RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Ontogenesis of the omasum: a comparative analysis of the Merino sheep and Iberian red deer

The aim of this study is to describe differences in the ontogenesis of the omasum in sheep (domestic ruminant) and deer (wild ruminant). A total of 50 embryos and fetuses of Merino sheep and 50 Iberian deer were used, from the first stages of prenatal life until birth. For the study, the animals were divided into five experimental groups according to the most relevant histological characteristics. The appearance of the omasum from the primitive gastric tube was earlier in sheep (22% gestation, 33 days) than in deer (25% gestation, 66 days). In both cases it displayed a primitive epithelium of a stratified, cylindrical, non-ciliary type. The appearance of four laminae of different sizes was always earlier in sheep than deer. At around 36% gestation in sheep (53 days) and 36% (97 days) in deer, the omasum consisted of 4 clearly-differentiated layers: mucosa (with epithelial layer and lamina propria), submucosa, tunica muscularis and serosa. The temporal order of appearance of the four order laminae and omasal papillae was always earlier in sheep than deer. The tegumentary mucosa of the omasum was without secretion capability in the first embryonic phases. From 67 days (26% gestation) the neutral mucopolysaccharides appeared in deer and at 46 days (30% gestation) in sheep. In both cases they continued to decrease until birth, this decrease being more pronounced in deer. Finally, the presence of neuroendocrine and glial cells was detected in deer at earlier stages than in sheep

Histomorphometric and immunohistochemical study of the goat reticulum during prenatal development

This study sought to describe the morphological changes taking place in the goat reticulum during prenatal development, using histomorphometric and immunohistochemical techniques. A total of 140 goat embryos and foetuses were used, from the first stages of prenatal life until birth. Differentiation of the reticulum as a separate compartment of the primitive gastric tube was observed at 35 days of prenatal life (23% gestation). By 38 days (25% gestation) the reticular wall comprised three layers: an internal epithelial layer, a middle layer of pluripotential blastemic tissue and an external layer or serosa. Primary reticular crests were visible at 59 days (38% gestation) as evaginations of the epithelial stratum basale, marking the earliest histological differentiation of future reticular cells. Secondary reticular crests were observed at 87 days (61% gestation). Corneum papillae first became apparent on the lateral surface of primary reticular crests at 101 days (64% gestation). The muscularis mucosae was visible by 101 days (64% gestation) in primary reticular crests. Neuroendocrine cells were detected by synaptophysin at 64 days (43% gestation), while glial cell markers (glial fibrillary acidic protein and vimentin) were observed at 64 days (43% gestation) and 38 days (25% gestation), respectively. The peptidergic innervation markers such as neuropeptide Y and vasoactive intestinal polypeptide were detected at 75 days (50% gestation). In conclusion, prenatal development of the reticulum - like that of the rumen - appears to take place somewhat earlier in goats than in sheep or cattle, but at a similar rate to that reported in deer

Histomorphometric and immunohistochemical study of the goat omasum during prenatal development

This work studies the morphological changes taking place in the goat omasum during prenatal development, using scanning electron microscope, light microscopy and immunohistochemical analysis. A total of 140 goat embryos and fetuses were used, from the first stages of prenatal life until birth. Differentiation of the omasum as a separate compartment of the primitive gastric tube was observed at 35 days of prenatal life ([crown-rump length (CRL)] 3 cm, 23% gestation). By 38 days (CRL 4.3 cm, 25% gestation) the omasal wall comprised three layers: an internal epithelial layer, a middle layer of pluripotential blastemic tissue and an external layer or serosa. Omasal laminae appeared in the following order: primary at 38 days (CRL 4.3 cm, 25% gestation), secondary at 50 days (CRL 7.7 cm, 33% gestation), tertiary at 59 days (CRL 12 cm, 39% gestation) and quaternary at 64 days (CRL 13.5 cm, 43% gestation). Neuroendocrine cells were detected by synaptophysin (SYP) at 52 days (CRL 8 cm, 35% gestation), while glial cell markers (glial fibrillary acidic protein - GFAP, and vimentin-VIM) were observed at 64 days (CRL 13.5 cm, 43% gestation) and 38 days (CRL 4.3 cm, 25% gestation), respectively. Sympathetic and parasympathetic nerve fibers and nerve bodies were detected via neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) at 95 days (CRL 20 cm, 63% gestation). In conclusion, prenatal development of the omasum - like that of the rumen - appears to take place somewhat earlier in goats than in sheep or cattle, but at a similar stage to that reported in deer

Prenatal histomorphological development of the rumen in Dama dama

This work studies the morphological changes taking place in the Dama dama rumen during prenatal development using histomorphometrics, surface microstructure and immunohistochemistry analysis as well as carrying out a comparative analysis of this species with other wild (red deer) and domestic-type ruminants. A total of 25 fallow deer embryos and fetuses were used, from the first stage of prenatal life until birth. The appearance of the rumen from the primitive gastric tube was observed at 51 days of prenatal life (CRL 3 cm, 21% gestation). By 57 days (CRL 4.3 cm, 24% gestation) the ruminal wall comprised three layers: an internal epithelial layer, a middle layer of pluripotential blastemic tissue and an external layer or serosa. Ruminal pillars were visible at 72 days (CRL 6 cm, 30% gestation), and by 85 days (CRL 7.2 cm, 35% gestation) ruminal papillae were starting to appear. Under scanning electron microscopy, by 80 days (CRL 7 cm, 33% gestation) small ruminal papillae were observed protruding from the surface. Morphometric results showed accelerated growth of the epithelial layer and the tunica muscularis at 180 days (75% gestation). By contrast, the growth-rate of the lamina propria and submucosa declined from the early embryonic stages until birth. The serosa maintained a steady rate of growth until birth. Neuroendocrine cells (synaptophysin) were detected at 85 days (CRL 7.2 cm CRL, 35% gestation), while glial cell markers (glial fibrillary acidic protein and vimentin) were found at 108 days (CRL 31 cm, 45% gestation) and 63 days (CRL 4.4 cm, 26% gestation) respectively. Neuropeptide Y and vasoactive intestinal polypeptide were detected immunohistochemically at 180 days (CRL 33 cm, 75% gestation) and 192 days (CRL 35 cm, 80% gestation) respectively. In comparison to other wild and domestic-type ruminants, histomorphogenesis of the rumen in Dama dama was similar to that reported in red deer and goats, but rather slower than that observed for sheep or cattle

Pseudorabies virus infection (Aujeszky's disease) in an Iberian lynx (Lynx pardinus) in Spain : a case report

The only natural hosts of Pseudorabies virus (PRV) are members of the family Suidae (Sus scrofa scrofa). In species other than suids infection is normally fatal. In these mammals, including carnivores, PRV typically causes serious neurologic disease. The endangered Iberian lynx (Lynx pardinus) is a wild feline endemic to south-western Europe (Iberian Peninsula). The Iberian lynx was found to be the world's most endangered felid species in 2002. In wild felines, PRV infection has only been previously reported once in a Florida panther in 1994. No seropositive lynxes have ever been found, nor has PRV been detected in dead Iberian lynxes to date. We describe the first reported case of pseudorabies in an Iberian lynx (Lynx pardinus). Pseudorabies was diagnosed in a young wild Iberian lynx from Extremadura (SW Spain) by histopathological examination, immunohistochemistry, polymerase chain reaction (PCR) and sequence analysis. Gross lesions included alopecia of the ventral neck, bloody gastro-intestinal contents and congestion of the brain. Histopathological analysis showed a moderate nonsuppurative meningoencephalitis with diffuse areas of demyelination, necrotizing gastritis and enteritis of the small intestine. Pseudorabies virus (PRV) antigen was found in neuronal and non-neuronal cells of the brain, tonsils, and gastric glandular epithelial cells by immunohistochemical analysis. The presence of the virus in the brain was confirmed by nested PCR. The sequence analysis of the 146 bp fragment (from the viral glycoprotein B gene) showed that the amplified sequence matched (with 100% identity) the PRV genome. Furthermore, specific DNA from glycoprotein D and E encoding-genes was detected by conventional and real-time PCR, respectively, confirming the latter that this infection was produced by a wild-type PRV strain. This study supports the suspicion that PRV could infect the Iberian lynx. The detection of PRV in a dead Iberian lynx suggests that the virus may have a negative impact on the survival of endangered lynxes in the wild. However, because this is the first verified instance of lynx mortality resulting from pseudorabies, its true impact on the population is unknown. The online version of this article (doi:10.1186/s12917-016-0938-7) contains supplementary material, which is available to authorized users

Rosiglitazone in the thawing medium improves mitochondrial function in stallion spermatozoa through regulating Akt phosphorylation and reduction of caspase 3.

BackgroundThe population of stallion spermatozoa that survive thawing experience compromised mitochondrial functionality and accelerated senescence, among other changes. It is known that stallion spermatozoa show very active oxidative phosphorylation that may accelerate sperm senescence through increased production of reactive oxygen species. Rosiglitazone has been proven to enhance the glycolytic capability of stallion spermatozoa maintained at ambient temperature.ObjectivesThus, we hypothesized that thawed sperm may also benefit from rosiglitazone supplementation.Materials and methodsThawed sperm were washed and resuspended in Tyrodes media, and the samples were divided and supplemented with 0 or 75 μM rosiglitazone. After one and two hours of incubation, mitochondrial functionality, Akt phosphorylation and caspase 3 activity were evaluated. Additional samples were incubated in the presence of an Akt1/2 inhibitor, compound C (an AMPK inhibitor) or GW9662 (an antagonist of the PPARγ receptor).ResultsRosiglitazone maintained Akt phosphorylation and reduced caspase 3 activation (pConclusionWe provide the first evidence that the functionality of frozen stallion spermatozoa can be potentially improved after thawing through the activation of pro survival pathways, providing new clues for improving current sperm biotechnology

The incorporation of cystine by the soluble carrier family 7 member 11 (SLC7A11) is a component of the redox regulatory mechanism in stallion spermatozoa

Oxidative stress is considered amajor mechanism causing sperm damage during cryopreservation and storage, and underlies male factor infertility. Currently, oxidative stress is no longer believed to be caused only by the overproduction of reactive oxygen species, but rather by the deregulation of redox signaling and control mechanisms. With this concept in mind, here, we describe for the first time the presence of the soluble carrier family 7 member 11 (SLC7A11) antiporter, which exchanges extracellular cystine (Cyss) for intracellular glutamate, in stallion spermatozoa, as well as its impact on sperm function using the specific inhibitor sulfasalazine. Spermatozoa incubated with Cyss exhibited an increased intracellular GSH content compared with controls (P amp;lt; 0.01): 50% in fresh extended stallion spermatozoa and 30% in frozen-thawed spermatozoa. This effect was prevented by the addition of sulfasalazine to the media. Cystine supplementation also reduced the oxidation-reduction potential of spermatozoa, with sulfasalazine only preventing this effect on fresh spermatozoa that were incubated for 3 h at 37 degrees C, but not in frozen-thawed spermatozoa. While sulfasalazine reduced the motility of frozen-thawed spermatozoa, it increased motility in fresh samples. The present findings provide new and relevant data on the mechanism regulating the redox status of spermatozoa and suggest that a different redox regulatory mechanism exists in cryopreserved spermatozoa, thus providing new clues to improve current cryopreservation technologies and treat male factor infertility. Summary Sentence The SLC7A11 antiporter that exchanges cystine by intracellular glutamate is present and functional in stallion spermatozoa, but cryopreserved spermatozoa may present altered functionality.Funding Agencies|Ministerio de Economia y CompetitividadEuropean Regional Development Fund (FEDER), Madrid, Spain [AGL2017-83149-R]; Junta de Extremadura-FEDEREuropean Union (EU) [IB16030, GR18008]; Swedish Research councils VRSwedish Research Council [521-2011-6553]; FORMAS, StockholmSwedish Research Council Formas [2017-00946]; Valhondo Calaaf Foundation, Caceres, Spain</p