In vivo studies with an intravascular and intracardiac reflection oximeter

1962 ◽  
Vol 17 (3) ◽  
pp. 552-558 ◽  
Author(s):  
Y. Enson ◽  
W. A. Briscoe ◽  
M. L. Polanyi ◽  
A. Cournand
Keyword(s):  
Oxygen Saturation ◽  
Glass Fibers ◽  
Blood Stream ◽  
In Vivo Studies ◽  
Pulsatile Blood Flow ◽  
Cardiac Catheter ◽  
Reflected Light

An oximeter is described which employs two bundles of flexible glass fibers to conduct appropriately filtered light into, and that light diffusely reflected by the blood out of, the blood stream for the determination of oxygen saturation or dye concentration within blood flowing past the tip of either an arterial needle or a cardiac catheter which contains both bundles. The ratio of intensities of the reflected light at two wavelengths is linearly related to oxygen saturation (IRR805/ IRR660) and dye concentration (IRR900/IRR805). Data is reported in vivo and in vitro with respect to accuracy of the determinations (± 1.9%). The effect of patient-to-patient variation in hematocrit and other factors, and of pulsatile blood flow, is described. Application of the technique to physiologic study is illustrated, and theoretical aspects of reflection oximetry, as they apply to the instrument, are discussed. Submitted on November 17, 1961

Determination of major metabolites of MAM-2201 and JWH-122 in in vitro and in vivo studies to distinguish their intake

2014 ◽  
Vol 244 ◽  
pp. 85-91 ◽  
Author(s):  
Moonhee Jang ◽  
Ilchung Shin ◽  
Wonkyung Yang ◽  
Hyejin Chang ◽  
Hye Hyun Yoo ◽  
...  
Keyword(s):  
In Vivo Studies

scholarly journals Environmental Modulation of Oral Treponeme Virulence in a Murine Model

1999 ◽  
Vol 67 (6) ◽  
pp. 2783-2789 ◽  
Author(s):  
Lakshmyya Kesavalu ◽  
Stanley C. Holt ◽  
Jeffrey L. Ebersole
Keyword(s):  
Lesion Size ◽  
In Vivo Studies ◽  
Iron Availability ◽  
Environmental Alteration ◽  
Induction Kinetics ◽  
Focus Of Infection ◽  
Systemic Manifestations

ABSTRACT This investigation examined the effects of environmental alteration on the virulence of the oral treponemes Treponema denticolaand Treponema pectinovorum. The environmental effects were assessed by using a model of localized inflammatory abscesses in mice. In vitro growth of T. denticola and T. pectinovorum as a function of modification of the cysteine concentration significantly enhanced abscess formation and size. In contrast, growth of T. denticola or T. pectinovorum under iron-limiting conditions (e.g., dipyridyl chelation) had no effect on abscess induction in comparison to that when the strains were grown under normal iron conditions. In vivo modulation of the microenvironment at the focus of infection with Cytodex beads demonstrated that increasing the local inflammation had no effect on lesion induction or size. In vivo studies involved the determination of the effects of increased systemic iron availability (e.g., iron dextran or phenylhydrazine) on the induction, kinetics, and size of lesions. T. denticola induced significantly larger lesions in mice with iron pretreatment and demonstrated systemic manifestations of the infectious challenge and an accompanying spreading lesion with phenylhydrazine pretreatment (e.g., increases in circulating free hemoglobin). In contrast, T. pectinovorum virulence was minimally affected by this in vivo treatment to increase iron availability. T. denticolavirulence, as evaluated by lesion size, was increased additively by in vivo iron availability, and cysteine modified growth of the microorganism. Additionally, galactosamine sensitized mice to a lethal outcome following infection with both T. denticola andT. pectinovorum, suggesting an endotoxin-like activity in these treponemes. These findings demonstrated the ability to modify the virulence capacity of T. denticola andT. pectinovorum by environmental conditions which can be evaluated by using in vivo murine models.

scholarly journals ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Silvia Pietrobono ◽  
Giulia Anichini ◽  
Cesare Sala ◽  
Fabrizio Manetti ◽  
Luciana L. Almada ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Treatment Options ◽  
Blood Stream ◽  
In Vivo Studies ◽  
Melanoma Metastasis ◽  
Melanoma Invasion ◽  
Molecular Events ◽  
Transcriptional Complex

AbstractUnderstanding the molecular events controlling melanoma progression is of paramount importance for the development of alternative treatment options for this devastating disease. Here we report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, we demonstrate that ST3GAL1 drives melanoma metastasis. Silencing of this enzyme suppresses melanoma invasion and significantly reduces the ability of aggressive melanoma cells to enter the blood stream, colonize distal organs, seed and survive in the metastatic environment. Analysis of glycosylated proteins reveals that the receptor tyrosine kinase AXL is a major effector of ST3GAL1 pro-invasive function. ST3GAL1 induces AXL dimerization and activation that, in turn, promotes melanoma invasion. Our data support a key role of the ST3GAL1-AXL axis as driver of melanoma metastasis, and highlight the therapeutic potential of targeting this axis to treat metastatic melanoma.

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches

2007 ◽  
Vol 27 (1-3) ◽  
pp. 151-163 ◽  
Author(s):  
M. C. Lara ◽  
M. L. Valentino ◽  
J. Torres-Torronteras ◽  
M. Hirano ◽  
R. Martí
Keyword(s):  
Molecular Genetic ◽  
In Vivo Studies ◽  
Gene Encoding ◽  
Mitochondrial Neurogastrointestinal Encephalomyopathy ◽  
Mtdna Replication ◽  
Biochemical Features

Over the last 15 years, important research has expanded our knowledge of the clinical, molecular genetic, and biochemical features of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The characterization of mitochondrial involvement in this disorder and the seminal determination of its genetic cause, have opened new possibilities for more detailed and deeper studies on the pathomechanisms in this progressive and fatal disease. It has been established that MNGIE is caused by mutations in the gene encoding thymidine phosphorylase (TP), which lead to absolute or nearly complete loss of its catalytic activity, producing systemic accumulations of its substrates, thymidine (dThd) and deoxyuridine (dUrd). Findings obtained from in vitro and in vivo studies indicate that the biochemical imbalances specifically impair mitochondrial DNA (mtDNA) replication, repair, or both leading to mitochondrial dysfunction. We have proposed that therapy for MNGIE should be aimed at reducing the concentrations of these toxic nucleosides to normal or nearly normal levels. The first treatment, allogeneic stem-cell transplantation (alloSCT) reported in 2006, produced a nearly full biochemical correction of the dThd and dUrd imbalances in blood. Clinical follow-up of this and other patients receiving alloSCT is necessary to determine whether this and other therapies based on a permanent restoration of TP will be effective treatment for MNGIE.

scholarly journals A general model to calculate the spin-lattice (T1) relaxation time of blood, accounting for haematocrit, oxygen saturation and magnetic field strength

2015 ◽  
Vol 36 (2) ◽  
pp. 370-374 ◽  
Author(s):  
Patrick W Hales ◽  
Fenella J Kirkham ◽  
Christopher A Clark
Keyword(s):  
Magnetic Field ◽  
Relaxation Time ◽  
Oxygen Saturation ◽  
In Vivo Studies ◽  
T1 Relaxation Time ◽  
Spin Lattice ◽  
T1 Relaxation ◽  
Improved Accuracy

Many MRI techniques require prior knowledge of the T1-relaxation time of blood ( T1 bl). An assumed/fixed value is often used; however, T1 bl is sensitive to magnetic field ( B0), haematocrit ( Hct), and oxygen saturation ( Y). We aimed to combine data from previous in vitro measurements into a mathematical model, to estimate T1 bl as a function of B0, Hct, and Y. The model was shown to predict T1 bl from in vivo studies with a good accuracy (±87 ms). This model allows for improved estimation of T1 bl between 1.5–7.0 T while accounting for variations in Hct and Y, leading to improved accuracy of MRI-derived perfusion measurements.

scholarly journals Gouda Cheese with Modified Content of β-Casein as a Source of Peptides with ACE- and DPP-IV-Inhibiting Bioactivity: A Study Based on In Silico and In Vitro Protocol

2021 ◽  
Vol 22 (6) ◽  
pp. 2949
Author(s):  
Anna Iwaniak ◽  
Damir Mogut ◽  
Piotr Minkiewicz ◽  
Justyna Żulewska ◽  
Małgorzata Darewicz
Keyword(s):  
In Silico ◽  
Ace Inhibition ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Quantitative Parameters ◽  
Dpp Iv ◽  
Gouda Cheese

In silico and in vitro methods were used to analyze ACE- and DPP-IV-inhibiting potential of Gouda cheese with a modified content of β-casein. Firstly, the BIOPEP-UWM database was used to predict the presence of ACE and DPP-IV inhibitors in casein sequences. Then, the following Gouda cheeses were produced: with decreased, increased, and normative content of β-casein after 1 and 60 days of ripening each (six variants in total). Finally, determination of the ACE/DPP-IV-inhibitory activity and the identification of peptides in respective Gouda-derived water-soluble extracts were carried out. The identification analyses were supported with in silico calculations, i.e., heatmaps and quantitative parameters. All Gouda variants exhibited comparable ACE inhibition, whereas DPP-IV inhibition was more diversified among the samples. The samples derived from Gouda with the increased content of β-casein (both stages of ripening) had the highest DPP-IV-inhibiting potency compared to the same samples measured for ACE inhibition. Regardless of the results concerning ACE and DPP-IV inhibition among the cheese samples, the heatmap showed that the latter bioactivity was predominant in all Gouda variants, presumably because it was based on the qualitative approach (i.e., peptide presence in the sample). Our heatmap did not include the bioactivity of a single peptide as well as its quantity in the sample. In turn, the quantitative parameters showed that the best sources of ACE/DPP-IV inhibitors were all Gouda-derived extracts obtained after 60 days of the ripening. Although our protocol was efficient in showing some regularities among Gouda cheese variants, in vivo studies are recommended for more extensive investigations of this subject.

scholarly journals Determination of potential solvents for novel N-substituted 5-(phenylamino)uracil derivatives and evaluation of their cytotoxic effects on Vero 76 Cells

2019 ◽  
pp. 19-29
Author(s):  
Noor Fahitah Abu Hanipah ◽  
Noor Farah Omar Ahmad ◽  
Minaketan Tripathy ◽  
Elena Gureeva ◽  
Michail Novikov ◽  
...  
Keyword(s):  
Cell Viability ◽  
Sodium Benzoate ◽  
Aqueous Media ◽  
In Vivo Studies ◽  
Cytotoxic Effects ◽  
Uracil Derivatives ◽  
Cytotoxicity Assays

N-substituted 5-(phenylamino)uracil derivatives have recently shown to possess potential antiviral properties. However, the high lipophilicity of these compounds has limited their ability to be dissolved in aqueous media for further in vitro and in vivo studies. This study aimed to determine the potential solvents for novel N-substituted 5-(phenylamino)uracil compounds and to evaluate the cytotoxic effects of these solvents on Vero 76 cells. Eight solvents, namely acetone, methanol, ethanol, dimethyl sulfoxide (DMSO), polyvinylpyrrolidone, nicotinamide, L-arginine, and sodium benzoate, were used to dissolve 1600 µM each of compound Z214 and compound Z276, which were chosen as the representatives of novel N-substituted 5-(phenylamino)uracil derivatives. Only L-arginine (700 mM), sodium benzoate (1500 mM), and DMSO (128 mM) were able to solubilise both compounds. Cytotoxicity assays on Vero 76 cells have shown that the maximum concentrations of L-arginine, sodium benzoate, and DMSO that demonstrated 100% cell viability were 108 mM, 10 mM, and 211 mM respectively. L-arginine at concentrations ranged from 215 mM to 860 mM have shown to significantly increased cell proliferation; while both sodium benzoate and DMSO have significantly reduced cell viability at concentrations ≥ 10 mM and ≥ 211 mM respectively. CC50 values were 23.22 mM and 214.92 mM for sodium benzoate and DMSO respectively. The findings in this study revealed that DMSO at a concentration of 211 mM was found to be the most appropriate solvent to solubilise 1600 µM and below of novel N-Substituted 5-(phenylamino)uracil derivatives.

In vitro and in vivo Evaluation of the Radiochemical Compound Based on 99mTechnetium Labelled DARPin 9_29 for Molecular Visualization of Malignancies Overexpressing Her2/neu

2020 ◽  
Vol 65 (1) ◽  
pp. 37-41
Author(s):  
O. Bragina ◽  
A. Vorobyeva ◽  
V. Tolmachev ◽  
A. Orlova ◽  
V. Chernov ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Radiochemical Yield ◽  
Blood Stream ◽  
The Body ◽  
Diagnostic Methods ◽  
In Vivo Studies ◽  
In Vivo Evaluation ◽  
High Accumulation

Purpose: Evaluation of a radiopharmaceutical based on 99mTc-labeled targeted molecules DARPin9_29 for radionuclide diagnostics of malignancies with Her2/neu overexpression. Material and methods: The DARPin9_29 sequence was amplified from the plasmid pET-DARP-6HIS for the DARPin9_29-His6 gene expression in E. coli cells. The eluent of 99mTcO4– (400–500 μl, 4 GBq) was added to the kit and incubated at a temperature of 100 °C for 20 minutes. After incubation, 40 μl of tricarbonyl technetium was added to 168 μg of DARPin9_29 in 100 μl of PBS (sodium phosphate buffer), followed by incubation at 40 °C for 60 minutes. The radiochemical yield and purity were determined by thin layer radiochromatography, the purification was performed using NAP-5 cleansing columns (GE Healthcare). Cell lines with different levels of Her2/neu expression were used: SKOV-3> BT474 >> DU-145 for the determination of the radiopharmaceutical specificity. Her2/neu expressing cell line SKOV-3 was used for in vitro study. The study was conducted 6 hours after the administration of the drug. Results: The radiochemical yield was 72 ± 8 %, the radiochemical purity after purification was 98.7 ± 1.0 %. The stability in PBS (phosphate buffered saline) solution after 1 hour was 99.8 ± 0.2; after 3 hours – 98.2 ± 0.1. In vitro studies showed that the accumulation of explored compound was directly proportional to the level of Her2/neu expression in cells, while blocking the receptors with an excess of unlabeled protein showed a significant reduction in binding in the group of cells. Data on biodistribution and SPECT/CT in the body of the animal BALB/c nu/nu demonstrated rapid removal of the compound from the blood stream and high accumulation in the liver, kidney and bladder 6 hours after the introduction of the radiopharmaceutical. Conclusion: The studies demonstrated high radiochemical yields and purity, as well as stability of the studied compound. The results of in vitro and in vivo analysis showed the specificity and affinity of the radiopharmaceutical to the Her2/neu receptor on the surface of tumor cells. The high accumulation of the drug in the liver and kidneys, detected in in vivo studies, is probably due to the lipophilicity of the 99mTc(CO)3-histidine tag and indicates the limitation of its further clinical use in assessing the condition of the above organs, which will require additional diagnostic methods, as well as possible modification chemical structure.

scholarly journals Lack of Evidence for In Vivo Transformation of Zidovudine Triphosphate to Stavudine Triphosphate in Human Immunodeficiency Virus-Infected Patients

2006 ◽  
Vol 50 (3) ◽  
pp. 835-840 ◽  
Author(s):  
Margarita Meléndez ◽  
Raúl Blanco ◽  
Wilfredo Delgado ◽  
Rosario García ◽  
Jorge Santana ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Immunodeficiency Virus ◽  
High Performance ◽  
In Vivo Studies ◽  
Tandem Mass ◽  
Limit Of Quantitation ◽  
Immunodeficiency Virus

ABSTRACT The in vivo and in vitro determination of significant intracellular stavudine (d4T) triphosphate (d4TTP) concentrations in human immunodeficiency virus (HIV)-infected subjects and NS-1 cells treated with zidovudine (ZDV) has recently been reported. This study was conducted to corroborate these findings with in vivo samples from HIV-infected subjects taking ZDV and in vitro CEMSS cells incubated with different ZDV concentrations. Previously, we have reported on our validated high-performance liquid chromatography coupled with tandem mass spectrometry methodology for the simultaneous determination of d4TTP, lamivudine triphosphate, and ZDV triphosphate (ZDVTP) concentrations. Using this methodology, we monitored the d4TTP concentration in more than 100 samples from HIV-infected subjects treated with d4T. In addition, we simultaneously monitored the concentrations of d4TTP and ZDVTP in more than 500 samples from HIV-infected individuals who were taking ZDV. Finally, we performed in vitro studies by incubating CEMSS cells with 10 μM, 50 μM, and 100 μM ZDV and monitored the formation of d4TTP at 24 and 48 h. We could measure d4TTP concentrations from HIV-infected individuals with a limit of quantitation (LOQ) of 2.7 fmol/106 cells (total injection, 54 fmol). In the in vivo studies, we measured the d4TTP concentrations among patients receiving d4T treatment, but the samples from patients taking ZDV did not provide d4TTP concentrations above the LOQ. Furthermore, in vitro samples did not produce any signal for d4TTP, despite the detection of substantial ZDVTP concentrations in CEMSS cells. Thus, contrary to the previous report, we found no evidence for the in vivo or in vitro transformation of ZDVTP to d4TTP in HIV-infected subjects or CEMSS cells.

Sign in / Sign up

Export Citation Format

Share Document