scholarly journals Regulation of monocyte procoagulant by chemoattractants

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 545-552 ◽  
Author(s):  
RL Janco ◽  
PJ Morris
Keyword(s):  
Kinetic Studies ◽  
Optimal Dose ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
High Dose ◽  
Fourfold Increase ◽  
Leukocyte Function ◽  
Chemotactic Peptides ◽  
Higher Doses

Abstract Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces a fourfold increase in procoagulant activity (PCA) in cultured human monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses inhibit PCA response. Although nonadherent lymphocytes are not absolutely required for PCA expression, their presence significantly amplifies monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them with FMLP and adherent cells abolishes their ability to amplify PCA. Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA over time whereas high- dose inhibition of PCA generation occurs at various incubation times. Cell viability is unaffected by inhibitory concentrations of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit later expression of PCA by cells exposed to endotoxin. The cellular procoagulant remains cell-bound and exhibits characteristics of thromboplastin (tissue factor), including inhibition by concanavalin A and phospholipase C as well as the ability to shorten the clotting times of factor VIII but not factor VII-deficient substrate plasmas. These results suggest a complex system of lymphoid cell regulation of procoagulant generation by monocytes exposed to various chemotactic peptides in vitro.

scholarly journals Regulation of monocyte procoagulant by chemoattractants

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 545-552
Author(s):  
RL Janco ◽  
PJ Morris
Keyword(s):  
Kinetic Studies ◽  
Optimal Dose ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
High Dose ◽  
Fourfold Increase ◽  
Leukocyte Function ◽  
Chemotactic Peptides ◽  
Higher Doses

Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces a fourfold increase in procoagulant activity (PCA) in cultured human monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses inhibit PCA response. Although nonadherent lymphocytes are not absolutely required for PCA expression, their presence significantly amplifies monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them with FMLP and adherent cells abolishes their ability to amplify PCA. Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA over time whereas high- dose inhibition of PCA generation occurs at various incubation times. Cell viability is unaffected by inhibitory concentrations of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit later expression of PCA by cells exposed to endotoxin. The cellular procoagulant remains cell-bound and exhibits characteristics of thromboplastin (tissue factor), including inhibition by concanavalin A and phospholipase C as well as the ability to shorten the clotting times of factor VIII but not factor VII-deficient substrate plasmas. These results suggest a complex system of lymphoid cell regulation of procoagulant generation by monocytes exposed to various chemotactic peptides in vitro.

scholarly journals Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582098216
Author(s):  
Bing Wang ◽  
Kaoru Tanaka ◽  
Takanori Katsube ◽  
Kouichi Maruyama ◽  
Yasuharu Ninomiya ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
High Dose ◽  
Cancer Treatments ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Radiation Induced ◽  
Potential Strategy ◽  
Higher Doses

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

scholarly journals The stable prostacyclin analog, iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 382-386 ◽  
Author(s):  
DJ Crutchley ◽  
MJ Hirsh
Keyword(s):  
Tissue Factor ◽  
Prostaglandin E1 ◽  
Human Peripheral Blood ◽  
Fold Increase ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Dependent Inhibition ◽  
Clinical Potential ◽  
Prostacyclin Analog

Abstract Exposure of human peripheral blood to 100 ng/mL of bacterial endotoxin for 2 hours resulted in a 20-fold increase in monocyte procoagulant activity. The activity was functionally identified as tissue factor, because it was not expressed in plasma deficient in factor VII and was specifically inhibited by a monoclonal antibody directed against human tissue factor. When the stable prostacyclin analog, iloprost, was added to blood 30 minutes before endotoxin, a dose-dependent inhibition of monocyte procoagulant activity occurred, with an I50 of 20 nmol/L. Prostaglandin E1 (PGE1) produced similar effects, with an I50 of 150 nmol/L. Exposure of THP-1 monocytic cells to 100 ng/mL endotoxin resulted in a threefold increase in procoagulant activity after 2 hours and a 20-fold increase after 6 hours. A 30-minute pretreatment with iloprost or PGE1 again inhibited development of procoagulant activity, with I50 values of 5 nmol/L and 150 nmol/L, respectively. Treatment of THP-1 cells with iloprost 2 hours after exposure to endotoxin significantly inhibited further increases in procoagulant activity. Iloprost was less potent under these conditions, 30% inhibition being obtained at 100 nmol/L and 70% at 1 mumol/L. These results suggest that prostacyclin may be a physiologic modulator of monocyte tissue factor expression; in addition, its stable analog, iloprost, may have clinical potential for the treatment of thrombotic disorders in which elevated monocyte procoagulant activity plays a role.

scholarly journals Evaluation of Standard- and High-Dose Daptomycin versus Linezolid against Vancomycin-Resistant Enterococcus Isolates in anIn VitroPharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

2012 ◽  
Vol 56 (6) ◽  
pp. 3174-3180 ◽  
Author(s):  
Ashley D. Hall ◽  
Molly E. Steed ◽  
Cesar A. Arias ◽  
Barbara E. Murray ◽  
Michael J. Rybak
Keyword(s):  
Bactericidal Activity ◽  
Optimal Dose ◽  
Pharmacodynamic Model ◽  
Colony Count ◽  
High Dose ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Sustained Reduction ◽  
Vancomycin Resistant

ABSTRACTDaptomycin MICs for enterococci are typically 1- to 2-fold higher than those forStaphylococcus aureus, and there is an imminent need to establish the optimal dose for appropriate treatment of enterococcal infections. We investigated the bactericidal activity of daptomycin at various dose exposures compared to that of linezolid against vancomycin-resistant enterococcus (VRE) in anin vitropharmacokinetic/pharmacodynamic model utilizing simulated endocardial vegetations over 96 h. Daptomycin at doses of 6, 8, 10, and 12 mg/kg of body weight/day and linezolid at a dose of 600 mg every 12 h were evaluated against two clinical vancomycin-resistantEnterococcus faeciumstrains (EFm11499 and 09-184D1051), one of which was linezolid resistant (09-184D1051), and one clinical vancomycin-resistantEnterococcus faecalisstrain (EFs11496). Daptomycin MICs were 4, 2, and 0.5 μg/ml for EFm11499, 09-184D1051, and EFs11496, respectively. Bactericidal activity, defined as a ≥3 log10CFU/g reduction from the initial colony count, was demonstrated against all three isolates with all doses of daptomycin; however, bactericidal activity was not sustained with the daptomycin 6- and 8-mg/kg/day regimens. Linezolid was bacteriostatic against EFm11499 and displayed no appreciable activity against 09-184D1051 or EFs11496. Concentration-dependent killing was displayed with more sustained reduction in colony count (3.58 to 6.46 and 5.89 to 6.56 log10CFU/g) at 96 h for the simulated regimen of daptomycin at doses of 10 and 12 mg/kg/day, respectively (P≤ 0.012). NoE. faeciummutants with reduced susceptibility were recovered at any dosage regimen; however, theE. faecalisstrain developed reduced daptomycin susceptibility with daptomycin at 6, 8, and 10 but not at 12 mg/kg/day. Daptomycin displayed a dose-dependent response against three VRE isolates, with high-dose daptomycin producing sustained bactericidal activity. Further research is warranted.

scholarly journals Immunologic Identification of Tissue Factor (Thromboplastin) Synthesized by Cultured Fibroblasts

Blood ◽  
1973 ◽  
Vol 41 (5) ◽  
pp. 671-678 ◽  
Author(s):  
Leo R. Zacharski ◽  
Leon W. Hoyer ◽  
O. Ross McIntyre
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Coagulation Factors ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Cultured Fibroblasts ◽  
Procoagulant Effect ◽  
Tissue Thromboplastin ◽  
Thromboplastin Factor

Abstract Immunologic methods were employed in an attempt to identify a potent procoagulant present in homogenates of human skin fibroblasts cultured in vitro. The activity of this procoagulant was restricted to the early stages of coagulation and was heretofore considered to be due to tissue factor (tissue thromboplastin, factor III) either alone or in combination with one or more of the first-stage coagulation factors (VIII, IX, XI, XII). The present studies demonstrated that procoagulant activity was not diminished by incubation with anti-VIII or anti-IX antibodies of human origin or with anti-VIII antibody of rabbit origin. Furthermore, cell culture homogenates failed to bind antifactor VIII antibody and did not contain an inhibitor of the reaction between factor VIII and its antibody. By contrast, procoagulant activity was obliterated by an antibody to tissue factor protein regardless of whether plasmas deficient in factor VIII, IX, XI, or XII were used in the assay system. The antitissue factor antibody failed to block the procoagulant effect after tissue factor had complexed factor VII. The procoagulant, therefore, consisted entirely of tissue factor.

MECHANISMS OF PROCOAGULANT GENERATION BY ALVEOLAR MACROPHAGES DURING MATURATION

1987 ◽  
Author(s):  
Maria McGee ◽  
Henry Rothberger
Keyword(s):  
Alveolar Macrophages ◽  
Cultured Cells ◽  
Factor Xa ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Complex Assembly

During maturation in vivo and in vitro alveolar macrophages generate procoagulant(s) capable of activating the extrinsic pathway. It is generally agreed that at least part of the activity is due to TF (tissue factor). However, whether or not macrophages also generate functional factor VII or X is controversial. To characterize procoagulant activity increases, we measured kinetic parameters defining interactions between components of the TF-VII complex on membranes of alveolar macrophages either freshly isolated or cultured in serum free medium. In incubation mixtures with fixed concentrations of macrophages and added factor VII, the rate of factor Xa formation (measured by S-2222 hydrolysis) approached a maximum as factor X concentration was increased. Estimated concentrations of factor X yielding 1/2 maximal activation rates, (apparent Km) were 127.1±26 nM and 99.7±34 nM for fresh and cultured cells, respectively. Vmax (maximal velocities) were 1.21±0.24 and 8.9±5 nM Xa/min/106 cells. When concentrations of added factor X were kept constant, the rate of factor X activation increased as the added factor VII concentration was increased. For fresh and cultured cells, the respective apparent Kd were 1.810.7 and 1.410.25 nM. Maximal rates observed with X concentration fixed at 108 nM were 0.46±10.06 and 5.7±1.6 nM Xa/min/106 cells. In the absence of either added factor X or added factor VII, no factor Xa generation was detected in fresh or cultured cells, during 10-20 min incubation periods used for kinetic studies. The observed increase in Vmax without changes in apparent Km and Kd indicate that gains in procoagulant activity during macrophage maturation are due to increases in the number of functional binding sites for factor VII, without significant generation of functional vitamin K dependent factors (VII and X) by the cells. The data also indicate that maturation does not alter the rate behaviour of the TF-VII enzymatic complex on macrophage membranes. Mechanisms of complex assembly that we observed on macrophage membranes are similar to those described for the TF-VII complex assembly on purified systems.

COMPARISON OF THE EFFECT OF FACTOR VII PREPARED FROM HUMAN PLASMA (pVIIa) AND RECOMBINANT Vila (rVIIa) IN VITRO AND IN RABBITS

1987 ◽  
Author(s):  
U Hender ◽  
T Lund-Hansen ◽  
D Winther
Keyword(s):  
Human Plasma ◽  
Factor Vii ◽  
Normal Plasma ◽  
Vitro Effect ◽  
Higher Doses

Purified human FVIIa has been shown to induce haemostasis in pat. with haemoph. A compl. with antibodies against VIII:C (Hedner & Kisiel 1983). The in vitro effect of addition of pVIIa or rVIIa was studied by adding 0, 44, or 180 u pVIIa/rVIIa/ml to haemoph. A or haemoph. B plasma. The APTT shortened from 61 s (mean of 5 determin.) without any Vila added to 38 s after addition of 44 u pVIIa to haemoph. A plasma, and to 33 s after addition of 180 u/ml. In haemoph. B plasma the corresponding APTTs were 64 s, 35 s (44 u pVIIa/ml Vila) and 31 s (180 u pVIIa/ ml). Similar results were obtained when rVIIa was added to the same plasmas. In haemoph. A plasma APTT was shortened from 66 S to 52 s (50 u rVIIa/ml) and to41s(159u rVIIa/ml), and in haemoph. B plasma 71 s,44 s,and 37 s.Also in plasma from pat. with acquired antibodies against VIII:C a shortening of APTT was found both of pVIIa (60 s, 37 s, and 32 s) and rVIIs (65 s, 38 s, and 33 s). In normal plasma the APTT only shortened a few seconds after addition of the same amounts of pVIIa/rVIIa per ml (30 s, 27 s, 25 s). The doses required to normalize the APTT in vitro exceed substantially the doses used in vivo so far. The pVIIa and rVIIa were therefore also given i.v. to rabbits.Plasma samples were drawn before inj., 15 min, 2 hrs,4 hrs, 8 hrs, and 24 hrs after and platelets, APTT, fib.gen, ATIII, α2M, α2AP, ethanol gel. test, FVII,Hb, Hkr were followed. Doses of 500 u/kgb.w.,1000 or 5000 u/kg b.w. were given. No signs of a gen.activ.of the coag. were observed. The FVII level in plasm rose adequately. In conclusion higher doses of Vila than used clin. so far may be needed to achieve full haemost. effect in haemoph. pat. or pat. with acq. antibodies against VIII:C. Such doses also seem to be safe. rVIIa was as active as pVIIa and as safe in rabbits.

scholarly journals EFFECTS OF SYNTHETIC ASTAXANTHIN, CHLORELLA, AND SPIRULINA SUPPLEMENTATION IN DIETS ON GROWTH AND PIGMENTATION OF KURUMOI RAINBOWFISH, Melanotaenia parva

2021 ◽  
Vol 15 (2) ◽  
pp. 67
Author(s):  
Nina Meilisza ◽  
Muhammad Agus Suprayudi ◽  
Dedi Jusadi ◽  
Muhammad Zairin Jr. ◽  
I Made Artika
Keyword(s):  
Optimal Dose ◽  
Water Soluble ◽  
Fish Growth ◽  
High Dose ◽  
Fish Feed ◽  
Chlorella Sp ◽  
Fish Diets ◽  
Study Results ◽  
Higher Doses ◽  
Different Doses

Several studies have recommended the supplementation of astaxanthin in the Kurumoi rainbowfish diet to enhance its color and growth. However, knowledge regarding the effects of naturally-sourced and synthetically-made carotenoids in fish diets is currently limited. This study’s objective was to compare the growth and color performances of Melanotaenia parva by supplementing fish feed with synthetic astaxanthin and natural carotenoids sourced from Chlorella and Spirulina. A total of 12 fish (weight of 1.27 ± 0.02 g and total length of 4.70 ± 0.07 cm) were stocked at a density of one fish per liter. Basal feed (B) was used as the control feed. The experimental feeds were: B added with different doses of synthetic astaxanthin (Carophyll® Pink 10% water-soluble) from low to higher doses as follows: 0.6 g kg-1 (AS-L), 2.6 g kg-1 (AS-O), and 5.1 g kg-1 (AS-H); and B added with natural carotenoids of Chlorella sp. (Ch) and Spirulina sp. (Sp) of 8.6 g kg-1 and 5.5 g kg-1, respectively. The experimental diets were given at satiation for 56 days at 8 am and 3 pm. The study results showed that the addition of synthetic astaxanthin at a dose of 2.6 g kg-1 could increase the fish growth up to 12% with carotenoid deposition in the fish fin of three times higher than that of the treatments without synthetic astaxanthin. This dose was considered the optimal dose to increase the fish’s growth performance and pigmentation compared with the high dose of 5.1 g kg-1. Despite having the same nutrient composition, natural carotenoids in Chlorella and Spirulina did not produce better results compared to the low dose of synthetic astaxanthin of 0.6 g kg-1.

Treatment of Congenital Factor VII Deficiency with a New Concentrate

1978 ◽  
Vol 39 (03) ◽  
pp. 675-682 ◽  
Author(s):  
G Mariani ◽  
P M Mannucci ◽  
M G Mazzucconi ◽  
A Capitanio
Keyword(s):  
Kinetic Studies ◽  
Factor Vii ◽  
Spontaneous Bleeding ◽  
Factor Vii Deficiency ◽  
Factor Ii ◽  
Plasma Factor ◽  
Circulatory Overload ◽  
Surgical Bleeding

SummaryA new factor VII concentrate, made from ACD plasma by a process involving successive absorptions of cryoprecipitate supernatant on DEAE Sephadex and of the resulting supernatant on Al(OH)3, was administered to 10 patients with severe factor VII deficiency. 5 patients received only one dose for treatment of a single bleeding episode, the remaining 5 were given multiple infusions (47) for spontaneous hemorrhages or for the prevention of surgical bleeding. In vivo factor VII recovery ranged from 43 to 126% (average 88%) of the assayed in vitro activity of the concentrate. A dose of 0.5 u/kg was found to produce a 1% rise of the plasma factor VII levels. The mean half-life on injected factor VII as assessed in 7 kinetic studies was 205 min (range 168-234). Spontaneous bleeding was easily controlled by the concentrate and major surgical procedures (two tonsillectomies) could be performed without complications. 1 patient developed HBsAg positive hepatitis, but otherwise no serious side effects were observed. Factor VII concentrate reduces the risk of precipitating circulatory overload associated with the use of plasma and avoids the unnecessary rise of factor II, IX and X which follows prothrombin complex concentrates.

scholarly journals The stable prostacyclin analog, iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 382-386
Author(s):  
DJ Crutchley ◽  
MJ Hirsh
Keyword(s):  
Tissue Factor ◽  
Prostaglandin E1 ◽  
Human Peripheral Blood ◽  
Fold Increase ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Dependent Inhibition ◽  
Clinical Potential ◽  
Prostacyclin Analog

Exposure of human peripheral blood to 100 ng/mL of bacterial endotoxin for 2 hours resulted in a 20-fold increase in monocyte procoagulant activity. The activity was functionally identified as tissue factor, because it was not expressed in plasma deficient in factor VII and was specifically inhibited by a monoclonal antibody directed against human tissue factor. When the stable prostacyclin analog, iloprost, was added to blood 30 minutes before endotoxin, a dose-dependent inhibition of monocyte procoagulant activity occurred, with an I50 of 20 nmol/L. Prostaglandin E1 (PGE1) produced similar effects, with an I50 of 150 nmol/L. Exposure of THP-1 monocytic cells to 100 ng/mL endotoxin resulted in a threefold increase in procoagulant activity after 2 hours and a 20-fold increase after 6 hours. A 30-minute pretreatment with iloprost or PGE1 again inhibited development of procoagulant activity, with I50 values of 5 nmol/L and 150 nmol/L, respectively. Treatment of THP-1 cells with iloprost 2 hours after exposure to endotoxin significantly inhibited further increases in procoagulant activity. Iloprost was less potent under these conditions, 30% inhibition being obtained at 100 nmol/L and 70% at 1 mumol/L. These results suggest that prostacyclin may be a physiologic modulator of monocyte tissue factor expression; in addition, its stable analog, iloprost, may have clinical potential for the treatment of thrombotic disorders in which elevated monocyte procoagulant activity plays a role.

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