Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans

Growing cells of the Candida albicans trehalose- deficient mutant tps1/tps1 were extremely sensitive to severe oxidative stress exposure (H2O2). However, their viability was not affected after saline stress or heatshock treatments, being roughly equivalent to that of the parental strain. In wild-type cells, these adverse conditions induced the intracellular accumulation of trehalose together with activation of trehalose-6P synthase, whereas the endogenous trehalose content and the corresponding biosynthetic activity were barely detectable in the tps1/tps1 mutant. The addition of cycloheximide did not prevent the marked induction of trehalose-6P synthase activity. Furthermore, the presence of H2O2 decreased the level of TPS1 mRNA expression. Hence, the conspicuous trehalose accumulation in response to oxidative stress is not induced by increased transcription of TPS1. Our results are consistent with a specific requirement of trehalose in order to withstand a severe oxidative stress in C. albicans, and suggest that trehalose accumulation observed under these conditions is a complex process that most probably involves post-translational modifications of the trehalose synthase complex

Lack of Functional Trehalase Activity in Candida parapsilosis Increases Susceptibility to Itraconazole

Central metabolic pathways may play a major role in the virulence of pathogenic fungi. Here, we have investigated the susceptibility of a Candida parapsilosis mutant deficient in trehalase activity (atc1Δ/ntc1Δ strain) to the azolic compounds fluconazole and itraconazole. A time-course exposure to itraconazole but not fluconazole induced a significant degree of cell killing in mutant cells compared to the parental strain. Flow cytometry determinations indicated that itraconazole was able to induce a marked production of endogenous ROS together with a simultaneous increase in membrane potential, these effects being irrelevant after fluconazole addition. Furthermore, only itraconazole induced a significant synthesis of endogenous trehalose. The recorded impaired capacity of mutant cells to produce structured biofilms was further increased in the presence of both azoles, with itraconazole being more effective than fluconazole. Our results in the opportunistic pathogen yeast C. parapsilosis reinforce the study of trehalose metabolism as an attractive therapeutic target and allow extending the hypothesis that the generation of internal oxidative stress may be a component of the antifungal action exerted by the compounds currently available in medical practice

Con la medida militar de convertir en baluarte desde 1836 para la defensa de la Ciudad contra los carlistas la iglesia parroquial de S. Isidoro, han desaparecido completamente algunos de sus altares, la pila bautismal...

Tít. Tomado del inicio del textoFecha de publicación deducida de la fecha del fin del texto (15 de marzo de 1841)Sin mención de imprenta ni lugar de impresión, pero con toda probabilidad impreso en Ovied

Effects of creatine supplementation in taekwondo practitioners

Introduction: Taekwondo (TKD) is a combat sport, which has also been proposed as a fitness program, with a strong anaerobic component. Creatine (Cr) supplementation is used to improve both anaerobic exercise performance and body composition. Therefore, Cr supplementation could be beneficial in TKD. Aims: To determine the effect of Cr supplementation (50 mg/kg body wt) on body composition, anaerobic power and blood chemistry in young male TKD practitioners. Methods: Ten male TKD practitioners (age [20 ± 2 yr], height [1.69 ± 0.06 m], and mass [67 ± 9.8 kg]) participated in a placebo-controlled, double blind, crossover study. Body composition (DEXA), anaerobic power (Wingate Test), blood lactate and blood chemistry were measured before and after supplementation. Differences between data before and after supplementation were calculated for each treatment (Cr and Placebo) and were compared using the Wilcoxon signed-rank test. Results: Fat mass (kg) decreased after placebo (Mdn [IqR] = -0.75 [-1.44 to 0.03]) and increased following Cr intake (0.17 [-0.77 to 1.13] kg) (Z = 2.191, p < 0.028, r = 0.49). Serum triglyceride concentration (mg/mL) increa - sed after Cr (45.00 [-7.50 to 75.00]) and decrease with placebo (-7.00 [-10.75 to 12.00]) (Z = 2.090, p < 0.037, r = 0.47). No changes were found in others parameters. Conclusion: Cr supplementation may increase fat mass and serum triglycerides concentration in young male TKD practitioners without improvement in anaerobic power. Cr supplementation appears to be safe, but athletes should be careful when they want to loss fat

Efficacy and safety of the metformin-mazindol anorectic combination in rat

The current study investigates the anorectic interaction and safety of the mazindol-metformin combination in rats. Isobologram and interaction index were used to determine anorectic interaction between mazindol and metformin in the sweetened milk model. The safety profile of the mazindol-metformin combination was determined by measuring anxiety, blood pressure, hematic biometry and blood chemistry. An acute dose of mazindol and metformin administered per os, individually or as a mixture, has reduced the milk consumption in rats in a dose-dependent manner. Theoretical effective dose 40 (ED40t) did not differ from the experimental effective dose 40 (ED40e) obtained with the mazindol-metformin mixture in the anorexia experiments, by Student´s t-test. In addition, the interaction index confirmed the additive anorectic effect between both drugs. A single oral dose of ED40e mazindol-metformin mixture induced anxiolysis in the elevated plus-maze test. Moreover, oral administration of mazindol-metformin combination for 3 months significantly decreased glycemia, but not blood pressure nor other parameters of hematic biometry and blood chemistry. Results suggest that mazindol-metformin combination exerts an additive anorectic effect, as well as anxiolytic and hypoglycemic properties. Mazindol-metformin combination might be useful in obese patients with anxiety disorders or diabetes risk factors

Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization

Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a physicochemical characterization of a biosimilar trastuzumab focused on the attributes related to the pharmacokinetic response. Capillary isoelectrofocusing (cIEF) and cation exchange chromatography (CEX) were used to evaluate charge heterogeneity; glycosylation profiles were assessed through hydrophilic interaction liquid chromatography (HILIC); aggregates content was evaluated through size exclusion chromatography (SEC) while binding affinity to FcRn was evaluated using isothermal titration calorimetry (ITC). The biosimilar trastuzumab and its reference product exhibited a high degree of similarity for the evaluated attributes. In regard to the pharmacokinetic parameters, randomized, double blind, and two-arm parallel and prospective study was employed after the administration of a single intravenous dose in healthy volunteers. No significant differences were found between the pharmacokinetic profiles of both products. Our results confirm that similarity of the critical quality attributes between a biosimilar product, obtained from a different manufacturing process, and the reference product resulted in comparable pharmacokinetic profiles, diminishing the uncertainty related to the biosimilar&apos;s safety and efficacy

Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.Estas recomendações baseadas na evidência detalham o uso da enteroscopia assistida por dispositivo no manejo clínico das doenças do intestino delgado. Um conjunto de Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta técnica, o seu papel nos algoritmos de manejo de cada indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores

Corrigendum to ‘a horizon scan exercise for aquatic invasive alien species in Iberian inland waters’

info:eu-repo/semantics/publishedVersio

Black list and Alert list of the Aquatic Invasive Alien Species in the Iberian Peninsula: an action of the LIFE INVASAQUA

Resumen del trabajo presentado en VI Congreso Nacional sobre Especies Exóticas Invasoras y I Congreso Ibérico sobre EEI (EEI 2022) celebrado en Navarra del 20 al 23 de abril de 2022.One of the objectives of LIFE INVASQUA project is to develop tools that will be more efficient the Early Warning and Rapid Response (EWRR) framework for Invasive Alien Species in the Iberian Peninsula. Horizon scanning for high-risk IAS is basic in implementing measures to reduce new invasions, developing Alert lists, and to focus effort in the species already established, for instance making a Black list. We developed a trans national horizon scanning exercise focused on inland waters of Spain and Portugal in order to provide a prioritized lists (Black list and Alert list) of aquatic IAS that may pose a threat to aquatic ecosystems and socio economic sectors in the future. We followed a step approach of existing information about IAS (Plants, Freshwater Invertebrates, Estuarine Invertebrates and Vertebrates; 127 established taxa in Black list; 90 non established taxa in Alert list) combining with an expert scoring of prioritized taxa. IAS established in the Iberian aquatic system consistently highlighted as the worst included vertebrates (e.g. Cyprinus carpio, Gambusia holbrooki, Silurus glanis), freshwater and estuarine invertebrates (e.g. Procambarus clarkii, Dreissena polymorpha, Pacifastacus leniusculus, Ficopomatus enigmaticus, Callinectes sapidus, Corbicula fluminea) and plants (e.g. Eichhornia crassipes, Azolla filiculoides, Ludwigia grandiflora). Amongst taxa not yet established (Alert list), expert pointed to Perna viridis, Hydroides dirampha, Dreissena bugensis, Procambarus fallax f. virginallis, Perccottus glenii with higher risk of invasion, ecological and socioeconomic impacts. Over 20.6% of the taxa in the preliminary black list received no votes (no prioritization) by experts, 17.8% in the innitial alert list. Our horizon scanning approach is inclusive of all-taxa, prioritizes both established and emerging biological threats across trans-national scales, and considers not only the ecological impact, but also potential direct economic consequences as well as the manageability of invasive species.This work received funds from the LIFE Programme (LIFE17 GIE/ES/000515)