Decreased susceptibility to oxidative stress underlies the resistance of specific dopaminergic cell populations to paraquat-induced degeneration.

The vulnerability of different dopaminergic cell populations to damage caused by the herbicide paraquat was assessed by stereological counts of tyrosine hydroxylase-positive and calbindin-D28k-immunoreactive neurons in A9 (substantia nigra pars compacta) and A10 (ventral tegmental area and other cell groups). In saline-treated control mice, tyrosine hydroxylase-immunoreactive neurons represented 80% and 45% of the total neuronal population in A9 and A10, respectively, and the number of calbindin-D28k-positive neurons was five times greater in A10 than A9. Sequential injections with paraquat resulted in a significant loss of dopaminergic neurons in A9. In contrast, tyrosine hydroxylase-positive cells in A10 were spared from paraquat-induced degeneration. Furthermore, expression of calbindin-D28k was consistently associated with neuronal resistance to the herbicide in both A9 and A10. Paraquat exposure also induced oxidative stress as indicated by an increase in the number of midbrain cells positive for 4-hydroxy-2-nonenal, a marker of lipid peroxidation. Co-localization studies revealed that calbindin-D28k immunoreactivity overlapped with tyrosine hydroxylase labeling and that, after paraquat administration, (i) the vast majority of midbrain 4-hydroxy-2-nonenal-immunoreactive cells were dopaminergic (tyrosine hydroxylase-immunoreactive), (ii) tyrosine hydroxylase/4-hydroxy-2-nonenal-positive neurons were much more prevalent in A9 than A10, and (iii) all calbindin-D28k-containing neurons were characterized by lack of lipid peroxidation (4-hydroxy-2-nonenal immunoreactivity). Results in this paraquat model emphasize that, despite sharing a similar dopaminergic phenotype, different groups of midbrain neurons vary dramatically in their vulnerability to injury. Data also indicate that these differences are attributable, at least in part, to a varying susceptibility of dopaminergic cell populations to oxidative stress.

Study of different parameters affecting the derivatization of acidic herbicides with trimethylsulfonium hydroxide to make them suitable for gas chromatography analysis.

In this study, an orthogonal array design was applied to know the way different parameters affected the derivatization of some herbicides that are commonly applied in the soils. Herbicides formulated as esters have been reported to rapidly hydrolyse, in contact with soil, to their corresponding acids and phenols. What involves is that both forms need to be monitored. Acidic herbicides and phenols cannot be detected by gas chromatography (GC) due to their polarity and low volatility that cause peak asymmetry. Therefore, masking of these polar groups by eliminating the active hydrogen atom with derivatization to their corresponding esters/ethers is needed in order to yield products that possess enhanced volatility and improved GC properties. A lot of derivatization reagents have been proposed but trimethylsulfonium hydroxide (TMSH) was selected due to its easy and quantitative formation of methyl esters/ethers. It was observed that the addition of TMSH promoted not only esterification of acids/phenols but trans-esterification of the original non-hydrolyzed remaining esters to their corresponding methyl ones. As a result, methyl esters/ethers were the final product of both reactions. Different parameters were studied in the statistical design for both TMSH promoted reactions: type of solvent, pH, temperature and time of incubation. The amount of derivatization reagent was calculated to be high enough to ensure the complete derivatization of all compounds present in the sample. The reaction medium was shown as an important factor. The formation of some methyl esters/ethers decreased with increasing time and temperature because trans-esterification, being an equilibrium where the formation of smaller structures is promoted, was not enough shifted. However, the statistical analysis revealed that only the pH of the solution played an important role during the derivatization process. The presence of the anionic form of the acids appeared to be essential for derivatization, being diminished in strong acidic conditions. In addition, pre-heating was shown not to improve derivatization reaction, being easily carried on in the injector port of the GC system.

Comparison of an acetonitrile extraction/partitioning and "dispersive solid-phase extraction" method with classical multi-residue methods for the extraction of herbicide residues in barley samples.

An acetonitrile/partitioning extraction and "dispersive solid-phase extraction (SPE)" method that provides high quality results with a minimum number of steps and a low solvent and glassware consumption was published in 2003. This method, suitable for the analysis of multiple classes of pesticide residues in foods, has been given an acronymic name, QuEChERS, that reflects its major advantages (quick, easy, cheap, effective, rugged, safe). In this work, QuEChERS method, which was originally created for vegetable samples with a high amount of water, was modified to optimise the extraction of a wide range of herbicides in barley. Then, it was compared with known conventional multi-residue extraction procedures such as the Luke method, which was simplified and shortened by eliminating the Florisil clean-up (mini Luke) and the ethyl acetate extraction, which involves a subsequent clean-up by gel permeation chromatography (GPC) and which is the official extraction method used by some of European authorities. Finally, a simple acetone extraction was carried out to check the differences with the other three methods. Extracts were analysed by gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mini Luke was significantly more effective for the extraction of non-polar and medium-polar compounds, but the best recoveries for polar compounds were achieved by QuEChERS and ethyl acetate methods. QuEChERS was the only method that provided an overall recovery value of 60-70% for non-, medium- and polar compounds, with some exceptions due to co-eluted matrix interferences. Clean-up by dispersive SPE was effective and did not differ so much with ethyl acetate extracts considering that QuEChERS clean-up step is much easier and less time-consuming. As a conclusion, it resulted to be the most universal extraction method by providing a well-defined phase separation without dilution and achieving acceptable recoveries in average including the extraction of the always difficult acidic herbicides. However, recoveries were not as good as required for validation purposes suggesting that residues are prone to strong matrix interactions in dry samples as barley and further method adaptation incrementing solvent strength, extraction time or more acidic or basic conditions is needed in order to achieve a complete extraction.

Effective centrality and explosive synchronization in complex networks.

Synchronization of networked oscillators is known to depend fundamentally on the interplay between the dynamics of the graph's units and the microscopic arrangement of the network's structure. We here propose an effective network whose topological properties reflect the interplay between the topology and dynamics of the original network. On that basis, we are able to introduce the effective centrality, a measure that quantifies the role and importance of each network's node in the synchronization process. In particular, in the context of explosive synchronization, we use such a measure to assess the propensity of a graph to sustain an irreversible transition to synchronization. We furthermore discuss a strategy to induce the explosive behavior in a generic network, by acting only upon a fraction of its nodes.

Effects of degree correlations on the explosive synchronization of scale-free networks.

We study the organization of finite-size, large ensembles of phase oscillators networking via scale-free topologies in the presence of a positive correlation between the oscillators' natural frequencies and the network's degrees. Under those circumstances, abrupt transitions to synchronization are known to occur in growing scale-free networks, while the transition has a completely different nature for static random configurations preserving the same structure-dynamics correlation. We show that the further presence of degree-degree correlations in the network structure has important consequences on the nature of the phase transition characterizing the passage from the phase-incoherent to the phase-coherent network state. While high levels of positive and negative mixing consistently induce a second-order phase transition, moderate values of assortative mixing, such as those ubiquitously characterizing social networks in the real world, greatly enhance the irreversible nature of explosive synchronization in scale-free networks. The latter effect corresponds to a maximization of the area and of the width of the hysteretic loop that differentiates the forward and backward transitions to synchronization.

High-performance liquid chromatographic determination of benomyl and carbendazim residues in apiarian samples.

Simple procedures for the extraction and chromatographic determination of benomyl and carbendazim in honey, bees wax, larvae, bees and pollen are proposed. The fungicides were extracted from honey, larvae and bees using ethyl acetate, while methanol was more suitable for wax and pollen samples. Pollen extracts need a further clean-up step with n-hexane. The determination is carried out by reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection. The procedures have been applied to the analysis of benomyl on honey and larvae samples from hives whose bees were nourished with artificial food mixed with benomyl.

Determination of the fungicide vinclozolin in honey and bee larvae by solid-phase and solvent extraction with gas chromatography and electron-capture and mass spectrometric detection.

Methods for the determination of residual vinclozolin in honey and bee larvae are proposed. The fungicide can be extracted with an n-hexane-acetone (70:30, v/v) mixture, or by passage through ODS cartridges which requires no subsequent clean-up. Vinclozolin is quantified by capillary gas chromatography with electron-capture and mass spectrometric detection. Recoveries from spiked samples exceed 90%, with a relative standard deviation of 3.5-4.5%.

Volatilisation of triallate as affected by soil texture and air velocity.

The rate of volatilisation of the formulated herbicide triallate was investigated in a wind tunnel under controlled wind-speed conditions. An experimental set-up is described which allows the monitoring of wind speed (w.s.), soil-water content, and the temperature of air and soil. A system controlling soil-water content is also described. The influence of air velocity and soil texture was investigated measuring the cumulative volatilisation losses of triallate from soil. The herbicide volatilisation losses after application ranged from 40% at 3 m/s to 53% at 9 m/s for loam soil and from 60% at 3 m/s to 73% at 9 m/s for sandy soil.

[Clinical usefulness of adrenal gland computed tomography in the etiologic diagnosis of Addison's disease]. / Utilidad clínica de la tomografía computadorizada suprarrenal en el diagnóstico etiológico de la enfermedad de Addison.

BACKGROUND: The aim of this study was to evaluate adrenal gland morphology by computerized tomography (CT) in the etiologic diagnosis of Addison's disease. METHODS: Twenty-two patients were grouped according to their etiology based on the study of antiadrenal antibodies at diagnosis of the disease: 7 were positive (autoimmune etiology or EAA), 11 were negative (tuberculous etiology or EAT) and in four serologic study was not available (undetermined etiology or EAI). Adrenal gland CT was performed with contiguous sections every 5 mm. In eight cases the examination was carried out upon diagnosis of the disease (initial stage) and in 14 between 2 and 17 years following diagnosis (evolutive stage). RESULTS: In all the patients of the EAA group, examined in either the initial or evolutive stages, the adrenal glands appeared atrophic without calcifications. In the patients of the EAT group adrenal masses of proven tuberculous origin were found in five who were studied in the initial stage and with atrophic glands with calcifications in the remaining patients examined in the evolutive stage, with the exception of two cases with atrophic adrenal glands without calcifications which could serologically be considered as false negatives having autoimmune etiology. The patients in the EAI groups were studied in the evolutive stage with three having atrophic glands with calcifications and one atrophic adrenal glands without calcifications. CONCLUSIONS: Adrenal gland computerized tomography is an useful examination to differentiate between autoimmune or tuberculous origin in Addison's disease. Clinical application may be justified in all patients of recent diagnosis when the study of the antiadrenal antibodies is negative or not possible.

[Behavioral and neuropsychological phenotype of the 48XXYY syndrome: a longitudinal study of a case]. / Fenotipo conductual y neuropsicológico del síndrome 48XXYY: estudio longitudinal de un caso.

INTRODUCTION: The 48XXYY syndrome is a clinical condition which has been little studied from the neuropsychological and neuropsychiatric points of view. We have not found any follow-up studies in the literature. The treatment used to date has not been successful. CLINICAL CASE: We made a longitudinal study of a boy with the 48XXYY syndrome. Neuropsychiatric evaluation was done when he was 6, 8, 10 and 12 years old. The course followed, both in conduct (bulimia, anorexia, disinhibition, depression, social isolation and heteroaggressivity) and in neuropsychology (evaluated using WISC-R and the Continuous Performance Test), was of progressive deterioration of sustained attention and also on the subscales of comprehension, arithmetic, similarities, vocabulary and WIS-R keys. On EEG there was hypofrontality and theta-delta activity in the occipito-parieto-temporal regions of both hemispheres. In the brainstem a low voltage IV wave was seen in the OI. The metabolic alterations were: hyperserotoninemia and hyperuricemia. On CAT there were lesions giving increased signals in the occipital horns. Prescription of risperidone at a dose of 2 mg/day led to improved behavior (with less heteroaggressivity and social isolation) and improved neurocognition (arithmetic, similarities and keys) with no modification of EEG activity. CONCLUSIONS: From the neuropsychological and behavior measurements and the clinical data in the bibliography, we suggest (for the first time) that there is a conduct and neuropsychological phenotype corresponding to this syndrome, although confirmation of this will require a larger number of longitudinal studies. Risperidone at a low dosage has been shown to be effective in controlling alterations of conduct and neuropsychology.

[Efficacy of parenteral glutamine in patients undergoing bone marrow transplantation]. / Eficacia de la glutamina parenteral en pacientes sometidos a trasplante autólogo de médula ósea.

INTRODUCTION: Autologous bone marrow transplant (ABMT) represents a high metabolic stress. Glutamine has proven to be effective in severe catabolic states, although there are controversial studies. OBJECTIVES: To assess the effect of parenteral nutrition (PN) therapy supplemented with glutamine on the occurrence of mucositis and mean hospital stay in patients submitted to ABMT. METHODS: Retrospective study of patients submitted to ABMT between 2006 and 2009. In 2008, one vial of L-alanyl-L-glutamine (20 g) was added by protocol to the PN formulations of these patients. Thirteen clinical charts since that date (glutamine group) and 13 previous charts (control group) were randomly selected (n = 26). We compared the degree of mucositis and hospital stay in both groups. In the subgroup of glutamine-treated patients, we compare the glutamine dose in the patients developing some degree of mucositis with that of those not having this complication. RESULTS: Mean hospital stay: 27.8 ± 7.4 days (control group) vs. 20.3 ± 5.3 days (glutamine group) (p = 0.01). The severity of mucositis was lower in the glutaminetreated group (p = 0.02). The weight-adjusted dose of L-alanyl-L-glutamine in the patients not developing mucositis was higher than in the other ones (0.32 vs. 0.24 g/kg/day; p = 0.02). CONCLUSIONS: Glutamine supplementation reduces the degree of mucositis and hospital stay in patients submitted to autologous bone marrow transplantation. The degree of mucositis is lower in the subgroup of patients receiving higher doses of glutamine.

Mechanical behaviour and rupture of normal and pathological human ascending aortic wall.

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart.

Response of human coronary arteries at different mechanical conditions.

The lack of reliable mechanical data on coronary arteries hampers the application of numerical models to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure. Knowledge of the mechanical response of human coronary arteries could be applied to optimize the election of vascular grafts or to prevent arterial damage during angioplasty.

Mechanical properties of human coronary arteries.

The lack of reliable mechanical data on coronary arteries and, more specifically, on their wall strength hampers the application of numerical models and simulations to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. Studies of the mechanical properties of coronary arteries have been carried out almost exclusively on animals. Only a few studies have tried to characterize the in vivo behavior of human coronaries through tests under physiological conditions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure.