Publications by authors named "Paloma Méndez"

5 Publications

  • Page 1 of 1

Presence of diclofenac, estradiol, and ethinylestradiol in Manzanares River (Spain) and their toxicity to zebrafish embryo development.

Environ Sci Pollut Res Int 2021 May 4. Epub 2021 May 4.

Unity of Antibacterial Resistance, Spanish Food Safety and Nutrition Agency, Madrid, Spain.

Diclofenac (DCF), 17-β-estradiol (E2), and 17-α-ethinylestradiol (EE2) are emerging pollutants included in the first watch list agreed by European countries and set in the EU Water Directive. The objective of the present study was the analytical monitoring of DCF, E2, and EE2 in surface water and sediment of the Manzanares River in a stretch that crosses the city of Madrid, Spain, and to assess whether such environmental levels could affect the development of aquatic vertebrates through a zebrafish embryo-larval assay. Samples taken during two campaigns in the spring of 2015 were analyzed for DCF, E2, and EE2 by LC-MS or GC-MS. The levels of E2 and EE2 measured in surface water and sediments of the Manzanares were within the ranges reported in other Spanish and European studies; however, DCF levels were higher in the present study. The zebrafish embryos exposed to the Manzanares River water (0-144h) showed lethal effects and sublethal effects (developmental delay, bradycardia, and reduced locomotion). Nevertheless, these effects were not primarily associated with the levels of DCF, E2, and EE2 present in the Manzanares River, because representative mixtures of the field study prepared in the laboratory did not exhibit such toxicity to the zebrafish embryos.
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http://dx.doi.org/10.1007/s11356-021-14167-zDOI Listing
May 2021

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

Lancet 2017 12 31;390(10114):2779-2789. Epub 2017 Oct 31.

Academic Medical Center, Amsterdam, Netherlands.

Background: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm.

Methods: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689.

Findings: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group.

Interpretation: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability.

Funding: AbbVie.
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http://dx.doi.org/10.1016/S0140-6736(17)32641-7DOI Listing
December 2017

Metal-catalyzed oxidation and epoxidation of alpha-hydroxy vinyl and dienyl sulfoxides.

J Org Chem 2006 Feb;71(4):1569-75

Instituto de Química Orgánica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain.

Treatment of acyclic alpha-hydroxyalkyl alpha,beta-unsaturated sulfoxides with t-BuOOH/VO(acac)2 results in rapid oxidation to the unsaturated sulfones followed by an unusual regio- and stereoselective epoxidation at the unsaturated sulfones; this methodology has been applied to the preparation of carbohydrate-like fragments.
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http://dx.doi.org/10.1021/jo052244dDOI Listing
February 2006

Pharmacokinetics and pharmacodynamics of a single bolus of propofol 2% in healthy volunteers.

J Clin Pharmacol 2003 Apr;43(4):397-405

Service of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.

This study was undertaken to assess the bioequivalence between a new formulation of propofol 2% and the commercially available product Diprivan. Secondary objectives were to compare the times to onset of and emergence from hypnosis, the hemodynamic effects, and the safety profiles. Twelve healthy male volunteers were included in a randomized crossover study. Subjects were administered a 2-mg/kg single bolus injection of each formulation separated by a 7- to 10-day washout period. Plasma propofol was determined by reversed-phase liquid chromatography with fluorescence detection. Eleven subjects completed the study, and both formulations were considered bioequivalent. There were no serious or severe adverse events. The concentration-time profiles of all the subjects could adequately be described using a three-compartment model. The mean times to cessation of counting out loud (17 vs. 18 s) and to eye opening (245 vs. 244 s) were not statistically different between treatment groups. Moreover, they seem to show some degree of pharmacodynamic bioequivalence, although a higher number of subjects are necessary to unequivocally demonstrate it.
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http://dx.doi.org/10.1177/0091270003251391DOI Listing
April 2003

Nucleophilic epoxidation of alpha'-hydroxy vinyl sulfoxides.

J Org Chem 2002 Nov;67(23):8166-77

Instituto de Química Orgánica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain.

The nucleophilic epoxidation of a variety of alpha'-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing scenario. The use of t-BuOOLi in Et(2)O allows for a highly syn-selective epoxidation-oxidation. The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing (S,S(S)) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In contrast, the (R,S(S)) diastereomers (4e-g) show diminished reactivities and a very substrate-dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical correlations and an X-ray crystal structure.
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http://dx.doi.org/10.1021/jo026182sDOI Listing
November 2002