Kinetics of oxytocin and deaminooxytocin displacement from the OXTR -receptor compartment in rat uterus ex vivo

The influence of human T-cell leukemia/lymphoma virus type II (HTLV-II) in individuals also infected with HIV-1 is poorly understood. To evaluate the reciprocal influence of HTLV-II and HIV-1 infection, primary peripheral blood mononuclear cell (PBMC) cultures from coinfected individuals were established in the presence of interleukin 2 (IL-2). In these cultures, the kinetics of HTLV-II replication always preceded those of HIV-1. Noteworthy, the kinetics of HIV-1 production were inversely correlated to the HTLV-II proviral load in vivo and its replication ex vivo. These observations suggested a potential interaction between the 2 retroviruses. In this regard, the levels of IL-2, IL-6, and tumor necrosis factor- (TNF-) were measured in the same coinfected PBMC cultures. Endogenous IL-2 was not produced, whereas IL-6 and TNF- were secreted at levels compatible with their known ability to up-regulate HIV-1 expression. The HIV-suppressive CC-chemokines RANTES, macrophage inflammatory protein-1 (MIP-1), and MIP-1β were also determined in IL-2–stimulated PBMC cultures. Of interest, their kinetics and concentrations were inversely related to those of HIV-1 replication. Experiments were performed in which CD8+ T cells or PBMCs from HTLV-II monoinfected individuals were cocultivated with CD4+ T cells from HIV-1 monoinfected individuals separated by a semipermeable membrane in the presence or absence of antichemokine neutralizing antibodies. The results indicate that HTLV-II can interfere with the replicative potential of HIV-1 by up-regulating viral suppressive CC-chemokines and, in particular, MIP-1. This study is the first report indicating that HTLV-II can influence HIV replication, at least in vitro, via up-regulation of HIV-suppressive chemokines.

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In Healthy Young Men, a Short Exhaustive Exercise Alters the Oxidative Stress Only Slightly, Independent of the Actual Fitness

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/9107210 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Maya Finkler ◽

Ayala Hochman ◽

Ilya Pinchuk ◽

Dov Lichtenberg

Keyword(s):

Physical Fitness ◽

Serum Lipids ◽

Ex Vivo ◽

Young Men ◽

Exhaustive Exercise ◽

Progressive Exercise ◽

Exercise Induced ◽

Induced Changes ◽

Kinetics Of ◽

Apparent Disagreement

The aim of the present study was to evaluate the apparent disagreement regarding the effect of a typical cycling progressive exercise, commonly used to assessVO2max, on the kinetics ofex vivocopper induced peroxidation of serum lipids. Thirty-two (32) healthy young men, aged 24–30 years, who do not smoke and do not take any food supplements, participated in the study. Blood was withdrawn from each participant at three time points (before the exercise and 5 minutes and one hour after exercise). Copper induced peroxidation of sera made of the blood samples was monitored by spectrophotometry. For comparison, we also assayed TBARS concentration and the activity of oxidation-related enzymes. The physical exercise resulted in a slight and reversible increase of TBARS and slight changes in the activities of the studied antioxidant enzymes and the lag preceding peroxidation did not change substantially. Most altered parameters returned to baseline level one hour after exercise. Notably, the exercise-induced changes in OS did not correlate with the physical fitness of the subjects, as evaluated in this study (VO2max= 30–60 mL/min/kg). We conclude that in healthy young fit men a short exhaustive exercise alters only slightly the OS, independent of the actual physical fitness.

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Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis

Journal of Virology ◽

10.1128/jvi.02471-06 ◽

2007 ◽

Vol 81 (9) ◽

pp. 4798-4807 ◽

Cited By ~ 23

Author(s):

David C. Thomas ◽

Yegor A. Voronin ◽

Galina N. Nikolenko ◽

Jianbo Chen ◽

Wei-Shau Hu ◽

...

Keyword(s):

Dna Synthesis ◽

Reverse Transcription ◽

Ex Vivo ◽

Dna Transfer ◽

Minus Strand ◽

Immunodeficiency Virus ◽

Specific Amplification ◽

Kinetics Of ◽

Hiv 1

ABSTRACT Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4+ T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthesis is initiated at multiple sites and that several reverse transcriptase inhibitors influence the kinetics of minus-strand DNA synthesis differently, providing insights into their mechanism of inhibition. The SSA technology provides a novel approach to analyzing DNA replication processes and should facilitate the development of new antiretroviral drugs that target specific steps in HIV-1 reverse transcription.

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Toxico-Kinetics of Recombinant VWF In Non-Human Primates and Rabbits

Blood ◽

10.1182/blood.v116.21.1414.1414 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1414-1414

Author(s):

Eva-Maria Muchitsch ◽

Barbara Dietrich ◽

Hanspeter Rottensteiner ◽

Herbert Gritsch ◽

Hartmut J. Ehrlich ◽

...

Keyword(s):

Ex Vivo ◽

Dependent Manner ◽

Cynomolgus Monkeys ◽

Toxicological Effect ◽

Safety Margins ◽

Hemostatic Activity ◽

Von Willebrand ◽

Willebrand Factor ◽

Kinetics Of

Abstract Abstract 1414 Von Willebrand factor (VWF) is cleaved by the plasma metalloprotease ADAMTS13 that regulates the hemostatic activity of VWF by limiting its multimeric size in the human system. We showed previously by in vitro and ex vivo studies that human recombinant VWF (rVWF) is virtually resistant to the proteolytic activity of murine and rat ADAMTS13, whereas ADAMTS13 from rabbits and cynomolgus monkeys is able to cleave human rVWF. Here we tested the pharmacological behavior of human rVWF in rabbits and cynomolgus monkeys. The animals were infused once with different doses of human rVWF. VWF antigen rose sharply in a dose-dependent manner (∼25 IU/ml VWF:Ag for the highest dose, 15 min after injection) and then declined gradually (∼7 IU/ml VWF:Ag for the highest dose, 18 hours after injection). By contrast, the ADAMTS13 activity did not show relevant changes throughout the entire test period in the rabbit or in the monkey samples, indicating that an excess of intravenously administered rVWF as the substrate does not exhaust its enzyme ADAMTS13. Most importantly, neither rabbits nor cynomolgus monkeys showed any exaggerated pharmacological or toxic effects upon rVWF administration. Even the administration of 14 daily doses of rVWF to cynomolgus monkeys did not lead to any toxicological effect. Our data indicate that rabbits and cynomolgus monkeys, two species with a sufficient rVWF cleavage capacity by endogenous ADAMTS13, are appropriate animal models for a meaningful preclinical evaluation of the rVWF product, which allows the therapeutic safety margins for human patients to be determined. Disclosures: Muchitsch: Baxter Innovations GmbH: Employment. Dietrich:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Gritsch:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment. Schwarz:Baxter Innovations GmbH: Employment.

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c-Myc inhibition is critical for HSC expansion and Rad51 expression

10.1101/403584 ◽

2018 ◽

Author(s):

Merve Aksoz ◽

Esra Albayrak ◽

Galip Servet Aslan ◽

Raife Dilek Turan ◽

Lamia Yazgi Alyazici ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Kinase Inhibitor ◽

Ex Vivo ◽

Fold Increase ◽

Hematopoietic Stem ◽

Cyclin Dependent Kinase Inhibitor ◽

Nos Inhibitor ◽

Kinetics Of

c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to downregulation of glycolytic and cyclin-dependent kinase inhibitor (CDKI) gene expression ex vivo and in vivo. In addition, c-Myc inhibition upregulates major HDR modulator Rad51 expression in hematopoietic cells. Besides, c-Myc inhibition does not alter proliferation kinetics of endothelial cells, fibroblasts or adipose derived mesenchymal stem cells, however; it limits bone marrow derived mesenchymal stem cell proliferation. We further demonstrate that a cocktail of c-Myc inhibitor 10074-G5 along with tauroursodeoxycholic acid (TUDCA) and i-NOS inhibitor L-NIL provides a robust HSC maintenance and expansion ex vivo as evident by induction of all stem cell antigens analyzed. Intriguingly, the cocktail of c-Myc inhibitor 10074-G5, TUDCA and L-NIL improves HDR related gene expression. These findings provide tools to improve ex vivo HSC maintenance and expansion, autologous HSC transplantation and gene editing through modulation of HSC glycolytic and HDR pathways.

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Evaluation of Nutritive Values of Agro-Industrial By-Products (AIBPS) and Effect of Their Nano Structural Characteristics on the Kinetics of Biogas Production and Methane Emission

10.21203/rs.3.rs-310347/v1 ◽

2021 ◽

Author(s):

Shahram Shirmohammadi ◽

Akbar Taghizadeh ◽

Hamid Paya ◽

Arash Javanmard ◽

Soheila Abachi ◽

...

Keyword(s):

Methane Emission ◽

Biogas Production ◽

Ex Vivo ◽

Structural Characteristics ◽

In Vitro Digestibility ◽

Fermentation Parameters ◽

Experimental Treatments ◽

Kinetics Of ◽

By Products

Abstract Over the past decades, the agro-industrial by-products (AIBP) has received considerable attention. With this motivation, the aim of this study was to investigate the effect of AIBP as a source of non-fiber carbohydrates on biogas production kinetic, methane emission and fermentation characteristics. Experimental treatments were (1) Sugar beet pulp (SBP) (control), (2) Apple pomace (AP), (3) Orange pulp (OP, (4) 33% AP + 66% OP, (5) 50% AP + 50% OP and (6) 66% AP + 33%OP. For this work, we analyzed the data collected from the kinetics of digestion through biogas production, ex-vivo methane emission, in-vitro digestibility of dry matter and fermentation parameters. Field emission scanning electron microscope was used to show the nano structural differences of the AIBPs. Our results demonstrated the significant differences of the crude protein among the treatments (P < 0.05). Biogas production and methane emission were significantly higher in SBP and OP treatments (P < 0.05). The most eminent and the lowest amounts of acetate were observed for AP and OP (61.84 mmol/L, 58.15 mmol/L), respectively. More broken edges were obvious in OP images. particle size was rather smaller in SBP. Images of AP showed a sleek surface which may act as a shield preventing more digestion. Overall, beside reducing environmental contamination by AIBP, our results showed a positive effect of AIBPs on degradation and biogas kinetics, methane emission and in vitro fermentation parameters describing that they can be used as a good source of non-fiber energy sources.

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Multiphoton and FLIM imaging in quantifying ex vivo and in vivo body organ kinetics of solutes

Multiphoton Microscopy in the Biomedical Sciences XX ◽

10.1117/12.2546058 ◽

2020 ◽

Author(s):

Michael S. Roberts ◽

Deborah Barkauskas ◽

Haolu Wang ◽

Xin Liu ◽

Hauke Studier ◽

...

Keyword(s):

Ex Vivo ◽

Body Organ ◽

Kinetics Of

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Kinetics of Metabolism in Human Kidney Transplants Measured by Dynamic 31P NMR Spectroscopy

Zeitschrift für Naturforschung C ◽

10.1515/znc-1995-5-616 ◽

1995 ◽

Vol 50 (5-6) ◽

pp. 439-450 ◽

Cited By ~ 6

Author(s):

Harald E. Möller ◽

Andreas Gaupp ◽

Thomas Vestring ◽

Karl-Heinz Dietl ◽

Peter Vermathen ◽

...

Keyword(s):

Nmr Spectroscopy ◽

31P Nmr ◽

Ex Vivo ◽

Human Kidney ◽

31P Nmr Spectroscopy ◽

H 41 ◽

Minimum Delay ◽

Detailed Kinetic Model ◽

Brain Dead ◽

Kinetics Of

The technique of ex vivo 31P NMR spectroscopy has been used for the investigation of metabolic turnover in 15 cadaveric human kidneys obtained from brain-dead donors for transplantation. Measurements were carried out at 1.5 T time-dependently during regular hypothermic storage in histidine-tryptophan-α-ketoglutarate solution. The minimum delay between explantation and spectroscopy was 2 h 41 min. In one case of a discarded organ the measurements could be extended over a period of 161 h 35 min. A detailed kinetic model describing monoexponential ischemic phosphate turnover, which accounts for various interrelations of the NMR visible metabolites, has been derived. Averaged velocity constants of the decays of nucleotides and phosphomono- and -diesters ranged from 0.0047 to 0.294 h-1 at approximately 4° C. Intracellular pH decreased monoexponentially with an averaged velocity constant of 0.31 h-1.

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KINETICS OF LOW MOLECULAR WEIGHT HEPARIN IN MAN DETERMINED BY PROTAMINE CHLORIDE

10.1055/s-0038-1644176 ◽

1987 ◽

Author(s):

V Bode ◽

R Franz ◽

D Welzel ◽

H Wolf ◽

C Harenberg

Keyword(s):

Molecular Weight ◽

Half Life ◽

Ex Vivo ◽

Plasma Concentrations ◽

Factor Xa ◽

Low Molecular Weight ◽

Plasma Samples ◽

Endogenous Compounds ◽

Antifactor Xa ◽

Kinetics Of

Low molecular weight (LMW) heparin is characterized by a higher affinity to antithrombin HI, less inhibition of thrombin and increased inhibition of factor Xa. The half life of the antifactor Xa activity of LMW heparin is doubled compared to normal heparin. However, these parameters reflect the pharmacodynamics rather than the kinetic of the compound. We, therefore, analyzed the kinetics of LMW heparin after i.v. injection in man using protamine chloride for gravimetric evaluation of LMW heparin in the plasma samples.Six healthy adults received 100 units per kg body weight normal heparin or 100 anti Xa units per kg LMW heparin (Sandoz AG, Niimberg, FRG). To serial samples of venous blood protamine chloride was added in serial dilutions until the thrombin inhibition was antagonized. Since factor Xa inhibition of LMW heparin cannot be abolished completely by protamine chloride, two amounts of protamine chloride were added to the plasma samples ex vivo, until factor Xa was inhibited up to 0,2 and 0,04 units/ml. The following maximal plasma concentrations (C max) and half lives (T/2) were calculated (average values):The pharmacokinetics of normal heparin show no differences on thrombin and factor Xa interaction. LMW heparin, however, interacts to 30 % with thrombin and to 100 % with factor Xa; the half life on factor Xa is twice as long as on thrombin; releases endogenous compounds with antifactor Xa activity, which are neutralized only hardly by protamine chloride;and these endogenous compounds mediate in part the longer half life.

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91. Differential Impact of Cytomegalovirus (CMV) Donor (D) Serostatus on Rates and Kinetics of CMV Viremia among CMV Seropositive Recipients (R+) of Ex vivo T-cell Depleted (TCD) and Unmodified (CONV) Hematopoietic Cell Transplants (HCT)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.015 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S7-S7

Author(s):

Anat Stern ◽

Yiqi Su ◽

Jiaqi Fang ◽

Miguel Perales ◽

Molly Maloy ◽

...

Keyword(s):

T Cell ◽

Ex Vivo ◽

Hematologic Malignancies ◽

T Cell Immunity ◽

Similar Frequency ◽

Viral Loads ◽

Cell Immunity ◽

Cell Transplants ◽

The Impact ◽

Kinetics Of

Abstract Background In unmodified (CONV) HCT, CMV donor seropositivity (D+) conveys partial protection against CMV disease mediated by the transfer of donor CMV T-cell immunity through the allograft. Ex vivo T-cell depletion by CD34 selection affords a stringent depletion of donor T cells, thus transfer of donor T-cell immunity to CMV would be negligible. We evaluate the impact of CMV D serostatus on rates and kinetics of CMV viremia by Day (D)100 post-HCT in a contemporary cohort of CONV and TCD recipients from a single center. Methods A retrospective cohort study of R+ adult recipients of first peripheral blood or marrow HCT for hematologic malignancies (excluding multiple myeloma) from June 2010 to December 2017 at MSKCC. Routine CMV monitoring by a quantitative PCR assay occurred weekly from D14 through D100. Patients were treated preemptively. CMV viral burden was assessed as the time-averaged area under the viremia curve over 100 days from HCT (AAUC) calculated as the sum of the area of trapezoids of AUC viral loads divided by the number of weeks of follow-up viremia. The median AAUC for all patients with CMV reactivation (AAUC50) was used to classify patients as CMV controllers (AAUC ≤ AAUC50) or noncontrollers (AAUC >AAUC50). Results Of 509 R+, 290 (57%) patients received CONV and 219 (43%) TCD HCT; from 300 (59%) D+ and 209 (41%) D− donors. In CONV, CMV viremia occurred with similar frequency in D+ (65%) and D− (62%), P = 0.6. In contrast, in TCD, CMV viremia occurred more frequently in D+ compared with D− (83% vs. 71%, P = 0.03). Among CONV, D+ was associated with lower CMV burden (median AAUC) compared with D− (0.791 vs. 1.13, respectively, P = 0.0004). In contrast, in TCD, AAUC was similar between D− and D+ (1.19 vs. 1.35; P = 0.86). Among CONV with CMV viremia, D− were more likely to be noncontrollers compared with D+ (56% vs. 31%, respectively, P = 0.001). In contrast, among TCD with CMV viremia the proportion of noncontrollers was similar between D− and D+ (61% vs. 60%, respectively; P = 1). Conclusion Donor CMV serostatus has a differential effect on rates and kinetics of CMV viremia in R+ TCD and CONV HCT recipients. D+ is associated with less CMV viremia and less CMV burden in CONV but not in TCD. Our findings, if confirmed, have implications for donor selection algorithms. Disclosures All Authors: No reported Disclosures.

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