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Farmakis D.,National and Kapodistrian University of Athens | Alvarez J.,University of Santiago de Compostela | Gal T.B.,Cardiology Clinic Rabin Medical Center | Fedele F.,University of Rome La Sapienza | And 30 more authors.
International Journal of Cardiology | Year: 2016

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Authors


Harari M.,RIDS the Joint Research Institute on Climatotherapy for Skin Diseases at the Dead Sea | Harari M.,Hadassah University Hospital Jerusalem | Harari M.,Ludwig Maximilians University of Munich | Czarnowicki T.,RIDS the Joint Research Institute on Climatotherapy for Skin Diseases at the Dead Sea | And 9 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2012

Background Plaque psoriasis has recently been divided in two types, which differ in severity and inheritance according to the age of the patient at the onset of the disease. Aim To compare the effect of Dead Sea climatotherapy (DSC) on these two types of disease, with early vs. late onset, and to determine the impact of this treatment on the response rate. Methods The files of 605 patients who were suffering from plaque psoriasis were retrieved from the database of the Research Institute at the Dead Sea (RIDS) and divided in two groups, types I and II, according to whether the age at the onset of the disease was under or over 40 years, respectively. The primary outcome for the assessment of DSC was Psoriasis Assessment of Severity Index of 95 (PASI 95), which indicates that the PASI improvement percentage reached 95%. Logistical regression was used to identify the factors that related to the observed outcome. Results By the end of the study, 74% of the patients in group 1 reached PASI 95 in comparison to 62% in group 2. The 95% confidence interval for the odds ratio (OR) of the effect in group 2 in comparison to that of group 1 was [0.31, 0.99], which implies that group 1 responded better to treatment in comparison to group 2. Cut-off values for patients who were aged 30 and 20, respectively, exhibited similar trends; 75% vs. 65% and 78% vs. 68% for groups 1 and 2, respectively. Conclusions Efficacy rates following DSC were impressively high for plaque psoriasis patients. Contrary to our hypothesis, the treatment effect was found to inversely correlate with the age of the patient at disease onset. © 2011 European Academy of Dermatology and Venereology.


PubMed | Hadassah University Hospital Jerusalem
Type: Journal Article | Journal: Annals of clinical and translational neurology | Year: 2015

Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimers diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases.To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE).We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of nave mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation.Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS.


PubMed | Carmel Medical Center, G Gennimatas General Hospital, National and Kapodistrian University of Athens, Hospital Of Sant Joan Despi Moises Broggi and 27 more.
Type: | Journal: International journal of cardiology | Year: 2016

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps.

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