Apparent desensitization of the effects of sigma receptor ligand haloperidol in isolated rat and guinea pig hearts after chronic treatmentThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 1019-1027 ◽  
Author(s):  
Katerina Fialova ◽  
Olga Krizanova ◽  
Jiri Jarkovsky ◽  
Marie Novakova
Keyword(s):  
Guinea Pig ◽  
Qt Interval ◽  
Ionic Channels ◽  
Fine Tuning ◽  
Sigma Receptors ◽  
Acute Administration ◽  
Cardiovascular Research ◽  
Electrophysiological Properties ◽  
Sigma Ligand

The supposed role of cardiac sigma receptors is fine tuning of contractility. Sigma receptors affect several ionic channels and hence their signaling is reflected by the electrophysiological properties of the heart. Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias, including severe ones. The effects of the prototypical sigma ligand haloperidol have been studied extensively in humans as well as in various animal models, primarily after acute administration. We examined the incidence of arrhythmias, changes in heart rate, and prolongation of QT interval in isolated Langendorff-perfused rat and guinea pig hearts after they were exposed to nanomolar concentrations of haloperidol. Hearts from both untreated (acute) and pretreated (chronic) animals were investigated. While QT prolongation and arrhythmias due to haloperidol administration were observed in untreated rat and guinea pig hearts, arrhythmias were completely prevented in both species of chronically treated animals. In treated guinea pigs, the results were generally less convincing. Since the hearts were exposed to nanomolar concentration of haloperidol, we conclude that our data may be explained by desensitization of sigma receptors.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

It Keeps Me Seeking

2018 ◽  
Author(s):  
Andrew Briggs ◽  
Hans Halvorson ◽  
Andrew Steane
Keyword(s):  
Evolutionary Biology ◽  
Quantum Physics ◽  
Natural World ◽  
Theological Reflection ◽  
Fine Tuning ◽  
Good Argument ◽  
The Difference ◽  
Argument From Design ◽  
Relationship Of

Two scientists and a philosopher aim to show how science both enriches and is enriched by Christian faith. The text is written around four themes: 1. God is a being to be known, not a hypothesis to be tested; 2. We set a high bar on what constitutes good argument; 3. Uncertainty is OK; 4. We are allowed to open up the window that the natural world offers us. This is not a work of apologetics. Rather, the text takes an overview of various themes and gives reactions and responses, intended to place science correctly as a valued component of the life of faith. The difference between philosophical analysis and theological reflection is expounded. Questions of human identity are addressed from philosophy, computer science, quantum physics, evolutionary biology and theological reflection. Contemporary physics reveals the subtle and open nature of physical existence, and offers lessons in how to learn and how to live with incomplete knowledge. The nature and role of miracles is considered. The ‘argument from design’ is critiqued, especially arguments from fine-tuning. Logical derivation from impersonal facts is not an appropriate route to a relationship of mutual trust. Mainstream evolutionary biology is assessed to be a valuable component of our understanding, but no exploratory process can itself fully account for the nature of what is discovered. To engage deeply in science is to seek truth and to seek a better future; it is also an activity of appreciation, as one may appreciate a work of art.

scholarly journals Effect of tungsten disulfide nanotubes on crystallization of polylactide under uniaxial deformation and annealing

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Fausta Loffredo ◽  
Loredana Tammaro ◽  
Tiziana Di Luccio ◽  
Carmela Borriello ◽  
Fulvia Villani ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Structural Evolution ◽  
Tungsten Disulfide ◽  
Fine Tuning ◽  
Nanocomposite Films ◽  
Uniaxial Deformation ◽  
Scanning Calorimetry ◽  
X Ray ◽  
X Ray Scattering

AbstractTungsten disulfide (WS2) nanotubes (NTs) are examined here as a filler for polylactide (PLA) for their ability to accelerate PLA crystallization and for their promising biocompatibility in relevant to biomedical applications of PLA-WS2 nanocomposites. In this work, we have studied the structural and thermal properties of PLA-WS2 nanocomposite films varying the concentration of WS2 NTs from 0 (neat PLA) to 0.6 wt%. The films were uniaxially drawn at 90 °C and annealed at the same temperature for 3 and 10 min. Using wide angle x-ray scattering, Raman spectroscopy and differential scanning calorimetry, we probed the effects of WS2 NT addition on the structure of the PLA films at various stages of processing (unstretched, stretching, annealing). We found that 0.6 wt% of WS2 induces the same level of crystallinity in as stretched PLA-WS2 as annealing in neat PLA for 10 min. These data provide useful insights into the role of WS2 NTs on the structural evolution of PLA-WS2 composites under uniaxial deformation, and extend their applicability to situations where fine tuning of PLA crystallinity is desirable.

scholarly journals Seed Gamma Irradiation of Arabidopsis thaliana ABA-Mutant Lines Alters Germination and Does Not Inhibit the Photosynthetic Efficiency of Juvenile Plants

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097924
Author(s):  
Darya Babina ◽  
Marina Podobed ◽  
Ekaterina Bondarenko ◽  
Elizaveta Kazakova ◽  
Sofia Bitarishvili ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Growth Response ◽  
Dose Range ◽  
Fine Tuning ◽  
Plant Tolerance ◽  
Inhibitory Effects ◽  
Γ Irradiation ◽  
Photosynthetic Responses ◽  
Mutant Lines

Plant growth response to γ-irradiation includes stimulating or inhibitory effects depending on plant species, dose applied, stage of ontogeny and other factors. Previous studies showed that responses to irradiation could depend on ABA accumulation and signaling. To elucidate the role of ABA in growth and photosynthetic responses to irradiation, lines Col-8, abi3-8 and aba3 -1 of Arabidopsis thaliana were used. Seeds were γ-irradiated using 60Co in the dose range 50-150 Gy. It was revealed that the dose of 150 Gy affected germination parameters of aba3 -1 and Col-8 lines, while abi3-8 line was the most resistant to the studied doses and even showed faster germination at early hours after γ-irradiation at 50 Gy. These results suggest that susceptibility to ABA is probably more important for growth response to γ-irradiation than ABA synthesis. The photosynthetic functioning of 16-day-old plants mainly was not disturbed by γ-irradiation of seeds, and no indication of photosystem II photoinhibition was noticed, revealing the robustness of the photosynthetic system of A. thaliana. Glutathione peroxidase activity and ABA concentrations in plant tissues were not affected in the studied dose range. These results contribute to the understanding of germination and photosynthesis fine-tuning and of mechanisms of plant tolerance to ionizing radiation.

scholarly journals Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

2021 ◽  
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Middle Phase ◽  
Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

scholarly journals MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Stephanie Maia Acuña ◽  
Lucile Maria Floeter-Winter ◽  
Sandra Marcia Muxel
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Small Rnas ◽  
Immune Cell ◽  
Fine Tuning ◽  
Biological Processes ◽  
Host Interactions ◽  
The Past ◽  
Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

scholarly journals Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation

2005 ◽  
Vol 566 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Min-Goo Lee ◽  
Donald W. MacGlashan ◽  
Bradley J. Undem
Keyword(s):  
Guinea Pig ◽  
Chloride Channels ◽  
C Fibre

scholarly journals Role of endothelial cell hyperpolarization in EDHF-mediated responses in the guinea-pig carotid artery

2000 ◽  
Vol 129 (6) ◽  
pp. 1103-1112 ◽  
Author(s):  
J -F Quignard ◽  
M Félétou ◽  
G Edwards ◽  
J Duhault ◽  
A H Weston ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Carotid Artery ◽  
Guinea Pig
Sign in / Sign up

Export Citation Format

Share Document