scholarly journals PSII-24 Assessment of the contractility of bovine lateral saphenous and digital veins in response to ergot alkaloids

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 375-375
Author(s):  
James L Klotz ◽  
Hannah Stokley ◽  
Huihua Ji ◽  
Nabanita Chattopadhyay ◽  
David L Harmon

Abstract Decreased blood flow caused by vasoconstriction is a hallmark of ergot alkaloid exposure. Previous research has utilized the cranial branch of the lateral saphenous vein as a model to characterize the impact of ergot alkaloids on bovine peripheral vasculature. The digital vein is more distal and closer to the hoof where damage caused by vasoconstriction occurs and may be more sensitive to ergot alkaloids. Thus, the objective was to compare contractility of the bovine lateral saphenous vein and the digital vein to increasing concentrations of ergot alkaloids. Blood vessels were collected from Holstein steers at slaughter (n = 12; 551 ±29 kg), cleaned, cut into 2-mm cross-sections, and mounted in a multi-myograph. In the myograph blood vessels were submersed in continuously gassed (95% O2/5% CO2) Krebs-Henseleit buffer. Following a 1.5-hr tension equilibration, blood vessels were exposed to a reference dose of 1x10-4 M norepinephrine. Digital and lateral saphenous veins from each steer were then exposed to increasing concentrations of a-ergocryptine (ERP), ergotamine (ERT), ergocristine (ERS), ergocornine (ERO), ergonovine (ERN), tall fescue seed extract (EXT; dilutions based on measured ergovaline concentration), lysergic acid (LSA), and lysergol (LYS) were diluted to final concentrations for use in the tissue bath of 5x10-10 to 1x10-4 M. All resultant contractile response data were normalized as a percentage of the 1x10-4 M norepinephrine response and analyzed as randomized design for effects of vein and alkaloid concentration. The maximal contractile response induced by EXT, ERT, ERO, ERS, and ERP did not differ by vein type and EXT was the most vasoactive alkaloid. The response to ERN was greater for the saphenous than the digital vein (P = 0.03) and LYS and LSA did not differ (P >0.05). These data confirm that the cranial branch of lateral saphenous vein is a representative model of peripheral vasculature of the bovine hindlimb.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 312-313
Author(s):  
James Klotz ◽  
Karen McDowell

Abstract Ergot alkaloids are secondary metabolites produced by the fungal endophyte (Epichloë coenophiala) found in tall fescue (Lolium arundinaceum). Previous research has demonstrated that ergot alkaloids are vasoactive in equine palmar artery and vein but less in uterine artery. Work in cattle has shown that ergot alkaloids interact with serotonin receptors causing prolonged vasoconstriction associated with fescue toxicosis. The objective of this study was to pharmacologically assess vasoactivity of equine palmar artery and vein and uterine artery using selective agonists for serotonin receptor subtypes 5HT1B, 1D, 2A, 2B, and 7. Following euthanasia, palmar arteries, veins and uterine arteries were collected from 6 mixed breed mares. Blood vessels were separated, cleaned of external connective and adipose tissue, divided into 2–3 mm cross-sections and suspended in multi-myograph chambers containing continuously oxygenated Krebs-Henseleit buffer (95%O2/5%CO2; pH=7.4; 37°C). Following a 90-min equilibration of vascular tension and recovery from a reference addition of 1x10-4 M norepinephrine, increasing concentrations of agonists CP 93129 dihydrochloride (5HT1B), PNU 142633 (5HT1D), and TCB-2 (5HT2A) were added in 15-min intervals to assess to role of these receptors in vasoconstriction. Agonists BW 723C86 (5HT2B) and LP 44 (5HT7) were added to blood vessels precontracted with 1x10-4 M ergonovine to assess these receptors and vasorelaxation. Data were normalized as percent contractile response induced by the reference additions and analyzed as a completely randomized design using SAS. The agonists for 5HT1B and 1D did not induce a contractile response in any blood vessels tested (P > 0.05). The agonist for 5HT2A induced contractile response in all vessels tested (P < 0.05). The agonists for 5HT2B and 7 did not induce vasorelaxation different from ergonovine control (only vehicle additions) (P > 0.05). These results indicate that future work with ergot alkaloid induced vasoconstriction in equine vasculature should target the 5HT2A receptor.


Toxins ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 9
Author(s):  
Eriton E. L. Valente ◽  
David L. Harmon ◽  
James L. Klotz

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10−7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10−10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids.


2020 ◽  
Vol 98 (7) ◽  
Author(s):  
Jensen E Cherewyk ◽  
Sarah E Parker ◽  
Barry R Blakley ◽  
Ahmad N Al-Dissi

Abstract Ergot alkaloids are produced by the fungus Claviceps purpurea and their levels are carefully monitored in animal and human diets due to their harmful effects and widespread contamination of cereal crops. Ergot alkaloids exist in two forms known as the (R)- and (S)-epimers with only the former being monitored in diets in North America. The (S)-epimers of ergot alkaloids are thought to be biologically inactive and, therefore, harmless. A major mechanism by which the (R)-epimers of ergot alkaloids produce their toxic effect is through vasoconstriction. Therefore, the objective of this study was to examine the vasoactivity potential (contractile response) of four (S)-epimers, namely ergocryptinine, ergocristinine, ergocorninine, and ergotaminine utilizing an in vitro arterial tissue bath system. Bovine metatarsal arteries (n = 6, ergocryptinine and ergocorninine; n = 6, ergocristinine and ergotaminine; n = 6 arteries/(S)-epimer, total n = 12) were collected from healthy mixed-breed beef steers immediately after slaughter, cut into 3-mm arterial cross sections, and suspended in a tissue bath with continuously oxygenated Krebs–Henseleit buffer. To assess the contractile response of each (S)-epimer, a cumulative contractile dose–response curve was constructed by incubating arteries with increasing concentrations (1 × 10−11 to 1 × 10−6 M) of that (S)-epimer. Contractile responses were recorded as grams of tension and were normalized to an initial contraction of phenylephrine. Contrary to the widespread belief, all tested (S)-epimers were found vasoactive and produced a concentration-dependent arterial contractile response similar to what has been reported for the (R)-epimers. The arterial contractile response to ergotaminine was strongest and was significantly greater than that of ergocryptinine and ergocristinine at the highest concentration used (P ≤ 0.01). Our results indicate that the (S)-epimers are biologically active and are likely harmful similar to the (R)-epimers. The levels of (S)-epimers should be carefully monitored in human and animal diets worldwide.


2017 ◽  
Vol 35 (0) ◽  
Author(s):  
R.A. VIDAL ◽  
M.V. FIPKE ◽  
A.R.S. QUEIROZ ◽  
D.S. SOARES ◽  
J. GHEREKHLOO

ABSTRACT Temperature affects the selectivity of post-emergence herbicides in a complex manner. The objective of this work was to develop a method to estimate the impact of temperature on herbicide selectivity using the white oat (Avena sativa) crop and iodosulfuron-methyl as study models. Greenhouse/growth-chamber experiments were conducted using a completely randomized design with the treatments arranged as a bi-factorial, with three repetitions. The first factor consisted of six temperatures (10, 15, 20, 24, 28 and 32 oC) to which the plants were submitted during one week after the herbicide spray. The second factor corresponded to seven doses of iodosulfuron-methyl (0, 0.2, 0.4, 0.8, 1.2, 5 and 20 g ha-1). For each temperature, regression curves were fitted to the dose-response data. The rate of herbicide efficacy was computed through the method first proposed in this study. The crop tolerance to the herbicide increased proportionally to the temperature, suggesting the product detoxification is improving crop selectivity. In practical terms, it is predicted that white oat crop tolerance to iodosulfuron-methyl increases in regions of the world with high temperatures. The method developed here also can be used to understand the effect of temperature on herbicide efficacy on weeds.


2016 ◽  
pp. 3564-3575 ◽  
Author(s):  
Ara Sergey Avetisyan

The efficiency of virtual cross sections method and MELS (Magneto Elastic Layered Systems) hypotheses application is shown on model problem about distribution of wave field in thin surface layers of waveguide when plane wave signal is propagating in it. The impact of surface non-smoothness on characteristics of propagation of high-frequency horizontally polarized wave signal in isotropic elastic half-space is studied. It is shown that the non-smoothness leads to strong distortion of the wave signal over the waveguide thickness and along wave signal propagation direction as well.  Numerical comparative analysis of change in amplitude and phase characteristics of obtained wave fields against roughness of weakly inhomogeneous surface of homogeneous elastic half-space surface is done by classical method and by proposed approach for different kind of non-smoothness.


2017 ◽  
Vol 5 (2) ◽  
pp. 93-96
Author(s):  
Shashi Kant Shukla ◽  
◽  
Awadhesh Kumar ◽  
Anupam Dikshit ◽  
◽  
...  

The present study aims the impact of Pseudomonas putida on different growth parameters of Trigonella sp., a leguminous plant to support the requirement of food, protein along with their medicinal value in the rural areas of India. A pot experiment was arranged based on completely randomized design with four replications at Biological Product Laboratory, Botany Department, University of Allahabad. Treatments were given at the seed level with one of control. Results indicated that application of P. putida significantly improved vegetative growth and showed an edge on the growth of the fenugreek as compared to the control.


2019 ◽  
Vol 34 (32) ◽  
pp. 1950259 ◽  
Author(s):  
S. M. Troshin ◽  
N. E. Tyurin

We comment briefly on relations between the elastic and inelastic cross-sections valid for the shadow and reflective modes of the elastic scattering. Those are based on the unitarity arguments. It is shown that the redistribution of the probabilities of the elastic and inelastic interactions (the form of the inelastic overlap function becomes peripheral) under the reflective scattering mode can lead to increasing ratio of [Formula: see text] at the LHC energies. In the shadow scattering mode, the mechanism of this increase is a different one, since the impact parameter dependence of the inelastic interactions probability is central in this mode. A short notice is also given on the slope parameter and the leading contributions to its energy dependence in both modes.


2020 ◽  
Vol 2020 (11) ◽  
Author(s):  
Claude Duhr ◽  
Falko Dulat ◽  
Bernhard Mistlberger

Abstract We present the production cross section for a lepton-neutrino pair at the Large Hadron Collider computed at next-to-next-to-next-to-leading order (N3LO) in QCD perturbation theory. We compute the partonic coefficient functions of a virtual W± boson at this order. We then use these analytic functions to study the progression of the perturbative series in different observables. In particular, we investigate the impact of the newly obtained corrections on the inclusive production cross section of W± bosons, as well as on the ratios of the production cross sections for W+, W− and/or a virtual photon. Finally, we present N3LO predictions for the charge asymmetry at the LHC.


Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 291
Author(s):  
Rossalin Yonpiam ◽  
Jair Gobbet ◽  
Ashok Jadhav ◽  
Kaushik Desai ◽  
Barry Blakley ◽  
...  

Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10−6 M; Exp EC50 = 1.079 × 10−6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.


2018 ◽  
Vol 98 (4) ◽  
pp. 688-700 ◽  
Author(s):  
T. Grusie ◽  
V. Cowan ◽  
J. Singh ◽  
J. McKinnon ◽  
B. Blakley

Cows were fed ration for 9 wk containing 5, 48, 201, and 822 μg kg−1 ergot alkaloids. The objective was to evaluate the impact of ergot consumption in beef cow–calf operations. Ergot alkaloids up to 822 μg kg−1 did not alter the weight of peripartum and postpartum beef cows (P = 0.93) or nursing calves (P = 0.08), rectal temperature (P = 0.16), or plasma prolactin concentrations (P = 0.30) at moderate ambient temperatures. Ergot did not influence the time (>1 ng mL−1; P = 0.79) or the progesterone concentration (P = 0.38) at the time of first postpartum rise or the size of the first (14 ± 0.6 mm; P = 0.40) and second (13 ± 0.5 mm; P = 0.41) follicles to ovulate. The maximum size of the first postpartum corpus luteum (CL) was 4 mm larger in the 822 μg kg−1 ergot group compared with the control (P = 0.03) for the first ovulation post partum, but not for the second (P = 0.11). There was no effect of ergot exposure on the number of days until the appearance of the first (43 ± 4 d; P = 0.95) or second (52 ± 4 d; P = 0.98) CL post partum. Ergot alkaloid concentrations up to 822 μg kg−1 did not affect pregnancy rates (X2 = 0.36). In conclusion, ergot alkaloid exposure for 9 wk to concentrations as high as 822 μg kg−1 did not alter performance in pregnant and postpartum beef cattle at moderate ambient temperatures.


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