scholarly journals Shock – Classification and Pathophysiological Principles of Therapeutics

2019 ◽  
Vol 15 (2) ◽  
pp. 102-113 ◽  
Author(s):  
Olga N. Kislitsina ◽  
Jonathan D. Rich ◽  
Jane E. Wilcox ◽  
Duc T. Pham ◽  
Andrei Churyla ◽  
...  
Keyword(s):  
Septic Shock ◽  
Clinical Trials ◽  
Hypovolemic Shock ◽  
Experimental Studies ◽  
Shock Therapy ◽  
Advantages And Disadvantages ◽  
Clinical Presentations ◽  
Endogenous Catecholamines ◽  
Omecamtiv Mecarbil ◽  
Vasopressor Agents

The management of patients with shock is extremely challenging because of the myriad of possible clinical presentations in cardiogenic shock, septic shock and hypovolemic shock and the limitations of contemporary therapeutic options. The treatment of shock includes the administration of endogenous catecholamines (epinephrine, norepinephrine, and dopamine) as well as various vasopressor agents that have shown efficacy in the treatment of the various types of shock. In addition to the endogenous catecholamines, dobutamine, isoproterenol, phenylephrine, and milrinone have served as the mainstays of shock therapy for several decades. Recently, experimental studies have suggested that newer agents such as vasopressin, selepressin, calcium-sensitizing agents like levosimendan, cardiac-specific myosin activators like omecamtiv mecarbil (OM), istaroxime, and natriuretic peptides like nesiritide can enhance shock therapy, especially when shock presents a more complex clinical picture than normal. However, their ability to improve clinical outcomes remains to be proven. It is the purpose of this review to describe the mechanism of action, dosage requirements, advantages and disadvantages, and specific indications and contraindications for the use of each of these catecholamines and vasopressors, as well as to elucidate the most important clinical trials that serve as the basis of contemporary shock therapy.

scholarly journals Experimental models of sepsis and septic shock: an overview

2004 ◽  
Vol 19 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Alejandra G. Garrido ◽  
Luiz Francisco Poli de Figueiredo ◽  
Maurício Rocha e Silva
Keyword(s):  
Septic Shock ◽  
Clinical Trials ◽  
Animal Models ◽  
Cecal Ligation ◽  
Experimental Studies ◽  
Treatment Strategies ◽  
Experimental Models ◽  
Contributing Factors ◽  
Human Sepsis ◽  
Sepsis And Septic Shock

Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

Experimental Studies on Axially Loaded Concrete Columns Confined by Different Materials

2008 ◽  
Vol 400-402 ◽  
pp. 513-518 ◽  
Author(s):  
Yong Chang Guo ◽  
Pei Yan Huang ◽  
Yang Yang ◽  
Li Juan Li
Keyword(s):  
Bearing Capacity ◽  
Glass Fiber ◽  
Failure Modes ◽  
Experimental Studies ◽  
Concrete Columns ◽  
Steel Tube ◽  
Ultimate Bearing Capacity ◽  
Advantages And Disadvantages ◽  
Axially Loaded ◽  
Normal Strength

The improvement of the load carrying capacity of concrete columns under a triaxial compressive stress results from the strain restriction. Under a triaxial stress state, the capacity of the deformation of concrete is greatly decreased with the increase of the side compression. Therefore, confining the deformation in the lateral orientation is an effective way to improve the strength and ductility of concrete columns. This paper carried out an experimental investigation on axially loaded normal strength concrete columns confined by 10 different types of materials, including steel tube, glass fiber confined steel tube (GFRP), PVC tube, carbon fiber confined PVC tube (CFRP), glass fiber confined PVC tube (GFRP), CFRP, GFRP, polyethylene (PE), PE hybrid CFRP and PE hybrid GFRP. The deformation, macroscopical deformation characters, failure mechanism and failure modes are studied in this paper. The ultimate bearing capacity of these 10 types of confined concrete columns and the influences of the confining materials on the ultimate bearing capacity are obtained. The advantages and disadvantages of these 10 types of confining methods are compared.

Think about it – can portrayals of homosexuality in advertising prime consumer-perceived social connectedness and empathy?

2017 ◽  
Vol 51 (1) ◽  
pp. 82-98 ◽  
Author(s):  
Nina Åkestam ◽  
Sara Rosengren ◽  
Micael Dahlen
Keyword(s):  
Design Methodology ◽  
Social Connectedness ◽  
Experimental Studies ◽  
Social Effects ◽  
Attitudes Toward Homosexuality ◽  
Content Type ◽  
Advantages And Disadvantages ◽  
Thought Listing ◽  
Societal Level ◽  
Practical Implications

Purpose This paper aims to investigate whether portrayals of homosexuality in advertising can generate social effects in terms of consumer-perceived social connectedness and empathy. Design/methodology/approach In three experimental studies, the effects of advertising portrayals of homosexuality were compared to advertising portrayals of heterosexuality. Study 1 uses a thought-listing exercise to explore whether portrayals of homosexuality (vs heterosexuality) can evoke more other-related thoughts and whether such portrayals affect consumer-perceived social connectedness and empathy. Study 2 replicates the findings while introducing attitudes toward homosexuality as a boundary condition and measuring traditional advertising effects. Study 3 replicates the findings while controlling for gender, perceived similarity and targetedness. Findings The results show that portrayals of homosexuality in advertising can prime consumers to think about other people, thereby affecting them socially. In line with previous studies of portrayals of homosexuality in advertising, these effects are moderated by attitudes toward homosexuality. Research limitations/implications This paper adds to a growing body of literature on the potentially positive extended effects of advertising. They also challenge some of the previous findings regarding homosexuality in advertising. Practical implications The finding that portrayals of homosexuality in advertising can (at least, temporarily) affect consumers socially in terms of social connectedness and empathy should encourage marketers to explore the possibilities of creating advertising that benefits consumers and brands alike. Originality/value The paper challenges the idea that the extended effects of advertising have to be negative. By showing how portrayals of homosexuality can increase social connectedness and empathy, it adds to the discussion of the advantages and disadvantages of advertising on a societal level.

scholarly journals Tissue engineering of urethra: Systematic review of recent literature

2017 ◽  
Vol 242 (18) ◽  
pp. 1772-1785 ◽  
Author(s):  
Stanislav Žiaran ◽  
Martina Galambošová ◽  
L'uboš Danišovič
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Clinical Trials ◽  
Animal Studies ◽  
Recent Literature ◽  
Cell Attachment ◽  
Experimental Studies ◽  
Clinical Results ◽  
Bioactive Molecules ◽  
Urethral Reconstruction

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

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