Publications by authors named "M Toledo"

619 Publications

Pharmacokinetic variability of eslicarbazepine in real clinical practice.

Epilepsy Behav 2021 Sep 11;124:108284. Epub 2021 Sep 11.

Department of Neurology, Instituto de investigacion Sanitaria Princesa, La Princesa University Hospital, Madrid, Spain.

Introduction: Eslicarbazepine acetate (ESL) is a sodium channel blocker indicated for partial-onset seizures with or without secondary generalization, at a single daily dose. There are very few publications on the levels of ESL metabolites in real clinical practice.

Objective: To describe the serum levels of licarbazepine (main metabolite of ESL) in patients with refractory epilepsy in real clinical practice. To evaluate the influence of age, sex, and polytherapy on levels and adverse effects.

Methods: This study involved a retrospective analysis of patients diagnosed with epilepsy treated with ESL for whom plasma levels of licarbazepine were available, measured by spectrophotometry.

Results: Sixty-four patients were included. One patient had licarbazepine levels of 0 (admitted not taking the drug) was not analyzed. Mean licarbazepine levels of 7.66 µg/mL (400 mg/day dose), 16.56 µg/mL (800-mg dose), and 20.80 µg/mL (1200 mg) were significantly different. There was a significant correlation between daily dose and serum levels (p < 0.05) and between the concentration/dose ratio and lower to higher doses (p < 0.05). Pharmacokinetic variability (coefficient of variation for the concentration/dose ratio) was 33.2%. We found a decrease in the concentration/dose ratio in the 1200 mg/day dose, compared to lower doses. We did not find differences by sex or intake of other antiepileptic inducers or metabolic inhibitors. Fifteen patients (23.8%) had mild nonsymptomatic hyponatremia.

Conclusion: These results suggest that it is not necessary to routinely determine licarbazepine levels. In specific cases, licarbazepine levels can be useful to assess adherence to treatment and for personalized dose adjustment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.108284DOI Listing
September 2021

Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy-expert opinion.

Epilepsy Behav 2021 Sep 8;123:108270. Epub 2021 Sep 8.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Clinical trial results have demonstrated that adjunctive cenobamate (CNB) substantially decreases seizure frequency in adults with uncontrolled focal onset seizures with an acceptable and well-identified safety profile. This manuscript summarizes an expert panel's recommendations regarding optimized CNB treatment of epilepsies with focal onset seizures. Cenobamate, when slowly titrated to the target maintenance dose, represents an effective new antiseizure medication (ASM) with a comparatively high rate of seizure freedom relative to existing treatment options. This paper reviews selection of suitable CNB treatment candidates, realistic treatment expectations and goals, appropriate CNB target doses, and methods to mitigate or avoid potential adverse events. Cenobamate can be a promising therapeutic choice for adult people with epilepsy with focal onset seizures who do not reach adequate seizure control despite treatment with conventional ASMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.108270DOI Listing
September 2021

Correlation of Hair Cortisol and Interleukin 6 with Structural Change in the Active Progression of Keratoconus.

J Cataract Refract Surg 2021 Aug 30. Epub 2021 Aug 30.

Department of Ophthalmology at University of Sao Paulo, Sao Paulo, Brazil Department of Ophthalmology at Federal University of Goias, Goiania, Brazil Department of Computer Science at Federal University of Minas Gerais, Belo Horizonte, Brazil Nucleus of Toxicopharmacological Studies and Research - NEPET, Faculty of Pharmacy, Federal University of Goias, Goiania, Brazil. Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil.

Purpose: Evaluate interleukin and hair cortisol concentrations (HCC) in progressive keratoconus (KC) and compare them with KC stable eyes and healthy controls. Determine the correlation of these inflammatory mediators and HCC and their relationship with structural damage represented by increased corneal curvature.

Setting: University of Sao Paulo.

Design: Prospective observational comparative study.

Methods: The study included 135 eyes of 75 patients.The concentrations of tear cytokines: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70 and tumor necrosis factor α (TNFα) were obtained by capillary flow and measured using flow cytometer.HCC were determined from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry.

Results: Only IL6 was increased in progressive KC tears compared with stable KC (6.59 ± 3.25 pg/ml vs. 4.72 ± 1.91pg/ml; p<0.0001) with a positive correlation between IL6 and maximum keratometry (Kmax) (p<0.0001).Progressive KC exhibited significantly higher HCC than stable KC (0.624 ± 0.160ng/mg vs. 0.368 ± 0.0647ng/mg; p< 0.0001) and healthy controls (0.624 ± 0.160ng/mg vs. 0.351 ± 0.0896ng/mg; p<0.0001).There was a significant correlation between HCC and Kmax (p<0.0001).

Conclusions: Keratoconus eyes that are progressing have a higher concentration of IL-6 and long-term cortisol than patients with stable forms of KC;Second, there is a significant correlation between this increase in IL6 and cortisol with corneal structural damage.Finally, there is a meaningful relationship between this interleukin and the past few months' cortisol levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.jcrs.0000000000000809DOI Listing
August 2021

A new Trypanosoma cruzi genotyping method enables high resolution evolutionary analyses.

Mem Inst Oswaldo Cruz 2021 30;116:e200538. Epub 2021 Aug 30.

Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Genômica Funcional, Curitiba, PR, Brasil.

Background: Trypanosoma cruzi is an important human pathogen in Latin America with nearly seven million people infected. It has a large degree of genetic diversity, classified into six discrete typing units (DTUs), which probably influences its physiological behavior and clinical manifestations. Several genotyping methods are available, with distinct performance on easiness, cost, resolution and applicability; no method excels in all parameters.

Objectives And Methods: To devise a molecular method for T. cruzi genotyping, based on polymerase chain reaction (PCR) amplification of a single target with multiple copies in the nuclear genome by large scale sequencing. We have applied this method to 29 T. cruzi isolates, comprising all described DTUs.

Findings: We were able to classify all samples into sub DTU level with high robustness. Evolutionary relationship between DTUs were ascertained, suggesting that TcIII and TcIV DTUs are non-hybrid, and DTU IV is more similar to the common ancestral.

Conclusion: As the TS-LSS method is based on a single PCR reaction, comprising several copies of the target, it is probably useful for clinical samples, when the amount of DNA is a limiting factor. As large scale sequencing systems become more common, the TS-LSS method can be increasingly applied for T. cruzi genotyping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0074-02760200538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405150PMC
September 2021

CRISPR/Cas9 mediated CXCL4 knockout in human iPS cells of polycythemia vera patient with JAK2 V617F mutation.

Stem Cell Res 2021 Aug 5;55:102490. Epub 2021 Aug 5.

Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. Electronic address:

The chemokine CXCL4/platelet factor 4 (PF4) gene, a key player in myelofibrosis, was knocked out by CRISPR/Cas9 in induced pluripotent stem cells (iPS cells) of a polycythemia vera (PV) patient with JAK2 V617F mutation. Two CXCL4 iPS cell lines with and without JAK2 V617F mutation (UKAi002-B-1 and UKAi002-A-1, respectively) were generated. CXCL4 iPS cells showed deletion of exon 1 and complete loss of CXCL4 protein. Pluripotency of iPS cells was confirmed by expression of pluripotency markers and trilineage differentiation. CXCL4 iPS cells are expected to provide a valuable tool for investigating the role of CXCL4 in human diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scr.2021.102490DOI Listing
August 2021
-->