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OBJETIVOS: Evaluar la prevalencia de calcificación vascular y fracturas vertebrales en una cohorte de pacientes sometidos a trasplante renal, y su asociación con mortalidad por todas las causas y disfunción del injerto, así como la relación con parámetros bioquímicos del metabolismo óseo y mineral. MATERIAL Y MÉTODOS: Estudio prospectivo, observacional, unicéntrico, en el que se incluyeron 405 pacientes sometidos a trasplante renal, con recogida de parámetros clínicos, bioquímicos, epidemiológicos y de calcificación vascular radiológica y fracturas vertebrales mediante radiografía simple en el momento del trasplante, con un seguimiento mínimo de dos años, evaluando mortalidad cardiovascular y por todas las causas y descenso del filtrado glomerular. Se dispuso además de 39 estudios de densitometría ósea realizados en los meses previos al trasplante. RESULTADOS: La supervivencia de los pacientes fue significativamente menor en el grupo de pacientes con calcificación vascular (131 ± 1,5 meses sin calcificación frente a 110 ± 3,5 meses con calcificación vascular, p < 0,001). Se observó un mayor descenso del filtrado glomerular estimado (FGE) mediante la fórmula CKD-EPI en todos los pacientes que presentaban calcificación vascular, siendo esta un factor de riesgo independiente (OR = 2,7; IC 95%: 1,6-4,4; p < 0,001). La prevalencia de fracturas vertebrales fue significativamente mayor en el grupo de calcificación vascular (12%), independientemente de otros factores de riesgo (OR = 9,2; IC 95%: 1,2-73,4; p = 0,036). Se ha asociado la prevalencia de fracturas vertebrales con menor masa ósea en cadera evaluada mediante densitometría ósea (T-score -1,2 vs. -2,4, p = 0,02) CONCLUSIONES: La calcificación vascular previa al trasplante, evaluada mediante un método sencillo, barato y accesible como la radiografía simple, condiciona la morbimortalidad del paciente sometido a trasplante renal y tiene un gran impacto sobre la evolución de la función del injerto, independientemente de otros factores de riesgo tradicionales. La asociación entre la fragilidad ósea, la calcificación vascular y el pronóstico del paciente y del injerto renal nos debe hacer pensar en añadir la densitometría ósea en el protocolo de inclusión en lista de espera de trasplante. Es relevante promover no sólo la mejor salud vascular posible sino también promover el menor impacto en el tejido óseo en la progresión de la enfermedad renal crónica antes del momento del trasplante

OBJETIVE: To assess the prevalence of vascular calcification and vertebral fractures in a cohort of patients undergoing kidney transplantation and its association with all graft-related causes of mortality and dysfunction, as well as the relationship with biochemical parameters of bone and mineral metabolism. MATERIAL AND METHODS: Prospective, observational, single-center study, which included 405 patients undergoing kidney transplants, with collection of clinical, biochemical, epidemiological parameters, and of radiological vascular calcification and vertebral fractures by simple radiography at the time of transplantation, with a minimum follow-up of two years. We assessed cardiovascular mortality and all causes and decreased glomerular filtration. In addition, 39 bone densitometry studies carried out in the months prior to transplantation were reported. RESULTS: Patient survival was significantly lower in the group of patients with vascular calcification (131 ± 1.5 months without calcification compared to 110 ± 3.5 months with vascular calcification, p < 0.001). A greater decrease in the estimated glomerular filtration rate (GFR) was observed using the CKD-EPI formula in all patients who presented vascular calcification, this being an independent risk factor (OR = 2.7; 95% CI: 1.6-4, 4; p < 0.001). The prevalence of vertebral fractures was significantly higher in the vascular calcification group (12%), independently of other risk factors (OR = 9.2; 95% CI: 1.2-73.4; p = 0.036). The prevalence of vertebral fractures has been associated with lower hip bone mass assessed by bone densitometry (T-score -1.2 vs. -2.4, p = 0.02) CONCLUSIONS: Vascular calcification prior to transplantation, evaluated using a simple, cheap and accessible method such as plain radiography, determines the morbidity and mortality of the patient undergoing a kidney transplant and has a great impact on the evolution of graft function, regardless of other risk factors. traditional. The association between bone fragility, vascular calcification and the prognosis of the patient and the renal graft should make us think about adding bone densitometry to the protocol for inclusion in the transplant waiting list. It is relevant to promote not only the best possible vascular health but also to promote the least impact on bone tissue in the progression of chronic kidney disease before the time of transplantation

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Our objective was to analyse the role of endothelin1 gene (EDN1) variation in essential left ventricular hypertrophy (LVH). We searched for EDN1 variants in 145 Spanish patients with an essential form of LVH (not secondary to hypertension, aortic stenosis, or any other disease that could explain the hypertrophy). The five EDN1 coding exons and 1.5 kilobases of the promoter region were analysed through single strand conformation analysis and direct sequencing. We found four nucleotide changes: -1224 C/A (promoter), -131 ins/del A (exon 1, 5'-non-translated sequence), A/G in codon 106 (exon 3, silent), and G/T in codon 198 (exon 5, lys198asn). To determine the association between these polymorphisms and cardiac hypertrophy, we compared the genotype frequencies from these 145 patients with 250 healthy controls. We found a higher frequency of patients homozygous for 198 lys (198 KK) (65% vs. 52%; p = 0.01; OR = 1.76) and for -1224 AA (73% vs. 66%; p = 0.19). Homozygotes for -1224 A + 198 K (AA+KK) were significantly more frequent in patients (62% vs. 45%; p = 0.0007; OR = 2.10; 95% CI = 1.35-3.25). The expression of the -1224 C/A and exon 5 K198N variants was analysed with cells in culture. These in vitro studies showed that these variations did not differ in their expression levels. In conclusion, our work has shown that EDN1 variation, and in particular homozygosity for the -1224A/198K haplotype, is associated with the risk of developing cardiac hypertrophy. However, these EDN1 variants do not affect in vitro gene expression.

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In multiple ovulation and embryo transfer (MOET) programmes in cattle, a considerable number of morphologically poor-quality embryos continue to be produced; this is one of the limiting factors of the technique. Apoptosis has often been implicated in developmental arrest and fragmentation; these are regarded as poor traits of embryonic quality in mammalian pre-implantation embryos. In the present study, apoptosis was assessed in morphologically poor-quality embryos in comparison with good-quality embryos that were recovered from a MOET programme. Retarded embryos (two to 16 cell stage), morulae with severe fragmentation and morphologically good-quality morulae recovered from superstimulated cows at day 7 post-insemination were subjected to TdT-mediated dUTP nick-end labelling (TUNEL) and Hoechst staining. Cell nuclei that showed both TUNEL staining and apoptotic morphology were considered to be apoptotic. Apoptotic index (AI) was calculated as the percentage of apoptotic cells per embryo. Fifteen of 17 retarded embryos and 10 of 15 morphologically poor-quality morulae did not show signs of apoptosis. The mean AIs in the morphologically poor-quality embryos (two to 16 cell stage, 2.2%; poor morulae, 1.3%) were as low as that in the good-quality embryos (2.9%). These results suggest that another mode of developmental arrest and/or fragmentation that is independent of apoptosis occurs in morphologically poor-quality embryos recovered from MOET programmes.

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BACKGROUND: The conversion of retinol (ROH) to retinoic acid (RA) is crucial during development but has been not studied during blastocyst formation. METHODS AND RESULTS: In vitro-produced bovine morulae were treated for 24 h with citral (which inhibits the synthesis of RA from ROH), citral + all trans retinoic acid (ATRA), ATRA or no additives. Citral interfered with blastocyst development, whereas exogenous RA had no effect. RA, however, reversed the effect of citral on development and stimulated cell proliferation. Neither citral nor RA changed the apoptotic index, but RA triggered an increase in the apoptotic frequency of the inner cell mass. Citral and RA reduced the necrotic index. Na/K-ATPase alpha1-subunit mRNA concentrations (analysed by real-time PCR) increased after hatching and showed dependence on retinoid activity, but no evidence was found of any retinoid effect on p53 expression. Nevertheless, the p53 mRNA concentration increased in response to proliferation in hatched blastocysts. CONCLUSION: The preimplantation bovine embryo metabolizes endogenous ROH to RA, which participates in important cell processes. The true extent of the influence of RA is unknown, although the modulation of retinoid metabolism seems to be a means of increasing cell proliferation. This knowledge might be used to improve embryo quality and the efficiency of stem cell derivation.

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Retinoids have been shown to enhance developmental competence of the oocyte in cattle, sheep and pigs. In this study we investigated whether exogenous retinol stimulates the bovine oocyte during its intrafollicular growth and the time limits of exposure to exogenous retinol. In addition, we also determined the efficiency of ovum pick-up techniques in combination with retinol treatment and the viability of embryos after transfer to recipients. In Experiment 1, heifers were injected with retinol or vehicle, and concentrations of retinol in the blood were analysed on Day 0 (prior to injection), Day 1 and, together with follicular fluid, Day 4. Blood retinol increased by Day 1 and cleared on Day 4, but retinol remained higher within the follicle. In Experiment 2, oocyte donors were injected weekly with retinol or vehicle four times during a twice-per-week cycle of eight recovery sessions (starting 4 days before the first session), followed by a second eight-session cycle without treatment. Oocytes recovered were fertilized and cultured in vitro. Retinol treatment yielded higher numbers of low-quality oocytes throughout, although retinol measured during cycles did not change. Total oocytes, and morulae and blastocyst rates, increased during the first five sessions following treatment with retinol. As previously shown with oocytes from slaughterhouse ovaries, retinoic acid stimulated blastocyst development. Following transfer to recipients, blastocysts from oocytes exposed to retinol were unable to establish pregnancy. Our study confirms the existence of an effect of retinol on the intrafollicular oocyte in the cow and provides evidence regarding the teratogenic effect of retinol.

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