Mineral metabolism in cats

The present Doctoral Thesis wa metabolism in the feline species. Through a series of studies, the relationship between calcium metabolism and the main hormones involved in it has been determined metabolism during the juvenile stage of growing cats effects linked to feeding calculolytic diets on feline mineral metabolism. The first part of the work was aimed the quantification of intact (I-PTH) and whole PTH) and to characterize the dynamics of PTH secretion, including the assessment of PTH-Ca curve in healthy cats. Thirteen clinically healthy cats were subjected to experimentally induced hypo study the PTH secretion in response to changes in plasma calcium concentration. The results obtained in these studies show assays used to quantify PTH (I-PTH and W for the determination of this hormone in feline patients. Furthermore, the feline PTH-Ca curve had a great similarity with canine PTH thus the previous knowledge on dynamics of PTH secretion in dogs could be extrapolated to cats. The second part was focused on the study of the major electrolytes and hormones involved in mineral metabolism in growing cats (from 3 to 15 months of age). Based on the hypothesis that growing animals are subjected to changes in mineral metabolism, a total of fourteen healt cats were studied between 3 and 15 months of age. The concentrations and changes of the main parameters related to mineral metabolism were determined. From 3 months of age to adulthood (15 months) animals experienced significant changes in the concentra electrolytes related to mineral metabolism. Therefore, the use of appropriate reference ranges is essential especially when pathological processes are evaluated in young animals. A b s t r a c t 99 was focused on the study of mineral . We also studied the changes in mineral g and analyzed the to validate a commercial assay for parathyroid hormone (Wand hypo- and hypercalcemia to n showed that the W-PTH) were suitable and reliable PTH-Ca curve and healthy concentration of...La presente Tesis Doctoral se ha centrado metabolismo mineral en la especie felina. A través de una serie de trabajos se ha estudiado en detalle la relación entre el metabolismo del calcio y las principales hormonas involucradas, incluyendo el estudio de los principales cambios que se producen en dichos parámetros durante la etapa juvenil de gatos en crecimiento, para finalmente culminar con el estudio de los posibles efectos ligados a la alimentación con dietas calculolíticas sobre el metabolismo mineral felino. El primer trabajo se planteó con el objeto de validar un ensayo comercial para la cuantificación de completa (W-PTH) y profundizar en el estudio de la dinámica de secreción de PTH y evaluación de la curva PTH se emplearon trece gatos clínicamente sanos los cuales fueron sometidos a hipo- e hipercalcemia inducidas experimentalmente a fin de estudiar la secreción de PTH frente a cambios en la conc plasmático. Los resultados obtenidos en esta serie de estudios mostraron que los ensayos empleados para la cuantificación de PTH (I fueron adecuados y fiables para la determinación de la concentración de dicha hormona en pacientes felinos. Además, la curva PTH en estudio fue similar a la curva PTH de estudios previos de dinámica de secreción en perros podrían ser extrapolados a la especie felina. El segundo trabajo se centró en el estudio de las concentraciones de los principales electrolitos y hormonas involucrados en el metabolismo mineral de gatos en crecimiento (desde los 3 a los 15 meses de edad). Basándonos en la hipótesis de que animales en crecimiento están sujetos a cambios del metabolismo fosfocálcico gatos sanos durante la etapa comprendida entre los 3 y 15 meses de edad a fin de cuantificar los niveles de los principales parámetros relacionados..

Vitamin E protects against extraskeletal calcification in uremic rats fed high fat diets

Background: High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets. Methods: Wistar rats ( n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rat s were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the ot her half were maintained on basic VitE requirements (27 mg/kg). Thus, rats were allotted to four experimental groups: Nx-NF ( n = 8), Nx-NF-VitE ( n =8),Nx-HF( n =8)and Nx-HF-VitE ( n = 8). At the time of sacrifice (day 66), blood and tissue samples were obtained. Results: Feeding a HF diet for 45 days did not increase body weight but elicited hyperglycemia, hypertriglyceridemia, an increase in plasma fibroblast growth factor 23 and a reduction in plasma calcitriol concentrations. After Nx, rats fed HF diet showed substantial extraskeletal calcification with aortic calcium content that was higher than in rats fed NF diet. Supplementation with VitE significantly ( p < 0.05) reduced aortic (from 38.4 ± 8.8 to 16.5 ± 1.4 mg/g), gastric (from 5.6 ± 2.7 to 1.2 ± 0.4 mg/g) and pulmonary (from 1.8 ± 0.3 to 0.3 ± 0.2 mg/g) calcium content in rats on HF diets. Conclusions: Uremic rats fed HF diets developed more severe extraosseous calcifications than their normocaloric-fed counterparts and dietary VitE supplementation protected against uremic calcifications in rats fed HF diets. Thus, eating energy-rich foods should be discouraged in patients with renal disease and their deleterious effect may be ameliorated with adequate antioxidant suppl

Chronic Vitamin D Intoxication in Captive Iberian Lynx (Lynx pardinus)

To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/ mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets

Implementation of a pilot classroom of practical skills for the clinical subjects of the Veterinary Degree

Las limitaciones temporales en la docencia de las asignaturas clínicas del Grado en Veterinaria, así como el elevado ratio estudiantes/profesor y sobre todo estudiantes/paciente, condicionan en gran medida la formación del alumnado, comprometiendo la adquisición de competencias específicas. Así, el alumnado debe amortizar el tiempo que dedica al aprendizaje de estas materias, integrar los conocimientos adquiridos en ellas para llegar a conseguir el fin de las mismas y ser capaz de enfrentarse a situaciones clínicas con la consecuente realización de los necesarios procedimientos manuales. En este artículo, generado a partir de un proyecto de innovación docente, consideramos la enseñanza basada en la práctica con modelos inanimados o maniquíes como imprescindible para complementar la enseñanza de habilidades clínicas y adquisición de competencias. Debido al alto número de alumnos y al escaso tiempo que pasan por rotaciones clínicas con animales, y teniendo en cuenta las consideraciones éticas, es muy difícil que todos ellos puedan realizar las habilidades clínicas básicas e incluso puedan verlas en situaciones reales. El alumnado debe conocer estos procedimientos dentro de la materia de las asignaturas Propedéutica Clínica, Anestesiología y Cuidados Intensivos, Patología Quirúrgica y Medicina Interna, así como desarrollar estas habilidades, puesto que serán evaluados de esas competencias. Para ello hemos propuesto la implantación en el Departamento de Medicina y Cirugía Animal de un aula piloto donde los alumnos pueden practicar varias veces en los modelos, con el fin de adquirir la pericia necesaria para el dominio de las habilidades clínicas. De esta forma se fomentará una enseñanza integrativa, que mejorará el aprendizaje y el desarrollo de competencias específicas, además de adquirir otras competencias transversales que ayudarán al futuro veterinario en el ejercicio de su profesión.Time limitations in the teaching of clinical subjects of the Veterinary Degree, as well as the high student/teacher ratio and especially student/patient, determine the training of students and compromising the acquisition of specific competences. Thus, students should amortize the time devoted to learning these subjects, integrate the knowledge acquired in them and be able to face clinical situations with the consequent accomplishment of the necessary manual procedures. In the present study, derived from a teaching innovation project, we consider the practice-based teaching with inanimate models or mannequins as a complement of the teaching of clinical skills and acquisition of competences. Due to the high number of students, the short time they spend in clinical rotations with animals and bearing in mind the ethical considerations, it is very difficult for the students to perform the basic clinical skills and even to see them in real situations. The students must know these procedures within the subjects: Clinical Propedeutics, Anesthesiology and Intensive Care, Surgical Pathology and Internal Medicine, as well as to develop these abilities since they will be evaluated of those competences. We have proposed the implementation of a pilot classroom in the Department of Animal Medicine and Surgery where students can practice several times in the inanimate models in order to acquire the necessary expertise for the successful development of clinical skills. This initiative will promote an integrative teaching which will improve the learning and development of specific skills, as well as the acquisition of other transversal competences that will help the future veterinarian in the exercise of their profession

Phosphorus restriction does not prevent the increase in fibroblast growth factor 23 elicited by high fat diet

This study was designed to evaluate the influence of phosphorus (P) restriction on the dele- terious effects of high fat diets on mineral metabolism. Twenty-four rats were allotted to 3 groups (n = 8 each) that were fed different diets for 7 months. Rats in group 1 were fed nor- mal fat-normal P (0.6%) diet (NF-NP), rats in group 2 were fed high fat- normal P diet (HF- NP) and rats in group 3 were fed high fat-low P (0.2%) diet (HF-LP). Blood, urine and tissues were collected at the end of the experiments. When compared with the control group (NF- NP), rats fed HF diets showed increases in body weight, and in plasma concentrations of tri- glycerides and leptin, and decreased plasma calcitriol concentrations. In rats fed HF-NP plasma fibroblast growth factor 23 (FGF23) was higher (279.6 ± 39.4 pg/ml vs 160.6 ± 25.0 pg/ml, p = 0.018) and renal klotho (ratio klotho/GAPDH) was lower (0.75 ± 0.06 vs 1.06 ± 0.08, p < 0.01) than in rats fed NF-NP. Phosphorus restriction did not normalize plasma FGF23 or renal klotho; in fact, rats fed HF-LP, that only ingested an average of 22.9 mg/day of P, had higher FGF23 (214.7 ± 32.4 pg/ml) concentratio ns than rats fed NF-NP (160.6 ± 25. 0 pg/ml), that ingested and average of 74.4 mg/day of P over a 7 month period. In conclusion, our results demonstrate that severe P restriction over a prolonged period of time (7 months) does not normalize the increase in circulating FGF23 induced by HF diets. These data indi- cate that the deleterious effects of high fat diet on the FGF23/klotho axis are not eliminated by reduced P intake

Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats

Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic V

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis