Rationale, experimental data, and emerging clinical evidence on early and preventive use of levosimendan in patients with ventricular dysfunction

2019 ◽  
Vol 6 (5) ◽  
pp. 310-316
Author(s):  
Nicola Cosentino ◽  
Giampaolo Niccoli ◽  
Francesco Fracassi ◽  
Antonio Rebuzzi ◽  
Piergiuseppe Agostoni ◽  
...  
Keyword(s):  
Experimental Data ◽  
Clinical Evidence ◽  
Ventricular Dysfunction ◽  
Potassium Channel Opener ◽  
Myocardial Stress ◽  
Pharmacodynamic Profile ◽  
Critical Phase ◽  
Therapeutic Procedures ◽  
Calcium Sensitizer ◽  
Substantial Morbidity

Abstract Acute ventricular dysfunction (AVD) is a complex condition with substantial morbidity and mortality, still featuring unique therapeutic challenges. Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that was developed as an inodilating drug for the treatment of acute heart failure and cardiogenic shock. Differently from other more widely used inotropic agents, levosimendan has some exclusive characteristics, in terms of mechanisms of action, pharmacodynamic profile, and haemodynamic effects. This may have important clinical implications. In particular, in patients with AVD or in patients with pre-existing severe ventricular impairment undergoing planned myocardial stress, the administration of levosimendan before the onset of overt symptoms or before cardiovascular therapeutic procedures may have the potential to bridge the patient through the critical phase. In this review, we will focus on the rationale, the existing experimental data, and the emerging clinical experience supporting an early, even preventive use of levosimendan in severe ventricular dysfunction, beyond its recognized indications.

scholarly journals Chronic Subdural Hematoma: Concepts of Physiopathogenesis A Review

1974 ◽  
Vol 1 (4) ◽  
pp. 222-225 ◽  
Author(s):  
Enrique L. Labadie ◽  
David Glover
Keyword(s):  
Experimental Data ◽  
Subdural Hematoma ◽  
Clinical Evidence ◽  
Freezing Point ◽  
Chronic Subdural Hematoma ◽  
Gradient Theory ◽  
Minimal Trauma ◽  
Subcutaneous Space ◽  
Evolution Proceeds ◽  
Progressive Enlargement

SUMMARY:From the present review it seems clear that the physiopathogenesis of the chronic subdural hematoma is far from being completely understood. However, an analysis of the known data can be summarized as follows:The development of subdural hematomas most likely occurs following minimal trauma in those patients with predisposing factors.Experimental data substantiates the fact that an accumulation of clotted blood in the subdural or subcutaneous space induces the formation of the fibroplastic neomembrane. The hypothesis that blood must come in contact with cerebrospinal fluid in order for the growth to occur, is still controversial.It has been virtually disproven that osmosis, referring to the electrolyte gradient as measured by freezing point depression, has any significance as a growth inducing factor.The protein oncotic gradient theory, having been the most widely accepted explanation as to the progressive enlargement of the subdural hematoma sac, has little experimental data supporting it.A larger body of clinical evidence exists supporting the concept that plasma and/or erythrocytes continuously penetrate into the subdural cavity, where enhanced fibrinolytic activity is present.However, this chronic rebleeding cannot fully explain the observed growth, because the composition of the hematoma fluid is somewhat different from serum or plasma, and the protein content is also progressively diluted by fluid arising from an unknown source.There is some clinical and experimental evidence to suggest that a production - reabsorption balance may be a significant growth variable.No work has been done to define the role, if any, of local inflammatory mechanisms in the chronic subdural hematoma.Sound clinical evidence has shown that after the initial formation of the subdural clot, growth follows, then a slow, complete reabsorption usually occurs. Aside from the plausible production - reabsorption balance concept, it is not known why the evolution proceeds in this manner.

Aspirin as a Potential Geroprotector: Experimental Data and Clinical Evidence

2021 ◽  
pp. 145-161
Author(s):  
Oleh Lushchak ◽  
Veronika Piskovatska ◽  
Olha Strilbytska ◽  
Iryna Kindrat ◽  
Nadya Stefanyshyn ◽  
...  
Keyword(s):  
Experimental Data ◽  
Clinical Evidence

Constitutive Modeling of Porous Shape Memory Alloys Using Gurson–Tvergaard–Needleman Model Under Isothermal Conditions

2020 ◽  
Vol 12 (04) ◽  
pp. 2050038
Author(s):  
Xiang Zhu ◽  
Liangliang Chu ◽  
Guansuo Dui
Keyword(s):  
Experimental Data ◽  
Phase Transformation ◽  
Shape Memory Alloys ◽  
Shape Memory ◽  
Strain Hardening ◽  
Constitutive Relationship ◽  
Model Parameters ◽  
Gtn Model ◽  
Critical Phase ◽  
Transformation Stress

Based on the Gurson–Tvergaard–Needleman (GTN) model, a constitutive relationship considering both the effects of strain hardening and hydrostatic stress for porous shape memory alloys (SMAs) is proposed. To capture the relationship between microscopic and mesoscopic behaviors, a representative volume element (RVE) containing an array of spherical voids is presented. In this paper, an approximate solution including strain hardening exponent [Formula: see text] is deduced by considering the porous SMA as a two phase composite with the SMA matrix and the second phase representing voids. The model parameters, [Formula: see text] and [Formula: see text], accounting for interactions between voids are investigated to take into account their influences on strain hardening, critical phase transformation stress and yield surface. In addition, the evolution equations of phase transformation are derived and then applied to the simulation of porous Ni–Ti SMAs with a porosity of 13%. Using the calibrated GTN model parameters, the critical phase transformation stress closer to experimental data is obtained. The predictions of stress–strain curve by the proposed constitutive model are found to be in excellent agreement with published experimental data and finite element results. The results prove that the model is capable of reproducing the features of porous SMAs such as superelasticity, tensile-compressive asymmetry and internal loops under uniaxial even combined loading conditions. A conclusion is drawn that the present constitutive relationship is powerful and useful for the analysis of porous SMAs.

A spectrum of disease in Human African trypanosomiasis: the host and parasite genetics of virulence

Parasitology ◽  
2010 ◽  
Vol 137 (14) ◽  
pp. 2007-2015 ◽  
Author(s):  
JEREMY M. STERNBERG ◽  
LORNA MACLEAN
Keyword(s):  
Experimental Data ◽  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Clinical Evidence ◽  
African Trypanosomiasis ◽  
Trypanosoma Brucei Rhodesiense ◽  
Host Genotype ◽  
Virulence Phenotype ◽  
Rate Of Progression ◽  
Virulence Variation

SUMMARYFor over 50 years it has been known that there are considerable differences in the severity and rate of progression of bothTrypanosoma brucei rhodesiense and T. b. gambienseinfection between individuals. Yet research into the factors, whether parasite or host, which control virulence in Human African trypanosomiasis is in its infancy. In this paper we review the clinical evidence for virulence variation and the epidemiological and experimental data that give clues as to the mechanisms involved. Evidence will be presented for both asymptomatic forms ofT. b. gambienseinfection and low virulence forms ofT. b. rhodesienseinfection in humans. While in both cases the mechanisms remain to be elucidated, the overall infection virulence phenotype is determined by both parasite and host genotype.

scholarly journals A Mathematical Model for the Immune-Mediated Theory of Metastasis

2019 ◽  
Author(s):  
Adam Rhodes ◽  
Thomas Hillen
Keyword(s):  
Experimental Data ◽  
Mathematical Model ◽  
Immune System ◽  
Immune Cells ◽  
Clinical Evidence ◽  
Blow Up ◽  
Metastatic Cancer ◽  
Poor Performance ◽  
Immune Mediated ◽  
Immune Response To Cancer

AbstractAccumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system — as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example — have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed “immune-mediated” theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti-and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor “education” of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the protumor effects of the immune system in metastatic cancer.

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