Measurement of Cholesterol Biosynthesis in vivo with Tritiated Water

1978 ◽  
Vol 6 (5) ◽  
pp. 871-874 ◽  
Author(s):  
ROBIN FEARS
Keyword(s):  
Cholesterol Biosynthesis ◽  
Tritiated Water

scholarly journals Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

2002 ◽  
Vol 39 (3) ◽  
pp. 203-210 ◽  
Author(s):  
John R Burnett ◽  
Samuel D Vasikaran
Keyword(s):  
Cardiovascular Disease ◽  
Bone Density ◽  
Vascular Calcification ◽  
Cholesterol Biosynthesis ◽  
Hormone Replacement ◽  
Plasma Lipid ◽  
Clinical Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
The Relationship

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

scholarly journals The BET Inhibitor JQ1 Augments the Antitumor Efficacy of Gemcitabine in Preclinical Models of Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3470
Author(s):  
Aubrey L. Miller ◽  
Patrick L. Garcia ◽  
Samuel C. Fehling ◽  
Tracy L. Gamblin ◽  
Rebecca B. Vance ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Cholesterol Biosynthesis ◽  
Antitumor Efficacy ◽  
Rna Seq ◽  
Bet Inhibitor ◽  
Bet Inhibitors ◽  
Xenograft Models

Gemcitabine is used to treat pancreatic cancer (PC), but is not curative. We sought to determine whether gemcitabine + a BET bromodomain inhibitor was superior to gemcitabine, and identify proteins that may contribute to the efficacy of this combination. This study was based on observations that cell cycle dysregulation and DNA damage augment the efficacy of gemcitabine. BET inhibitors arrest cells in G1 and allow increases in DNA damage, likely due to inhibition of expression of DNA repair proteins Ku80 and RAD51. BET inhibitors (JQ1 or I-BET762) + gemcitabine were synergistic in vitro, in Panc1, MiaPaCa2 and Su86 PC cell lines. JQ1 + gemcitabine was more effective in vivo than either drug alone in patient-derived xenograft models (P < 0.01). Increases in the apoptosis marker cleaved caspase 3 and DNA damage marker γH2AX paralleled antitumor efficacy. Notably, RNA-seq data showed that JQ1 + gemcitabine selectively inhibited HMGCS2 and APOC1 ~6-fold, compared to controls. These proteins contribute to cholesterol biosynthesis and lipid metabolism, and their overexpression supports tumor cell proliferation. IPA data indicated that JQ1 + gemcitabine selectively inhibited the LXR/RXR activation pathway, suggesting the hypothesis that this inhibition may contribute to the observed in vivo efficacy of JQ1 + gemcitabine.

IN VIVO INHIBITION OF CHOLESTEROL BIOSYNTHESIS BY A MITOCHONDRIAL EXTRACT

1961 ◽  
Vol 39 (4) ◽  
pp. 747-755 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Liver Mitochondria ◽  
Blood Cholesterol ◽  
Active Principle ◽  
Aqueous Extracts ◽  
Inhibitory Substance ◽  
Cholesterol Levels ◽  
Mitochondrial Extract

Aqueous extracts of liver mitochondria were administered to rats by intraperitoneal, subcutaneous, and oral routes, and C14-acetate or mevalonate was injected intraperitoneally 3 hours later. Cholesterol synthesis in vivo from C14-acetate was depressed by the inhibitory substance in the mitochondrial extracts. Synthesis from C14-mevalonate was not inhibited.Active extracts were prepared from livers of rat, rabbit, pig, and sheep. An inhibitory substance is present in blood serum and administration of active mitochondrial extracts depressed blood cholesterol levels. Pending its identification, the active principle has been provisionally termed I.C.S. (inhibitor of cholesterol synthesis).

Body composition in vivo. III. The composition of living ruminants and its relation to the tritiated water spaces

1963 ◽  
Vol 14 (6) ◽  
pp. 944 ◽  
Author(s):  
BA Panaretto
Keyword(s):  
Body Composition ◽  
Tritiated Water ◽  
The Body ◽  
Precise Method

Two methods for predicting the body composition of living goats from the tritiated water spaces derived in them were proposed previously from results obtained with 11 goats. The relation of tritiated water spaces to body composition has been studied in an addltlonal 10 goats and 9 sheep, and these results together with those previousl y published have yielded a more precise method for calculating the body composition of living ruminants in terms of water, fat, protein, and ash.

scholarly journals Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo

2020 ◽  
Vol 62 (1) ◽  
pp. 34-45
Author(s):  
Hong Li ◽  
Yaru Yin ◽  
Jing Liu ◽  
Binghui Lu ◽  
Huimin Wan ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Tritiated Water ◽  
Intragastric Administration ◽  
Dna Oxidative Damage ◽  
Intracellular Ros ◽  
Endogenous Antioxidants ◽  
Production Industry ◽  
Radioprotective Agent

Abstract Radionuclide tritium is widely used in the nuclear energy production industry and creates a threat to human health through radiation exposure. Herein, the radioactive elimination and radioprotective effect of hydrogen-rich water (HRW), a potential antioxidant with various medical applications, on tritiated water (HTO) exposure, was studied in vitro and in vivo. Results showed that intragastric administration of HRW effectively promoted the elimination of urinary tritium, decreased the level of serum tritium and tissue-bound tritium (OBT), and attenuated the genetic damage of blood cells in mice exposed to HTO (18.5 MBq/kg). Pretreatment with HRW effectively reduces tritium accumulation in HTO-treated human blood B lymphocyte AHH-1 cells. In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO−), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to be an effective radioactive elimination agent through the competition effect of isotope exchange or a radioprotective agent by scavenging free radicals induced by HTO exposure.

Body composition in vivo. II. The composition of mature goats and its relationship to the antipyrine, tritiated water, and N-acetyl-4-aminoantipyrine spaces

1963 ◽  
Vol 14 (6) ◽  
pp. 926 ◽  
Author(s):  
BA Panaretto ◽  
AR Till
Keyword(s):  
Body Composition ◽  
Total Body Water ◽  
Tritiated Water ◽  
Body Water ◽  
Total Body

The antipyrine, tritiated water, and N-acetyl-4-aminoantipyrine spaces were determined simultaneously in goats which had been deprived of feed and water for 48 hr. The animals were then killed, minced, and analysed for water, fat, protein, and ash contents. The compositions of the whole and empty bodies of the goats were calculated, and the relationships between the bodily components were compared with those reported for cattle, sheep, and some monogastric species. The relationships found between the components of the whole bodies compared favourably with those derived from the empty bodies. The relationships of the spaces determined in vivo to total body water, fat, and protein were found, and confidence statements were placed on predicted estimates.

scholarly journals The prediction of body composition in poultry by estimation in vivo of total body water with tritiated water and deuterium oxide

1988 ◽  
Vol 59 (1) ◽  
pp. 109-124 ◽  
Author(s):  
R. J. Johnson ◽  
D. J. Farrell
Keyword(s):  
Body Composition ◽  
Isotope Dilution ◽  
Total Body Water ◽  
Deuterium Oxide ◽  
Tritiated Water ◽  
Live Weight ◽  
Body Water ◽  
Regression Equations ◽  
Total Body

1. Birds (n169) which varied in age, live weight, nutritional history, physiological state and genotype were slaughtered and analysed for total body water. Before slaughter, birds were injected with the water isotopes tritiated water (TOH) or deuterium oxide (D2O), or both, to determine TOH space or D2O space, or both, as estimates of total body water in vivo.2. At the mean total body water of all birds determined by desiccation, of 1096·4 (SD 424·1) g, TOH space and D2O space overestimated total body water by 10·4 and 8·5 % respectively. The difference between the isotopes was significant (P< 0·05).3. Based on recovery of isotope it was postulated that the main reason for the observed overestimation of total body water in vivo was incomplete recovery of isotope due to the vacuum sublimation technique. The mean recovery (%) of added isotope to whole blood after vacuum sublimation was 93·0 (SD 2·6) and 92·4 (SD 5·5) of the theoretical concentrations of TOH and D2O respectively.4. Nevertheless, accurate prediction of total body water was obtained from regression equations which included live weight and isotope-dilution space. Values required logarithmic (base 10) transformation before derivation of linear and multiple linear regression equations, and the precision of prediction was determined by the residual standard deviation (RSD).5. Total body water could be predicted with nearly equal accuracy from live weight or isotope-dilution space (RSD 0·025 and 0·020 respectively). Prediction of carcass protein was more accurate from live weight (RSD 0·033) than from TOH space (RSD 0·036), and inclusion of both variables resulted in only a marginal decrease in RSD to 0·031.6. The prediction of carcass fat and energy was markedly improved by the inclusion of isotope-dilution space in conjunction with live weight compared with live weight alone.7. The relations show the developmental nature of body composition of domestic fowl given diets adequate in nutrients. The prediction equations demonstrate the precision possible for studies in which estimates of body composition in poultry are required without slaughter.

scholarly journals Combination of Tenofovir and Emtricitabine with Efavirenz Does Not Moderate Inhibitory Effect of Efavirenz on Mitochondrial Function and Cholesterol Biosynthesis in Human T Lymphoblastoid Cell Line

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Min Li ◽  
Anuoluwapo Sopeyin ◽  
Elijah Paintsil
Keyword(s):  
Cell Line ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Lymphoblastoid Cell Line ◽  
Cholesterol Biosynthesis ◽  
Real Life ◽  
Mitochondrial Toxicity ◽  
And Function

ABSTRACT Efavirenz (EFV), the most popular nonnucleoside reverse transcriptase inhibitor, has been associated with mitochondrial dysfunction in most in vitro studies. However, in real life the prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the agents given in combination with EFV moderate the effect of EFV on mitochondrial function. To test this hypothesis, we cultured a human T lymphoblastoid cell line (CEM cells) with EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) to investigate the effects on mitochondrial respiration and function and cholesterol biosynthesis. There was a statistically significant concentration- and time-dependent apoptosis, reduction in mitochondrial membrane potential, and increase in production of reactive oxygen species in cells treated with either EVF alone or in combination with TDF plus FTC. Compared to dimethyl sulfoxide-treated cells, EFV-treated cells had significant reduction in oxygen consumption rate contributed by basal mitochondrial respiration and decreased protein expression of electron transport chain complexes (CI, CII, and CIV). Treatment with EFV resulted in a decrease in mitochondrial DNA content and perturbation of more coding genes (n = 13); among these were 11 genes associated with lipid or cholesterol biosynthesis. Our findings support the growing body of knowledge on the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. Interestingly, combining TDF and FTC with EFV did not alter the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. The gap between the prevalence of EFV-induced mitochondrial toxicity in in vitro and in vivo studies could be due to individual differences in the pharmacokinetics of EFV.

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