scholarly journals Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation

2021 ◽  
Vol 10 (12) ◽  
pp. 2657
Author(s):  
Shauna McBride ◽  
Sahar Avazzadeh ◽  
Antony M. Wheatley ◽  
Barry O’Brien ◽  
Ken Coffey ◽  
...  
Keyword(s):  
Cell Death ◽  
Irreversible Electroporation ◽  
Structural Heart Disease ◽  
Electrical Energy ◽  
Cell Types ◽  
Fine Tuning ◽  
Specific Cell ◽  
Negative Effects ◽  
Reversible Electroporation ◽  
Disease Focus

Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF.

scholarly journals Distinct cell death pathways triggered by the adenovirus early region 4 ORF 4 protein

2002 ◽  
Vol 158 (3) ◽  
pp. 519-528 ◽  
Author(s):  
Amélie Robert ◽  
Marie-Joëlle Miron ◽  
Claudia Champagne ◽  
Marie-Claude Gingras ◽  
Philip E. Branton ◽  
...  
Keyword(s):  
Cell Death ◽  
Critical Role ◽  
Adenovirus Type ◽  
Cell Types ◽  
Specific Cell ◽  
Nuclear Targeting ◽  
Early Region ◽  
Delayed Cell Death ◽  
Distinct Cell ◽  
Early Region 4

In transformed cells, induction of apoptosis by adenovirus type 2 (Ad2) early region 4 ORF 4 (E4orf4) correlates with accumulation of E4orf4 in the cell membrane–cytoskeleton fraction. However, E4orf4 is largely expressed in nuclear regions before the onset of apoptosis. To determine the relative contribution of nuclear E4orf4 versus membrane-associated E4orf4 to cell death signaling, we engineered green fluorescent fusion proteins to target E4orf4 to specific cell compartments. The targeting of Ad2 E4orf4 to cell membranes through a CAAX-box or a myristylation consensus signal sufficed to mimic the fast Src-dependent apoptotic program induced by wild-type E4orf4. In marked contrast, the nuclear targeting of E4orf4 abolished the early induction of extranuclear apoptosis. However, nuclear E4orf4 still induced a delayed cell death response independent of Src-like activity and of E4orf4 tyrosine phosphorylation. The zVAD.fmk-inhibitable caspases were dispensable for execution of both cell death programs. Nevertheless, both pathways led to caspase activation in some cell types through the mitochondrial pathway. Finally, our data support a critical role for calpains upstream in the death effector pathway triggered by the Src-mediated cytoplasmic death signal. We conclude that Ad2 E4orf4 induces two distinct cell death responses, whose relative contributions to cell killing may be determined by the genetic background.

Natural post-translational modifications of chemokines

2006 ◽  
Vol 34 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
P. Proost ◽  
S. Struyf ◽  
J. Van Damme
Keyword(s):  
Transcriptional Activation ◽  
Chemokine Receptors ◽  
Cell Types ◽  
Proteolytic Processing ◽  
Fine Tuning ◽  
Specific Cell ◽  
Receptor Specificity ◽  
Post Translational Modifications ◽  
N Terminus ◽  
Acute And Chronic Inflammation

Chemokines, adhesion molecules, cytokines and proteases regulate the extravasation of leucocytes during acute and chronic inflammation and leucocyte homing. Chemokines are produced after transcriptional activation by inflammatory mediators such as cytokines or microbial Toll-like receptor ligands and their effect depends on the expression of chemokine receptors on specific cell types. More and more evidence points towards a role for post-translational modifications in the fine-tuning of chemokine activity. Although both glycosylation and proteolytic processing of the C- and/or N-terminus of chemokines has been reported, mainly proteolytic processing of the N-terminus appears to affect the receptor specificity, chemotactic property and signalling potency of these low-molecular-mass proteins. N-terminal processing of chemokines by aminopeptidases or endoproteases may alter the receptor specificity and may result in up- or down-regulation of their chemotactic, antiviral or angiogenic activity.

Irreversible Electroporation (IRE) to Treat Brain Tumors

2008 ◽  
Author(s):  
Paulo A. Garcia ◽  
John Robertson ◽  
John Rossmeisl ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Brain Tumors ◽  
High Voltage ◽  
Electric Pulse ◽  
Irreversible Electroporation ◽  
Transient Effect ◽  
Electric Pulses ◽  
Thermal Cell ◽  
Reversible Electroporation

Electroporation is the phenomenon in which permeability of the cell membrane to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high voltage electric pulses [1]. The application of the electric pulse can have no effect, can have a transient effect known as reversible electroporation, or can cause permanent permeation known as irreversible electroporation (IRE) which leads to non-thermal cell death by necrosis [1, 2].

scholarly journals Identification of tissue-specific cell death using methylation patterns of circulating DNA

2016 ◽  
Vol 113 (13) ◽  
pp. E1826-E1834 ◽  
Author(s):  
Roni Lehmann-Werman ◽  
Daniel Neiman ◽  
Hai Zemmour ◽  
Joshua Moss ◽  
Judith Magenheim ◽  
...  
Keyword(s):  
Cell Death ◽  
Minimally Invasive ◽  
Dna Sequences ◽  
Cell Types ◽  
The Body ◽  
Specific Cell ◽  
Circulating Dna ◽  
Cell Type ◽  
Tissue Specific ◽  
Methylation Patterns

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.

scholarly journals Evaluation of electroporated area using 2,3,5-triphenyltetrazolium chloride in a potato model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung Jeong ◽  
Hongbae Kim ◽  
Junhyung Park ◽  
Ki Woo Kim ◽  
Sung Bo Sim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Target Tissue ◽  
Triphenyltetrazolium Chloride ◽  
Tissue Model ◽  
Electric Pulses ◽  
Reversible Electroporation ◽  
Over Time

AbstractIrreversible electroporation (IRE) is a tissue ablation method, uses short high electric pulses and results in cell death in target tissue by irreversibly permeabilizing the cell membrane. Potato is commonly used as a tissue model for electroporation experiments. The blackened area that forms 12 h after electric pulsing is regarded as an IRE-ablated area caused by melanin accumulation. Here, the 2,3,5-triphenyltetrazolium chloride (TTC) was used as a dye to assess the IRE-ablated area 3 h after potato model ablation. Comparison between the blackened area and TTC-unstained white area in various voltage conditions showed that TTC staining well delineated the IRE-ablated area. Moreover, whether the ablated area was consistent over time and at different staining times was investigated. In addition, the presumed reversible electroporation (RE) area was formed surrounding the IRE-ablated area. Overall, TTC staining can provide a more rapid and accurate electroporated area evaluation.

scholarly journals Identification of 13 independent genetic loci associated with cognitive resilience in healthy aging in 330,097 individuals in the UK Biobank

2021 ◽  
Author(s):  
Joan Fitzgerald ◽  
Laura Fahey ◽  
Laurena Holleran ◽  
Pilib Ó Broin ◽  
Gary Donohoe ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Genome Wide Association Study ◽  
Cell Types ◽  
Brain Regions ◽  
Specific Cell ◽  
Uk Biobank ◽  
Negative Effects ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

AbstractCognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. Here we employed a proxy phenotype approach to create a longitudinal cognitive resilience phenotype using past education years and current processing speed, reflecting an average time span of 40 years, in 330,097 individuals from the UK Biobank. A genome-wide association study identified 13 independent genome-wide significant loci that implicate 33 genes. A portion of resilience’s genetic signal is distinct from the genetics of intelligence. Functional analyses showed enrichment in several brain regions and involvement of specific cell types, including GABAergic neurons (P=6.59×10−8) and glutamatergic neurons (P=6.98×10−6) in the cortex. Gene-set analyses implicated the biological process “neuron differentiation” (P=9.7×10−7) and the cellular component “synaptic part” (P=2.14×10−6). Mendelian randomization analysis showed a causative effect of white matter volume on cognitive resilience. These results enhance neurobiological understanding of resilience.

scholarly journals Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats

2007 ◽  
Vol 192 (1) ◽  
pp. 215-227 ◽  
Author(s):  
Ana I Arroba ◽  
Alfonso M Lechuga-Sancho ◽  
Laura M Frago ◽  
Jesús Argente ◽  
Julie A Chowen
Keyword(s):  
Cell Death ◽  
Anterior Pituitary ◽  
Cell Types ◽  
Diabetic Rats ◽  
Inhibitor Of Apoptosis ◽  
Specific Cell ◽  
Cell Protection ◽  
Specific Expression ◽  
Cell Death Pathway ◽  
Apoptosis Protein

Cell death is increased in the anterior pituitary of poorly controlled diabetic rats, but anti-apoptotic mechanisms are also activated. We hypothesized that specific cell types are selectively protected against diabetes-induced cell death. To determine when anti-apoptotic mechanisms are activated, streptozotocin-induced diabetic rats were killed after 1, 4, 6 and 8 weeks of evolution. Anterior pituitaries were processed for western blot analysis to determine changes in the intrinsic cell death pathway and upstream kinases involved in cell protection mechanisms. An increase in cell death was detected by ELISA at 4 weeks of diabetes. TUNEL labelling demonstrated that this corresponded to death of primarily lactotrophs, a few somatotrophs, and no thyrotrophs, corticotrophs or gonadotrophs. Levels of phosphorylated (p) Akt were increased at 1 week of diabetes, while pERK1/2 levels increased at 4 weeks and pJNK at 6 weeks. Activation of caspase 3 decreased and anti-apoptotic members of the Bcl-2 protein family increased as early as 1 week after diabetes onset. These changes were coincident with increased IGF-I receptor levels. Levels of X-linked inhibitor of apoptosis protein (XIAP) increased significantly after 6 weeks of diabetes, as did activation of nuclear factor (NF)κB. Double immunohistochemistry indicated that XIAP was expressed in less than 1% of lactotrophs and gonadotrophs, approximately 50% of somatotrophs and more than 90% of corticotrophs and thyrotrophs. These results suggest that some cell survival mechanisms are rapidly activated in the anterior pituitary, even before increased cell death can be detected, while others are more delayed. Furthermore, both pituitary cell death and expression of protective mechanisms such as XIAP are cell-type specific.

scholarly journals High Frequency Electroporation for Cancer Therapy

2011 ◽  
Author(s):  
Christopher B. Arena ◽  
Michael B. Sano ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
High Frequency ◽  
Thermal Injury ◽  
Transmembrane Potential ◽  
Irreversible Electroporation ◽  
Chemotherapeutic Drugs ◽  
Reversible Electroporation ◽  
Biophysical Mechanism ◽  
Membrane Defects

Electroporation is a non-linear biophysical mechanism in which the application of an external pulsed electric field leads to an increase in the permeability of cellular membranes. The extent of electroporation is attributed to the induced buildup of charge across the membrane, and consequently, transmembrane potential (TMP). Increasing the TMP has been described to produce various permeabilizing effects, wherein the formation of hydrophilic, aqueous pores becomes energetically favorable [1]. If the pulse parameters are tuned such that the membrane defects are only temporary, and the cell remains viable, the process is termed reversible electroporation. As a cancer therapy, reversible electroporation has been employed to increase the cellular uptake of chemotherapeutic drugs. Irreversible electroporation (IRE) results when membrane defects are permanent, leading to cell death. Recently, IRE has been recognized as an independent means to destroy tumors without the use of adjuvant drugs and prior to the onset of thermal injury [2].

Correlative transmission and high-resolution scanning electron microscopic studies on pituitary cells

1990 ◽  
Vol 48 (3) ◽  
pp. 20-21
Author(s):  
S. Tai
Keyword(s):  
Cell Types ◽  
Depth Of Field ◽  
Secretory Cells ◽  
Specific Cell ◽  
Pituitary Cells ◽  
Electron Microscopic ◽  
3 Dimensional ◽  
Microscopic Studies ◽  
Structure And Activity ◽  
Intracellular Structure

Extensive cytological and histological research, correlated with physiological experimental analysis, have been done on the anterior pituitaries of many different vertebrates which have provided the knowledge to create the concept that specific cell types synthesize, store and release their specific hormones. These hormones are stored in or associated with granules. Nevertheless, there are still many doubts - that need further studies, specially on the ultrastructure and physiology of these endocrine cells during the process of synthesis, transport and secretion, whereas some new methods may provide the information about the intracellular structure and activity in detail.In the present work, ultrastructural study of the hormone-secretory cells of chicken pituitaries have been done by using TEM as well as HR-SEM, to correlate the informations obtained from 2-dimensional TEM micrography with the 3-dimensional SEM topographic images, which have a continous surface with larger depth of field that - offers the adventage to interpretate some intracellular structures which were not possible to see using TEM.

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