Novel insight on the impact of choline-deficiency in sepsis

Abstract Choline (Ch) exerts a key role as methyl donor in the one carbon pathway and is an essential nutrient for the optimal development and function of a number of biological systems including the cardiovascular and urinary system. Ch-deprivation has been associated with heart function impairment, insulin resistance, abnormal fat metabolism and acute kidney injury. Diabetes mellitus is a common metabolic disorder with increased prevalence in aging and diabetic patients are of higher risk to develop heart and kidney failure. This study aims to investigate the impact of dietary Ch-deprivation on cardiac and renal function in a streptozotocin (STZ) experimentally induced diabetic setting. Twenty-four male adult Wistar rats, were randomly separated into four groups: control, choline deficient through choline deficient diet (CD), STZ induced diabetic (DM) and diabetic-choline deficient (DM+CD) group. After 5 weeks of dietary intervention, echocardiographic measurements, myocardium and kidney histological examination along with Vascular Endothelial Growth Factor-A (VEGF-A165) and Kidney Injury Molecule-1 (KIM-1) immunohistochemistry expression were performed. DM+CD rats demonstrated an exacerbation of myocardial inflammation and fibrosis accompanied by preserved ejection fraction but with an increased left ventricular (LV) wall tension index and velocity and a decreased LV posterior wall thickness compared to DM group. VEGF-A165 expression both in heart and kidneys was abruptly upregulated in the CD rats with a downward trend under the diabetes mellitus entity reaching significant downregulation in the renal tissue. KIM-1 expression was significantly increased under the insult of both choline deficiency and diabetes mellitus depicting a possible synergistic, though detrimental, effect compared to each condition alone. In conclusion, five weeks of dietary choline deprivation aggravates the inflammation and fibrosis in the heart and kidneys of diabetic rats leading to organ dysfunction. The structural impairment of the choline deprived diabetic heart with evidence of stiffness and dilation of the left ventricular cavity with preserved systolic function indicates the emergence of a new distinct phenotype of cardiomyopathy that combines features of the restrictive and dilated type at the same time. Moreover, in this setting the kidney injury gets worse implying that diabetic nephropathy might establish earlier and accelerate more quickly in choline deficiency conditions.

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Carnitine modulates crucial myocardial adenosine triphosphatases and acetylcholinesterase enzyme activities in choline-deprived rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0165 ◽

2014 ◽

Vol 92 (1) ◽

pp. 78-84 ◽

Cited By ~ 1

Author(s):

Athina A. Strilakou ◽

Stylianos T. Tsakiris ◽

Konstantinos G. Kalafatakis ◽

Aikaterini T. Stylianaki ◽

Petros L. Karkalousos ◽

...

Keyword(s):

Atpase Activity ◽

Enzyme Activities ◽

Cardiac Contraction ◽

Carnitine Supplementation ◽

Choline Deficiency ◽

Deficient Diet ◽

Adenosine Triphosphatases ◽

Essential Nutrient ◽

Acetylcholinesterase Enzyme ◽

The Impact

Choline is an essential nutrient, and choline deficiency has been associated with cardiovascular morbidity. Choline is also the precursor of acetylcholine (cholinergic component of the heart’s autonomic nervous system), whose levels are regulated by acetylcholinesterase (AChE). Cardiac contraction–relaxation cycles depend on ion gradients established by pumps like the adenosine triphosphatases (ATPases) Na+/K+-ATPase and Mg2+-ATPase. This study aimed to investigate the impact of dietary choline deprivation on the activity of rat myocardial AChE (cholinergic marker), Na+/K+-ATPase, and Mg2+-ATPase, and the possible effects of carnitine supplementation (carnitine, structurally relevant to choline, is used as an adjunct in treating cardiac diseases). Adult male albino Wistar rats were distributed among 4 groups, and were fed a standard or choline-deficient diet for one month with or without carnitine in their drinking water (0.15% w/v). The enzyme activities were determined spectrophotometrically in the myocardium homogenate. Choline deficiency seems to affect the activity of the aforementioned parameters, but only the combination of choline deprivation and carnitine supplementation increased myocardial Na+/K+-ATPase activity along with a concomitant decrease in the activities of Mg2+-ATPase and AChE. The results suggest that carnitine, in the setting of choline deficiency, modulates cholinergic myocardial neurotransmission and the ATPase activity in favour of cardiac work efficiency.

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Formation of Lunar Craters and Bright Rays as a Result of Meteorite Impacts

Symposium - International Astronomical Union ◽

10.1017/s0074180900178404 ◽

1962 ◽

Vol 14 ◽

pp. 415-418

Author(s):

K. P. Stanyukovich ◽

V. A. Bronshten

Keyword(s):

Explosive Charge ◽

The Moon ◽

Meteorite Impacts ◽

The Earth ◽

Lunar Craters ◽

The Impact

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.

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The Geosciences Applied to Lunar Exploration

Symposium - International Astronomical Union ◽

10.1017/s0074180900178222 ◽

1962 ◽

Vol 14 ◽

pp. 169-257 ◽

Cited By ~ 9

Author(s):

J. Green

Keyword(s):

Lunar Surface ◽

Probable Mechanism ◽

Point Of View ◽

Lunar Exploration ◽

Geological Model ◽

Apply Geophysics ◽

Surface Features ◽

The Impact

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.

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Asteroid and Comet Impact Speeds upon Mars: Significance for Panspermia and the Supply of Organics

International Astronomical Union Colloquium ◽

10.1017/s0252921100014718 ◽

1997 ◽

Vol 161 ◽

pp. 197-201 ◽

Cited By ~ 1

Author(s):

Duncan Steel

Keyword(s):

Probability Distributions ◽

Regions Of Interest ◽

Significant Fraction ◽

Organic Chemicals ◽

Impact Speed ◽

The Mean ◽

The Impact

AbstractWhilst lithopanspermia depends upon massive impacts occurring at a speed above some limit, the intact delivery of organic chemicals or other volatiles to a planet requires the impact speed to be below some other limit such that a significant fraction of that material escapes destruction. Thus the two opposite ends of the impact speed distributions are the regions of interest in the bioastronomical context, whereas much modelling work on impacts delivers, or makes use of, only the mean speed. Here the probability distributions of impact speeds upon Mars are calculated for (i) the orbital distribution of known asteroids; and (ii) the expected distribution of near-parabolic cometary orbits. It is found that cometary impacts are far more likely to eject rocks from Mars (over 99 percent of the cometary impacts are at speeds above 20 km/sec, but at most 5 percent of the asteroidal impacts); paradoxically, the objects impacting at speeds low enough to make organic/volatile survival possible (the asteroids) are those which are depleted in such species.

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Organic Syntheses During the Impact of a Comet with a Gaseous Planet

International Astronomical Union Colloquium ◽

10.1017/s0252921100014706 ◽

1997 ◽

Vol 161 ◽

pp. 189-195

Author(s):

Cesare Guaita ◽

Roberto Crippa ◽

Federico Manzini

Keyword(s):

Polymeric Material ◽

Molecular Form ◽

Parent Compound ◽

Blue Filter ◽

Organic Syntheses ◽

The Impact

AbstractA large amount of CO has been detected above many SL9/Jupiter impacts. This gas was never detected before the collision. So, in our opinion, CO was released from a parent compound during the collision. We identify this compound as POM (polyoxymethylene), a formaldehyde (HCHO) polymer that, when suddenly heated, reformes monomeric HCHO. At temperatures higher than 1200°K HCHO cannot exist in molecular form and the most probable result of its decomposition is the formation of CO. At lower temperatures, HCHO can react with NH3 and/or HCN to form high UV-absorbing polymeric material. In our opinion, this kind of material has also to be taken in to account to explain the complex evolution of some SL9 impacts that we observed in CCD images taken with a blue filter.

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Hydrogen Cyanide Polymers from the Impact of Comet P/Shoemaker-Levy 9 on Jupiter

International Astronomical Union Colloquium ◽

10.1017/s025292110001469x ◽

1997 ◽

Vol 161 ◽

pp. 179-187

Author(s):

Clifford N. Matthews ◽

Rose A. Pesce-Rodriguez ◽

Shirley A. Liebman

Keyword(s):

Amino Acids ◽

Solar System ◽

Hydrogen Cyanide ◽

Nitrogen Heterocycles ◽

Laboratory Studies ◽

Heterogeneous Solids ◽

The Many ◽

Comet Halley ◽

The Impact ◽

By Products

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.

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Unusual Microstructure in Shock-Compacted Graphite

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069363 ◽

1970 ◽

Vol 28 ◽

pp. 474-475

Author(s):

Lucien F. Trueb

Keyword(s):

Mechanical Characteristic ◽

Compression Wave ◽

Gray Zone ◽

Flyer Plate ◽

Compacted Graphite ◽

The Impact

Crushed and statically compressed Madagascar graphite that was explosively shocked at 425 kb by means of a planar flyer-plate is characterized by a black zone extending for 2 to 3 nun below the impact plane of the driver. Beyond this point, the material assumes the normal gray color of graphite. The thickness of the black zone is identical with the distance taken by the relaxation wave to overtake the compression wave.The main mechanical characteristic of the black material is its great hardness; steel scalpels and razor blades are readily blunted during attempts to cut it. An average microhardness value of 95-3 DPHN was obtained with a 10 kg load. This figure is a minimum because the indentations were usually cracked; 14.8 DPHN was measured in the gray zone.

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Mitochondrial Changes in Choline-Deficient Rat Myocardium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100305 ◽

1968 ◽

Vol 26 ◽

pp. 112-113

Author(s):

F. G. Zaki

Keyword(s):

Muscle Fibers ◽

Liver Mitochondria ◽

Ultrastructural Changes ◽

Choline Deficiency ◽

Nutritional Disorder ◽

Low Protein ◽

Structural Abnormalities ◽

Cross Striation ◽

Pericardial Edema ◽

Myocardial Lesions

Choline-deficiency was induced in Holtzman young rats of both sexes by feeding them a high fat - low protein diet.Preliminary studies of the ultrastructural changes in the myocardium of these animals have been recently reported from this laboratory. Myocardial lesions first appeared in the form of intraventricular mural thrombi, loss of cross striation of muscle fibers and focal necrosis of muscle cells associated with interstitial myocarditis. Prolonged choline-deficiency induced cardiomegaly associated with pericardial edema.During the early phase of this nutritional disorder, heart mitochondria - despite of not showing any swelling similar to that usually encountered in liver mitochondria of the same animal - ware the most ubiquitous site of marked structural abnormalities. Early changes in mitochondria appeared as vacuolation, disorganization, disruption and loss of cristae. Degenerating mitochondria were often seen quite enlarged and their matrix was replaced by whorls of myelin figures resembling lysosomal structures especially where muscle fibers were undergoing necrosis. In some areas, mitochondria appeared to be unusually clumped together where some contained membranelined vacuoles and others enclosed dense bodies and granular inclusions.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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