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Introduction: the scientific literature suggests that two in every three patients with chronic pain every so often suffer from transient exacerbations because of various causes, some of them predictable and some unexpected. In addition to the suffering they bring about, these episodes represent a relevant issue for patients as they trigger anxiety and add functional disability, which translates into greater difficulties in controlling baseline pain and lower quality of life. In 1990 the term "breakthrough pain" was coined in the United States to define transient cancer pain exacerbations under appropriate pain management with major opioids. In 2002, Sociedad Española de Oncología Médica (SEOM), Sociedad Española de Cuidados Paliativos (SECPAL), and Sociedad Española del Dolor (SED) defined a consensus document wherein the term "dolor irruptivo" (irruptive pain) was adopted to define sudden, transient (usually less than 20-30 minutes), severe (VAS > 7) pain breakouts on the background of stable, persistent pain that remains tolerable (VAS < 5) under primarily major opioids. Overall, three etiologies are recognized for irruptive pain: incidental irruptive pain; idiopathic or spontaneous irruptive pain, and irruptive pain from end-of-dose medication failure. Objectives: the main goal of this work was to retrospectively study the effectiveness of sublingual fentanyl citrate in 180 patients treated for irruptive pain in Andalusian pain units during 1 month. Secondary goals included a description of the clinical indications and epidemiologic features of patients with irruptive pain under sublingual fentanyl citrate; understanding sublingual fentanyl citrate regimens for patients with irruptive pain; and a research of adverse events potentially associated with the use of sublingual fentanyl citrate in patients with irruptive pain. Material and methods: a retrospective, observational study of 180 patients, of whom 173 completed the study. Inclusion criteria (patients had to, Introducción: la literatura científica indica que dos de cada tres pacientes con dolor crónico sufren con cierta frecuencia exacerbaciones puntuales del mismo debido a diferentes causas, en ocasiones previsibles, y en otras inesperadas. Además del sufrimiento que conllevan, estos episodios constituyen un problema importante para el paciente pues generan ansiedad y añaden incapacidad funcional, lo cual se traduce en una mayor dificultad para controlar el dolor basal y una menor calidad de vida. En 1990 se acuñó en Estados Unidos el término "break-through pain", para definir a las exacerbaciones transitorias de un dolor oncológico, que está bien controlado con la utilización de opioides mayores. En el año 2002, la Sociedad Española de Oncología Médica (SEOM), la Sociedad Española de Cuidados Paliativos (SECPAL) y la Sociedad Española del Dolor (SED), establecieron un documento de consenso en el que asumieron el término "dolor irruptivo", para definir una exacerbación del dolor de forma súbita y transitoria, de gran intensidad (EVA > 7) y de corta duración (usualmente inferior a 20-30 minutos), que aparece sobre la base de un dolor persistente estable, cuando este se encuentra reducido a un nivel tolerable (EVA < 5) mediante el uso fundamental de opioides mayores. De forma general se acepta la existencia de tres tipos etiológicos de dolor irruptivo: dolor irruptivo incidental; dolor irruptivo idiopático o espontáneo, y dolor irruptivo por fallo de final de dosis. Objetivos: el objetivo principal de este trabajo fue estudiar retrospectivamente la efectividad del citrato de fentanilo sublingual en 180 pacientes tratados por dolor irruptivo en las Unidades de Dolor de Andalucía durante 1 mes. Como objetivos secundarios se buscó describir las indicaciones clínicas y características epidemiológicas de los pacientes con dolor irruptivo que se encuentran en tratamiento con citrato de fentanilo sublingual; conocer las pautas de administración del citrato de fentanilo sublingua

Contains fulltext : 48583.pdf (publisher's version ) (Closed access), Hyperhomocysteinemia is a risk factor for atherosclerosis and vascular disease; however, the mechanism underlying this association remains poorly understood. Increased levels of intracellular S-adenosylhomocysteine (AdoHcy), secondary to homocysteine-mediated reversal of the AdoHcy hydrolase reaction, have been associated with reduced DNA methylation patterns and pointed as responsible for the hyperhomocysteinemia-related endothelial dysfunction. Methylation is an epigenetic feature of genomic DNA, which leads to alterations in gene expression. So far, the effect of intracellular AdoHcy accumulation on DNA methylation patterns has not yet been fully substantiated by experimental evidence. The present study was designed to evaluate, in cultured endothelial cells, the effect of AdoHcy accumulation on genomic global DNA methylation status. Experimental intracellular accumulation of AdoHcy was induced by adenosine-2,3-dialdehyde (ADA), an inhibitor of AdoHcy hydrolase. Increased concentrations of inhibitor were tested, and unsupplemented medium incubations were used as controls. Cytosolic and nuclear fractions were obtained from trypsinized cells after 72 h of incubation. Total homocysteine concentration was quantified (culture medium and cytosolic fractions) by high-performance liquid chromatography (HPLC). S-Adenosylmethionine and AdoHcy concentrations were measured (cytosolic fractions) by stable-isotope dilution LC-tandem mass spectrometry method. Genomic DNA was obtained from the nuclear fraction, and global DNA methylation status was evaluated by the cytosine extension assay. The results showed that supplementation of the culture medium with ADA had no cytotoxic effect and increased the intracellular AdoHcy concentration in a dose-dependent manner. A significant negative correlation was observed between intracellular AdoHcy and genomic DNA methylation status. These findings strongly point to the importance of AdoHcy as a pivotal biomarker of genomic DNA methylatio

Contains fulltext : 57374.pdf (publisher's version ) (Closed access)

The genotypic diversity of Brazilian Cryptococcus neoformans strains was analyzed. The majority of the samples were alphaA (65%), followed by alphaB (17.5%), alphaD (9%), alphaAaD hybrids (5%), and alphaC (3.5%). A considerable genotypic diversity occurred within C. neoformans var. grubii, and a new amplified fragment length polymorphism genotype, 1B, was recognized.

Item does not contain fulltext, BACKGROUND: The pathogenic mechanism of homocysteine's effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. METHODS: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. RESULTS: Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [(3)H]dCTP incorporation/ micro g of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios. CONCLUSION: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.

Item does not contain fulltext, BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Elevated plasma total homocysteine (tHcy) is a major risk for cardiovascular disease. A common 677C-->T mutation in the MTHFR gene results in decreased enzymic activity, and contributes to increased plasma tHcy, in association with low plasma folate. A recently described 1298A-->C mutation in the MTHFR gene clearly reduces MTHFR activity (although to a lesser extent than the 677C-->T) but its effect on plasma tHcy levels is not yet clear. AIM: To investigate the frequency of these two MTHFR polymorphisms in a Portuguese population, and to correlate the MTHFR genotype with the biochemical phenotype at the level of homocysteine and folate concentrations. DESIGN: Prospective population survey. METHODS: We studied 117 healthy volunteers (71 females, 46 males). The 677C-->T and 1298A-->C mutations were screened by PCR-RFLP. Levels of plasma tHcy and folate, and red blood cell folate, were determined. RESULTS: The allele frequencies of the 677C-->T and 1298A-->C mutations were 0.33 and 0.28, respectively. Homozygotes for the 677C-->T mutation had significantly elevated plasma tHcy and RBC folate levels and significantly lowered plasma folate concentrations than subjects without the mutation. The 1298A-->C mutation showed a significant effect on plasma tHcy, but not on plasma folate or RBC folate levels. DISCUSSION: The observed 677T allele frequency is not consistent with the idea of a north-south gradient as previously suggested. The 1298A-->C mutation is common in Portugal. Both MTHFR mutations showed effects on plasma tHcy levels.