A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins

Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45‐year‐old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non‐specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins α‐actin, α‐actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102708/1/ejhf2004-09-012.pd

Diet, Muscle Protein Synthesis and Autophagy Relationships in Cancer. An Attempt to Understand Where Are We Going, and Why

Protein-based structures are indispensable to maintain life, so identification and removal of worn out structures achieved through proteostasis, the sum of micro and macro-autophagy (autophagy) plus ubiquitin-proteasome system, must balance renewal by new synthesis. Many of the elements controlling dynamically equilibria between protein synthesis and protein degradation have been identified and modalities of activation actively studied, still we are quite far from mastering how this balance is ruled. Failure to maintain a positive balance between protein synthesis and protein degradation would result in sarcopenia, defined as the loss of skeletal muscle mass and function, a major clinical problem frequently accompanying chronic illnesses, but peculiarly spotted in cancer and in elderly patients. Also, how cancer is fed, and how nutrition in cancer patients may affect evolution and therapy effectiveness is another field of opinions and uncertainty. On the other hand, exercise and nutrition tailored to provide adequate amounts of amino acids are widely considered a necessary strategy for prevention and treatment of protein synthetic deficits in muscles. This paper will synthetically review how different nutritional strategies and energy production may interconnect efficiently synthesis and scavenging of aged and overused protein molecules by autophagy. Finally, since energy availability rules life and death of cells and organisms, an hypothesis predicting how energy may control the ratios among protein synthesis and autophagy is proposed: in normal conditions, protein syntheses have a key role in autophagy activation by consuming large amounts of energy when forming peptidic bonds, that is adenosine tri-phosphate (ATP) is consumed to monophospahate (AMP), thus decreasing ATP to AMP ratios. Conversely, both protein syntheses and autophagy may be scarcely activated when low availability of ATP would result also in lowest concentrations of AMP. In this peculiar setting, reduced rates of both protein syntheses and autophagy would be observed, resulting in worsening of protein balance and functions

El Siglo de las Luces di Alejo Carpentier: alla ricerca di un Mondo Migliore, tra lampi rivoluzionari e frammenti di paradiso

In El siglo de las luces, an apparently historical novel, Alejo Carpentier analyzes the American experience of European modernity through the dislocation of both French Revolution objects and ideas.In this novel, the writer considers the Caribbean (and, so, Latin America) as a paradisiac place coping with theories and ideologies generated in Other centres. Therefore, the Revolution movements towards the suburbs, the intersections of perspectives, visions and translations, organized as a network without a proper centre, lead to a new interpretation of the "American contradistinction" based on accumulation, contradiction and paradox.This article illustrates the challenges to the Revolution paradigm as proposed by Alejo Carpentier, the essential starting point to consider the construction of the “American Being" and the myth of the Promised Land.

Suboptymalna kontrola poziomu glikemii a jej związek z niezależnym od czasu trwania odstępu QT zwiększonym ryzykiem wystąpienia arytmii komorowych u pacjentów z populacji dużego ryzyka

Wstęp: Mimo że choroby układu sercowo-naczyniowego są główną przyczyną śmiertelności wśród chorych na cukrzycę wciąż niewiele wiadomo na temat wpływu kontroli poziomu glikemii na częstość występowania częstoskurczów komorowych (VT). Celem pracy było zbadanie, czy stężenie hemoglobiny glikowanej wpływa na częstość VT. Metody: Przeprowadzono retrospektywne badanie obejmujące 336 osób z implantowanym kardiowerterem-defibrylatorem serca - zarówno chorych na cukrzycę, jak i bez tego schorzenia. Wyniki: Stężenie HbA1c w granicach 8-10% istotnie wiąże się ze zwiększoną częstością występowania spontanicznego VT, niezależnie od czasu trwania odstępu QT lub QTc. Wnioski: Indeks glikemiczny jest istotnym predykatorem wystąpienia spontanicznego VT, niezależnie od czasu trwania odstępu QT. Optymalna kontrola poziomu glikemii pomaga zredukować częstość występowania VT oraz przypadków nagłej śmierci sercowej u chorych na cukrzycę z grupy dużego ryzyka. (Folia Cardiologica Excerpta 2006; 1: 484-491

Diamela Eltit: poner el cuerpo en lo común

Diamela Eltit: poner el cuerpo en lo común (Mónica Barrientos, La pulsión comunitaria en la obra de Diamela Eltit, Pittsburgh, Latin American Research Commons, 2019. DOI: https://doi.org/10.25154/book1 Licencia: CC BY-NC 4.0) por Laura Scarabell

La narrativa de Diamela Eltit y los límites del testimonio hispanoamericano

This paper attempts to analyse the narrative testimony written by the Chilean novelist Diamela Eltit focusing on the limits and transformations of \u201ctestimonio\u201d in Latin America during the last decade. Through the rupture of the conventional linguistic codes, the author tries to materialize and \u201cname\u201d the unnameable, creating alternative cartographies of representation. The use of the schizophrenic language disorder as a new form of expression and the peculiar treatment of the madness produce unusual possibilities of symbolizing and refiguring the nation. The analysis of the discourse in El Padre M\uedo and El infarto del alma provides unusual perspectives in order to study the representation of mental infirmity.La propuesta est\ue9tico-narrativa de Diamela Eltit, en el marco del testimonio hispanoamericano, se centra en la representaci\uf3n de una sociedad en crisis, configurada alrededor de las din\ue1micas opresoras de la dictadura. A trav\ue9s de la ruptura de los c\uf3digos ling\ufc\uedsticos convencionales, la autora quiere \u201cmaterializar narrativamente\u201d lo que no se puede y debe \u201cnombrar\u201d, edificando cartograf\uedas alternativas de dicibilidad de lo indecible, abiertas a los dominios de la alteridad. El an\ue1lisis del habla esquizoide de El Padre m\uedo y su desarrollo en El infarto del alma, ser\ue1n el punto de partida para una reflexi\uf3n sobre el peculiar tratamiento de la enfermedad mental, sus l\uedmites, signos y \u201cpuestas en escena\u201d

Esercitare il potere visionario della letteratura : "Sumar" di Diamela Eltit (Santiago de Chile, Seix Barral, 2018, 177 pp., ISBN 978-956-329-077-6)

Esercitare il potere visionario della letteratura: Sumar di Diamela Eltit (Santiago de Chile, Seix Barral, 2018, pp. 177, ISBN 978-956-329-077-6) di Laura Scarabell

MOLECULAR DYNAMICS SIMULATIONS OF BIOLOGICAL MACROMOLECULES: APPLICATIONS TO STRUCTURAL VACCINOLOGY AND PEPTIDE DESIGN

This thesis work is splitted into two parts. The first one is about a computational method for epitope predictions on antigenic proteins, while the second one is related to the characterization of folding/unfolding processes of small natural polypeptides. Starting with the first topic, an increasing number of functional studies of proteins have shown that sequence and structural similarities alone may not be sufficient for reliable prediction of their interaction properties. This is particularly true for proteins recognizing specific antibodies, where the prediction of antibody-binding sites, called epitopes, has proven challenging. The antibody-binding properties of an antigen depend on its structure and related dynamics. Aiming to predict the antibody-binding regions of a protein, we investigate a new approach based on the integrated analysis of the dynamical and energetic properties of antigens, to identify nonoptimized, low-intensity energetic interaction networks in the protein structure isolated in solution. The method is based on the idea that recognition sites may correspond to localized regions with low-intensity energetic couplings with the rest of the protein, which allows them to undergo conformational changes, to be recognized by a binding partner, and to tolerate mutations with minimal energetic expense. Upon analyzing the results on isolated proteins and benchmarking against antibody complexes, it is found that the method successfully identifies binding sites located on the protein surface that are accessible to putative binding partners. The combination of dynamics and energetics can thus discriminate between epitopes and other substructures based only on physical properties. A public web server (BEPPE) has been implemented with MLCE method in order to make it available to the scientific community. Changing topic to folding/unfolding, the analysis of the folding mechanism in peptides adopting well defined secondary structure is fundamental to understand protein folding. Herein, we describe the thermal unfolding of two 15-mer polypeptides (called QK and QK-L10A) homologue to the vascular endothelial growth factor binding region. In particular, on the basis of the temperature dependencies, we characterize the molecules through the combination of spectroscopic (CD and NMR) and computational analyses (MD) highlighting their folding/unfolding steps and how these structures can be used in peptide design