Thickness dependence of the room-temperature ethanol sensor properties of Cu2O polycrystalline films.

This study investigates the fabrication process of copper thin films via thermal evaporation, with precise control over film thickness achieved throughZ-position adjustment. Analysis of the as-fabricated copper films reveals a discernible relationship between grain size (〈D〉) andZ-position, characterized by a phenomenological equation〈D〉XRDn(Z)=〈D〉0n1+32rZ2+158rZ4, which is further supported by a growth exponent (n) of 0.41 obtained from the analysis. This value aligns well with findings in the literature concerning the growth of copper films, thus underlining the validity and reliability of our experimental outcomes. The resulting crystallites, ranging in size from 20 to 26 nm, exhibit a resistivity within the range of 3.3-4.6µΩ · cm. Upon thermal annealing at 200 °C, cuprite Cu2O thin films are produced, demonstrating crystallite sizes ranging from ∼9 to ∼24 nm with increasing film thickness. The observed monotonic reduction in Cu2O crystallites relative to film thickness is attributed to a recrystallization process, indicating amorphization when oxygen atoms are introduced, followed by the nucleation and growth of newly formed copper oxide phase. Changes in the optical bandgap of the Cu2O films, ranging from 2.31 to 2.07 eV, are attributed mainly to the quantum confinement effect, particularly important in Cu2O with size close than the Bohr exciton diameter (5 nm) of the Cu2O. Additionally, correlations between refractive index and extinction coefficient with film thickness are observed, notably a linear relationship between refractive index and charge carrier density. Electrical measurements confirm the presence of a p-type semiconductor with carrier concentrations of ∼1014cm-3, showing a slight decrease with film thickness. This phenomenon is likely attributed to escalating film roughness, which introduces supplementary scattering mechanisms for charge carriers, leading to a resistivity increase, especially as the roughness approaches or surpasses the mean free path of charge carriers (8.61 nm). Moreover,ab-initiocalculations on the Cu2O crystalline phase to investigate the impact of hydrostatic strain on its electronic and optical properties was conducted. We believe that our findings provide crucial insights that support the elucidation of the experimental results. Notably, thinner cuprite films exhibit heightened sensitivity to ethanol gas at room temperature, indicating potential for highly responsive gas sensors, particularly for ethanol breath testing, with significant implications for portable device applications.

Efecto de la N-acetilcisteína en la mortalidad de pacientes ingresados por COVID-19: estudio de cohorte retrospectivo / Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study

Introducción y objetivo La N-acetilcisteína se ha propuesto para el tratamiento de COVID-19 gracias a sus efectos mucolítico, antioxidante y antiinflamatorio. El presente estudio tiene como objetivo evaluar su efecto en pacientes ingresados con COVID-19, en términos de mortalidad. Material y métodos Estudio de cohorte retrospectivo unicéntrico. Se incluyeron todos los pacientes ingresados por COVD-19 entre marzo y abril de 2020 en nuestro hospital. Resultados Un total de 378 pacientes fueron incluidos; de ellos, 196 (51,9%) fueron hombres, la edad media fue de 73,3±14,5 años. Un total de 199 (52,6%) pacientes recibieron tratamiento con N-acetilcisteína. Más del 70% tuvieron tos, fiebre y/o disnea. La mortalidad hospitalaria global fue del 26,7%. Un análisis multivariante mediante regresión logística identificó la edad de los pacientes [mayores de 80 años; OR: 8,4 (IC95%: 3-23,4)], una afectación radiológica moderada o grave medida por la escala RALE [OR: 7,3 (IC95%: 3,2-16,9)], el consumo de tabaco [OR: 2,8 (IC95%: 1,3-6,1)] y arritmia previa [OR: 2,8 (IC95%: 1,3-6,2)] como factores de riesgo que se asociaron independientemente con la mortalidad durante el ingreso. El tratamiento con N-acetilcisteína fue identificado como factor protector [OR: 0,57 (IC95%: 0,31-0,99)]. El asma podría representar asimismo un factor protector de mortalidad, aunque en el presente estudio no alcanza significación estadística [OR: 0,19 (IC95%: 0,03-1,06)]. Conclusiones Los pacientes con COVID-19 tratados con N-acetilcisteína presentaron una menor mortalidad y mejor evolución en nuestro estudio. Futuros estudios prospectivos o ensayos clínicos aleatorizados deben confirmar el papel de la N-acetilcisteína en pacientes con COVID-19 (AU)

Introduction and aim N-acetylcysteine has been proposed for the treatment of COVID-19 thanks to its mucolytic, antioxidant and anti-inflammatory effects. Our aim is to evaluate its effect on patients admitted with COVID-19 in mortality terms. Material and methods Retrospective single-center cohort study. All patients admitted to our hospital for COVID-19 from March to April 2020 have been considered. Results A total of 378 patients were included, being 196 (51.9%) men, with an average age of 73.3±14.5 years. The 52.6% (199) received treatment with N-acetylcysteine. More than 70% presented coughs, fever, and/or dyspnea. The global hospital mortality was 26.7%. A multivariate analysis through logistic regression identified the age of patients [older than 80; OR: 8.4 (95% CI: 3–23.4)], a moderate or severe radiologic affectation measured by the RALE score [OR: 7.3 (95% CI: 3.2–16.9)], the tobacco consumption [OR: 2.8 (95% CI: 1.3–6.1)] and previous arrhythmia [OR 2.8 (95% CI: 1.3–6.2)] as risk factor that were independently associated with mortality during the admission. The treatment with N-acetylcysteine was identified as a protective factor [OR: 0.57 (95% CI: 0.31–0.99)]. Asthma also seems to have a certain protective factor although it was not statistically significant in our study [OR: 0.19 (95% CI: 0.03–1.06)]. Conclusions Patients with COVID-19 treated with N-acetylcysteine have presented a lower mortality and a better evolution in this study. Future prospective studies or randomized clinical trials must confirm the impact of N-acetylcysteine on COVID-19 patients (AU)

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Percutaneous closure of a ruptured right coronary sinus of Valsalva aneurysm that mimics severe aortic regurgitation.

A 34-year-old male was admitted with presumed acute, severe aortic regurgitation. Multimodal imaging was performed and showed a ruptured right coronary sinus of Valsalva aneurysm into the right atrium. He underwent a percutaneous closure of the ruptured sinus of Valsalva aneurysm. The patient had major clinical improvement.

Bioecological aspects of triatomines and marsupials as wild Trypanosoma cruzi reservoirs in urban, peri-urban and rural areas in the Western Brazilian Amazon.

In the Amazon region, Trypanosoma cruzi transmission cycles involve a great diversity of Triatominae vectors and mammal reservoirs. Some Rhodnius spp. mainly inhabit palm trees that act as microhabitats for hosts and vectors. The current study aimed to describe aspects of the bio-ecology of the vectors and reservoirs of T. cruzi in relation to human populations resident near areas with large quantities of palm trees, in rural, peri-urban and urban collection environments, located in the Western Brazilian Amazon. Rhodnius pictipes and Didelphis marsupialis were respectively the most predominant vector and reservoir, with rates of 71% for R. pictipes and 96.5% for D. marsupialis. The vast majority of T. cruzi isolates clustered with TcI. The most prevalent haplotype was TcI COII1 (69.7%). Mauritia flexuosa and Attalea phalerata were the main ecological indicators of infestation by triatomines. Birds were the most common food source (27,71%). T. cruzi isolated from R. robustus has the haplotype HUM-13, previously detected in a chronic Chagas patient living in the same area. Our results demonstrate the relevance of this study, with the occurrence of elevated infection rates in animals, and suggest the importance of the Amazon zones where there is a risk of infection in humans.

Ethanolic extract of Artemisia campestris subsp. glutinosa (Besser) Batt. inhibits HIV-1 replication in vitro through the activity of terpenes and flavonoids on viral entry and NF-κB pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: The genus Artemisia spp. is well known for its anti-infectious properties and its high content in anti-infectious compounds, like the well-known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. AIM OF THE STUDY: The aim of this study is to investigate the anti-HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. MATERIALS AND METHODS: Antiviral activity of isolated compounds and extracts was evaluated in HIV-1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV-1 and VSV pseudotyped HIV-1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV-1 or NF-κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. RESULTS: Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti-HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 µg/mL). Bio-guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2', 4'-trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV-1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti-HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF-κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. CONCLUSION: We describe here the anti-HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV-1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti-infectious activity of wormwood species and their use in treating infectious diseases.

Determination of the fundamental absorption and optical bandgap of dielectric thin films from single optical transmittance measurements.

In this work, we propose a method to retrieve the thickness and optical constants of dielectric thin films from single optical transmittance measurements. The method is based on the envelope method and requires a simple dispersion model for the real part of the refractive index with few fitting parameters, while the absorption coefficient can be determined without the aid of a dispersion model. The wavelength-dependent optical constants can be obtained even from spectra that exhibit few interference fringes. We have tested the method with simulated and real transmittance data from thin films in the spectral range covering the fundamental absorption. In order to assess the method's reliability to retrieve the optical constants and optical bandgap, a comparison is performed with the method by Chambouleyron, known as the Pointwise Unconstrained Minimization Approach, and a fit using the Cody-Lorentz dispersion model. We evaluate the methods' capability to retrieve the fundamental absorption and optical bandgap, and their compromise with film thickness accuracy. Finally, the methods are tested and contrasted using optical transmittance of three different semiconductor material thin films.

Combinatorial approach toward optimization of the light emission intensity of AlOxNy:Yb3+ thin films.

To obtain an adequate luminescent emission, a significant effort must be made to find a suitable host material. An interesting and highly efficient method is a combinatorial approach, which allows high velocity screening of a wider range of properties. In the present work, a compositional gradient-based, thin-film library of a-AlOxNy:Yb3+ has been prepared by radio frequency co-sputtering from two targets. The ytterbium concentration range spreads from 0.9 to 4.2 at. % and the oxygen to nitrogen ratio from 0.6 to 3.6. Using different annealing temperatures, the activation energy of the rare earth ions and activation mechanisms can be evaluated. Finally, optimal elemental compositions in the investigated range are proposed.

Pretreatment neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte, and neutrophil/monocyte ratios and outcome in elderly breast cancer patients.

PURPOSE: Several studies have found an association between peripheral inflammatory cells and outcome. However, no study has explored their impact specifically in elderly patients. We have retrospectively examined pretreatment peripheral neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and neutrophil/monocyte ratio (NMR) in 113 elderly breast cancer patients and correlated our findings with disease-free survival (DFS) and overall survival (OS). METHODS: All patients ≥ 65 years diagnosed from 2004 to 2018 with locally advanced breast cancer were included and classified as high vs low NLR, PLR, LMR, and NMR based on previously identified cutoffs. Estimated 1-, 3-, and 5-year DFS and OS were compared by Chi square analysis. RESULTS: Among 104 evaluable patients, only PLR was significantly associated with estimated 3-year DFS (85.1% vs 63.6%; P = 0.04) and OS (89.3% vs 68.1%; P = 0.03). Among 69 patients with three or more years of follow-up, PLR (P = 0.05), absolute lymphocyte count (ALC) (P = 0.01), polychemotherapy (P = 0.04), number of comorbidities (P = 0.02), polypharmacy (P = 0.005), and clinical stage (P = 0.03) were associated with 3-year DFS. Polypharmacy (OR 4.9; P = 0.02) and ALC (OR 4.6; P = 0.04) retained their significance in the multivariate analysis. CONCLUSIONS: We have found an association between low PLR and longer DFS in elderly breast cancer patients that is in line with findings in patients with a wider range of ages. Our findings on NLR contrast with those of other studies, indicating a potential differential effect in elderly patients. In addition, the effect of polypharmacy on outcome in elderly patients warrants further investigation.

Results and functional outcomes of acute ischemic stroke patients who underwent mechanical thrombectomy admitted to intensive care unit. / Resultados y evolución funcional de pacientes críticos con ictus isquémico sometidos a trombectomía mecánica.

PURPOSE: To study the results and complications of endovascular treatment (EVT) in acute ischemic stroke patients admitted to Intensive Care Unit (ICU). To analyse the possible factors related to mortality and level of disability at ICU discharge and one year after stroke. DESIGN: Observational prospective study. SETTING: Mixed ICU. Third level hospital. PATIENTS: Sixty adult patients. Consecutive sample. INTERVENTIONS: None. VARIABLES OF INTEREST: Epidemiological data, time from symptom onset to EVT, angiographic result, length of stay, days on mechanical ventilation, neurological complications, National Institutes of Health Stroke Scale (NIHSS) at ICU admission and discharge, modified Rankin scale score (mRS) at one year. RESULTS: Mean age 68,90±8,84years. Median time from symptom onset to EVT: 180minutes. Median NIHSS at admission: 17,5; at discharge: 3. Distal flow was achieved in 90% of cases. Median ICU stay: 3 days. Mechanical ventilation: 81,7.%. Functional independence (mRS≤2) 50% at one year. Deaths: 22 (36,6%) of which 8 (13,3%) died during UCI stay and the rest during the first year. CONCLUSIONS: The factors relating to a worse functional outcome were symptomatic hemorrhage transformation, lack of recanalization and complications during EVT. The factors relating to mortality were symptomatic hemorrhage and hydrocephalus. Distal flow was achieve in most cases with a low complication rate. Half of the patients presented functional independence one year after the stroke.

Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors.

To improve survival in young children with malignant brain tumors, irradiation-avoiding or -minimizing marrow-ablative chemotherapy (HDCx) with autologous hematopoietic cell transplantation (AuHCT) has been investigated. We evaluated the outcome of 44 children with malignant brain tumors treated with HDCx and tandem AuHCT at Children's Hospital Los Angeles between June 1999 and July 2012. Forty-four children with malignant brain tumors were studied. Twenty-one had medulloblastoma/primitive neuro-ectodermal tumor, eight atypical teratoid/rhabdoid tumor (ATRT), five high-grade glioma, four malignant germ cell tumor, three ependymoma and three choroid plexus carcinoma. Twenty-nine patients received three tandem transplants and 15 received two tandem transplants, respectively. The 5-year PFS and overall survivals (OS) for all patients were 46.3±8.2% and 51.7±8.5%, respectively. The PFS and OS for 27 newly diagnosed patients were 68.9±9.9% and 73.5±9.3%, respectively, compared with 17 transplanted at relapse 11.8±9.8% (P<0.001) and 15.1±12.3% (P=0.0231), respectively. The 5-year PFS and OS in 13 previously unirradiated patients were 74±13% and 74±13% versus 33.2±9.8% and 40.2±10.6% in 31 irradiated patients (P=0.11 and P=0.239), respectively. One patient died of transplant-related toxicity. HDCx with tandem AuHCT is feasible and safe in children with malignant brain tumors with encouraging irradiation-free survival in newly diagnosed children.

Functional variations in MBL2 gene are associated with cutaneous leishmaniasis in the Amazonas state of Brazil.

Functional variations in the mannose-binding lectin (MBL2) gene causing low levels of serum MBL are associated with susceptibility to numerous infectious diseases. We investigated whether there is genetic association of MBL2 variant alleles with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis. We used PCR-restriction fragment length polymorphism to genotype six MBL2 variants, three in the promoter region and three in the exon 1. An association was noted between the single nucleotide polymorphism -221X/Y of the MBL2 gene and CL (P=2.9 × 10(-6); odds ratio (OR)=1.9 (1.4-2.5) consistent with the hypothesis that the -221X allele confers high risk to development of CL among L. guyanensis-infected individuals. Furthermore, L. guyanensis-infected individuals bearing the codon 57 allele C had a higher risk of developing CL (P=5 × 10(-5); OR=1.9 (1.4-2.6)). The low MBL expressor haplotype LXPB was also associated to CL (P=6 × 10(-4)). This study raises the possibility that functional polymorphisms in MBL2 gene play a role in clinical outcome of Leishmania infection.

Scratch and abrasion properties of polyurethane-based micro- and nano-hybrid obturation materials.

Polyurethane-based micro- and nano-hybrid composites were produced with controlled porosity to be used as obturation materials. In addition to hydroxyapatite (HAp) micro-particles in the composites, two different ceramics particle types were also added: alumina micro-particles and silica nano-particles. Particles of different sizes provide the materials with improved mechanical properties: the use of micro- and nano-particles produces a better packing because the nano-particles fill the interstitial space left by the micro-particles, rendering an improvement in the mechanical properties. The silica and alumina particles provide the materials with appropriate abrasion and scratching properties, while the HAp provides the required bio-acceptance. The polymeric matrix was a mono-component solvent-free polyurethane. The porosity was selected by controlling the chemical reaction.

Use of hydrogen as a carrier gas for the analysis of steroids with anabolic activity by gas chromatography-mass spectrometry.

Due to the impact in the media and the requirements of sensitivity and robustness, the detection of the misuse of forbidden substances in sports is a really challenging area for analytical chemistry, where any study focused on enhancing the performance of the analytical methods will be of great interest. The aim of the present study was to evaluate the usefulness of using hydrogen instead of helium as a carrier gas for the analysis of anabolic steroids by gas chromatography-mass spectrometry with electron ionization. There are several drawbacks related with the use of helium as a carrier gas: it is expensive, is a non-renewable resource, and has limited availability in many parts of the world. In contrast, hydrogen is readily available using a hydrogen generator or high-pressure bottled gas, and allows a faster analysis without loss of efficiency; nevertheless it should not be forgotten that due to its explosiveness hydrogen must be handled with caution. Throughout the study the impact of the change of the carrier gas will be evaluated in terms of: performance of the chromatographic system, saving of time and money, impact on the high vacuum in the analyzer, changes in the fragmentation behaviour of the analytes, and finally consequences for the limits of detection achieved with the method.

[The development of neurotoxic agents as chemical weapons during the National Socialist period in Germany]. / Desarrollo de agentes neurotóxicos como herramientas de guerra química durante el período nacionalsocialista alemán.

INTRODUCTION: The discovery and development of the so-called 'nerve agents' (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research. DEVELOPMENT: The first neurotoxic substance to be incorporated into the category of 'chemical warfare agent' did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, a chemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researchers later synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. CONCLUSIONS: Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that an excess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect.

Desarrollo de agentes neurotóxicos como herramientas de guerra química durante el período nacionalsocialista alemán / The development ofneurotoxic agents as chemical weapons during the national socialist period in Germany

Introducción. El descubrimiento y desarrollo de los denominados ‘agentes nerviosos’ (sustancias neurotóxicas destinadas al arsenal bélico) tuvieron lugar en la Alemania del Tercer Reich, gracias, en gran medida, al enorme desarrollo de la farmacología en este país, tanto en el ámbito académico como industrial. Asimismo, la organización por parte de los sucesivos gobiernos nacionalsocialistas de una red colaborativa entre el estamento académico, la industria química y los responsables militares favoreció esta línea de investigación. Desarrollo. En la incorporación del primer agente neurotóxico a la categoría de ‘arma de guerra química’ influyó decisivamente el azar. En el marco de investigaciones sobre pesticidas e insecticidasde naturaleza organofosforada, Gerhard Schrader, químico de la compañía I.G. Farben, sintetizó el tabún (etil-N,N-dimetil- fosforamidocianidato), y una contaminación accidental del personal del laboratorio con esta sustancia puso de manifiesto su potencialidad tóxica. Este mismo grupo sintetizó posteriormente otra sustancia dotada de las mismas propiedades, el sarín(isopropil-metil-fosfonofluoridato). Ambos agentes fueron estudiados como armas químicas por Wolfgang Wirth. Simultáneamente, el grupo liderado por Richard Kuhn, premio Nobel de Química en 1938, sintetizó el pinacolil-metil-fosfonofluoridato, conocido como somán. Conclusión. Los estudios farmacológicos confirmaron que el mecanismo de acción neurotóxico de estassustancias era la inhibición irreversible de la enzima acetilcolinesterasa, responsable de la metabolización de la acetilcolina, y que el exceso de este neurotransmisor ocasionaba una sobreestimulación continuada de los receptores colinérgicos (nicotínicos y muscarínicos), responsable de la aparición del amplio espectro de síntomas de intoxicación y de su rápido efecto letal

Introduction. The discovery and development of the so-called ‘nerve agents’ (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research.Development. The first neurotoxic substance to be incorporated into the category of ‘chemical warfare agent’ did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, achemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researcherslater synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. Conclusions. Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that anexcess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect

Daño neurológico en intoxicación por monóxido de carbono / Neurologic damage in carbon monoxide

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Automated sample preparation and gas chromatographic-mass spectrometric analysis of urinary androgenic anabolic steroids.

This paper presents an automated method for extracting anabolic agents from urine samples for their GC-MS analysis by selected-ion monitoring. The sample preparation was carried out in a Hewlett-Packard 7686 SPE PrepStation system. Each 0.6-ml aliquot was hydrolyzed, extracted, dried and trimethylsilyl (TMS) derivatized in a 2-ml vial without any hands-on labor. When sample preparation was finished 2 microl of the extract was injected into the gas chromatograph by split (1:10) mode. Due to the small amount of free space in the 2-ml vials for handling the sample, parameters like time of hydrolysis, type of shaking, number of extractions and some TMS derivatization parameters had to be adjusted to achieve the best recovery for all of the compounds in the screening. Manual and automated sample preparation schemes were compared in terms of linearity, precision, accuracy, limit of detection and recovery data. When large concentrations were analyzed using the automated method no carry-over effect was observed.

Search for antiviral activity in higher plant extracts.

In the course of our search for plant natural products as antiviral agents, extracts of ten plants from the Iberian Peninsula were tested for antiviral activity against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. Aqueous extracts of five of these medicinal plants, namely Nepeta nepetella (150-500 microg/mL), Nepeta coerulea (150-500 microg/mL), Nepeta tuberosa (150-500 microg/mL), Dittrichia viscosa (50-125 microg/mL) and Sanguisorba minor magnolii (50-125 microg/mL), showed a clear antiviral activity against two different DNA and RNA viruses, i.e. HSV-1 and VSV. Only the medicinal plant Dittrichia viscosa was active against an additional virus, poliovirus type 1.

Análisis de anfetamina en orina por medio de microextracción en fase sólida / Analysis of amphetamine in urine by headspace solid phase microextraction

En este trabajo se presenta un método automatizado de extracción y análisis por GC (gas chromatography)-MS (mass spectrometry) para la detección de anfetamina en muestras de orina. El sistema esta constituido por un muestreador automatico, un cromatografo de gases y un espectrometro de masas de trampa de iones. El muestrador esta equipado con una aguja en cuyo interior hay una pequeña fibra retráctil de polidimetil siloxano, que puesta en contacto con la muestra, líquido o gas, absorbe selectivamente los analitos. La técnica es conocida como microextracción en fase sólida, SPME (Solid Phase MicroExtraction). En el estudio se hace un análisis detallado de todos los parámetros que afectan al rendimiento de las fibras, esto es; volumen de muestra, tipo de fibra, temperatura de absorción, tiempo de absorción, pH y fuerza ionica del medio. En la preparación de la muestra, tras ajustar manualmente el pH (pH 12) e incrementar la fuerza ionica de la muestra, 200 ml de orina son dispensados en un vial encapsulado de 2 ml. Tras solocar el vial en el carrusel termostatizado, Tª absorción 60°C, la fibra es introducida en el vial. Pasados 10 minutos de absorción, la fibra se retrae en la aguja y se inserta en el portal de inyección del cromatografo de gases, donde debido a alta temperatura, Ta desorbción 200°C, el analito desorbe de modo inmediato. El límite de detección es de 0.25 mg/l, el coeficiente de correlación lineal es de 0.9916 y la desviación estándar relativa menor del 5 por ciento. La concentración mínima de anfetamina que en la muestra pudo ser confirmada mediante un espectro de masas con índice de correlación mayor del 90 por ciento con su correspondiente espectro de librería, fue de 0.5 mg/l(AU)