Mercury in the brain (tumor tissues) and in markers (hair and blood) of exposure in Western Amazonia patients.

BACKGROUND: Central nervous system tumors (CNSTs) represent the second most frequent form of malignant tumors in childhood and the second leading cause of death associated with neurological diseases, affecting individuals of all age groups. In adults, CNSTs are the sixth most common cause of death in patients with malignant tumors. Additionally, the brain is the most sensitive and studied organ for mercury (Hg) toxicity. METHOD: We studied total Hg (THg) in tissue samples (of benign and malignant CNSTs) and explored its associations with THg in exposure markers (hair and blood) from 65 patients (40 females and 25 males) who underwent surgical treatment. RESULTS: No statistically significant differences were found in THg concentrations in brain tumors or in blood and hair from these patients (classified as malignant/benign or glioma/non-glioma); also, there were no statistically significant differences between males and females. However, statistically significant correlations were found between THg in CNSTs and in hair (rs = 0.4967; p = 0.0001) and in blood (rs = 0.4702; p = 0.0058); but no significant correlations were found between THg in hair and blood (rs = 0.1229; p = 0.5332). In the Western Amazon, with endemic exposure to fish-methylmercury, these urban patients were low to moderate fish consumers; THg concentrations in blood (median: 0.645 µg.L-1; range: 8.01-21.02 µg.L-1; n = 56) and hair (median: 0.686 µg.g-1; range: 0.01-10.02 µg.g-1; n = 65) were relatively low, whereas THg levels in brain tumors (median: 8.194 ng.g-1; range: <0.10-69.16 ng.g-1; n = 65) were within range of published studies in brain autopsies. Additionally, no statistically significant correlations (p = 0.4828) were observed between frequency of fish consumption and THg in the brain. CONCLUSION: Although no significant THg concentrations in the type of brain tumors (benign versus malignant) were found, the significantly positive correlation between markers of THg exposure (hair and blood) and THg in the brain tissues indicates its usefulness as a marker/proxy for brain-THg load. These findings confirm the value of using hair and blood as constructs of THg in the brain of exposed populations.

Inflammatory and metabolic markers and short-time outcome in patients with acute ischemic stroke in relation to TOAST subtypes.

The aim of this study was to evaluate the association between inflammatory and metabolic markers and short-time outcome with acute ischemic stroke subtypes. A total of 121 patients was classified according to TOAST criteria, such as large artery atherosclerosis (LAAS), lacunar infarct (LAC), cardioembolic infarct (CEI), other determined etiology (ODE), and undetermined etiology (UDE). The functional impairment was evaluated within the first eight hours of stroke and the outcome after three-month follow-up using the modified Rankin Scale. Blood samples were obtained up to 24 h of stroke. Compared with 96 controls, patients with LAAS, CEI, and LAC subtypes showed higher levels of white blood cells, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), metalloproteinase 9 (MMP-9), glucose, and iron (p < 0.05); and lower high-density lipoprotein cholesterol (HDL-C) (p < 0.0001); platelets, insulin, insulin resistance, and homocysteine were higher in LAC (p < 0.0001); ferritin was higher in LAAS (p < 0.0001); and total cholesterol (TC) was lower in LAAS and CEI (p < 0.01). When stroke subtypes were compared, insulin was higher in LAAS vs. LAC and in LAC vs. CEI (p < 0.05); and TC was lower in LAAS vs. LAC (p < 0.05). Outcome and rate of mortality after three-month were higher in LAAS vs. LAC (p < 0.001 and p = 0.0391 respectively). The results underscored the important role of the inflammatory response and metabolic changes in the pathogenesis of ischemic stroke subtypes that might be considered on the initial evaluation of stroke patients to identify those that could benefit with individualized therapeutic strategies that taken into account these markers after acute ischemic event.

Tumor necrosis factor beta NcoI polymorphism (rs909253) is associated with inflammatory and metabolic markers in acute ischemic stroke.

Polymorphisms in genes coding for pro-inflammatory molecules represent important factors for the pathogenesis and outcome of stroke. The aim of this study was to evaluate the relationship between the tumor necrosis factor beta (TNF-ß) NcoI (rs909253) polymorphism with inflammatory and metabolic markers in acute ischemic stroke. Ninety-three patients and 134 controls were included. The TNF-ß polymorphism was determined using PCR-RFLP with NcoI restriction enzyme. Stroke subtypes and neurological deficit score were evaluated. White blood cell counts, erythrocyte sedimentation rate (ESR), plasma levels of IL-6 and TNF-α, serum high sensitivity C-reactive Protein (hsCRP), serum lipid profile, plasma levels of glucose and insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Stroke patients presented higher white blood cell counts, hsCRP, ESR, glucose, insulin, and HOMA-IR, and lower HDL cholesterol than controls (p < 0.01). There was no difference in genotypic and allelic frequency of TNF-ß NcoI polymorphism among patients and controls (p > 0.05). However, stroke patients carrying the TNFB2/B2 genotype presented higher levels of TNF-α, white blood cell counts, total cholesterol, LDL cholesterol, glucose, insulin, and HOMA-IR than those with other genotypes (p < 0.05). White blood cells, IL-6, hsCRP, and ESR were positively correlated with the neurological deficit of the patients (p < 0.05). Taken together, TNF-ß NcoI polymorphism, by itself, was not associated with increased susceptibility for stroke development. However, the homozygous genotype for the allele TNFB2 was associated with higher expression of classical inflammatory and metabolic markers of development and outcome of stroke than other genotypes. The identification of variant alleles might allow both better prediction of susceptibility for stroke as well the identification of novel stroke mechanisms that could be target to new therapeutic approaches. Stroke patients carrying the TNFB2 variant allele could have a beneficial effect with the anti-inflammatory therapies in the early inflammatory phase of stroke.