Biosynthesis of Trimethylammonium Compounds in Aquatic Animals: I. Formation of Trimethylamine Oxide and Betaine from C14-labelled Compounds by Lobster (Homarus americanus)

1960 ◽  
Vol 17 (6) ◽  
pp. 895-902 ◽  
Author(s):  
E. Bilinski
Keyword(s):  
Homarus Americanus ◽  
Abdominal Muscle ◽  
Whole Body ◽  
Aquatic Animals ◽  
Radioactive Carbon ◽  
Trimethylamine Oxide ◽  
Good Precursor

The formation of trimethylamine oxide and betaine in lobster has been studied in vivo with radioactive carbon. C14-labelled compounds, tested as possible precursors, were administered to lobsters by injection into the abdominal muscle. Incorporation of the tracer into trimethylamine oxide and betaine, isolated from the whole body, was followed after a metabolic period of 24 and 72 hours.Administration of Na formate-C14, DL-serine-3-C14and glycine-2-C14does not lead to labelling of trimethylamine oxide. L-methionine-methyl-C14was a poor precursor of trimethylamine oxide, compared with choline-methyl-C14. These findings suggest a possible function for choline or a derivative in trimethylamine oxide biosynthesis.It appears that the formation of betaine in lobster takes place by oxidation of choline rather than by methylation of glycine. Choline-methyl-C14was found to be a very good precursor, whereas glycine-2-C14was not converted to betaine.

Biosynthesis of Trimethylammonium Compounds in Aquatic Animals: III. Choline Metabolism in Marine Crustacea

1962 ◽  
Vol 19 (3) ◽  
pp. 505-510 ◽  
Author(s):  
E. Bilinski
Keyword(s):  
Homarus Americanus ◽  
The Other ◽  
Intramuscular Administration ◽  
Cancer Magister ◽  
Aquatic Animals ◽  
Choline Metabolism ◽  
Trimethylamine Oxide

The incorporation in vivo of radioactivity into phospholipid-bound choline has been studied in lobster (Homarus americanus) following intramuscular administration of Na-formate-C14, glycine-2-C14, DL-serine-3-C14, L-methionine-methyl-C14 and choline-methyl-C14. Choline and methionine were utilized for formation of phospholipid choline at both metabolic periods of 24 and 72 hours, whereas the other compounds gave only a very limited labelling.When choline-methyl-C14 was administered to crab (Cancer magister), after 24 hours 1.9% of the administered radioactivity was found in phospholipid choline and 0.1% in trimethylamine oxide.

Biosynthesis of Trimethylammonium Compounds in Aquatic Animals: IV. Precursors of Trimethylamine Oxide and Betaine in Marine Teleosts

1964 ◽  
Vol 21 (4) ◽  
pp. 765-771 ◽  
Author(s):  
E. Bilinski
Keyword(s):  
Metabolic Pathways ◽  
Sodium Acetate ◽  
Sodium Formate ◽  
Whole Body ◽  
Platichthys Stellatus ◽  
Trimethylamine Oxide ◽  
Dragendorff Reagent ◽  
Limited Degree ◽  
Parophrys Vetulus

An in-vivo study was made of potential precursors of trimethylamine oxide (TMAO) in marine teleosts (lemon sole, Parophrys vetulus, and starry flounder, Platichthys stellatus). C14-labelled compounds were administered intraperitoneally and the incorporation of tracer into TMAO, isolated from the whole body, was determined. Trimethylamine (TMA)-C14 was found to be a much better precursor than the other compounds tested. A limited labelling of TMAO was observed after administration of γ-butyrobetaine-methyl-C14, betaine-methyl-C14 and methionine-methyl-C14. There was little or no incorporation of C14 into TMAO after administration of methylamine-C14, carnitine-methyl-C14, gIycine-2-C14, sodium formate-C14, sodium acetate-1-C14, sodium acetate-2-C14 and NaHCO3-C14. The conversion of choline-methyl-C14 to TMAO was higher after intraperitoneal than after intramuscular injection and only trace amounts of radioactivity were found after intravenous injection. The results provide support for formation of TMAO in fish by oxidation of TMA but they give no clear indication for metabolic pathways leading to this oxidative step.Betaine was isolated from fish after administration of choline-methyl-C14, methionine-methyl-C14 and glycine-2-C14. Evidence of extensive conversion of choline to betaine was obtained. Betaine also was found to be labelled after administration of methionine-methyl-C14, but only a limited degree of labelling was observed after administration of glycine-2-C14. The results indicate that betaine is formed by oxidation of choline in fish.A modification of the Dragendorff reagent for use as a spray for detecting trimethylammonium compounds on paper chromatograms is described.

Maintenance and accumulation of trimethylamine oxide by winter skate (Leucoraja ocellata): reliance on low whole animal losses rather than synthesis

2006 ◽  
Vol 291 (6) ◽  
pp. R1790-R1798 ◽  
Author(s):  
Jason R. Treberg ◽  
William R. Driedzic
Keyword(s):  
Whole Body ◽  
In Vitro Techniques ◽  
Organic Osmolyte ◽  
Trimethylamine Oxide ◽  
Endogenous Synthesis

Trimethylamine oxide (TMAO) is typically accumulated as an organic osmolyte in marine elasmobranchs to levels second only to urea (which can reach >400 mM); however, little is known about the whole animal regulation of TMAO in elasmobranchs. In the present study on the winter skate ( Leucoraja ocellata), we determine whether this species can maintain levels of TMAO in the absence of feeding, and if so, is this due to endogenous synthesis or low whole animal losses. Winter skates maintain plasma TMAO levels for up to 45 days without feeding. The liver displays methimazole oxidation, which is consistent with the presence of flavin-containing monooxygenase (E.C. 1.14.13.8 ) activity, the class of enzymes responsible for the physiological oxygenation of trimethylamine (TMA) to TMAO in mammals. However, no evidence for TMA oxygenation by winter skates was found using in vivo or in vitro techniques, indicating no significant capacity for endogenous TMAO synthesis. Fed skates displayed low, but measurable (∼4–13 μmol·kg−1·h−1), efflux of TMAO (plus TMA), whereas fasted skates did not. Using the loss of injected [14C]TMAO, it was determined that whole animal TMAO losses are likely <1% of whole body TMAO per day. These results demonstrate that winter skates utilize low whole animal TMAO losses, rather than endogenous synthesis, to maintain TMAO levels when not feeding.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

scholarly journals Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
KyeongJin Kim ◽  
Jin Ku Kang ◽  
Young Hoon Jung ◽  
Sang Bae Lee ◽  
Raffaela Rametta ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Whole Body ◽  
Acid Oxidation ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Ph Domain ◽  
Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

The Hemostatic Effect of 51Cr-Labelled Platelets

1975 ◽  
Author(s):  
J. Björnson ◽  
I. Aursnes
Keyword(s):  
Whole Body ◽  
Platelet Concentrates ◽  
Platelet Aggregability ◽  
Hemostatic Effect ◽  
Normal Platelet ◽  
Labelling Procedure

In the interpretation of data obtained with 51Cr-labelled platelets it is vital to know whether they are functionally normal. Although survival of 51Cr-labelled platelets in vivo appears to be normal, platelet aggregability- has recently been shown to be reduced after the labelling procedure (Björnson, J., Sc and. J. Haemat. 13, 252–259).The aim of the present study was to examine the hemostatic effect of labelled platelets. Rabbits were made thrombocytopenic (< 35,000/μ1) by whole body irradiation. Bleeding times were recorded after standardized cuts on the inner side of the ear, a method showing an acceptable reproducibility (< 3 min in normals). The animals were then transfused with labelled platelet concentrates, increasing the platelet levels to about 200,000/μ) blood. Bleeding times of more than 15 min before transfusion were almost normalized 1 and 4 hours after transfusion. In controls transfusion of PRP led to similar shortening of bleeing time.It is concluded that platelets subjected to the 51Cr-labelling procedure to a large extent retain their hemostatic ability.

scholarly journals IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Lan Hoang-Minh ◽  
Angelie Rivera-Rodriguez ◽  
Fernanda Pohl-Guimarães ◽  
Seth Currlin ◽  
Christina Von Roemeling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Adoptive T Cell Therapy ◽  
Whole Body ◽  
T Cell Therapy ◽  
Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

scholarly journals Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Andrew M. Holwerda ◽  
Philippe J. M. Pinckaers ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

Pressure Changes Induced by Whole Body Acceleration Shocks

1991 ◽  
Vol 113 (1) ◽  
pp. 27-29 ◽  
Author(s):  
E. Belardinelli ◽  
M. Ursino ◽  
G. Fabbri ◽  
A. Cevese ◽  
F. Schena
Keyword(s):  
Mathematical Model ◽  
Carotid Artery ◽  
Normal Pressure ◽  
Compressed Air ◽  
Whole Body ◽  
Body Acceleration ◽  
Vascular Bed ◽  
Pressure Changes ◽  
The Mathematical Model

In the present paper pressure changes induced by sudden body acceleration are studied “in vivo” on the dog and compared to the results obtainable with a recently developed mathematical model. A dog was fixed to a movable table, which was accelerated by a compressed air piston for less than 1 s. Acceleration was varied by changing the air pressure in the piston. Pressure was measured during the experiment at different points along the vascular bed. However, only data obtained in the carotid artery and abdominal aorta are presented here. The results demonstrated that impulse body accelerations cause significant pressure peaks in the vessel examined (about + 25 mmHg in the carotid artery with body acceleration of g/2). Moreover, pressure changes are rapidly damped, with a time constant of about 0.1s. From the present results it may be concluded that, according to the prediction of the mathematical model, body accelerations such as those occurring in normal life can induce pressure changes well beyond the normal pressure value.

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