Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

A constituição de um locutor como idoso: uma análise enunciativa

The  aim  of  the  discussions  presented  in  this  article  was  to  analyze  the identification  (or  not)  of  a  speaker  with  the  subject-position  of  an  elderly person. We selected an interview from the Portal do Envelhecimento (Aging Portal)  website  as  the  corpus  of  the  analysis.  In  this  interview,  a  book organizer describes her book-drafting process, whose theme focuses on issues related to aging. We based the analysis on the enunciative studies proposed by  Benveniste  (1989,  1995)  and  Guimarães  (1989,  1995,  1996,  2005). This  theoretical  approach  allowed  us  to  observe  how  the  enunciation  was established in that interview. By observing the use of personal pronouns, we performed the linguistic analysis of this material. This enabled us to establish the interviewed author as the focus and, therefore, as the main speaker. As for the other people brought into this enunciation process, the interviewer was referred to as you and the elderly as he. In general, the analysis highlighted the following considerations: a) in the enunciator’s speech, there is a deletion of the you and an alternation between the I and the we, when referring to the first person; b) the use of the we, in some situations, joins the speaker to the group who helped to produce the book, and in others, it is not defined, allowing the interpretation of the he (the elderly) as included; c) such use of pronouns shows that the speaker builds just an implicit identification of the elderly in the subject-position.As  discussões  apresentadas  neste  artigo  têm  como  objetivo  analisar  a identificação (ou não) de um locutor com a posição-sujeito de idoso. Como corpus de análise foi selecionada uma entrevista veiculada no site Portal do Envelhecimento,  na  qual  a  organizadora  de  um  livro  expõe  o  trabalho  de elaboração da obra, cuja temática centra-se em questões relativas à velhice. A  análise  foi  embasada  nos  Estudos  Enunciativos,  a  partir  de  propostas  de Benveniste (1989, 1995) e de Guimarães (1989, 1995, 1996, 2005). Esse aporte teórico permitiu observar como se dá, ao longo do texto da referida entrevista, a instauração das pessoas da enunciação. Para tanto, a entrada linguística neste material se deu pela observação dos pronomes pessoais utilizados, os quais permitiram  estabelecer  a  autora  entrevistada  como  foco  e,  portanto,  como locutora principal. Em relação às demais pessoas instauradas nesse processo enunciativo, a entrevistadora constituiu-se como o tu e o idoso como o ele. Em  linhas  gerais,  a  análise  apontou  para  as  seguintes  considerações:  a)  na fala da enunciadora, há um apagamento do tu e uma alternância entre eu e nós para se referir à primeira pessoa; b) o uso do nós, em algumas situações, junta a locutora ao grupo que colaborou na confecção do livro e em outras é indeterminado, o que permite a interpretação do ele (idoso) como incluso; c) tal utilização dos pronomes demonstra que a locutora constrói uma identificação apenas implícita à posição-sujeito idoso.Las discusiones presentadas en este artículo poseen el objetivo de analizar la identificación (o no) de un locutor con la posición-sujeto mayor. Como corpus del  análisis  se  eligió una  entrevista  que  se  reprodujo  en  el  sitio  “Portal  do Envelhecimento” (Portal del Envejecimiento), en el cual la organizadora de un libro expone el trabajo de elaboración de la obra, cuya temática se centra en cuestiones relacionadas a la vejez. El análisis está basado en los Estudios Enunciativos,  desde  las  propuestas  de  Benveniste  (1989,  1995)  y  las  de Guimarães (1989, 1995, 1996, 2005). Esta base teórica permitió observar como ocurre, a lo largo del texto de la susodicha entrevista, la instauración de las personas de la enunciación. Para esto, la entrada lingüística en este material se dio por la observación de los pronombres personales utilizados, los cuales han permitido establecer la autora que se entrevistó como foco y, por lo tanto, como locutora principal. En relación a las demás personas instauradas en ese proceso enunciativo, la entrevistadora se constituyó como tú y el mayor como él. De forma general, el análisis ha direccionado para las siguientes consideraciones: a) en el habla de la enunciadora, se borra el tú y hay una alternancia entre yo y nosotros para referirse a la primera persona; b) el uso de nosotros, en algunas situaciones,  une  la  locutora  al  grupo  que  ha  colaborado  en  la  confección del libro y en otras es indeterminado, lo que permite la interpretación del él (mayor) como incluso; c) tal uso de los pronombres demuestra que la locutora construye una identificación solamente implícita a la posición-sujeto mayor

Fatal myocardial damage due to zinc phosphide intentional ingestion

We present a case of fatal myocardial damage caused by zinc phosphide ingestion. It is a highly toxic poison that causes life-threatening complications (cardiac and respiratory acute failure above all) by its active metabolite phosphine. Phosphine toxicity’s case reports from Europe (and Italy), United States and western countries are rare. A 69-year-old man drunk a great amount of alcohol and unspecified amount of diluted zinc phosphide and was admitted to emergency department with a mild metabolic acidosis and acute respiratory failure. After gastro-intestinal decontamination, a transient improvement of his clinical conditions was observed. In the emergency medicine unit a sudden onset of severe bradycardia and hypotension appeared, electrocardiogram showed an increase in QRS duration with STelevation in many leads; 2 min later a thirddegree atrio-ventricular block was evident. Bradycardia went into asystole and the patient had cardiac arrest. Despite all resuscitative maneuvers, 6 h after zinc phosphide ingestion the patient died. No antidote or specific therapy or management of this potentially lifethreatening poison are actually available, but only supportive and resuscitative measures

APOE and longevity: study of a population of Sardinian Centenarians

Apolipoprotein E is a major determinant in lipoprotein metabolism and cardiovascular disease, it has emerged as an important molecule in several biological processes including Alzheimer's disease and cognitive function. ApoE is a polymorphic protein (ε2, ε3, ε4) with three proteic isoforms, ApoE2, ApoE3, ApoE4 (1). The aim of the study was to verify the frequencies of allelic variants a population of healthy elderly people. ApoE polymorphisms were determined by Real Time-PCR. The genotype frequencies of ApoE in our group of 71 centenarians (mean age 100.9 ±1.3) were: ε2/ε3 (12.67%); ε3/ε4 (5.63%). In the control group, consisting of 97 individuals (mean age 92.98 ±2.53), the genotype frequencies were: ε2/ε3 (7.21%); ε3/ε4 (15.46%). Differences between genotype frequencies in centenarians and control group were statistically significant (P<0.05). Results confirm that the frequency of ε2 allele is increased in centenaries, suggesting that this allele could be correlated to longevity

Polimorfismo del gene ACE:gene della longevit\ue0 o fattore di rischio nella patologia ipertensiva

Negli ultimi decenni l\u2019allungamento della vita media ha stimolato un particolare interesse nello studio dei processi dell\u2019invecchiamento e nella ricerca di possibili geni coinvolti nella longevit\ue0. In particolare i centenari dimostrano di avere una prevalenza minore di malattie cardiovascolari e dei fattori di rischio ad essa correlati. L\u2019enzima di conversione dell\u2019angiotensina (ACE), presente in tutte le cellule endoteliali, gioca un ruolo essenziale nel mantenimento dell\u2019omeostasi del flusso vascolare, regolando sia la produzione del vasocostrittore angiotensina II sia inattivando la bradichinina. In particolare alcuni studi hanno riportato una possibile correlazione tra il polimorfismo Inserzione/Delezione (I/D) localizzato all\u2019interno dell\u2019introne 16 del gene ACE e la patologia ipertensiva nonch\ue9 un suo possibile ruolo nella longevit\ue0. Lo studio \ue8 stato condotto su 200 soggetti di et\ue0 >90 anni provenienti dalla Regione Sardegna, 123 pazienti ipertesi (24-76 anni) e 112 soggetti normotesi (30-65 anni). Il polimorfismo (I/D) \ue8 stato tipizzato mediante PCR; gli amplificati di 490bp (allele I) e di 190bp (allele D) sono stati visualizzati su gel di agarosio al 2%. I nostri risultati mostrano una frequenza del genotipo D/D maggiore nei soggetti ipertesi rispetto ai soggetti normotesi (49% vs 36%, P = 0.027) e maggiore nel gruppo dei centenari sia rispetto ai soggetti ipertesi che normotesi ( 52% vs 49%, P = 0.016; 52% vs 36% , P < 0.01 ) . Sebbene il ruolo del gene ACE nel processo della longevit\ue0 e nella patogenesi delle malattie cardiovascolari rimanga controverso, il nostro studio suggerisce una possibile associazione tra longevit\ue0 e varianti alleliche di geni coinvolti nella patogenesi dell\u2019ipertensione

Synthesis of epibatidine-related Delta(2)-isoxazoline derivatives and evaluation of their binding affinity at neuronal nicotinic acetylcholine receptors

The group of \u3942-isoxazoline derivatives 5a\u2013c and 6a\u2013c, structurally related to epibatidine, and the simplified analogues 7a\u2013c were synthesized by means of a 1,3-dipolar cycloaddition-based strategy and tested at \u3b14\u3b22 and \u3b17 neuronal acetylcholine receptor (nAChR) subtypes. Competition binding experiments at \u3b14\u3b22 nAChR subtypes showed an overall significant reduction in affinity for the compounds under study in comparison to the reference radioligand [3H]-epibatidine. These outcomes have been rationalized by taking into account the ligand-based pharmacophore models reported in the literature and the recently proposed molecular model of the \u3b14\u3b22 receptor subtype. Conversely, compounds 5b, 5c, and 6b exhibited a noticeable affinity for the \u3b17 receptors and, in the case of 5c, also some subtype selectivit

Synthesis and binding affinity at neuronal nicotinic acetylcholine receptors of novel epibatidine-related delta2-isoxazoline derivatives

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a number of functional processes as well as several pathological conditions of the central nervous system, thereby representing a target for the development of novel therapeutic agents [1]. In the last few years many efforts have been directed towards the discovery of potent and selective nAChR ligands, in particular agonists at alpha4beta2 or alpha7 receptor subtypes, which are the two major populations of nAChRs found in the brain. In this context, epibatidine, a naturally occurring alkaloidal toxin which is one of the most powerful nicotinic agonists known, has become a model structure for the design of new high affinity and subtype selective ligands for nAChRs [2,3]. We designed and synthesized a set of novel compounds (1a-c and 2a-c), in which the two structural elements featuring epibatidine, i.e. the 7-azabicyclo[2.2.1]heptane system and the pyridine ring, have been distanced by insertion of a Delta2-isoxazoline moiety, either spiro-condensed or fused to the azanorbornane core, respectively. In addition, we designed compounds 3a-c as simplified analogues of derivatives 2a-c, where the ethylene bridge of the bicyclic system has been removed. The overall binding data evaluated on derivatives 1-3 indicated a relevant reduction of the alpha4beta2 affinity, typical of ebipatidine, coupled to the appearance of a noticeable affinity for the alpha7 receptor subtype. The results of further structural modifications on the compounds under investigation will be presented and discussed. [1] Paterson, D.; Nordberg, A. Neuronal Nicotinic Receptors in the Human Brain. Progr. Neurobiol. 2000; 61: 75-111. [2] Carroll, F. I. Epibatidine Structure-Activity Relationships. Bioorg. Med. Chem. Lett. 2004; 14: 1889-1896. [3] Wei, Z-L.; Petukhov, Y. X.; T\ufcckmantel, W.; George, C.; Kellar, K. J.; Kozikowski, A. P. Synthesis, Nicotinic Acetylcholine Receptor Binding Affinities, and Molecular Modeling of Constrained Epibatidine Analogues. J. Med. Chem. 2003; 46: 921-924

New analogues of epiboxidine incorporating the 4,5-dihydroisoxazole nucleus: Synthesis, binding affinity at neuronal nicotinic acetylcholine receptors, and molecular modeling investigations

A group of novel 4,5-dihydro-3-methylisoxitzolyl derivatives, structurally related to epiboxidine (= (1R,4S,6S)-6-(3-methylisoxazol-5-yl)-7-azzibicyclo[2.2.1]heptane), was prepared via 1,3-dipolar cyclo-addition of acetonitrile oxide to different olefins. Target compounds 1a and 1b, 2a and 2b, 3, 4, and 5 were tested for affinity at neuronal nicotinic heteromeric (alpha 4 beta 2) and homomeric (alpha 7) acetylcholine receptors. Notably, diastereoisomers 1a and 1b were characterized by a massive drop of the affinity at the alpha 4 beta 2 subtypes (K(i) values spanning the range 4.3-126 mu M), when compared with that of epiboxidine (Ki = 0.6 nM). Therefore, the replacement of the 3-methylisoxazole ring of epiboxidine with the 4.5-dihydro-3-methylisoxazole nucleus is detrimental for the affinity at alpha 4 beta 2 receptors. A comparable lack of affinity/selectivity for the two nACh R subtypes under study was evidenced for the remaining epiboxidine-related dihydroisoxazole derivatives 2a and 2b. and 3-5. Diastereoisomers 1a and 1b, and spirocyclic derivative 3 were docked into molecular models of the receptor subtypes under study, and their binding mode was compared with that of reference ligands endowed with high binding affinity