RAGE gene polymorphism in heart failure patients with and without angiographic evidence of significant coronary atherosclerosis.

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE-RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) <45%, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (p<0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin

Soluble RAGE Plasma Levels in Patients with Coronary Artery Disease and Peripheral Artery Disease

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE

Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients

In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology

Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis

<p>Abstract</p> <p>Background</p> <p>K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab.</p> <p>Methods</p> <p>Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible.</p> <p>A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis.</p> <p>Results</p> <p>Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN ≥ 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN ≥ 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively).</p> <p>Conclusion</p> <p>FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.</p

Estudo de populações de Rhodnius neglectus e R. prolixus (Hemiptera, Reduviidae, Triatominae) mantidas em laboratório por meio de marcadores mitocondriais, morfológicos e morfométricos

Estima-se que 6 a 7 milhões de pessoas estejam infectadas com Trypanosoma cruzi no mundo, a maioria na América Latina, sendo a transmissão vetorial responsável ainda por, aproximadamente, 80% dos casos. Atualmente são descritas 151 espécies de triatomíneos agrupadas em cincos tribos formadas por 18 gêneros. O gênero Rhodnius conta com 19 espécies de potenciais vetores, podendo veicular T. cruzi e Trypanosoma rangeli. É considerado um dos gêneros taxonomicamente mais complexos da subfamília Triatominae, devido as semelhanças morfológicas e a distribuição geográfica que podem se sobrepor entre algumas de suas espécies dificultando seu estudo, apesar das diversas técnicas empregadas para sua distinção. Com o desenvolvimento atual das técnicas moleculares tornou-se possível a caracterização de espécies de triatomíneos por meio de marcadores mitocondriais e nucleares, tendo essa se tornado uma variável a mais para a taxonomia dos triatomíneos, assim como a já utilizada morfologia e a recentemente popularizada morfometria geométrica. A adição de novas variáveis possibilita que dados já existentes possam ser comprovados e/ou corrigidos. Neste trabalho foram obtidos subsídios que ampliam o conhecimento e que agregados aos já existentes podem proporcionar uma diferenciação mais minuciosa e precisa de espécies englobadas no gênero Rhodnius, de modo a contribuir para estabelecer uma classificação mais apropriada. A obtenção dos dados foi conduzida, por meio de estudo molecular, utilizando-se os marcadores mitocondriais – citocromo b e citocromo oxidase I, além de estudos morfológicos, utilizando-se como caracteres o processo mediano do pigóforo, o ângulo ânterolateral e a presença de colarinho nos ovos, a morfometria geométrica da cabeça também foi empregada, a fim de se distinguir populações de R. neglectus e R. prolixus. Os resultados obtidos a partir dessa análise multiparamétrica sugeriram que, as colônias identificadas como Rhodnius prolixus pertencem à espécie, que algumas colônias de R. neglectus analisadas apresentaram padrões condizentes com R. prolixus, já as demais apresentaram padrões condizentes com a espécie.Worlwide, it is estimated that 6 to 7 million people are infected with Trypanosoma cruzi, mostly in Latin America and the vector transmission is still responsible for approximately 80% of the cases. There are currently 151 described species of triatomine, grouped into five tribes, formed by 18 genres. The Rhodnius genre includes 19 species, which can transmit T. cruzi and Trypanosoma rangeli. It is considered one of the most complex taxonomically genera of Triatominae, due to its morphological similarities and geographical distribution that may overlap among some species hindering their study, despite the various techniques used for their distinction. With the current development of molecular techniques it has become possible to characterize triatomine species through mitochondrial and nuclear markers, this became one more toll for the taxonomy of triatomines, just as the already used morphology and recently popularized geometric morphometry. The addition of new variables enables the verification and or correction of existing data. This work has generated valueable data that amplify the knowledge which in addition to the existing may provide a more accurate differentiation of species included in the genre Rhodnius, in order to help establish a more appropriate classification. Data collection was performed by DNA analysis, using mitochondrial markers - cytochrome b and cytochrome oxidase I, in addition to morphological parameters, as, median process of pygophore, the anterolateral angle and the presence of collar in eggs, geometric morphometry of the head was also used in order to help distinguish populations of R. neglectus and R. prolixus. The results obtained from this multiparameter analysis suggested that colonies identified as R. prolixus belong to the species, a few colonies of R. neglectus analyzed showed consistent patterns with R. prolixus, the others colonies of R. neglectus showed consistent patterns to the species originally identified.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

A dynamical model for wave-particle interaction in collisionless plasmas

Dottorato di Ricerca in Fisica, Ciclo XX, a.a. 2004-2007Università della Calabri

Correlazione tra livelli plasmatici di galactina e aterosclerosi coronarica: nuovo marcatore di instabilità clinica?

L’infiammazione gioca un ruolo chiave nella aterosclerosi. La galactina-3 è un mediatore dell’attivazione dei macrofagi derivato dall’endotelio, attivamente coinvolto nella regolazione di molti aspetti del comportamento delle cellule infiammatorie. Lo scopo di questo studio è quello di quantificare i livelli plasmatici di galactina-3 nei pazienti con malattia coronarica (CAD) e le sue diverse manifestazioni cliniche al momento dell’osservazione, per verificare se la galactina-3 potrebbe essere un biomarker utile nella valutazione della malattia aterosclerotica. Sono stati arruolati 125 pazienti affetti da CAD angiograficamente documentata (70 stabili, 55 instabile). I livelli plasmatici di galactina-3 sono stati quantificati utilizzando un kit ELISA. Pazienti instabili (n=55) avevano livelli plasmatici di galactina-3 superiori rispetto ai soggetti stabili [27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001]. Sembra inoltre essere presente una correlazione tra i livelli plasmatici di galactina-3 e il numero di vasi compromessi: i pazienti con CAD trivasale avevano livelli più elevati di galactina-3 rispetto ai pazienti con malattia mono- o bivasale [17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p=0.058]. Il riscontro di livelli plasmatici di galactina-3 significativamente più elevati nei pazienti con angina instabile rispetto a quelli con angina stabile conferma il coinvolgimento di galactina-3 nel promuovere l’attivazione dei macrofagi e l’attrazione dei monociti. Nonostante la distribuzione della CAD nei pazienti con malattia coronarica acuta e cronica malattia siano simili, si può ipotizzare che la galactina-3 possa essere un utile biomarker di placca aterosclerotica e in particolare della sua destabilizzazion

Possible Role of −374T/A Polymorphism of RAGE Gene in Longevity

Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of −374T/A polymorphism in subjects aged &gt;90 years and in middle-aged individuals. We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders