A CASE-CONTROL STUDY OF NEUROTOXIC METALS IN CEREBROSPINAL FLUID AND RISK OF AMYOTROPHIC LATERAL SCLEROSIS

Many studies have investigated the possible relation between exposure to heavy metals and risk of amyotrophic lateral sclerosis (ALS). We aimed at assessing the levels of two neurotoxic metals, cadmium (Cd), lead (Pb) and mercury (Hg) in cerebrospinal fluid (CSF) of ALS patients and hospital controls. CSF heavy metal content was determined using inductively coupled plasma sector field mass spectrometry (ICP-SF-MS) according to methodologies previously established for biological matrices and specifically for CSF. We obtained CSF samples from 38 ALS cases, including 16 men and 22 women, and from 38 hospital-referred subjects undergoing lumbar puncture because of suspected but later unconfirmed neurological disease, with mean age of 55.5 and 52.26 respectively (range 30\u2013 85). Median heavy metal concentrations were higher in ALS cases compared to controls for Pb (155 vs. 132 ng/l) but lower for Cd (36 vs. 72) and Hg (196 vs. 217). In unconditional multiple logistic regression analysis adjusting for age and sex, we found a disease odds ratio (OR) for the middle and the upper exposure tertiles of 0.8 (0.2-2.6) and 1.4 (95% CI 0.5 to 4.2) for Pb, 0.9 (0.3-2.8) and 0.3 (0.1 to 1.0) for Cd, and 12.4 (2.7-57.3) and 3.03 (0.52-17.55) for Hg. We also conducted sensitivity analyses with log transformed values and with winsorized values by setting data exceeding the 95th percentile to the 95th percentile, but the risk estimates did not substantially change. Our results and particularly the lack of dose-response relations give little support for an involvement of these heavy metals in ALS etiology, with the possible exception of Hg. However, caution should be used in the interpretation of these results due to some study limitations, such as the statistical imprecision of the risk estimates, the hospital-based design of the study, and the potential for unmeasured confounding

Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species

Introduction: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. Methods: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. Results: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. Conclusions: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite

Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study

Exposure to neurotoxic chemicals such as pesticides, selenium, and heavy metals have been suggested toplay a role in the etiology of amyotrophic lateral sclerosis (ALS). We assessed exposure to lead, cadmium,and mercury in 38 ALS patients (16 men and 22 females) and 38 hospital-admitted controls by using theircerebrospinal fluid (CSF) content as biomarker. We determined CSF heavy metal levels with inductivelycoupled plasma sector field mass spectrometry, according to a methodology specifically developed forthis biological matrix. ALS patients had higher median values for Pb (155 vs. 132 ng/L) but lower levelsfor Cd (36 vs. 72 ng/L) and Hg (196 vs. 217 ng/L). In the highest tertile of exposure, ALS odds ratio was1.39 (95% CI 0.48–4.25) for Pb, 0.29 (0.08–1.04) for Cd and 3.03 (0.52–17.55) for Hg; however, no dose-response relation emerged. Results were substantially confirmed after conducting various sensitivityanalyses, and after stratification for age and sex. Though interpretation of these results is limited by thestatistical imprecision of the estimates, and by the possibility that CSF heavy metal content may notreflect long-term antecedent exposure, they do not lend support to a role of the heavy metals cadmium,lead and mercury in ALS etiology

Dietary determinants of serum selenium species in Italian populations

We investigated the correlation between dietary habits with serum levels of selenium (Se) species collected from an Italian community. Consumption of food items was assessed using a food frequency questionnaire. Cereal intake showed a positive relation with total and organic Se, but null/negative with inorganic Se. Fish and seafood positively correlated with inorganic Se and negatively with organic Se. Correlations were generally negative/null in vegetables (only Se-Cys was positively correlated), while in fruits they were positive with organic species, mainly Se-Cys. Legumes showed inverse relation with overall organic Se, but positive with Se-Cys, Se-TrXr and inorganic Se. Correlation of potatoes intake was negative with Se forms, except a positive one with Se-Cys and selenate. Our results show highly specific associations between intake of selected foods and circulating Se species levels

Instabilities and Oscillations in Isotropic Active Gels

We present a generic formulation of the continuum elasticity of an isotropic crosslinked active gel. The gel is described by a two-component model consisting of an elastic network coupled frictionally to a permeating fluid. Activity is induced by active crosslinkers that undergo an ATP-activated cycle and transmit forces to the network. The on/off dynamics of the active crosslinkers is described via rate equations for unbound and bound motors. For large activity motors yield a contractile instability of the network. At smaller values of activity, the on/off motor dynamics provides an effective inertial drag on the network that opposes elastic restoring forces, resulting in spontaneous oscillations. Our work provides a continuum formulation that unifies earlier microscopic models of oscillations in muscle sarcomeres and a generic framework for the description of the large scale properties of isotropic active solids.Comment: 13 pages, 5 figure

Improving outcome over time of percutaneous coronary interventions in unstable angina

AbstractOBJECTIVEThis study was performed to evaluate the recent changes in the outcome of coronary interventions in patients with unstable angina (UA).BACKGROUNDAn early invasive strategy has not been shown to be superior to conservative treatment in patients with UA. Earlier studies had utilized older technology. Interventional approaches have changed in the recent past, but to our knowledge, no large studies have addressed the impact of these changes on the outcome of coronary interventions.METHODSWe analyzed the in-hospital and intermediate-term outcome in 7,632 patients with UA who underwent coronary interventions in the last two decades. The study population was divided into three groups: group 1, n = 2,209 who had coronary intervention from 1979 to 1989; group 2, n = 2,212 with interventions from 1990 to 1993; and group 3, n = 3,211 treated from 1994 to 1998.RESULTSGroup 2 and 3 patients were older and sicker compared with group 1 patients. The clinical success improved significantly in group 3 (94.1%) compared with group 2 (87%) and group 1 (76.5%) (p < 0.001). There was a significant reduction in in-hospital mortality, Q-wave myocardial infarction and need for emergency bypass surgery in group 3 compared with the earlier groups. One-year event-free survival was also significantly higher in the recent group compared with the earlier groups: 77% in group 3, 70% in group 2 and 74% in group 1 (p < 0.001). With the use of multivariate models to adjust for clinical and angiographic variables, treatment during the most recent era was found to be independently associated with improved in-hospital and intermediate-term outcomes.CONCLUSIONSThere has been significant improvement in the in-hospital and intermediate-term outcome of coronary interventions in patients with UA in recent years; newer trials comparing conservative and invasive strategies are therefore needed