Closing the knowledge gap on the composition of the asbestos bodies.

Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.

Selenium distribution and speciation in plant parts of wheat (Triticum aestivum) and Indian mustard (Brassica juncea) from a seleniferous area of Punjab, India.

The concentration, distribution, and speciation of selenium in different parts of wheat and Indian mustard, grown in a seleniferous area in Punjab, were investigated using synchrotron based (XAS) and classical acid digestion and extraction methods. The analyses revealed a high Se enrichment in all investigated plant parts, with Se levels in the range of 133-931 mg/kg (dry weight, dw). Such high Se enrichment is mainly due to the considerable amounts of easily available Se detected in the soil, which are renewed on a yearly basis to some extent via irrigation. Speciation analysis in soil and plants indicated selenate and organic Se as major Se species taken up by plants, with a minor presence of selenite. The analyses also revealed that the highest Se enrichment occurs in the upper plant parts, in agreement with the high uptake rate and mobility of selenate within plants. In both wheat and mustard, highest Se enrichments were found in leaves (387 mg/kg·dw in wheat and 931 mg/kg·dw in mustard). Organic species (dimethylselenide and methylselenocysteine) were found in different parts of both plants, indicating that an active detoxification response to the high Se uptake is taking place through methylation and/or volatilization. The high proportion of selenate in wheat and mustard leaves (47% and 70%, respectively) is the result of the inability of the plant metabolism to completely transform selenate to non-toxic organic forms, if oversupplied. Methylselenocysteine, a common Se species in accumulating plants, was detected in wheat, suggesting that, in the presence of high Se concentration, this plant develops similar response mechanisms to accumulator plants.

The local environment of Co2+ ions intercalated in vanadium oxide/hexadecylamine nanotubes.

Vanadium oxide nanotubes constitute promising materials for applications in nanoelectronics as cathode materials, in sensor technology and in catalysis. In this work we present a study on hybrid vanadium oxide/hexadecylamine multiwall nanotubes doped with Co ions using state of the art x-ray diffraction and absorption techniques, to address the issue of the dopant location within the nanotubes' structure. The x-ray absorption near-edge structure analysis shows that the Co ions in the nanotubes are in the 2 + oxidation state, while extended x-ray absorption fine structure spectroscopy reveals the local environment of the Co(2+) ions. Results indicate that Co atoms are exchanged at the interface between the vanadium oxide's layers and the hexadecylamines, reducing the amount of amine chains and therefore the interlayer distance, but preserving the tubular shape. The findings in this work are important for describing Co(2+) interaction with vanadium oxide nanotubes at the molecular level and will help to improve the understanding of their physicochemical behavior, which is desired in view of their promising applications.

Nature of "disorder" in the ordered double perovskite Sr2FeMoO6.

The degree of B/B;{'} alternate cation order is known to heavily influence the magnetic properties of A_{2}BB;{'}O_{6} double perovskites although the nature of such disorder has never been critically studied. Our detailed x-ray absorption fine structure studies in conjunction with synchrotron radiation x-ray diffraction experiments on polycrystalline Sr_{2}FeMoO_{6} samples with various degrees of disorder reveal that a very high degree of short range order is preserved even in samples with highly reduced long range chemical order. Based on these experimental results and with the help of detailed structural simulations, we are able to model the nature of the disorder in this important class of materials and discuss the consequent implications on its physical properties.

Setup for optimized grazing incidence x-ray absorption experiments on thin films on substrates.

We present a state-of-the-art experimental apparatus and a proper setup to perform x-ray absorption spectroscopy (XAS) experiments in grazing incidence mode. This geometry is appropriate for doped thin films or interfaces buried at moderate depth in a thick matrix, whenever the scattering and/or fluorescence from the matrix has to be strongly attenuated. Both the calculation and the experimental data demonstrate that the specific setup that consists in a grazing incidence and grazing collection geometry is extremely advantageous. In fact, with respect to the standard geometry used to perform XAS experiments in fluorescence mode, the present setup allows an enhancement in the interesting fluorescence signal from the surface layer without a corresponding increase in the elastic scattering contribution from the matrix. The sample holder especially designed for this kind of experiment can work in vacuum and at low temperature. An easy and quick automatic sample alignment procedure is detailed.

Local structure of Sr(2)FeMo(x)W(1-x)O(6) double perovskites across the composition-driven metal to insulator transition.

Sr(2)FeMoO(6) oxides exhibit a half-metallic ferromagnetic (HM-FM) ground state and peculiar magnetic and magnetotransport properties, which are interesting for applications in the emerging field of spintronics and attractive for fundamental research in the field of heavily correlated electron systems. Sr(2)FeWO(6) is an insulator with an antiferromagnetic (I-AFM) ground state. The solid solutions Sr(2)FeMo(x)W(1-x)O(6) also have peculiar properties-W doping enhances chemical order which allows stabilization of the HM-FM state; as the W content exceeds a certain value a metal to insulator transition (MIT) occurs. The role of W in determining the physical properties of Sr(2)FeMo(x)W(1-x)O(6) systems has been a matter of intense investigation. This work deals with the problem of the structural and electronic changes related to the MIT from a local perspective by means of x-ray absorption spectroscopy (XAS). This technique allows one to probe in detail the local structure and electronic modifications around selected absorber ions (W, Mo, Fe and Sr in our case). The results of XAS analysis in the whole composition range (0≤x≤1), in the near edge (XANES) and extended (EXAFS) regions, demonstrate an abrupt change of the local structure around the Fe and Mo sites at the critical composition, x(c). This change represents the microstructural counterpart associated with the MIT. Conversely, the local structure and electronic configuration of W ions remain unaltered in the whole composition range, suggesting indirect participation of W in the MIT.

Effectiveness and safety of cholinesterase inhibitors in elderly subjects with Alzheimer's disease: a "real world" study.

Clinical trials have demonstrated the efficacy of cholinesterase inhibitors (ChEI) in improving cognitive status and disability in subjects with mild to moderate Alzheimer's disease (AD). However, little is known about the effectiveness of ChEI in clinical practice, and no large clinical trials comparing different ChEI are available at present. Aim of this study was to evaluate safety and effectiveness of ChEI in a sample of elderly outpatients diagnosed with mild to moderate AD. We selected 407 subjects for ChEI treatment (donepezil,rivastigmine or galantamine). Their cognitive function was evaluated by means of the mini mental state examination (MMSE), and the global functional status was estimated by using the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales at baseline (To), then after 1 (T1), 3 (T2) and 9 months (T3), respectively. T3 follow-up was completed by 212 subjects. The patients were considered as responders (R), if the MMSEscore at T2 was unchanged or improved, if compared to that of T0. In 35 patients (8.6 %)treatment was withdrawn because of mostly gastrointestinal adverse events. Compared to the other drugs, donepezil was associated with a lower incidence of withdrawals due to adverse events. Subjects who completed T3 follow-up (age 78 +/- 6 years, MMSE scores 18.8 +/- 3.9) showed an increase at T2 of 0.7 +/- 2.7 (p = 0.001) and a decrease at T3 of -0.6 +/- 3.4 (p = 0.008) in the MMSE scores, as compared to To . The ADL and IADL scores did not show significant changes at T2; however, both decreased significantly at T3. The patients Rat-T2 showed a better cognitive and functional outcome at T3 , compared to the nonresponders(NR-at-T2), displaying values of MMSE R-at-T2 0.4 +/- 3.1 vs. NR-at-T2 -3.0 +/- 2.5, p = 0.001, and ADL values of -0.3 +/- 1.2 vs. -0.7 +/- 1.3, p = 0.03, respectively. No significant difference was found in the changes of MMSE scores between donepezil and rivastigmine (galantamine was not included in the comparison due to the small number of treated subjects). In conclusion, in this sample of elderly subjects with mild to moderate AD,treated with ChEI, a small but significant decline in cognitive and functional status was observed after 9 months. Subjects who showed a good response to treatment after 3 months, had a better cognitive and functional outcome at 9 months. No significant difference in cognitive outcome was found between drugs, while donepezil was better tolerated.

Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis.

Several reports have evaluated the correlation between cathepsin-D and overall survival or disease-free survival in node-negative breast cancer patients. Because conflicting data have so far been reported, a meta-analysis was conducted to clarify this problem. Eleven studies were included in our meta-analysis (total of 2690 patients). A specific meta-analytical methodology for censored data was used, and disease-free survival was the primary end point. Patients with low cathepsin-D levels had a significantly better disease-free survival than patients with high cathepsin-D values (meta-analytical odds ratio from 0.59 to 0.60 over the interval from 1 to 7 years). A secondary meta-analysis conducted exclusively on the data from eight studies based on cytosol assay gave substantially similar results. One limitation of our study is that the cut-off values to define high and low cathepsin-D concentrations were not identical in the various studies included in our meta-analysis (range from 20 to 78 pmol mg(-1) protein), thus introducing a possible bias in the statistical analysis of the data. However, a simulation based on the well-accepted method of the so-called publication bias showed that more than 100 null studies would be required to lead our results to a statistical level of non-significance. Considering the results of our meta-analysis, we conclude that the data presently available confirm a statistically significant association between high cathepsin-D values and poor disease-free survival in node-negative breast cancer patients.

Effectiveness of Immunoglobulins for the Prevention of Systemic Infections : A Meta-Analysis of 8 Clinical Studies in Premature Infants.

The prophylactic administration of immunoglobulins to preterm neonates has a controversial effectiveness in reducing the incidence of nosocomial infections. Since the clinical trials conducted so far have given conflicting results, a metaanalysis was carried out to summarise the overall information presently available on this issue. Eight randomised clinical trials were identified by our literature search that met the inclusion criteria of our meta-analysis. In each study, the effectiveness of intravenous immunoglobulins was compared with that of no treatment or placebo. The overall number of patients included in our metaanalysis was 3739. The end-point was the incidence of proven infections. The results of our meta-analysis demonstrate that prophylactic immunoglobulins significantly reduced the incidence of proven infections (pooled odds ratio = 0.79, 95% CI: 0.69 to 0.91; p = 0.0014; reduction in the incidence of infection from 23.2 to 19.3%). There was, however, a significant intertriai heterogeneity. A cost-effectiveness analysis indicated that the prophylactic administration of immunoglobulins implies a cost of approximately $US8000 to prevent each case of infection in premature infants. This cost seems to be at least equal to the cost of treating an episode of sepsis in an infant.

Biochemical purification of monkey and human LDH isoenzyme 5 suitable as immunization antigen.

A method consisting in an ion-exchange chromatography on DEAE-Sephadex A50 and an affinity chromatography on Oxamate-hexyl-Sepharose for the purification of monkey and human LDH isoenzyme 5 is presented. Analytical isoelectric focusing reveals minor variants in the monkey LDH isoenzyme 5. This material has been used to produce an antiserum from rabbits which recognizes all the human LDH isoenzymes containing the M subunit, without cross-reacting with LDH1.

A simple and rapid immunoenzymatic assay of prostatic acid phosphatase in serum.

A method is described for the quantitative assay of human prostatic acid phosphatase after its isolation from serum by a double antibody technique employing a specific rabbit antiserum and a goat anti-rabbit gammaglobulin serum. After centrifugation, the precipitate is analyzed for phosphatase activity using p-nitrophenylphosphate as substrate. The method allows a rapid, precise, specific and sensitive assay.

The 4-hydroxybenzoate/4-aminophenazone chromogenic system used in the enzymic determination of serum cholesterol.

A single reagent, containing cholesterol oxidase, cholesterol esterase, peroxidase, 4-hydroxybenzoate, and 4-aminophenazone, is used in determining serum cholesterol. Analysis time is 15 min, and the standard curve is linear to 6.0 g/liter. Analytical recovery of cholesterol was 100.1 +/- 0.4%. Within-run precision (CV) was less than or equal to 1.4 1.4%, between-run less than or equal to 4.8%. Comparison with results by a Liebermann Burchard method [Clin. Chim. Acta 5, 637 (1960)] gave a linear regression of y = 1.08x--0.05, with a correlation coefficient (r) of 0.985. Comparison with the Roeschlau enzymic method [J. Clin. Chem. Clin. Biochem, 12, 226 (1974)] gave y = 1.02x + 0.01 (r = 0.958). Comparison with the enzymic method of Allain et al. [Clin. Chem. 20, 470 (1974)] gave y = 1.01x--0.00 (r = 0.995). The following substances do not interfere up to the indicated concentrations (mg/liter): hemoglobin (5000), bilirubin (100), reduced glutathione (150), l-cysteine (400), urea (3000), creatinine (200), uric acid (200), d-glucose (10000), L-ascorbic acid (50), acetylsalicylic acid (500), L-DOPA (10), ergothioneine (1000), 2,5-dihydroxybenzoic acid (20), and 3,4-dihydroxybenzoic acid (10). Stored in an amber-colored bottle, the working reagent is stable for three months at 2--8 degrees C and for three weeks at 25 degrees C.