scholarly journals Pharmacology of treatment of vascular diseases with the help of endothelioprotectors

2020 ◽  
pp. 199-201
Author(s):  
V.I. Mamchur

Background. Endothelioprotectors (EP) are a group of drugs with different pathogenetic mechanisms of action that prevent disruption and/or restore the structural and functional properties of vascular endothelium. EP are mainly used in the treatment and prevention of cardiovascular and cerebrovascular diseases and their complications. Objective. To describe the role of EP in modern therapy of vascular diseases on the example of L-arginine (Tivortin, “Yuria-Pharm”). Materials and methods. Analysis of literature data on this topic. Results and discussion. The endothelium can be considered as a separate organ that regulates the work of blood vessels. Nitric oxide (NO) is the main signaling molecule of the endothelium. In humans, NO is produced from L-arginine. The latter is a conditionally essential amino acid, which means that it is synthesized in sufficient quantities only in perfectly healthy adults. Arginine is practically not synthesized in children under 5 years of age and in persons over 50 years of age. The main food sources of arginine are meat (pork, poultry), chocolate, soybeans, however, nutrition may not always provide the necessary need for L-arginine. The effects of NO include decreased intracellular calcium, smooth muscle cell relaxation, and vasodilation. As a result, the total peripheral vascular resistance and blood pressure decrease. One of the leading negative factors affecting the heart and blood vessels is hypercholesterolemia, which disrupts the production and release of NO. An improvement in endothelium-dependent vasodilation and a reduction in the size of atherosclerotic plaques with L-arginine have been demonstrated in a rabbit model with hypercholesterolemia. Endothelial dysfunction is an important concept in modern cardiology and medical science. Its main manifestation is a decrease in the NO bioavailability, so in order to eliminate endothelial dysfunction, EP are prescribed. The ideal EP should have such properties as a pronounced cardio- and cerebroprotective effect, rapid onset of action, no side effects, and low cost. L-arginine (Tivortin) is one of the best known EP. It can be used in the treatment of chronic heart failure to increase exercise tolerance. Tivortin supplies the depleted endothelium with a substrate for NO synthesis, facilitating cell function. Tivortin can be used not only in cardiological patients. The research of V.V. Bezugla et al. (2017) showed that Tivortin aspartate for oral administration improves the general and special performance of athletes in cyclic and strength sports, as well as reduces the severity of psychophysiological stress. In addition, the neuro-rehabilitation properties of Tivortin are demonstrated, which justifies its feasibility in the treatment and prevention of stroke. In the study of M.M. Sunychuk et al. (2014) the inclusion of Tivortin (100 ml infusion once a day from the 4th day after stroke for 10-14 days) in the complex therapy contributed to a more positive dynamics of assessments on the NIHSS, Bartel and Rankin scales than the use of standard therapy only. Improvement of the cerebral blood flow with the use of Tivortin is shown in other scientific papers (Mankovsky B.N. et al., 2014). The beneficial effect of L-arginine on the course of hypertension has also been proven (West S.G. et al., 2005). Studies conducted at the Department of Pharmacology and Clinical Pharmacology of the Dnipropetrovsk Medical Academy confirmed the cardiotropic and vasotropic properties of L-arginine. Conclusions. 1. NO – the main signaling molecule of the endothelium – is produced from L-arginine, the production of which almost stops after 50 y. o. 2. EP supply the endothelium with a substrate for NO synthesis, facilitating its function. 3. L-arginine (Tivortin, “Yuria-Pharm”) improves clinical, laboratory and functional parameters in patients with cardiovascular and cerebrovascular diseases.

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.


2020 ◽  
Vol 19 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Sevket Balta

: Vascular diseases are the main reason for morbidity and mortality worldwide. As we know, the earlier phase of vascular diseases is endothelial dysfunction in humans, the endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via organizing ligand-receptor associations and the various mediators’ secretion. We can use many inflammatory non-invasive tests (flowmediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and anklebrachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von Willebrand factor, endothelial microparticles and endothelial progenitor cells) can be used to evaluate endothelial dysfunction. We have focused on the relationship between endothelial dysfunction and inflammatory markers of vascular disease in this review.


Toxics ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 33
Author(s):  
Po-Ching Chu ◽  
Charlene Wu ◽  
Ta-Chen Su

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.


2021 ◽  
Vol 22 (1) ◽  
pp. 83-86
Author(s):  
O. A. Kicherova ◽  
◽  
L. I. Reikhert ◽  
O. N. Bovt ◽  
◽  
...  

In recent years, cerebral vascular diseases have been increasingly detected in young patients. It is due not only to better physicians’ knowledge about this pathology, but also to the improvement of its diagnosis methods. Modern neuroimaging techniques allow us to clarify the nature of hemorrhage, to determine the volume and location of intracerebral hematoma, and to establish the degree of concomitant edema and dislocation of the brain. However, despite the high accuracy of the research, it is not always possible to establish the cause that led to a brain accident, which greatly affects the tactics of management and outcomes in this category of patients. A special feature of the structure of cerebrovascular diseases of young people is the high proportion of hemorrhagic stroke, the causes of which are most often arterio-venous malformations. Meanwhile, there are a number of other causes that can lead to hemorrhage into the brain substance. These include disorders of blood clotting, and various vasculitis, and exposure to toxic substances and drugs, and tumor formations (primary and secondary). All these pathological factors outline the range of diagnostic search in young patients who underwent hemorrhagic stroke. Diagnosis of these pathological conditions with the help of modern visualization techniques is considered to be easy, but this is not always the case. In this article, the authors give their own clinical observation of a hemorrhagic stroke in a young patient, which demonstrates the complexity of the diagnostic search in patients with this pathology.


2021 ◽  
Vol 2 (12) ◽  
pp. 32-35
Author(s):  
E. V. Usenkova ◽  
◽  
P. S. Kulakova ◽  

The article discusses the rehabilitation process of persons who have suffered from cerebro-vascular diseases, traumatic brain injuries, brain tumors within the framework of a multidisciplinary approach in a rehabilitation center. Emphasis is placed on the importance and timeliness of team work of specialists, setting goals, tasks for optimal improvement of the patient's quality of life and social adaptation.


2021 ◽  
Vol 13 (1) ◽  
pp. 57-66
Author(s):  
V. V. Kovalchuk

COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (p<0.05). According to Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Multidimensional Fatigue Inventory (MFI-20), and Spiegel Sleep Questionnaire (SSQ), the average indicators improved significantly more in Group 1 than in Group 2 (p<0.05). The absence of quality of life impairment and their minimal severity were observed in Group 1 in 77.9%; in Group 2 – in 33.7% (p<0.001). Statistically significant differences between the groups of patients were also observed in relation to emotional state recovery according to the Wakefield Questionnaire and the Spielberger State Trait Anxiety inventory.Conclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Martha Lappas

A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases.


Author(s):  
Neeti Sharma

Being a developing sector, biotechnology combines both medical science and various facets of a sustainable environment. Scientific innovations from academics and industry contribute towards the rise of bioentrepreneurship across the world. Medical biotechnology helps the treatment and prevention of human diseases by using living cells and cell materials to research and produce pharmaceutical and diagnostic products. It requires incubation of research, product, and its yield for the improvement of humans to transform medical research into an entrepreneurial industry. Biotechnology provides an opportunity for entrepreneurs to harness the power of genomics for the development and marketing of new therapeutics. These opportunities allow entrepreneurs to visualize the creation of both disruptive business and disruptive technologies for today's business models. This chapter will summarize multiple features of entrepreneurship in the biotechnology industry in combination with other industries and will explain the significance of bio-entrepreneurship in the field of medical biotechnology.


2020 ◽  
Vol 22 (1) ◽  
pp. 103-126 ◽  
Author(s):  
Gilles Soulat ◽  
Patrick McCarthy ◽  
Michael Markl

Magnetic resonance imaging (MRI) has become an important tool for the clinical evaluation of patients with cardiac and vascular diseases. Since its introduction in the late 1980s, quantitative flow imaging with MRI has become a routine part of standard-of-care cardiothoracic and vascular MRI for the assessment of pathological changes in blood flow in patients with cardiovascular disease. More recently, time-resolved flow imaging with velocity encoding along all three flow directions and three-dimensional (3D) anatomic coverage (4D flow MRI) has been developed and applied to enable comprehensive 3D visualization and quantification of hemodynamics throughout the human circulatory system. This article provides an overview of the use of 4D flow applications in different cardiac and vascular regions in the human circulatory system, with a focus on using 4D flow MRI in cardiothoracic and cerebrovascular diseases.


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