergone APLD following up from 6 to 54 months retrospectively. Results: The effective ratios were excellent in 40.2%, good for 46.6% and bad of 13.3%. No occurrance of intervertebral inflammation and paradiscal hematoma, there were only 1 case complicated with injuried cauda equina, and 4 cases with broken appliance within disc. Conclusions: APLD is effective and safe, not only indicative for inclusion disc herniation, but also for noninclusion herniation. (authors)

  19. How to Lower Cholesterol

    Science.gov (United States)

    ... includes high triglyceride levels, low HDL (good) cholesterol levels, and being overweight with a large waist measurement (more than 40 inches for men and more than 35 inches for women). Physical Activity. Everyone should get regular physical activity (30 minutes ...

  20. Cholesterol and Health

    Indian Academy of Sciences (India)

    fats and oil in the diet on the other hand. Gallstones result from ... such factors as high levels of estrogens, multiple pregnancies, obesity, genetic factors and certain ... protein with an inner core of cholesterol and triglycerides. Lipoproteins are ...

  1. Reference intervals for serum total cholesterol, HDL cholesterol and ...

    African Journals Online (AJOL)

    Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

  2. Cholesterol in unusual places

    International Nuclear Information System (INIS)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

    2010-01-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  3. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  4. Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

    Directory of Open Access Journals (Sweden)

    Park SY

    2017-06-01

    Full Text Available Sun Young Park,1 Seon Yeong Chae,1,2 Jin Oh Park,2 Kyu Jin Lee,2 Geuntae Park1,2 1Bio-IT Fusion Technology Research Institute, 2Department of Nanofusion Technology, Graduate School, Pusan National University, Busan, Republic of Korea Abstract: Recently, environment-friendly synthesis of gold nanoparticles (GNPs has been extensively explored by biologists and chemists. However, significant research is still required to determine whether “eco-friendly” GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs, prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen–glucose deprivation/reoxygenation (OGD/R-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet–visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm and zeta potential (-20.3±0.04 mV were determined by dynamic light scattering. The average diameter (41.07±3.05 nm was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O–H, C–C, and C–N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p

  5. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  6. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  7. Biogenesis of plasma membrane cholesterol

    International Nuclear Information System (INIS)

    Lange, Y.

    1986-01-01

    A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from [ 3 H] acetate moved to the plasma membrane with a half-time of 1 h at 37 0 C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane

  8. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

  9. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  10. Transintestinal cholesterol excretion in humans

    NARCIS (Netherlands)

    Reeskamp, Laurens F.; Meessen, Emma C. E.; Groen, Albert K.

    2018-01-01

    Purpose of review To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. Recent findings TICE is the net effect of cholesterol excretion by

  11. Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet.

    Science.gov (United States)

    Saher, Gesine; Rudolphi, Fabian; Corthals, Kristina; Ruhwedel, Torben; Schmidt, Karl-Friedrich; Löwel, Siegrid; Dibaj, Payam; Barrette, Benoit; Möbius, Wiebke; Nave, Klaus-Armin

    2012-07-01

    Duplication of PLP1 (proteolipid protein gene 1) and the subsequent overexpression of the myelin protein PLP (also known as DM20) in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy without therapeutic options. PLP binds cholesterol and is contained within membrane lipid raft microdomains. Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis. Transgenic mice with extra copies of the Plp1 gene are accurate models of PMD. Dysmyelination followed by demyelination, secondary inflammation and axon damage contribute to the severe motor impairment in these mice. The finding that in Plp1-transgenic oligodendrocytes, PLP and cholesterol accumulate in late endosomes and lysosomes (endo/lysosomes), prompted us to further investigate the role of cholesterol in PMD. Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD.

  12. Cholesterol in brain disease: sometimes determinant and frequently implicated

    Science.gov (United States)

    Martín, Mauricio G; Pfrieger, Frank; Dotti, Carlos G

    2014-01-01

    Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell–cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function. PMID:25223281

  13. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  14. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  15. HDL cholesterol: atherosclerosis and beyond

    NARCIS (Netherlands)

    Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

  16. Nasal Colivelin treatment ameliorates memory impairment related to Alzheimer's disease.

    Science.gov (United States)

    Yamada, Marina; Chiba, Tomohiro; Sasabe, Jumpei; Terashita, Kenzo; Aiso, Sadakazu; Matsuoka, Masaaki

    2008-07-01

    Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Abeta induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

  17. Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and ...

    African Journals Online (AJOL)

    Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and physical exercise on ... Conclusion: Crataegus oxyacantha extract has shown positive affect to ameliorate on ... Key words: Crataegus oxyacantha, physical activity, epilepsy, gerbil, ...

  18. Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway

    Directory of Open Access Journals (Sweden)

    Hong Sun

    2013-01-01

    Full Text Available Diabetic nephropathy (DN has been associated with the presence of lipid deposition. We hypothesized that the disruption of intracellular cholesterol feedback may contribute to DN. Diabetes was induced by high fat/sucrose diet and low-dose intraperitoneal injection of streptozocin (STZ in male Sprague-Dawley rats. Then diabetic rats were randomly divided into two groups: untreated diabetic group (DM and atorvastatin-treated group (DM + AT. We found that the levels of serum blood urea nitrogen and creatinine, as well as 24-hour urine protein and urinary neutrophil gelatinase-associated lipocalin, were significantly increased in diabetic rats. This result indicated that the diabetic rats suffered from functional renal damage. We also observed lipid droplet accumulation and increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR, low density lipoprotein receptor (LDLr, sterol regulatory element binding protein-2 (SREBP-2, and SREBP-cleavage activating protein (SCAP in the kidneys of diabetic rats. However, atorvastatin ameliorated renal lipid accumulation and improved the renal function of diabetic rats despite an increase in mRNA and protein expressions of HMG-CoAR, LDLr, and SREBP-2. These results demonstrated that intracellular cholesterol feedback regulation is disrupted in rats with type 2 diabetes, thereby causing renal cholesterol accumulation. Atorvastatin ameliorated renal cholesterol accumulation by reducing renal cholesterol synthesis.

  19. What Are High Blood Cholesterol and Triglycerides?

    Science.gov (United States)

    ... Reduction Cholesterol What Are High Blood Cholesterol and Triglycerides? Cholesterol travels to the body’s cells through the ... doctor about medicines that can help. What are triglycerides? Triglycerides are the most common type of fat ...

  20. Cholesterol Perturbs Lipid Bilayers Nonuniversally

    International Nuclear Information System (INIS)

    Pan Jianjun; Mills, Thalia T.; Tristram-Nagle, Stephanie; Nagle, John F.

    2008-01-01

    Cholesterol is well known to modulate the physical properties of biomembranes. Using modern x-ray scattering methods, we have studied the effects of cholesterol on the bending modulus K C , the thickness D HH , and the orientational order parameter S xray of lipid bilayers. We find that the effects are different for at least three classes of phospholipids characterized by different numbers of saturated hydrocarbon chains. Most strikingly, cholesterol strongly increases K C when both chains of the phospholipid are fully saturated but not at all when there are two monounsaturated chains

  1. Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

    International Nuclear Information System (INIS)

    Wilson, M.D.

    1985-01-01

    The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

  2. Flurbiprofen ameliorates glucose deprivation-induced leptin resistance

    Directory of Open Access Journals (Sweden)

    Toru Hosoi

    2016-09-01

    Full Text Available Leptin resistance is one of the mechanisms involved in the pathophysiology of obesity. The present study showed that glucose deprivation inhibited leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3 and signal transducer and activator of transcription 5 (STAT5 in neuronal cells. Flurbiprofen reversed glucose deprivation-mediated attenuation of STAT3, but not STAT5 activation, in leptin-treated cells. Glucose deprivation increased C/EBP-homologous protein (CHOP and glucose regulated protein 78 (GRP78 induction, indicating the activation of unfolded protein responses (UPR. Flurbiprofen did not affect the glucose deprivation-induced activation of UPR, but did attenuate the glucose deprivation-mediated induction of AMP-activated protein kinase (AMPK phosphorylation. Flurbiprofen may ameliorate glucose deprivation-induced leptin resistance in neuronal cells.

  3. Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content.

    Directory of Open Access Journals (Sweden)

    Hanna Appelqvist

    Full Text Available Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1 protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2, which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determineD the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

  4. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    Science.gov (United States)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2010-03-01

    Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

  5. Imaging appearances of cholesterol pneumonia

    International Nuclear Information System (INIS)

    Miao Yanwei; Zhang Jingwen; Wu Jianlin; Zhou Yong; Li Mingwu; Lei Zhen; Shi Lifu

    2006-01-01

    Objection: To analyze the imaging appearances of cholesterol pneumonia. Methods We retrospectively analyzed the X-ray and CT findings of 3 patients with cholesterol pneumonia confirmed pathologically and reviewed correlative literature. Results: Lesions similar to mass were found in X-ray and CT imaging of three cases. Two of them appeared cavity with fluid-level and one showed multiple ring enhancement after CT contrast. The course of disease was very. long and it had no respond to antibiotic therapy. Amounts of foam cells rich in cholesterol crystal were detected in pathological examination. Conclusions: Cholesterol pneumonia is a rare chronic pulmonary idiopathic disease, and the radiological findings can do some help to its diagnosis. (authors)

  6. Beta-glucans and cholesterol

    Czech Academy of Sciences Publication Activity Database

    Šíma, Petr; Vannucci, Luca; Větvička, V.

    2017-01-01

    Roč. 41, č. 4 (2017), s. 1799-1808 ISSN 1107-3756 Institutional support: RVO:61388971 Keywords : cholesterol * beta-glucans * diet Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.341, year: 2016

  7. to HDL-cholesterol functionality

    Directory of Open Access Journals (Sweden)

    Malara Marzena

    2016-05-01

    Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

  8. Cholesterol and related sterols autoxidation.

    Science.gov (United States)

    Zerbinati, Chiara; Iuliano, Luigi

    2017-10-01

    Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

  9. High Cholesterol in Children and Teens

    Science.gov (United States)

    ... dairy products. The body needs some cholesterol to work properly. But if your child or teen has high cholesterol (too much cholesterol in the blood), he or she has a higher risk of coronary artery disease and other heart diseases. What causes high cholesterol in children and teens? Three main ...

  10. Cholesterol Medicines: MedlinePlus Health Topic

    Science.gov (United States)

    ... heart diseases . There are two main types of cholesterol. LDL is the "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in ... 75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher You ...

  11. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  12. Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

    Science.gov (United States)

    Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

    2018-01-01

    The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

  13. Cholesterol-lowering effects of dietary pomegranate extract and inulin in mice fed an obesogenic diet.

    Science.gov (United States)

    Yang, Jieping; Zhang, Song; Henning, Susanne M; Lee, Rupo; Hsu, Mark; Grojean, Emma; Pisegna, Rita; Ly, Austin; Heber, David; Li, Zhaoping

    2018-02-01

    It has been demonstrated in animal studies that both polyphenol-rich pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic changes induced by a high-fat diet, but little is known about the specific mechanisms. This study evaluated the effect of PomX (0.25%) and inulin (9%) alone or in combination on cholesterol and lipid metabolism in mice. Male C57BL/6 J mice were fed high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose)] diets supplemented with PomX (0.25%) and inulin (9%) alone or in combination for 4 weeks. At the end of intervention, serum and hepatic cholesterol, triglyceride levels, hepatic gene expression of key regulators of cholesterol and lipid metabolism as well as fecal cholesterol and bile acid excretion were determined. Dietary supplementation of the HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol. Supplementation with PomX and inulin together resulted in lower hepatic and serum total cholesterol compared to individual treatments. Compared to HF/HS control, PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid synthesis pathways. Inulin decreased gene expression of key regulators of cholesterol de novo synthesis Srebf2 and Hmgcr and significantly increased fecal elimination of total bile acids and neutral sterols. Only PomX in combination with inulin reduced liver and lipid weight significantly compared to the HF/HS control group. PomX showed a trend to decrease liver triglyceride (TG) levels, while inulin or PomX-inulin combination had no effect on either serum or liver TG levels. Dietary PomX and inulin supplementation decreased hepatic and serum total cholesterol by different mechanisms and the combination leading to a significant enhancement of the cholesterol-lowering effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  15. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam; Noutsi, Bakiza Kamal; Chaieb, Saharoui

    2016-01-01

    to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration

  16. Cholesterol overload impairing cerebellar function: the promise of natural products.

    Science.gov (United States)

    El-Sayyad, Hassan I H

    2015-05-01

    The cerebellum is the part of the brain most involved in controlling motor and cognitive function. The surface becomes convoluted, forming folia that have a characteristic internal structure of three layers including molecular, Purkinje cell, and granular layer. This complex neural network gives rise to a massive signal-processing capability. Cholesterol is a major constituent, derived by de novo synthesis and the blood-brain barrier. Cholesterol is tightly regulated between neurons and glia-that is, astrocytes, microglia, and oligodendrocytes-and is essential for normal brain development. The axon is wrapped by myelin (cholesterol, phospholipids, and glycosphingolipids) and made up of membranes of oligodendrocytes, separated by periodic gaps in the myelin sheath, called nodes of Ranvier. Hypercholesterolemia is associated with increased oxidative stress and the development of neurotoxicity and Alzheimer's disease. Treatment with natural products has been found to support improved brain function and reduce low-density-lipoprotein cholesterol level. Fish oil is one such product; among the many plant products are: Morus alba leaves, fruit, and bark; pomegranate fruit and peel; Barley β - glucans; date palm; and Allium sativum. The therapeutic potential was discussed in relation with the antilipidemic drugs, statins (HMG-CoA reductase inhibitors). Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol

  18. Cholesterol Levels: What You Need to Know: MedlinePlus Health Topic

    Science.gov (United States)

    ... lipoprotein ( LDL ) cholesterol and high-density lipoprotein ( HDL ) cholesterol. LDL (bad) cholesterol - the main source of cholesterol buildup ... Teens How to Lower Cholesterol How to Lower Cholesterol with Diet LDL: The "Bad" Cholesterol Nutrition Statins Triglycerides VLDL Cholesterol ...

  19. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  20. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

    OpenAIRE

    Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

    2009-01-01

    Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

  1. Lecithin intake and serum cholesterol.

    NARCIS (Netherlands)

    Knuiman, J.T.; Beynen, A.C.; Katan, M.B.

    1989-01-01

    To find out whether the consumption of lecithin has a more beneficial effect on serum cholesterol than does the consumption of equivalent amounts of polyunsaturated oils, we scrutinized 24 studies on the effect of supplementary lecithin intakes ranging from 1 to 54 mg/d. Most of the studies lacked

  2. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten

    2004-01-01

    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  3. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  4. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  5. Cholesterol autoxidation in phospholipid membrane bilayers

    International Nuclear Information System (INIS)

    Sevanian, A.; McLeod, L.L.

    1987-01-01

    Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

  6. Amelioration of High Cholesterol Diet Caused Lipids Accumulation in Hepatic Cells by Rutin and Ascorbic Acid

    OpenAIRE

    Abdulaziz M. Aleisa

    2013-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) has become a very common metabolic disorder. It refers to a group of conditions where excess fats are deposited in hepatic cells. Several approaches have been considered for the management of NAFLD including dietary changes, which were reported to suppress hepatic lipids accumulation in previous studies. The present study was designed to investigate the possible synergistic effects of Rutin (RT) and Ascorbic Acid (AA) against lipids accumulation in he...

  7. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  8. Covalent immobilization of cholesterol esterase and cholesterol oxidase on polyaniline films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Solanki, Pratima R. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Pandey, M.K. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India)]. E-mail: bansi@mail.nplindia.ernet.in

    2006-05-24

    Cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been covalently immobilized on electrochemically prepared polyaniline (PANI) films. These PANI/ChEt/ChOx enzyme films have been characterized using UV-visible, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Electrochemical behavior of these films has been studied using cyclic voltammetry (CV) and amperometric techniques, respectively. The PANI/ChEt/ChOx enzyme films show broad oxidation peak from 0.2 to 0.5 V. These PANI/ChEt/ChOx biosensing electrodes have a response time of about 40 s, linearity from 50 to 500 mg/dl of cholesterol oleate concentration. These PANI/ChEt/ChOx films are thermally stable up to 46 deg. C. This polyaniline based cholesterol biosensor has optimum pH in the range of 6.5-7.5, sensitivity as 7.5 x 10{sup -4} nA/mg dl and a lifetime of about 6 weeks.

  9. Specific immunotherapy ameliorates ulcerative colitis.

    Science.gov (United States)

    Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

    2016-01-01

    Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

  10. Nanoscale Membrane Domain Formation Driven by Cholesterol

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

    2017-01-01

    Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

  11. Cholesterol, bile acid and triglyceride metabolism intertwined

    NARCIS (Netherlands)

    Schonewille, Marleen

    2016-01-01

    Hyperlipidemie wordt gekarakteriseerd door verhoogd plasma cholesterol en/of triglyceriden en sterk geassocieerd met het risico op cardiovasculaire aandoeningen. Dit proefschrift beschrijft onderzoek naar de regulatie van plasma cholesterol en triglyceriden concentraties en de achterliggende

  12. Cholesterol Level: Can It Be Too Low?

    Science.gov (United States)

    ... total cholesterol level has been associated with some health problems. Doctors are still trying to find out more about the connection between low cholesterol and health risks. There is no consensus on how to ...

  13. Cholesterol: the debate should be terminated.

    Science.gov (United States)

    Nathan, David G

    2017-07-01

    Here, I offer personal perspectives on cholesterol homeostasis that reflect my belief that certain aspects of the debate have been overstated.-Nathan, D. G. Cholesterol: the debate should be terminated. © FASEB.

  14. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  15. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  16. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  17. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  18. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  19. Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

    Science.gov (United States)

    Musolino, V; Gliozzi, M; Carresi, C; Maiuolo, J; Mollace, R; Bosco, F; Scarano, F; Scicchitano, M; Maretta, A; Palma, E; Iannone, M; Morittu, V M; Gratteri, S; Muscoli, C; Fini, M; Mollace, V

    2017-01-01

    Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

  20. Peptide mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  1. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  2. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    International Nuclear Information System (INIS)

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [ 14 C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans

  3. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy...... and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly....

  4. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  5. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol

  6. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    Boer, J.F. de; Schonewille, M.; Boesjes, M.; Wolters, H.; Bloks, V.W.; Bos, T.; Dijk, T.H. van; Jurdzinski, A.; Boverhof, R.; Wolters, J.C.; Kuivenhoven, J.A.; Deursen, J.M.A. van; Elferink, R.P.; Moschetta, A.; Kremoser, C.; Verkade, H.J.; Kuipers, F.; Groen, A.K.

    2017-01-01

    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE)

  7. Rational heterodoxy: cholesterol reformation of the amyloid doctrine.

    Science.gov (United States)

    Castello, Michael A; Soriano, Salvador

    2013-01-01

    According to the amyloid cascade hypothesis, accumulation of the amyloid peptide Aβ, derived by proteolytic processing from the amyloid precursor protein (APP), is the key pathogenic trigger in Alzheimer's disease (AD). This view has led researchers for more than two decades and continues to be the most influential model of neurodegeneration. Nevertheless, close scrutiny of the current evidence does not support a central pathogenic role for Aβ in late-onset AD. Furthermore, the amyloid cascade hypothesis lacks a theoretical foundation from which the physiological generation of Aβ can be understood, and therapeutic approaches based on its premises have failed. We present an alternative model of neurodegeneration, in which sustained cholesterol-associated neuronal distress is the most likely pathogenic trigger in late-onset AD, directly causing oxidative stress, inflammation and tau hyperphosphorylation. In this scenario, Aβ generation is part of an APP-driven adaptive response to the initial cholesterol distress, and its accumulation is neither central to, nor a requirement for, the initiation of the disease. Our model provides a theoretical framework that places APP as a regulator of cholesterol homeostasis, accounts for the generation of Aβ in both healthy and demented brains, and provides suitable targets for therapeutic intervention. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Intracellular transport of cholesterol in mammalian cells

    International Nuclear Information System (INIS)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of [ 3 H]cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth

  9. Cholesterol

    Science.gov (United States)

    ... eating habits, such as eating lots of bad fats. One type, saturated fat, is found in some meats, dairy products, chocolate, ... goods, and deep-fried and processed foods. Another type, trans fat, is in some fried and processed foods. Eating ...

  10. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers......, at least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

  11. Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

    Science.gov (United States)

    Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

    2013-01-01

    Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

  12. Ameliorative Effect of Different Concentration of Mushroom ...

    African Journals Online (AJOL)

    Prof. Ogunji

    ameliorative effect of mushroom in the post-experimental stage. Samples of liver and ... except in the liver which showed mild periportal chronic inflammatory cell. However, the .... alcohol for 12 hours and through absolute alcohol to remove ...

  13. Portulaca oleracea Linn seed extract ameliorates hydrogen ...

    African Journals Online (AJOL)

    Portulaca oleracea Linn seed extract ameliorates hydrogen ... induced cell death by inhibiting oxidative stress and ROS generation. Keywords: ... culture medium; therefore the stock solutions of ... acetic acid (1 %) and ethanol (50 %) to extract.

  14. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. L Barkat, A Boumendjel, C Abdennour, MS Boulakoud, A El Feki, M Messarah ...

  15. Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

    Science.gov (United States)

    Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin

    2016-04-01

    Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Dietary Amelioration of Helicobacter Infection

    Science.gov (United States)

    Fahey, Jed W.; Stephenson, Katherine K.; Wallace, Alison J.

    2015-01-01

    We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on: (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H. pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H. pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability and cultural acceptability. This review therefore highlights specific foods, food components, and food products, grouped as follows: bee products (e.g. honey and propolis), probiotics, dairy products, vegetables, fruits, oils, essential oils, and herbs, spices and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and pre-clinical evidence must now be followed up with rationally designed, unambiguous human trials. PMID:25799054

  17. Amelioration of some biochemical parameters in irradiated male albino rats by garlic

    International Nuclear Information System (INIS)

    El-masry, F.S.H.; El-sayed, N.M.; Hussein, A.H.

    2005-01-01

    Garlic extract has various medical effects on the treatment of many diseases as hypertension, atherosclerosis, inflammation and diabetes. The alteration of the biochemical parameters in blood serum of irradiated rats may play an important role in determining the pathogenesis of radiation exposure. Many of the damaging effects of ionizing radiation are mediated by reactive free radicals. This study was designed to evaluate the protective role of garlic against gamma irradiation (5Gy) induced biochemical disorders in rats. Samples were collected at 1, 7 and 14 days post-irradiation. Lipid peroxide content (malondialdehyde), cholesterol, HDL-C, LDL-C, fatty acids, glucose, insulin, glycogen, haemoglobin, ferritin andiron were estimated.Garlic was orally administered to rats (100 mg/kg body weight) for 14 days before exposure to single dose of gamma irradiation at dose level 5 Gy. The data revealed significant increase in the levels of lipid peroxide, cholesterol, LDL-cholesterol, fatty acids, insulin, glucose and iron accompanied with significant decrease in the levels of HDL-cholesterol, glycogen, haemoglobin and ferritin due to radiation exposure. Administration of garlic alone to the rats caused nonsignificant changes in the estimated parameters indicating its safe use, but the treatment with garlic to rats before radiation exposure ameliorated the changes induced by gamma irradiation and tended to normalize their levels.It could be concluded that garlic administration may has a beneficial role in restoring the biochemical disorders induced by 5 Gy gamma irradiation

  18. Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Paola eGamba

    2015-06-01

    Full Text Available Alzheimer’s disease (AD, the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis.

  19. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  20. The cholesterol space of the rat

    International Nuclear Information System (INIS)

    Chevallier, F.

    1959-01-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [fr

  1. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  2. Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

    Science.gov (United States)

    Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

    2014-04-27

    The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

  3. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  4. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr

    2016-01-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low...... and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have...

  5. Impact of heme oxygenase-1 on cholesterol synthesis, cholesterol efflux and oxysterol formation in cultured astroglia.

    Science.gov (United States)

    Hascalovici, Jacob R; Song, Wei; Vaya, Jacob; Khatib, Soliman; Fuhrman, Bianca; Aviram, Michael; Schipper, Hyman M

    2009-01-01

    Up-regulation of heme oxygenase-1 (HO-1) and altered cholesterol (CH) metabolism are characteristic of Alzheimer-diseased neural tissues. The liver X receptor (LXR) is a molecular sensor of CH homeostasis. In the current study, we determined the effects of HO-1 over-expression and its byproducts iron (Fe(2+)), carbon monoxide (CO) and bilirubin on CH biosynthesis, CH efflux and oxysterol formation in cultured astroglia. HO-1/LXR interactions were also investigated in the context of CH efflux. hHO-1 over-expression for 3 days ( approximately 2-3-fold increase) resulted in a 30% increase in CH biosynthesis and a two-fold rise in CH efflux. Both effects were abrogated by the competitive HO inhibitor, tin mesoporphyrin. CO, released from administered CORM-3, significantly enhanced CH biosynthesis; a combination of CO and iron stimulated CH efflux. Free iron increased oxysterol formation three-fold. Co-treatment with LXR antagonists implicated LXR activation in the modulation of CH homeostasis by heme degradation products. In Alzheimer's disease and other neuropathological states, glial HO-1 induction may transduce ambient noxious stimuli (e.g. beta-amyloid) into altered patterns of glial CH homeostasis. As the latter may impact synaptic plasticity and neuronal repair, modulation of glial HO-1 expression (by pharmacological or other means) may confer neuroprotection in patients with degenerative brain disorders.

  6. Following Intracellular Cholesterol Transport by Linear and Non-Linear Optical Microscopy of Intrinsically Fluorescent Sterols

    DEFF Research Database (Denmark)

    Wustner, D.

    2012-01-01

    Elucidation of intracellular cholesterol transport is important for understanding the molecular basis of several metabolic and neuronal diseases, like atheroclerosis or lysosomal storage disorders. Progress in this field depends crucially on the development of new technical approaches to follow...... is on recent developments in imaging technology to follow the intracellular fate of intrinsically fluorescent sterols as faithful cholesterol markers. In particular, UV-sensitive wide field and multiphoton microscopy of the sterol dehydroergosterol, DHE, is explained and new methods of quantitative image...... analysis like pixel-wise bleach rate fitting and multiphoton image correlation spectroscopy are introduced. Several applications of the new technology including observation of vectorial sterol trafficking in polarized human hepatoma cells for investigation of reverse cholesterol transport are presented....

  7. Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Zhong-he Liu

    2015-01-01

    Full Text Available Objective. The effects of Flos Puerariae extract (FPE on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA and total cholesterol (TCH in serum, malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, and acetylcholinesterase (AChE activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

  8. β-glycosphingolipids ameliorated non-alcoholic steatohepatitis in the Psammomys obesus model

    Directory of Open Access Journals (Sweden)

    Zigmond E

    2014-10-01

    Full Text Available Ehud Zigmond,1,* Oshrat Tayer-Shifman,1,* Gadi Lalazar,1 Ami Ben Ya'acov,1 Sarah Weksler-Zangen,2 David Shasha,1 Miriam Sklair-Levy,3 Lidya Zolotarov,1 Zvi Shalev,1 Rony Kalman,2 Ehud Ziv,2 Itamar Raz,2 Yaron Ilan1 1Liver Unit, 2Diabetes Unit, 3Department of Radiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel *These authors contributed equally to this workAbstract: Liver steatosis is a common characteristic of obesity and type 2 diabetes, and fatty liver disease is increasingly recognized as a major health burden. Accumulating evidence suggests that β-glycosphingolipids play an important role in insulin sensitivity and thus could affect hepatic steatosis. To determine the effect associated with β-glycosphingolipid-mediated amelioration of liver injury, seven groups of Psammomys obesus on a high-energy diet were studied. Animals were treated with daily injections of β-glucosylceramide, β-lactosylceramide, or a combination of both. β-glycosphingolipids ameliorated the hepatic injury manifested by decreased liver enzymes, liver weight, and hepatic fat, and improved liver histology. Administration of both β-glucosylceramide and β-lactosylceramide also decreased interferon (IFN-γ serum levels. These effects were associated with improved serum cholesterol and triglyceride levels. These data suggest that β-glycosphingolipids ameliorate liver injury in an animal model of nonalcoholic steatohepatitis.Keywords: NAFLD, glycolipids, STAT, NASH, insulin resistance, diabetes

  9. Altered GPM6A/M6 Dosage Impairs Cognition and Causes Phenotypes Responsive to Cholesterol in Human and Drosophila

    NARCIS (Netherlands)

    Gregor, A.; Kramer, J.M.; Voet, M. van der; Schanze, I.; Uebe, S.; Donders, R.; Reis, A.; Schenck, A.; Zweier, C.

    2014-01-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral

  10. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  11. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  12. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A.M.; Vonk, R.J.; Niezen-Koning, K.; Berger, R.; Fernandes, J.

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  13. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  14. Cholesterol Transport Revisited : A New Turbo Mechanism to Drive Cholesterol Excretion

    NARCIS (Netherlands)

    de Boer, Jan Freark; Kuipers, Folkert; Groen, Albert K.

    A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are

  15. The cholesterol space of the rat; L'espace cholesterol du rat

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [French] Les experiences ont consiste a faire ingerer quotidiennement une meme masse de cholesterol radioactif a des rats, durant des laps de temps variables. L'evolution de la radioactivite specifique du carbone-14 du cholesterol des organes en fonction du temps permet d'obtenir des renseignements relatifs au transport du cholesterol dans l'organisme. 1) L'espace cholesterol defini comme l'ensemble des molecules susceptibles d'etre transferees des organes dans le serum, et vice-versa, represente au plus 50 pour cent du cholesterol total du rat adulte. 2) Le va et vient incessant entre le cholesterol tissulaire et le cholesterol serique renouvelle en totalite ou en

  16. Phytosterol glycosides reduce cholesterol absorption in humans

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636

  17. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  18. Nuclear receptors in control of cholesterol transport

    NARCIS (Netherlands)

    van der Veen, Jelske Nynke

    2007-01-01

    Cholesterol is een structurele component van celmembranen en een grondstof voor de aanmaak van steroïde hormonen en galzouten en vervult dus een aantal essentiële fysiologische functies. Een goede balans van cholesterol opname, synthese, afbraak en uitscheiding is noodzakelijk, omdat verhoogde

  19. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-03-01

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice.

    Science.gov (United States)

    Kim, Jong Min; Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Kang, Jin Yong; Ha, Jeong Su; Lee, Du Sang; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

    2017-04-05

    The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.

  1. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    Science.gov (United States)

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Use of Some Methods for Amelioration Heat Stress in Friesian Calves

    International Nuclear Information System (INIS)

    Aboulnaga, A.I.; Kamal, T.H.

    2008-01-01

    Twenty Friesian calves of 3-4 months of age and 90 kg average body weight, were used to investigate the effect of hot climate (36 degree C, 65% R.H.) and evaluate two methods of ameliorating heat stress, the first method was feed supplementation with urea and mineral mixture and the second was water sprinkling and supplying the heat stressed animals with cool water. Daily body gain (DBG) was calculated, while serum protein, urea N, cholesterol, creatine, alkaline phosphatase (Alk-P) and acid phosphatase (Ac-P) were determined in this study. The first and second treatments were carried out inside the climatic chamber and the third was undertaken outdoors (36.5± 2.5 degree C, 62.5±4.5% R.H.). Heat stress induced a significant decrease in DBG, serum protein, urea N, cholesterol, creatine and plasma aldosterone (P<0.01) and serum Alk-P (P<0.05), while the serum Ac-P decreased insignificantly. The nutritional treatment caused a significant increase in DBG serum protein And urea N (P<0.01) and serum creatine (P<0.05). Sprinkling and drinking cooled water caused an increase in serum cholesterol, plasma aldosterone (P<0.01), DBG, serum protein and creatine (P<0.05)

  3. Ameliorative effect of Lentinus squarrosulus mycomeat against ...

    African Journals Online (AJOL)

    Ameliorative effect of Lentinus squarrosulus mycomeat against Pseudomonas aeruginosa infection using albino rat as animal model. ... Morphological appearance and behavior of the rats were used as the assessment method for adverse reactions. After a period of 26 days, the rats were sacrificed with the liver, spleen and ...

  4. Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions.

    Science.gov (United States)

    Czuba, Ewelina; Steliga, Aleksandra; Lietzau, Grażyna; Kowiański, Przemysław

    2017-08-01

    The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

  5. Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization

    NARCIS (Netherlands)

    van den Berg, A. A.; van Buul, J. D.; Tytgat, G. N.; Groen, A. K.; Ostrow, J. D.

    1998-01-01

    Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in

  6. Tuberculosis treatment raises total cholesterol level and restores ...

    African Journals Online (AJOL)

    aghomotsegin

    2013-10-09

    Oct 9, 2013 ... and restores high density lipoprotein cholesterol (HDL- ... cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined .... However, we found a strong negative correlation (r = - 0.96,.

  7. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and

  8. Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.

    Science.gov (United States)

    Nordström, Viola; Willershäuser, Monja; Herzer, Silke; Rozman, Jan; von Bohlen Und Halbach, Oliver; Meldner, Sascha; Rothermel, Ulrike; Kaden, Sylvia; Roth, Fabian C; Waldeck, Clemens; Gretz, Norbert; de Angelis, Martin Hrabě; Draguhn, Andreas; Klingenspor, Martin; Gröne, Hermann-Josef; Jennemann, Richard

    2013-01-01

    Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis.

  9. Ameliorating role of chromium ingestion on biochemical, histological and trigluconate disorders induced by diabetes and / or gamma irradiation in pregnant albino rats and their fetuses

    International Nuclear Information System (INIS)

    RAMADAN, F.L.; REZK, R.G.

    2006-01-01

    Chromium is an essential trace element in human nutrition for the regulation of insulin action thereby influencing carbohydrate and lipid metabolism The aim of the present study was to evaluate the role of chromium intake on radiation-induced damage in diabetic mothers. Diabetes was induced in female rats by intraperitoneal injection of 150 mg/kg alloxan dissolved in saline. Pregnant diabetic mothers were received chromium (20 mg/kg) from the 1st up to the 19 th day of gestation. Meanwhile, pregnant diabetic rats were exposed to 0.3 Gy gamma radiation on the 6th and the 12 th day of gestation. Chromium treatment of diabetic mothers ameliorated radiation-induced damage, which was obvious by diminishing the increase of glucose, malonaldehyde (MDA), total cholesterol levels and by ameliorating the decrease of glutathione level in blood serum. In addition,chromium treatment ameliorated the radiation-induced changes in cholesterol levels of the fetuses. Moreover, chromium treatment led to the regeneration of the normal architecture of maternal hepatic cells and blood vessels. It could be concluded that chromium supplementation to diabetic mothers ameliorated the radiation-induced biochemical, histopathological and teratological disorders. Furthermore, the results obtained showed that chromium administration caused a significant protection to diabetic pregnant females against radiation-induced spontaneous abortion and embryo malformations

  10. Interaction of pathogens with host cholesterol metabolism.

    Science.gov (United States)

    Sviridov, Dmitri; Bukrinsky, Michael

    2014-10-01

    Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

  11. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    Ponz de Leon, M.; Carubbi, F.; Di Donato, P.; Carulli, N.

    1985-01-01

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14 C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  12. Cholesterol asymmetry in synaptic plasma membranes.

    Science.gov (United States)

    Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

    2011-03-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  13. [Cholesterol reducing food certainly is useful].

    Science.gov (United States)

    Stalenhoef, A F

    1997-12-27

    The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

  14. Efficacy of functional foods mixture in improving hypercholesterolemia, inflammatory and endothelial dysfunction biomarkers-induced by high cholesterol diet.

    Science.gov (United States)

    Al-Muzafar, Hessah Mohammed; Amin, Kamal Adel

    2017-10-06

    Hypercholesterolemia associated with cardiovascular diseases is a global health issue that could be alleviated by functional foods. This study aimed to explore the effects of a high-cholesterol diet on lipid profile, cardiac, inflammatory, and endothelial dysfunction biomarkers, and the possible improvement by functional foods mixture. Male albino rats weighing 100-150 g were randomly divided into four equal groups: 1st control, giving a normal diet; the 2nd received high-cholesterol diet for 8 weeks, the 3rd received the high-cholesterol diet + functional foods mixture, and the 4th administered high-cholesterol diet +atorvastatin (20 mg) orally. The results showed a significant increase in lipid profile and cardiac biomarkers levels (lactate dehydrogenase, creatine kinase and homocystein), also inflammatory markers, as, tumor necrotic factor alpha and chronic reactive proteins were elevated, moreover, vascular adhesion molecule-1 and nitric oxide synthase were disturbed in high-cholesterol diet compared with normal group. While administration of atorvastatin and functional foods mixture ameliorated these alterations. Administration of functional foods mixture and atorvastatin were effective in treating hypercholesterolemia, reduce the risk of inflammation and cardiovascular biomarkers with a high safety margin. These efficiencies may be due to its active ingredient that improve the imbalance in the measured biomarkers.

  15. HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Vladmila Bojanic

    2004-01-01

    Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

  16. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    Science.gov (United States)

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  17. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

    Science.gov (United States)

    Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-06-01

    Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

  18. Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

    Science.gov (United States)

    Olatunji, L A; Soladoye, A O

    2007-06-01

    Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

  19. HDL (Good), LDL (Bad) Cholesterol and Triglycerides

    Science.gov (United States)

    ... Are Cholesterol-Lowering Medications? How Statins Work Medication Tracker Personal ... or Sudden Cardiac Arrest: How Are They Different? 7 Warning Signs of a Heart Attack 8 Low Blood Pressure - ...

  20. Overview of Cholesterol and Lipid Disorders

    Science.gov (United States)

    ... Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version ... Cholesterol and triglycerides are important ...

  1. Biochemical characterization of cholesterol-reducing Eubacterium.

    OpenAIRE

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-01-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addit...

  2. Impact of a public cholesterol screening program.

    Science.gov (United States)

    Fischer, P M; Guinan, K H; Burke, J J; Karp, W B; Richards, J W

    1990-12-01

    The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease.

  3. Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

    Science.gov (United States)

    Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

    2012-05-01

    In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

  4. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  5. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

    International Nuclear Information System (INIS)

    Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

    1987-01-01

    Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

  6. Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

    Science.gov (United States)

    2014-01-01

    The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication. PMID:25202970

  7. Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet.

    Science.gov (United States)

    Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

    2017-10-01

    The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet. Copyright © 2017. Published by Elsevier B.V.

  8. Red algae (Gelidium amansii hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Tsung-Han Yang

    2017-10-01

    Full Text Available The purpose of this study was to investigate the effects of Gelidium amansii (GA hot-water extracts (GHE on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1 control diet group (CON; (2 high-fat diet group (HF; (3 HF with GHE diet group (HF + GHE; (4 HF with probucol diet group (HF + PO. All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal weight. The HF diet induced an increase in plasma triacylglycerol (TG, total cholesterol (TC, low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP-activated protein kinase (AMPK protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet.

  9. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  10. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  11. Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

    Science.gov (United States)

    Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

    2015-06-15

    Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

  12. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

  13. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

    Directory of Open Access Journals (Sweden)

    Se-Jin Jeong

    2017-03-01

    Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

  14. Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

    Science.gov (United States)

    Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

    2016-07-01

    We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

  15. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

    NARCIS (Netherlands)

    Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

    2007-01-01

    BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

  16. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice

    NARCIS (Netherlands)

    Bura, Kanwardeep S.; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A.; Sawyer, Janet K.; Shah, Ramesh; Wilson, Martha D.; Dikkers, Arne; Tietge, Uwe J. F.; Collet, Xavier; Rudel, Lawrence L.; Temel, Ryan E.; Brown, J. Mark

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the non-biliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI

  17. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    OpenAIRE

    Matthias Orth; Stefano Bellosta

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein...

  18. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  19. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.

  20. The evolution of violence in men: the function of central cholesterol and serotonin.

    Science.gov (United States)

    Wallner, Bernard; Machatschke, Ivo H

    2009-04-30

    Numerous studies point to central serotonin as an important modulator of maladaptive behaviors. In men, for instance, low concentrations of this neurotransmitter are related to hostile aggression. A key player in serotonin metabolism seems to be central cholesterol. It plays a fundamental role in maintaining the soundness of neuron membranes, especially in the exocytosis transport of serotonin vesicles into the synaptic cleft. In this review, we attempt an evolutionary approach to the neurobiological basis of human male violence. Hominid evolution was shaped by periods of starvation but also by energy demands of an increasingly complex brain. A lack of food resources reduces uptake of glucose and results in a decreased energy-supply for autonomous brain cholesterol synthesis. Consequently, concentrations of neuromembrane cholesterol decrease, which lead to a failure of the presynaptic re-uptake mechanism of serotonin and ultimately to low central serotonin. We propose that starvation might have affected the larger male brains earlier than those of females. Furthermore, this neurophysiological process diminished the threshold for hostile aggression, which in effect represented a prerequisite for being a successful hunter or scavenger. In a Darwinian sense, the odds to acquire reliable energetic resources made those males to attractive spouses in terms of paternal care and mate support. To underpin these mechanisms, a hypothetical four-stage model of synaptic membrane destabilization effected by a prolonged shortage of high-energy, cholesterol-containing food is illustrated.

  1. Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

    Science.gov (United States)

    Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

    2000-04-01

    Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

  2. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

    Science.gov (United States)

    Kumar, Narendra; Kar, Anand; Panda, Sunanda

    2014-08-01

    Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  4. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  5. Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements based on an enzyme-coupled reaction that detects both free cholesterol (membrane and cholesteryl esters (stored in lipid droplets, revealed that oocytes and cumulus cells present different levels of cholesterol depending on the seasonal period. Variations at membrane cholesterol level of oocytes were enough to account for the differences found in total cholesterol. Differences found in total cholesterol of cumulus cells were explained by the differences found in both the content of membrane cholesterol and of cholesterol esters. Cholesterol was incorporated into the oocyte plasma membrane as evidenced by comparative labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased membrane cholesterol after incubation with MβCD/cholesterol and recovered their original level after cholesterol removal, regardless of the season. Finally, we evaluated the effect of vitrification on the putative raft molecule GM1. Cholesterol modulation also preserved membrane organization by maintaining ganglioside level at the plasma membrane. Results suggest a distinctive cholesterol metabolic status of cumulus-oocyte complexes (COCs among seasons and a dynamic organizational structure

  6. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo

    2009-01-01

    Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins....... In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

  7. Characteristics of human hypo- and hyperresponders to dietary cholesterol.

    Science.gov (United States)

    Katan, M B; Beynen, A C

    1987-03-01

    The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

  8. Coconut oil attenuates the effects of amyloid-β on cortical neurons in vitro.

    Science.gov (United States)

    Nafar, Firoozeh; Mearow, Karen M

    2014-01-01

    Dietary supplementation has been studied as an approach to ameliorating deficits associated with aging and neurodegeneration. We undertook this pilot study to investigate the effects of coconut oil supplementation directly on cortical neurons treated with amyloid-β (Aβ) peptide in vitro. Our results indicate that neuron survival in cultures co-treated with coconut oil and Aβ is rescued compared to cultures exposed only to Aβ. Coconut oil co-treatment also attenuates Aβ-induced mitochondrial alterations. The results of this pilot study provide a basis for further investigation of the effects of coconut oil, or its constituents, on neuronal survival focusing on mechanisms that may be involved.

  9. [Screening and optimization of cholesterol conversion strain].

    Science.gov (United States)

    Fan, Dan; Xiong, Bingjian; Pang, Cuiping; Zhu, Xiangdong

    2014-10-04

    Bacterial strain SE-1 capable of transforming cholesterol was isolated from soil and characterized. The transformation products were identified. Fermentation conditions were optimized for conversion. Cholesterol was used as sole carbon source to isolate strain SE-1. Morphology, physiological and biochemical characteristics of strain SE-1 were studied. 16S rRNA gene was sequenced and subjected to phylogenetic analysis. Fermentation supernatants were extracted with chloroform, the transformation products were analyzed by silica gel thin layer chromatography and Sephadex LH20. Their structures were identified by 1H-NMR and 13C-NMR. Fermentation medium including carbon and nitrogen, methods of adding substrates and fermentation conditions for Strain SE-1 were optimized. Strain SE-1 was a Gram-negative bacterium, exhibiting the highest homologs to Burkholderia cepacia based on the physiological analysis. The sequence analysis of 16S rRNA gene of SE-1 strain and comparison with related Burkholderia show that SE-1 strain was very close to B. cepacia (Genbank No. U96927). The similarity was 99%. The result of silica gel thin layer chromatography shows that strain SE-1 transformed cholesterol to two products, 7beta-hydroxycholesterol and the minor product was 7-oxocholesterol. The optimum culture conditions were: molasses 5%, (NH4 )2SO4 0.3%, 4% of inoculation, pH 7.5 and 36 degrees C. Under the optimum culture condition, the conversion rate reached 34.4% when concentration of cholesterol-Tween 80 was 1 g/L. Cholesterol 7beta-hydroxylation conversion rate under optimal conditions was improved by 20.8%. Strain SE-1 isolated from soil is capable of converting cholesterol at lab-scale.

  10. Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

    Science.gov (United States)

    Iannella, Giannicola; Di Gioia, Cira; Carletti, Raffaella; Magliulo, Giuseppe

    2017-08-01

    This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. Retrospective study. Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. 3b. Laryngoscope, 127:E283-E290, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  11. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    Directory of Open Access Journals (Sweden)

    Frans Stellaard

    2017-01-01

    Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

  12. Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

    NARCIS (Netherlands)

    Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

    Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

  13. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

  14. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    Aigueperse, Jocelyne

    1979-01-01

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author) [fr

  15. 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?

    NARCIS (Netherlands)

    Bangalore, Sripal; Fayyad, Rana; Kastelein, John J.; Laskey, Rachel; Amarenco, Pierre; Demicco, David A.; Waters, David D.

    2016-01-01

    The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether

  16. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  17. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  18. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  19. Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures

    Science.gov (United States)

    Palanca, José M.; Aguirre-Rueda, Diana; Granell, Manuel V.; Aldasoro, Martin; Garcia, Alma; Iradi, Antonio; Obrador, Elena; Mauricio, Maria Dolores; Vila, Jose; Gil-Bisquert, Anna; Valles, Soraya L.

    2013-01-01

    Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types. PMID:23983586

  20. Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Borup, Rehannah; Marstrand, Troels

    2007-01-01

    could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol...... of neuronal CCK are incompletely understood. To identify genes regulated by neuronal CCK, we generated neuronal PC12 cells stably expressing the CCK-2 receptor (CCK-2R) and treated the cells with sulphated CCK-8 for 2-16 h, before the global expression profile was examined. The changes in gene expression...... peaked after 2 h, with 67 differentially expressed transcripts identified. A pathway analysis indicated that CCK was implicated in the regulation of the circadian clock system, the plasminogen system and cholesterol metabolism. But transcripts encoding proteins involved in dopamine signaling, ornithine...

  1. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  2. Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

    International Nuclear Information System (INIS)

    AlRowaily, Meshref A

    2008-01-01

    The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

  3. Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice

    Science.gov (United States)

    Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-01-01

    Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications. PMID:22474522

  4. High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

    Science.gov (United States)

    Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

    2017-12-01

    Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

  5. EFFICACY OF TOMATO AND / OR GARLIC IN AMELIORATING CARDIAC DISORDERS INDUCED BY FEEDING RATS FRYING OIL

    International Nuclear Information System (INIS)

    OSMAN, N.N.

    2007-01-01

    Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidaemia, thrombosis, hypertension and diabetes. Tomato has anti-mutagenic activities and contains lycopene (a powerful antioxidant) that appears to prevent oxidation of low density lipoprotein cholesterol (LDL-c) and reduces the risk of developing atherosclerosis and coronary heart disease. The present study was carried out to investigate the potential protective effects of tomato or garlic alone or their combination against cardiac disorders in rats fed commercial diet fortified with frying oil (15% w/w) for 30 days. Thirty male Wistar albino rats were used and were divided into five groups; group 1, control (rats fed diet containing 15% w/w fresh oil); group 2, animals fed diets fortified with frying oil; groups 3-5, rats fed as in group 2 and received tomato (500 mg/kg body weight), garlic (125 mg/kg body weight) and a combination of tomato and garlic by gavage, respectively.Total cholesterol (TC), triacylglycerols (TAG), phospholipids (PL), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c),and very low density lipoprotein cholesterol (VLDL-c) were estimated in the serum of different animal groups. Lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT), triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were determined in the serum as well as lipid peroxidation level (TBARS) and reduced glutathione (GSH) content were assessed in cardiac tissues.The results obtained revealed that, feeding rats on frying oil induced a notable increase in lipid profile, LDL-c, VLDL-c and TBARS associated with a marked depletion in GSH. Elevation in specific heart enzymes, LDL, CPK, ALT

  6. Cholesterol metabolism in blood cells of irradiated rats

    International Nuclear Information System (INIS)

    Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

    1985-01-01

    Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

  7. MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and scavenging the pro-inflammatory cytokines.

    Science.gov (United States)

    Chandramoorthy, Harish C; Bin-Jaliah, Ismaeel; Karari, Hussian; Rajagopalan, Prasanna; Ahmed Shariff, Mohammed Eajaz; Al-Hakami, Ahmed; Al-Humayad, Suliman M; Baptain, Fawzi A; Ahmed, Humeda Suekit; Yassin, Hanaa Z; Haidara, Mohamed A

    2018-02-01

    The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1β, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-β and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca 2+ ] i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine signaling and [Ca 2+ ] i homeostasis. © 2017 Wiley Periodicals, Inc.

  8. Blood cholesterol : a public health perspective

    NARCIS (Netherlands)

    Verschuren, W.M.M.

    1995-01-01

    Changes in total cholesterol levels (TC) were studied using data from three epidemiological studies: about 30,000 men and women aged 37-43 were examined between 1974 and 1980 (CB Project), about 80,000 men aged 33-37 between 1981 and 1986 (RIFOH Project) and 42,000 men and women aged 20-59 from 1987

  9. The Success Story of LDL Cholesterol Lowering.

    Science.gov (United States)

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 American Heart Association, Inc.

  10. Cholesterol oxidation products and their biological importance

    Czech Academy of Sciences Publication Activity Database

    Kulig, W.; Cwiklik, Lukasz; Jurkiewicz, P.; Rog, T.; Vattulainen, I.

    2016-01-01

    Roč. 199, Sep (2016), s. 144-160 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : cholesterol * oxidation * oxysterols * biological membranes * biophysical properties Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.361, year: 2016

  11. Resveratrol protects rabbits against cholesterol diet- induced ...

    African Journals Online (AJOL)

    ... groups compared to HFD group only. In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis. Keywords: Cholesterol diet, Lipidaemia, Rabbit; Resveratrol, LDL-c, HDL-c, TC, TG ...

  12. Biochemical characterization of cholesterol-reducing Eubacterium.

    Science.gov (United States)

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-12-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addition to plasmenylethanolamine, five other lipids which contain an alkenyl ether residue supported growth of Eubacterium strain 403 in a lecithin-cholesterol base medium. Of six steroids tested, cholesterol, cholest-4-en-3-one, cholest-4-en-3 beta-ol (allocholesterol), and androst-5-en-3 beta-ol-17-one supported growth of Eubacterium strain 403. All four steroids were reduced to the 3 beta-ol, 5 beta-H products. The delta 5 steroids cholest-5-en-3 alpha-ol (epicholesterol) and 22,23-bisnor-5-cholenic acid-3-beta-ol were not reduced and did not support growth of the Eubacterium strain.

  13. Stroke secondary to multiple spontaneous cholesterol emboli.

    Science.gov (United States)

    Pascual, M; Baumgartner, J M; Bounameaux, H

    1991-01-01

    We describe one male, 49-year-old diabetic patient in whom regressive stroke with aphasia and right-sided hemiparesia was related to multiple small emboli in the left paraventricular cortex. Simultaneous presence of several cholesterol emboli in the left eye ground and detection of an atheromatous plaque at the homolateral carotid bifurcation let assume that the cerebral emboli originated from that plaque and also consisted of cholesterol crystals. The patient was discharged on low-dose aspirin (100 mg/day) after neurologic improvement. Follow-up at one year revealed clinical stability, recurrence of the cholesterol emboli at the eye ground examination and no change of the carotid plaque. Cholesterol embolization with renal failure, hypertension and peripheral arterial occlusions causing skin ulcerations is classical in case of atheromatous aortic disease but stroke has rarely been reported in this syndrome. However, more frequent use of invasive procedures (arteriography, transluminal angioplasty, vascular surgery) or thrombolytic treatment might increase its incidence in the near future.

  14. Cholesterol oxidation products and their biological importance

    Czech Academy of Sciences Publication Activity Database

    Kulig, W.; Cwiklik, Lukasz; Jurkiewicz, Piotr; Rog, T.; Vattulainen, I.

    2016-01-01

    Roč. 199, SI (2016), s. 144-160 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GBP208/12/G016; GA ČR GA15-14292S Institutional support: RVO:61388955 Keywords : cholesterol * oxidation * oxysterols Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.361, year: 2016

  15. estimations of cholesterol, triglycerides and fractionation

    African Journals Online (AJOL)

    Preferred Customer

    *Corresponding author. E-mail: eiadeyeye@yahoo.com. ESTIMATIONS OF CHOLESTEROL, TRIGLYCERIDES AND FRACTIONATION OF. LIPOPROTEINS IN SERUM SAMPLES OF SOME NIGERIAN FEMALE SUBJECTS. E.I. Adeyeye1* and I. Oluwadare2. 1Department of Chemistry, University of Ado Ekiti, P.M.B. 5363, ...

  16. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

    Directory of Open Access Journals (Sweden)

    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

  17. EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES FORMULATION.

    Science.gov (United States)

    Belletti, D; Grabrucker, A M; Pederzoli, F; Menrath, I; Cappello, V; Vandelli, M A; Forni, F; Tosi, G; Ruozi, B

    2016-09-10

    The biocompatibility of polymers, lipids and surfactants used to formulate is crucial for the safe and sustainable development of nanocarriers (nanoparticles, liposomes, micelles, and other nanocarriers). In this study, Cholesterol (Chol), a typical biocompatible component of liposomal systems, was formulated in Chol-based solid nanoparticles (NPs) stabilized by the action of surfactant and without the help of any other formulative component. Parameters as type (Solutol HS 15, cholic acid sodium salt, poly vinyl alcohol and Pluronic-F68), concentration (0.2; 0.5 and 1% w/v) of surfactant and working temperature (r.t. and 45°C) were optimized and all samples characterized in terms of size, zeta potential, composition, thermal behavior and structure. Results demonstrated that only Pluronic-F68 (0.5% w/v) favors the organization of Chol chains in structured NPs with mean diameter less than 400nm. Moreover, we demonstrated the pivotal role of working temperature on surfactant aggregation state/architecture/stability of Chol-based nanoparticles. At room temperature, Pluronic-F68 exists in solution as individual coils. In this condition, nanoprecipitation of Chol formed the less stable NPs with a 14±3% (w/w) of Pluronic-F68 prevalently on surface (NP-Chol/0.5). On the contrary, working near the critical micelle temperature (CMT) of surfactant (45°C), Chol precipitates with Pluronic-F68 (9±5% w/w) in a compact stable matricial structure (NP-Chol/0.5-45). In vitro studies highlight the low toxicity and the affinity of NP-Chol/0.5-45 for neuronal cells suggesting their potential applicability in pathologies with a demonstrated alteration of neuronal plasticity and synaptic communication (i.e. Huntington's disease). Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Silymarin ameliorates metabolic dysfunction associated with Diet-induced Obesity via activation of farnesyl X receptor

    Directory of Open Access Journals (Sweden)

    Ming Gu

    2016-09-01

    Full Text Available AbstractBACKGROUND AND PURPOSESilymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis and other types of toxic liver damage. . Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. EXPERIMENTAL APPROACHC57BL/6 mice were fed high-fat diet (HFD for 3 months to induce obesity, insulin resistance, hyperlipidaemia and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. FXR and NF-κB transactivities were analysed in liver using a gene reporter assay based onquantitative RT-PCR.KEY RESULTSSilymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signalling, which was enhanced by FXR activation. CONCLUSIONS AND IMPLICATIONSOur results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signalling. Key words: silymarin; silybin; metabolic syndrome; non-alcoholic fatty liver disease; farnesyl X receptorAbbreviationsALT, alanine aminotransferase; AST, aspartate transaminase; BA, bile acid; DIO, diet-induced obesity; CA, cholic acid; DMSO, dimethylsulfoxide; FXR, farnesyl X receptor; HDL-c, high density lipoprotein cholesterol; HF, high-fat; IPITT, intraperitoneal insulin tolerance test; LDL-c, low density lipoprotein cholesterol; NAFLD, non-alcoholic fatty liver disease; NF-κB, nuclear factor kappa B; NR, nuclear receptor; MS, metabolic syndrome

  19. Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

    Science.gov (United States)

    Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

    2017-01-01

    Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

  20. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    Science.gov (United States)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  1. Cholesterol transfer at endosomal-organelle membrane contact sites.

    Science.gov (United States)

    Ridgway, Neale D; Zhao, Kexin

    2018-06-01

    Cholesterol is delivered to the limiting membrane of late endosomes by Niemann-Pick Type C1 and C2 proteins. This review summarizes recent evidence that cholesterol transfer from endosomes to the endoplasmic reticulum and other organelles is mediated by lipid-binding proteins that localize to membrane contact sites (MCS). LDL-cholesterol in the late endosomal/lysosomes is exported to the plasma membrane, where most cholesterol resides, and the endoplasmic reticulum, which harbors the regulatory complexes and enzymes that control the synthesis and esterification of cholesterol. A major advance in dissecting these cholesterol transport pathways was identification of frequent and dynamic MCS between endosomes and the endoplasmic reticulum, peroxisomes and plasma membrane. Positioned at these MCS are members of the oxysterol-binding protein (OSBP) and steroidogenic acute regulatory protein-related lipid-transfer family of lipid transfer proteins that bridge the opposing membranes and directly or indirectly mediate cholesterol transfer. OSBP-related protein 1L (ORP1L), ORP5 and ORP6 mediate cholesterol transfer to the endoplasmic reticulum that regulates cholesterol homeostasis. ORP1L and STARD3 also move cholesterol from the endoplasmic reticulum-to-late endosomal/lysosomes under low-cholesterol conditions to facilitate intraluminal vesicle formation. Cholesterol transport also occurs at MCS with peroxisomes and possibly the plasma membrane. Frequent contacts between organelles and the endo-lysosomal vesicles are sites for bidirectional transfer of cholesterol.

  2. Effects of apolipoproteins on the kinetics of cholesterol exchange

    International Nuclear Information System (INIS)

    Letizia, J.Y.; Phillips, M.C.

    1991-01-01

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

  3. The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

    Science.gov (United States)

    La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

    2014-07-01

    Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. © 2014

  4. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  5. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-01-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD 50 ) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo and in

  6. The performance of maize crop during acid amelioration with ...

    African Journals Online (AJOL)

    Tanzania Journal of Science ... This study evaluated acid ameliorative potential and their effects on maize growth of four organic residues namely wild spikenard, cordia, cowpea and pigeon peas ... The finding suggests different acid ameliorating potential of residues, pigeon peas and cordia being the most effective.

  7. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  8. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  9. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  10. Statins: Are These Cholesterol-Lowering Drugs Right for You?

    Science.gov (United States)

    Statins: Are these cholesterol-lowering drugs right for you? Find out whether your risk factors for heart disease make you a ... risk prediction. In addition to your cholesterol numbers, these risk calculators also ask about your age, race, ...

  11. Dietary Rhus coriaria L. powder reduces the blood cholesterol ...

    African Journals Online (AJOL)

    Dietary Rhus coriaria L. powder reduces the blood cholesterol, VLDL-c and ... of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-c), low ... birds had higher feed conversion ratio compared with birds in the other treatments.

  12. Membrane cholesterol mediates the cellular effects of monolayer graphene substrates.

    Science.gov (United States)

    Kitko, Kristina E; Hong, Tu; Lazarenko, Roman M; Ying, Da; Xu, Ya-Qiong; Zhang, Qi

    2018-02-23

    Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene's cellular effects, providing insight into the biological impact of graphene.

  13. An update on the measurement and management of cholesterol with ...

    African Journals Online (AJOL)

    ... and management of cholesterol with specific reference to secondary prevention of ... Serum-cholesterol has emerged as the dominant risk factor for coronary ... reduce the incidence of secondary myocardial infarctions, strokes and death ...

  14. High cholesterol level is essential for myelin membrane growth.

    Science.gov (United States)

    Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

    2005-04-01

    Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

  15. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  16. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    International Nuclear Information System (INIS)

    Singh, Suman; Singhal, Rahul; Malhotra, B.D.

    2007-01-01

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL -1 (12 mM), shelf life of 1 month, detection limit of 12 mg dL -1 and sensitivity as 5.4 x 10 -5 Abs. mg -1 dL -1

  17. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Central Mechanical Engineering Research Institute, G. Avenue, Durgapur 713209, West Bengal (India); Singhal, Rahul [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India)]. E-mail: bansi.malhotra@gmail.com

    2007-01-23

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL{sup -1} (12 mM), shelf life of 1 month, detection limit of 12 mg dL{sup -1} and sensitivity as 5.4 x 10{sup -5} Abs. mg{sup -1} dL{sup -1}.

  18. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.

    Science.gov (United States)

    Lee, Kuan-I; Chiang, Chin-Wei; Lin, Hui-Ching; Zhao, Jin-Feng; Li, Cheng-Ta; Shyue, Song-Kun; Lee, Tzong-Shyuan

    2016-05-01

    Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring.

  19. The possible influences of dietary oil supplementation in ameliorating metabolic disturbances and oxidative stress in Alloxan injected rats

    International Nuclear Information System (INIS)

    Farag, M.F.S.; Osman, N.N.; Darwish, M.M.

    2005-01-01

    Diabetes mellitus (DM) is a multifactor disease that is associated with a number of different metabolic abnormalities. Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with DM. The present work was conducted to examine the protective or treating effects of two different dietary oils rich in medium chain fatty acids (MCFA) as coconut oil (CO) or omega-3-polyunsaturated fatty acids (ω-3-PUFAs)as flaxseed oil (FO) on the severity of DM induced experimentally by alloxan injection. Wistar strain albino rats (17 Og) were fed commercial rat chow diet supplemented with either CO or FO for four weeks. A single dose of alloxan (150 mg/kg) resulted in hyperglycemia, decreases in serum insulin, thyroxine (T 4 ), and high density lipoprotein-cholesterol levels, elevated triglycerides, total cholesterol and low density lipoprotein-cholesterol concentrations. Concurrent with those changes, an increased liver malonaldehyde (MDA) level was observed. This oxidative stress was related to decreases in superoxide dismutase (SOD) activity and glutathione (GSH) content in the liver of alloxan diabetic rats. Oils supplementation after diabetes induction ameliorated hyperglycemia, increased insulin and thyroxine hormone levels, improved lipid profiles, blunted the increase in MDA, modulated the levels of hepatic SOD activity and GSH content of alloxan treated rats. It could be suggested that each of CO or FO could be used as antidiabetic complement in case of DM. This may be related to their anti oxidative properties

  20. Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats.

    Science.gov (United States)

    Rony, K A; Ajith, T A; Nima, N; Janardhanan, K K

    2014-03-01

    Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  2. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Elferink, Ronald P. J. Oude; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux ( TICE) contributes significantly to cholesterol removal in mice. Our aim

  3. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Oude Elferink, Ronald P. J.; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux (TICE) contributes significantly to cholesterol removal in mice. Our aim

  4. Hypercholesterolemia: The Role of Schools in Cholesterol Screening.

    Science.gov (United States)

    Price, James H.; Casler, Suzanne M.

    1997-01-01

    Examines the prevalence of cardiovascular disease risk factors among children and adolescents, the pros and cons of cholesterol screening among youth, cholesterol assessments of at-risk youth, and the role of schools in cholesterol education and screening (focusing on comprehensive school health education and services). (SM)

  5. Plasma cholesterol and related lipid levels of seemingly healthy ...

    African Journals Online (AJOL)

    The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. Methods: One hundred and seventy four ...

  6. Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

    Directory of Open Access Journals (Sweden)

    Ingemar Björkhem

    2013-09-01

    Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

  7. Alcohol consumption stimulates early stemps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, van der M.S.; Tol, van A.; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

  8. Alcohol consumption stimulates early steps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, M.S. van der; Tol, A. van; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

  9. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    OpenAIRE

    Tomaro-Duchesneau, Catherine; Jones, Mitchell L.; Shah, Divya; Jain, Poonam; Saha, Shyamali; Prakash, Satya

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and ch...

  10. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

    NARCIS (Netherlands)

    Beulens, J.W.J.; Sierksma, A.; Tol, A. van; Fournier, N.; Gent, T. van; Paul, J.L.; Hendriks, H.F.J.

    2004-01-01

    Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the

  11. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally as...

  12. A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

    Directory of Open Access Journals (Sweden)

    Steffen Steinert

    . CONCLUSIONS/SIGNIFICANCE: The current work presents the characterization and trafficking behavior of a novel sphingolipid-binding fluorescent probe, the SBD peptide. We show that SBD binding to membranes is dependent on the presence of cholesterol, sphingomyelin, and complex glycolipids. In addition, SBD targeting through the endolysosomal pathway in neurons is highly sensitive to cholesterol perturbations, making it a potentially useful tool for the analysis of sphingolipid trafficking in disease models that involve changes in cholesterol metabolism and storage.

  13. Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist – tegaserod

    Directory of Open Access Journals (Sweden)

    Shaffer Eldon

    2006-02-01

    -treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. Conclusion A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves.

  14. Cholesterol Crystal Embolism and Chronic Kidney Disease.

    Science.gov (United States)

    Li, Xuezhu; Bayliss, George; Zhuang, Shougang

    2017-05-24

    Renal disease caused by cholesterol crystal embolism (CCE) occurs when cholesterol crystals become lodged in small renal arteries after small pieces of atheromatous plaques break off from the aorta or renal arteries and shower the downstream vascular bed. CCE is a multisystemic disease but kidneys are particularly vulnerable to atheroembolic disease, which can cause an acute, subacute, or chronic decline in renal function. This life-threatening disease may be underdiagnosed and overlooked as a cause of chronic kidney disease (CKD) among patients with advanced atherosclerosis. CCE can result from vascular surgery, angiography, or administration of anticoagulants. Atheroembolic renal disease has various clinical features that resemble those found in other kidney disorders and systemic diseases. It is commonly misdiagnosed in clinic, but confirmed by characteristic renal biopsy findings. Therapeutic options are limited, and prognosis is considered to be poor. Expanding knowledge of atheroembolic renal disease due to CCE opens perspectives for recognition, diagnosis, and treatment of this cause of progressive renal insufficiency.

  15. Cytosolic cholesterol ester hydrolase in adrenal cortex

    OpenAIRE

    Tocher, Douglas R.

    1983-01-01

    Cholesterol ester hydrolase (CEH) in adrenocortical cytosol was known to be phosphorylated and activated, in response to ACTH in a cAMPdependent protein kinase mediated process. The purification of CEH from bovine adrenocortical cytosol was attempted. The use of detergents to solubilise the enzyme from lipid-rich aggregates was investigated and sodium cholate was found to be effective. A purification procedure using cholate solubilised enzyme was developed. The detergent int...

  16. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

  17. Potent and selective mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K; Johansson, Jan

    2015-03-24

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  18. Human plasma lecithin-cholesterol acyltransferase

    International Nuclear Information System (INIS)

    Jauhiainen, M.; Stevenson, K.J.; Dolphin, P.J.

    1988-01-01

    Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the fatty acid at the sn-2 position of lecithin to cholesterol forming lysolecithin and cholesteryl ester. The substrates for and products of this reaction are present within the plasma lipoproteins upon which the enzyme acts to form the majority of cholesteryl ester in human plasma. The authors proposed a covalent catalytic mechanism of action for LCAT in which serine and histidine residues mediate lecithin cleavage and two cysteine residues cholesterol esterification. With the aid of sulfhydryl reactive trivalent organoarsenical compounds which are specific for vicinal thiols they have probed the geometry of the catalytic site. They conclude that the two catalytic cysteine residues of LCAT (Cys 31 and Cys 184 ) are vicinal with a calculated distance between their sulfur atoms of 3.50-3.62 A. The additional residue alkylated by teh bifunctional reagent is within the catalytic site and may represent a previously identified catalytic serine or histidine residue

  19. Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone

    International Nuclear Information System (INIS)

    Hu, Z.Y.; Bourreau, E.; Jung-Testas, I.; Robel, P.; Baulieu, E.E.

    1987-01-01

    Oligodendrocyte mitochondria from 21-day-old Sprague-Dawley male rats were incubated with 100 nM [ 3 H]cholesterol. It yielded [ 3 H]pregnenolone at a rate of 2.5 +/- 0.7 and 5-[ 3 H]pregnene-3β,20α-diol at a rate of 2.5 +/- 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19- to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with [ 3 H]mevalonolactone. [ 3 H]Cholesterol, [ 3 H]pregnenolone, and 5-[ 3 H]pregnene-3β,20α-diol were characterized in cellular extracts. The formation of the 3 H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of neurosteroids applied to Δ 5 -3β-hydroxysteroids previously isolated from brain

  20. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  1. Smart Soup, a traditional Chinese medicine formula, ameliorates amyloid pathology and related cognitive deficits.

    Directory of Open Access Journals (Sweden)

    Yujun Hou

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS, a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT, Poria cum Radix Pini (PRP and Radix Polygalae (RP, is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease.

  2. Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

    Directory of Open Access Journals (Sweden)

    Xiaorui Wu

    2017-05-01

    Full Text Available Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE, which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS, alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

  3. Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

    Science.gov (United States)

    Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

    2016-09-01

    Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

  4. Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

    International Nuclear Information System (INIS)

    Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

    2004-01-01

    Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

  5. Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study

    International Nuclear Information System (INIS)

    Zhang, Liyuan; Li, Kun; Sun, Rui; Zhang, Yuan; Ji, JianFeng; Huang, Peigeng; Yang, Hongying; Tian, Ye

    2014-01-01

    It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation

  6. Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

    DEFF Research Database (Denmark)

    Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra

    2016-01-01

    : The results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum from skin...

  7. Endoscopic Transnasal Approach for Cholesterol Granuloma of the Petrous Apex

    Directory of Open Access Journals (Sweden)

    Mohammad Samadian

    2015-01-01

    Full Text Available Cholesterol granulomas are rare round or ovoid cysts. They contain cholesterol crystals surrounded by foreign bodies of giant cells and are characterized by chronic inflammation. Large cholesterol granuloma can compress surrounding tissue especially cranial nerves. There are several types of surgery for the resection of cholesterol granuloma. We describe 4 cases of cholesterol granuloma operated on via transnasal endoscopic approach. In this report, we describe radiologic and pathologic features of this lesion and explain the advantages and disadvantages of transsphenoidal endoscopic approach for these rare lesions.

  8. The influence of saponins on cell membrane cholesterol.

    Science.gov (United States)

    Böttger, Stefan; Melzig, Matthias F

    2013-11-15

    We studied the influence of structurally different saponins on the cholesterol content of cellular membranes. Therefore a cell culture model using ECV-304 urinary bladder carcinoma cells was developed. To measure the cholesterol content we used radiolabeled (3)H-cholesterol which is chemically and physiologically identical to natural cholesterol. The cells were pre-incubated with (3)H-cholesterol and after a medium change, they were treated with saponins to assess a saponin-induced cholesterol liberation from the cell membrane. In another experiment the cells were pre-incubated with saponins and after a medium change, they were treated with (3)H-cholesterol to assess a saponin-induced inhibition of cholesterol uptake into the cell membrane. Furthermore, the membrane toxicity of all applied saponins was analyzed using extracellular LDH quantification and the general cytotoxicity was analyzed using a colorimetric MTT-assay and DNA quantification. Our results revealed a correlation between membrane toxicity and general cytotoxicity. We also compared the results from the experiments on the saponin-induced cholesterol liberation as well as the saponin-induced inhibition of cholesterol uptake with the membrane toxicity. A significant reduction in the cell membrane cholesterol content was noted for those saponins who showed membrane toxicity (IC50 saponins either liberated (3)H-cholesterol from intact cell membranes or blocked the integration of supplemented (3)H-cholesterol into the cell membrane. Saponins with little influence on the cell membrane (IC50 >100 μM) insignificantly altered the cell membrane cholesterol content. The results suggested that the general cytotoxicity of saponins is mainly dependent on their membrane toxicity and that the membrane toxicity might be caused by the loss of cholesterol from the cell membrane. We also analyzed the influence of a significantly membrane toxic saponin on the cholesterol content of intracellular membranes such as those

  9. Association between cholesterol plasma levels and craving among heroin users.

    Science.gov (United States)

    Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

    2012-12-01

    Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

  10. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

  11. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  12. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

    2013-09-15

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

  13. THE REDUCTION OF CHOLESTEROL WITH CUPPING THERAPY ON CHOLESTEROL REDUCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

    Directory of Open Access Journals (Sweden)

    Zahid Fikri

    2017-04-01

    Full Text Available Introduction: Hypercholesterolemia is a risk factor causes of death at younger ages. Hypercholesterolemia may increase the risk of atherosclerosis, coronary heart disease, pancreatitis (pancreas inflammation in organs, diabetes mellitus, thyroid disorders, liver disease and kidney disease. Many patients with hypercholesterolemia using cupping therapy. Cupping therapy is alternative treatment process of throwing dirty blood from the body through the skin surface. The objective of this study was to determine the effect of cupping therapy to decrease cholesterol levels in patients with hypercholesterolemia. Method: Design used in this study was quasy experimental design. The population is all patients with hypercholesterolemia in the health center plaza Gresik. The total sample is 18 respondents, taken according to inclusion criteria. Independent variable is the cupping therapy. The dependent variable was the decrease in cholesterol levels. Data were collected using a questionnaire and observation of cholesterol. Data were analyzed using independent t-test and paired t tests with signi fi cance level α < 0.05. Result: The results show that cholesterol levels in patients with hypercholesterolemia treated groups decreased majority. Independent statistical analysis using t-test showed p = 0.001 and with the Paired t-test p value = 0.003. Discussion: This result means that there are significant effects of cupping therapy on cholesterol reduction in patients with hypercholesterolemia aged 45 years and over. Further research needs to be done in control diet, lifestyle and daily activities for the success of cupping therapy.

  14. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    International Nuclear Information System (INIS)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S.

    2013-01-01

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 °C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5–700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 °C

  15. Microwave assisted direct saponification for the simultaneous determination of cholesterol and cholesterol oxides in shrimp.

    Science.gov (United States)

    Souza, Hugo A L; Mariutti, Lilian R B; Bragagnolo, Neura

    2017-05-01

    A novel microwave-assisted direct saponification method for the simultaneous determination of cholesterol and cholesterol oxides in shrimp was developed and validated. Optimal saponification conditions, determined by means of an experimental design, were achieved using 500mg of sample and 20mL of 1mol/L KOH ethanol solution for 16min at 45°C at maximum power at 200W and magnetic stirring at 120rpm. Higher extraction of cholesterol oxides in a reduced saponification time (∼75 times) was achieved in comparison with the direct cold saponification method. The new method showed low detection (≤0.57μg/mL) and quantification (≤1.73μg/mL) limits, good repeatability (≤10.50% intraday and ≤8.56% interday) and low artifact formation (evaluated by using a deuterated cholesterol-D6 standard). Raw, salted and dried-salted shrimps were successfully analyzed by the validated method. The content of cholesterol oxides increased after salting and decreased after drying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Dietary cholesterol, heart disease risk and cognitive dissonance.

    Science.gov (United States)

    McNamara, Donald J

    2014-05-01

    In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

  17. Cholesterol in the retina: the best is yet to come

    Science.gov (United States)

    Pikuleva, Irina A.; Curcio, Christine A.

    2014-01-01

    Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

  18. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  19. The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

    Science.gov (United States)

    Miettinen, T A; Gylling, H; Nissinen, M J

    2011-10-01

    To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

    Science.gov (United States)

    Wu, Guozhen; Zhu, Lili; Yuan, Xing; Chen, Hao; Xiong, Rui; Zhang, Shoude; Cheng, Hao; Shen, Yunheng; An, Huazhang; Li, Tiejun; Li, Honglin; Zhang, Weidong

    2017-10-10

    Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. The herb-derived compound, Britanin, is a potent inducer of the Nrf2 system. Britanin can induce the expression of protective enzymes and reverse oxygen-glucose deprivation, followed by reperfusion (OGD-R)-induced neuronal injury in primary cortical neurons in vitro. Furthermore, the administration of Britanin significantly ameliorated middle cerebral artery occlusion-reperfusion (MCAO-R) insult in vivo. We report here the crystal structure of the complex of Britanin and the BTB domain of Keap1. Britanin selectively binds to a conserved cysteine residue, cysteine 151, of Keap1 and inhibits Keap1-mediated ubiquitination of Nrf2, leading to induction of the Nrf2 pathway. Britanin is a potent inducer of Nrf2. The complex crystal structure of Britanin and the BTB domain of Keap1 help clarify the mechanism of Nrf2 induction. Britanin was proven to protect primary cortical neurons against OGD-R-induced injury in an Nrf2-dependant way. Additionally, Britanin had excellent cerebroprotective effect in an MCAO-R model. Our results demonstrate that the natural product Britanin with potent Nrf2-activating and neural protective activities both in vitro and in vivo could be developed into a cerebroprotective therapeutic agent. Antioxid. Redox Signal. 27, 754-768.

  1. Ameliorative Effects of Herbal Combinations in Hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Nishant P. Visavadiya

    2011-01-01

    Full Text Available The roots of Glycyrrhiza glabra, Withania somnifera, Asparagus racemosus, and Chlorophytum borivilianum and seeds of Sesamum indicum are ayurvedic medicinal plants used in India to treat several ailments. Our previous studies indicated that these plants possess hypolipidemic and antioxidant potential. The present study was aimed at investigating the composite effects of these plants on hypercholesterolemic rats. Three different combinations (5 gm%, given for four weeks used in this study effectively reduced plasma and hepatic lipid profiles and increased fecal excretion of cholesterol, neutral sterol, and bile acid along with increasing the hepatic HMG-CoA reductase activity and bile acid content in hypercholesterolemic rats. Further, all three combinations also improved the hepatic antioxidant status (catalase, SOD, and ascorbic acid levels and plasma total antioxidant capacity with reduced hepatic lipid peroxidation. Overall, combination I had the maximum effect on hypercholesterolemic rats followed by combinations II and III due to varying concentrations of the different classes of phytocomponents.

  2. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

    Science.gov (United States)

    Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

    2015-02-27

    ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

  3. Cold labelled substrate and estimation of cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

    International Nuclear Information System (INIS)

    Dobiasova, M.; Schuetzova, M.

    1986-01-01

    A new method is described of cold labelling of blood serum, plasma and body fluids containing lecithin cholesterol acyltransferase (LCAT) and/or lipoproteins for radioassay to assess the cholesterol esterification rate. The method uses the principle of transfer, in refrigeration conditions, of 14 C-cholesterol from filter paper discs to the fluids. The preparation of the disc guarantees homogeneous labelling and high stability. The use of the labelling disc was shown to be reliable, easy and fast and suitable for accurate assessment of LCAT reaction, applicable in the widest possible enzyme concentration range. It was also, found suited for the measurement of the esterification rate of rabbit intraocular fluid which is a medium with the lowest contents of the substrate and LCAT. (L.O.)

  4. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  5. Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

    International Nuclear Information System (INIS)

    Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

    1987-01-01

    We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  7. Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice

    Directory of Open Access Journals (Sweden)

    Kuipers Folkert

    2010-07-01

    Full Text Available Abstract Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT. After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day plasma triglycerides were lower (p

  8. Is the use of antioxidants mixture ameliorating the double stress effect of radiation and hyperlipidaemia?

    International Nuclear Information System (INIS)

    Michael, M.I.; Amer, M.M.

    2010-01-01

    Radiation hazards, due to free radical generation, present an enormous challenge for biological and medical safety. In the same time, hyperlipidaemia represents one of the most important and recognized risk factor for atherosclerosis development as an event of accumulation of cells containing excess lipids within the arterial wall. Under normal physiological conditions, there is a critical balance in the generation of oxygen free radicals and antioxidant defense systems. In this study, we assumed that a subject encountered to both radiation and hyperlipidaemia oxidative stress and inquired if a mixture of three well known antioxidants can ameliorate this dramatically disorder. To answer the question, four groups of adult male albino rats were used; the control group (A) fed and drank ad libitum normal laboratory diet, the second group (B) fed normally and exposed to 5 Gy gamma radiation, the third group (C) fed high-fat diet (HFD) for two months then exposed to the same dose of radiation and the fourth group (D) subjected to the same treatment as group (C) and administrated a mixture of tryptophan (100 mg/kg b.w.), hawthorn extract (50 mg/100 g b.w.) and coenzyme Q10 (50 mg/kg b.w.) for one month. Body weight was recorded twice a week during the experimental period then all the animals were decapitated after one month and sera were collected to estimate total lipids, triglycerides, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), T3, T4, testosterone and corticosterone hormones besides glutathione. The results declared that radiation-hyperlipidaemia double stressors inadequately distorted the lipogram, hormonal and antioxidant status and the antioxidants mixture administrated could ameliorate these alterations and successfully brought back all the parameters investigated nearly to the control level.

  9. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

  10. Bacterial mediated amelioration of drought stress in drought tolerant ...

    African Journals Online (AJOL)

    Bacterial mediated amelioration of drought stress in drought tolerant and susceptible cultivars of rice ( Oryza sativa L.) ... and IR-64 (drought sensitive) cultivars of rice (Oryza sativa L.) under different level of drought stress. ... from 32 Countries:.

  11. Improvement for Amelioration Inventory Model with Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Han-Wen Tuan

    2017-01-01

    Full Text Available Most inventory models dealt with deteriorated items. On the contrary, just a few papers considered inventory systems under amelioration environment. We study an amelioration inventory model with Weibull distribution. However, there are some questionable results in the amelioration paper. We will first point out those questionable results in the previous paper that did not derive the optimal solution and then provide some improvements. We will provide a rigorous analytical work for different cases dependent on the size of the shape parameter. We present a detailed numerical example for different ranges of the sharp parameter to illustrate that our solution method attains the optimal solution. We developed a new amelioration model and then provided a detailed analyzed procedure to find the optimal solution. Our findings will help researchers develop their new inventory models.

  12. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  13. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  14. Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway.

    Science.gov (United States)

    Raish, Mohammad

    2017-04-01

    The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  17. The effects of cholesterol on learning and memory.

    Science.gov (United States)

    Schreurs, Bernard G

    2010-07-01

    Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

  18. Pitfalls in the detection of cholesterol in Huntington's disease models.

    Science.gov (United States)

    Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

    2012-10-11

    Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

  19. The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice.

    Directory of Open Access Journals (Sweden)

    Hiroaki Kanouchi

    Full Text Available Kurozu is a traditional Japanese rice vinegar. During fermentation and aging of the Kurozu liquid in an earthenware jar over 1 year, a solid residue called Kurozu Moromi is produced. In the present study, we evaluated whether concentrated Kurozu or Kurozu Moromi could ameliorate cognitive dysfunction in the senescence-accelerated P8 mouse. Senescence-accelerated P8 mice were fed 0.25% (w/w concentrated Kurozu or 0.5% (w/w Kurozu Moromi for 4 or 25 weeks. Kurozu suppressed cognitive dysfunction and amyloid accumulation in the brain, while Kurozu Moromi showed a tendency to ameliorate cognitive dysfunction, but the effect was not significant. We hypothesize that concentrated Kurozu has an antioxidant effect; however, the level of lipid peroxidation in the brain did not differ in senescence-accelerated P8 mice. DNA microarray analysis indicated that concentrated Kurozu increased HSPA1A mRNA expression, a protein that prevents protein misfolding and aggregation. The increase in HSPA1A expression by Kurozu was confirmed using quantitative real-time PCR and immunoblotting methods. The suppression of amyloid accumulation by concentrated Kurozu may be associated with HSPA1A induction. However, concentrated Kurozu could not increase HSPA1A expression in mouse primary neurons, suggesting it may not directly affect neurons.

  20. Lack of P2Y(13) in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Lichtenstein, Laeticia; Serhan, Nizar; Annema, Wijtske; Combes, Guillaume; Robaye, Bernard; Boeynaems, Jean-Marie; Perret, Bertrand; Tietge, Uwe J. F.; Laffargue, Muriel; Martinez, Laurent O.

    2013-01-01

    Background: The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and

  1. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

    Science.gov (United States)

    Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

    2014-12-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. © 2014 WILEY PERIODICALS, INC.

  2. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  3. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  4. Inhibition of colony-stimulating factor 1 receptor early in disease ameliorates motor deficits in SCA1 mice.

    Science.gov (United States)

    Qu, Wenhui; Johnson, Andrea; Kim, Joo Hyun; Lukowicz, Abigail; Svedberg, Daniel; Cvetanovic, Marija

    2017-05-25

    Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1. Transgenic mouse model of SCA1, ATXN1[82Q] mice, and wild-type littermate controls were treated with PLX from 3 weeks of age. The effects of PLX on microglial density, astrogliosis, motor behavior, atrophy, and gene expression of Purkinje neurons were examined at 3 months of age. PLX treatment resulted in the elimination of 70-80% of microglia from the cerebellum of both wild-type and ATXN1[82Q] mice. Importantly, PLX ameliorated motor deficits in SCA1 mice. While we have not observed significant improvement in the atrophy or disease-associated gene expression changes in Purkinje neurons upon PLX treatment, we have detected reduced expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and increase in the protein levels of wild-type ataxin-1 and post-synaptic density protein 95 (PSD95) that may help improve PN function. A decrease in the number of microglia during an early stage of disease resulted in the amelioration of motor deficits in SCA1 mice.

  5. Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile

    NARCIS (Netherlands)

    Groen, A. K.; Ottenhoff, R.; Jansen, P. L.; van Marle, J.; Tytgat, G. N.

    1989-01-01

    Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human

  6. VPS35 Deficiency or Mutation Causes Dopaminergic Neuronal Loss by Impairing Mitochondrial Fusion and Function

    Directory of Open Access Journals (Sweden)

    Fu-Lei Tang

    2015-09-01

    Full Text Available Vacuolar protein sorting-35 (VPS35 is a retromer component for endosomal trafficking. Mutations of VPS35 have been linked to familial Parkinson’s disease (PD. Here, we show that specific deletion of the VPS35 gene in dopamine (DA neurons resulted in PD-like deficits, including loss of DA neurons and accumulation of α-synuclein. Intriguingly, mitochondria became fragmented and dysfunctional in VPS35-deficient DA neurons, phenotypes that could be restored by expressing VPS35 wild-type, but not PD-linked mutant. Concomitantly, VPS35 deficiency or mutation increased mitochondrial E3 ubiquitin ligase 1 (MUL1 and, thus, led to mitofusin 2 (MFN2 degradation and mitochondrial fragmentation. Suppression of MUL1 expression ameliorated MFN2 reduction and DA neuron loss but not α-synuclein accumulation. These results provide a cellular mechanism for VPS35 dysfunction in mitochondrial impairment and PD pathogenesis.

  7. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  8. Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

    Science.gov (United States)

    Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

    2017-06-01

    Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (Pjuice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Functional food red yeast rice (RYR) for metabolic syndrome amelioration: a review on pros and cons.

    Science.gov (United States)

    Patel, Seema

    2016-05-01

    Red yeast rice (RYR), the fermentation product of mold Monascus purpureus has been an integral part of Oriental food and traditional Chinese medicine, long before the discovery of their medicinal roles. With the identification of bioactive components as polyketide pigments (statins), and unsaturated fatty acids, RYR has gained a nutraceutical status. Hypercholesterolemic effect of this fermented compound has been validated and monacolin K has been recognized as the pivotal component in cholesterol alleviation. Functional similarity with commercial drug lovastatin sans the side effects has catapulted its popularity in other parts of the world as well. Apart from the hypotensive role, ameliorative benefits of RYR as anti-inflammatory, antidiabetic, anticancer and osteogenic agent have emerged, fueling intense research on it. Mechanistic studies have revealed their interaction with functional agents like coenzyme Q10, astaxanthin, vitamin D, folic acid, policosanol, and berberine. On the other hand, concurrence of mycotoxin citrinin and variable content of statin has marred its integration in mainstream medication. In this disputable scenario, evaluation of the scopes and lacunae to overcome seems to contribute to an eminent area of healthcare. Red yeast rice (RYR), the rice-based fermentation product of mold Monascus purpureus is a functional food. Its bioactive component monacolin K acts like synthetic drug lovastatin, without the severe side effects of the latter. RYR has been validated to lower cholesterol, control high blood pressure; confer anti-flammation, hypoglycaemic, anticancer and osteogenic properties. However, dose inconsistency and co-occurrence of toxin citrinin hampers its dietary supplementation prospect. Further research might facilitate development of RYR as a nutraceutical.

  10. Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2011-10-30

    We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

  11. Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

    Science.gov (United States)

    Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

    1986-02-12

    Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

  12. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  13. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  14. Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

    Science.gov (United States)

    Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

    2016-10-01

    Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

  15. Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Xiao-Yuan Mao

    2014-05-01

    Full Text Available The present study was designed to probe the effects of Huperzine A (HupA on diabetes-associated cognitive decline (DACD using a streptozotocin (STZ-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT, Acetylcholinesterase (AChE, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

  16. Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Mao, Xiao-Yuan; Cao, Dan-Feng; Li, Xi; Yin, Ji-Ye; Wang, Zhi-Bin; Zhang, Ying; Mao, Chen-Xue; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-01-01

    The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. PMID:24857910

  17. Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

    Science.gov (United States)

    Al-Ramahi, Ismael; Panapakkam Giridharan, Sai Srinivas; Chen, Yu-Chi; Patnaik, Samarjit; Safren, Nathaniel; Hasegawa, Junya; de Haro, Maria; Wagner Gee, Amanda K; Titus, Steven A; Jeong, Hyunkyung; Clarke, Jonathan; Krainc, Dimitri; Zheng, Wei; Irvine, Robin F; Barmada, Sami; Ferrer, Marc; Southall, Noel; Weisman, Lois S; Botas, Juan; Marugan, Juan Jose

    2017-12-26

    The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders.

  18. Pairing of cholesterol with oxidized phospholipid species in lipid bilayers

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka

    2014-01-01

    We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary...... shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid–cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded...... vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present...

  19. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  20. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  1. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  2. Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

    OpenAIRE

    Rousset, Xavier; Shamburek, Robert; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.

    2011-01-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanisti...

  3. LDL cholesterol estimation in patients with the metabolic syndrome

    OpenAIRE

    Gazi, Irene; Tsimihodimos, Vasilis; Filippatos, Theodosios D; Saougos, Vasilios G; Bairaktari, Eleni T; Tselepis, Alexandros D; Elisaf, Moses

    2006-01-01

    Abstract Background The Friedewald formula (LDL-F) for the estimation of low-density lipoprotein (LDL) cholesterol concentrations is the most often used formula in clinical trials and clinical practice. However, much concern has been raised as to whether this formula is applicable in all patient populations such as the presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present study was to evaluate various LDL cholesterol calculation formulas as well as LDL cholesterol ...

  4. A convenient method to synthesize specifically labelled cholesterol with tritium

    International Nuclear Information System (INIS)

    Malik, S.; Kenny, M.; Ahmad, S.; Washington Univ., Seattle, WA

    1992-01-01

    A simple method is described to label cholesterol with tritium. Cholesterol was first oxidized to 5-cholesten-3-one which was then purified by HPLC. Its structure was established by electron impact (EI) mass spectrometry and 1 H-NMR spectroscopy. The ketone was reduced with NaB 3 H 4 to give specifically labelled cholesterol (C-3 3 H) at low specific activity. (author)

  5. A Cholesterol-Sensitive Regulator of the Androgen Receptor

    Science.gov (United States)

    2010-07-01

    Oncogene (2010) 29, 3745–3747; doi:10.1038/onc.2010.132; published online 3 May 2010 Cholesterol is a sterol that serves as a metabolic precursor to other...bioactive sterols , such as nuclear receptor ligands, and also has a major role in plasma membrane structure. Cholesterol and long- chain...cholesterol synthesis (these drugs are generically termed ‘statins’), have been reported to inhibit cancer incidence or progres- sion in some studies. Although

  6. In vitro cholesterol uptake by Lactobacillus delbrueckii subsp. bulgaricus isolates

    OpenAIRE

    Małgorzata Ziarno

    2009-01-01

    Background. Some researchers have indicated that Lactobacillus delbrueckii subsp. bulgaricus may provide additional health benefits, reduce serum cholesterol level, for example. The aim of this study was to determine cholesterol uptake by Lb. delbrueckii subsp. bulgaricus commercial yoghurt starter isolates in artificial GIT fluids. Material and methods. Lb. delbrueckii subsp. bulgaricus isolates were cultured in MRS broth and in artificial GIT fluids contained cholesterol at initial con...

  7. Downregulation of RBO-PI4KIIIα Facilitates Aβ42 Secretion and Ameliorates Neural Deficits in Aβ42-Expressing Drosophila.

    Science.gov (United States)

    Zhang, Xiao; Wang, Wen-An; Jiang, Li-Xiang; Liu, Hai-Yan; Zhang, Bao-Zhu; Lim, Nastasia; Li, Qing-Yi; Huang, Fu-De

    2017-05-10

    Phosphoinositides and their metabolizing enzymes are involved in Aβ 42 metabolism and Alzheimer's disease pathogenesis. In yeast and mammals, Eighty-five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO), forms a plasma membrane-localized protein complex with phosphatidylinositol-4-kinase Type IIIα (PI4KIIIα) and a scaffold protein to tightly control the level of plasmalemmal phosphatidylinositol-4-phosphate (PI 4 P). Here, we report that RBO binds to Drosophila PI4KIIIα, and that in an Aβ 42 -expressing Drosophila model, separate genetic reduction of PI4KIIIα and RBO, or pharmacological inhibition of PI4KIIIα ameliorated synaptic transmission deficit, climbing ability decline, premature death, and reduced neuronal accumulation of Aβ 42 Moreover, we found that RBO-PI4KIIIa downregulation increased neuronal Aβ 42 release and that PI4P facilitated the assembly or oligomerization of Aβ 42 in/on liposomes. These results indicate that RBO-PI4KIIIa downregulation facilitates neuronal Aβ 42 release and consequently reduces neuronal Aβ 42 accumulation likely via decreasing Aβ 42 assembly in/on plasma membrane. This study suggests the RBO-PI4KIIIα complex as a potential therapeutic target and PI4KIIIα inhibitors as drug candidates for Alzheimer's disease treatment. SIGNIFICANCE STATEMENT Phosphoinositides and their metabolizing enzymes are involved in Aβ 42 metabolism and Alzheimer's disease pathogenesis. Here, in an Aβ 42 -expressing Drosophila model, we discovered and studied the beneficial role of downregulating RBO or its interacting protein PI4KIIIα-a protein that tightly controls the plasmalemmal level of PI 4 P-against the defects caused by Aβ 42 expression. Mechanistically, RBO-PI4KIIIα downregulation reduced neuronal Aβ 42 accumulation, and interestingly increased neuronal Aβ 42 release. This study suggests the RBO-PI4KIIIα complex as a novel therapeutic target, and PI4KIIIα inhibitors as new drug candidates. Copyright

  8. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

    Science.gov (United States)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

    2013-04-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

  9. Colorimetric detection of cholesterol based on enzyme modified gold nanoparticles

    Science.gov (United States)

    Nirala, Narsingh R.; Saxena, Preeti S.; Srivastava, Anchal

    2018-02-01

    We develop a simple colorimetric method for determination of free cholesterol in aqueous solution based on functionalized gold nanoparticles with cholesterol oxidase. Functionalized gold nanoparticles interact with free cholesterol to produce H2O2 in proportion to the level of cholesterol visually is being detected. The quenching in optical properties and agglomeration of functionalized gold nanoparticles play a key role in cholesterol sensing due to the electron accepting property of H2O2. While the lower ranges of cholesterol (lower detection limit i.e. 0.2 mg/dL) can be effectively detected using fluorescence study, the absorption study attests evident visual color change which becomes effective for detection of higher ranges of cholesterol (lower detection limit i.e. 19 mg/dL). The shades of red gradually change to blue/purple as the level of cholesterol detected (as evident at 100 mg/dL) using unaided eye without the use of expensive instruments. The potential of the proposed method to be applied in the field is shown by the proposed cholesterol measuring color wheel.

  10. The metabolic syndrome using the National Cholesterol Education ...

    African Journals Online (AJOL)

    The metabolic syndrome using the National Cholesterol Education Program and International Diabetes Federation definitions among urbanised black South Africans with established coronary artery disease.

  11. Effect of doxazosin on cholesterol synthesis in cell culture

    International Nuclear Information System (INIS)

    D'Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent

  12. Cholesterol monohydrate nucleation in ultrathin films on water

    DEFF Research Database (Denmark)

    Rapaport, H.; Kuzmenko, I.; Lafont, S.

    2001-01-01

    The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a tri......The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity...... in pathological lipid deposits....

  13. Cholesterol granuloma of the petrous apex: CT diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-12-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

  14. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2014-01-01

    Full Text Available Excess cholesterol is associated with cardiovascular diseases (CVD, an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18 ± 0.55 mg/1010 cfu in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70 ± 63.33 mg/1010 cfu of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic.

  15. Cholesterol granuloma of the petrous apex: CT diagnosis

    International Nuclear Information System (INIS)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-01-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment

  16. Cholesterol turnover and metabolism in two patients with abetalipoproteinemia

    International Nuclear Information System (INIS)

    Goodman, D.S.; Deckelbaum, R.J.; Palmer, R.H.; Dell, R.B.; Ramakrishnan, R.; Delpre, G.; Beigel, Y.; Cooper, M.

    1983-01-01

    Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received [14C]cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels

  17. Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Yi Tan

    2015-01-01

    Full Text Available The aim of this study was to determine whether inhibition of resistin by a synthetic antiresistin RNA (oligonucleotide oligo ameliorates metabolic and histological abnormalities in nonalcoholic fatty liver disease (NAFLD induced by high-fat diet (HFD in mice. The antiresistin RNA oligo and a scrambled control oligo (25 mg/kg of body weight were i.p. injected to HFD mice. Serum metabolic parameters and hepatic enzymes were measured after 4-week treatment. The treatment significantly reduced epididymal fat and attenuated the elevated serum resistin, cholesterol, triglycerides, glucose, and insulin with an improved glucose tolerance test. Antiresistin RNA oligo also normalized serum AST and ALT levels with improved pathohistology of NAFLD. Immunoblotting and qRT-PCR revealed that decreased protein and mRNA expression of resistin in fat and liver tissues of the treated mice were associated with reduction of adipose TNF-α and IL-6 expression and secretion into circulation. mRNA and protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK and sterol regulatory element-binding protein-1c (SREBP-1c were also significantly decreased in the treated mice. Our results suggest that resistin may exacerbate NAFLD in metabolic syndrome through upregulating inflammatory cytokines and hepatic PEPCK and SREBP-1c. Antiresistin RNA oligo ameliorated metabolic abnormalities and histopathology of NAFLD through attenuating proinflammatory cytokines.

  18. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    , S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...

  19. The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Cruz

    2013-09-01

    Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

  20. Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

    Science.gov (United States)

    Li, Yong; Chen, Youliang; Li, Hua

    2017-01-01

    Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  2. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  3. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  4. Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

    Science.gov (United States)

    Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

    2017-08-01

    Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  5. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  6. The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol.

    Science.gov (United States)

    Trinidad, Trinidad P; Loyola, Anacleta S; Mallillin, Aida C; Valdez, Divinagracia H; Askali, Faridah C; Castillo, Joan C; Resaba, Rosario L; Masa, Dina B

    2004-01-01

    This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.

  7. Synthesis of cholesterol 26. C{sup 14} (1961); Synthese du cholesterol {sup 14}C-26 (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Cholesterol 26 {sup 14}C is synthesized from methylmagnesium iodide {sup 14}C with a 48 per cent overall yield. Cholesterol is purified by chromatography on alumina. The various intermediates of the synthesis are characterized by thin-layer chromatography according to Stahl. (authors) [French] Le cholesterol {sup 14}C-26 est synthetise a partir d'iodure de methyl magnesium {sup 14}C, avec un rendement de 48 pour cent par rapport a l'iodure de methyl {sup 14}C mis en jeu. Le cholesterol est purifie par chromatographie sur alumine. Les intermediaires de la synthese sont caracterises par chromatographie en couche mince, selon Stahl. (auteurs)

  8. The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats.

    Directory of Open Access Journals (Sweden)

    Yinghua Shi

    Full Text Available To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC and total bile acids (TBA levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1 The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group (P<0.05. (2 Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05. TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05. (3 mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05, as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05. The activities of these enzymes also paralleled the observed changes in mRNA levels. (4 There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1 the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2 the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

  9. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

  10. Whole body and tissue cholesterol turnover in the baboon

    International Nuclear Information System (INIS)

    Dell, R.B.; Mott, G.E.; Jackson, E.M.; Ramakrishnan, R.; Carey, K.D.; McGill, H.C. Jr.; Goodman, D.S.

    1985-01-01

    Cholesterol turnover was studied in four baboons by injecting [ 14 C]cholesterol 186 days and [ 3 H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body and for many tissues. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions, provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates

  11. The hedgehog receptor patched is involved in cholesterol transport.

    Directory of Open Access Journals (Sweden)

    Michel Bidet

    Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

  12. 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

  13. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-12-01

    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

  14. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

    Science.gov (United States)

    Suresh Babu, P; Srinivasan, K

    1998-04-01

    Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.

  15. ZINC-INDUCED HYPERLEPTINEMIA IN RATS RELATED TO THE AMELIORATION OF SUCROSE-INDUCED OBESITY WITH ZINC REPLETION

    International Nuclear Information System (INIS)

    HEIBASHY, M.I.; EL-NAHLA, A.M.; ASHOUR, I.; SALEH, SH.Y.A.

    2008-01-01

    Thirty adult albino rats (Rattus rattus) at 6 weeks of age were divided into three groups (ten for each). The first group was fed a standard laboratory diet for 8 weeks (control). The second group was made obese by giving them 32% sucrose solution in addition to the standard laboratory diet .The third group was received zinc supplementation (50 mg zinc acetate/ litre) with their sucrose solution. Body weight of all rats was measured weekly for 8 weeks. At 14 weeks of age, rats were killed and fasting blood samples were obtained. Serum glucose, insulin, cholesterol, triglyceride, leptin, tumour necrosis factor-α and zinc were measured.Results showed remarkable changes in body weights in sucrose fed rats only when compared to control and supplemented zinc rats group. Serum glucose, insulin, cholesterol and triglycerides were significantly increased in sucrose fed rats than both control and sucrose with zinc group. Serum leptin showed significant increase in sucrose fed rats than control and also showed higher significant value in sucrose fed rats supplemented with zinc comparing with sucrose fed rats and control ones. Tumour necrosis factor-? did not show any significant difference between all groups. Serum zinc concentration was decreased significantly in sucrose fed rats as compared to control. On the other hand, it was increased significantly in sucrose fed rats supplemented with zinc than other both groups. It could be concluded that zinc supplementation induced hyperleptinemia caused ameliorating effects in obese rats

  16. Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

    Science.gov (United States)

    Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi

    2016-01-01

    Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2′-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring. PMID:26105135

  17. Membrane cholesterol effect on the 5-HT2A receptor: Insights into the lipid-induced modulation of an antipsychotic drug target.

    Science.gov (United States)

    Ramírez-Anguita, Juan Manuel; Rodríguez-Espigares, Ismael; Guixà-González, Ramon; Bruno, Agostino; Torrens-Fontanals, Mariona; Varela-Rial, Alejandro; Selent, Jana

    2018-01-01

    The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT 2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane-induced alterations of receptor dynamics and points to cholesterol-induced stabilizing and destabilizing effects on the conformational variability of GPCRs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  18. Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance.

    Science.gov (United States)

    Hattori, Sachiko

    2017-11-28

    Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. In the present study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type 2 diabetes patients who have insulin resistance. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood pressure, plasma triglycerides, liver transaminases and estimated glomerular filtration rate, and increased high-density lipoprotein cholesterol. Furthermore, EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In the placebo group, there were no significant changes in these factors except for slight increases in liver transaminases. Multiple regression analysis showed that the change in homeostatic model assessment of insulin resistance (P = 0.0102) and the change in alanine aminotransferase (P = 0.0301) were significantly associated with the change in RLP-C in the EMPA group. The change in RLP-C significantly correlated with the change in homeostatic model assessment of insulin resistance (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P = 0.00241). EMPA decreases RLP-C levels, which is closely associated with amelioration of insulin sensitivity in diabetes patients who have insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  19. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may...

  20. Cholesterol: Top Five Foods to Lower Your Numbers

    Science.gov (United States)

    ... enough trans fats in a day to be unhealthy and increase cholesterol. If a food label lists "partially hydrogenated oil," it has trans fat, and it's best to avoid it. In addition to changing your diet, making other heart-healthy lifestyle changes is key to improving your cholesterol. Exercising, ...

  1. Endoscopic transsphenoidal surgery for cholesterol granulomas involving the petrous apex

    NARCIS (Netherlands)

    Georgalas, C.; Kania, R.; Guichard, J.-P.; Sauvaget, E.; Tran Ba Huy, P.; Herman, P.

    2008-01-01

    Surgery for cholesterol granulomas involving the petrous apex has traditionally been performed via a lateral skull base approach. We present a case-series of four cholesterol granulomas treated through the endoscopic-transsphenoid approach over the last 10 years. Drainage was successful and

  2. [Phytosterols: another way to reduce LDL cholesterol levels].

    Science.gov (United States)

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  3. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

    NARCIS (Netherlands)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel; Swartz, Melody A.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J.

    2013-01-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic

  4. The structure of a cholesterol-trapping protein

    Science.gov (United States)

    cholesterol-trapping protein Contact: Dan Krotz, dakrotz@lbl.gov Berkeley Lab Science Beat Lab website index Institute researchers determined the three-dimensional structure of a protein that controls cholesterol level in the bloodstream. Knowing the structure of the protein, a cellular receptor that ensnares

  5. Lowering of cholesterol bioaccessibility and serum concentrations by saponins

    NARCIS (Netherlands)

    Vinarova, Liliya; Vinarov, Zahari; Atanasov, Vasil; Pantcheva, Ivayla; Tcholakova, Slavka; Denkov, Nikolai; Stoyanov, Simeon

    2015-01-01

    Using an in vitro digestion model, we studied the effect of six saponin extracts on the bioaccessibility of cholesterol and saturated fatty acids (SFAs). In the absence of saponins, around 78% of the available cholesterol was solubilized in the simulated intestinal fluids. The addition of two

  6. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Serum cholesterol decline and depression in the postpartum period

    NARCIS (Netherlands)

    Dam, van R.M.; Schuit, A.J.; Schouten, E.G.; Vader, H.L.; Pop, V.J.M.

    1999-01-01

    We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for

  8. Serum cholesterol decline and depression in the postpartum period

    NARCIS (Netherlands)

    van Dam, R M; Schuit, A.J.; Schouten, E G; Vader, H L; Pop, V.J.

    We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for

  9. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

    Directory of Open Access Journals (Sweden)

    Dhritiman Samanta

    2017-05-01

    Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

  10. Low serum cholesterol, serotonin metabolism, and violent death

    NARCIS (Netherlands)

    P.H.A. Steegmans

    1995-01-01

    textabstractA high serum cholesterol level is a well documented risk factor for atherosclerotic cardiovascular disease. Consequently, a low serum cholesterol has in general been viewed as beneficial. However, since the early 70s, results from several cohort studies and randomized trials have

  11. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Peng, Shi-Kaung; Phillips, G.A.; Xia, Guang-Zhi; Morin, R.J.

    1987-01-01

    Radiolabeled pure [4- 14 C] cholesterol was kept at 60 0 C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  12. Plasma cholesterol and sodium in some Nigerians | Ighoroje ...

    African Journals Online (AJOL)

    Cholesterol moderates the fluidity of cell membrane and this in turn controls the transmembrane movement of Na+. We have thus attempted to investigate the relationship of serum cholesterol and Na+ concentrations in some Nigerians. Blood samples were obtained from 122 healthy adult Nigerians and the plasma ...

  13. Rare cause of post-squalene disorder of cholesterol biosynthesis ...

    African Journals Online (AJOL)

    Errors of cholesterol biosynthesis represent a heterogeneous group of metabolic disorders. The aim of the authors of this article is to present a case of a patient with typical symptoms of a rare post-squalene disorder of cholesterol biosynthesis, its diagnostics and progress in neonatal period. The differential diagnosis of a ...

  14. Recognition of Odontogenic Cyst-Fluid Cholesterol Concentration ...

    African Journals Online (AJOL)

    Background: Hypercholesterolaemia is a risk factor for cardiovascular diseases. Serum cholesterol is usually determined to know if a subject is at a risk of heart diseases. This lipid is found in most fluids in the body including the odontogenic cyst-fluid. We investigated the concentration of cholesterol in the odontogenic ...

  15. Strategies for increasing house staff management of cholesterol with inpatients.

    Science.gov (United States)

    Boekeloo, B O; Becker, D M; Levine, D M; Belitsos, P C; Pearson, T A

    1990-01-01

    This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

  16. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.

  17. Exercise Enhances Whole-Body Cholesterol Turnover in Mice

    NARCIS (Netherlands)

    Meissner, Maxi; Havinga, Rick; Boverhof, Renze; Kema, Ido; Groen, Albert K.; Kuipers, Folkert

    MEISSNER, M., R. HAVINGA, R. BOVERHOF, I. KEMA, A. K. GROEN, and F. KUIPERS. Exercise Enhances Whole-Body Cholesterol Turnover in Mice. Med. Sci. Sports Exerc., Vol. 42, No. 8, pp. 1460-1468, 2010. Purpose: Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels, but

  18. Cholesterol Check (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    High blood cholesterol is a risk factor for cardiovascular disease. This podcast discusses the importance of a healthy diet and regular cholesterol screening.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  19. marital status and occupation versus serum total cholesterol and hdl

    African Journals Online (AJOL)

    DR. AMIN

    ABSTRACT. The influence of marital status and occupation on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL – CH) concentrations was studied in sixty one (61) adult male and female Hausa subjects aged 20 – 50 years. Irrespective of marital status and occupation, female subjects had higher ...

  20. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  1. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  2. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  3. Immobilization of cholesterol oxidase in LbL films and detection of cholesterol using ac measurements

    International Nuclear Information System (INIS)

    Moraes, Marli L.; Souza, Nara C. de; Hayasaka, Caio O.; Ferreira, Marystela; Rodrigues Filho, Ubirajara P.; Riul, Antonio; Zucolotto, Valtencir; Oliveira, Osvaldo N.

    2009-01-01

    The preserved activity of immobilized biomolecules in layer-by-layer (LbL) films can be exploited in various applications, including biosensing. In this study, cholesterol oxidase (COX) layers were alternated with layers of poly(allylamine hydrochloride) (PAH) in LbL films whose morphology was investigated with atomic force microscopy (AFM). The adsorption kinetics of COX layers comprised two regimes, a fast, first-order kinetics process followed by a slow process fitted with a Johnson-Mehl-Avrami (JMA) function, with exponent ∼ 2 characteristic of aggregates growing as disks. The concept based on the use of sensor arrays to increase sensitivity, widely employed in electronic tongues, was extended to biosensing with impedance spectroscopy measurements. Using three sensing units, made of LbL films of PAH/COX and PAH/PVS (polyvinyl sulfonic acid) and a bare gold interdigitated electrode, we were able to detect cholesterol in aqueous solutions down to the 10 -6 M level. This high sensitivity is attributed to the molecular-recognition interaction between COX and cholesterol, and opens the way for clinical tests to be made with low cost, fast experimental procedures

  4. Enzymatic-fluorometric quantification of cholesterol in bovine milk

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    The present paper describes an enzymatic–fluorometric method for the determination of cholesterol in milk and other opaque matrices. The initial step of the method is to liberate chemically and physically bound cholesterol from the milk fat globule membrane by enzymatic action. The method is able...... to discriminate between esterified and free cholesterol in milk. The analysis is cost effective and is developed to work directly on whole, fresh milk thereby eliminating time consuming and tedious pre-treatment procedures of the sample. More than 1000 milk samples were analysed on the day of sampling. The total...... concentration of milk cholesterol ranged from 80 to 756 μM (n = 1068; mean 351 μM). Milk cholesterol was significantly correlated to milk fat concentration as analysed by mid-infra red spectrometry (r = 0.630; n = 853) and by an enzymatic–fluorometric method (triacylglycerol) (r = 0.611; n = 842)....

  5. Effect of medicinal plants on the crystallization of cholesterol

    Science.gov (United States)

    Saraswathi, N. T.; Gnanam, F. D.

    1997-08-01

    One of the least desirable calcifications in the human body is the mineral deposition in atherosclerosis plaques. These plaques principally consist of lipids such as cholesterol, cholesteryl esters, phospholipids and triglycerides. Chemical analysis of advanced plaques have shown the presence of considerable amounts of free cholesterol identified as cholesterol monohydrate crystals. Cholesterol has been crystallized in vitro. The extracts of some of the Indian medicinal plants detailed below were used as additives to study their effect on the crystallization behaviour of cholesterol. It has been found that many of the herbs have inhibitory effect on the crystallization such as nucleation, crystal size and habit modification. The inhibitory effect of the plants are graded as Commiphora mughul > Aegle marmeleos > Cynoden dactylon > Musa paradisiaca > Polygala javana > Alphinia officinarum > Solanum trilobatum > Enicostemma lyssopifolium.

  6. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Zaater, M.K.

    2011-01-01

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  7. Effect of ionizing radiation on cholesterol in aqueous dispersion

    International Nuclear Information System (INIS)

    Lakritz, L.; Maerker, G.

    1989-01-01

    Aqueous sodium stearate dispersions of cholesterol were irradiated at 0-2 degrees C with absorbed doses ranging from 2.5 to 50 kGy. The resulting mixture of cholesterol derivatives was isolated and examined for 7-ketocholesterol and cholesterol 5 alpha, 6 alpha-epoxide and 5 beta, 6 beta-epoxide content. Concentrations of all three compounds increased with dose, while the ratio of 7-ketocholesterol to total epoxides decreased with increasing dose. The ratio of 7-ketocholestrol to the epoxides was approximately 1 or below at all dose levels while the same ratio in autoxidations of cholesterol in dispersions was normally 6 or greater. The change in the keto/epoxide ratio may be a means for determining whether meat or other foods containing cholesterol have been subjected to ionizing radiation

  8. Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury

    DEFF Research Database (Denmark)

    Owen, Michael C; Kulig, Waldemar; Rog, Tomasz

    2018-01-01

    In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC...... in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also...... resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does...

  9. Cholesterol biosynthesis in polychlorinated biphenyl-treated rats

    International Nuclear Information System (INIS)

    Kling, D.; Gamble, W.

    1982-01-01

    After administration of polychlorinated biphenly (PCB) at 0.055 (w/w) of the diet to Wistar rats for 30 days, followed by intraperitioneal injection of tritiated water, [ 14 C]mevalonate, and [ 14 C]acetate, there was a decrease in cholesterol biosynthesis in rat liver. No significant change in cholesterol formation was observed when PCB was administered at 0.01% (w/w) of the diet. In vitro inhibition of cholesterol synthesis by rat liver microsomes was observed with PCB. Squalene 2,3-oxidocyclase activity of rat liver microsomes was not significantly altered. Desmosterol delta 24 reductase activity was inhibited only at relatively high concentrations of PCB. There was increased incorporation of radioactivity into squalene and lanosterol, in vitro, in the presence of PCB. The primary inhibition of cholesterol biosynthesis appears to be at the demethylation and rearrangement reactions between lanosterol and cholesterol in the biosynthetic pathway

  10. Bad cholesterol and good mood: exploring the link

    Directory of Open Access Journals (Sweden)

    Yashaswi Gupta

    2016-01-01

    Full Text Available It is a well-known fact that high cholesterol increases the risks of heart disease. Hence, physicians actively encourage cholesterol-lowering interventions using medications and lifestyle modifications. However, there is considerable evidence that aggressive lowering of cholesterol is associated with depression, bipolar disorders, violent behaviour, and suicidal ideation. It has been hypothesised that low cholesterol leads to low levels of serotonin, a chemical that is responsible for maintaining mood balance. South Korea and India have highest number of suicides in Asia. It is a significant challenge for physicians to search an alternative that will not only maintain healthy level of cholesterol, but also contribute to psychological well-being of the patient. Generally, the role of diet and physical activity is considered secondary to medications. However, dietary supplements like coenzyme Q10 (CoQ10, omega-3 fatty acids, niacin, and physical activity like Yoga are extremely beneficial for improving lipid profile and symptoms of depression.

  11. The free radical scavenger, edaravone, ameliorates delayed neuropsychological sequelae after acute carbon monoxide poisoning in rabbits.

    Science.gov (United States)

    Qingsong, Wang; Yeming, Guan; Xuechun, Liu; Hongjuan, Liu; Jing, Wang

    2013-01-01

    The mechanism underlying delayed neuropsychological sequelae (DNS) after acute carbon monoxide (CO) poisoning is unclear. There are no effective treatments for DNS. As part of a new generation of antioxidants, edaravone has been reported to improve clinical outcomes in patients exhibiting ischemic strokes. There has been little data about edaravone in relationship to DNS prevention and treatment. We hypothesized that edaravone could ameliorate DNS: Here we test that hypothesis in rabbits Rabbits were randomly divided into sham control,DNS group, saline group and edaravone group. DNS model was made by intraperitoneal injection of CO. Normal saline or edaravone (1 mg/kg, twice daily, a total of one course for 14 days) was infused through the ear vein from Day 15 since the DNS model was established. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) were measured in each group. Magnetic resonance spectroscopy (MRS) was used to examine regions of the brain for various compounds. The apoptotic index and neuronal density in the hippocampal CA1 area were also investigated. SOD activity decreased significantly and MDA content increased substantially in the DNS group and saline group when compared with the sham control (p edaravone group, serum SOD activity significantly increased and MDA levels significantly decreased when compared with DNS and saline group (p edaravone group (p edaravone group was significantly lower than that of the DNS and saline groups (p edaravone group was significantly higher than that of the DNS and saline group in the hippocampal CA1 area (p edaravone could ameliorate DNS after acute carbon monoxide poisoning in rabbits. These results suggest free radicals could be involved in the underlying mechanisms of DNS. Furthermore, brain MRS shows promise as a tool for early diagnosis for DNS.

  12. Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons.

    Science.gov (United States)

    Lopez, Jose R; Uryash, A; Kolster, J; Estève, E; Zhang, R; Adams, J A

    2018-03-26

    We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca 2+ ([Ca 2+ ] i ) and Na + ([Na + ] i ), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit. In this study, we assessed the potential therapeutic properties of the whole body periodic acceleration (pGz) to ameliorate the pathology observed in cortical neurons from the mdx mouse. pGz adds small pulses to the circulation, thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of nitric oxide (NO). We found [Ca 2+ ] i and [Na + ] i overload along with reactive oxygen species (ROS) overproduction in mdx neurons and cognitive dysfunction. mdx neurons showed increased activity of superoxide dismutase, glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell viability. mdx neurons were more susceptible to hypoxia-reoxygenation injury than WT. pGz ameliorated the [Ca 2+ ] i , and [Na + ] i elevation and ROS overproduction and further increased the activities of superoxide dismutase, glutathione peroxidase and reduced the malondialdehyde and calpains. pGz diminished cell damage and elevated [Ca 2+ ] i during hypoxia-reoxygenation and improved cognitive function in mdx mice. Moreover, pGz upregulated the expression of utrophin, dystroglycan-β and CAPON, constitutive nitric oxide synthases, prosaposin, brain-derived neurotrophic, and glial cell line-derived neurotrophic factors. The present study demonstrated that pGz is an effective therapeutic approach to improve mdx neurons function, including cognitive functions.

  13. Effect of cholesterol deposition on bacterial adhesion to contact lenses.

    Science.gov (United States)

    Babaei Omali, Negar; Zhu, Hua; Zhao, Zhenjun; Ozkan, Jerome; Xu, Banglao; Borazjani, Roya; Willcox, Mark D P

    2011-08-01

    To examine the effect of cholesterol on the adhesion of bacteria to silicone hydrogel contact lenses. Contact lenses, collected from subjects wearing Acuvue Oasys or PureVision lenses, were extracted in chloroform:methanol (1:1, v/v) and amount of cholesterol was estimated by thin-layer chromatography. Unworn lenses were soaked in cholesterol, and the numbers of Pseudomonas aeruginosa strains or Staphylococcus aureus strains that adhered to the lenses were measured. Cholesterol was tested for effects on bacterial growth by incubating bacteria in medium containing cholesterol. From ex vivo PureVision lenses, 3.4 ± 0.3 μg/lens cholesterol was recovered, and from Acuvue Oasys lenses, 2.4 ± 0.2 to 1.0 ± 0.1 μg/lens cholesterol was extracted. Cholesterol did not alter the total or viable adhesion of any strain of P. aeruginosa or S. aureus (p > 0.05). However, worn PureVision lenses reduced the numbers of viable cells of P. aeruginosa (5.8 ± 0.4 log units) compared with unworn lenses (6.4 ± 0.2 log units, p = 0.001). Similarly, there were fewer numbers of S. aureus 031 adherent to worn PureVision (3.05 ± 0.8 log units) compared with unworn PureVision (4.6 ± 0.3 log units, p = 0.0001). Worn Acuvue Oasys lenses did not affect bacterial adhesion. Cholesterol showed no effect on the growth of any test strain. Although cholesterol has been shown to adsorb to contact lenses during wear, this lipid does not appear to modulate bacterial adhesion to a lens surface.

  14. Changes to cholesterol trafficking in macrophages by Leishmania parasites infection.

    Science.gov (United States)

    Semini, Geo; Paape, Daniel; Paterou, Athina; Schroeder, Juliane; Barrios-Llerena, Martin; Aebischer, Toni

    2017-08-01

    Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected. This is correlated with a reduction or absence of detectable NPC1 (Niemann-Pick disease, type C1), a protein responsible for cholesterol efflux from endocytic compartments, in the Leishmania mexicana habitat and infected cells. Filipin staining revealed a halo around parasites within parasitophorous vacuoles (PV) likely representing free cholesterol accumulation. Labeling of host cell membranous cholesterol by fluorescent cholesterol species before infection revealed that this pool is also trafficked to the PV but becomes incorporated into the parasites' membranes and seems not to contribute to the halo detected by filipin. This cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis. Thus, sequestration of cholesterol by Leishmania amastigotes early after infection provides a basis to understand perturbation of cholesterol-dependent processes in macrophages that were shown previously by others to be necessary for their proper function in innate and adaptive immune responses. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  15. Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

    Directory of Open Access Journals (Sweden)

    Xin Wan

    Full Text Available BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic renovascular disease (ARD may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation. METHODS: Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively. RESULTS: Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ. CONCLUSIONS: We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating

  16. What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

    DEFF Research Database (Denmark)

    Falkovich, Stanislav G.; Martinez-Seara, Hector; Nesterenko, Alexey M.

    2016-01-01

    Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations ...

  17. Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

    NARCIS (Netherlands)

    Moschetta, Antonio

    2001-01-01

    Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

  18. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  19. Dl-3-n-Butylphthalide Treatment Enhances Hemodynamics and Ameliorates Memory Deficits in Rats with Chronic Cerebral Hypoperfusion

    Directory of Open Access Journals (Sweden)

    Zhilin Xiong

    2017-07-01

    Full Text Available Our previous study has revealed that chronic cerebral hypoperfusion (CCH activates a compensatory vascular mechanism attempting to maintain an optimal cerebral blood flow (CBF. However, this compensation fails to prevent neuronal death and cognitive impairment because neurons die prior to the restoration of normal CBF. Therefore, pharmacological invention may be critical to enhance the CBF for reducing neurodegeneration and memory deficit. Dl-3-n-butylphthalide (NBP is a compound isolated from the seeds of Chinese celery and has been proven to be able to prevent neuronal loss, reduce inflammation and ameliorate memory deficits in acute ischemic animal models and stroke patients. In the present study, we used magnetic resonance imaging (MRI techniques, immunohistochemistry and Morris water maze (MWM to investigate whether NBP can accelerate CBF recovery, reduce neuronal death and improve cognitive deficits in CCH rats after permanent bilateral common carotid artery occlusion (BCCAO. Rats were intravenously injected with NBP (5 mg/kg daily for 14 days beginning the first day after BCCAO. The results showed that NBP shortened recovery time of CBF to pre-occlusion levels at 2 weeks following BCCAO, compared to 4 weeks in the vehicle group, and enhanced hemodynamic compensation through dilation of the vertebral arteries (VAs and increase in angiogenesis. NBP treatment also markedly reduced reactive astrogliosis and cell apoptosis and protected hippocampal neurons against ischemic injury. The escape latency of CCH rats in the MWM was also reduced in response to NBP treatment. These findings demonstrate that NBP can accelerate the recovery of CBF and improve cognitive function in a rat model of CCH, suggesting that NBP is a promising therapy for CCH patients or vascular dementia.

  20. Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

    Science.gov (United States)

    Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling

    2016-01-27

    A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin

  1. Generation of induced neurons by direct reprogramming in the mammalian cochlea.

    Science.gov (United States)

    Nishimura, K; Weichert, R M; Liu, W; Davis, R L; Dabdoub, A

    2014-09-05

    Primary auditory neurons (ANs) in the mammalian cochlea play a critical role in hearing as they transmit auditory information in the form of electrical signals from mechanosensory cochlear hair cells in the inner ear to the brainstem. Their progressive degeneration is associated with disease conditions, excessive noise exposure and aging. Replacement of ANs, which lack the ability to regenerate spontaneously, would have a significant impact on research and advancement in cochlear implants in addition to the amelioration of hearing impairment. The aim of this study was to induce a neuronal phenotype in endogenous non-neural cells in the cochlea, which is the essential organ of hearing. Overexpression of a neurogenic basic helix-loop-helix transcription factor, Ascl1, in the cochlear non-sensory epithelial cells induced neurons at high efficiency at embryonic, postnatal and juvenile stages. Moreover, induced neurons showed typical properties of neuron morphology, gene expression and electrophysiology. Our data indicate that Ascl1 alone or Ascl1 and NeuroD1 is sufficient to reprogram cochlear non-sensory epithelial cells into functional neurons. Generation of neurons from non-neural cells in the cochlea is an important step for the regeneration of ANs in the mature mammalian cochlea. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  3. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  4. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  5. Relevance of hereditary defects in lipid transport proteins for the pathogenesis of cholesterol gallstone disease

    NARCIS (Netherlands)

    vanBerge-Henegouwen, G. P.; Venneman, N. G.; Portincasa, P.; Kosters, A.; van Erpecum, K. J.; Groen, A. K.

    2004-01-01

    In the formation of cholesterol gallstones, cholesterol hypersecretion into bile causing cholesterol supersaturation and crystallization appears to be the primary factor, with disturbed gallbladder and intestinal motility as secondary factors. Although intestinal uptake mechanisms have not yet been

  6. Cholesterol-lowering drugs: science and marketing.

    Science.gov (United States)

    Garattini, Livio; Padula, Anna

    2017-02-01

    Long-term use of statin therapy is essential to obtain clinical benefits, but adherence is often suboptimal and some patients are also reported to fail because of 'statin resistance'. The identification of PCSK9 as a key factor in the LDL clearance pathway has led to the development of new monoclonal antibodies. Here we critically review the economic evaluations published in Europe and focused on statins. We searched the PubMed database to select the studies published from July 2006 to June 2016 and finally selected 19 articles. Overall, the majority of studies were conducted from a third-party payer's viewpoint and recurred to modelling. Most studies were sponsored by industry and funding seemed to play a pivotal role in the study design. Patients resistant to LDL-C level reduction were considered only in a few studies. The place in therapy of the new class of biologic should be considered a kind of 'third line' for cholesterol-lowering, after patients have failed with restricted dietary regimens and then with current drug therapies. Otherwise they could result in hardly sustainable expenses even for developed countries.

  7. The effects of probiotics on total cholesterol

    Science.gov (United States)

    Wang, Lang; Guo, Mao-Juan; Gao, Qing; Yang, Jin-Feng; Yang, Lin; Pang, Xiao-Li; Jiang, Xi-Juan

    2018-01-01

    Abstract Background: Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies. Methods: Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis. Results: Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = −13.27, 95% CI (−16.74 to 9.80), P  6 weeks: [MD = −22.18, 95% CI (−28.73, −15.63), P probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects. Conclusion: Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect. PMID:29384846

  8. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  9. Introducing inducible fluorescent split cholesterol oxidase to mammalian cells.

    Science.gov (United States)

    Chernov, Konstantin G; Neuvonen, Maarit; Brock, Ivonne; Ikonen, Elina; Verkhusha, Vladislav V

    2017-05-26

    Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments. The addition of rapamycin reconstituted a fluorescent enzyme, termed split GFP-COase, the fluorescence level of which correlated with its oxidation activity. A rapid decrease of cellular cholesterol induced by intracellular expression of the split GFP-COase promoted the dissociation of a cholesterol biosensor D4H from the plasma membrane. The process was reversible as upon rapamycin removal, the split GFP-COase fluorescence was lost, and cellular cholesterol levels returned to normal. These data demonstrate that the split GFP-COase provides a novel tool to manipulate cholesterol in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice

    Directory of Open Access Journals (Sweden)

    Yin Lu

    2012-01-01

    Full Text Available Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, triglyceride, glucose, and hepatic cholesterol storage were determined. Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24±7.94% (P<0.0001 with 5 mg/kg allicin, 39.28±5.03% (P<0.0001 with 10 mg/kg allicin, and 41.18±5.00% (P<0.0001 with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.

  11. Break the fast? Update on patient preparation for cholesterol testing.

    Science.gov (United States)

    Naugler, Christopher; Sidhu, Davinder

    2014-10-01

    To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety. Copyright© the College of Family Physicians of Canada.

  12. Absorption and transport of cholesterol autoxidation derivatives in rabbits

    International Nuclear Information System (INIS)

    Peng, S.K.; Morin, R.J.; Phillips, G.A.; Xia, G.Z.

    1986-01-01

    Spontaneously autoxidized products of cholesterol have been demonstrated to be angiotoxic and possibly atherogenic. This study investigates the absorption and transport of these cholesterol oxidation derivatives (COD's) as compared to cholesterol. 14 C-labeled cholesterol autoxidized by incubation in a 60 0 C water bath for 5 weeks, then suspended in gelatin and given to New Zealand white rabbits by gastric gavage. Rabbits were sacrificed 24 hours after treatment. COD's were separated by thin layer chromatography (TLC) and radioactivities of each COD and cholesterol were measured. Percentages of each COD and cholesterol in the original mixture before administration and in the rabbits' serum after administration are almost identical, suggesting that the rates of absorption of COD's are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each COD separated by TLC in each lipoprotein fraction showed that cholestane-3β,5α,6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were predominantly present in VLDL (3 x serum concentration) and 25-hydroxycholesterol was predominantly in LDL (2.5 x serum concentration). HDL contained only minute amounts of COD's. The increased levels of COD's in VLDL and LDL may contribute to the atherogenicity of these lipoprotein

  13. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  14. Non-Cell Autonomous Influence of the Astrocyte System xc − on Hypoglycaemic Neuronal Cell Death

    Directory of Open Access Journals (Sweden)

    Nicole A Jackman

    2012-01-01

    Full Text Available Despite longstanding evidence that hypoglycaemic neuronal injury is mediated by glutamate excitotoxicity, the cellular and molecular mechanisms involved remain incompletely defined. Here, we demonstrate that the excitotoxic neuronal death that follows GD (glucose deprivation is initiated by glutamate extruded from astrocytes via system xc −– – an amino acid transporter that imports L-cystine and exports L-glutamate. Specifically, we find that depriving mixed cortical cell cultures of glucose for up to 8 h injures neurons, but not astrocytes. Neuronal death is prevented by ionotropic glutamate receptor antagonism and is partially sensitive to tetanus toxin. Removal of amino acids during the deprivation period prevents – whereas addition of L-cystine restores – GD-induced neuronal death, implicating the cystine/glutamate antiporter, system xc−–. Indeed, drugs known to inhibit system xc −– ameliorate GD-induced neuronal death. Further, a dramatic reduction in neuronal death is observed in chimaeric cultures consisting of neurons derived from WT (wild-type mice plated on top of astrocytes derived from sut mice, which harbour a naturally occurring null mutation in the gene (Slc7a11 that encodes the substrate-specific light chain of system xc −– (xCT. Finally, enhancement of astrocytic system xc −– expression and function via IL-1β (interleukin-1β exposure potentiates hypoglycaemic neuronal death, the process of which is prevented by removal of L-cystine and/or addition of system xc −– inhibitors. Thus, under the conditions of GD, our studies demonstrate that astrocytes, via system xc −–, have a direct, non-cell autonomous effect on cortical neuron survival.

  15. The Effect of Vitamin E on Ameliorating Primary Dysmenorrhea: A ...

    African Journals Online (AJOL)

    Dysmenorrhea or painful menstruation is one of the most common problems of women. Using systematic review and meta‑analysis, this study aimed to determine the effect of vitamin E on ameliorating the intensity of pain of primary dysmenorrhea. Available databases comprising PubMed, Google Scholar, ISI, Science ...

  16. Designing urban parks that ameliorate the effects of climate change

    NARCIS (Netherlands)

    Brown, R.D.; Vanos, J.; Kenny, N.; Lenzholzer, S.

    2015-01-01

    Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects

  17. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  18. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  19. Ameliorative effect of the hydroethanolic whole plant extract of ...

    African Journals Online (AJOL)

    At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

  20. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and changes in osmotic fragility, deformability ...

  1. Does fat in milk, butter and and cholesterol differently?

    DEFF Research Database (Denmark)

    Tholstrup, T,; Høy, Carl-Erik; Andersen, L.N.

    2004-01-01

    and 8 hours following intake of the meals. Results: Fasting LDL cholesterol concentration was significantly higher after butter than cheese diet (p 0.037), with a borderline significant difference in total cholesterol (p = 0.054) after the experimental periods of three weeks. Postprandial glucose showed...... a higher response after cheese diet than after milk diet (p = 0.010, diet X time interaction). Conclusions: A different effect of fat in milk and butter could not be confirmed in this study. The moderately lower LDL cholesterol after cheese diet compared to butter diet should be investigated further....

  2. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

    The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others

  3. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  4. Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.

    Science.gov (United States)

    Yang, Weichun; Shi, He; Zhang, Jianfen; Shen, Ziyi; Zhou, Guangyu; Hu, Minyu

    2017-01-31

    The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P neurons, had increased (P neurons had increased (P neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight

  5. The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial.

    Science.gov (United States)

    Lin, X; Racette, S B; Lefevre, M; Spearie, C A; Most, M; Ma, L; Ostlund, R E

    2010-12-01

    Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers. The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), Pphytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), Pphytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

  6. Lactobacillus plantarum MYS6 Ameliorates Fumonisin B1-Induced Hepatorenal Damage in Broilers

    Directory of Open Access Journals (Sweden)

    B. V. Deepthi

    2017-11-01

    Full Text Available Fumonisin B1 (FB1, a mycotoxin produced by Fusarium species is a predominant Group 2B carcinogen occurring in maize and maize-based poultry feeds. It is shown to be nephrotoxic, hepatotoxic, neurotoxic, and immunosuppressing in animals. In this study, we report the ameliorating effects of a probiotic strain, Lactobacillus plantarum MYS6 on FB1-induced toxicity and oxidative damage in broilers. A 6-week dietary experiment consisting of 48 broilers was performed in six treatment groups. Probiotic treatment (109 cells/mL involved pre-colonization of broilers with L. plantarum MYS6 while co-administration treatment involved supplementation of probiotic and FB1-contaminated diet (200 mg/Kg feed simultaneously. At the end of the treatment period, growth performance, hematology, serum biochemistry, and markers of oxidative stress in serum and tissue homogenates were evaluated in all the broilers. The histopathological changes in hepatic and renal tissues were further studied. The results demonstrated that administration of L. plantarum MYS6 efficiently improved the feed intake, body weight and feed conversion ratio in broilers. It mitigated the altered levels of hematological indices such as complete blood count, hemoglobin, and hematocrit. Serum parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, creatinine, cholesterol, triglycerides, and albumin were significantly restored after administering the probiotic in FB1-intoxicated broilers. Additionally, L. plantarum MYS6 alleviated the levels of oxidative stress markers in serum and tissue homogenate of liver. The histopathological data of liver and kidney further substantiated the overall protection offered by L. plantarum MYS6 against FB1-induced cellular toxicity and organ damage in broilers. Our results indicated that co-administration of probiotic along with the toxin had better effect in detoxification compared to its pre-colonization in broilers

  7. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  8. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Blockade of store-operated calcium entry alleviates high glucose-induced neurotoxicity via inhibiting apoptosis in rat neurons.

    Science.gov (United States)

    Xu, Zhenkuan; Xu, Wenzhe; Song, Yan; Zhang, Bin; Li, Feng; Liu, Yuguang

    2016-07-25

    Altered store-operated calcium entry (SOCE) has been suggested to be involved in many diabetic complications. However, the association of altered SOCE and diabetic neuronal damage remains unclear. This study aimed to investigate the effects of altered SOCE on primary cultured rat neuron injury induced by high glucose. Our data demonstrated that high glucose increased rat neuron injury and upregulated the expression of store-operated calcium channel (SOC). Inhibition of SOCE by a pharmacological inhibitor and siRNA knockdown of stromal interaction molecule 1 weakened the intracellular calcium overload, restored mitochondrial membrane potential, downregulated cytochrome C release and inhibited cell apoptosis. As well, treatment with the calcium chelator BAPTA-AM prevented cell apoptosis by ameliorating the high glucose-increased intracellular calcium level. These findings suggest that SOCE blockade may alleviate high glucose-induced neuronal damage by inhibiting apoptosis. SOCE might be a promising therapeutic target in diabetic neurotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

  11. Reverse Cholesterol Transport: Molecular Mechanisms and the Non-medical Approach to Enhance HDL Cholesterol

    Directory of Open Access Journals (Sweden)

    Leandro R. Marques

    2018-05-01

    Full Text Available Dyslipidemia (high concentrations of LDL-c and low concentrations of HDL-c is a major cause of cardiovascular events, which are the leading cause of death in the world. On the other hand, nutrition and regular exercise can be an interesting strategy to modulate lipid profile, acting as prevention or treatment, inhibiting the risk of diseases due to its anti-inflammatory and anti-atherogenic characteristics. Additionally, the possibility of controlling different training variables, such as type, intensity and recovery interval, can be used to maximize the benefits of exercise in promoting cardiovascular health. However, the mechanisms by which exercise and nutrients act in the regulation of cholesterol and its fractions, such as reverse cholesterol transport, receptors and transcription factors involved, such as PPARs and their role related to exercise, deserve further discussion. Therefore, the objective of this review is to debate about non-medical approaches to increase HDL-c, such as nutritional and training strategies, and to discuss the central mechanisms involved in the modulation of lipid profile during exercise, as well as that can be controlled by physical trainers or sports specialists in attempt to maximize the benefits promoted by exercise. The search for papers was performed in the databases: Medline (Pubmed, Science Direct, Scopus, Sport Discus, Web of Science, Scielo and Lilacs until February 2016.

  12. Induction of lipid peroxidation in erythrocytes during cholesterol oxidation catalyzed by cholesterol oxidase

    International Nuclear Information System (INIS)

    Kagan, V.E.; Monovich, O.; Ribarov, S.R.

    1986-01-01

    The authors study the ability of cholesterol oxidase (ChO), which catalyzes oxidation of cholesterol (Ch) to cholest-4-en-3-one and, at the same time, reduction of O 2 to H 2 O 2 , to induce the lipid peroxidation (LPO) in plasma membranes. Erythrocyte ghosts were obtained from guinea pig blood; the reaction of oxidation of Ch in the erythrocyte ghosts or in micelles with Triton X-100 was carried out in the following medium: Tris-HCl 0.2 M, pH 7.0 (at 37 C), Triton X-100 0.25%, and ChO 0.05 U/ml. At the present time ChO is often used to study the asymmetry of distribution of Ch in biomembranes and the velocity of its transbilayer migration. It is suggested that changes in membrane permeability do not take place during the reaction catalyzed by the enzyme, and no products capable of affecting flip-flop in biological are formed. Accumulation of LPO products in erythrocyte membranes discovered in this investigation under the influence of ChO compels critical re-examination of the resutls

  13. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-01

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

  14. Are You Taking the Right Treatment for Your High Cholesterol?

    Science.gov (United States)

    ... open('/content/cro/en/health/prescription-drugs/best-buy-drugs/evaluating-statin-drugs-to-treat--high-cholesterol-and- ... talking with your doctor How to share Best Buy Drug reports About us Less common issues: Diabetes, memory ...

  15. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  16. Plasma Triglyceride and Cholesterol Levels in Normotensive and ...

    African Journals Online (AJOL)

    Plasma Triglyceride and Cholesterol Levels in Normotensive and Hypertensive Pregnant and Parturient Nigerian Women. Kashope D. Thomas, Oyebola G. Adeosun, Norah O. Akinola, Uche Onwudiegwu, Alexander T. Owolabi ...

  17. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

    Science.gov (United States)

    Patton, N M; Brown, R V; Middleton, C C

    1975-01-01

    Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

  18. High Cholesterol and Complementary Health Practices: What the Science Says

    Science.gov (United States)

    ... professionals High Cholesterol and Complementary Health Practices: What the Science Says Share: February 2013 Dietary Supplements Red Yeast ... to exploring complementary health products and practices in the context of rigorous ... health researchers, and disseminating authoritative information ...

  19. Vertically aligned carbon nanotube probes for monitoring blood cholesterol

    Science.gov (United States)

    Roy, Somenath; Vedala, Harindra; Choi, Wonbong

    2006-02-01

    Detection of blood cholesterol is of great clinical significance. The amperometric detection technique was used for the enzymatic assay of total cholesterol. Multiwall carbon nanotubes (MWNTs), vertically aligned on a silicon platform, promote heterogeneous electron transfer between the enzyme and the working electrode. Surface modification of the MWNT with a biocompatible polymer, polyvinyl alcohol (PVA), converted the hydrophobic nanotube surface into a highly hydrophilic one, which facilitates efficient attachment of biomolecules. The fabricated working electrodes showed a linear relationship between cholesterol concentration and the output signal. The efficacy of the multiwall carbon nanotubes in promoting heterogeneous electron transfer was evident by distinct electrochemical peaks and higher signal-to-noise ratio as compared to the Au electrode with identical enzyme immobilization protocol. The selectivity of the cholesterol sensor in the presence of common interferents present in human blood, e.g. uric acid, ascorbic acid and glucose, is also reported.

  20. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...