Search results for: endothelin

Authors: Chro Kawyan

Abstract:

Endothelin-1 (ET-1), the principal individual from the newfound mammalian endothelin group of organically dynamic peptides, was initially distinguished as a 21 buildup powerful vasoconstrictor peptide in vascular endothelial cells. However, it has since been demonstrated to have a wide range of pharmacological activities in tissues both inside and outside the cardiovascular system. Additionally, peptides that have a striking resemblance to ET-1 have been identified as the primary toxic component of snake venom. In addition, late examinations have proposed that warm blooded creatures, including people, produce three unmistakable individuals from this peptide family, ET-1, ET-2 and ET-J, which might have various profiles of organic action and may follow up on particular subtypes of endothelin receptor. Masashi Yanagisawa and Tomoh Masaki survey the ongoing status of the organic chemistry and sub-atomic science of endothelin.

Keywords: thelin, microbiology, molecular biology, cell

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Authors: Ryan M. Monti, Bijal Mehta

Abstract:

In cases of massive pulmonary embolism, defined as acute pulmonary embolism presenting with systemic hypotension or right ventricular dysfunction and impending failure, there is indication that unconventional therapies, such as phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs may decrease the morbidity and mortality. Based on the premise that dilating the pulmonary artery will decrease the pulmonary vascular pressure, while simultaneously decreasing the aggregation of platelets, it can be hypothesized that increased blood flow through the pulmonary artery will decrease right heart strain and subsequent morbidity and mortality. While this theory has yet to be formally studied, the recommendations for treating massive pulmonary embolism with phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs in conjunction with the current standards of care in massive pulmonary embolism should be formally studied. In particular, patients with massive PE who are unable to undergo thrombolysis/surgical intervention may be the ideal population to study the use of these treatments to determine any decrease in mortality and morbidity (short term and long term).

Keywords: acute pulmonary thromboembolism, treatment of pulmonary embolism, use of phosphodiesterase inhibitors, endothelin receptor antagonists, prostacyclin analogs in PE

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Authors: Mai M. Helmy

Abstract:

Although the role of either nitric oxide (NO) or endothelin receptors modulation in the severity of cisplatin-induced nephrotoxicity has been recognized in previous studies including our own, the possible interaction between the two pathways remains obscure. In this study, we tested the possible interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats. Sprague Dawley male rats (200 to 250 g) were divided into four groups: Control (given a single dose of normal saline, i.p.), cisplatin (6 mg/kg, i.p.), cisplatin+Sildenafil (2 mg/kg, i.p.), cisplatin+Sildenafil+BQ-123 (1 mg/kg, i.p.). Each of the co-administered drugs was given in two doses; one hour before and one day after the cisplatin dose. Acute cisplatin administration resulted in significant increases in BUN and serum creatinine levels at 96 h following cisplatin injection. Increased levels of MDA, TNF-α and caspase-3, decreased nitrite/nitrate level and SOD activity in kidney homogenates were also observed following cisplatin injection. According to the obtained results, the co-adminstration of sildenafil alone with cisplatin offered a reno-protective effect comparable to that obtained following the concurrent administration of both sildenafil and the selective ETAR antagonist BQ-123. Thus, the current study is the first to reveal that the presence of an intact NO/cGMP system may offer a moderate reno-protective effect against cisplatin-induced nephrotoxicity even in the presence of ETAR-mediated vasoconstriction, suggesting the absence of obvious functional interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats.

Keywords: BQ-123, cisplatin, endothelin-1, nephrotoxicity, sildenafil

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Authors: Edite Kulmane, Mara Pilmane, Romans Lacis

Abstract:

Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.

Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin

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Authors: Neeraj Kumar Mishra, In Su Kim

Abstract:

The isoindoline, indazole and indole heterocycles are ubiquitous structural motif found in heterocyclic compounds as they exhibit biological and medicinal applications. For example, isoindoline motif is present in molecules that act as endothelin-A receptor antagonists and dipeptidyl peptidase inhibitors. Moreover, isoindoline derivatives are very crucial constituents in the field of materials science as attractive candidates for organic light-emitting devices. However, compounds containing the indazole motif are known to exhibit to a variety of biological activities, such as estrogen receptor, HIV protease inhibition and anti-tumor activity. The prevalence of indazoles and indoles has led to the development of many useful methods for their preparation. Thus, isoindoline, indazole and indole heterocycles can be new candidates for the next generation of pharmaceuticals. Therefore, the development of highly efficient strategies for the formation of these heterocyclic architectures is an area of great interest in organic synthesis. The past years, transition-metal-catalyzed C−H activation followed by annulation reaction has been frequently used as a powerful tool to construct various heterocycles. Herein, we describe our recent achievements about the transition-metal-catalyzed tandem cyclization reactions of N-benzyltriflamides, 1,2-disubstituted arylhydrazines, acetanilides, etc. via C−H bond activation to access the corresponding bioactive heterocylic scaffolds.

Keywords: biologically active, C-H activation, heterocyclic compounds, transition-metal catalysts

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Authors: Abeer Rababa'h, Ragad Bsoul, Mohammad Alkhatatbeh, Karem Alzoubi

Abstract:

Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.

Keywords: atherosclerotic biomarkers, cardiovascular disease, matrix metalloproteinase, waterpipe

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