Non-immediate hypersensitivity reactions to iomeprol: Diagnostic value of skin tests and cross-reactivity with other iodinated contrast media.

BACKGROUND: Iodinated contrast media produce non-immediate hypersensitivity reactions (NIHR). The goal of this prospective study was to determine the utility of skin tests and the subsequent tolerance to negative skin-tested iodinated contrasts in patients with NIHR caused by iomeprol. METHODS: Prick and intradermal tests with iomeprol, iopamidol, iopromide, and iobitridol were performed in all patients. IV challenge with the causative contrast (iomeprol in 90%) was made if skin tests were negative. In case of a positive skin test with the causal contrast, or a positive challenge test with it, IV challenge test with an alternative, negative skin-tested contrast was performed in all patients. RESULTS: Skin tests were positive in 47.6% (20/42) of patients with NIHR induced by iomeprol. Of the 66 challenge tests performed with negative skin-tested iodinated contrasts, tolerance was confirmed in 35 (53%): 32 iomeron, 2 iobitridol, 1 iopamidol. Cross-reactivity between iomeprol and iopamidol was 22% (4/20 in patients with positive skin tests and 5/21 in patients with negative skin tests). CONCLUSIONS: Sensitivity of the skin tests was less than 50% NIHRs due to iomeprol, while the negative predictive value of skin tests in patients who tolerated challenges with alternative contrasts (mainly iopamidol) was 53% (35 tolerated out of 66 performed). The cross-reactivity between iomeprol and iopamidol is high.

[Tobacco use in Spain during COVID-19 lockdown: an evaluation through social media.] / Consumo de tabaco en España durante el estado de alarma por COVID-19: resultados de una evaluación a través de redes sociales.

OBJECTIVE: During the state of alarm and once the confinement decreed by the COVID-19 pandemic ended, a cross-sectorial study was carried out in Spain between May 4th and 22nd, 2020 by volunteers who completed a self-administered online survey. The objective of this study was to know how the confinement period affected the consumption of tobacco and other related products in the adult Spanish population. METHODS: The survey consisted of 18 questions concerning sociodemographic characteristics, the consumption of tobacco and other related products, exposure to secondhand smoke and perception of COVID-19 risk associated with consumption. Questions about tobacco and other related products were posed in order to compare consumption prior to and during confinement. The survey was completed by 17,017 people. The analysis of association of variables was carried out with T-student. Variable frequency analysis was performed with χ2. RESULTS: There was a reduction in the prevalence of daily tobacco smoking and no changes were observed in the products consumed in either period (6.73%). The prevalence of exposure to secondhand smoke at home during confinement among non-smokers decreased (61.83%). Most of survey respondents reported that tobacco and e-cigarette consumption increased the risk of contracting COVID-19 and suffering severe complications (39.09% and 31.80% respectively). CONCLUSIONS: During the COVID-19 lockdown in Spain, the tobacco consumption decreased. Also, secondhand smoke exposition reduces in Spain during this period.

OBJETIVO: Durante el estado de alarma y una vez finalizado el confinamiento decretado por la pandemia por COVID-19, en España se realizó, entre el 4 y el 22 de mayo de 2020, un estudio transversal en voluntarios aplicando una encuesta autocumplimentada online. El objetivo de este estudio fue conocer cómo afectó el periodo de confinamiento al consumo de tabaco y relacionados en la población adulta española. METODOS: El cuestionario constaba de 18 preguntas e incluía características sociodemográficas, el consumo de tabaco y otros productos relacionados, exposición al humo ambiental de tabaco y percepción del riesgo de enfermedad por COVID-19 asociada a su consumo. La encuesta fue completada por 17.017 personas. El análisis de la asociación entre variables cuantitativas, fue realizado mediante el test de la T de Student y el de frecuencias de las variables categóricas mediante el test de χ2. RESULTADOS: Se observó reducción en la prevalencia de fumadores diarios de tabaco (6,73%) y no se observaron cambios en los productos consumidos. La prevalencia de exposición al humo ambiental en casa durante el confinamiento entre personas no fumadoras disminuyó (61,83%). Los encuestados declararon que el consumo de tabaco y de cigarrillos electrónicos aumentaba el riesgo de contraer la enfermedad del COVID-19 y sufrir complicaciones (39,09% y 31,80% respectivamente). CONCLUSIONES: Durante el periodo de confinamiento en España debido al COVID-19, se produjo una reducción en el consumo de tabaco y similares. Además de observó una reducción a la exposición al humo ambiental.

Día Mundial sin Tabaco (31 de mayo de 2019) / No disponible

No disponible

Aplasia medular severa secundaria a triple terapia para virus hepatitis C: a propósito de un caso / Severe bone marrow aplasia due to triple therapy for hepatitis C virus infection: Apropos of a case

No disponible

Combined effects of ultrasound and immobilization protocol on butyl acetate synthesis catalyzed by CALB.

It is well established that the performance of lipase B from Candida antarctica (CALB) as catalyst for esterification reactions may be improved by the use of ultrasound technology or by its immobilization on styrene-divinylbenzene beads (MCI-CALB). The present research evaluated the synthesis of butyl acetate using MCI-CALB under ultrasonic energy, comparing the results against those obtained using the commercial preparation, Novozym 435. The optimal conditions were determined using response surface methodology (RSM) evaluating the following parameters: reaction temperature, substrate molar ratio, amount of biocatalyst, and added water. The optimal conditions for butyl acetate synthesis catalyzed by MCI-CALB were: temperature, 48.8 °C; substrate molar ratio, 3.46:1 alcohol:acid; amount of biocatalyst, 7.5%; and added water 0.28%, both as substrate mass. Under these conditions, 90% of conversion was reached in 1.5 h. In terms of operational stability, MCI-CALB was reused in seven cycles while keeping 70% of its initial activity under ultrasonic energy. The support pore size and resistance are key points for the enzyme activity and stability under mechanical stirring. The use of ultrasound improved both activity and stability because of better homogeneity and reduced mechanical stress to the immobilized system.

Evaluation of styrene-divinylbenzene beads as a support to immobilize lipases.

A commercial and very hydrophobic styrene-divinylbenzene matrix, MCI GEL® CHP20P, has been compared to octyl-Sepharose® beads as support to immobilize three different enzymes: lipases from Thermomyces lanuginosus (TLL) and from Rhizomucor miehie (RML) and Lecitase® Ultra, a commercial artificial phospholipase. The immobilization mechanism on both supports was similar: interfacial activation of the enzymes versus the hydrophobic surface of the supports. Immobilization rate and loading capacity is much higher using MCI GEL® CHP20P compared to octyl-Sepharose® (87.2 mg protein/g of support using TLL, 310 mg/g using RML and 180 mg/g using Lecitase® Ultra). The thermal stability of all new preparations is much lower than that of the standard octyl-Sepharose® immobilized preparations, while the opposite occurs when the inactivations were performed in the presence of organic co-solvents. Regarding the hydrolytic activities, the results were strongly dependent on the substrate and pH of measurement. Octyl-Sepharose® immobilized enzymes were more active versus p-NPB than the enzymes immobilized on MCI GEL® CHP20P, while RML became 700-fold less active versus methyl phenylacetate. Thus, the immobilization of a lipase on this matrix needs to be empirically evaluated, since it may present very positive effects in some cases while in other cases it may have very negative ones.

Improving the catalytic properties of immobilized Lecitase via physical coating with ionic polymers.

Lecitase Ultra has been immobilized on cyanogen bromide agarose (via covalent attachment) and on octyl agarose (via physical adsorption on the hydrophobic support by interfacial activation). Both immobilized preparations have been incubated in dextran sulfate (DS) or polyethylenimine (PEI) solutions to coat the enzyme surface. Then, the activity versus different substrates and under different experimental conditions was evaluated. The PEI coating generally produced a significant increase in enzyme activity, in some cases even by more than a 30-fold factor (using the octyl-Lecitase at pH 5 in the hydrolysis of methyl phenyl acetate). In opposition, the DS coating usually produced some negative effects on the enzyme activity. The rate of irreversible inhibition of the covalent preparation using diethyl p-nitrophenylphosphate did not increase after PEI coating suggesting that the increase in Lecitase activity is not a consequence of the stabilization of the open form of Lecitase. Moreover, the coating greatly increased the stability of the immobilized Lecitase, for example using DS and the covalent preparation, the half-life was increased by a 30-fold factor in 30% acetonitrile. The stabilizing effect was not found in all cases, in certain cases even a certain destabilization is found (e.g., octyl-Lecitase-DS at pH 7). Thus, the effects of the ionic polymer coating strongly depend on the substrate, experimental conditions and immobilization technique employed.

Malestar general en el paciente anciano como presentación de síndrome antisintetasa sin afectación muscular / General malaise in the elderly patient as a presentation of antisynthetase syndrome without muscle involvement

No disponible

Optimized butyl butyrate synthesis catalyzed by Thermomyces lanuginosus lipase.

Butyl butyrate is an ester present in pineapple flavor, which is very important for the food and beverages industries. In this work, the optimization of the reaction of butyl butyrate synthesis catalyzed by the immobilized lipase Lipozyme TL-IM was performed. n-Hexane was selected as the most appropriate solvent. Other reaction parameters such as temperature, substrate molar ratio, biocatalyst content and added water, and their responses measured as yield, were evaluated using a fractional factorial design, followed by a central composite design (CCD) and response surface methodology. In the fractional design 2(4-1) , the four variables were tested and temperature and biocatalyst content were statistically significant and then used for optimization on CCD. The optimal conditions for butyl butyrate synthesis were found to be 48°C; substrate molar ratio 3:1 (butanol:butyric acid); biocatalyst content of 40% of acid mass. Under these conditions, over 90% of yield was obtained in 2 h. Enzyme reuse was tested by washing the biocatalyst with n-hexane or by direct reuse. The direct reuse produced a rapid decrease on enzyme activity, while washing with n-hexane allowed reusing the enzyme for five reactions cycles keeping approximately 85% of its activity.

Stabilization of the hexameric glutamate dehydrogenase from Escherichia coli by cations and polyethyleneimine.

The enzyme glutamate dehydrogenase (GDH) from Escherichia coli is a hexameric protein. The stability of this enzyme was increased in the presence of Li(+) in concentrations ranging from 1 to 10mM, 1M of sodium phosphate, or 1M ammonium sulfate. A very significant dependence of the enzyme stability on protein concentration was found, suggesting that subunit dissociation could be the first step of GDH inactivation. This effect of enzyme concentration on its stability was not significantly decreased by the presence of 10mM Li(+). Subunit crosslinking could not be performed using neither dextran nor glutaraldehyde because both reagents readily inactivated GDH. Thus, they were discarded as crosslinking reagents and GDH was incubated in the presence of polyethyleneimine (PEI) with the aim of physically crosslinking the enzyme subunits. This incubation does not have a significant effect on enzyme activity. However, after optimization, the PEI-GDH was found to almost maintain the full initial activity after 2h under conditions where the untreated enzyme retained only 20% of the initial activity, and the effect of the enzyme concentration on enzyme stability almost disappeared. This stabilization was maintained in the pH range 5-9, but it was lost at high ionic strength. This PEI-GDH composite was also much more stable than the unmodified enzyme in stirred systems. The results suggested that a real adsorption of the PEI on the GDH surface was required to obtain this stabilizing effect. A positive effect of Li(+) on enzyme stability was maintained after enzyme surface coating with PEI, suggesting that the effects of both stabilizing agents could not be exactly based on the same mechanism. Thus, the coating of GDH surface with PEI seems to be a good alternative to have a stabilized and soluble composite of the enzyme.

Improved production of butyl butyrate with lipase from Thermomyces lanuginosus immobilized on styrene-divinylbenzene beads.

Two immobilized preparations from Thermomyces lanuginosus lipase (TLL) were compared in the synthesis of butyl butyrate. The commercial Lipozyme TL-IM, and TLL immobilized on styrene-divinylbenzene beads (MCI-TLL) were tested in the esterification reaction using n-hexane as solvent. The variables temperature (30-60°C), substrate molar ratio (1:1 to 5:1), added water (0-1%), and biocatalyst content (3-40%) were evaluated in terms of initial reaction rate for each biocatalyst. SDS-PAGE analysis revealed that MCI-TLL had an immobilized enzymatic load twice as high as Lipozyme TL-IM, but with an activity 3-fold higher. MCI-TLL presented high initial reaction rates up to 1.0 M butyric acid, while Lipozyme TL-IM showed a decrease in its activity above 0.5 M. Moreover, MCI-TLL allowed a productivity of 14.5 mmol g(-1) h(-1), while Lipozyme TL-IM 3.2 mmol g(-1) h(-1), both by mass of biocatalyst.

Immobilization of lipase B from Candida antarctica on porous styrene-divinylbenzene beads improves butyl acetate synthesis.

A new biocatalyst of lipase B from Candida antarctica (MCI-CALB) immobilized on styrene-divinylbenzene beads (MCI GEL CHP20P) was compared with the commercial Novozym 435 (immobilized lipase) in terms of their performances as biocatalysts for the esterification of acetic acid and n-butanol. The effects of experimental conditions on reaction rates differed for each biocatalyst, showing different optimal values for water content, temperature, and substrate molar ratio. MCI-CALB could be used at higher acid concentrations, up to 0.5 M, while Novozym 435 became inactivated at these acid concentrations. Although Novozym 435 exhibited 30% higher initial activity than MCI-CALB for the butyl acetate synthesis, the reaction course was much more linear using the new preparation, meaning that the MCI-CALB allows for higher productivities per cycle. Both preparations produced around 90% of yield conversions after only 2 h of reaction, using 10% (mass fraction) of enzyme. However, the main advantage of the new biocatalyst was the superior performance during reuse. While Novozym 435 was fully inactivated after only two batches, MCI-CALB could be reused for six consecutive cycles without any washings and keeping around 70% of its initial activity. It is proposed that this effect is due to the higher hydrophobicity of the new support, which does not retain water or acid in the enzyme environment. MCI-CALB has shown to be a very promising biocatalyst for the esterification of small-molecule acids and alcohols.

Simple and efficient immobilization of lipase B from Candida antarctica on porous styrene-divinylbenzene beads.

Two commercial porous styrene-divinylbenzene beads (Diaion HP20LX and MCI GEL CHP20P) have been evaluated as supports to immobilize lipase B from Candida antarctica (CALB). MCI GEL CHP20P rapidly immobilized the enzyme, permitting a very high loading capacity: around 110mgCALB/wetg of support compared to the 50mg obtained using decaoctyl Sepabeads. Although enzyme specificity of the enzyme immobilized on different supports was quite altered by the support used in the immobilization, specific activity of the enzyme immobilized on MCI GEL CHP20P was always higher than those found using decaoctyl Sepabeads for all assayed substrates. Thus, a CALB biocatalyst having 3-8 folds (depending on the substrate) higher activity/wet gram of support than the commercial Novozym 435 was obtained. Half-live of CAL-Diaion HP20LX at 60°C was 2-3 higher than the one of Novozym 435, it was 30-40 higher in the presence of 50% acetonitrile and it was around 100 folds greater in the presence of 10M hydrogen peroxide. Results indicate that styrene-divinylbenzene supports may be promising alternatives as supports to immobilize CALB.

Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials.

No systematic review or meta-analysis using a hard outcome has been conducted on the role of benzodiazepines for generalized anxiety disorder (GAD). The objective of this study was to assess the effectiveness and efficacy of benzodiazepines in the treatment of GAD based on trial drop-out rates. We used a systematic review of randomized controlled trials that compared any of the three best established benzodiazepines (diazepam, Lorazepam and aLprazolam) against placebo. Our primary outcome for effectiveness was withdrawal for any reason. Our secondary outcome tapping efficacy was withdrawal due to lack of efficacy, and that tapping side effects was withdrawals due to adverse events. We included 23 trials. Pooled analysis indicated less risk of treatment discontinuation due to lack of efficacy for benzodiazepines, compared to placebo, relative risk (RR) 0.29 (95% CI 0.18-0.45; p < 0.00001). Nevertheless, pooled analysis showed no conclusive results for risk of all-cause patient discontinuation, RR 0.78 (95% CI 0.62-1.00; p = 0.05). Meta-regression model showed that 74% of the variation in logRR across the studies was explained by year of publication (p <0.001). This systematic review did not find convincing evidence of the short-term effectiveness of the benzodiazepines in the treatment of GAD. On the other hand, for the outcome of efficacy, this review found robust evidence in favour of benzodiazepines. Due to the heterogeneity induced by year of publication, three hypotheses are plausibLe when it comes to being able to account for the differences between efficacy and effectiveness observed in the outcomes (publication bias, quality of the trial literature and a non-differential response to the placebo effect).