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2.
Sci Rep ; 14(1): 11780, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782938

ABSTRACT

The study analyzes how the magnitude and angle of the speed of soccer players change according to the distance to the ball and the phases of the game, namely the defensive and attacking phases. We observed how the role played in the team (goalkeeper, defender, midfielder, or forward) strongly determines the speed pattern of players. As a general trend, the speed's modulus is incremented as their position is closer to the ball, however, it is slightly decreased when arriving at it. Next, we studied how the angle of the speed with the direction to the ball is related to the distance to the ball and the game phases. We observed that, during the defensive phase, goalkeepers are the players that run more parallel to the ball, while forwards are the ones running more directly to the ball position. Importantly, this behavior changes dramatically during the attacking phase. Finally, we show how the proposed methodology can be used to analyze the speed-angle patterns of specific players to understand better how they move on the pitch according to the distance to the ball.

3.
Front Public Health ; 11: 1195409, 2023.
Article in English | MEDLINE | ID: mdl-37546295

ABSTRACT

Introduction: Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022. Methods: In 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis. Results: In 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting). Discussion: Over five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Adult , Aged , Child , Humans , Cohort Studies , COVID-19 Vaccines , Europe/epidemiology , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Seasons , Vaccine Efficacy , Male , Female , Adolescent , Young Adult , Middle Aged
4.
Lancet Reg Health Eur ; 31: 100675, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37547274

ABSTRACT

Background: Vaccine effectiveness (VE) studies with long-term follow-up are needed to understand durability of protection against severe COVID-19 outcomes conferred by primary-series vaccination in individuals not receiving boosters. COVIDRIVE is a European public-private partnership evaluating brand-specific vaccine effectiveness (VE). We report a prespecified interim analysis of primary-series AZD1222 (ChAdOx1 nCoV-19) VE. Methods: Seven Study Contributors in Europe collected data on individuals aged ≥18 years who were hospitalised with severe acute respiratory infection (June 1st, 2021-September 5th, 2022) and eligible for COVID-19 vaccination prior to hospitalisation. In this test-negative case-control study, individuals were defined as test-positive cases or test-negative controls (SARS-CoV-2 RT-PCR) and were either fully vaccinated (two AZD1222 doses, 4-12 weeks apart, completed ≥14 days prior to symptom onset; no booster doses) or unvaccinated (no COVID-19 vaccine prior to hospitalisation). The primary objective was to estimate AZD1222 VE against COVID-19 hospitalisation. A literature review and meta-regression were conducted to contextualise findings on durability of protection. Findings: 761 individuals were included during the 15-month analysis period. Overall AZD1222 VE estimate was 72.8% (95% CI, 53.4-84.1). VE was 93.8% (48.6-99.3) in participants who received second AZD1222 doses ≤8 weeks prior to hospitalisation, with spline-based VE estimates demonstrating protection (VE ≥ 50%) 30 weeks post-second dose. Meta-regression analysis (data from seven publications) showed consistent results, with ≥80% protection against COVID-19 hospitalisation through ∼43 weeks post-second dose, with some degree of waning. Interpretation: Primary-series AZD1222 vaccination confers protection against COVID-19 hospitalisation with enduring levels of VE through ≥6 months. Funding: AstraZeneca.

5.
Expert Rev Vaccines ; 21(12): 1701-1710, 2022 12.
Article in English | MEDLINE | ID: mdl-36261918

ABSTRACT

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Influenza, Human/prevention & control , Public-Private Sector Partnerships
6.
Article in English | MEDLINE | ID: mdl-35742384

ABSTRACT

Post-marketing safety surveillance of new vaccines aimed to be administered during pregnancy is crucial to orchestrate efficient adverse events evaluation. This is of special relevance in the current landscape of new vaccines being introduced in the pregnant women population, and particularly due to the recent administration of COVID-19 vaccines in pregnant women. This multi-center prospective cohort study, nested within the WHO-Global Vaccine Safety-MCC study, involved two hospitals in the Valencia region. Hereby, the incidence rates of seven perinatal and neonatal outcomes in the Valencia region are presented. The pooled data analysis of the two Valencian hospitals allowed the estimation of incidence rates in the Valencia Region (per 1000 live births): 86.7 for low birth weight, 78.2 for preterm birth, 58.8 for small for gestational age, 13 for congenital microcephaly, 0.4 for stillbirth, 1.2 for neonatal death and 6.5 for neonatal infection. These figures are in line with what is expected from a high-income country and the previously reported rates for Spain and Europe, except for the significantly increased rate for congenital microcephaly. Regarding the data for maternal immunization, the vaccination status was collected for 94.4% of the screened pregnant women, highlighting the high quality of the Valencian Vaccine Registry. The study also assessed the Valencian hospitals' capacity for identifying and collecting data on maternal immunization status, as well as the applicability of the GAIA definitions to the identified outcomes.


Subject(s)
COVID-19 , Microcephaly , Premature Birth , Vaccines , Adolescent , COVID-19 Vaccines , Female , Hospitals , Humans , Infant, Newborn , Morbidity , Pregnancy , Pregnancy Outcome , Premature Birth/epidemiology , Prospective Studies
7.
Sci Educ (Dordr) ; : 1-21, 2022 May 13.
Article in English | MEDLINE | ID: mdl-35582209

ABSTRACT

A study is presented that analyzed the pedagogical efficacy of reading opinion articles about methods of science, published in the media, in order to improve the meta-scientific understanding of 52 preservice primary teachers (PPTs) with regard to the topic. To this end, an activity was designed taking an explicit and reflective approach. The design of the activity required a short teaching intervention when being implemented in class in order to facilitate its integration into the program of the subject of science teaching. Before doing the activity, the PPTs' prior conceptions about the nature of methods of science were diagnosed using the Opinions about Science, Technology and Society Questionnaire (COCTS, in its Spanish acronym). The activity consisted of reading the articles, and then responding in small work groups to a series of questions for reflection and debate on the topic. The groups' responses were then shared and discussed in class. Once the activity had finished, the PPTs responded to the questionnaire again (post-test) in order to evaluate how their conceptions had progressed. There was an improvement in their understanding of various aspects of the nature of methods of science (e.g., scientists use a variety of methods in their research depending on the object of study, the context, and the resources available, or that the scientific method is an idealized, simplistic, and therefore poor representation of how scientists do research). These results show that the activity was effective in getting the PPTs to reflect and learn about the topic. Finally, the limitations of the study are discussed (e.g., the limited time frame to implement the activity and evaluate results), and some future research perspectives are given to improve the understanding of PPTs about the nature of methods of science.

9.
Sci Educ (Dordr) ; 31(3): 685-711, 2022.
Article in English | MEDLINE | ID: mdl-34548752

ABSTRACT

The obstacles and difficulties that science teachers face when teaching the nature of science (NOS) are well-known. Nonetheless, little is known of what science teacher educators (STEs) know, do, and think about this issue. Thus, a study with 142 Spanish STEs was conducted. This was aimed at analysing (i) what preparation the STEs have to teach NOS, (ii) what educational experience they have about NOS, (iii) what importance they give to NOS in their training plans, (iv) when NOS should be taught, (v) how to integrate NOS in science education, (vi) how to teach NOS, (vii) what to teach about NOS, and (viii) the influences interconnecting the STEs' preparation, experience, and opinions regarding NOS teaching. Among the results, it was found that most STEs state that they have ample knowledge of NOS, are well prepared pedagogically to teach it, and have extensive experience in teaching it. However, there was some mismatch between their stated preparation and their experience teaching NOS. In addition, they think that NOS should be taught from early ages and be treated as cross-cutting content in science education. They also consider that, when teaching NOS, an implicit approach is just as effective as an explicit-reflective one. As for their selection of NOS content to include, they are fundamentally divided into two groups - those who select only epistemic aspects of NOS and those who select a balanced proportion of both epistemic and non-epistemic aspects. The limitations of the study are reported along with the issues that require further research.

10.
Cult Stud Sci Educ ; 16(4): 1015-1028, 2021.
Article in English | MEDLINE | ID: mdl-34868385

ABSTRACT

The global COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a plethora of information published in the media. Conceived as a socioscientific issue of great relevance currently, this article highlight the educational potential of some media news about the pandemic to reflect and learn about the nature of science (NOS). To this end, a theoretical foundation is first presented regarding the reading of science news published in the media as an educational resource to learn about NOS. Secondly, a proposal is presented on how this might be addressed in the science classroom. The proposal is illustrated by four news items, intentionally selected as examples, which have been published in the Spanish digital press. The aspects of NOS that are discussed in the context of the news items selected are: tentativeness of scientific knowledge, role of error in scientific research, role of debate in the development of science, importance of models and modelling in scientific research, and ethics in science.


La pandemia mundial de la COVID-19, provocada por el virus SARS-CoV-2, ha dado lugar a una gran cantidad de información publicada en los medios. Concebida como problemática sociocientífica de relevancia en la actualidad, este artículo destaca el potencial educativo de algunas noticias de los medios sobre la pandemia para reflexionar y aprender sobre naturaleza de la ciencia (NOS). Para ello, en primer lugar, se expone una fundamentación teórica relativa a la lectura de noticias de ciencia publicadas en los medios como recurso didáctico para aprender sobre NOS. En segundo lugar, se presenta una propuesta de cómo se podría abordar esto en clases de ciencia. La propuesta se ilustra mediante cuatro noticias, seleccionadas intencionadamente y a modo de ejemplos, que fueron publicadas en la prensa digital española. Los aspectos de NOS que se discuten en el contexto de las noticias son: provisionalidad del conocimiento científico, importancia de los modelos y la modelización en la investigación científica, y la ética en la ciencia.

11.
Vaccine ; 39(29): 3964-3973, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34092427

ABSTRACT

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) is an IMI funded public-private platform that aims to annually estimate brand-specific influenza vaccine effectiveness (IVE), for public health and regulatory purposes. IVE analyses and reporting are conducted by public partners in the consortium. In 2019/20, four primary care-based test-negative design (TND) studies (Austria, England, Italy (n = 2)), eight hospital-based TND studies (Finland, France, Italy, Romania, Spain (n = 4)), and one population-based cohort study (Finland) were conducted. The COVID-19 pandemic affected influenza surveillance in all participating study sites, therefore the study period was truncated on February 29, 2020. Age-stratified (6 m-17y, 18-64y, ≥65y), confounder-adjusted, site-specific adjusted IVE estimates were calculated and pooled through meta-analysis. Parsimonious confounder-adjustment was performed, adjusting the estimates for age, sex and calendar time. TND studies included 3531 cases (351 vaccinated) and 5546 controls (1415 vaccinated) of all ages. IVE estimates were available for 8/11 brands marketed in Europe in 2019. Most children and adults < 64y were captured in primary care setting and the most frequently observed vaccine brand was Vaxigrip Tetra. The estimate against any influenza for Vaxigrip Tetra in primary care setting was 61% (95%CI 38-77) in children and 32% (95%CI -13-59) in adults up to 64y. Most adults ≥ 65y were captured in hospital setting and the most frequently observed brand was Fluad, with an estimate of 52% (95%CI 27-68). The population-based cohort covered 511,854 person-years and two vaccine brands. In children aged 2-6y, the IVE against any influenza was 68% (95%CI 58-75) for Fluenz Tetra and 71% (56-80) for Vaxigrip Tetra. In adults ≥ 65y, IVE against any influenza was 29% (20-36) for Vaxigrip Tetra. DRIVE is a growing platform. Public health institutes with surveillance data and hospitals in countries with high influenza vaccine coverage are encouraged to join DRIVE.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Adult , Austria , Case-Control Studies , Child , Cohort Studies , England , Europe/epidemiology , Finland , France , Humans , Influenza A Virus, H3N2 Subtype , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Italy , Pandemics , Romania , SARS-CoV-2 , Seasons , Spain , Vaccination
12.
Article in English | MEDLINE | ID: mdl-33916143

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) forced a stoppage in the 2019/2020 season of LaLiga™, possibly influencing performance indicators in the return to competition. Therefore, here, we evaluated whether the stoppage due to the coronavirus 2019 disease (COVID-19) lockdown influenced physical performance compared to the start of LaLigaTM in terms of high-intensity efforts. Using a semi-automatic, multiple-camera system, running activities during 22 matches were analyzed. We compared the first 11 matches of the season (pre-lockdown) with the 11 matches just after the restart of LaLiga™ (post-lockdown). The results showed higher (p < 0.05) performance in the pre-lockdown period compared with the post-lockdown period, including in medium-speed running (14.1-21 km/h), high-speed running (21.1-24 km/h), and sprinting speed running distances (>24 km/h). However, the number of accelerations/min and decelerations/min were significantly higher during the post-lockdown period. Therefore, we conclude that the stoppage due to the COVID-19 lockdown generated lower physical performance in the post-lockdown period compared with the pre-lockdown period, most likely due to the accumulation of matches (congested schedules).


Subject(s)
Athletic Performance , COVID-19 , Soccer , Communicable Disease Control , Humans , SARS-CoV-2
13.
Article in English | MEDLINE | ID: mdl-33504081

ABSTRACT

The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project is a public-private partnership aiming to build capacity in Europe for yearly estimation of brand-specific influenza vaccine effectiveness (IVE). DRIVE is a five-year project funded by IMI (Innovative Medicines Initiative). It was initiated as a response to the guidance on influenza vaccines by EMA (European Medicines Agency), which advised vaccine manufacturers to work with public health institutes to set up a joint IVE study platform. The COVID-19 pandemic reached Europe in February 2020 and overlapped with the 2019/2020 influenza season only in the last weeks. However, several elements of the DRIVE study network were impacted. The pandemic specifically affected the study sites' routines and the subsequent assessment of the 2019/20 influenza season. Moreover, the current social distancing measures and lockdown policies across Europe are expected to also limit the circulation of influenza for the 2020/21 season, and therefore the impact of COVID-19 will be higher than in the season 2019/20. Consequently, DRIVE has planned to adapt its study platform to the COVID-19 challenge, encompassing several COVID-19 particularities in the study procedures, data collection and IVE analysis for the 2020/21 season. DRIVE will study the feasibility of implementing these COVID-19 components and establish the foundations of future COVID-19 vaccine effectiveness studies.


Subject(s)
COVID-19 , Influenza Vaccines/administration & dosage , Influenza, Human , Communicable Disease Control , Europe , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics , Seasons , Vaccination
14.
Article in English | MEDLINE | ID: mdl-33333901

ABSTRACT

Soccer is a high-complexity sport in which 22 players interact simultaneously in a common space. The ball-holder interacts with their teammates by passing actions, establishing a unique communication among them in the development of the game in its offensive phase. The main aim of the present study was to analyze the pass action according to the trajectory of the ball receiver and the space for receiving the ball in terms of success at the end of play. Twenty La Liga 2018/2019 matches of two elite teams were analyzed. A system of notational analysis was used to create 11 categories based on context, timing and pass analysis. The data were analyzed using chi-squared analysis. The results showed that the main performance indicators were the efficiency of the pass, the zone of the field, the trajectory of the receiver and the reception space of the ball, which presented a moderate association with the end of play (p < 0.001). We concluded that receiving the ball on approach and in separation increased the probability of success by 5% and 7%, respectively, and a diagonal run increased the probability by 7%. Moreover, the combined analysis of these variables would improve the team performance.


Subject(s)
Athletic Performance , Soccer , Achievement , Probability
15.
Arq. bras. oftalmol ; 83(1): 65-68, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088960

ABSTRACT

ABSTRACT We describe a case of keratomycosis caused by Arthographis kalrae after excimer laser keratomileusis. A 38-year-old female developed stromal keratitis eight weeks after refractive surgery. She developed severe corneal stromal infiltration and mild anterior segment inflammation, which could not be treated with topical voriconazole 1%, but topical natamycin 5% ameliorated her condition. A reactivation of keratomycosis symptoms was observed; therefore, longer treatment was administered to the patient. It has been reported that A. kalrae keratomycosis is associated with exposure to soil and contact lens usage. However, the patient, who lived in a rural location, was neither involved in gardening activities nor had a history of wearing contact lenses. This is the first case of post-refractive A. kalrae keratomycosis.


RESUMO Descrevemos um caso de ceratomicose por Arthographis kalrae após ceratomileusis por excimer laser. Uma mulher de 38 anos desenvolveu ceratite estromal oito semanas após a cirurgia refrativa. Ela desenvolveu infiltração estromal grave da córnea e uma leve inflamação do segmento anterior, que não pode ser tratada com voriconazol tópico a 1%, mas a natamicina tópica a 5% melhorou sua condição. Uma reativação dos síntomas de ceratomicose foi observada; portanto, tratamento mais prolongado foi administrado a paciente. Tem sido relatado que a ceratomicose por A. kalrae está associada à exposição ao solo e ao uso de lentes de contato. No entanto, a paciente, que vivía em um local rural, não estava envolvida em atividades de jardinagem e nem tinha histórico de uso de lentes de contato. Este é o primeiro caso de ceratomicose pós-refrativa por A. kalrae.


Subject(s)
Humans , Female , Adult , Eye Infections, Fungal/microbiology , Keratitis/microbiology , Ascomycota/isolation & purification , Eye Infections, Fungal/drug therapy , Natamycin/therapeutic use , Keratomileusis, Laser In Situ/adverse effects , Voriconazole/therapeutic use , Keratitis/drug therapy
16.
Arq Bras Oftalmol ; 83(1): 65-68, 2020.
Article in English | MEDLINE | ID: mdl-31531550

ABSTRACT

We describe a case of keratomycosis caused by Arthographis kalrae after excimer laser keratomileusis. A 38-year-old female developed stromal keratitis eight weeks after refractive surgery. She developed severe corneal stromal infiltration and mild anterior segment inflammation, which could not be treated with topical voriconazole 1%, but topical natamycin 5% ameliorated her condition. A reactivation of keratomycosis symptoms was observed; therefore, longer treatment was administered to the patient. It has been reported that A. kalrae keratomycosis is associated with exposure to soil and contact lens usage. However, the patient, who lived in a rural location, was neither involved in gardening activities nor had a history of wearing contact lenses. This is the first case of post-refractive A. kalrae keratomycosis.


Subject(s)
Eye Infections, Fungal/microbiology , Keratitis/microbiology , Adult , Ascomycota/isolation & purification , Eye Infections, Fungal/drug therapy , Female , Humans , Keratitis/drug therapy , Keratomileusis, Laser In Situ/adverse effects , Natamycin/therapeutic use , Voriconazole/therapeutic use
17.
Nat Commun ; 10(1): 3105, 2019 07 15.
Article in English | MEDLINE | ID: mdl-31308371

ABSTRACT

Fas plays a major role in regulating ligand-induced apoptosis in many cell types. It is well known that several cancers demonstrate reduced cell surface levels of Fas and thus escape a potential control system via ligand-induced apoptosis, although underlying mechanisms are unclear. Here we report that the endosome associated trafficking regulator 1 (ENTR1), controls cell surface levels of Fas and Fas-mediated apoptotic signalling. ENTR1 regulates, via binding to the coiled coil domain protein Dysbindin, the delivery of Fas from endosomes to lysosomes thereby controlling termination of Fas signal transduction. We demonstrate that ENTR1 is cleaved during Fas-induced apoptosis in a caspase-dependent manner revealing an unexpected interplay of apoptotic signalling and regulation of endolysosomal trafficking resulting in a positive feedback signalling-loop. Our data provide insights into the molecular mechanism of Fas post-endocytic trafficking and signalling, opening possible explanations on how cancer cells regulate cell surface levels of death receptors.


Subject(s)
Antigens, Neoplasm/physiology , Endocytosis/physiology , Intracellular Signaling Peptides and Proteins/physiology , Vesicular Transport Proteins/physiology , Antigens, Neoplasm/analysis , Antigens, Neoplasm/metabolism , Apoptosis , Dysbindin/metabolism , Fas Ligand Protein/analysis , Fas Ligand Protein/metabolism , HeLa Cells , Humans , Intracellular Signaling Peptides and Proteins/analysis , Intracellular Signaling Peptides and Proteins/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 13/analysis , Protein Tyrosine Phosphatase, Non-Receptor Type 13/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 13/physiology , Signal Transduction , Vesicular Transport Proteins/analysis , Vesicular Transport Proteins/metabolism , fas Receptor/analysis , fas Receptor/metabolism
18.
Front Physiol ; 9: 1599, 2018.
Article in English | MEDLINE | ID: mdl-30483154

ABSTRACT

The aim of this study was to investigate if urinary glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), Klotho and hydroxyproline can be considered as potential biomarkers of renal injury and fibrosis in an experimental model of obesity. Male Zucker lean (ZL) and obese (ZO) rats were studied from 2 to 8 months old. Kidneys from ZO rats at the end of the study (8 months old) developed mild focal and segmental glomerulosclerosis as well as moderate tubulointerstitial injury. Urinary excretion of Klotho was higher in ZO rats at 2, 5, and 8 months of study, plasma Klotho levels were reduced and protein abundance of Klotho in renal tissue was similar in ZL and ZO rats. GluAp and AlaAp urinary activities were also increased in ZO rats throughout the time-course study. ZO rats showed an augmentation of hydroxyproline content in renal tissue and a significant increase of tubulointerstitial fibrosis. Correlation studies demonstrated that GluAp, AlaAp, and Klotho are early diagnostic markers of renal lesions in Zucker obese rats. Proteinuria and hydroxyproline can be considered delayed diagnostic markers because their contribution to diagnosis starts later. Another relevant result is that GluAp, AlaAp, and Klotho are related not only with diagnosis but also with prognosis of renal lesions in Zucker obese rats. Moreover, strong predictive correlations of aminopeptidasic activities with the percentage of renal fibrosis or with renal hydroxyproline content at the end of the experiment were observed, indicating that an early increased excretion of these markers is related with a higher later extent of fibrosis in Zucker obese rats. In conclusion, GluAp, AlaAp, and Klotho are early diagnostic markers that are also related with the extent of renal fibrosis in Zucker obese rats. Therefore, they have a potential use not only in diagnosis, but also in prognosis of obesity-associated renal lesions.

19.
Arch Toxicol ; 89(10): 1847-60, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25160661

ABSTRACT

A frequent mechanism for drug-induced liver injury (DILI) is mitochondrial impairment, and early evaluation of new drugs for their potential to cause mitochondrial dysfunction is becoming an important task for drug development. To this end, we designed a high-content screening assay to study mitochondrial-induced hepatotoxicity in HepG2 cells in detail. Simultaneous assessment of mitochondrial mass and cell viability in cells exposed for 24 h to compounds provides preliminary information on the mitochondrial- or nonmitochondrial-related hepatotoxic potential of compounds. To fully address the mechanisms implicated in mitochondrial impairment, prelethal changes in mitochondrial superoxide production, mitochondrial membrane potential, mitochondrial permeability transition, intracellular calcium concentration and apoptotic cell death were studied in cells incubated for 1 h with compounds. The assay correctly classified a set of well-known mitochondrial toxicants and negative controls and revealed high sensitivity for the detection of mitochondrial DILI and the establishment of different mitochondrial toxicity risks (low to high). This procedure was used for analysing the potential mitochondrial impairment of six statins to determine their clinical risk. All the tested statins produced mitochondrial impairment, although they showed different levels of toxicity (low-medium toxicity risk). The results suggest that this cell-based assay is a promising in vitro approach to predict the potential of drug candidates to induce mitochondrial-associated hepatotoxicity.


Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity , Mitochondria, Liver/drug effects , Apoptosis/drug effects , Calcium/metabolism , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/pathology , Hep G2 Cells , Hepatocytes/drug effects , Hepatocytes/pathology , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Liver/pathology
20.
Rev. med. nucl. Alasbimn j ; 9(34)oct. 2006. tab
Article in Spanish | LILACS | ID: lil-445748

ABSTRACT

Con la reciente publicación del estudio del Pioped II sobre la utilidad del Tac multicorte (CTA) en el diagnostico de embolismo pulmonar y con su inconsistencia diagnostica en los casos discordantes con la probabilidad clínica o pretest vuelve la atención a los estudios isotópicos de ventilación y perfusion a sus ventajas y a sus adelantos tecnológicos. Esta revisión incluye el análisis de los resultados del pioped II y los compara con los estudios más recientes utilizando technegas, spect y tres dimensiones. El Pioped II tenia dos objetivos, ver la utilidad del Tac multicorte toráxico (CTA) en descartar o diagnosticar embolismo pulmonar y el de comparar dos modalidades diagnosticas relacionadas pero diferentes, el Tac multicorte toráxico (CTA) solo y el CTA toráxico combinado con la fase venosa (CTA-CVT). Las sensibilidades obtenidas fueron, 83 por ciento para el CTA y 90 por ciento para el CTA-CVT con especificidades a su vez del 96 por ciento para el primero y de 95 por ciento para el Segundo. Sin embargo en los pacientes con baja probabilidad pretest la presencia de falsos positivos fue del 42 por ciento y en los pacientes con alta probabilidad pretest la presencia de falsos negativos fue del 40 por ciento. Esto indica que el Tac multicorte per. se no descarta el embolismo pulmonar y no tiene la trascendencia de una gamagrafia pulmonar de V-Q normal. El Tac toráxico multicorte produce de tres hasta 10 veces mas radiación que la que produce una gamagrafia pulmonar de ventilación perfusion y la adición del estudio venoso mediante Tac multicorte multiplica 1.5 veces la tasa de exposición radiológica del Tac toráxico solo. La gamagrafia de ventilación pulmonar se ha modificado al utilizar ahora compuestos marcados con tecnecio 99m, ya sea technegas o micro aerosoles que brindan mejores imágenes que el Xe 133 y el Kr 81m y que facilitan un mayor numero de proyecciones. También es posible ahora realizar spect ventilatorio con technegas. El spect pulmonar con re...


Subject(s)
Humans , Tomography, Emission-Computed, Single-Photon , Angiography/methods , Pulmonary Embolism , Pulmonary Embolism , Ventilation-Perfusion Ratio , Tomography, Spiral Computed/methods , Probability , Lung , Lung , False Negative Reactions , False Positive Reactions , Sensitivity and Specificity , Venous Thrombosis/complications , Predictive Value of Tests
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