scholarly journals Disordered Myocardial Ca2+ Homeostasis Results in Substructural Alterations That May Promote Occurrence of Malignant Arrhythmias

2016 ◽  
pp. S139-S148 ◽  
Author(s):  
N. TRIBULOVA ◽  
V. KNEZL ◽  
B. SZEIFFOVA BACOVA ◽  
T. EGAN BENOVA ◽  
C. VICZENCZOVA ◽  
...  

We aimed to determine the impact of Ca2+-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca2+ handling. Langedorff-perfused rat or guinea pig hearts subjected to K+-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca2+ disturbances and Ca2+ overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca2+]i-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca2+-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.

2007 ◽  
Vol 280-283 ◽  
pp. 1689-1692 ◽  
Author(s):  
Juan Liu ◽  
Long Hao Qi ◽  
Hong Yuan Xu ◽  
He Zhuo Miao

Engineering ceramics have a high application potential for wear-protection of different equipment used for electric power generating, mining and mineral industries. The ZTA (zirconia toughened alumina) and alumina (92%, 95%) have been prepared. Effects of varying the impact velocity and volume content of erodent particle and erosive time are investigated. Scanning electron microscopic examination of the eroded ceramic surfaces provides insights into the erosive wear mechanisms. The material removal processes include chipping out of lateral cracks caused by impact of the erodent particles, grain boundary cracking and grain pull out, as well as plastic deformation caused by the repeated sliding and impact of the particles.


Open Medicine ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Nilufer Kocak ◽  
Candan Ozogul ◽  
Suleyman Kaynak ◽  
Ulker Sonmez ◽  
Mehmet Zengin ◽  
...  

AbstractTo analyze the retinal toxicity of bevacizumab at various doses both in vitrectomized and non-vitrectomized rabbit models. Twenty- eight rabbits were included in the study. Twenty- four rabbits were assigned to six groups, with 4 of the rabbits in the control group. The animals in Groups 1, 2 and 3 received bevacizumab at a dose of 0.3 mg, 0.5 mg and 1.5 mg /eye, respectively. The rabbits in Groups 4, 5 and 6 received intravitreal bevacizumab of 0.3 mg, 0.5 mg and 1.5mg/eye, respectively, after gas compression vitrectomy. Two weeks after the procedure, the rabbits were euthanized. Retina tissue samples were then obtained and examined with both light and electron microscopes. In Groups 1, 2 and 3 after bevacizumab injection, toxic degeneration in the photoreceptor and retinal pigment epithelium cells was observed via electron microscopic examination. The findings in Groups 4 and 5 were normal as compared to the control group. In Group 6, toxicity in the bipolar neurons and photoreceptor cells was noticed. Increased toxicity and retinal penetration were noticed in all administered doses of bevacizumab in the presence of vitreous. In addition, ocular toxicity occurred through the injection of the highest dose of bevacizumab after vitrectomy. It is possible that the bevacizumab dose and the, vitreous are as important as the drug half-life in the vitreous.


2016 ◽  
Vol 242 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Da-wei Zhao ◽  
Meng Tian ◽  
Jian-zheng Yang ◽  
Peng Du ◽  
Jie Bi ◽  
...  

The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P < 0.05). Subgroups MEUS1 (0.346 ± 0.345 g) and MEUS2 (2.232 ± 2.256 g) exhibited significantly lower post-treatment bleeding weight than the US and MB groups (5.698 ± 1.938 and 5.688 ± 2.317 g, respectively; all, P < 0.05). Additionally, MEUS subgroups 1–3 exhibited significantly lower post-treatment blood perfusion levels (PI ratios, 0.64 ± 0.085, 0.73 ± 0.045, and 0.84 ± 0.034, respectively) than the US and MB groups (PI ratios, 1.00 ± 0.005 and 0.99 ± 0.005, respectively; all, P < 0.05). In the MEUS group, hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma.


2016 ◽  
Vol 29 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Rui Li ◽  
Cheng Zhou ◽  
Yang Chen ◽  
Huawei Zou ◽  
Mei Liang ◽  
...  

In this work, a series of silicone-containing epoxy copolymers (E231) were synthesized through a condensation reaction between the Si-OCH3 of SY231 and the –OH of E51. The chemical structural determinations of the copolymer were carried out with the Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR), and an epoxy equivalent weight test. Besides, the grafting content of SY231 in E231 copolymers was determined by the proton (1H) NMR integration technique. The mechanical properties, thermal stabilities, and morphology of impact fractured surface of cured products were also investigated. The experimental results show that increased impact strength was observed for the cured E231 products, meanwhile the improvement of the impact strength was closely related to the content of silicone in copolymers. A smooth surface was observed on the neat epoxy specimen, while a rough surface was observed by scanning electron microscopic examination on the impact fractured surface of the cured E231 products. The data of TGA indicated that silicone exerted its thermal stability through thermal decomposition energy dissipation, acted as thermal insulation, and finally enhanced the solid residue at 800°C. Dynamic thermomechanical analysis tests displayed that the glass transition temperature of epoxy systems decreased slightly with the introduction of the flexible organosilicone.


Author(s):  
Wun-Ju Shieh ◽  
Austin Demby ◽  
Tara Jones ◽  
Cynthia S Goldsmith ◽  
Pierre E Rollin ◽  
...  

Abstract Background Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the “at risk” seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of three million, and fatalities up to 67,000, demonstrating the serious impact of the disease on the region and global health. Methods Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. Results Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. Conclusions The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of LF is multifactorial and additional studies are needed.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Mine ◽  
H Kishima ◽  
E Fukuhara ◽  
R Kitagaki ◽  
M Ishihara

Abstract Background The abnormal conduction zone (ACZ) in the left atrium (LA) has attracted attention as an arrhythmia substrate in atrial fibrillation (AF). Purpose We investigated whether the ACZ affects outcomes after catheter ablation (CA) for AF. Methods We studied 78 patients (42 Non-paroxysmal AF, 49 males, and 68±10 years) who received CA for AF. High-density LA mapping during high right atrial pacing was constructed gaining than 2000 points (average 4377±846 points). Isochronal activation maps created at 5-ms interval setting. ACZ was identified by locating a site with isochronal crowding of ≥3 isochrones, and ≥8 isochrones were defined as the conduction block zone (CBZ) in a 4-mm diameter tag (conduction velocity were calculated as ≤27 cm/s and≤10 cm/s, respectively). Result Recurrent AF was detected in 25/78 patients (32%) during the follow-up period (9.2±3.0 month). ACZ and CBZ were distributed linearly, and ACZ was observed in 73 of 78 patients and 8 of these 73 patients had the CBZ. Univariate analysis revealed that elevated body mass index (26.2±3.8 vs. 24.3±3.3 kg/m2, P=0.0303), the higher prevalence of non-paroxysmal AF (72% vs. 45%, P=0.0272), larger LA diameter (47.6±6.6 vs. 42.1±6.9 mm, P=0.0014), and longer length of ACZ (79.7±45.1 vs. 52.9±35.7 mm, P=0.0058) were associated with recurrent AF after CA. On multivariate analysis, longer ACZ was independently associated with recurrent AF. Moreover, patients with longer ACZ (cutoff value: 84 mm) had a higher risk of recurrent AF than shorter ACZ (12/22; 55% vs 13/56; 23%, log-rank P=0.0024). Conclusion The length of ACZ was associated with recurrent AF after CA. FUNDunding Acknowledgement Type of funding sources: None.


2015 ◽  
Vol 48 (3) ◽  
pp. 434-440 ◽  
Author(s):  
Narcis Tribulova ◽  
Barbara Szeiffova Bacova ◽  
Tamara Benova ◽  
Csilla Viczenczova

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S6.2-S6 ◽  
Author(s):  
N Tribulova ◽  
V Nagibin ◽  
T Benova ◽  
C Viczenczova ◽  
J Radosinska ◽  
...  

2020 ◽  
Vol 48 (5) ◽  
pp. 669-676
Author(s):  
Ayako Sayama ◽  
Keiko Okado ◽  
Mayu Yamaguchi ◽  
Naozumi Samata ◽  
Masako Imaoka ◽  
...  

Mer proto-oncogene tyrosine kinase (MerTK), expressed in the retinal pigment epithelium (RPE), regulates the phagocytosis of shed photoreceptor outer segments. To investigate the influence of dosing time on MerTK inhibitor UNC569-induced retinal toxicity, UNC569 at 100 mg/kg was orally administered to male mice at 2 different Zeitgeber times (ZT5.5 or ZT22) for 28 days. Electron microscopy was conducted at ZT2 after the final dosing. Additionally, the visual cycle components (11-cis-retinal, all-trans-retinal, all-trans-retinol, and 11-cis-retinol), which play an important role in maintaining retinal homeostasis, were quantified by liquid chromatography/mass spectrometry/mass spectrometry. Under electron microscopic examination, the number of phagosomes and phagolysosomes in the RPE increased in both the ZT5.5 and ZT22 administered groups, while endoplasmic reticulum dilatation in the RPE and chromatin aggregation of photoreceptor nuclei were observed only in the ZT22 administered group. No change was observed in any of the visual cycle components. These results suggest that the timing of the dosing in relation to the physiological MerTK phosphorylation affected the severity of changes in the RPE, leading to the apoptosis of the photoreceptor cells.


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