Resultados totales (Incluyendo duplicados): 33514
Encontrada(s) 3352 página(s)
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245392
Dataset. 2021

DATASET RELATED TO ARTICLE: ARIPIPRAZOLE CYTOTOXICITY COINCIDES WITH ACTIVATION OF THE UNFOLDED PROTEIN RESPONSE IN HUMAN HEPATIC CELLS

  • Forno, Francesca
  • Maatuf, Yossi
  • Boukeileh, Shatha
  • Dipta, Priya
  • Mahameed, Mohamed
  • Darawshi, Odai
  • Ferreira, Vítor
  • Rada, Patricia
  • García Martínez, Irma
  • Gross, Einav
  • Priel, Avi
  • Valverde, Ángela M.
  • Tirosh, Boaz
Folder 1. Aripiprazole at Low Micromolar Concentration Induces ER Stress. This folder contains four folders Folder 1a These jpg files show the analysis by immunoblotting for phosphorylated IRE1, total IRE1, total PERK of cell extracts. Folder 1b. These pzt files show the relative quantification of phosphorylated IRE1 after 24 hours of treatment. Statistical significance is indicated by **P < 0.01; ***P < 0.001 Folder 1c. These 2 jpg files represent a time course of an cell extract vs control (4, 8, 12 and 24 h of IRE1 phosphorylation after Ari treatment. Folder 1d. The jpg files represent analysis of the extract cells after a treatment with Olanzapine., Folder 2. Aripiprazole promotes immobilization of calcium to the cytoplasm. The pzt file show the levels of intracellular calcium, the changes on it after the treatment with aripiprazole Statistical significance is indicated by *P < 0.05 of at least five independent measurements by ANOVA., Folder 3. IRE1 contributes more than PERK to Ari-induced cytotoxicity. Representative dot plots of forward vs. side scattering properties and percentage of PI-positive cells after treatment with ari are shown in the .pzt files of folders 3a and 3b. The data for the percentage of PI-positive cells shown in the files were obtained by measure with flow cytometry, after overnight treatment with DMSO, Ari (30 µM), and Ari with Z-VAD-FMK (25 µM) Statistical significance is indicated by *P < 0.05; **P < 0.01 by ANOVA for Z-VAD-FMK treatment and for the KO cells by paired Student’s t test., Folder 4 N-acetyl cysteine (NAC), BAPTA-AM, and EGTA do not protect from Aripiprazole-induced cell death. The .pzt files shown the data obtained by the treatment overnight of the cells HepG2 with DMSO and 30 µM of Ari in the absence or presence of NAC, BAPTA-AM, or EGTA. Percentage of PI-positive cells, as measured by flow cytometry after treatment, is shown. Data of three independent experiments ± S.D. is shown., Folder 5. GSH ethyl ester protects from Aripiprazole-induced cell death. The .pzt file shown the data obtained by the treatment overnight of the cells with DMSO and 30 µM of Ari in the absence or presence of GSH ethyl ester. Percentage of PI-positive cells, as measured by flow cytometry after treatment, is shown., Folder 6. Aripiprazole induces ER stress, and accumulation of lipids and calcium mobilization form the ER in primary mouse hepatocytes These folder contains several subfolders with the data for the panels A to H of the article, Demographics and pharmacokinectics data of the study. This folder contains five docs file with those data 1. Demographic characteristics of the volunteers from the studies, Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty-one healthy volunteers receiving a 10-mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro-aripiprazole plasma concentrations were measured by HPLC-MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0-12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245392
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245392
HANDLE: http://hdl.handle.net/10261/245392
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245392
PMID: http://hdl.handle.net/10261/245392
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245392
Ver en: http://hdl.handle.net/10261/245392
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245392

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245430
Dataset. 2020

DATASET RELATED TO ARTICLE: DETERMINING THE CONTRIBUTION OF A HIGH-FRUCTOSE CORN SYRUP FORMULATION TO HEPATIC GLYCOGEN SYNTHESIS DURING AD-LIBITUM FEEDING IN MICE

  • Nunzio, Giada di
  • Belew, Getachew D.
  • Torres, Alejandra N.
  • Silva, João Gabriel
  • Silva, Luis P.
  • Barosa, Cristina
  • Tavares, Ludgero
  • Jones, John G.
Folder 1. Raw 1H and 2H NMR data for the liver glycogen samples. Folder names with CTL refer to mice fed standard chow, folder names with HS1 refer to mice given sugar supplements with U-13C-glucose and folder names with HS2 refer to mice given sugar enriched with U-13C-fructose. These data can be opened and processed by widely available NMR processing software such as ACD labs, Mestre Nova and NUTS. Folder 2. Raw 1H and 13C NMR data for the liver glycogen samples. Folder names with CTL refer to mice fed standard chow, folder names with HS1 refer to mice given sugar supplements with U-13C-glucose and folder names with HS2 refer to mice given sugar enriched with U-13C-fructose. These data can be opened and processed by widely available NMR processing software such as ACD labs, Mestre Nova and NUTS. Folder 3. Spreadsheets for the NMR signal areas measured from the 2H NMR spectra and estimation of glycogen synthesis sources from direct and indirect pathways based on these data (Excel 1) and the NMR signals measured from the 13C NMR spectra and estimation of the contributions of [U-13C]glucose and [U-13C]fructose to glycogen synthesis (Excel 2)., Excessive sugar intake including high-fructose corn syrup (HFCS) is implicated in the rise of obesity, insulin resistance and non-alcoholic fatty liver disease. Liver glycogen synthesis is influenced by both fructose and insulin signaling. Therefore, the effect of HFCS on hepatic glycogenesis was evaluated in mice feeding ad-libitum. Using deuterated water: the fraction of glycogen derived from triose-P sources, Krebs cycle substrates, and direct pathway + cycling, was measured in 9 normal-chow fed mice (NC) and 12 mice fed normal chow plus a 55% fructose/45% glucose mix in the drinking water at 30% w/v (HFCS-55). This was enriched with [U-13C]fructose or [U-13C]glucose to determine the contribution of each to glycogenesis. For NC, direct pathway + cycling, Krebs cycle, and triose-P sources accounted for 66 ± 0.7%, 23 ± 0.8% and 11 ± 0.4% of glycogen synthesis, respectively. HFCS-55 mice had similar direct pathway + cycling (64 ± 1%) but lower Krebs cycle (12 ± 1%, p < 0.001) and higher triose-P contributions (24 ± 1%, p < 0.001). HFCS-55-fructose contributed 17 ± 1% via triose-P and 2 ± 0% via Krebs cycle. HFCS-55-glucose contributed 16 ± 3% via direct pathway and 1 ± 0% via Krebs cycle. In conclusion, HFCS-55 supplementation resulted in similar hepatic glycogen deposition rates. Indirect pathway contributions shifted from Krebs cycle to Triose-P sources reflecting HFCS-55-fructose utilization, while HFCS-55-glucose was incorporated almost exclusively by the direct pathway., European Commission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245430
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245430
HANDLE: http://hdl.handle.net/10261/245430
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245430
PMID: http://hdl.handle.net/10261/245430
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245430
Ver en: http://hdl.handle.net/10261/245430
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245430

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245436
Dataset. 2021

DATASET RELATED TO ARTICLE: ESTIMATING PENTOSE PHOSPHATE PATHWAY ACTIVITY FROM THE ANALYSIS OF HEPATIC GLYCOGEN 13C-ISOTOPOMERS DERIVED FROM [U-13C]FRUCTOSE AND [U-13C]GLUCOSE

  • Belew, Getachew D.
  • Nunzio, Giada di
  • Tavares, Ludgero
  • Silva, João Gabriel
  • Torres, Alejandra N.
  • Jones, John G.
Folder 1. Raw 13C NMR data for the liver glycogen samples. Folder names with CTL refer to mice fed standard chow, folder names with HS1 refer to mice given sugar supplements with U-13C-glucose and folder names with HS2 refer to mice given sugar enriched with U-13C-fructose. These data can be opened and processed by widely available NMR processing software such as ACD labs, Mestre Nova and NUTS. Folder 2. Spreadsheets for the NMR signal areas measured from the 13C NMR spectra and estimation of PPP fluxes from these signal areas, Hepatic PPP fluxes from both [U-13C] glucose and [U-13C]fructose precursors were assessed by 13C NMR analysis of glycogen 13C isotopomers Glucose-6-phosphate generated via glucokinase and the direct pathwayis preferentially utilized by PPP., European Commission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245436
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245436
HANDLE: http://hdl.handle.net/10261/245436
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245436
PMID: http://hdl.handle.net/10261/245436
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245436
Ver en: http://hdl.handle.net/10261/245436
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245436

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245445
Dataset. 2021

TRANSECTS AND VERTICAL PROFILES OF PMX AEROSOLS IN SANTO ANTÃO AND SÃO VICENTE, CAPE VERDE, IN OCTOBER 2019 - DATASET

  • Rodríguez, Sergio
  • López-Darias, Jessica
This file contains data of atmospheric aerosols particulate matter smaller than 10, 2.5 and 1 micron (PM10, PM2.5 and PM1) measured: -in vertical profiles, in sheets P1 to P3, -transects T1 to T3, -in ambient air at Porto Novo, Cova de Paul and Ribeira Grande each sheet contains the time, hour, latitude, longitude, temperature and humidity. Details on the methods used is described in: Sergio Rodríguez & Jessica López-Darias. Dust and tropical PMx aerosols in Cape Verde: sources, vertical distribution and stratified transport from North Africa. Atmospheric Research, 2021. DOI: xxx, This file contains data of aerosol PMx concentrations measured in Cape Verde (islands of Santo Antão and São Vicente) in October 2019 in the frame of the project VARDUSTSAL (PGC2018-099166-B-100; IP: Sergio Rodríguez) funded by the State Research Agency, the Ministry of Science, Innovation and Universities of Spain and the European Regional Development Fund. Data of vertical distributions and transfects of PMx near sources and in ambient air (including remote conditions) are reported. Details are provided in Rodríguez & López-Darias (2021)., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/245445
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245445
HANDLE: http://hdl.handle.net/10261/245445
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245445
PMID: http://hdl.handle.net/10261/245445
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245445
Ver en: http://hdl.handle.net/10261/245445
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245445

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245485
Dataset. 2021

DATASET RELATED TO ARTICLE: SAFETY AND CARDIOVASCULAR EFFECTS OF MULTIPLE-DOSE ADMINISTRATION OF ARIPIPRAZOLE AND OLANZAPINE IN A RANDOMISED CLINICAL TRIAL

  • Koller, Dora
  • Almenara, Susana
  • Mejía, Gina
  • Saiz-Rodríguez, Miriam
  • Zubiaur, Pablo
  • Román, Manuel
  • Ochoa, Dolores
  • Wojnicz, Aneta
  • Martín, Samuel
  • Romero-Palacián, Daniel
  • Navares-Gómez, Marcos
  • Abad-Santos, Francisco
[Adverse Drug Reactions and CT] The xls file shows relevant information about the treatment with aripiprazole and olanzapine, as well as about their possible adverse effects and the frequency with which they occur. [Genotypes] This is a doc files where It is showm the genotype and phenotype frequencies of the analysed polymorphisms, [Objective] To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. [Conclusions] OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245485
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245485
HANDLE: http://hdl.handle.net/10261/245485
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245485
PMID: http://hdl.handle.net/10261/245485
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245485
Ver en: http://hdl.handle.net/10261/245485
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245485

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245504
Dataset. 2021

DATASET RELATED TO ARTICLE: METABOLIC EFFECTS OF ARIPIPRAZOLE AND OLANZAPINE MULTIPLE-DOSE TREATMENT IN A RANDOMISED CROSSOVER CLINICAL TRIAL IN HEALTHY VOLUNTEERS: ASSOCIATION WITH PHARMACOGENETICS

  • Koller, Dora
  • Almenara, Susana
  • Mejía, Gina
  • Saiz-Rodríguez, Miriam
  • Zubiaur, Pablo
  • Román, Manuel
  • Ochoa, Dolores
  • Navares-Gómez, Marcos
  • Santos-Molina, Elena
  • Pintos-Sánchez, Elena
  • Abad-Santos, Francisco
The data generated or analysed during this study are obtained included in the clinical trial registry name, URL and registration number: TREATMENT-HV; EUDRACT 2018-000744-26; https://eudract.ema. europa.eu/. File1 Adverse events after the treatment with antipsychotics, Short-term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245504
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245504
HANDLE: http://hdl.handle.net/10261/245504
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245504
PMID: http://hdl.handle.net/10261/245504
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245504
Ver en: http://hdl.handle.net/10261/245504
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245504

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245512
Dataset. 2021

DATASET RELATED TO ARTICLE: SIMULTANEOUS DETERMINATION OF SIX ANTIPSYCHOTICS, TWO OF THEIR METABOLITES AND CAFFEINE IN HUMAN PLASMA BY LC-MS/MS USING A PHOSPHOLIPID-REMOVAL MICROELUTION-SOLID PHASE EXTRACTION METHOD FOR SAMPLE PREPARATION

  • Koller, Dora
  • Zubiaur, Pablo
  • Saiz-Rodríguez, Miriam
  • Abad-Santos, Francisco
  • Wojnicz, Aneta
File 1. This xls files shows the data related to the main charateristics used for the development and validation of the new method as long as the measures for letting assure the repeatability and intermediate precision and accuracy values. The results obtained for the pharmacokinetic parameters are also included in the file File 2 This jpg file shows the product ion spectra and chemical structures of the antipsychotics and their metabolites obtained by collision-induced dissociation (CID) of the indicated precursor ions [M+H]+. The fragmentation patterns of all analytes are indicated by an arrow on their chemical structure of each analyte. The results are presented as the percentage of counts versus Mass-to-Charge (m/z). All mass peaks have been normalized to the most abundant, A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in human plasma for the simultaneous determination of aripiprazole (ARI) and its metabolite dehydro-aripiprazole (DARI); olanzapine (OLA), risperidone (RIS), paliperidone (PAL), quetiapine (QUE), clozapine (CLO) and caffeine (CAF). CAF is included to the method because it can have an influence on drug metabolism due to competitive inhibition. The above mentioned compounds and their isotope-labeled internal standards were extracted from 200 µL human plasma samples by both, effective phospholipids-eliminating three-step microelution-solid-phase extraction (µ-SPE) and protein precipitation (PPT) for comparison. A combination of formic acid (0.2%)-acetonitrile (pH 3.0; 65:35, v/v) was used as mobile phase and the chromatogram was run under gradient conditions at a flow rate of 0.6 mL/min. Run time lasted 6 min, followed by a re-equilibration time of 3 min. All analytes were monitored by mass spectrometric detection operating in multiple reaction monitoring mode and the method was validated covering the corresponding therapeutic ranges: 0.18-120 ng/mL for ARI, 0.25-80 ng/mL for DARI, 1.00-100 ng/mL for OLA, 0.70-60 ng/mL for RIS, 0.20-30 ng/mL for PAL, 0.50-160 ng/mL for QUE, 0.50-1000 ng/mL for CLO, and finally 1200-3700 ng/mL for CAF. The method was validated based on the recommendations of regulatory agencies through tests of precision, accuracy, extraction recovery, identity confirmation, trueness, matrix effect, process efficiency, stability, selectivity, linearity and carry-over effect fulfilling the guideline requirements. Our µ-SPE method results in the elimination of more than 99% of early eluting and more than 92% of late-eluting phospholipids compared to PPT. Additionally, the method was successfully applied for quantifying ARI and OLA plasma concentrations from healthy volunteers., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245512
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245512
HANDLE: http://hdl.handle.net/10261/245512
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245512
PMID: http://hdl.handle.net/10261/245512
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245512
Ver en: http://hdl.handle.net/10261/245512
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245512

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245521
Dataset. 2021

DATASET RELATED TO ARTICLE: EFFECTS OF ARIPIPRAZOLE ON CIRCADIAN PROLACTIN SECRETION RELATED TO PHARMACOGENETICS IN HEALTHY VOLUNTEERS

  • Koller, Dora
  • Belmonte, Carmen
  • Saiz-Rodríguez, Miriam
  • Zubiaur, Pablo
  • Román, Manuel
  • Ochoa, Dolores
  • Abad-Santos, Francisco
File 1. Demographic characteristics of the volunteers from the aripiprazole study. File 2. Prolactin pharmacokinetic parameters after aripiprazole and ibuprofen administration. This xls file shows the modifications in the prolactin concentrations after the administration of aripiprazole or ibuprofen A It is been shown the prolactin concentrations versus time in women and men treated with aripiprazole compared to ibuprofen File 3 Genotype Matrix. The xls file show the detected genetic polymorphism associated with the effects of aripiprazole File 4 Aripiprazole and dehydro-aripiprazole pharmacokinetic parameters. File 5 The influence of polymorphisms on prolactin concentrations., Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty-one healthy volunteers receiving a 10-mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro-aripiprazole plasma concentrations were measured by HPLC-MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0-12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245521
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245521
HANDLE: http://hdl.handle.net/10261/245521
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245521
PMID: http://hdl.handle.net/10261/245521
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245521
Ver en: http://hdl.handle.net/10261/245521
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245521

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245524
Dataset. 2021

DATASET RELATED TO DOCTORAL THESIS: EVALUATION OF GENETIC POLYMORPHISMS ASSOCIATED WITH THE METABOLIC EFFECTS OF ARIPIPRAZOLE AND OLANZAPINE

  • Koller, Dora
File 1. Adverse events_TREATMENT The xls file shows relevant information about the treatment with aripiprazole and olanzapine, as well as about their possible adverse effects and the frequency with which they occur. File 2. Genotype Matrix. The xls file show the detected genetic polymorphism associated with the effects of aripiprazole and olanzapine, Aripiprazole altered pupil contraction. Olanzapine caused significant prolactin and weight elevation. Glucose levels in glucose tolerance test were higher after olanzapine treatment. Moreover, olanzapine had more cardiovascular effects than aripiprazole. However, aripiprazole was associated to more psychiatric and nervous system adverse drug reactions. Many polymorphisms may influence pupillometric and metabolic parameters along with cardiovascular changes and adverse events. Moreover, several polymorphisms had an effect on aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics. It seems that aripiprazole provokes less severe metabolic and cardiovascular changes, however, more adverse drug reactions were registered to it compared to olanzapine., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245524
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245524
HANDLE: http://hdl.handle.net/10261/245524
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245524
PMID: http://hdl.handle.net/10261/245524
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245524
Ver en: http://hdl.handle.net/10261/245524
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245524

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245528
Dataset. 2021

DATASET RELATED TO DOCTORAL THESIS: EFFECTS OF THE SECOND GENERATION ANTIPSYCHOTICS OLANZAPINE AND ARIPIPRAZOLE IN BETA CELL FUNCTIONALITY AND PANCREATIC ISLET PLASTICITY

  • Grajales, Diana
Folder 1. Analysis of in vivo chronic dietary treatment with both olanzapine and aripiprazole (5.5-6 mg/kg/d) for 6 months in WT females to assess disturbances in glucose metabolism as well as beta-cell dysfunction. Metabolic tests have been done before sacrifice: glucose tolerance test (GTT), insulin tolerance test (ITT), and glucose-stimulated insulin secretion (GSIS). The xls file shows the statistics analysis and raw data analysis of the parameters measured. The immunofluorescence and immunohistochemistry analysis are also included in xls file. The pzfx files can be opened with GraphPad Prism 8 XML Project show the relationships between some of the parameters showed in xls files. Folder 2. In vitro data in INS-1 cells. The xls files showed the quantification of the short-term impact of olanzapine (1-6 µM) and the long-term impact of both olanzapine and aripiprazole (1-6 µM) in glucose-stimulated insulin secretion (GSIS) and the western blot quantification of the molecular machinery associated with ER stress activation (mainly PERK/eIF2a and IRE1-alpha) in INS-1 cells after olanzapine/aripiprazole treatment with different concentrations (1-6 µM) for 4h. The pzfx files can be opened with GraphPad Prism 8 XML Project and show the relationships between some of the parameters showed in xls files., The incidence of Type 2 Diabetes Mellitus (T2DM) is reaching epidemic proportions. Recent investigations have demonstrated that long-term treatment with Second Generation Antipsychotics (SGAs), the main-line treatment for schizophrenia, can induce T2DM. Beta cell dysfunction is proposed as a plausible mechanism by which SGAs cause T2DM, but the process remains largely unknown. In this Thesis, we have investigated whether two unrelated SGAs, olanzapine, a common prescribed SGA with diabetogenic properties, and aripiprazole, a more recently developed SGA with less explored metabolic-side effects, can impact on beta cells. We analyzed beta cell functionality and pancreatic islet plasticity in two in vivo studies: female mice treated with olanzapine for 6 weeks via intraperitoneal and female mice fed an olanzapine- or aripiprazole-supplemented diet for 6 months. Additionally, we conducted gene expression analysis in islets of mice receiving the medicated diet and in vitro studies to evaluate beta cell functionality and the molecular mechanisms associated to the treatments. Our results evidenced that long-term treatment with olanzapine or aripiprazole induced weight gain, glucose intolerance and beta cell dysfunction, but the mechanisms behind these alterations are specific for each SGA. Whereas olanzapine effects in the pancreas in female mice seem to be dependent on an obesogenic-like phenotype, it activated endoplasmic reticulum (ER) stress in both INS-1 cells and pancreatic islets. Alleviation of olanzapine-induced ER stress with Tauroursodeoxycholic acid (TUDCA) recovered insulin secretion, suggesting that inhibition of insulin secretion by olanzapine is dependent on ER stress activation. On the other hand, aripiprazole treatment during 6 months induced serotonin production through tryptophan hydroxylase 1 (TPH1) activation in pancreatic islets. Moreover, beta cell hypertrophy and higher beta cell mass were found in aripiprazole-treated mice concomitantly to the activation of mTORC1/S6. Additionally, ex vivo experiments using pancreatic islets revealed that aripiprazole inhibition of insulin secretion was due to a reduction in calcium entry into the beta cell. Until now, regulation of the serotonergic system in islets has been associated to beta cell compensation in pregnancy and postnatal growth. Thus, in this Thesis, we have described for the first time the modulation of the serotonergic system in pancreatic islets by pharmacological treatment with aripiprazole, showing that serotonin production induced by this SGA plays a critical role in intra-islet functionality and beta cell mass and it might also explain other metabolic disturbances associated with aripiprazole treatment, European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

Proyecto: EC/H2020/721236
DOI: http://hdl.handle.net/10261/245528
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245528
HANDLE: http://hdl.handle.net/10261/245528
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245528
PMID: http://hdl.handle.net/10261/245528
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245528
Ver en: http://hdl.handle.net/10261/245528
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/245528

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