scholarly journals Phase-2 reentry in cardiac tissue: Role of the slow calcium pulse

2010 ◽  
Vol 82 (1) ◽  
Author(s):  
Inma R. Cantalapiedra ◽  
Angelina Peñaranda ◽  
Blas Echebarria ◽  
Jean Bragard
Keyword(s):  
2020 ◽  
Vol 21 (7) ◽  
pp. 541-547
Author(s):  
Bao Sun ◽  
Yue Yang ◽  
Mengzi He ◽  
Yanan Jin ◽  
Xiaoyu Cao ◽  
...  

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.


2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.


2021 ◽  
Vol 27 ◽  
Author(s):  
Anja Steinmaurer ◽  
Isabella Wimmer ◽  
Thomas Berger ◽  
Paulus Stefan Rommer ◽  
Johann Sellner

: Significant progress has been made in understanding the immunopathogenesis of multiple sclerosis (MS) over recent years. Successful clinical trials with CD20-depleting monoclonal antibodies have corroborated the fundamental role of B cells in the pathogenesis of MS and reinforced the notion that cells of the B cell lineage are an attractive treatment target. Therapeutic inhibition of Bruton's tyrosine kinase (BTK), an enzyme involved in B cell and myeloid cell activation and function, is regarded as a next-generation approach that aims to attenuate both errant innate and adaptive immune functions. Moreover, brain-penetrant BTK inhibitors may impact compartmentalized inflammation and neurodegeneration within the central nervous system by targeting brain-resident B cells and microglia, respectively. Preclinical studies in animal models of MS corroborated an impact of BTK inhibition on meningeal inflammation and cortical demyelination. Notably, BTK inhibition attenuated the antigen-presenting capacity of B cells and the generation of encephalitogenic T cells. Evobrutinib, a selective oral BTK inhibitor, has been tested recently in a phase 2 study of patients with relapsing-remitting MS. The study met the primary endpoint of a significantly reduced cumulative number of Gadolinium-enhancing lesions under treatment with evobrutinib compared to placebo treatment. Thus, the results of ongoing phase 2 and 3 studies with evobrutinib, fenobrutinib, and tolebrutinib in relapsing-remitting and progressive MS are eagerly awaited. This review article introduces the physiological role of BTK, summarizes the pre-clinical and trial evidence, and addresses the potential beneficial effects of BTK inhibition in MS.


2016 ◽  
Vol 97 ◽  
pp. 187-198 ◽  
Author(s):  
Sayantani Chowdhury ◽  
Sumit Ghosh ◽  
Kahkashan Rashid ◽  
Parames C. Sil

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Michael Connolly ◽  
Mary Ryder ◽  
Kate Frazer ◽  
Eileen Furlong ◽  
Teresa Plazo Escribano ◽  
...  

Abstract Background Special palliative care is provided in a range of settings including a patient’s home (their primary place of dwelling), a hospice in-patient unit, or an acute hospital. The aim of the study was to evaluate the role of the specialist in palliative care clinical nurse specialist (SPC CNS) role in an acute hospital setting. Methods This study was conducted using a mixed methods sequential explanatory approach in two phases; phase 1 involved completion of a study questionnaire (n = 121) and phase 2 involved part-taking in a focus group (n = 6) or individual interview (n = 4). Results Phase 1 results indicated that respondents held positive attitudes towards the Specialist Palliative Care Clinical Nurses Specialist (SPC CNS) in relation to clinical care, education and patient advocacy. Phase 2 qualitative findings identified the importance of the role in terms of symptom management, education and support. Conclusions This study provides an evaluation of a SPC CNS role since it was established in an acute hospital setting. The evidence indicates that there is a varied understanding of the role of the SPC CNS. The role was seen as an important one particularly in terms of referrals to and support provided by the SPC CNS, as well as recognition of the importance of the role is providing ongoing education to staff.


2021 ◽  
Vol 26 (3) ◽  
pp. 45-47
Author(s):  
Peter Michael Reil ◽  
Teodor Traian Maghiar ◽  
Karlheinz Seidl ◽  
Claudia Teodora Judea Pusta ◽  
Ciprian Borza ◽  
...  

Abstract Septic cardiomyopathy remains a difficult medical problem to manage in critically ill patients. With all currently available therapeutic options, the mortality rate in these patients remains high. Our study included 29 patients diagnosed clinically with sepsis. A control group was used to compare the results. In all patients, p53 expression was assessed in cardiac tissue obtained from these patients and a statistical correlation was made with clinical data. The different expression rates of p53 do not correlate with patient’s age, having appropriate means in years, but with an increasing tendency with increasing expression (p=0.2110). The pulmonary infections are responsible for the majority of the septic state in the study group (over 55%). The difference between the infection sites is statistically significant (p<0.0001).


2014 ◽  
Vol 307 (1) ◽  
pp. H73-H79 ◽  
Author(s):  
Wei Kong ◽  
Vladimir G. Fast

Previous experiments in cultures of neonatal rat myocytes demonstrated that the shape of Cai2+ transients measured using high-affinity Ca2+-sensitive dyes may be misrepresented. The purpose of this study was to examine the role of dye affinity in Cai2+ measurements in intact adult cardiac tissue by comparing optical recordings obtained with high- and low-affinity dyes. Experiments were carried out in porcine left ventricular (LV) wedge preparations stained locally by intramural injection via microcapillaries (diameter = 150 μm) with a low-affinity Ca2+-sensitive dye Fluo-4FF or Fluo-2LA (nominal Kd, ∼7–10 μmol/l), high-affinity dye Rhod-2 ( Kd = 0.57 μmol/l), and Fluo-4 or Fluo-2MA ( Kd, ∼0.4 μmol/l); in addition, tissue was stained with transmembrane potential ( Vm)-sensitive dye RH-237. Optical recordings of Vm and Cai2+ were made using optical fibers (diameter = 325 μm) glued with the microcapillaries. The durations of Cai2+ transients measured at 50% level of recovery (CaD50) using high-affinity Fluo-4/Fluo-2MA dyes were up to ∼81% longer than those measured with low-affinity Fluo-4FF/Fluo-2LA at long pacing cycle lengths (CL). In Fluo-4/Fluo-2MA measurements at long CLs, Cai2+ transients often (∼50% of cases) exhibited slow upstroke rise and extended plateau. In Rhod-2 measurements, CaD50 was moderately longer (up to ∼35%) than in Fluo-4FF recordings, but Cai2+ transient shapes were similar. In all series of measurements, mean action potential duration values were not significantly different ( P > 0.05). The delays between Vm and Cai2+ upstrokes were comparable for low- and high-affinity dyes ( P > 0.05). In conclusion, measurements of Cai2+ transient in ventricular myocardium are strongly affected by the affinity of Ca2+ dyes. The high-affinity dyes may overestimate the duration and alter the shape of Cai2+ transients.


1999 ◽  
Vol 26 (12) ◽  
pp. 964-969 ◽  
Author(s):  
Kawonia P Mull ◽  
Qadriyyah Debnam ◽  
Syeda M Kabir ◽  
Mohit Lal Bhattacharyya

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