85 research outputs found
Cardiac contractility modulation in left ventricular systolic dysfunction: trick or treat?
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Ivabradine, coronary artery disease, and heart failure: beyond rhythm control
No full textPietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny curren
Wind regime change from mis 5.5 aeolian dunes in the Apulia region. A key for the reconstruction of a Meditterranean pressure pattern during the last interglacial
No full textWe studied two geo/morphological elements located southern the town of Gallipoli (Apulia region, southern Italy): the Il Carmine-Li Foggi paleo littoral ridge (CLlr) and the fossil dunes of Il Campo locality, both dating back to MIS 5.5.
A detailed study was conducted on the aeolian units present within CLlr (AU1 and AU2) and at Il Campo locality (unit AU3), in order to reconstruct the paleo-directions of the winds andthe atmospheric pressure patterns. AU1 is the first aeolian unit to settle, it is concentrated at the northern and southern extremities of CLlr and shows wavy to cross-bedding co-sets, dipping in various directions. The accumulation of AU1 at the northern and southern edges of CLlr indicates an effective aeolian transport both northward (due to winds from the southern quadrants) and southward (due to winds from the northern quadrants); the same conclusion can be drawn from the internal structure of AU1. The AU1 unit therefore allows us to recognise a “first aeolian phase”. It involved an autumn-winter pressure pattern characterised by an Atlantic footprint similar to the current one: the Atlantic lows entering the Mediterranean caused, as happens today, the onset of winds from the S and NW, respectively before and after the passage of the low-pressure minima over Apulia. Even in spring-summer, the pressure fields were likely very similar to the current one, with the Azores high on the central-western Mediterranean and the low pressure on the eastern Mediterranean: consequently, the prevailing winds showed a marked unimodality from NW but their speed was generally weak, and therefore these winds were not able, just as it happens today, to significantly impact wind transport; this summer regime leaved the prevailing imprint of the Atlantic winter regime, therefore NW-S bimodality, as recorded by AU1.
AU2 and AU3 settled later than AU1, in a “second aeolian phase” of MIS 5.5. AU2 is characterised by south-eastward-dipping foresets. AU3 consists of domal-linear dunes, the latter oriented in the NW-SE direction. We interpret AU2 and AU3 as coastal dunes originating in a prevailing NW wind regime.
Based on the principle of actualism and on literature data, we conclude that AU2 and AU3 settled under a pressure pattern similar to the current one in fall-winter, that is, characterised by Atlantic cyclones transiting over the Mediterranean, and consequent NW-S bimodality of the winds; in the spring-summer, instead, the regime was characterised by a pressure gradient from west (high) to east (low) much stronger than the current one, causing NW winds stronger than today. Such strong summer winds from NW, effective for wind transport, coupled with the NW-S bimodality in fall-winter, caused the overall prevalence of NW winds during the “second aeolian phase”. This pressure gradient on the Mediterranean greater than today was caused by a summer strengthening of the east Mediterranean low-pressure, in turn caused by the northward shift of the ITCZ, widely documented during the Sapropel S5 event and verified during the MIS 5.5 after sea level had risen to the highstand
Implementing a cartographic repository of the postglacial Antarctic paleo-shorelines
No full textAn improved understanding of the chronology of Antarctic ice sheet deglaciation since the Last Glacial
Maximum-LGM represents a fundamental tool to better define the origin of past and future meltwater influx in
the global oceans (Whitehouse et al., 2012).
Relict shorelines and other evidence of past Relative Sea Level (RSL) evolution were widely used to
understand past ice sheet history and to improve predictions of climate-sea level relationship evolution (Khan
et al., 2015). In the last decades, RSL data in the Antarctic region have been mostly produced using raised
marine features such as beach and marine deposits, marine terraces and isolation basins. The chronology of
these paleo sea-level stands has been established through geomorphological and stratigraphic techniques (John
& Sugden, 1971; Fretwell at al., 2010) and supported by radiometric dating from samples found in beach
deposits and marine/freshwater sediments (Simms et al., 2011; Watcham et al., 2011).
Here we present a new cartographic approach, currently carried out along the Antarctic Peninsula and South
Shetland Islands, which has a twofold aim: (i) the creation of an open access dataset including information
about paleo-shorelines by using a uniform collecting pattern, and (ii) the production of a coherent database
which can be used for improved spatial analyses useful to define the Antarctic shoreline evolution as well as
better constrain the chronology of the deglacial history. As demonstrated by other free data-repositories (https://
www.bgs.ac.uk/geological-data/national-geological-repository/) and similar examples (https://warmcoasts.eu/
world-atlas.html), the new cartographic instrument, built in web-GIS format, will represent a very important
tool for Antarctic coast investigations and a tool for better focusing future researches
Optimizing Therapies in Heart Failure: The Role of Potassium Binders
No full textHeart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K(+) and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K(+) levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting
Reoccupation of late Quaternary relative sea level indicators in a tectonically quasi-stable coastal area in Southern Italy (Cilento headland): Insights into the Last Interglacial stillstands
No full textA geomorphological-stratigraphical study, integrated with a modelling approach, has been employed to constrain the age of relative sea-level indicators (RSLi) along the quasi-stable Mt. Bulgheria coast in the southern Apennines, located on the eastern margin of the Tyrrhenian Sea. Focusing on the geological evidence of late Quaternary sea-level fluctuations within the 0 to 12 m above sea level (a.s.l.) elevation range, we describe RSLi along ca. 8 km of coastline and constrain their elevation, including those of previously undated RSLi in the same area. The reassessment of field data was needed to address the phenomenon of the reoccupation of older RSLi by younger ones. The approach employs the synchronous correlation method, integrating highstand peak elevations
from global sea-level curves and a calibrated uplift rate value, derived from the correlation of RSLi-2 (currently at 8 ± 1 m a.s.l.) with Marine Isotope Stage (MIS) 9c, as suggested by recent findings.
Overall, four RSLi are identified in the investigated coastal zone: RSLi-1 (11 ± 1 m a.s.l.), correlated with MIS 11; RSLi-2 (8 ± 1 m a.s.l.), correlated with MIS 9c and reoccupied during the first MIS 5e peak; RSLi-3 (4 ± 0.5 m a.s.l.) formed during an earlier, undefined stage and reoccupied during MIS 5e; RSLi-4 (2.5 ± 0.5 m a.s.l.) also assigned to MIS 5e. Notably, two cases of reoccupation of older RSLi by younger ones are here reported.
By testing multiple global sea-level curves, we derived a range of possible uplift rates for the chronologically constrained RSLi-2. Consequently, assuming a constant uplift rate throughout the final part of the Middle Pleistocene, we sought the optimal match between all observed RSLi and predicted elevation of palaeo sea levels during past highstands.
The preferred best fit was obtained using a composite eustatic curve from Waelbroeck et al. (2002) and Kopp et al. (2013, for within the MIS5e), and a constant uplift rate of 0.009 mm/yr. Our modelling of MIS 5e (Last Interglacial) identifies three sea-level stillstands and a rapid drop in sea level following the first and higheststillstand. Our results emphasize the importance of the reoccupation problem in sea-level reconstruction studies, especially for RSLi located in regions that are tectonically stable or with relatively low rates of crustal vertical movements. In such contexts, the sea level during younger interglacials may reach or exceed the elevations of older interglacials, reusing or modifying existing RSLi and complicating the identification of which sea-level stand created a specific shoreline feature. The calibrated model supports scenarios where MIS 5e, MIS 9c and MIS 11 had higher peaks than the Holocene (so far). Finally, this work challenges the assumption that RSL indicators ranging between 5 and 8 m a.s.l. in stable regions were exclusively formed during MIS 5e, emphasising
the need for precise age constraints in these interpretations
[Vitamin D deficiency and cardiovascular diseases]
No full textVitamin D deficiency is a condition that affects a high percentage of individuals of all ages. Considerable attention has been paid recently to the possible role of deficiency of this vitamin in the development of several chronic diseases, including cardiovascular and metabolic diseases. In particular, vitamin D deficiency is associated with an increase in conditions such as obesity, insulin-resistance, hypertension, diabetes, and an increased risk of death from these pathologies. There is also a significant correlation with mortality for major cardiovascular events such as heart failure, myocardial infarction, sudden cardiac death, stroke, atrial fibrillation, and peripheral vascular disease. The pathophysiological mechanisms of these correlations are yet to be determined, but hyperactivity of the renin-angiotensin-aldosterone system seems to play a leading role. The role of therapy with vitamin D supplements in improving cardiovascular outcome in patients with low levels of vitamin D remains to be determined
Endocytosis and intracellular localisation of type 1 ribosome-inactivating protein saporin-s6.
No full textSaporin-S6 is a single-chain ribosome-inactivating protein (RIP) that has low toxicity in cells and animals. When the protein is bound to a carrier that facilitates cellular uptake, the protein becomes highly and selectively toxic to the cellular target of the carrier. Thus, saporin-S6 is one of the most widely used RIPs in the preparation of immunoconjugates for anti-cancer therapy. The endocytosis of saporin-S6 by the neoplastic HeLa cells and the subsequent intracellular trafficking were investigated by confocal microscopy that utilises indirect immunofluorescence analysis and transmission electron microscopy that utilises a direct assay with gold-conjugated saporin-S6 and an indirect immunoelectron microscopy assay. Our results indicate that saporin-S6 was taken up by cells mainly through receptor-independent endocytosis. Confocal microscopy analysis showed around 30% co-localisation of saporin-S6 with the endosomal compartment and less than 10% co-localisation with the Golgi apparatus. The pathway identified by the immunofluorescence assay and transmission electron microscopy displayed a progressive accumulation of saporin-S6 in perinuclear vesicular structures. The main findings of this work are the following: i) the nuclear localisation of saporin-S6 and ii) the presence of DNA gaps resulting from abasic sites in HeLa nuclei after intoxication with saporin-S6
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