Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis

1997 ◽  
Vol 16 (2) ◽  
pp. 115-122 ◽  
Author(s):  
B. Rio ◽  
D. Parent-Massin ◽  
S. Lautraite ◽  
H. Hoellinger
Keyword(s):  
Cellular Proliferation ◽  
Diphenyl Ether ◽  
Protoporphyrinogen Oxidase ◽  
Phytotoxic Activity ◽  
The Common ◽  
High Concentrations ◽  
Haemoglobin Content ◽  
Haemoglobin Synthesis ◽  
Chlorophyll Formation

The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis. The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Ery throid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the develop ment of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentia tion showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10-4 M) that have no adverse effect on cellular proliferation.

Molecular Aspects of Herbicide Action on Protoporphyrinogen Oxidase

1993 ◽  
Vol 48 (3-4) ◽  
pp. 326-333 ◽  
Author(s):  
Beate Nicolaus ◽  
Gerhard Sandmann ◽  
Peter Böger
Keyword(s):  
Diphenyl Ether ◽  
Protoporphyrin Ix ◽  
Protoporphyrinogen Oxidase ◽  
Relative Specificity ◽  
Oxidase Inhibition ◽  
Dilution Experiments ◽  
Membrane Bound ◽  
The Common ◽  
Molecular Aspects ◽  
Derivatives Of

Abstract Protoporphyrinogen oxidase, the last enzyme of the common tetrapyrrole biosynthetic pathway, is inhibited by several peroxidizing compounds resulting in accumulation of photodynamic tetrapyrroles, mainly protoporphyrin IX. The inhibition characteristics of two chemi­cally unrelated compounds were studied using membrane bound protoporphyrinogen oxidase from corn etioplasts. As shown by Lineweaver-Burk-analysis, the inhibition of enzyme activity by the diphenyl ether oxyfluorfen and the cyclic imide MCI 15 are competitive with respect to the substrate. The competitive interaction of protoporphyrinogen and the two chemically un­related inhibitors indicate a relative specificity of the binding site. The reversibility of oxyfluorfen inhibition was evaluated by dilution experiments and was shown to be independent of the presence of DTT. The analysis of structure-activity-relationship on protoporphyrinogen oxidase inhibition was investigated with para-substituted derivatives of phenyl-3,4,5,6-tetrahydro-phthalimides. The results obtained by QSAR -calculation yielded a good correlation of the inhibitory activity determined by the lipophilicity of the para-substituent. These data point to one binding region of the inhibitors within a lipophilic environment associated with the active center of the enzyme.

The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins

1980 ◽  
Vol 58 (10) ◽  
pp. 1234-1244 ◽  
Author(s):  
R. Couture ◽  
P. Gaudreau ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Substance P ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Low Concentrations ◽  
Pharmacological Preparation ◽  
The Common ◽  
High Concentrations

In order to develop a sensitive pharmacological preparation which would allow the measurement of the inhibitory effects of kinins and substance P (SP) in vascular smooth muscles, several large arteries of the dog were studied in vitro. The common carotid artery was found to be one of the most sensitive preparations to SP and kinins. When contracted with low concentrations of noradrenaline (between 3.0 × 10−8 and 3.0 × 10−7 M), this artery responds to SP (6.5 × 10−11 − 6.5 × 10−9 M) and bradykinin (BK) (8.1 × 10−11 − 9.1 × 10−8 M) with relaxations that are proportional to the concentrations of the two peptides. SP and BK appear to exert their relaxant effects through the activation of specific receptors as the exposure of the common carotid artery to concentrations of [Leu8]-angiotensin II, propranolol, methysergide, cimetidine, or atropine sufficient to inhibit the effects of the corresponding agonists do not affect the relaxing effect of SP and BK. [Leu8]-des-Arg9-BK (1.0 × 10−s M), indomethacin (2.8 × 10−5 M), and lioresal (4.7 × 10−5 M) are also inactive. When the dog common carotid artery is desensitized with high concentrations of SP, BK, eledoisin, and physalaemin a cross-desensitization is observed only between SP and physalaemin. These results support the conclusion that SP and kinins act on different receptors. The order of potency of kinins is the following: BK = [Tyr(Me)8]-BK > des-Arg9-BK, suggesting that the receptor for kinins is of the B2 type. The order of potency of peptides related to SP is SP > C-terminal 4-11 > C-terminal hexapeptide 6-11, similar to that observed in other vascular preparations.The results summarized in this paper indicate that the dog common carotid artery is a preparation sensitive to SP and BK and useful for studying the relaxant effect of these two peptides on vascular smooth muscles.

scholarly journals A Trp574Leu Target-Site Mutation Confers Imazamox Resistance in Multiple Herbicide-Resistant Wild Poinsettia Populations from Brazil

Agronomy ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1057 ◽  
Author(s):  
Rafael R. Mendes ◽  
Hudson K. Takano ◽  
Rubem S. Oliveira ◽  
Fernando S. Adegas ◽  
Todd A. Gaines ◽  
...  
Keyword(s):  
Acetolactate Synthase ◽  
Southern Brazil ◽  
Weed Species ◽  
Site Mutation ◽  
Protoporphyrinogen Oxidase ◽  
Herbicide Resistant ◽  
High Concentrations ◽  
Als Inhibitors ◽  
Biomass Reduction

Wild poinsettia (Euphorbia heterophylla L.) is an important weed species in southern Brazil, especially due to the evolution of multiple herbicide resistance (e.g., acetolactate synthase (ALS)- inhibitors, protoporphyrinogen oxidase inhibitors, and glyphosate). The mechanism of resistance to imazamox was investigated in two wild poinsettia populations (R1 and R2) from southern Brazil and compared to a known susceptible (S) population. Imazamox dose-response experiments revealed high levels of resistance: 45-fold and 224.5-fold based on dry biomass reduction, for R1 and R2, respectively. Extremely high concentrations of imazamox (20,000 µM) were not sufficient to provide 50% inhibition of ALS enzyme activity (I50) for R1 or R2. Hence, resistance levels were estimated to be greater than 123-fold for both populations based on in vitro ALS assays. The ALS gene from all R1 and R2 plants had a Trp574Leu mutation. A genotyping assay was developed to discriminate resistant and susceptible alleles based on the Trp574Leu mutation.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Aggregation of Cat Platelets in Vitro

1970 ◽  
Vol 23 (03) ◽  
pp. 601-620 ◽  
Author(s):  
Th. B Tschopp
Keyword(s):  
Adenosine Monophosphate ◽  
Blood Collection ◽  
Base Line ◽  
Reversible Aggregation ◽  
Low Concentrations ◽  
Irreversible Aggregation ◽  
High Concentrations ◽  
Two Phases ◽  
Improved Technique

SummaryAggregation of cat platelets in the citrated plasma is examined by means of Born’s absorptiometer. A marked tendency of the platelets of this species to spontaneous aggregation necessitated first of all the development of an improved technique of blood collection.A hypothesis according to which 5-HT is released from the platelets, explains the absence of oscillations on the base line of the absorptiometer, the absence of platelet swelling, when ADP is added, and the effect of stirring on the aggregation curves in cat PRP. The average volume of cat platelets amounts to 10.46 μ3 when directly fixed in the blood, when fixed from PRP to 12.17 μ3, when fixed from stirred PRP to 13.51 μ3.In low concentrations (0.3-2 μM) ADP produce reversible aggregation; in narrowly restricted, individually dissimilar mean concentrations irreversible aggregation in two phases and in high concentrations, irreversible aggregation in one phase. Like ADP serotonin produces 2 phase irreversible aggregation in concentrations of 3-10 μM, but unlike ADP, the aggregation velocity decreases again with high 5-HT concentrations (>100 μM). Adrenaline does not produce aggregation and it is likely that adenosine and adenosine monophosphate inhibit the aggregation by serotonin but not by ADP. Species differences in the aggregation of human, rabbit and cat platelets are discussed.

Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

1997 ◽  
Vol 78 (04) ◽  
pp. 1173-1177 ◽  
Author(s):  
Jacek Musiał ◽  
Jakub Swadźba ◽  
Miłosz Jankowski ◽  
Marek Grzywacz ◽  
Stanisława Bazan-Socha ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Skin Incision ◽  
Anticardiolipin Antibodies ◽  
Small Blood Vessel ◽  
Anionic Phospholipids ◽  
Increased Risk ◽  
High Concentrations

SummaryAntiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and (β2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were signiF1cantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of F1brinopeptide A were detected already in the F1rst samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated signiF1cantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalciF1ed plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the F1rst time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

Inhibition of Platelet Function by Antiarrhythmic Drugs, Verapamil and Disopyramide

1982 ◽  
Vol 47 (02) ◽  
pp. 150-153 ◽  
Author(s):  
P Han ◽  
C Boatwright ◽  
N G Ardlie
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Antiarrhythmic Drugs ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Second Phase ◽  
Ionophore A23187 ◽  
High Concentrations ◽  
Artery Disease

SummaryVarious cardiovascular drugs such as nitrates and propranolol, used in the treatment of coronary artery disease have been shown to have an antiplatelet effect. We have studied the in vitro effects of two antiarrhythmic drugs, verapamil and disopyramide, and have shown their inhibitory effect on platelet function. Verapamil, a calcium channel blocker, inhibited the second phase of platelet aggregation induced by adenosine diphosphate (ADP) and inhibited aggregation induced by collagen. Disopyramide similarly inhibited the second phase of platelet aggregation caused by ADP and aggregation induced by collagen. Either drug in synergism with propranolol inhibited ADP or collagen-induced platelet aggregation. Disopyramide at high concentrations inhibited arachidonic add whereas verapamil was without effect. Verapamil, but not disopyramide, inhibited aggregation induced by the ionophore A23187.

Needleless electrospinning of PVP/PGS fibrous scaffolds for skin tissue engineering applications

2018 ◽  
Author(s):  
Antonios Keirouz ◽  
Giuseppino Fortunato ◽  
Anthony Callanan ◽  
Norbert Radacsi
Keyword(s):  
Tissue Engineering ◽  
Tensile Modulus ◽  
Dermal Fibroblasts ◽  
Skin Tissue ◽  
Skin Substitute ◽  
Electrospinning Technique ◽  
Skin Tissue Engineering ◽  
Needleless Electrospinning ◽  
High Concentrations

Scaffolds and implants used for tissue engineering need to be adapted for their mechanical properties with respect to their environment within the human body. Therefore, a novel composite for skin tissue engineering is presented by use of blends of Poly(vinylpyrrolidone) (PVP) and Poly(glycerol sebacate) (PGS) were fabricated via the needleless electrospinning technique. The formed PGS/PVP blends were morphologically, thermochemically and mechanically characterized. The morphology of the developed fibers related to the concentration of PGS, with high concentrations of PGS merging the fibers together plasticizing the scaffold. The tensile modulus appeared to be affected by the concentration of PGS within the blends, with an apparent decrease in the elastic modulus of the electrospun mats and an exponential increase of the elongation at break. Ultraviolet (UV) crosslinking of PGS/PVP significantly decreased and stabilized the wettability of the formed fiber mats, as indicated by contact angle measurements. In vitro examination showed good viability and proliferation of human dermal fibroblasts over the period of a week. The present findings provide important insights for tuning the elastic properties of electrospun material by incorporating this unique elastomer, as a promising future candidate for skin substitute constructs.

Sign in / Sign up

Export Citation Format

Share Document