Person: Cruz López, Fátima
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First Name
Fátima
Last Name
Cruz López
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
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Item Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2(Veterinary Research, 2024) Sánchez Morales, Lidia; Porras, Néstor; García-Seco Romero, María Teresa; Pérez Sancho, Marta; Cruz López, Fátima; Chinchilla, Blanca; Barroso Arévalo, Sandra; Diaz Frutos, Marta; Buendía, Aránzazu; Moreno, Inmaculada; Briones Dieste, Víctor; Risalde, María de los Ángeles; de la Fuente, José; Juste, Ramón; Garrido, Joseba; Balseiro, Ana; Gortázar, Christian; Rodríguez Bertos, Antonio Manuel; Domínguez, Mercedes; Domínguez Rodríguez, Lucas JoséIn the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3–4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3–4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3–4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.Item Hemolysis, icterus and lipemia interfere with the determination of two oxidative stress biomarkers in canine serum(BMC Veterinary Research, 2023) Pérez Montero, Blanca; Fermín Rodríguez, María Luisa; Miró Corrales, Guadalupe; Juan Ferré, Lucía De; Cruz López, FátimaBackground: Oxidative stress has been proven to play a role in numerous human and canine diseases. Among the biomarkers of oxidative stress, Thiobarbituric Acid Reactive Substances (TBARS) and Total Antioxidant Status (TAS) are two of the most widely used. Preanalytical factors are crucial for obtaining accurate results in these assays. Hemolysis, icterus and lipemia (HIL) are common sources of preanalytical errors in the laboratory; however, limited information is available regarding the considerations for canine specimens. Therefore, the objective of this study was to evaluate the potential interferences of HIL in the determination of TBARS and TAS in canine serum. Methods: Solutions of pooled canine serum samples were prepared by adding increasing concentrations of hemolysate, bilirubin and a synthetic lipid emulsion. TBARS and TAS were determined, and biases from the control value caused by the interfering substances were calculated. Results: Hemolysis, icterus and lipemia induced significant interferences on TBARS and TAS, albeit to varying degrees depending on the specific biomarker and interfering substance. TBARS appeared to be more susceptible to interferences in this study. Slight hemolysis, moderate icterus and slight lipemia caused notable deviations in TBARS values, surpassing the acceptable threshold for interference. TAS assay was also affected by HIL, although to a lesser extent compared to TBARS. Significant biases from TAS control value were observed when icterus was moderate, and when hemolysis and lipemia were more pronounced. Conclusions: In light of our results, we conclude that hemolyzed, icteric and lipemic specimens are not suitable for TBARS and TAS determination in canine serum. Our findings hold considerable practical utility, as a simple visual inspection would be sufficient for identifying and excluding such specimens.- Project number: 371
Item Infequus 2.0: Plataforma de enfermedades infecciosas en équidos(2022) Juan Ferré, Lucía De; Cruz López, Fátima; Álvarez Sánchez, Julio; Ancochea Nodal, Carlos; Bezos Garrido, Javier; Briones Dieste, Víctor; García Benzaquén, Nerea; González Domínguez, Sergio; Hernández Carrillo, Javier; Pérez Sancho, Marta; Rodríguez Bertos, Antonio Manuel; Romero Martínez, Beatriz; Santiago Llorente, Isabel; Domínguez Rodríguez, Lucas José Item First report and molecular characterization of cases of natural Taylorella asinigenitalis infection in three donkey breeds in Spain(Veterinary Microbiology, 2023) Dorrego Rodríguez, Abel; Herranz Benito, Carmen; Pérez Sancho, Marta; Camino Gutiérrez, Eliazar; Gómez Arrones, Vanesa; Carrasco, Juan Jesús; Gabriel Pérez, Jesús de; Serres Dalmau, María Consolacion; Cruz López, FátimaTaylorella asinigenitalis is a non-pathogenic bacteria isolated from the genital tract of donkeys but also a cause of metritis and vaginal discharge in mares. It is closely related to Taylorella equigenitalis, the cause of Contagious Equine Metritis (CEM) in horses, and has been present in different countries in Europe since 1995. Up to date, there are no studies on the prevalence of T. asinigenitalis in the equine or asinine populations in Spain; this is the first report of the presence of T. asinigenitalis in donkeys (Equus asinus) from different breeds in three regions of Spain. A total of 106 healthy animals of three different Spanish donkey breeds: Andaluza (26), Majorera (12) and Zamorano-Leonés (68) were sampled between June and July 2017 and a real-time PCR was used to detect T. asinigenitalis in all samples. A total of 39/221 (17,65 %) samples from 22/106 (20,75 %) animals yielded a positive result and were further characterized by MLST; an allelic profile and Sequence Type (ST) could be assigned to 11 of the 39 positive samples, resulting in four novel STs and no clonal complexes within the PubMLST database. There were statistically significant differences in the percentage of positive animals by breed and sex, and also in the variability of STs between farms. Breeding management would have an influence on the percentage of positives in a farm; artificial insemination and separating jacks from jennies should be implemented. Further studies to detect and characterize T. asinigenitalis in donkeys and horses from Spain would be required to obtain a broader epidemiological picture in this country.Item Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2(Veterinary Research, 2024) Sánchez Morales, Lidia; Porras González, Néstor; García-Seco Romero, María Teresa; Pérez Sancho, Marta; Cruz López, Fátima; Chinchilla Rodríguez, Blanca; Barroso Arévalo, Sandra; Díaz Frutos, Marta; Buendía Andrés, Aránzazu; Moreno, Inmaculada; Briones Dieste, Víctor; Risalde, María A.; De la Fuente, José; Juste, Ramón; Garrido, Joseba; Balseiro, Ana; Gortázar, Christian; Rodríguez Bertos, Antonio Manuel; Domínguez, Mercedes; Domínguez Rodríguez, Lucas JoséIn the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3–4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3–4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3–4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.Item Detection of equine herpesvirus-1 (EHV-1) in urine samples during outbreaks of equine herpesvirus myeloencephalopathy(Equine Veterinary Journal, 2023) Velloso Álvarez, Ana; Jose Cunilleras, E.; Dorrego Rodríguez, Abel; Santiago Llorente, Isabel; De la Cuesta Torrado, María; Troya Portillo, Lucas; Rivera Arroyo, Belén; Vitale, Valentina; Juan Ferré, Lucía De; Cruz López, FátimaBackground: Real-time PCR is the diagnostic technique of choice for the diagnosis and control of equine herpesvirus-1 (EHV-1) in an outbreak setting. The presence of EHV-1 in nasal swabs (NS), whole blood, brain and spinal cord samples has been extensively described; however, there are no reports on the excretion of EHV-1 in urine, its DNA detection patterns, and the role of urine in viral spread during an outbreak. Objectives: To determine the presence of EHV-1 DNA in urine during natural infection and to compare the DNA detection patterns of EHV-1 in urine, buffy coat (BC) and NS. Study design: Descriptive study of natural infection. Methods: Urine and whole blood/NS samples were collected at different time points during the hospitalisation of 21 horses involved in two EHV-1 myeloencephalopathy outbreaks in 2021 and 2023 in Spain. Quantitative real-time PCR was performed to compare the viral DNA load between BC-urine samples in 2021 and NS-urine samples in 2023. Sex, age, breed, presence of neurological signs, EHV-1 vaccination status and treatment data were recorded for all horses. Results: A total of 18 hospitalised horses during the 2021 and 2023 outbreaks were positive for EHV-1, and viral DNA was detected in urine samples from a total of 11 horses in both outbreaks. Compared with BC samples, DNA presence was detected in urine samples for longer duration and with slightly higher concentration; however, compared with NS, detection of EHV-1 in urine was similar in duration with lower DNA concentrations. Main limitations: Limited sample size, different sampling times and protocols (BC vs. NS) in two natural infection outbreak settings. Conclusions: EHV-1 was detected in the urine from naturally infected horses. Urine should be considered as complimentary to blood and NS in diagnosis of EHV-1 infection.Item Haemato-biochemical characterization of equine piroplasmosis asymptomatic carriers and seropositive, real-time PCR negative horses(Veterinary Parasitology, 2023) Dorrego Rodríguez, Abel; Camino Gutiérrez, Eliazar; Gago, Paloma; Buendia Andrés, Aranzazu; Acurio, Kiara; González Domínguez, Sergio; Juan Ferré, Lucía De; Cruz López, FátimaEquine piroplasmosis (EP) is caused by Theileria equi and Babesia caballi, transmitted by tick vectors. Horses can suffer an acute, subacute, and chronic forms of the disease, with clinical signs such as poor performance, fever, pale mucosal membranes, and jaundice. The diagnosis of EP subclinical cases is complex due to the sensitivity of real-time PCR and the limited parasite load in some carriers, making it challenging to differentiate them from seropositive, PCR negative (S+PCR-) individuals. This study aimed to describe haematological and biochemical changes in asymptomatic EP carriers, EP S+PCR- horses and control horses (EP seronegative and PCR negative). It also investigated potential haemato-biochemical markers to aid in distinguishing true EP carriers alongside molecular and serological tests. A comprehensive haematology and biochemistry profile was conducted on 410 sera and EDTA blood samples, comprising 130 EP positives by real-time PCR and competitive ELISA (cELISA) (carriers), 130 EP negatives by real-time PCR but positive to cELISA (S+PCR-) and 150 EP negative horses to real-time PCR and c-ELISA (controls). Our study confirmed that a haematological and biochemistry profile could help to differentiate between EP carriers/S+PCR- from healthy horses. Carriers and S+PCR- horses showed significant increases in the white blood cell count (WBC), high total proteins (TP) and total globulins (GLOB) concentration, and liver function markers compared to controls. Additionally, the evaluation of uric acid (UA) suggested oxidative stress in carrier horses. However, no useful haemato-biochemical diagnostic markers were identified to aid the challenging differentiation of EP carriers and S+PCR- horses, highlighting the need for improvement in molecular/serological diagnosis for these horses.