Search

Background:: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach. Methods:: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma. Results:: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma. Conclusions:: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for β- radio-guided surgery.

Nitroimidazoles are a class of chemicals with a remarkable broad spectrum of applications from the production of explosives to the use as radiosensitizers in radiotherapy. The understanding of thedynamics of their fragmentation induced by ionizing sources is of fundamental interest. The goal of this work is to theoretically investigate the kinetic competition between the two most important decomposition channels of 2, 4 and 5-Nitroimidazole cations: the NO and NO2 losses. The calculated rate constants of the two processes are in very good agreement with the experimental Photoelectron-Photoion Coincidence (PEPICO) branching ratio. This study solves the intriguing and theoretically unexplained experimental observation that 2-Nitroimidazole, at variance with the other two regio-isomers is a source for only NO at low energies (

The influence of NGF in male reproduction in some animal species and humans has already been assessed. Many of these effects are mediated by the distribution and abundance of tropomyosin receptor kinase A (TrKA) and p75 neurotrophin (p75NTR) receptors on sperm cells. The aim of this research was to investigate the role of NGF and its receptors, TrKA and p75NTR, in rabbit sperm outcomes during in vitro storage. Major semen traits (kinetic parameters, apoptotic, necrotic and live sperm) were recorded in rabbit semen samples from 0 to 12 h of storage (every 4 h). Three experimental hypotheses were formulated: i) sperm storage changes NGF receptor abundance in rabbit sperm; ii) TrKA and p75NTR differently modulate NGF signalling (assessed by the neutralisation of receptors); iii) NGF-receptor interactions show different responses during storage (evaluated by the addition of exogenous NGF). The results demonstrate that: (i) the receptor number changed in a time-dependent manner with a significant increase in p75NTR after 8–12 h of storage; ii) the neutralisation of NGF receptors largely affected VCL, apoptotic, necrotic and live cells during sperm storage, i.e. blockade of TrKA significantly increased speed, capacitation, necrosis and apoptosis, whereas blockade of p75NTR improved motility and live cells; iii) the addition of exogenous human NGF (100 ng/mL) at different time points of storage (0, 4, 8 h) differently influenced sperm traits i.e. NGF addition at time 0 positively affected all the pro-vital traits (kinetic, live cells) whereas, after 4–8 h, the effect of NGF was null or negative. In conclusion, NGF affects kinetic and other physiological traits (capacitation, apoptosis and necrosis) of rabbit sperm in a time-dependent manner. Most of these modifications are modulated by the receptors involved (TrKA or p75NTR), which changed considerably during sperm storage (increase of p75NTR).

Summary Salmonella is the second main cause of foodborne illness in poultry production. It is one of the most problematic zoonoses in terms of public health worldwide because of the difficulty in controlling it and its significant morbidity and mortality rates. Recent surveys have shown that small flocks of laying hens have the same or higher prevalence of salmonellosis than larger flocks, mainly due to a lack of control actions, that is, the control of mice and wild animals, employees, and poor management practices. In this regard, different physical and chemical procedures have proven efficacious for reducing external and/or internal Salmonella contamination. This research evaluated the effect of ozone and UV-C rays on Salmonella growth and hen egg quality. Microbiological evaluation was performed on 120 eggs: negative control (C−), eggs not contaminated with Salmonella; positive control (C+), eggs contaminated; contaminated ozonate-treated (O, 600 mg/h for 2 h); and contaminated UV-C–irradiated (ʎ, 254 nm for 15 s) eggs. Moreover, 30 eggs were used (10/group) for the quality assessments of the C, O, and UV-C groups. A 2 log10 CFU/g reduction in Salmonella on contaminated eggs was found in the UV-C group compared with the C+ and O groups. Compared with UV-C treatment, ozonization reduced the amount of yolk tocols and carotenoids (by 2 times). The lipid oxidative status decreased (−1.5 times), similar to the cholesterol level (−28.5%), whereas the amount of cholesterol and its oxidized products increased (+82.1%) in the O group compared with the C group. UV-C irradiation is an effective strategy to reduce Salmonella contamination in eggs without negatively affecting the quality. Therefore, UV treatments remain among the more promising procedures.

Understanding the variations of muscle and plasma metabolites in response to high environmental temperature can provide important information on the molecular mechanisms related to body energy homeostasis in heat-stressed broiler chickens. In this study, we investigated the effect of chronic heat stress conditions on the breast muscle (Pectoralis major) and plasma metabolomics profile of broiler chickens by means of an innovative, high-throughput analytical approach such as the proton nuclear magnetic resonance (1H NMR) spectrometry. A total of 300 Ross 308 male chicks were split into two experimental groups and raised in either thermoneutral conditions for the entire rearing cycle (0–41 days) (TNT group; six replicates of 25 birds/each) or exposed to chronic heat stress conditions (30 °C for 24 h/day) from 35 to 41 days (CHS group; six replicates of 25 birds/each). At processing (41 days), plasma and breast muscle samples were obtained from 12 birds/experimental group and then subjected to 1H NMR analysis. The reduction of BW and feed intake as well as the increase in rectal temperature and heterophil: lymphocyte ratio confirmed that our experimental model was able to stimulate a thermal stress response without significantly affecting mortality. The 1H NMR analysis revealed that a total of 26 and 19 molecules, mostly related to energy and protein metabolism as well as antioxidant response, showed significantly different concentrations respectively in the breast muscle and plasma in response to the thermal challenge. In conclusion, the results obtained in this study indicated that chronic heat stress significantly modulates the breast muscle and plasma metabolome in fast-growing broiler chickens, allowing to delineate potential metabolic changes that can have important implications in terms of body energy homeostasis, growth performance and product quality.

Chicken meat is rich in unsaturated fatty acids. Therefore, it is more susceptible to lipid oxidation and production of volatile organic compounds (VOC). In this study, we evaluated the fatty acids, antioxidants, and VOC profiles of raw and cooked meat samples derived from 4 strains of chicken differing in their growth rates, which were as follows: slow-growing (SG, Leghorn), medium-growing (MG, Hubbard and Naked Neck), and fast-growing (FG, Ross). The VOC profile of meat was measured using proton-transfer reaction–mass spectrometry (PTR–MS). The VOC were identified using PTR–time of flight-MS (PTR-ToF-MS). The data were analyzed using both univariate and multivariate models. Twenty main VOC were identified, which were classified into the following chemical categories: aldehydes, alkadienes, alkenes, furans, amides, alcohols, and other compounds. Our results revealed that the chicken genotype and the method of cooking strongly influenced the VOC profile of the meat. Identifying the relationships between these traits allowed us to highlight the trade-off of the main substrates such as n-3 and n-6 polyunsaturated fatty acids (PUFA), protective substances (antioxidants), and degradation products (VOC) of the poultry meat produced during cooking. The extent of VOC production and n-3 loss was found to be higher for the SG genotype. Reduction of n-6 was higher in MG, whereas small losses in antioxidants and PUFA were observed in the FG genotype, consequently, resulting in the lowest production of VOC. The SG and MG are genotypes more active from a kinetic point of view respect to the FG ones. For this reason, in the FG genotypes, the antioxidants are less involved in the oxidative stress induced by the movement; thus, they were available to protect the lipid of the meat during the cooking process. These results suggested that the use of SG and MG genotypes requires a specific dietary protocol (i.e., increasing the antioxidants content) to counteract the lipid oxidations in all the phases: in vivo, postmortem, and during/after cooking.

Objectives During the lockdown that started in Italy on 10 March 2020 to address the COVID-19 pandemic, aggressive procedures were implemented to prevent SARS-CoV-2 transmission in SARS-CoV-2-negative patients with haematological malignancies. These efforts progressively reduced Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) spread among these patients. Here we evaluated the potential effects of measures against COVID-19 that reduced KPC-KP transmission. Patients and methods We analysed KPC-KP spread among 123 patients with haematological malignancies, hospitalized between March and August 2020, who were managed using measures against COVID-19. Their outcomes were compared with those of 80 patients hospitalized during the preceding 4 months (November 2019–February 2020). Results During March–August 2020, 15.5% of hospitalized patients were KPC-KP positive, compared with 52.5% in November 2019–February 2020 (P Conclusions Aggressive strategies to prevent SARS-CoV-2 transmission were applied to all hospitalized patients, characterized by high levels of KPC-KP endemicity and nosocomial transmission. Such measures prevented SARS-CoV-2 infection acquisition and KPC-KP horizontal transmission. Reduced KPC-KP spread, fewer associated clinical complications and decreased ceftazidime/avibactam consumption represented unexpected ‘collateral benefits’ of strategies to prevent COVID-19.

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype. Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.

Methanol is one of the most abundant and ubiquitous molecules in the space. Its chemistry is fundamental to understand the molecular growing from prebiotic molecules, ions and radicals. In this work the reaction of labelled methanol CD3OH•+ radical cation, produced with different internal energies by monochromatic synchrotron radiation, with neutral CD3OH was studied. The dynamics of the main reaction channels were investigated by theoretical calculations. The results show how these processes can be considered suitable pathways for the formation of fundamental species as CH3O(H)H+, CH3O•, •CH2OH, CH2O which are potential precursors to prebiotic molecules.

The aim of this study was to analyze the relationship between the kinetic behavior, carcass characteristics, oxidative status (blood and meat), and meat fatty acid profiles of 6 organically reared slower growing chicken genotypes (SrG). One hundred male chickens of 6 SrG were used: Ranger Classic (RC), Ranger Gold (RG), Rowan Ranger (RR), RedJA (RJ), CY Gen 5 JA87 (CY), and M22 × JA87 (M). Twenty chickens/genotype were selected to analyze behavior, while, 15 individuals were slaughtered and different traits were analyzed in the blood and drumstick meat. The variables were grouped into different principal components: kinetic activity (PC1, with explorative attitude as the highest score), productive performance (PC2, carcass and head/feet yields), blood (PC3, carbonyls, and TBARS) and meat (PC6, thiols, and TBARS) markers, technological traits (PC4, pH, and color), proximate meat composition (PCA5, moisture, lipids, protein, and ash), fatty acid profile, and nutritional indexes (PC7, IP, and PUFAn-3). Uni- and bivariate analyses showed a strong positive association between kinetic behaviors and blood and meat oxidation and a medium positive association with fatty acid profile and nutritional indexes, whereas a negative association was found between productive performance loads and the technological traits of meat. Generalized linear models showed that all PCs were influenced by genotype. In particular, CY and M resulted as less active genotypes; conversely, RR showed more kinetic activity, whereas RJ, RG, and RC exhibited intermediate levels of activity. Cluster analysis of kinetic behavior and blood or meat oxidative status highlighted 2 groups: nonwalking (NW: CY and M) and walking (W: RC, RG, RR, and RJ) animals. However, in the W group, another was visualized, constituted by genotypes with high kinetic activity resulting in the worst oxidative balance (Walking not trained-genotypes, Wnt: RR and RJ). The present results confirmed that the kinetic behavior of SrG genotypes is negatively correlated with productive performance. Furthermore, a significant association between kinetic behavior and blood (positively correlated) or meat (negatively correlated) oxidative status was noted. Such differences are mainly due to the intrinsic response of the genotypes used (i.e., training-walking capacity).

The aim of the present study was to investigate the effect of transport on welfare traits, several haematological parameters and carcase hygiene in two different chicken genotypes (fast- and slow-growing strains) reared under free-range conditions. For this aim, two hundred male chicks, 100 from fast-growing (Ross 308, R) and 100 from slow-growing (Naked Neck, NN) strain were farmed. At the end of the rearing period, at 81 days of age, 56 birds/strain were randomly selected for slaughtering and submitted to two different pre-slaughter conditions: no transport (0h) or 4 hours of transport (4h). Tonic immobility (TI), blood parameters and carcase hygiene traits were determined. Strain and transport significantly affected TI of birds. Both experimental factors and their interaction significantly affected plasma creatine kinase, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. Cholesterol and triglycerides were not different between the experimental groups, whereas glucose decreased after 4 hours of transport in both strains. A significant difference between groups for the heterophils/lymphocytes ratio after transport was also observed, with NN being higher than Ross. Concerning the oxidative stress, we observed a higher ROS production in NN chickens. The carcase microbial characteristics showed a higher level of contamination after the transport (total viable counts), but not concerning the Enterobacteriaceae counts.

Dihalomethanes XCH2Y (X and Y = F, Cl, Br, and I) are a class of compounds involved in several processes leading to the release of halogen atoms, ozone consumption, and aerosol particle formation. Neutral dihalomethanes have been largely studied, but chemical physics properties and processes involving their radical ions, like the pathways of their decomposition, have not been completely investigated. In this work the photodissociation dynamics of the ClCH2I molecule has been explored in the photon energy range 9-21 eV using both VUV rare gas discharge lamps and synchrotron radiation. The experiments show that, among the different fragment ions, CH2I+ and CH2Cl+, which correspond to the Cl- and I-losses, respectively, play a dominant role. The experimental ionization energy of ClCH2I and the appearance energies of the CH2I+ and CH2Cl+ ions are in agreement with the theoretical results obtained at the MP2/CCSD(T) level of theory. Computational investigations have been also performed to study the isomerization of geminal [ClCH2I]o+ into the iso-chloroiodomethane isomers: [CH2I-Cl]o+ and [CH2Cl-I]o+.

The objective of this study was to compare the effect of the dietary beer trub, alone or in combination with linseed, on meat quality, oxidative status and cholesterol content of rabbit. Eighty New Zealand White rabbits were divided at weaning (30 d) into four dietary groups: control (C) fed a standard diet, trub (T, 2% of lyophilized trub), linseed (L, 3% of extruded linseed), and trub-linseed in combination (TL, 2% of lyophilized trub and 3% of extruded linseed). At slaughtering (80 d) the oxidative parameters of blood and quality of Longissimus thoracis et lumborum were analysed. The in vivo lipid oxidation was similar in the supplemental groups, whereas it was higher in T, L and TL meat compared to C. Trub supplementation in rabbit diets slightly affected the fatty acid profile (MUFA) and worsened the oxidative status of meat, and its inclusion in combination with linseed did not counteract the oxidative instability induced by the higher PUFA content.

The aim of the present work has been the mass spectrometry characterization of the Nimotuzumab (NIM) antibody chemically modified with the bifunctional chelating agent para-S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza cyclododecanetetraacetic acid (p-SCN-Bn-DOTA). The conjugate, upon labeling with the pure β--emitter 90Y3+, could represent a promising candidate as radiotracer for an innovative radio-guided surgery (RGS) technique, developed and patented by researchers of our group, which uses a probe system for intraoperative detection of tumor residues exploiting the selective uptake of β--emitting tracers. The results reported in this study show that multiple DOTA molecules bind to lysine residues of both light and heavy chains of the antibody and, probably, some of them are linked to the variable region of antibody. Moreover, the new mass spectrometric analysis highlights the presence of unreacted NIM in the final product. The information obtained by this work is of fundamental importance in the perspective to utilize this conjugate as a radiocompound after its labeling with 90Y3+ radioisotope. Indeed, the conjugation efficiency and the presence of unreacted NIM affect the specific activity of the final radiotracer which binds specific receptor.

Flaxseed is a rich source of α-linolenic acid and phytoestrogens, mainly lignans, whose metabolites (enterodiol and enterolactone) can affect estrogen functions. The present study evaluated the influence of dietary flaxseed supplementation on reproductive performance and egg characteristics (fatty acids, cholesterol, lignans and isoflavones) of 40 Hy-Line hens (20/group) fed for 23 weeks a control diet or the same diet supplemented with 10% of extruded flaxseed. The flaxseed diet had approximately three times the content of lignans (2608.54 ng/g) as the control diet, mainly secoisolariciresinol diglucoside (1534.24 v. 494.72 ng/g). When compared with the control group, hens fed flaxseed showed a similar deposition rate (72.0% v. 73.9%) and egg yield. Furthermore, there was no effect of flaxseed on the main chemical composition of the egg and on its cholesterol content. Estradiol was higher in the plasma of the control group (1419.00 v. 1077.01 pg/ml) probably due to the effect of flaxseed on phytoestrogen metabolites. The plasma lignans were higher in hens fed flaxseed, whereas isoflavones were lower, mainly due to the lower equol value (50.52 v. 71.01 ng/ml). A similar trend was shown in eggs: the flaxseed group had higher level of enterodiol and enterolactone, whereas the equol was lower (198.31 v. 142.02 ng/g yolk). Secoisolariciresinol was the main lignan in eggs of the flaxseed group and its concentration was three times higher then control eggs. Flaxseed also improved the n-3 long-chain polyunsaturated fatty acids of eggs (3.25 v. 0.92 mg/g egg), mainly DHA, however, its oxidative status (thiobarbituric reactive substances) was negatively affected. In conclusion, 10% dietary flaxseed did not affect the productive performance of hens or the yolk cholesterol concentration, whereas the lignans and n-3 polyunsaturated fatty acid content of eggs improved. Further details on the competition between the different dietary phytoestrogens and their metabolites (estrogen, equol, enterodiol and enterolactone) should be investigated.

The aim of the study was to evaluate the effect of transport length on in vivo oxidative status and breast meat characteristics in two chicken genotypes reared under free range conditions. A total of 200 male chicks, 100 from fast-growing (Ross 308) and 100 from medium-growing (Naked Neck) strain were used. Fifty-six of these, 28 for genotype, before slaughtering, were randomly allocated to 2 pre-slaughter conditions: absence (0 h) or 4 h of transport. The transport length significantly affected the in vivo oxidative status of broiler greatly reducing the α and δ-tocopherol, retinol and lutein + zeaxanthin content of plasma, and increased the oxidative stress (thiobarbituric acid reactive substances, TBARS) in both strains. Concerning meat quality, the pH (0, 2 and 24 h post-mortem) of breast muscles of chickens transported for 4 h, showed higher values, and respect to strains, Naked Neck had lower values. The pH values were negatively correlated with the lightness (2–24 h) and the shear force of meat. The transport length significantly affected the fatty acid profile of breast muscle, with a decrease in polyunsaturated fatty acids and an increase in TBARS value. Even the antioxidants content of breast was reduced by chicken transport (α-tocotrienol, α-, δ-tocopherol and lutein + zeaxanthin), especially in Naked Neck birds. In conclusion, the results indicate that transport for 4 h prior to slaughter, negatively affect the meat quality of poultry. Slow-growing chickens seem more sensible to stress transport due to the higher kinetic behaviour of these strains.

BACKGROUND: Fresh sprouts are healthy foods, low in fats and high in phytochemicals, but have a short shelf‐life, hence the need for processing methods that preserve their nutritional value. This work was aimed at evaluating the effect of heat‐drying (HD) and freeze‐drying (FD) on the phytochemical and fatty acid profiles of alfalfa and flax sprouts, as compared to fresh material. RESULTS: Both FD and HD reduced the phytochemical contents compared to fresh sprouts. FD better preserved phytoestrogens, phytosterols and total tocols compared to HD. However, phytoestrogen and tocol content remained quite high also in HD. The fatty acid profile was affected only by sprouts species, with higher amounts of α‐linolenic acid in flax and linoleic acid in alfalfa sprouts. CONCLUSIONS: This work demonstrates that drying does not severely compromise the nutritional value of sprouts and provides a valid support for the choice of the drying method depending on the compound to be preserved, and taking into consideration the different cost of the methods. In addition, sprout powder is easy to handle and, due to its low volume, does not imply a decrease of feed consumption and energy intake, which is relevant in its use as a supplement in human and animal feeding. © 2019 Society of Chemical Industry

The present research studied the effect of liquorice extract (in feed and/or directly in burgers) on the shelf-life of rabbit meat. Before weaning, 28 individually caged rabbit does with their litters were divided in two dietary groups: Control, receiving a commercial diet, and Liquorice, receiving the Control diet supplemented with 6 g liquorice extract/kg (L). At 12 weeks of age, 15 fattened rabbits/treatment (one rabbit/cage) were slaughtered and their hindlegs dissected. Hindleg meat was trimmed, individually minced and divided into two parts: one of them was mixed with 0.25% (w/w) L. Storage time significantly reduced the amount of polyunsaturated fatty acids in the burger, to a different magnitude depending on the unsaturation level, experimental group and storage time. The α-tocopherol content showed higher levels during storage in the burgers from the Liquorice group. Also TBARs values showed a significant positive effect of dietary liquorice and a progressive increase at days 3 and 6 of storage.

Radiolabeled nanoparticles are promising tools in cancer diagnosis and therapy. Moreover, yttrium-90 (90Y) is a good candidate as suitable β− emitting radioisotope for a new approach to radio-guided surgery (RGS) proposed by some researchers of our group. In this work, we developed new composite nanoparticles, based on polymethylmethacrylate (PMMA), and poly(methylmethacrylate-co-acrylic acid), P(MMA/AA), embedded with yttrium ion (89Y3+), as a first step for the development of new 90Y3+ based nanocomposites. The composite nanoparticles were synthesised by emulsion polymerization technique, in the presence of potassium persulfate (KPS) as radical initiator, toluene as cosolvent, diethylenetriamine penta acetic acid dianhydride (DTPA) as chelating agent, using different MMA/89Y3+ molar ratios. The yttrium doped polymeric nanoparticles were characterized by means of FTIR spectroscopy, SEM-EDX, AFM, and DLS measurements. The influence of experimental parameters, such as cosolvent and reaction time, on morphology and dimension of composite nanoparticles was investigated, and monodispersed nanospheres with diameters from 20 nm to 400 nm were obtained. The composite material was purified and studied by means of DLS to confirm the colloid stability in water solution at different temperatures (25 °C and 37 °C) up to 3 weeks.

Nitromidazoles are relevant compounds of multidisciplinary interest, and knowledge of their physical chemical parameters as well as their decomposition under photon irradiation is needed. Here we report an experimental and theoretical study of the mechanisms of VUV photo fragmentation of 2- and 4(5)-nitromidazoles, compounds used as radiosensitizers in conjunction with radiotherapy as well as high-energy density materials. Photoelectron photoion coincidence experiments, measurements of the appearance energies of the most important ionic fragments, density functional theory, and single-point coupled cluster calculations have been used to provide an overall insight into the energetics and structure of the different ionic/neutral products of the fragmentation processes. The results show that these compounds can be an efficient source of relevant CO, HCN, NO, and NO2 molecules and produce ions of particular astrophysical interest, like the isomers of azirinyl cation (m/z 40), predicted to exist in the interstellar medium, and protonated hydrogen cyanide (m/z 28).

[object Object]The fragmentation of the isolated 5-bromouracil (5BrU) molecule and pure and nano-hydrated 5BrU clusters induced by low energy C-12(4+) ions has been studied. A comparison indicates that the environment, on the one hand, protects the system against the complete break-up into small fragments, but, on the other hand, triggers 'new' pathways for fragmentation, for example the loss of the OH group. The most striking result is the observation of several series of hydrated fragments in the hydrated cluster case, with water molecules bound to hydrophilic sites of 5BrU. This highlights the strong interaction between 5BrU and water molecules and the blocking of specific fragmentation pathways, such as the loss of the BrC2H group for example.

Endocannabinoids have emerged as a new class of lipid mediators, with manifold roles in the central nervous system and in the periphery. Several studies have identified 2-arachidonoyl-glycerol (2-AG) as a major endogenous agonist of cannabinoid receptors. Here, the chemical synthesis of 2-AG is reported, along with the synthesis of its tritium-labeled derivative. These unlabeled and radiolabeled compounds are suitable tools for unravelling some metabolic routes and biological activities of 2-AG in various cells and tissues.

In this work an experimental and theoretical study on the formation of HSO2+ ion from the SO2⋅+ +CH4 and SO2⋅+ +H2 O ion-molecule reactions at different temperatures is reported. Tunable synchrotron radiation was used to produce the SO2⋅+ ion in excited ro-vibrational levels of the ionic ground state X2 A1 and mass spectrometry was employed to identify the product ions. Calculations in the frame of the density functional theory and variational transition state theory were combined to explore the dynamics of the reactions. The experimental results show that HSO2+ is the only product in both reactions. Its yield decreases monotonically with photon energy in the SO2⋅+ +H2 O reaction, while it decreases at first and then increases in the SO2⋅+ +CH4 reaction. Theory confirms this trend by calculating the rate constants at different temperatures and explains the results by means of the polar, spin and charge effects as well as structural reorganization occurring in the reaction coordinate. The dynamic behavior observed in these two reactions is of general and fundamental interest. It can also provide some insights on the role of these reactions in astrochemistry as well as in their use as models for bond-activation reactions.

This is the accepted manuscript of the paper""position" does matter : the photofragmentation of the nitroimidazole isomers" published as final paper in Journal of Physics: Conference Series 2017, 875, 032007

The Proton Affinity and Gas-Phase Basicity of Sulfur Dioxide

A combined experimental and theoretical approach has been used to disentangle the fundamental mechanisms of the fragmentation of the three isomers of nitroimidazole induced by vacuum ultra-violet (VUV) radiation, namely, 4-, 5-, and 2-nitroimidazole. The results of mass spectrometry as well as photoelectron-photoion coincidence spectroscopy display striking differences in the radiation-induced decomposition of the different nitroimidazole radical cations. Based on density functional theory (DFT) calculations, a model is proposed which fully explains such differences, and reveals the subtle fragmentation mechanisms leading to the release of neutral species like NO, CO, and HCN. Such species have a profound impact in biological media and may play a fundamental role in radiosensitising mechanisms during radiotherapy.

International audience; The fragmentation of uracil molecules and pure and nano-hydrated uracil clusters by 12C4+ ion impact is investigated. This work focuses on the fragmentation behavior of complex systems and the effect of the environment. On the one hand, it is found that the environment in the form of surrounding uracil or water molecules has a significant influence on the fragmentation dynamics, providing an overall ‘protective’ effect, while on the other hand we observe the opening of specific fragmentation channels. In particular, we report on the first observation of a series of hydrated fragments. This indicates a strong interaction between uracil and water molecules, holding the water clusters bound to the observed molecular fragments.

Purpose Preemptive strategies in neutropenic patients based on serum galactomannan (GM) –guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. Patients and Methods Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions. Results Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found. Conclusion A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.

Purpose To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL). Patients and Methods Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P ≤ .0001). This was due mainly to significantly more relapses after EF-RT only (arm A, 22%; arm B, 3%). No patient treated with CMT experienced relapse before year 3. Relapses were treated mainly with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, or with the combination cyclophosphamide, vincristine, procarbazine, and prednisone/ABVD; treatment of relapse was significantly more successful in arm A than in arm B (P = .017). In total, there were 39 second malignancies, with 21 in arm A and 18 in arm B, respectively. The incidence was approximately 0.8% per year during years 2 to 9 and was highest in older patients (P < .0001) and those with “B” symptoms (P = .012). Conclusion CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone.

The conversion of the cellular prion protein (PrP C ) into a misfolded isoform (PrP TSE ) that accumulates in the brain of affected individuals is the key feature of transmissible spongiform encephalopaties (TSEs). Susceptibility to TSEs is influenced by polymorphisms of the prion gene suggesting that the presence of certain amino acid residues may facilitate the pathological conversion. In this work, we describe a quantitative, fast and reliable HPLC–MS method that allowed to demonstrate that in the brain of 109 Met/Ile heterozygous bank voles infected with the mouse adapted scrapie strain 139A, there are comparable amounts of PrP TSE with methionine or isoleucine in position 109, suggesting that in this TSE model the two allotypes have similar rates of accumulation. This method can be easily adapted for the quantitative determination of PrP allotypes in the brain of other natural or experimental TSE models.

O biodiesel substituto renovável do diesel convencional é quimicamente definido como ésteres monoalquílicos de ácidos graxos derivados de óleos vegetais e gorduras animais. O processo mais empregado para a sua produção é a transesterificação em meio alcalino. Este processo consiste em uma reação química na qual óleos vegetais e/ou gorduras animais reagem com um álcool de cadeia curta utilizando catalisador alcalino (usualmente hidróxido de potássio e metilato de sódio) resultando na mistura de ésteres monoalquílicos (biodiesel) e glicerina. O presente trabalho teve como objetivo avaliar o desempenho dos catalisadores alcalinos: metilato de sódio e hidróxido de potássio na produção de biodiesel pela rota metílica utilizando óleo de soja como fonte de triglicerídeo. A avaliação foi dividida em 3 partes: 1- Técnica: Qualidade do biodiesel, da glicerina gerada e a eficiência da conversão de óleo de soja em biodiesel. 2- Econômica: Custo de produção global do biodiesel. 3- Ambiental: Geração de resíduo quantitativa e qualitativa. A metodologia consistiu em realizar 3 bateladas com cada catalisador em um reator de vidro tipo batelada de 2.000 mL com circulação externa de água. Foi utilizado o mesmo óleo de soja refinado, metanol, procedimento experimental e metodologia analítica. Os resultados demonstraram que o catalisador metilato de sódio apresentou eficiência 4,8% superior ao hidróxido de potássio na conversão de óleo de soja em biodiesel, o custo de produção global teve redução de 3,2% (R$ 0,080/Kg de biodiesel produzido) e a geração de resíduo em volume foi reduzida em 9,8%. Ambos catalisadores apresentaram resultados dentro da especificação da resolução ANP no42. Estes resultados demonstram a grande vantagem do metilato de sódio frente ao hidróxido de sódio e exalta a importância da escolha do catalisador que oferece o melhor desempenho que é fundamental para a viabilidade técnica, financeira e ambiental do Programa Nacional de Produção de Biodiesel (PNPB). Biodiesel is a renewable alternative to petroleum diesel fuel and is chemically defined as mono-alkyl esters of fatty acid derived of vegetable oils and animal fat. The most commonly used process in its production is alkaline transesterification. This process consists in a chemical reaction in which vegetable oil and/or animal fats react with a short chain alcohol, using an alkaline catalyst (usually potassium hydroxide and sodium methylate), resulting in a mixture of mono- alkyl esters (biodiesel) and glycerin. The objective of the present research is to evaluate the performance of alkaline catalysts: sodium methylate and potassium hydroxide in the production of biodiesel by the methylic route, using soybean as a triglyceride source. The evaluation was divided in 3 parts: 1 - Technical: biodiesel quality, generated glycerin quality and the soybean oil to biodiesel conversion efficiency. 2 - Economical: Biodiesel\'s global production cost. 3 - Environmental: Quantitative and qualitative waste generation. The methodology consisted in carrying through 3 (three) batches with each catalyst in a 2.000 mL batch type glass reactor with external water circulation. The same refined soybean, methanol, experimental procedure and analytical methodology were used. The results demonstrated that the sodium methylate catalyst presented an efficiency 4,8% higher than potassium hydroxide in the conversion of soybean into biodiesel, that the global production cost had a 3,2% reduction (R$ 0.08/Kg of produced biodiesel) and that waste generation in volume was reduced in 9,8%. Both catalysts presented results, within the specification of ANP no42 Ordinance. These results demonstrate the great advantage of sodium methylate in comparison to potassium hydroxide and exalts the importance of chossing the catalyst that offers the best performance that is necessary for the technical, financial and environmental viability of the National Biodiesel Production Program.

Boldenone is an androgenic anabolic steroid (AAS) intensively used for growth promoting purposes in animals destined for meat production and as a performance enhancer in athletics. Therefore its use is officially banned either in animals intended for consumption or in humans. Because most anabolic steroids are completely metabolized and usually no parent steroid is excreted, metabolite identification is crucial to detect the illegal use of anabolic steroids either in humans or in livestock. The aim of this work is the investigation of 17-boldenone and its main metabolites, 17-sulphate, 17-glucuronide, 5-androst-1-en17-ol-3-one and 17-boldenone, in human and bovine urine developing a multiresidue analysis. After solid phase extraction of urine samples, detection is carried out by high performance liquid chromatography–tandem mass spectrometry in multiple reaction monitoring. The average recovery for all the investigated compounds is above 70%. The developed method is very easy, quick and highly specific. Linearity, precision, decision limit and detection capability were also evaluated. © 2005 Elsevier B.V. All rights reserved.

We show that the pseudoperoxidase activity of ferrylmyoglobin (MbIV) promotes oxidative degradation of doxorubicin (DOX), an anticancer anthracycline known to induce severe cardiotoxicity. MbIV, formed in vitro by reacting horse heart MbIII with H2O2, caused disappearance of the spectrum of DOX at 477 nm and appearance of UV-absorbing chromophores that indicated opening and degradation of its tetracyclic ring. Electron spray ionization mass spectrometry analyses of DOX/MbIV ultrafiltrates showed that DOX degradation resulted in formation of 3-methoxyphthalic acid, the product of oxidative modifications of its methoxy-substituted ring D. Other methoxy-substituted anthracyclines similarly released 3-methoxyphthalic acid after oxidation by MbIV, whereas demethoxy analogs released simple phthalic acid. Kinetic and stoichiometric analyses of reactions between DOX and MbIII/H2O2 or hemin/H2O2 showed that the porphyrin radical of MbIV-compound I and the iron-oxo moiety of MbIV-compound II were sequentially involved in oxidizing DOX; however, oxidation by compound I formed more 3-methoxyphthalic acid than oxidation by compound II. Sizeable amounts of 3-methoxyphthalic acid were formed in the heart of mice treated with DOX, in human myocardial biopsies exposed to DOX in vitro, and in human cardiac cytosol that oxidized DOX after activation of its endogenous myoglobin by H2O2. Importantly, H9c2 cardiomyocytes were damaged by low concentrations of DOX but could tolerate concentrations of 3-methoxyphthalic acid higher than those measured in murine or human myocardium. These results unravel a novel function for MbIV in the oxidative degradation of anthracyclines to phthalic acids and suggest that this may serve a salvage pathway against cardiotoxicity.

This paper describes a method for analysing some acids of milk whey by Capillary Zone Electrophoresis. After eliminating the whey proteins by ultrafiltration, the whey underwent electrophoretic separation in the presence of anodic electroosmotic flow. The following analytes were detected: citric, orotic, uric, and hippuric acids. A procedure is described for sample preparation and the operating conditions for electrophoretic capillary separation established. Finally, orotic acid is quantitatively determined.

This communication reports a study of the effect of ionic strength and electrolyte composition on fractions, separately collected by flow FFF, of a mixture of humic substances. Reverse phase HPLC analysis of three early eluting fractions suggests that the components released by the column behave as organic acids. The baseline-resolved peaks of the first two fractions, subject to higher retention in solutions of lower pH and/or higher polarity, substantiate this suggestion. The fraction with larger components, as measured by flow FFF, also appears to contain acidic species. Their retention level, however, may not be accurately modulated by varying the mobile phase properties as these species are either totally retained in acidic phases or released before the void peak at pH ≥ 4.2. Besides showing the effective separation achieved in the flow FFF channel, this study reveals the pronounced difference in the physicochemical properties of some components of a humic mixture even with very close particle size.

Zilpaterol, (±)-trans-4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino) imidazo [4,5,1-jk]-[1]benzazepin-2(1H)-one, is an adrenergic agonist drug licensed in Mexico and South Africa as feed additive for cattle at slaughter age. In contrast, the EU legislative framework prohibits the use of beta-agonists as growth promoters to produce lean meat. In this study, the compound was quantified as its TMS derivative both by gas chromatography-mass spectrometry (GC-MS) with a quadrupole detector (QUADR) and by GC-MS/MS with an ion trap detector (ITD), in Electron Impact (EI) ionization. Subsequently, an extraction and clean-up procedure for the identification of Zilpaterol in commercial feeds was set up. Different extraction solvents and matrices were considered for their influence on Zilpaterol yield. The analytical method led to good recoveries and limits of detection and quantification in feeds well below the 5–20 μg/g dose proposed for animal nutrition.

Zilpaterol is an adrenergic drug currently licensed in Mexico and South Africa as a feed additive for cattle close to consignment. In this study an analytical method to detect zilpaterol in commercial feeds was set up. The influence of extraction solvent and matrix was evaluated. The drug as a trimethylsilyl derivative was characterized by GC-MS, on a quadrupole detector, in the electron impact mode. Acidic extraction, solid-phase extraction C(18) non-endcapped clean-up and mass characterization on ions m/z 308, 291, 405, 390 provided zilpaterol recoveries >75.3% and repeatability

A liquid chromatographic–tandem mass spectrometric (LC–MS–MS) method has been developed for the determination of trenbolone in bovine urine and serum. The aim was a control of the misuse of trenbolone in food-producing animals. The procedure involved, in both cases, a preliminary solid-phase clean-up followed by a liquid–liquid extraction for urine samples after a preliminary enzymatic hydrolysis. The extracts have been directly analysed by reversed-phase LC–MS–MS in selected reaction monitoring (SRM), acquiring two diagnostic product ions from the chosen precursor [M+H] + . The procedures were validated across the concentration range of 1–1500 ng/ml. The linearity, the inter- and intra-day accuracy and precision have been determined. The procedure was specific and the accuracy values were better than 20% at the limit of quantitation of spiked samples. The limit of quantification (LOQ) and the limit of detection (LOD) were, respectively, 1 ng/ml and 350 pg/ml for urine and serum. According to the draft, SANCO/1805/2000, we determined the decision limit CC α and the detection capability CC β . The recovery values for urine ranged from 87 to 128%, and for plasma the recovery was 70±4%. The procedure proved to be simple and suitable for routine and confirmatory purposes such as those developed for residue studies.

The room-temperature C-H activation of ethane by metal-free SO2 center dot+ radical cations has been investigated under different pressure regimes by mass spectrometric techniques. The major reaction channel is the conversion of ethane to ethylene accompanied by the formation of H2SO2 center dot+ the radical cation of sulfoxylic acid. The mechanism of the double C-H activation, in the absence of the single activation product HSO2+, is elucidated by kinetic studies and quantum chemical calculations. Under near single-collision conditions the reaction occurs with rate constant k = 1.0 x 10(-9) (+/-30%) cm(3) s(-1) molecule(-1), efficiency = 90%, kinetic isotope effect k(H)/k(D)=1.1, and partial H/D scrambling. The theoretical analysis shows that the interaction of SO2 center dot+ with ethane through an oxygen atom directly leads to the C-H activation intermediate. The interaction through sulfur leads to an encounter complex that rapidly converts to the same intermediate. The double C-H activation occurs by a reaction path that lies below the reactants and involves intermediates separated by very low energy barriers, which include a complex of the ethyl cation suitable to undergo H/D scrambling. Key issues in the observed reactivity are electron-transfer processes, in which a crucial role is played by geometrical constraints. The work shows how mechanistic details disclosed by the reactions of metal-free electrophiles may contribute to the current understanding of the C-H activation of ethane.

The chemical physics of halomethanes is an important and challenging topic in several areas of chemistry in particular in the chemistry of the atmosphere. Among the class of halomethanes, the diiodomethane molecule has attracted some interest in the last years, but despite this, the information on its radical cation [CH2I2](⋅+) is still limited. In this work, we measured and calculated the appearance energy (AE) of the ionic fragments I2(⋅+) and CH2(⋅+) and correlated the different fragmentation channels to the electronic states of the cation via photoelectron-photoion coincidence (PEPICO) experiments. In the case of the CH2/I2(⋅+) channel, the experimentally determined AE is in excellent agreement with the adiabatic theoretical value while a discrepancy is observed for the CH2(⋅+)/I2 channel. This discrepancy can be understood accounting for a fragmentation involving the formation of two I atoms (CH2(⋅+)/2I channel), which, as explained by time dependent density functional theory (TD-DFT) calculations, occurs when [CH2I2](⋅+) excited states are involved.

In this study the fragmentation of isolated uracil molecules, uracil clusters and hydrated uracil clusters induced by 12 C 4+ ions at 36 keV energy has been investigated. The mass spectra obtained by a TOF mass spectrometer are analyzed and compared to each other in order to see how the environment affects the fragmentation dynamics. The main differences between the mass spectra are highlighted and possible fragmentation pathways are proposed.

International audience; The fragmentation of the 2Br-pyrimidine molecule following direct valence photoionization or inner shell excitation has been studied by electron–ion coincidence experiments. 2Br-pyrimidine has been chosen as a model for the class of pyrimidinic building blocks of three nucleic acids and several radiosensitizers. It is known that the site- and state-localization of energy deposition, typical of inner shell excitation, results in the enhancement of the total ion yield as well as in changes in the relative intensity of the different fragmentation channels. Here we address the question of the origin of this selective fragmentation by using electron–ion coincidence techniques. The results show that the fragmentation is strongly selective in the final singly charged ion state, independently of the process that leads to the population of that state, and the dominant fragmentation patterns correlate with the nearest appearance potential.