Estudo associativo entre a esquizofrenia e o polimorfismo G22A no gene da adenosina deaminase (ADA)

Made available in DSpace on 2015-04-14T14:50:52Z (GMT). No. of bitstreams: 1 401915.pdf: 528070 bytes, checksum: d3061dc4db639040f254d5c17da71d31 (MD5) Previous issue date: 2008-06-09O sistema purin?rgico, especialmente a adenosina, pode desempenhar um papel na patofisiologia da esquizofrenia. A ativa??o dos receptores de adenosina A1 inibe a libera??o de v?rios neurotransmissores como o glutamato, a dopamina, a serotonina e a acetilcolina, e diminui a atividade neuronal pela hiperpolariza??o p?s-sin?ptica. A adenosina (ADA) participa no metabolismo da adenosina convertendo-a em inosina. O polimorfismo funcional mais freq?ente da ADA (22 G - (seta)A) (ADA1 *2) exibe 20-30% menos atividade enzim?tica em indiv?duos com o gen?tipo G/A do que em indiv?duos com o gen?tipo G/G. Esse polimorfismo foi avaliado em 152 pacientes esquizofr?nicos e 111 controles saud?veis. N?s observamos uma diminui??o significativa na freq??ncia do alelo de baixa atividade ADA1 *2 em pacientes esquizofr?nicos (7 4,6%) em rela??o aos controles (13 17%, p= 0,032, OR= 2,6). Esses resultados sugerem que o alelo ADA1 *2 associado ? baixa atividade da ADA, e conseq?entemente a altos n?veis de adenosina, ? menos freq?ente entre os pacientes esquizofr?nicos

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients Diminuição da frequência da variante alélica de baixa atividade da adenosina desaminase (ADA1*2) em pacientes esquizofrênicos

OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G&#8594;A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G&#8594;A (ADA1*2) in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G&#8594;A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6%) relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6). CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.<br>OBJETIVO: A adenosina pode ter um papel importante na fisiopatologia da esquizofrenia, uma vez que modula a liberação de vários neurotransmissores, tais como glutamato, dopamina, serotonina e acetilcolina, diminui a atividade neuronal por hiperpolarização pós-sináptica e inibe a atividade dopaminérgica. A adenosina desaminase participa do metabolismo das purinas pela conversão de adenosina em inosina. O mais frequente polimorfismo funcional da adenosina desaminase (22G &#8594;A) (ADA1*2) exibe uma diminuição de 20-30% da atividade funcional em indivíduos com genótipo G/A quando comparados com indivíduos com o genótipo G/G. O objetivo deste estudo foi avaliar o polimorfismo 22G&#8594;A (ADA1*2) em pacientes esquizofrênicos e em controles saudáveis. MÉTODO: Os genótipos da ADA 22G &#8594;A foram identificados através de uma estratégia de PCR alelo-específica em 152 pacientes esquizofrênicos e 111 controles saudáveis. RESULTADOS: Foi observada uma diminuição significativa na frequência do genótipo G/A em pacientes esquizofrênicos (7 - 4,6%) em relação ao grupo controle (13 - 11,7%, p = 0,032, OR = 2,6). CONCLUSÃO: Estes resultados sugerem que o genótipo G/A associado com baixa atividade de adenosina desaminase, e potencialmente com níveis aumentados de adenosina, é menos frequente entre pacientes esquizofrênicos

Democracia y derechos humanos. Desafíos para la emancipación.

El libro tiene su origen en dos simposios del congreso internacional "Ciencia, tecnologías y culturas. Diálogos entre las disciplinas del conocimiento. Mirando al futuro de América Latina y el Caribe”, organizado por la Universidad de Santiago de Chile y celebrado del 30 de octubre al 2 de noviembre de 2008. En principio, en vista de la calidad de las ponencias del simposio “Democracia: ideas y prácticas”, se pensó en la posibilidad de editar su memoria. Sin embargo, cuando, conversando con Luisa Ripa, se habló de que el simposio, “Derechos humanos: en el cruce con la religión, la ética y la educación”, del cual ella fue la principal coordinadora, se sumara a nuestro esfuerzo, se consideró que se podía hacer algo más ambicioso de lo inicialmente previsto, no sólo en cuanto a la cantidad de los trabajos que esta obra podría incorporar, sino también en cuanto a su calidad, al contemplar la conveniencia, que después se hizo realidad, de que los trabajos presentados en los respectivos simposios fueran revisados por sus autores para poder ser publicados en esta obra. Además, cinco trabajos que no fueron expuestos en el mencionado congreso se incorporaron a la primera parte del libro. De esta manera, la idea de publicar una memoria con las ponencias de un simposio acabó dando lugar al libro que ahora presentamos al público, coeditado por la Universidad Autónoma del Estado de México, la Universidad Nacional de Quilmes (Argentina) y El Colegio Mexiquens

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk