The effects of sildenafil citrate on the fetoplacental development and hemodynamics in a rabbit model of intrauterina growth restriction

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto–placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown–rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation

Reduced plasma levels of Ang-2 and sEng as novel biomarkers in Hereditary Hemorrhagic Telangiectasia (HHT)

6 páginas, 2 figuras, 4 tablas -- PAGS. nros. 494-499Hereditary hemorrhagic telangiectasia (HHT; OMIM 187300) is an autosomal dominant vascular disorder characterized by telangiectases and internal arteriovenous malformations caused by mutations in certain elements of the TGF-β receptor complex. In the case of HHT1 mutations in the endoglin gene are responsible, whereas mutations in the ALK1 gene (an activin receptor-like kinase 1), lead to HHT2. Another two loci found at chromosome 5 and chromosome 7, whose target genes remain unidentified, lead to types 3 and 4 of the disease, respectively. Mutations in the MADH4/SMAD4 gene, another member of the TGF-β signalling pathway, lead to a combined syndrome of familial juvenile polyposis associated with HHTThis work was supported by the Ministerio de Ciencia e Innovación (SAF2007-61827 to Carmelo Bernabeu and SAF08-01218 to Luisa Botella), Instituto de Salud Carlos III (ISCIII-CIBER Carmelo Bernabeu 06/07/0038 and ISCIII-RETICC RD06/0020) and the Fundación Ramón Areces of Spain (2007 grant for rare diseasesPeer reviewe

Metformin alleviates obesity and systemic oxidative stress in obese young swine

The present study assessed the relationship between obesity induced by lifestyle and systemic oxidative stress and possible modulations by oral metformin treatments in young individuals, by using a translational swine model of obesity and associated cardiometabolic disorders (Iberian pig). The results indicate the existence of an age-related increase in both adiposity and systemic oxidative stress (using hydrogen peroxide as a marker), which is higher in individuals with obesogenic lifestyle and increased weight and obesity. Such effect was not found in individuals treated with metformin. The translation of these results suggests that childhood obesity increases production of reactive oxygen species (ROS), and therefore systemic oxidative stress. Treatment with metformin would improve such oxidative status

The impact of prenatal environment on postnatal life and performance: future perspectives for prevention and treatment

La presente revisión tiene como objetivo ofrecer un resumen no exhaustivo de las perspectivas actuales y futuras sobre herramientas de manejo y terapéuticas para la restricción del crecimiento intrauterino (RCIU) y la programación prenatal asociada en especies humanas y animales. Los animales se utilizan como modelos para el estudio de fenómenos relacionados con la RCIU, pero también para la investigación en terapias prenatales con el objetivo principal de diseñar y desarrollar estrategias preventivas y terapéuticas. Actualmente, la investigación está prestando atención a los tratamientos farmacológicos y estrategias nutricionales centrados en la madre, pero también a los tratamientos centrados en el feto. Tratamientos centrados en el feto, administrados directamente en el feto o mediante infusión de cordón umbilical, saco amniótico o placenta, lo que evita la administración de sustancias a altas dosis a la madre para permitir su disponibilidad a nivel fetoplacentario. Los resultados obtenidos en esta área de investigación con animales grandes (conejos, cerdos y rumiantes) tienen un doble interés, para la biomedicina traslacional y para la medicina veterinaria y la producción animal.The present review aims to offer a non-comprehensive outline of the current state-of-the-art and future perspectives on management and therapeutic tools for intrauterine growth restriction (IUGR) and associated prenatal programming in both human and animal species. Animals are used as models for the study of phenomena related to IUGR, but also for research on prenatal therapies with the main objective of designing and developing preventive and therapeutic strategies. The research is currently paying attention on maternal-focused pharmacological treatments and nutritional strategies but also on fetal-focused treatments. Fetal-focused treatments, administered either directly at the fetus or by using infusion of umbilical cord, amniotic sac or placenta, which avoids the administration of substances at high doses to the mother for allowing their availability at the fetoplacental level. The results obtained in this area of research using large animals (rabbits, pigs and ruminants) have a dual interest, for translational biomedicine and for veterinary medicine and animal production

Administration of glycerol-based formulations in sheep results in similar ovulation rate to eCG but red blood cell indices may be affected

15Pág.The objective of this study was to investigate the metabolic and osmotic effects of different doses of glycerol or a glycerol - propylene glycol mixture in Sarda sheep with the aim to identify those able to beneficially modify ewe's metabolic status without harmful changes in red blood cell (RBC) indices. Thereafter, the selected doses were tested for their effects on ewe's ovarian activity during an induced follicular phase and compared to the effects of a hormonal treatment with equine chorionic gonadotrophin (eCG).This study was financed by a doctoral grant from the Italian Ministry of Education, University and Research (Programma Operativo Nazionale Ricerca e Innovazione 2014–2020 - CCI 2014IT16M2OP005 - Fondo Sociale Europeo, Azione I.1 “Dottorati Innovativi con caratterizzazione Industriale). The funding institution financed laboratory analysis, the dietary treatments, and FDS. The funding institution had no role in the design of the study; in the collection, analysis, and interpretation of data; or in the writing of the manuscript.Peer reviewe

STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis

STAG/SA proteins are specific cohesin complex subunits that maintain sister chromatid cohesion in mitosis and meiosis. Two members of this family, STAG1/SA1 and STAG2/SA2,(‡) are classified as mitotic cohesins, as they are found in human somatic cells and in Xenopus laevis as components of the cohesin(SA1) and cohesin(SA2) complexes, in which the shared subunits are Rad21/SCC1, SMC1 and SMC3 proteins. A recently reported third family member, STAG3, is germinal cell-specific and is a subunit of the meiotic cohesin complex. To date, the meiosis-specific cohesin complex has been considered to be responsible for sister chromatid cohesion during meiosis. We studied replacement of the mitotic by the meiotic cohesin complex during mouse germinal cell maturation, and we show that mammalian STAG2 and Rad21 are also involved in several meiosis stages. Immunofluorescence results suggest that a cohesin complex containing Rad21 and STAG2 cooperates with a STAG3-specific complex to maintain sister chromatid cohesion during the diplotene stage of meiosis

Humoral responses to SARS-CoV-2 by healthy and sick dogs during the COVID-19 pandemic in Spain.

COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.Study funded by Fundación Universidad Alfonso X el Sabio (1.011.115 grant to A.J.P-B.; 1.011.101 to A.B-F.) and Comunidad de Madrid (COV20/01398 grant to A.J.P-B. and A.B-F.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S