Effects of common polymorphisms in the α1A-, α2B-, β1- and β2-adrenoreceptors on haemodynamic responses to adrenaline

2003 ◽  
Vol 104 (5) ◽  
pp. 509-520 ◽  
Author(s):  
Amir SNAPIR ◽  
Juha KOSKENVUO ◽  
Jyri TOIKKA ◽  
Marju ORHO-MELANDER ◽  
Susanna HINKKA ◽  
...  
Keyword(s):  
Coronary Flow ◽  
Plasma Adrenaline ◽  
Coding Regions ◽  
Naturally Occurring ◽  
Pr Interval ◽  
Before And After ◽  
Adrenaline Infusion ◽  
Β2 Adrenoreceptors

Common naturally occurring polymorphisms have been identified in the coding regions of the α1A-, α2B-, β1- and β2-adrenoceptor (AR) genes [α1A-AR R492C, α2B-AR insertion/deletion (I/D), β1-AR R389G, β2-AR G16R and β2-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160ng/kg of body weight per min; 5min for each infusion rate) before and after β-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the α1A-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the α2B-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before β-blockade. The β1-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the β2-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the α2B-AR D/D genotype confers increased vasoconstriction and that the β2-AR GG genotype confers reduced vasodilatation.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

scholarly journals In Vivo and In Vitro Protein Ligation by Naturally Occurring and Engineered Split DnaE Inteins

PLoS ONE ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. e5185 ◽  
Author(s):  
A. Sesilja Aranko ◽  
Sara Züger ◽  
Edith Buchinger ◽  
Hideo Iwaï
Keyword(s):  
Protein Ligation ◽  
Naturally Occurring ◽  
Vitro Protein

scholarly journals Detection of Anthrax Toxin in the Serum of Animals Infected with Bacillus anthracis by Using Engineered Immunoassays

2006 ◽  
Vol 13 (6) ◽  
pp. 671-677 ◽  
Author(s):  
Robert Mabry ◽  
Kathleen Brasky ◽  
Robert Geiger ◽  
Ricardo Carrion ◽  
Gene B. Hubbard ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Lethal Factor ◽  
Systemic Circulation ◽  
Rapid Identification ◽  
Anthrax Toxin ◽  
Soluble Form ◽  
Before And After

ABSTRACT Several strategies that target anthrax toxin are being developed as therapies for infection by Bacillus anthracis. Although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. We developed a series of sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) for detection of both the protective antigen (PA) and lethal factor (LF) components of the anthrax exotoxin in serum. The assays utilize as capture agents an engineered high-affinity antibody to PA, a soluble form of the extracellular domain of the anthrax toxin receptor (ANTXR2/CMG2), or PA itself. Sandwich immunoassays were used to detect and quantify PA and LF in animals infected with the Ames or Vollum strains of anthrax spores. PA and LF were detected before and after signs of toxemia were observed, with increasing levels reported in the late stages of the infection. These results represent the detection of free PA and LF by ELISA in the systemic circulation of two animal models exposed to either of the two fully virulent strains of anthrax. Simple anthrax toxin detection ELISAs could prove useful in the evaluation of potential therapies and possibly as a clinical diagnostic to complement other strategies for the rapid identification of B. anthracis infection.

Tracings of Behavior of Myoblasts Cultured Under Couette Type of Shear Flow Between Parallel Disks

2021 ◽  
Author(s):  
Shigehiro Hashimoto ◽  
Hiroki Yonezawa
Keyword(s):  
Shear Stress ◽  
Shear Flow ◽  
Rotating Disk ◽  
Time Lapse ◽  
Mechanical Stimuli ◽  
Parallel Disks ◽  
Before And After ◽  
A Cell

Abstract A cell deforms and migrates on the scaffold under mechanical stimuli in vivo. In this study, a cell with division during shear stress stimulation has been observed in vitro. Before and after division, both migration and deformation of each cell were analyzed. To make a Couette-type shear flow, the medium was sandwiched between parallel disks (the lower stationary culture-disc and the upper rotating disk) with a constant gap. The wall shear stress (1.5 Pa &lt; τ &lt; 2 Pa) on the surface of the lower culture plate was controlled by the rotational speed of the upper disc. Myoblasts (C2C12: mouse myoblast cell line) were used in the test. After cultivation without flow for 24 hours for adhesion of the cells to the lower disk, constant τ was applied to the cells in the incubator for 7 days. The behavior of each cell during shear was tracked by time-lapse images observed by an inverted phase contrast microscope placed in the incubator. Experimental results show that each cell tends to divide after higher activities: deformation and migration. The tendency is remarkable at the shear stress of 1.5 Pa.

Fistulous-type vein of Galen malformation phantom model for endovascular training and research

2016 ◽  
Vol 9 (9) ◽  
pp. 880-886
Author(s):  
Dan Meila ◽  
Katharina Melber ◽  
Dominik Grieb ◽  
Collin Jacobs ◽  
Heinrich Lanfermann ◽  
...  
Keyword(s):  
Treatment Options ◽  
Endovascular Embolization ◽  
High Flow ◽  
Vein Of Galen ◽  
Vein Of Galen Malformation ◽  
Phantom Model ◽  
Before And After ◽  
And Training

IntroductionVein of Galen malformation (VGM), a high-flow intracranial arteriovenous shunt, is among the most severe neurovascular diseases in childhood. In many cases untreated children die or survive only severely disabled. Endovascular embolization is the preferred treatment.ObjectiveTo develop a simple fistulous-type VGM phantom model for teaching and training of different endovascular treatment methods and to investigate new treatment options and devices.MethodsAn experimental in vitro pulsatile phantom model was developed imitating a high-flow fistulous-type VGM, which is typical, especially in the neonatal phase. Pressure measurements at different arterial sites were performed before and after closure of the VGM. Closure of the VGM was achieved by coiling using a combined microcatheter-based transvenous and transarterial approach called ‘kissing microcatheter technique’.ResultsThe behaviour of the phantom model in vitro under fluoroscopy and under angiographic runs was extremely similar to that in in vivo conditions in children. The results showed that intra-arterial pressures changed and increased statistically significantly at all measurement sites after embolization, as in human arteriovenous malformation. We also demonstrated different and complementary visualizations of hemodynamics and angioarchitecture by antegrade and retrograde microcatheter injections.ConclusionsOur phantom model behaves like a typical fistulous-type VGM and can be used in vitro for teaching and training and for further research. It offers a new and better understanding of hemodynamics and angioarchitecture in the endovascular management of VGM.

scholarly journals In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

2013 ◽  
Vol 49 (4) ◽  
pp. 803-809
Author(s):  
Monica Lacerda Lopes Martins ◽  
Henrique Poltronieri Pacheco ◽  
Iara Giuberti Perini ◽  
Dominik Lenz ◽  
Tadeu Uggere de Andrade ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Assay ◽  
Hypotensive Effect ◽  
Ace Inhibition ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Total Phenolic ◽  
Before And After

In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES), a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE) activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE) and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg), with acetylcholine (ACh) as positive control (5 µg/kg, i.v.). The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg) in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.). Captopril (30 mg/kg) was used as positive control. Bulbostylis capillaris (86.89 ± 15.20%) and ERE (74.89 ± 11.95%, ERE) were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%). ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

scholarly journals Fluoride Treatment and In Vitro Corrosion Behavior of Mg-Nd-Y-Zn-Zr Alloys Type

Materials ◽  
2022 ◽  
Vol 15 (2) ◽  
pp. 566
Author(s):  
Pham Hong Quan ◽  
Iulian Antoniac ◽  
Florin Miculescu ◽  
Aurora Antoniac ◽  
Veronica Manescu (Păltânea) ◽  
...  
Keyword(s):  
Corrosion Behavior ◽  
Orthopedic Implants ◽  
Immersion Test ◽  
Nacl Solution ◽  
Fluoride Ions ◽  
Fluoride Treatment ◽  
Cardiovascular Stents ◽  
Before And After

Fluoride conversion coatings on Mg present many advantages, among which one can find the reduction of the corrosion rate under “in vivo” or “in vitro” conditions and the promotion of the calcium phosphate deposition. Moreover, the fluoride ions released from MgF2 do not present cytotoxic effects and inhibit the biofilm formation, and thus these treated alloys are very suitable for cardiovascular stents and biodegradable orthopedic implants. In this paper, the biodegradation behavior of four new magnesium biodegradable alloys that have been developed in the laboratory conditions, before and after surface modifications by fluoride conversion (and sandblasting) coatings, are analyzed. We performed structural and surface analysis (XRD, SEM, contact angle) before and after applying different surface treatments. Furthermore, we studied the electrochemical behavior and biodegradation of all experimental samples after immersion test performed in NaCl solution. For a better evaluation, we also used LM and SEM for evaluation of the corroded samples after immersion test. The results showed an improved corrosion resistance for HF treated alloy in the NaCl solution. The chemical composition, uniformity, thickness and stability of the layers generated on the surface of the alloys significantly influence their corrosion behavior. Our study reveals that HF treatment is a beneficial way to improve the biofunctional properties required for the studied magnesium alloys to be used as biomaterials for manufacturing the orthopedic implants.

scholarly journals Single amino acid mutations effect Zika virus replication in vitro and virulence in vivo

2020 ◽  
Author(s):  
Nicole M. Collette ◽  
Victoria H.I. Lao ◽  
Dina R. Weilhammer ◽  
Barbara Zingg ◽  
Shoshana D. Cohen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Zika Virus ◽  
Model Systems ◽  
Single Amino Acid ◽  
Replication Rate ◽  
Adult Mice ◽  
Naturally Occurring ◽  
Viral Virulence

AbstractThe 2014-2016 Zika virus (ZIKV) epidemic in the Americas resulted in large deposits of next-generation sequencing data from clinical samples. This resource was mined to identify emerging mutations and trends in mutations as the outbreak progressed over time. Information on transmission dynamics, prevalence and persistence of intra-host mutants, and the position of a mutation on a protein were then used to prioritize 544 reported mutations based on their ability to impact ZIKV phenotype. Using this criteria, six mutants (representing naturally occurring mutations) were generated as synthetic infectious clones using a 2015 Puerto Rican epidemic strain PRVABC59 as the parental backbone. The phenotypes of these naturally occurring variants were examined using both cell culture and murine model systems. Mutants had distinct phenotypes, including changes in replication rate, embryo death, and decreased head size. In particular, a NS2B mutant previously detected during in vivo studies in rhesus macaques was found to cause lethal infections in adult mice, abortions in pregnant females, and increased viral genome copies in both brain tissue and blood of female mice. Additionally, mutants with changes in the region of NS3 that interfaces with NS5 during replication displayed reduced replication in the blood of adult mice. This analytical pathway, integrating both bioinformatic and wet lab experiments, provides a foundation for understanding how naturally occurring single mutations affect disease outcome and can be used to predict the of severity of future ZIKV outbreaks.Author summaryTo determine if naturally occurring individual mutations in the Zika virus epidemic genotype effect viral virulence or replication rate in vitro or in vivo, we generated an infectious clone representing the epidemic genotype of stain Puerto Rico, 2015. Using this clone, six mutants were created by changing nucleotides in the genome to cause one to two amino acid substitutions in the encoded proteins. The six mutants we generated represent mutations that differentiated the early epidemic genotype from genotypes that were either ancestral or that occurred later in the epidemic. We assayed each mutant for changes in growth rate, and for virulence in adult mice and pregnant mice. Three of the mutants caused catastrophic embryo effects including increased embryonic death or significant decrease in head diameter. Three other mutants that had mutations in a genome region associated with replication resulted in changes in in vitro and in vivo replication rates. These results illustrate the potential impact of individual mutations in viral phenotype.

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