124 results on '"M. A. Orden"'
Search Results
2. The veterinary medicinal products market supply gap: A practical insight based on the Regulation (EU) 2019/6
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Rafaela Nogueira, Catarina Jota Baptista, Lio Gonçalves, Ana Claúdia Coelho, Ana I. Faustino-Rocha, Marta Regueiro Purriños, José M. Gonzalo-Orden, and Paula A. Oliveira
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medical prescription ,pharmacology ,pharmacy ,veterinarian ,therapeutics ,Agriculture ,Agriculture (General) ,S1-972 ,Veterinary medicine ,SF600-1100 - Abstract
The Regulation (EU) 2019/6 establishes that the veterinary prescriptions should follow a cascade, according to their availability of the market. In sum, the veterinarian is authorized to use a medicine for human use only if there is no product available for the same or other therapeutic indication, in the same or another animal species. This study aims to analyse the application of Regulation (EU) 2019/6 in the pharmacological prescription at the Veterinary Hospital of the University of León. A total of 121 clinical cases, 89 dogs (73.55%) and 32 cats (26.45%) were included. Results revealed that 95 medicines were prescribed, 51 (53.68 %) as veterinary medicines and 44 (46.32 %) as human medicines. From the human medicines, 22 (50.00%) did not have a veterinary alternative in the market; four (9.00%) presented a veterinary medicine in the appropriate formulation for the species; 10 (23.00%) had no alternative in the desired formulation; and 8 (18.00%) had no alternatives for the target species. This study suggested that the cascade was not strictly followed, and several reasons may justify it, such as the lack of veterinary products, different formulations, and differences in costs. An effective, safe and sustainable use of the therapeutic option available can only be accomplished with a rational use of the prescription cascade and a correct use of the Regulation (EU) 2019/6.
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- 2024
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3. Commentary: Do people really care less about their cats than about their dogs? A comparative study in three European countries
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, and Paula A. Oliveira
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dog ,cat ,pet care ,caregiver ,letter (to the Editor) ,Veterinary medicine ,SF600-1100 - Published
- 2024
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4. Re: Toxic metals in Loggerhead sea turtles (Caretta caretta) stranded freshly dead along Sicilian coasts
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Catarina Jota Baptista, José M. Gonzalo-Orden, Fernanda Seixas, and Paula A. Oliveira
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Metal ,metalloid ,wildlife ,Veterinary medicine ,SF600-1100 - Published
- 2023
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5. Effects of testosterone and exercise training on bone microstructure of rats
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Catarina Jota-Baptista, Ana I. Faustino-Rocha, Margarida Fardilha, Rita Ferreira, Paula A. Oliveira, Marta Regueiro-Purriños, José A. Rodriguez-Altonaga, José M. Gonzalo-Orden, and Mário Ginja
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bone ,exercise training ,hypogonadism ,micro-computed tomography ,osteoporosis ,testosterone ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Background and Aim: Male hypogonadism results from failure to produce physiological levels of testosterone. Testosterone in men is essential in masculine development, sperm production, and adult man's health. Osteoporosis is one of the consequences of hypogonadism. Regular physical exercise and exogenous testosterone administration are frequently used to prevent or treat this condition. This study aimed to understand the effects of lifelong exercise training and testosterone levels (isolated and together) in the main bone structure parameters. Materials and Methods: A total of 24 rats were used and randomly divided into four groups: Control group (CG; n=6), exercised group (EG, n=6), testosterone group (TG, n=6), and testosterone EG (TEG, n=6). A micro-computed tomography equipment was used to evaluate 15 bone parameters. Results: Both factors (exercise training and testosterone) seem to improve the bone resistance and microstructure, although in different bone characteristics. Testosterone influenced trabecular structure parameters, namely, connectivity density, trabecular number, and trabecular space. The exercise promoted alterations in bone structure as well, although, in most cases, in different bone structure parameters as bone mineral density and medullar mineral density. Conclusion: Overall, exercise and testosterone therapy seems to have a synergistic contribution to the general bone structure and resistance. Further studies are warranted, comparing different individual factors, as gender, lifestyle, or testosterone protocols, to constantly improve the medical management of hypogonadism (and osteoporosis).
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- 2022
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6. High Levels of Heavy Metal(loid)s Related to Biliary Hyperplasia in Hedgehogs (Erinaceus europaeus)
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, Carla Patinha, Pedro Pato, Eduardo Ferreira da Silva, María Casero, Erica Brazio, Ricardo Brandão, Daniela Costa, Teresa Letra Mateus, and Paula A. Oliveira
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metal ,biliary hyperplasia ,hepatotoxicity ,histopathology ,wildlife ,One Health ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Heavy metal(loid) pollution of ecosystems is a current One Health problem. The liver is one of the most affected organs in cases of acute or chronic exposure to abnormal amounts of these substances, inducing histopathologic lesions. In order to assess the influence of heavy metal(loids), forty-five European hedgehogs (Erinaceus europaeus) were submitted to necropsy, and liver samples were collected for a routine histopathology exam and metal(loid)s determination (As, Cd, Co, Cr, Cu and Pb) by ICP-MS. Age was estimated during the necropsy exam. Biliary hyperplasia was the most frequent lesion observed (16/45; 35.56%). No statistically significant associations were found between biliary hyperplasia and age or sex. Metal(loid)s’ concentrations were higher in animals with biliary hyperplasia (except for As). There was a statistically significant difference for both Cd and Co. For As, Cd and Co, cubs and juveniles animals showed significantly lower concentrations than elder individuals. Only for Pb were significant differences found between females and males. As described in the literature, exposure to metal(loid)s may be a cause of biliary hyperplasia, although further research (including the use of biochemical methods) is needed to support these results. To the authors’ knowledge, this is the first report of this association in hedgehogs.
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- 2023
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7. Heavy metals: true enemies of Mammalian and bird fauna
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, and Paula A. Oliveira
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trace element ,toxic ,wildlife ,toxicology ,Medicine - Published
- 2022
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8. Poisoning of Portuguese fauna
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, and Paula A. Oliveira
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xenobiotic ,poisoning ,wildlife ,health ,Portugal ,Medicine - Published
- 2022
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9. Do Urban Hedgehogs (Erinaceus europaeus) Represent a Relevant Source of Zoonotic Diseases?
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Catarina Jota Baptista, Paula A. Oliveira, José M. Gonzalo-Orden, and Fernanda Seixas
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hedgehog ,wildlife ,zoonotic pathogens ,habitat ,one health ,Medicine - Abstract
Urban fauna is defined as animal species that can live in urban environments. Several species, including the western-European hedgehog (Erinaceus europaeus), have now been identified as part of this urban fauna, becoming permanent residents of parks and gardens in different cities across Europe. Due to the importance that this phenomenon represents for zoonotic disease surveillance, several authors have been conducting zoonotic agents’ surveys on hedgehog. The aim of this study is to compare zoonotic diseases’ prevalence in hedgehogs in urban environments with those from more rural areas. A systematic review with meta-analysis of twelve studied of zoonotic diseases’ (in urban and rural areas of Europe) was therefore conducted for this purpose. Fifteen different zoonoses have been assessed in urban environments and six in rural areas. Anaplasma phagocytophilum was the most prevalent zoonotic agent found in urban habitats (96%). Dermatophytosis shows statistically significant differences between locations (p-value < 0.001), with a higher prevalence in urban Poland (55%; n = 182). Our results suggest further research and a standardized monitoring of different hedgehog populations are essential to understanding the epidemiology of several zoonotic pathogens in different habitat types (urban, rural, natural, industrial, etc.) and preventing possible disease outbreaks.
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- 2023
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10. Wild Boars (Sus scrofa, L. 1758) from Castile and Leon Region (Spain): A Histopathology Survey
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Catarina Jota Baptista, José M. Gonzalo-Orden, Luís J. Merino-Goyenechea, Paula A. Oliveira, and Fernanda Seixas
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parasitic pneumonia ,hydropic change ,vacuolar change ,histopathology ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Wild boars are wild ungulates with a wide distribution in Europe, with a relevant role in wildlife and public health. In Spain, high (and sometimes artificial) densities of wild boars are responsible for several health problems. Regular surveys, with hunters’ collaboration, are crucial to monitor these diseases. Histological analyses were performed for lung, liver, and kidneys from 72 wild boars (58 from Zamora, 16 from Palencia). Lungs were the most affected organs, mainly revealing parasitic pneumonia (34.7%). Hydropic, vacuolar, and other cellular changes (33.3%) and congestion (16.7%) were found in the liver, and only 30.6% of the wild boars presented no alterations in this organ. Regarding the kidney, non-purulent nephritis (22.2%) was the most common lesion. This study gives an overview of the health status of wild boar populations in Castile and León. Other laboratory analyses are needed to obtain definitive diagnoses of these lesions, reach other conclusions, or apply any mitigation strategies to protect animals’ or consumers’ health.
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- 2022
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11. Biomonitoring of heavy metals and metalloids with wild mammals in the Iberian Peninsula: a systematic review
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, and Paula A. Oliveira
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General Environmental Science - Abstract
Trace elements (including heavy metals) can negatively affect the environment and the health of living beings. Biomonitoring is a transdisciplinary tool to evaluate this pollution type and its respective consequences in ecosystems, food chains, and webs. This review used systematic methods to identify published literature on biomonitoring of heavy metal(loid)s using wild mammals on the Iberian Peninsula. A total of 30 different mammalian species (30/141) were included in 62 Iberian biomonitoring studies: 22 species from terrestrial habitats and 8 from aquatic habitats. Carnivores (including piscivores) were the most represented in both habitat types (7/22 in terrestrial; 8/8 in aquatic). Most studies used more than one tissue (2.8 ± 1.3), with a preference for the liver and kidney. Cd was the most determined metal, measured in 45% of the biomonitoring studies analysed, highlighting its potential health impact on mammals. Further research is crucial to provide more information on mammalian species' susceptibility to this One Health problem, and to cover more habitats, trophic chains, and (or) geographical areas.
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- 2023
12. Biomonitoring metals and metalloids in wild mammals: invasive versus non-invasive sampling
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Catarina Jota Baptista, Fernanda Seixas, José M. Gonzalo-Orden, and Paula A. Oliveira
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Health, Toxicology and Mutagenesis ,Environmental Chemistry ,General Medicine ,Pollution - Published
- 2022
13. Wild Boars (
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Catarina, Jota Baptista, José M, Gonzalo-Orden, Luís J, Merino-Goyenechea, Paula A, Oliveira, and Fernanda, Seixas
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Wild boars are wild ungulates with a wide distribution in Europe, with a relevant role in wildlife and public health. In Spain, high (and sometimes artificial) densities of wild boars are responsible for several health problems. Regular surveys, with hunters' collaboration, are crucial to monitor these diseases. Histological analyses were performed for lung, liver, and kidneys from 72 wild boars (58 from Zamora, 16 from Palencia). Lungs were the most affected organs, mainly revealing parasitic pneumonia (34.7%). Hydropic, vacuolar, and other cellular changes (33.3%) and congestion (16.7%) were found in the liver, and only 30.6% of the wild boars presented no alterations in this organ. Regarding the kidney, non-purulent nephritis (22.2%) was the most common lesion. This study gives an overview of the health status of wild boar populations in Castile and León. Other laboratory analyses are needed to obtain definitive diagnoses of these lesions, reach other conclusions, or apply any mitigation strategies to protect animals' or consumers' health.
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- 2022
14. Comparative Study of Clinical Outcomes of Severe and Critical COVID-19 Patients With and Without Hemoperfusion Admitted in a Referral Hospital
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M W Tibubos, R M Royeca, P R Evangelista, M C Orden, G Ong-Cabrera, A P Estabillo, and R Mora
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- 2022
15. Can the European Hedgehog (Erinaceus europaeus) Be a Sentinel for One Health Concerns?
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Catarina Vinhas Jota Baptista, Paula A. Oliveira, José M. Gonzalo-Orden, and Fernanda Seixas
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0301 basic medicine ,2019-20 coronavirus outbreak ,Erinaceus ,biology ,Animal health ,040301 veterinary sciences ,Ecology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,04 agricultural and veterinary sciences ,General Medicine ,biology.organism_classification ,0403 veterinary science ,03 medical and health sciences ,030104 developmental biology ,Antibiotic resistance ,One Health ,General health ,Hedgehog - Abstract
Erinaceus europaeus is a cosmopolitan mammalian species broadly distributed in Europe, from natural to suburban areas. Due to its ecological role and susceptibility to distinct zoonotic agents, E. europaeus could be a suitable sentinel candidate for many global problems that negatively affect human and animal health. Hedgehogs can work as bioindicators to environmental contamination and can be hosts for multiple tickborne zoonotic agents. Thus, people who directly or indirectly make physical contact with this species are exposed to a variety of threats. Moreover, it has also been studied as an indicator for antibiotic resistance, which was already confirmed for tetracyclines. Additionally, it was also reported as a reservoir for methicillin-resistant Staphylococcus aureus (MRSA). More recently, hedgehogs have been recently recognised as potential reservoirs of MERS-CoV-like strains. Among other animals, this species can possibly represent an intermediate reservoir for SARS-CoV-2. The aim of this review is to briefly expose the scientific attainments about hedgehog health, namely agents, diseases, and threats that significantly affect general health concerns and that contribute to achieve One Health principles.
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- 2021
16. The role of morphometric and respiratory factors in predicting the severity and evolution of urinary symptoms in patients with obstructive sleep apnea syndrome
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Safwan S. Escaf, Luis Rodríguez Villamil, José M. Gonzalo-Orden, Rodrigo Gil, Amelia A. Alzueta, and Sergio Fernández-Pello
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Spirometry ,medicine.medical_specialty ,medicine.medical_treatment ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Lower urinary tract symptoms ,Internal medicine ,medicine ,Nocturia ,Continuous positive airway pressure ,Prospective cohort study ,medicine.diagnostic_test ,business.industry ,Sleep apnea ,respiratory system ,medicine.disease ,respiratory tract diseases ,Obstructive sleep apnea ,030228 respiratory system ,Otorhinolaryngology ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
To assess the severity, evolution, and behaviour of several urinary symptoms in patients with obstructive sleep apnea syndrome (OSAS) before and after the treatment with continuous positive airway pressure (CPAP). A prospective study was performed on patients with a recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. The symptom incidence was analysed seeking predictive factors for initial nocturia, nocturnal polyuria (NP), and unfavourable International Prostate Symptoms Score (IPSS) before and after a 1-year period of treatment using a CPAP device. Morphometric variables (body mass index, BMI; neck and abdominal diameter) and functional respiratory variables (FEV1, FVC, and FEV1/FVC) were analysed. A multivariate analysis was performed with a calculation of Pearson’s correlation coefficient to establish a linear relation between the variables. A total of 43 patients completed the two-step study (IPSS and bladder diary before and after the CPAP treatment). IPSS decreased by 3.58 points. Nocturia decreased to once per night. Neck diameter, FEV1, and FEV1/FVC significantly predicted the initial severity of some lower urinary tract symptoms (LUTS), (p=0.015, p=0.029, p=0.008, respectively). Neck diameter, abdominal perimeter, and FEV1/FVC significantly predicted the LUTS evolution throughout the study (p=0.023, p=0.007, p=0.05, respectively). Some pre-treatment morphometry and spirometry parameters such as abdominal or neck diameter, FEV1, and FEV1/FVC were predictive of the severity and evolution of LUTS in patients with OSAS.
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- 2021
17. Anatomy and Imaging of Rat Prostate: Practical Monitoring in Experimental Cancer-Induced Protocols
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Mário Ginja, Maria J. Pires, José M. Gonzalo-Orden, Fernanda Seixas, Miguel Correia-Cardoso, Rita Ferreira, Margarida Fardilha, Paula A. Oliveira, and Ana I. Faustino-Rocha
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computed tomography (CT) ,macroscopy ,magnetic resonance imaging (MRI) ,microscopy ,ultrasonography ,Medicine (General) ,R5-920 - Abstract
The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).
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- 2019
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18. Poisoning of Portuguese fauna: a significant threat?
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Jota Baptista, Catarina, primary, Seixas, Fernanda, additional, M. Gonzalo-Orden, José, additional, and A. Oliveira, Paula, additional
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- 2022
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19. Heavy metals: true enemies of Mammalian and bird fauna
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Jota Baptista, Catarina, primary, Seixas, Fernanda, additional, M. Gonzalo-Orden, José, additional, and A. Oliveira, Paula, additional
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- 2022
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20. Adventitial histopathological changes after coronary stenting in a porcine model
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V Caballero-Manso, María López-Benito, José R. Altónaga, José M. Gonzalo-Orden, Claudia Pérez-Martínez, MG de Garnica Garcia, F Fernandez Vazquez, T Benito-Gomez, A Perez De Prado, M Regueiro-Purrino, and Carlos Cuellas-Ramón
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medicine.medical_specialty ,General Veterinary ,Internal medicine ,medicine ,Cardiology ,Coronary stenting - Published
- 2020
21. Biomonitoring metals and metalloids in wild mammals: invasive versus non-invasive sampling
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Catarina, Jota Baptista, Fernanda, Seixas, José M, Gonzalo-Orden, and Paula A, Oliveira
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Mammals ,Metals, Heavy ,Animals ,Humans ,Biological Monitoring ,Environmental Monitoring ,Metalloids - Abstract
Heavy metal and metalloid pollution is a matter of concern in animal, human and environmental health (One Health) and also in wildlife conservation worldwide. Studying wild mammals in toxicology has been contributing significantly to our knowledge, namely to find out the most critical regions, to understand bioaccumulation and biomagnification phenomena or to evaluate their toxic effects. However, not all the animal tissues and organs provide the same information or should be interpreted in the same way. The best sample to use will depend on the objectives and conditions of the study. This review aims to compare invasive and non-invasive samples to biomonitor heavy metals, providing a brief resume of their advantages, limitations and examples of use. Further research, using a wider range of mammalian species, is required to establish what information can be obtained in biomonitoring studies that use non-invasive samples (such as hair, faeces and parasites) and/or invasive samples (such as blood, liver, kidney, bone and other organs).
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- 2021
22. Lower urinary tract symptoms and obstructive sleep apnea syndrome: Urodynamic evolution before and after one year of treatment with continuous positive airway pressure
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S. Fernández-Pello, José M. Gonzalo-Orden, Rodrigo Gil, L. Rodríguez Villamil, A. Alzueta, S. Escaf, and C. Rodríguez
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business.industry ,Urinary system ,medicine.medical_treatment ,030232 urology & nephrology ,Sleep apnea ,General Medicine ,urologic and male genital diseases ,medicine.disease ,respiratory tract diseases ,Obstructive sleep apnea ,03 medical and health sciences ,0302 clinical medicine ,Nocturnal sleep ,Lower urinary tract symptoms ,Anesthesia ,Medicine ,Nocturia ,Continuous positive airway pressure ,medicine.symptom ,business ,Prospective cohort study - Abstract
Objective To report the clinical evolution and the urodynamic behaviour of several lower tract urinary symptoms in patients with obstructive sleep apnea syndrome before and after the treatment with continuous positive airway pressure (CPAP) devices. Methods A prospective study was performed; patients with recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. In order to discard important lower urinary tract conditions, urological examinations were previously performed. Urinary symptoms were evaluated using the IPSS and OAB-V8 validated questionnaires, three-day Bladder Diary and invasive urodynamic examinations with a gap of one year before and one year after using the CPAP. Results 84 urodynamic studies were carried out in 43 patients. The IPSS score decreased by 3.58 points. The OAB-V8 score decreased by 2.87 points. Nocturia episodes decreased to one per night. The percentage of patients with nocturnal polyuria went down to 26%. The bladder compliance significantly increased (97.39 vs 200.40 ml/cm H2O). The presence of detrusor overactivity decreased from 11 (before CPAP) to 5 patients (after CPAP). Conclusion The proper treatment with CPAP showed a statistical and clinical improvement of several LUTS with limited urodynamic modifications.
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- 2019
23. Síntomas de tramo urinario inferior y síndrome de apnea obstructiva del sueño: evolución urodinámica antes y después de un año de tratamiento con presión continua positiva de la vía aérea
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S. Fernández-Pello, A. Alzueta, C. Rodríguez, S. Escaf, José M. Gonzalo-Orden, Rodrigo Gil, and L. Rodríguez Villamil
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03 medical and health sciences ,0302 clinical medicine ,business.industry ,Urology ,030232 urology & nephrology ,Medicine ,business ,Humanities - Abstract
Resumen Objetivo Demostrar el potencial impacto urodinamico que puede tener el uso adecuado de presion continua positiva de la via aerea (CPAP) en pacientes con sindrome de apnea-hipopnea obstructiva del sueno y observar si la posible mejoria de los sintomas de tramo urinario inferior es debida a alguna modificacion urodinamica. Metodos Estudio prospectivo con pacientes recientemente diagnosticados de sindrome de apnea-hipopnea obstructiva del sueno mediante poligrafia del sueno. Se estudian desde el punto de vista urologico para descartar importantes patologias urologicas. Se utilizan cuestionarios validados IPSS y OAB-V8, diarios miccionales de 3 dias y estudios urodinamicos invasivos, todos ellos antes de comenzar con CPAP y tras un ano de su uso adecuado. Resultados Se llevan a cabo 84 estudios urodinamicos en 43 pacientes. La puntuacion IPSS disminuye 3,58 puntos. La puntuacion OAB-V8 disminuye 2,87 puntos. Los episodios de nicturia disminuyen mas de uno por noche. El porcentaje de pacientes con poliuria nocturna disminuye un 26%. La acomodacion vesical significativamente aumenta (97,39 vs. 200,40 ml/cm H2O). Disminuye la presencia de detrusor hiperactivo en el estudio urodinamico de 11 (antes de CPAP) a 5 pacientes (tras CPAP). Conclusion Tras el tratamiento apropiado con CPAP se observa una mejoria estadistica y clinica de distintos sintomas de tramo urinario inferior con escasa repercusion urodinamica.
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- 2019
24. Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies
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Marta Regueiro-Purriños, Ana Isabel Cortina-Rivero, José R. Altónaga, Armando Pérez de Prado, David Viñuela-Baragaño, Carlos Cuellas-Ramón, Rodrigo Estévez-Loureiro, María López-Benito, Armando Tellez, José M. Gonzalo-Orden, Felipe Fernández-Vázquez, and Claudia Pérez-Martínez
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DOCA ,medicine.medical_specialty ,hypertension ,Urology ,Disease ,Article ,histology ,radiofrequency ,lcsh:Zoology ,medicine ,lcsh:QL1-991 ,cardiovascular diseases ,renal denervation ,Denervation ,lcsh:Veterinary medicine ,General Veterinary ,business.industry ,High mortality ,Histology ,swine ,Gradient Increase ,Blood pressure ,immunohistochemistry ,lcsh:SF600-1100 ,Animal Science and Zoology ,business ,Large animal - Abstract
New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity®, system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >, 10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <, 10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.
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- 2020
25. Stafne's bone defects from Spain: report of four cases and brief archaeological literature review
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José M. Gonzalo-Orden, Sofia N. Wasterlain, Susana Gómez-González, and Laura González-Garrido
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Adult ,Male ,Archeology ,Adolescent ,Paleopathology ,Computed tomography ,Mandible ,Mandibular first molar ,Pathology and Forensic Medicine ,Young Adult ,Medicine ,Humans ,0601 history and archaeology ,Mandibular Diseases ,Inferior alveolar canal ,History, 15th Century ,Orthodontics ,Angle of the mandible ,060101 anthropology ,060102 archaeology ,Osteology ,medicine.diagnostic_test ,business.industry ,Ct analysis ,History, 19th Century ,06 humanities and the arts ,Middle Aged ,Bone defect ,History, Medieval ,medicine.anatomical_structure ,History, 16th Century ,Spain ,Female ,Bone Diseases ,business ,Tomography, X-Ray Computed - Abstract
Objective To present for the first time in the north-western Spanish osteological record prevalence data on Stafne’s bone defect, to compare the results with those reported by other studies, and to increase the dataset for future inter-population comparisons. Material In all, 143 complete adult mandibles recovered from two necropolises were analyzed (n = 118, San Juan Bautista of Guardo, Palencia province, 16th-19th centuries; n = 25, Plaza del Grano, city of Leon, 12th-15th centuries). Methods Differential diagnosis of the lesions was made through macroscopic and Computed Tomography (CT) analyses. Results Four mandibles (n = 3, Guardo, Palencia; n = 1, Leon) presented bone cavities on the lingual aspect of the mandible below the mylohyoid channel, between the first molar and the angle of the mandible. CT scan showed unilateral well-defined unilocular oval/round concavities in the lingual mandibular cortex below the inferior alveolar canal. Neither the macroscopic nor the radiological characteristics are compatible with inflammatory or malignant pathology, favoring instead a diagnosis of Stafne’s bone defect. Conclusions Four cases of Stafne’s defects are added to the bioarchaeological inventory. The calculated prevalence is 2.54% for San Juan Bautista and 4% for Plaza del Grano, values in close agreement to those presented in other osteoarchaeological studies. Significance The identification of all examples of Stafne’s bone defects in past populations will contribute to elucidate which factors may be responsible for this trait’s cultural, ecological, temporal, and geographical patterning. Limitations The skeletal samples are relatively small. Suggestions for Further Research In future investigations of Stafne’s bone defects, CT analysis of dry bone specimens is recommended, whenever possible.
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- 2020
26. Multi-headed (bifid and trifid) mandibular condyles in archaeological contexts: Two posttraumatic cases
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Laura González-Garrido, Sofia N. Wasterlain, Susana Gómez-González, and José M. Gonzalo-Orden
- Subjects
Adult ,Mandibular Condyles ,Angle of the mandible ,Temporomandibular Joint ,medicine.diagnostic_test ,business.industry ,Mandibular Condyle ,Computed tomography ,Mandible ,Cell Biology ,General Medicine ,Temporomandibular Joint Disorders ,Archaeology ,Condyle ,medicine.anatomical_structure ,stomatognathic system ,Otorhinolaryngology ,medicine ,Humans ,Gonial angle ,Joint dysfunction ,Tomography, X-Ray Computed ,business ,General Dentistry - Abstract
Objective Bifid and trifid mandibular condyles are infrequent morphological alterations of the mandibular condyle. With the aim of better identifying its possible causing factors in the past and provide clues on the potential types and severities of joint dysfunction that may occur if clinical intervention is not undertaken, two archaeological cases of multi-headed mandibular condyles are presented, and their possible aetiology and pathogenesis are discussed. Design In this study, 143 adult mandibles recovered in the northwest of Spain were examined: 91 exhumed from San Juan Bautista church (Guardo, Palencia; 16th-19th centuries), and 52 from San Salvador de Palat de Rey church (Leon, 13th-19th centuries). All mandibles were observed macroscopically for the presence of any morphological and/or pathological alterations. When justified, the mandibles were also scrutinized through computed tomography. Results Two isolated mandibles (n = 1, Palencia; n = 1, Leon) with multi-headed mandibular condyles (bifid and trifid) were identified. The computed tomography scan of the affected mandibles revealed alterations compatible with traumatic events, namely line fractures and deformations at the angle of the mandible. Conclusions Both the bifid and trifid mandibular condyles here described probably result from traumatic events during childhood leading to a posttraumatic deformation. Although no severe impairment of mandibular use was identified, some asymmetries probably resulted in some sort of malfunction, with TMJ-OA and gonial angle eversion as supporting evidence. Nevertheless, the degree of bone remodelling observed indicates that both individuals lived long after the traumatic occurrence.
- Published
- 2022
27. The influence of Ringer's lactate or HES 130/0.4 administration on the integrity of the small intestinal mucosa in a pig hemorrhagic shock model under general anesthesia
- Author
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Helena Vala, João R. Mesquita, Carlos Venâncio, Aura Silva, David A. Ferreira, A. L. Ortiz, and José M. Gonzalo-Orden
- Subjects
Resuscitation ,General Veterinary ,business.industry ,Ileum ,Hydroxyethyl starch ,Small intestine ,Jejunum ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030202 anesthesiology ,Anesthesia ,Hypovolemia ,Edema ,Duodenum ,Medicine ,030212 general & internal medicine ,medicine.symptom ,business ,medicine.drug - Abstract
Objective To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringer's lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. Design Prospective experimental study. Setting University teaching hospital. Animals Twenty-eight healthy Large White pigs, 3 months of age. Interventions Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. Measurements and Main Results The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, inflammatory infiltration, cellular degeneration, necrosis, and epithelial detachment. Mucosal loss percentage (%ML) and crypt:interstitium ratio (C:I) were also assessed. In the duodenum, jejunum, and ileum, and the entire small intestine, the %ML was significantly higher in Group 1, than in Groups 2 and 3. Hyperemia in the small intestine was significantly higher in pigs resuscitated with HES 130/0.4 compared to pigs resuscitated with RL. Conclusions and Clinical Relevance In a setting of controlled hemorrhage, resuscitation with HES 130/0.4 was associated with a lower percentage of mucosal loss on the small intestine, compared with resuscitation with RL solution. Our study also suggests that the duodenum may be more sensitive to hypovolemia induced by severe hemorrhage.
- Published
- 2016
28. Inpatient dermatology consultations in a tertiary care hospital in Spain: A retrospective study of 750 patients
- Author
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C, Prada-García, J M, Gonzalo-Orden, J A, Benítez-Andrades, and A, Carvajal-Urueña
- Abstract
Medical consultations are a healthcare task that is generally undervalued and understudied. The main objective of this study was to describe and analyse the consultations requested of dermatology departments and the aspects that are involve in resolving the consultations.We conducted an observational retrospective study that collected the consultations for patients hospitalised over a period of 36 months. We analysed variables related to the management of patients and the quality of the care.The study included 750 patients with a mean age of 64.85 (±20.23) years. The medical departments requested the most consultations, mainly internal medicine departments (37.9%). The most common topic for the consultations was inflammatory dermatoses (36.2%). The most common individual diagnosis was drug rash (8.1%).Consultation activities have a significant impact on the management of hospitalised patients, resulting in improved quality of care and reduced healthcare costs. These activities are also of training value for resident physicians.
- Published
- 2019
29. Anatomy and Imaging of Rat Prostate: Practical Monitoring in Experimental Cancer-Induced Protocols
- Author
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Paula A. Oliveira, Miguel Correia-Cardoso, José M. Gonzalo-Orden, Ana I. Faustino-Rocha, Rita Ferreira, Margarida Fardilha, Maria João Pires, Fernanda Seixas, and Mário Ginja
- Subjects
magnetic resonance imaging (MRI) ,Magnetic Resonance Imaging (MRI) ,Clinical Biochemistry ,030232 urology & nephrology ,Computed tomography ,Review ,computed tomography (CT) ,Macroscopy ,Imaging modalities ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,macroscopy ,medicine ,Ultrasonography ,Microscopy ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Computed Tomography (CT) ,Cancer ,Magnetic resonance imaging ,Anatomy ,ultrasonography ,medicine.disease ,Rat Prostate ,Microscopic Anatomy ,030220 oncology & carcinogenesis ,microscopy ,business ,lcsh:Medicine (General) - Abstract
The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).
- Published
- 2019
30. Post-ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia
- Author
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Diego Pérez-Rodríguez, María Santos-Galdiano, Paloma González-Rodríguez, Berta Anuncibay-Soto, Enrique Font-Belmonte, Arsenio Fernández-López, José M. Gonzalo-Orden, and Irene F. Ugidos
- Subjects
0301 basic medicine ,Male ,Programmed cell death ,Cell Survival ,Necroptosis ,Ischemia ,Pharmacology ,Biochemistry ,Brain Ischemia ,Salubrinal ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Animals ,Protein kinase A ,Cerebral Cortex ,business.industry ,Thiourea ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,Cerebral cortex ,Cinnamates ,Unfolded protein response ,Tumor necrosis factor receptor 1 ,business ,030217 neurology & neurosurgery - Abstract
Ischemic stroke is one of the most important causes of death and disability worldwide. Subroutines underlying cell death after stroke are largely unknown despite their importance in the design of novel therapies for this pathology. Necroptosis, a recently described form of regulated cell death, has been related with inflammation and, in some models, with endoplasmic reticulum (ER) stress. We hypothesize that alleviation of ER stress following a salubrinal treatment will reduce the ischemic-dependent necroptosis. To probe the hypothesis, we measured, at 48 and 72 h after transient global cerebral ischemia in rat, in cerebral cortex and cornu ammonis 1, the main hallmarks of necroptosis: mRNA levels and phosphorylation of mixed lineage kinase domain like pseudokinase as well as receptor interacting serine/threonine protein kinase 3, along the years 2017-2018. Selective neuronal loss after 7 days of the ischemic insult, and other markers related with the inflammatory response were also measured. This study shows that necroptosis in cerebral cortex can be detected after 72 h of the insult and seems to be elicited before 48 h of reperfusion. The type of necroptosis here observed seems to be tumor necrosis factor receptor 1 independent. Necroptotic response is less evident in the cornu ammonis 1 hippocampal area than in cerebral cortex. The treatment with salubrinal administered 1 and 24 h after the ischemia, decreased the necroptotic marker levels and reduced the areas of selective neuronal loss, supporting the presence of ischemic-dependent necroptosis, and the notion that ER stress is involved in the necroptotic response. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.
- Published
- 2019
31. Magnetic resonance imaging: findings of osteochondrosis like-lesions in glenoid fossa and proximal humeral metaphyses in a dog: a case report
- Author
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M. Garcia-Gomez, José M. Gonzalo-Orden, F. S. Roman-Llorens, J. R. Altonaga, M. A. Orden, Mário Ginja, and N. Orellana-Jaimes
- Subjects
Fossa ,040301 veterinary sciences ,Glenoid cavity ,behavioral disciplines and activities ,0403 veterinary science ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Medicine ,Humerus ,030222 orthopedics ,General Veterinary ,medicine.diagnostic_test ,biology ,Osteochondritis ,business.industry ,Magnetic resonance imaging ,04 agricultural and veterinary sciences ,Anatomy ,medicine.disease ,biology.organism_classification ,Osteochondritis dissecans ,medicine.anatomical_structure ,Lameness ,Osteochondrosis ,business - Abstract
Osteochondritis dissecans (OCD) of the humeral head is a common cause of forelimb lameness in dogs. OCD represents the late phase of osteochondrosis (OC). Magnetic resonance imaging (MRI) is a useful technique for detection and characterisation of this disease. The main objective of this study was to show MRI findings of OCD in the humeral head, OC like-lesions in glenoid fossa and proximal humeral metaphyses of a dog. MRI analysis revealed the extent and severity of the inflammatory changes within the subchondral bones in both the glenoid cavity and humeral head. OCD and OC like-lesions were also evaluated in histopathological studies.
- Published
- 2015
32. Safety and Efficacy of New Sirolimus-eluting Stent Models in a Preclinical Study
- Author
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José M. Gonzalo-Orden, Carlos Cuellas-Ramón, Claudia Pérez-Martínez, Luis Duocastella-Codina, Marta Regueiro-Purriños, María López-Benito, María Molina-Crisol, Armando Pérez de Prado, Rodrigo Estévez-Loureiro, and Felipe Fernández-Vázquez
- Subjects
medicine.medical_specialty ,Swine ,medicine.medical_treatment ,Sus scrofa ,Coronary Angiography ,Prosthesis Design ,Coronary Restenosis ,Random Allocation ,Restenosis ,Coronary stent ,Animals ,Medicine ,cardiovascular diseases ,Sirolimus ,business.industry ,Stent ,Drug-Eluting Stents ,General Medicine ,equipment and supplies ,medicine.disease ,Coronary Vessels ,Coronary arteries ,Disease Models, Animal ,surgical procedures, operative ,medicine.anatomical_structure ,Drug-eluting stent ,Radiology ,business ,Immunosuppressive Agents ,Angiographic restenosis ,Artery ,medicine.drug - Abstract
Initial preclinical studies are required during the process of improving polymers, platforms, and drug-eluting systems for new coronary stent designs. Our objective was to analyze the efficacy and safety of new drug-eluting stent models compared with a conventional stent and commercialized drug-eluting stents in an experimental model with healthy porcine coronary arteries.Sixty stents (conventional stent, new sirolimus-eluting stents: drug-eluting stents 1, 2 and 3; Cypher(®) and Xience(®)) were randomly placed in the coronary arteries of 20 Large White domestic pigs. Angiographic and histomorphometric studies were done 28 days later.The stents were implanted at a stent/artery ratio of 1.34±0.15, with no significant differences between groups. The new stents showed less late loss and angiographic restenosis than conventional stents (P=.006 and P.001, respectively). Histologically, restenosis and neointimal area were lower with all the new platforms than with the conventional stents (P.001 for each variable), and no differences were found vs the drug-eluting stents on the market. Safety data showed that endothelialization was lower with drug-eluting stents than with conventional stents, except for drug-eluting stent 3 (P=.084). Likewise, inflammation was lower with drug-eluting stent 3 than with other stents.The new drug-eluting stent platforms studied are associated with less restenosis than conventional stents and showed no significant differences in safety or efficacy vs commercialized drug-eluting stents.
- Published
- 2015
33. Lower urinary tract symptoms and obstructive sleep apnea syndrome: Urodynamic evolution before and after one year of treatment with continuous positive airway pressure
- Author
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S, Fernández-Pello, R, Gil, S, Escaf, L, Rodríguez Villamil, A, Alzueta, C, Rodríguez, and J M, Gonzalo-Orden
- Subjects
Adult ,Male ,Sleep Apnea, Obstructive ,Urodynamics ,Time Factors ,Continuous Positive Airway Pressure ,Lower Urinary Tract Symptoms ,Humans ,Female ,Prospective Studies ,Middle Aged ,Aged - Abstract
To report the clinical evolution and the urodynamic behaviour of several lower tract urinary symptoms in patients with obstructive sleep apnea syndrome before and after the treatment with continuous positive airway pressure (CPAP) devices.A prospective study was performed; patients with recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. In order to discard important lower urinary tract conditions, urological examinations were previously performed. Urinary symptoms were evaluated using the IPSS and OAB-V8 validated questionnaires, three-day Bladder Diary and invasive urodynamic examinations with a gap of one year before and one year after using the CPAP.84 urodynamic studies were carried out in 43 patients. The IPSS score decreased by 3.58 points. The OAB-V8 score decreased by 2.87 points. Nocturia episodes decreased to one per night. The percentage of patients with nocturnal polyuria went down to 26%. The bladder compliance significantly increased (97.39 vs 200.40ml/cm H2O). The presence of detrusor overactivity decreased from 11 (before CPAP) to 5 patients (after CPAP).The proper treatment with CPAP showed a statistical and clinical improvement of several LUTS with limited urodynamic modifications.
- Published
- 2018
34. Brain-derived neurotrophic factor alleviates the oxidative stress induced by oxygen and glucose deprivation in an ex vivo brain slice model
- Author
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Paloma González-Rodríguez, Arsenio Fernández-López, María Santos-Galdiano, Irene F. Ugidos, Diego Pérez-Rodríguez, Enrique Font-Belmonte, José M. Gonzalo-Orden, and Berta Anuncibay-Soto
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Transcription, Genetic ,Physiology ,Cell Survival ,Clinical Biochemistry ,Ischemia ,Hippocampus ,Hippocampal formation ,medicine.disease_cause ,Models, Biological ,Antioxidants ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Slice preparation ,Cytosol ,Neurotrophic factors ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Phosphorylation ,Brain-derived neurotrophic factor ,Cell Death ,Chemistry ,Brain-Derived Neurotrophic Factor ,Brain ,NADPH Oxidases ,Cell Biology ,medicine.disease ,Oxygen ,Oxidative Stress ,Phospholipases A2 ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Glucose ,nervous system ,Cerebral cortex ,030220 oncology & carcinogenesis ,Reperfusion ,Lipid Peroxidation ,Reactive Oxygen Species ,Oxidative stress - Abstract
Brain-derived neurotrophic factor (BDNF) is considered as a putative therapeutic agent against stroke. Since BDNF role on oxidative stress is uncertain, we have studied this role in a rat brain slice ischemia model, which allows BDNF reaching the neural parenchyma. Hippocampal and cerebral cortex slices were subjected to oxygen and glucose deprivation (OGD) and then returned to normoxic conditions (reperfusion-like, RL). OGD/RL increased a number of parameters mirroring oxidative stress in the hippocampus that were reduced by the BDNF presence. BDNF also reduced the OGD/RL-increased activity in a number of antioxidant enzymes in the hippocampus but no effects were observed in the cerebral cortex. In general, we conclude that alleviation of oxidative stress by BDNF in OGD/RL-exposed slices relies on decreasing cPLA2 activity, rather than modifying antioxidant enzyme activities. Moreover, a role for the oxidative stress in the differential ischemic vulnerability of cerebral cortex and hippocampus is also supported.
- Published
- 2018
35. Syndecan-1 and Outcome of Ambulatory Patients with Stable Heart Failure
- Author
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José M. Gonzalo-Orden, Miguel Angel Rodriguez-Garcia, Felipe Fernández-Vázquez, Ignacio Iglesias-Garriz, and Abel García del Egido
- Subjects
medicine.medical_specialty ,business.industry ,Heart failure ,Internal medicine ,Ambulatory ,medicine ,Cardiology ,medicine.disease ,business ,Outcome (game theory) ,Syndecan 1 - Published
- 2018
36. D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis
- Author
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Universitat Rovira i Virgili, Jara-Palomares L; Solier-Lopez A; Elias-Hernandez T; Asensio-Cruz M; Blasco-Esquivias I; Sanchez-Lopez V; de la Borbolla M; Arellano-Orden E; Suarez-Valdivia L; Marin-Romero S; Marin-Barrera L; Ruiz-Garcia A; Montero-Romero E; Navarro-Herrero S; Lopez-Campos J; Serrano-Gotarredona M; Praena-Fernandez J; Sanchez-Diaz J; Otero-Candelera R, Universitat Rovira i Virgili, and Jara-Palomares L; Solier-Lopez A; Elias-Hernandez T; Asensio-Cruz M; Blasco-Esquivias I; Sanchez-Lopez V; de la Borbolla M; Arellano-Orden E; Suarez-Valdivia L; Marin-Romero S; Marin-Barrera L; Ruiz-Garcia A; Montero-Romero E; Navarro-Herrero S; Lopez-Campos J; Serrano-Gotarredona M; Praena-Fernandez J; Sanchez-Diaz J; Otero-Candelera R
- Abstract
© 2018, Cancer Research UK. Background: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT. Methods: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence. Results: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3–15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19–52) and 5.81 for DD (95% CI: 1.1–31.7). Conclusions: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.
- Published
- 2018
37. Contrast-enhanced dynamic magnetic resonance nephrography in healthy dogs
- Author
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C.C. Pérez-García, M. A. Orden, Mário Ginja, J.M. Fonseca-Matheus, J. R. Altonaga, and José M. Gonzalo-Orden
- Subjects
Gadolinium DTPA ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Urinary system ,Gadolinium ,media_common.quotation_subject ,Contrast Media ,chemistry.chemical_element ,Kidney ,Dogs ,Urinary excretion ,Reference Values ,Animals ,Medicine ,Contrast (vision) ,media_common ,General Veterinary ,medicine.diagnostic_test ,business.industry ,Low dose ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,chemistry ,Excretory system ,Animal Science and Zoology ,Signal intensity ,business ,Nuclear medicine - Abstract
Twenty-three healthy mixed-breed male adult dogs were examined using serial magnetic resonance (MR) renograms. The images were obtained using a dynamic gradient-echo, fast SPGR, T1-weighted sequence and low doses of gadolinium chelates (0.025 mmol/kg). Time–intensity curves were obtained to assess typical urinary excretion parameters, namely, time to vascular peak (TVP), time to vascular drop (TVD), time to glomerular peak (TGP), parenchymal phase length (PPL), gradient of parenchymal phase (GPP) and pattern of excretory segment. The mean TVP, TVD, TGP and PPL were 31.6 ± 11.8, 43.4 ± 11.2, 154.0 ± 36.2 and 115.2 ± 37.7 s, respectively. The GPP was 24.1 ± 8.6% of signal intensity per min. The excretory segment was concave in all cases, and at the end of the examination, 87.1% of kidneys had shown a reduction in signal intensity of 50%. This MR nephrography protocol can provide adequate time–intensity curve parameters for the urinary system of dogs, offers excellent anatomical detail, and represents an alternative to radionuclide nephrography.
- Published
- 2011
38. Modelos animales para el aprendizaje de la cirugía endovascular
- Author
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M. Ballesteros-Pomar, M.C. Fernández-Morán, Marta Regueiro-Purriños, José M. Gonzalo-Orden, F. Vaquero-Morillo, and José R. Altónaga
- Subjects
Cardiology and Cardiovascular Medicine - Abstract
Resumen La evolucion y transformacion de la especialidad de Angiologia y Cirugia Vascular en los ultimos 20 anos hacia modos minimamente invasivos, materializados en la cirugia endovascular, ha constituido un punto de inflexion en el aprendizaje de las tecnicas y procedimientos quirurgicos vasculares. El uso de modelos animales para la adquisicion de las habilidades y destreza quirurgica necesarias para la realizacion de cirugia endovascular representa la culminacion en el aprendizaje de la misma como paso previo necesario y exigible para su ejecucion en el humano. En este articulo se describe el contenido y evolucion de los cursos de cirugia endovascular en modelos animales, como reflejo de la evolucion de la especialidad a lo largo de los ultimos 15 anos.
- Published
- 2014
39. Análisis de la eficacia y la seguridad de distintos balones liberadores de paclitaxel en un modelo animal
- Author
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Luis Duocastella Codina, Carlos Cuellas Ramón, Alex Gómez Castel, María Molina Crisol, Felipe Fernández-Vázquez, José M. Gonzalo-Orden, Alejandro Diego Nieto, Armando Pérez de Prado, Marta Regueiro Purriños, and Claudia Pérez-Martínez
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Resumen Introduccion y objetivos Los balones liberadores de paclitaxel tienen demostrada eficacia en el tratamiento y la prevencion de la restenosis. Sin embargo, no todos los dispositivos comercializados son igualmente efectivos; por ello es importante comparar los resultados en un modelo preclinico. Nuestro objetivo es analizar la seguridad y la eficacia preclinicas de distintos dispositivos. Metodos En 17 cerdos domesticos (25 ± 3 kg) se implantaron 51 stents metalicos (Architect®, iVascular), uno en cada rama coronaria principal, y se sobredilataron con distintos balones de control (n = 10) o liberadores de paclitaxel: balon liberador de paclitaxel 1 (iVascular) (n = 15); balon liberador de paclitaxel 2 (iVascular) (n = 16) e In.Pact Falcon® (Medtronic) (n = 10). Tras 28 dias, se analizaron los resultados de restenosis (angiografia e histomorfometria) y de reparacion vascular: dano vascular, endotelizacion, persistencia de fibrina e inflamacion. Resultados Los distintos balones liberadores de paclitaxel mostraron valores similares de estenosis en el seguimiento significativamente menores que los controles: angiografia, el 9 ± 12% frente al 34 ± 18% (p Conclusiones En este modelo preclinico, los balones liberadores de paclitaxel analizados mostraron una reduccion significativa de la restenosis. Aunque no se observaron datos de dano vascular o inflamacion persistentes, si se apreciaron los efectos de la accion farmacologica en forma de endotelizacion retrasada y acumulacion de fibrina.
- Published
- 2014
40. Magnetic resonance imaging and immunohistochemistry of primary vertebral hemangiosarcoma in a dog and implications for diagnosis and therapy
- Author
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Claudia, Pérez-Martínez, Marta, Regueiro-Purriños, Beatriz, Fernández-Martínez, José R, Altónaga, José M, Gonzalo-Orden, and María J, García-Iglesias
- Subjects
Male ,Dogs ,Lumbar Vertebrae ,Spinal Neoplasms ,Hemangiosarcoma ,Animals ,Bone Neoplasms ,Scientific ,Dog Diseases ,Immunohistochemistry ,Magnetic Resonance Imaging - Abstract
A vertebral mass in a dog with an acute onset paraparesis was identified by magnetic resonance imaging. A poorly differentiated hemangiosarcoma was diagnosed by histopathology and immunohistochemistry. Endothelial nitric oxide synthase could be a new differential marker for poorly differentiated hemangiosarcoma in dogs. Immunohistochemical detection of p53 phosphorylated at Serine392, p53, CD117, and CD44 suggest targets for design of therapeutic strategies.
- Published
- 2016
41. Cross-Sectional Anatomy, Computed Tomography and Magnetic Resonance Imaging of the Thoracic Region of Common Dolphin (Delphinus delphis) and Striped Dolphin (Stenella coeruleoalba)
- Author
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J. M. Ajenjo, J. D. Barreiro-Vázquez, J. M. Alonso-Farré, Andrés Barreiro-Lois, M. Llarena-Reino, E. Degollada, and M. Gonzalo-Orden
- Subjects
Male ,Common dolphin ,Common Dolphins ,Radiography ,Stenella coeruleoalba ,Delphinus delphis ,Stenella ,Reference Values ,biology.animal ,medicine ,Animals ,General Veterinary ,biology ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,General Medicine ,Anatomy ,Thorax ,biology.organism_classification ,Magnetic Resonance Imaging ,Sagittal plane ,medicine.anatomical_structure ,Gross anatomy ,Female ,Radiography, Thoracic ,Tomography ,Tomography, X-Ray Computed ,business ,human activities - Abstract
The aim of this study was to provide a detailed anatomical description of the thoracic region features in normal common (Delphinus delphis) and striped dolphins (Stenella coeruleoalba) and to compare anatomical cross-sections with computed tomography (CT) and magnetic resonance imaging (MRI) scans. CT and MRI were used to scan 7 very fresh by-caught dolphin cadavers: four common and three striped dolphins. Diagnostic images were obtained from dolphins in ventral recumbency, and after the examinations, six dolphins were frozen (−20°C) and sliced in the same position. As well as CT and MRI scans, cross-sections were obtained in the three body planes: transverse (slices of 1 cm thickness), sagittal (5 cm thickness) and dorsal (5 cm thickness). Relevant anatomical features of the thoracic region were identified and labelled on each section, obtaining a complete bi-dimensional atlas. Furthermore, we compared CT and MRI scans with anatomical cross-sections, and results provided a complete reference guide for the interpretation of imaging studies of common and striped dolphin's thoracic structures
- Published
- 2013
42. Sub-acute and chronic MRI findings in bilateral canine fibrotic contracture of the infraspinatus muscle
- Author
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M. Regueiro, Mário Ginja, N. G. Orellana-james, Adelina Gama, Paula A. Oliveira, José M. Gonzalo-Orden, and José Antonio Rodríguez-Altónaga
- Subjects
Shoulder ,Contracture ,medicine.diagnostic_test ,Shoulder surgery ,business.industry ,Shoulders ,Lameness, Animal ,medicine.medical_treatment ,Infraspinatus muscle ,Magnetic resonance imaging ,Physical examination ,Anatomy ,Degeneration (medical) ,Fibrosis ,Magnetic Resonance Imaging ,Dogs ,Lameness ,Animals ,Medicine ,Female ,Dog Diseases ,medicine.symptom ,Small Animals ,business - Abstract
A six-year-old, 30-kg female German pointer dog was presented for examination with a history of pre-existing right-forelimb lameness and more recent (3 months) persistent lameness in the left-forelimb. Physical examination revealed mild left-forelimb lameness and a mild circumduction movement. There were no signs of pain or crepitation detected during manipulation of the shoulders, but the animal was unable to fully flex both glenohumeral joints. Magnetic resonance imaging, using fast recovery fast spin echo T2-weighted and fat saturated proton density sequences, revealed abnormal heterogeneous hypointensity in the right infraspinatus muscle and a heterogeneous hyperintense area in the left infraspinatus muscle. Surgical treatment consisting of a bilateral infraspinatus tenectomy resulted in improved limb function. Histopathological examination demonstrated tissue changes in the right infraspinatus, characterised by myofibre degeneration and fibrosis, compatible with a chronic degenerative process, while changes in the left infraspinatus muscle were characterised by variable degrees of fibre degeneration, haemorrhage and interstitial oedema.
- Published
- 2013
43. Anestesia en el modelo animal de investigación cardiovascular
- Author
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José M. Gonzalo-Orden, José M. Ajenjo, Marta Regueiro-Purriños, Manuel García-Gómez, José R. Altónaga, Felipe Fernández-Vázquez, and Armando Pérez de Prado
- Subjects
medicine.medical_specialty ,Animal model ,business.industry ,Animal welfare ,Cardiovascular research ,medicine ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,Surgery - Abstract
Preclinical cardiovascular research employs of a wide range of animal models, including large and small animals and a variety of species. Selecting a species for use as an animal model is one of the most important decisions that has to be taken before starting a biomedical study. The appropriate choice of anesthesia increases the survival rate and improves animal welfare, both of which increase the ethical acceptability of this kind of research and ensure that the experimental models are used as efficiently as possible. This review discusses the specific characteristics of the different animal models used in cardiovascular research from the point of view of anesthesia and analgesia and, in each case, describes the most appropriate techniques, drugs and dosages.
- Published
- 2013
44. Resonancia magnética cardiaca en modelos animales
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José R. Altónaga, Alejandro Diego-Nieto, Armando Pérez de Prado, José M. Ajenjo, José M. Gonzalo-Orden, Marta Regueiro-Purriños, Felipe Fernández-Vázquez, and Carlos Cuellas-Ramón
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business.industry ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Humanities - Abstract
Resumen La resonancia magnetica se ha erigido en la tecnica de eleccion para el diagnostico y manejo de multiples enfermedades. En el campo cardiaco permite alcanzar una precision muy alta en la cuantificacion y la caracterizacion tisular gracias a su elevada resolucion espacial y temporal a la vez que permite una muy buena caracterizacion tisular. Por ello, su aplicacion a la investigacion traslacional resulta clave en la valoracion de muchos de los resultados. En este original se revisan las aplicaciones de la tecnica en distintos modelos animales, desde los mas pequenos hasta el mas empleado en la investigacion cardiovascular traslacional, el porcino. Se analizan los distintos medios de contraste empleados y se sistematizan los estudios cardiacos para la obtencion de los mejores resultados anatomicos y funcionales.
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- 2013
45. Investigación traslacional en isquemia, infarto de miocardio y reperfusión
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Felipe Fernández-Vázquez, José M. Gonzalo-Orden, Carlos Cuellas-Ramón, Armando Pérez de Prado, Claudia Pérez-Martínez, and Alejandro Diego-Nieto
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medicine.medical_specialty ,Beating heart ,Myocardial ischemia ,business.industry ,Infarction ,Disease ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Internal medicine ,medicine ,Cardiology ,In patient ,Myocardial necrosis ,Cardiology and Cardiovascular Medicine ,business ,Reperfusion injury ,Artery - Abstract
Preclinical research into all aspects of myocardial ischemia, infarction and reperfusion has made use of a range of models, from ex vivo models of the isolated beating heart to animal models of coronary artery occlusion produced using surgical or endovascular techniques. In the area of cardiac ischemia, such research has led to the development of several forms of treatment that were subsequently found to be effective in patients. The principle tools for reducing the extent of myocardial necrosis, and thereby improving prognosis, comprise different techniques for recanalization of the occluded artery responsible for an infarction, all of which must be implemented as soon as possible (“time is muscle”). However, reperfusion can itself result in injury that exacerbates the effects of an infarction. A number of ways of limiting reperfusion injury have been tested successfully in animal models (e.g. various pharmacological treatments and different forms of myocardial conditioning) but none has proven effective when applied clinically. The recent explosion of interest in regenerative medicine has been particularly important in the area of cardiovascular disease, and future development will require the best possible set of preclinical tests. Animal models continue to be refined, with the ultimate goal being the perfect model that replicates all aspects of human biology and pathology.
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- 2013
46. Histology and immunochemistry evaluation of autologous translocation of retinal pigment epithelium-choroid graft in porcine eyes
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Jose-Carlos Pastor, José M. Gonzalo-Orden, Marta Regueiro-Purriños, Anna Sala-Puigdollers, Girish K. Srivastava, Denise Hileeto, Maria Luisa Parrado, Enrique Rodríguez de la Rúa, and Ivan Fernandez-Bueno
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Proliferative vitreoretinopathy ,Pathology ,medicine.medical_specialty ,Retina ,Retinal pigment epithelium ,Retinal detachment ,Retinal ,General Medicine ,Biology ,medicine.disease ,eye diseases ,Transplantation ,Ophthalmology ,chemistry.chemical_compound ,medicine.anatomical_structure ,RPE65 ,chemistry ,medicine ,sense organs ,Choroid - Abstract
Purpose: To evaluate structure and cellular functionality of retinal pigment epithelium (RPE)-choroid grafts after autologous translocation in porcine eyes. Methods: Retinal pigment epithelium-choroid grafts were obtained from the nasal midperiphery donor site and translocated to the central area in 12 pigs (12 eyes). Grafts were placed under the central retina through a retinotomy. Ophthalmoscopic and pathological evaluations were performed immediately (n = 1) and at 15 (n = 3) and 30 (n = 3) days after surgery. Untranslocated nasal RPE-choroid grafts were obtained at time of surgery and used as controls. Specimens were evaluated by standard histology and by immunochemical studies of RPE65, CRALBP and GFAP. Results: Five animals were lost to follow-up owing to surgery or anaesthesia complications. Ophthalmoscopic examination revealed that the grafts remained in place at all time-points studied. Fifteen and thirty days postsurgery, some areas of the transplanted RPE maintained a monolayered structure. Retinal pigment epithelium cells were firmly attached to Bruch’s membrane and predominantly preserved polarity and pigment distribution. However, RPE65, CRALBP and GFAP patterns of expression and distribution were diminished and modified during follow-up. Ophthalmoscopic retinal detachment and proliferative vitreoretinopathy (PVR), confirmed by microscopic evaluation, complicated all cases at 30 days of follow-up. Conclusion: Autologous RPE-choroid grafts survived up to 30 days in porcine eyes. Histological and immunochemical evaluation revealed preserved transplanted RPE cells morphology accompanied by alterations in the immunoreactivity expression of functional proteins, and development of significant PVR. The data presented in this manuscript provide insights into the fate, viability and cellular functionality of the transplanted RPE-choroid graft, serving as foundation for further knowledge and improvement of this technique.
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- 2012
47. Preclinical Evaluation of Coronary Stents: Focus on Safety Issues
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Carlos Cuellas, José M. Gonzalo-Orden, J. Francisco G. Marin, Armando Pérez de Prado, B. Martínez-Fernández, Alejandro Diego, José R. Altónaga, Marta Regueiro, Claudia Pérez-Martínez, and Felipe Fernández-Vázquez
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Drug ,Pharmacology ,medicine.medical_specialty ,Iliac artery ,business.industry ,media_common.quotation_subject ,Drug Evaluation, Preclinical ,Coronary stenting ,Translational research ,Coronary Artery Disease ,medicine.disease ,Coronary artery disease ,Restenosis ,Internal medicine ,medicine ,Cardiology ,Animals ,Humans ,Stents ,Stent thrombosis ,business ,Complication ,Cardiology and Cardiovascular Medicine ,media_common - Abstract
In recent years, we have witnessed a revolution in the treatment of coronary artery disease. The development and improvement of drug eluting stents (DES) have lowered the incidence of restenosis to one-digit figures. In the search for a superior efficacy, animal models have played a key role. The classical swine model of coronary stenting remains the preferred model to measure restenosis, although the rabbit iliac artery stenting has become an accepted alternative. After widespread clinical use of DES, an unforeseen complication arose: late stent thrombosis. In a back-to-bench step, some data from animal models helped to explain the phenomenon. A delayed and incomplete vascular healing was detected. Toxic and hypersensitivity reactions to polymers and/or drugs seem to be the underlying causes. So, translational research focused on the safety aspect of these devices: development of better drug carriers as absorbable polymers or fully bioresorbable scaffolds, selection of different drugs and assessment of the re-endothelialization process. We review and evaluate the efficacy and safety of coronary stents in different animal models. Further improvements in this field such as, the selection of better animal models (e.g. hyperlipidemic, diabetic, atherosclerotic) that closely mimic the clinical setting and longer follow-up periods to detect late complications are also discussed.
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- 2012
48. Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders
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María José Díez Liebana, Ana M. Sahagún, Jose M. Gonzalo Orden, Matilde Sierra Vega, Nélida Fernández Martínez, Juan José García Vieitez, and Cristina López Cadenas
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medicine.medical_specialty ,Time Factors ,animal diseases ,Mammary Glands, Animal ,Internal medicine ,Enrofloxacin ,Animals ,Medicine ,Tissue Distribution ,Tissue distribution ,Udder ,Sheep ,Chromatography ,General Veterinary ,business.industry ,General Medicine ,Anti-Bacterial Agents ,Perfusion ,Intramammary route ,Endocrinology ,medicine.anatomical_structure ,Tyrode solution ,Systemic administration ,Female ,Sample collection ,Uv detection ,business ,Fluoroquinolones ,medicine.drug - Abstract
Objective—To determine the tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders by measuring its concentration at various sample collection sites. Sample—26 udders (obtained following euthanasia) from 26 healthy lactating sheep. Procedures—For each isolated udder, 1 mammary gland was perfused with warmed, gassed Tyrode solution. Enrofloxacin (1 g of enrofloxacin/5 g of ointment) was administered into the perfused gland via the intramammary route or systemically via the perfusion fluid (equivalent to a dose of 5 mg/kg). Samples of the perfusate were obtained every 30 minutes for 180 minutes; glandular tissue samples were obtained at 2, 4, 6, and 8 cm from the teat base after 180 minutes. The enrofloxacin content of the perfusate and tissue samples was analyzed via high-performance liquid chromatography with UV detection. Results—After intramammary administration, maximun perfusate enrofloxacin concentration was detected at 180 minutes and, at this time, mean tissue enrofloxacin concentration was detected and mean tissue enrofloxacin concentration was 123.80, 54.48, 36.72, and 26.42 μg/g of tissue at 2, 4, 6, and 8 cm from the teat base, respectively. Following systemic administration, perfusate enrofloxacin concentration decreased with time and, at 180 minutes, tissue enrofloxacin concentrations ranged from 40.38 to 35.58 μg/g of tissue. Conclusions and Clinical Relevance—By 180 minutes after administration via the intramammary or systemic route in isolated perfused sheep mammary glands, mean tissue concentration of enrofloxacin was greater than the minimum inhibitory concentration required to inhibit growth of 90% of many common mastitis pathogens in sheep. Use of either route of administration (or in combination) appears suitable for the treatment of acute mastitis in sheep.
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- 2012
49. Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol
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David A. Ferreira, José M. Gonzalo-Orden, Luís Antunes, Susana Brás, and L. Ribeiro
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Male ,Correlation ,Acepromazine ,Depth of anaesthesia ,Consciousness Monitors ,Dogs ,medicine ,Animals ,Corneal reflex ,Infusions, Intravenous ,Propofol ,Blinking ,General Veterinary ,Electromyography ,business.industry ,Hemodynamics ,Electroencephalography ,Prediction probability ,Burst suppression ,Neutering ,Anesthesia ,Anesthesia, Intravenous ,Female ,business ,Anesthetics, Intravenous ,medicine.drug - Abstract
Objective To evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations. Study design Prospective clinical study. Animals Fourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures. Methods Dogs were premedicated with 0.05 mg kg−1 acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 μg dL−1 was set initially, then PropCps were increased in 1 μg dL−1 steps to 7, 9 and then 11 μg dL−1. Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of ‘planes’ based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated. Results The PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively. Conclusion and clinical relevance The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia.
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- 2012
50. Endogenous Cardiac Stem Cell Activation by Insulin-Like Growth Factor-1/Hepatocyte Growth Factor Intracoronary Injection Fosters Survival and Regeneration of the Infarcted Pig Heart
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Armando Pérez de Prado, Manuel Galiñanes, Felipe Fernández-Vázquez, José M. Gonzalo-Orden, Valter Agosti, Santo Dellegrottaglie, Georgina M. Ellison, Andrew J. Smith, Saranya Purushothaman, Carlos Cuellas Ramón, Michele Torella, Claudio Iaconetti, Valentina Galuppo, Carla Vicinanza, Bernardo Nadal-Ginard, Ciro Indolfi, Cheryl D. Waring, Claudia Pérez-Martínez, and Daniele Torella
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Cardiac function curve ,medicine.medical_specialty ,Cell Survival ,Swine ,cardiac magnetic resonance imaging ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,growth factors ,Medicine ,Animals ,Humans ,Myocytes, Cardiac ,Artery occlusion ,Myocardial infarction ,Progenitor cell ,Insulin-Like Growth Factor I ,Endogenous cardiac stem cell ,030304 developmental biology ,0303 health sciences ,business.industry ,Hepatocyte Growth Factor ,Stem Cells ,cardiac stem cells ,Cell Differentiation ,medicine.disease ,Coronary Vessels ,3. Good health ,Transplantation ,Endocrinology ,myocardial infarction ,Injections, Intra-Arterial ,myocardial regeneration ,Hepatocyte growth factor ,Drug Therapy, Combination ,Female ,Stem cell ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Objectives The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. Background In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). Methods Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. Results The IGF-1/HGF activated c-kit positive–CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive–CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. Conclusions In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.
- Published
- 2011
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