GSTA1*-69C/T and GSTO2*N142D as asthma- and allergy-related risk factors in Italian adult patients.

1. Asthma and allergies are characterized by variable and subjective symptoms influenced by many genes, molecular mechanisms and environmental factors. The presence of inflammation and oxidative stress in the airways are important biochemical features of asthma and respiratory allergies. Glutathione S-transferase (GSTs) enzymes play an important role in cellular protection against inflammation, and functional genetic polymorphisms in GST genes show a significant association with asthma and allergy risk. Specifically, our previous study on asthmatic children highlighted GSTA1 and GSTO2 as novel susceptibility loci for asthma. 2. In the present study we focused our attention on GSTA1*-69C/T (rs3957357) and GSTO2*N142D (rs156697) polymorphisms to confirm our previous results in an independent adult study population and to clarify whether GSTA1 and GSTO2 gene polymorphisms are involved in a non-discriminative pathway towards asthma and respiratory allergy. 3. To accomplish this, we recruited 103 patients with respiratory allergies, 199 patients with asthma and 200 healthy controls. Genomic DNA extracted from buccal cells was screened for GSTA1*-69C/T and GSTO2*N142D single nucleotide polymorphisms. 4. The GSTA1*-69T and GSTO2*D142 variants are both associated with a significantly increased risk of asthma, whereas only GSTA1*-69C/T is significantly associated with allergies. These outcomes confirm the involvement of GSTO2 loci in asthma and suggest that GSTA1 is a common risk factor for asthma and allergies.

Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease.

The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.

Blood cell counting in neonates: a comparison between a low volume micromethod and the standard laboratory method.

BACKGROUND: Iatrogenic anaemia caused by repeated blood sampling to monitor laboratory parameters can contribute, particularly in neonates, to the need for transfusion. "Point of care" laboratory equipment uses smaller amounts of blood for analytic determinations and could, therefore, help to prevent secondary anaemia. In this study we compared the results of haematological parameters measured using a standard laboratory method and using a "point of care" micromethod, with the aim of validating the use of this latter method in clinical practice in neonatology. MATERIALS AND METHODS: One hundred and fifty venous or capillary blood samples were taken from full-term or premature neonates 2-4 hours or 48 hours after birth. Each sample was processed by a standard haematology analyser and another micromethod instrument. Bland-Altman plots were constructed for each parameter and intra-class coefficients of correlation were calculated in order to evaluate the concordance between the two analysers. RESULTS: The concordance between the data obtained with the two analysers, expressed as the intra-class correlation, was 0.98 for white blood cell count, 0.97 for haemoglobin concentration, 0.96 for haematocrit, 0.95 for mean red cell volume and 0.98 for platelet count. The micromethod produced overestimated mean values for the leucocyte count (+1.27; p<0.001), haematocrit (+1.80; p<0.001) and platelet count (+13.55; p<0.001). CONCLUSIONS: Overall, the concordance between the values obtained with the two analysers was high for each of the parameters taken into consideration. In the case of haemoglobin and leucocytes, give the high intra-class correlation and lack of systematic overestimation of one method over another, the micromethod guarantees a correct evaluation; however, despite the high intra-class correlations for platelet counts, the systemic error seems to suggest that the micromethod cannot guarantee an appropriate evaluation of this parameter.

Ceruloplasmin/Transferrin system is related to clinical status in acute stroke.

BACKGROUND AND PURPOSE: In acute stroke, Iron (Fe) may amplify reperfusion injury by catalyzing the conversion of superoxide and hydrogen peroxide into highly reactive radicals. Transferrin (Tf) is the main protein regulating Fe homeostasis, whereas Ceruplasmin (CP) is a circulating ferroxidase enzyme able to oxidize ferrous ions to less toxic ferric forms. This study aims at investigating whether CP, Copper (Cu), Tf, and Fe play a role in the pathophysiology of acute stroke. METHODS: We enrolled 35 acute stroke patients and 44 controls. All patients underwent: neurological examination assessed by National Institutes of Health Stroke Scale (NIHSS), ultrasound evaluation of carotid atherosclerosis, brain MRI to quantify ischemic lesion volume and measurement of serum levels of CP, Cu, Tf, Fe, hydro-peroxides, and Total plasmatic antioxidant capacity. RESULTS: In patients, NIHSS scores were associated with Tf (r=-0.48, P=0.004), hydro-peroxides (r=0.34, P=0.046), CP (r=0.43, P=0.012), and lesion volume (r=0.50, P=0.004). Lesion volume was inversely associated with Tf (r=-0.44, P=0.012). CP and hydro-peroxides were also largely related (r=0.81, P<0.001). The model multiple R was 0.57, resulting in a 32.5% of explained NIHSS variance with Tf accounting for 23.4% and CP for 9.1%. CONCLUSIONS: CP and Tf levels are representative of clinical status in acute stroke patients. Our findings suggest a protective role of Tf in acute stroke and a possible ambivalent role of CP.