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1.
J Anim Sci ; 1022024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38795007

RESUMEN

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ±â€…0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.


This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.


Asunto(s)
Alimentación Animal , Antioxidantes , Dieta , Suplementos Dietéticos , Ácido Glutámico , Lisina , Manganeso , Animales , Lisina/farmacología , Lisina/administración & dosificación , Lisina/metabolismo , Alimentación Animal/análisis , Manganeso/farmacología , Manganeso/administración & dosificación , Manganeso/metabolismo , Dieta/veterinaria , Antioxidantes/metabolismo , Antioxidantes/farmacología , Suplementos Dietéticos/análisis , Porcinos/crecimiento & desarrollo , Ácido Glutámico/farmacología , Ácido Glutámico/metabolismo , Masculino , Femenino , Fenómenos Fisiológicos Nutricionales de los Animales , Destete , Distribución Aleatoria , Huesos del Metacarpo/metabolismo , Huesos del Metacarpo/efectos de los fármacos
2.
PLoS One ; 16(6): e0253744, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34166462

RESUMEN

The aim of the study was to assess the effect of the inclusion of dried fermented soybean and/or rapeseed meal in piglet feed on immune parameters, blood lipid parameters, and mineral content in the blood and metacarpal bones. The study was conducted on 150 28-day-old piglets divided into 5 groups. Piglets in the control group (C) received a standard diet with soybean meal. Animals in group FR (group receiving a diet with 8% FRSM) received a diet in which a portion of the soybean meal was replaced with 8% dried fermented rapeseed meal (FRSM). Animals in group FR/FS received a diet in which a portion of the soybean meal was replaced with 6% FRSM and 2% fermented dried soybean meal (FSBM). The piglets in group FS/FR received a diet with 6% FSBM and 2% FRSM. Group FS received a diet in which a portion of the soybean meal was replaced with an 8% share of FSBM. The inclusion of 8% or 6% fermented rapeseed meal (group FR or FR/FS) in the diet of piglets had a beneficial effect on their immune status, as evidenced by the increase in plasma levels of IgG and IgA and the decrease in IL-6 relative to the control group. It also significantly increased the concentrations of minerals, i.e. P, Ca and Zn, in the blood plasma and metacarpal bones of piglets and improved the availability of iron, a key bioelement involved in haemoglobin. The use of 8% or 6% fermented soybean meal in the diet (groups FS and FS/FR) of piglets had a positive effect on blood lipid parameters, reducing CHOL and LDL-cholesterol in the plasma. In conclusion, the fermentation process enables better utilization of rapeseed or soybean meal by pigs. Dried fermented rapeseed meal could partially replace protein components from GMO (genetically modified ogranism) crops (soybean meal) used in diets for pigs.


Asunto(s)
Alimentación Animal , Brassica napus , Glycine max , Lípidos , Huesos del Metacarpo , Minerales , Porcinos , Animales , Densidad Ósea/inmunología , Femenino , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lípidos/sangre , Lípidos/inmunología , Masculino , Huesos del Metacarpo/inmunología , Huesos del Metacarpo/metabolismo , Minerales/sangre , Minerales/inmunología , Porcinos/sangre , Porcinos/inmunología
3.
Arthritis Res Ther ; 20(1): 203, 2018 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-30170626

RESUMEN

BACKGROUND: Comprehensive simultaneous quantification of bone erosion and enthesiophytes in the joints of patients with psoriatic arthritis (PsA) has not been performed. Herein, we aimed to compare the extent of bone erosion and enthesiophytes in patients with PsA, psoriasis (PSO) and healthy controls, assess the influence of age and disease duration on the development of erosions and enthesiophytes and define their impact on physical function. METHODS: Patients with PsA or with PSO and controls were analysed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The extent of bone erosions and enthesiophytes was assessed and plotted according to different categories of age, duration of PSO and duration of PsA, respectively. In addition, demographic and disease-specific data, including physical function (health assessment questionnaire) were collected. RESULTS: A total of 203 patients were analysed; 101 had PsA, 55 had PSO and 47 were healthy individuals. Patients with PsA had significantly more and larger erosions (p = 0.002/p = 0.003) and enthesiophytes (p < 0.001) compared to patients with PSO and healthy controls. Patients with PSO and healthy controls did not differ in erosions, while enthesiophytes were more frequent in patients with PSO than in healthy controls. Bone erosions, but not enthesiophytes, showed strong age-dependency in all three groups. In contrast, enthesiophytes were mostly influenced by the duration of PSO and PsA and, in contrast to bone erosions, were associated with poorer physical function. CONCLUSIONS: Bone erosions are age-dependent, enhanced in PsA and increase with disease duration. Enthesiophytes are less age-dependent, are enhanced in both PSO and PsA and strongly influenced by disease duration. Enthesiophytes impact physical function in PsA suggesting the need for early therapeutic interventions to prevent damage.


Asunto(s)
Artritis Psoriásica/diagnóstico por imagen , Enfermedades Óseas/diagnóstico por imagen , Progresión de la Enfermedad , Entesopatía/diagnóstico por imagen , Cápsula Articular/diagnóstico por imagen , Huesos del Metacarpo/diagnóstico por imagen , Adulto , Factores de Edad , Artritis Psoriásica/metabolismo , Enfermedades Óseas/metabolismo , Entesopatía/metabolismo , Femenino , Humanos , Cápsula Articular/metabolismo , Masculino , Huesos del Metacarpo/metabolismo , Persona de Mediana Edad , Psoriasis/diagnóstico por imagen , Psoriasis/metabolismo , Adulto Joven
4.
PLoS One ; 13(6): e0194406, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29874224

RESUMEN

The objective of this study was to describe the three-dimensional shape and subchondral bone mineral density (BMD) variation of the equine distal third metacarpal bone (MC3) using a statistical shape model. The association between form and function builds upon previous two-dimensional observations of MC3 epiphyseal structure. It was expected that the main source of variation would be an increase in overall MC3 bone size, correlated to an increase in subchondral BMD. Geometry and bone mineral density was obtained from CT image data of 40 healthy Thoroughbred horses. This was used to create a statistical shape model, in which the first ten components described 75% of the variation in geometry and BMD. The first principal component described an increase in overall size of the MC3 distal epiphysis, coupled with higher BMD on the disto-palmar and dorso-proximal surfaces. The second component was qualitatively described as an increased convexity of the sagittal ridge at the dorsal junction of the epiphysis and the metaphysis, coupled to increased BMD in that region. The third component showed an increase in lateral condylar surface area relative to medial condylar area. As the condyle reduced in relative surface area, the BMD at both dorsal condyles increased. The statistical shape analysis produced a compact description of 3-D shape and sub-chondral bone mineral density variation for the third metacarpal bone. This study uniquely illustrates the shape variations in a sample population of MC3 bones, and the corresponding changes in subchondral BMD.


Asunto(s)
Densidad Ósea/fisiología , Imagenología Tridimensional , Huesos del Metacarpo , Animales , Caballos , Huesos del Metacarpo/anatomía & histología , Huesos del Metacarpo/metabolismo
5.
J Bone Miner Res ; 32(4): 722-730, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27787923

RESUMEN

The objective of this cross-sectional study was to define normal sex- and age-dependent values of intra-articular bone mass and microstructures in the metacarpal heads of healthy individuals by high-resolution peripheral quantitative computed tomography (HR-pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra-articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR-pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra-articular (intracapsular) bone margins. These data were applied in measuring intra-articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra-articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra-articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm3 ) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra-articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex- and age-adjusted controls. Standard sex- and age-dependent values for physiological intra-articular bone were defined. Postmenopausal state and RA led to significant decrease of intra-articular bone. © 2016 American Society for Bone and Mineral Research.


Asunto(s)
Envejecimiento , Artritis Reumatoide , Densidad Ósea , Huesos del Metacarpo , Radio (Anatomía) , Caracteres Sexuales , Tomografía Computarizada por Rayos X , Adulto , Factores de Edad , Anciano , Envejecimiento/metabolismo , Envejecimiento/patología , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/metabolismo , Femenino , Humanos , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Huesos del Metacarpo/metabolismo , Persona de Mediana Edad , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/metabolismo , Factores Sexuales
6.
J Perinatol ; 36(5): 394-400, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26765552

RESUMEN

OBJECTIVE: The objective of this study was to evaluate possible influences of parenteral nutrition on growth and bone development in preterms and to search for markers of bone status. STUDY DESIGN: Metacarpus bone transmission time (mc-BTT) was performed at birth, 21 days and 36 weeks of gestational age (GA) in preterms, receiving two different nutritional regimens, together with biochemical analysis. RESULT: A total of 234 patients were studied. Newborns with aggressive nutrition had significantly better growth rate and higher values of mc-BTT until discharge. Mc-BTT at day 21 correlates positively with nutritional intakes and phosphatemia; lower limb length positively correlated with mc-BTT (P<0.01). Newborns with low energy intake in the first week of life (<70 kcal kg(-1) per day) and low serum phosphate level (<1.4 mmol l(-1)) at 21 days had lower mc-BTT at 36 weeks of GA (P<0.01). CONCLUSION: Aggressive parenteral intakes in preterms improve growth and bone status in the short-medium term, suggesting that early nutrition could influence bone development.


Asunto(s)
Biomarcadores/sangre , Densidad Ósea , Desarrollo Óseo/fisiología , Enfermedades Óseas , Enfermedades del Prematuro , Nutrición Parenteral/métodos , Fosfatos/sangre , Absorciometría de Fotón/métodos , Enfermedades Óseas/sangre , Enfermedades Óseas/diagnóstico , Enfermedades Óseas/prevención & control , Intervención Médica Temprana/métodos , Ingestión de Energía , Femenino , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Recien Nacido Prematuro/crecimiento & desarrollo , Enfermedades del Prematuro/sangre , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/prevención & control , Italia , Masculino , Huesos del Metacarpo/metabolismo , Huesos del Metacarpo/patología
7.
Am J Med Genet A ; 170(3): 615-21, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26581570

RESUMEN

Synpolydactyly (SPD) is a rare congenital limb disorder characterized by syndactyly between the third and fourth fingers and an additional digit in the syndactylous web. In most cases SPD is caused by heterozygous mutations in HOXD13 resulting in the expansion of a N-terminal polyalanine tract. If homozygous, the mutation results in severe shortening of all metacarpals and phalanges with a morphological transformation of metacarpals to carpals. Here, we describe a novel homozygous missense mutation in a family with unaffected consanguineous parents and severe brachydactyly and metacarpal-to-carpal transformation in the affected child. We performed whole exome sequencing on the index patient, followed by Sanger sequencing of parents and patient to investigate cosegregation. The DNA-binding ability of the mutant protein was tested with electrophoretic mobility shift assays. We demonstrate that the c.938C>G (p.313T>R) mutation in the DNA-binding domain of HOXD13 prevents binding to DNA in vitro. Our results show to our knowledge for the first time that a missense mutation in HOXD13 underlies severe brachydactyly with metacarpal-to-carpal transformation. The mutation is non-penetrant in heterozygous carriers. In conjunction with the literature we propose the possibility that the metacarpal-to-carpal transformation results from a homozygous loss of functional HOXD13 protein in humans in combination with an accumulation of non-functional HOXD13 that might be able to interact with other transcription factors in the developing limb.


Asunto(s)
Braquidactilia/genética , Proteínas de Homeodominio/genética , Homocigoto , Mutación Missense , Sindactilia/genética , Factores de Transcripción/genética , Adulto , Secuencia de Bases , Braquidactilia/diagnóstico , Braquidactilia/patología , Huesos del Carpo/anomalías , Huesos del Carpo/metabolismo , Preescolar , Consanguinidad , Ensayo de Cambio de Movilidad Electroforética , Exoma , Femenino , Expresión Génica , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Huesos del Metacarpo/anomalías , Huesos del Metacarpo/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Linaje , Sindactilia/diagnóstico , Sindactilia/patología
8.
Osteoarthritis Cartilage ; 23(12): 2158-2166, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26067518

RESUMEN

OBJECTIVE: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. DESIGN: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline µCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. RESULTS: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60). CONCLUSION: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.


Asunto(s)
Cartílago Articular/diagnóstico por imagen , Huesos del Metacarpo/diagnóstico por imagen , Articulación Metacarpofalángica/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Densidad Ósea , Cadáver , Cartílago Articular/metabolismo , Cartílago Articular/patología , Fuerza Compresiva , Medios de Contraste , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Ácido Yoxáglico , Modelos Lineales , Masculino , Huesos del Metacarpo/metabolismo , Huesos del Metacarpo/patología , Articulación Metacarpofalángica/metabolismo , Articulación Metacarpofalángica/patología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Microtomografía por Rayos X
9.
Nat Commun ; 6: 6798, 2015 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-25865282

RESUMEN

The diverse morphology of vertebrate skeletal system is genetically controlled, yet the means by which cells shape the skeleton remains to be fully illuminated. Here we perform quantitative analyses of cell behaviours in the growth plate cartilage, the template for long bone formation, to gain insights into this process. Using a robust avian embryonic organ culture, we employ time-lapse two-photon laser scanning microscopy to observe proliferative cells' behaviours during cartilage growth, resulting in cellular trajectories with a spreading displacement mainly along the tissue elongation axis. We build a novel software toolkit of quantitative methods to segregate the contributions of various cellular processes to the cellular trajectories. We find that convergent-extension, mitotic cell division, and daughter cell rearrangement do not contribute significantly to the observed growth process; instead, extracellular matrix deposition and cell volume enlargement are the key contributors to embryonic cartilage elongation.


Asunto(s)
Cartílago/ultraestructura , Condrocitos/ultraestructura , Fibroblastos/ultraestructura , Placa de Crecimiento/ultraestructura , Huesos del Metacarpo/ultraestructura , Osteogénesis/fisiología , Animales , Cartílago/embriología , Cartílago/metabolismo , División Celular , Movimiento Celular , Tamaño de la Célula , Embrión de Pollo , Condrocitos/metabolismo , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Expresión Génica , Genes Reporteros , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Placa de Crecimiento/embriología , Placa de Crecimiento/metabolismo , Huesos del Metacarpo/embriología , Huesos del Metacarpo/metabolismo , Microscopía Confocal , Técnicas de Cultivo de Órganos , Fotones , Retroviridae/genética , Imagen de Lapso de Tiempo
10.
Hum Mol Genet ; 24(12): 3399-409, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-25759469

RESUMEN

Autosomal dominant omodysplasia is a rare skeletal dysplasia characterized by short humeri, radial head dislocation, short first metacarpals, facial dysmorphism and genitourinary anomalies. We performed next-generation whole-exome sequencing and comparative analysis of a proband with omodysplasia, her unaffected parents and her affected daughter. We identified a de novo mutation in FRIZZLED2 (FZD2) in the proband and her daughter that was not found in unaffected family members. The FZD2 mutation (c.1644G>A) changes a tryptophan residue at amino acid 548 to a premature stop (p.Trp548*). This altered protein is still produced in vitro, but we show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2. We therefore conclude that the FRIZZLED2 mutation is a de novo, novel cause for autosomal dominant omodysplasia.


Asunto(s)
Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Húmero/anomalías , Huesos del Metacarpo/anomalías , Mutación , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Vía de Señalización Wnt , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Huesos/diagnóstico por imagen , Huesos/patología , Análisis Mutacional de ADN , Exoma , Facies , Femenino , Receptores Frizzled/química , Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Húmero/metabolismo , Lactante , Huesos del Metacarpo/metabolismo , Osteocondrodisplasias/diagnóstico , Linaje , Fenotipo , Unión Proteica , Transporte de Proteínas , Radiografía
11.
Horm Res Paediatr ; 81(3): 196-203, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24481334

RESUMEN

BACKGROUND: GNAS encodes the α subunit of the stimulatory G protein (Gsα). Maternal inherited Gsα mutations cause pseudohypoparathyroidism type Ia (PHP-Ia), associated with shortening of the 4th and 5th metacarpals. AIMS: Here we investigated the Gsα pathway in short patients with distinct shortening of the 4th and 5th metacarpals. METHODS: In 571 children with short stature and 4 patients with PHP-Ia metacarpal bone lengths were measured. In identified patients we analysed the Gsα protein function in platelets, performed GNAS sequencing, and epigenetic analysis of four significant differentially methylated regions. RESULTS: In 51 patients (8.9%) shortening of the 4th and 5th metacarpals was more pronounced than their height deficit. No GNAS coding mutations were identified in 20 analysed patients, except in 2 PHP-Ia patients. Gsα activity was reduced in all PHP-Ia patients and in 25% of the analysed patients. No significant methylation changes were identified. CONCLUSIONS: Our findings suggest that patients with short stature and distinct metacarpal bone shortening could be part of the wide variety of PHP/PPHP, therefore it was worthwhile analysing the Gsα protein function and GNAS gene in these patients in order to further elucidate the phenotype and genotype of Gsα dysfunction.


Asunto(s)
Sitios Genéticos , Trastornos del Crecimiento , Huesos del Metacarpo , Seudohipoparatiroidismo , Adolescente , Niño , Preescolar , Femenino , Trastornos del Crecimiento/diagnóstico por imagen , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/metabolismo , Humanos , Lactante , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Huesos del Metacarpo/metabolismo , Tamaño de los Órganos/genética , Seudohipoparatiroidismo/diagnóstico por imagen , Seudohipoparatiroidismo/genética , Seudohipoparatiroidismo/metabolismo , Radiografía
12.
Dev Biol ; 385(1): 83-93, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24161848

RESUMEN

The morphology of bones is genetically determined, but the molecular mechanisms that control shape, size and the overall gestalt of bones remain unclear. We previously showed that metacarpals in the synpolydactyly homolog (spdh) mouse, which carries a mutation in Hoxd13 similar to the human condition synpolydactyly (SPD), were transformed to carpal-like bones with cuboid shape that lack cortical bone and a perichondrium and are surrounded by a joint surface. Here we provide evidence that spdh metacarpal growth plates have a defect in cell polarization with a random instead of linear orientation. In parallel prospective perichondral cells failed to adopt the characteristic flattened cell shape. We observed a similar cell polarity defect in metacarpals of Wnt5a(-/-) mice. Wnt5a and the closely related Wnt5b were downregulated in spdh handplates, and HOXD13 induced expression of both genes in vitro. Concomitant we observed mislocalization of core planar cell polarity (PCP) components DVL2 and PRICKLE1 in spdh metacarpals indicating a defect in the WNT/PCP pathway. Conversely the WNT/ß-CATENIN pathway, a hallmark of joint cells lining carpal bones, was upregulated in the perichondral region. Finally, providing spdh limb explant cultures with cells expressing either HOXD13 or WNT5A led to a non-cell autonomous partial rescue of cell polarity the perichondral region and restored the expression of perichondral markers. This study provides a so far unrecognized link between HOX proteins and cell polarity in the perichondrium and the growth plate, a failure of which leads to transformation of metacarpals to carpal-like structures.


Asunto(s)
Cartílago/embriología , Placa de Crecimiento/embriología , Proteínas de Homeodominio/metabolismo , Huesos del Metacarpo/embriología , Factores de Transcripción/metabolismo , Proteínas Wnt/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Cartílago/metabolismo , Polaridad Celular , Células Cultivadas , Proteínas Dishevelled , Placa de Crecimiento/metabolismo , Proteínas de Homeodominio/genética , Humanos , Proteínas con Dominio LIM/metabolismo , Huesos del Metacarpo/metabolismo , Ratones , Ratones Noqueados , Morfogénesis/genética , Fosfoproteínas/metabolismo , Receptores de Fenciclidina/metabolismo , Sindactilia/genética , Factores de Transcripción/genética , Proteínas Wnt/genética , Proteína Wnt-5a , beta Catenina/metabolismo
13.
Ann Rheum Dis ; 73(8): 1522-8, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23709244

RESUMEN

OBJECTIVE: The primary objective of this prospective case-control study was to assess the diagnostic value of several intra-articular and periarticular ultrasound (US)-detected abnormalities in the upper and lower limbs in gout. The secondary objective was to test the concurrent validity of US abnormalities using as gold standard the microscopic demonstration of monosodium urate (MSU) crystals. METHODS: Ninety-one men with gout and 42 age-matched controls were prospectively recruited. All patients with gout and controls underwent US assessment of several US abnormalities in 26 joints, six bursae, eight tendons, 20 tendon compartments, four ligaments, and 18 articular cartilages by experts in US blinded to the patients' group. Patients with gout and controls with US abnormalities were asked to undergo US-guided aspiration for microscopic identification of MSU crystals. Interobserver and intraobserver reliability of the US assessment was evaluated in a web-based exercise. RESULTS: The assessment of one joint (ie, radiocarpal joint) for hyperechoic aggregates (HAGs), two tendons (ie, patellar tendon and triceps tendon) for HAGs and three articular cartilages (ie, first metatarsal, talar and second metacarpal/femoral) for double contour sign showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively). Intraobserver reliability was good (mean κ 0.75) and interobserver reliability was moderate (κ 0.52). The aspirated material from HAGs was positive for MSU crystals in 77.6% of patients with gout and negative in all controls. CONCLUSIONS: Our results suggest that US bilateral assessment of one joint, three articular cartilages and two tendons may be valid for diagnosing gout with acceptable sensitivity and specificity.


Asunto(s)
Gota/diagnóstico por imagen , Enfermedades Musculoesqueléticas/diagnóstico por imagen , Ultrasonografía/normas , Ácido Úrico/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/metabolismo , Estudios de Casos y Controles , Cristalización , Femenino , Gota/complicaciones , Gota/metabolismo , Humanos , Articulaciones/diagnóstico por imagen , Articulaciones/metabolismo , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Huesos del Metacarpo/metabolismo , Huesos Metatarsianos/diagnóstico por imagen , Huesos Metatarsianos/metabolismo , Persona de Mediana Edad , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/metabolismo , Variaciones Dependientes del Observador , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tendones/diagnóstico por imagen , Tendones/metabolismo , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricos , Ácido Úrico/química
14.
Equine Vet J ; 43(5): 509-15, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21545647

RESUMEN

REASONS FOR PERFORMING STUDY: The effect of palmar osteochondral disease lesions on performance of Thoroughbred (TB) racehorses is unclear. There is a need to describe patterns of radiopharmaceutical uptake (IRU) in fetlock joints of TB racehorses and to evaluate post scintigraphy performance. HYPOTHESES: IRU in the metacarpal (MC) and metatarsal (MT) condyles is more common than IRU in the parasagittal grooves and is associated with poorer post diagnosis performance than controls. METHODS: Location of IRU within the fetlock region was identified and graded subjectively in TB racehorses. Performance variables were determined from race records for horses with moderate/marked MC/MT condylar IRU (cases), other horses undergoing scintigraphy (scintigraphy controls) and age/sex matched controls from the last race in which a case participated (controls). Statistical analyses included quantile regression, Fisher's exact test, Kaplan-Meier survival curves, log-rank test and Cox regression. RESULTS: Metacarpal/MT condylar IRU was identified in 103/220 horses with only 3/220 having parasagittal IRU. Moderate/marked IRU was identified in the MC and MT condylar regions in 62 and 39 horses, respectively, with palmaromedial and plantarolateral IRU most common. Fore- and hindlimb cases had fewer starts, reduced earnings (P<0.001) and reduced earnings/start than controls respectively. Cases were more likely to return to racing later than controls following a rest period. Cases were older than scintigraphy controls. CONCLUSIONS: In TB racehorses presenting for lameness MC/MT condylar IRU is the most common abnormality identified within the fetlock joint. Racehorses with moderate/marked condylar IRU have a shortened racing career, are less successful than age/sex matched controls and are older than other racehorses presented for scintigraphy. POTENTIAL RELEVANCE: Overload of the MC/MT condyles is a common and significant problem in TB racehorses that is readily identified with scintigraphy. Scintigraphy of horses that are lame or performing poorly is less useful for screening for potential condylar fractures.


Asunto(s)
Miembro Anterior/patología , Enfermedades de los Caballos/diagnóstico , Artropatías/veterinaria , Huesos del Metacarpo/metabolismo , Compuestos de Organotecnecio/farmacocinética , Cintigrafía/veterinaria , Animales , Femenino , Caballos , Artropatías/diagnóstico , Cojera Animal/diagnóstico , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Radiofármacos/farmacocinética , Carrera , Deportes
15.
J Anim Sci ; 89(2): 460-6, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20952526

RESUMEN

The relative bioavailability of P in 5 sources of inorganic P was determined using growing pigs. The 5 sources of inorganic P were dicalcium phosphate (DCP), monocalcium phosphate (MCP) containing 50% MCP (MCP50), MCP containing 70% MCP (MCP70), MCP containing 100% MCP (MCP100), and monosodium phosphate (MSP). A total of 11 diets were formulated. The basal diet was formulated to contain 0.10% P, and 10 additional diets were formulated by adding 0.07 or 0.14% P from each of the 5 P sources to the basal diet. Growing pigs (n = 44; initial BW: 16.8 ± 4.3 kg) were individually housed and randomly allotted to the 11 experimental diets. Feed was provided on an ad libitum basis throughout the 28-d experimental period. At the conclusion of the experiment, all pigs were killed, and 4 bones (i.e., the third and fourth metacarpals on both front feet) were harvested. Bone-breaking strength, bone ash, and Ca and P concentrations were determined. The concentration of bone ash increased (P < 0.05) as MCP50, MCP70, MCP100, or MSP were added to the basal diet, and the concentration of bone P also increased (P < 0.05) as MCP70, MCP100, or MSP were added to the basal diet. The relative bioavailability of P in each of the feed phosphates was determined using slope ratio methodologies based on breaking strength, and expressed relative to MSP. The slope of the regression line for diets containing MSP or MCP100 was steeper (P < 0.05) than the slope for pigs fed the diet containing DCP, but not different (P > 0.05) from that of pigs fed diets supplemented with MCP50 or MCP70. In conclusion, P in MSP and MCP100 is more bioavailable than P in DCP, but there were no differences within MCP sources.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Huesos del Metacarpo/metabolismo , Fósforo Dietético/farmacocinética , Fósforo/farmacocinética , Porcinos/metabolismo , Animales , Disponibilidad Biológica , Huesos del Metacarpo/química , Minerales/análisis , Minerales/farmacocinética , Fósforo/administración & dosificación , Distribución Aleatoria , Análisis de Regresión
16.
J Nutr Health Aging ; 13(6): 545-9, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19536423

RESUMEN

OBJECTIVES: To clarify the annual changes and effects of nutrition and physical activity on bone mass at the second metacarpal using computed X-ray densitometry. DESIGN: Population-based prospective follow-up study. MEASUREMENTS: Bone mass measurements and assessments of nutritional intake, exercise habits, and health status were conducted twice with a one-year interval. PARTICIPANT: 269 Japanese women aged 40 - to -80 - years old. RESULTS: The annual change rate among subjects who started menopause during the observation period was -4.2 +/- 4.9%. Bone mass subsequently continued to decrease 3% annually until 6 years after menopause. Subjects who consumed high levels of milk or calcium in the first year showed no substantial decrease in bone mass among the post-menopausal subjects. Premenopausal subjects who began or continued exercise evidenced increased bone mass, and peri-menopausal subjects who continued exercise or a high level of daily physical activity showed inhibited bone loss. CONCLUSION: Second metacarpal bone changed by menopause, nutrition and physical activity similar with other bone site presented in the previous studies.


Asunto(s)
Densidad Ósea , Calcio de la Dieta/farmacología , Dieta , Ejercicio Físico/fisiología , Menopausia/metabolismo , Huesos del Metacarpo/metabolismo , Actividad Motora , Absorciometría de Fotón , Adulto , Análisis de Varianza , Animales , Densidad Ósea/efectos de los fármacos , Femenino , Humanos , Japón , Huesos del Metacarpo/anatomía & histología , Persona de Mediana Edad , Leche , Fenómenos Fisiológicos de la Nutrición , Estudios Prospectivos , Factores de Tiempo
17.
BMC Musculoskelet Disord ; 10: 27, 2009 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-19245707

RESUMEN

BACKGROUND: There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis. METHODS: Expression levels for 12 genes representative of musculoskeletal tissues, including the proposed tendon progenitor marker scleraxis, relative to validated reference genes, were evaluated in matched samples of equine tendon (harvested from the superficial digital flexor tendon), cartilage and bone using quantitative PCR (qPCR). Expression levels of genes associated with tendon phenotype were then evaluated in healthy, including developmental, and diseased equine tendon tissue and in tendon fibroblasts maintained in both monolayer culture and in three dimensional (3D) collagen gels. RESULTS: Significantly increased expression of scleraxis was found in tendon compared with bone (P = 0.002) but not compared to cartilage. High levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be most representative of adult tensional tendon phenotype. While, relative expression of scleraxis in developing mid-gestational tendon or in acute or chronically diseased tendon did not differ significantly from normal adult tendon, tenascin-C message was significantly upregulated in acutely injured equine tendon (P = 0.001). Relative scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower than in normal adult tendon (P = 0.002, P = 0.02 respectively). CONCLUSION: The findings of this study indicate that high expression of both COL1A2 and scleraxis, and low expression of tenascin-C is representative of a tensional tendon phenotype. The in vitro culture methods used in these experiments however, may not recapitulate the phenotype of normal tensional tendon fibroblasts in tissues as evidenced by gene expression.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Cartílago Articular/metabolismo , Técnicas de Cultivo de Célula/métodos , Expresión Génica , Huesos del Metacarpo/metabolismo , Tendinopatía/metabolismo , Tendones/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Cartílago Articular/patología , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Geles , Marcadores Genéticos , Caballos , Huesos del Metacarpo/patología , Tendinopatía/patología , Tendones/patología
18.
Biol Trace Elem Res ; 121(2): 149-59, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17992476

RESUMEN

Twenty calves were placed on study at 3 days of age and were placed according to birth order into one of two groups: SS, which received 0.05% BW sodium zeolite A (SZA) added to their milk replacer, and CO, which received only milk replacer. Blood samples were taken on days 0, 30, and 60 for osteocalcin (OC) and deoxypyridinoline (DPD) analysis. On day 60, the calves were euthanized, and synovial fluid, articular cartilage, and both fused metacarpals were collected for bone quality analyses such as architecture and mechanical properties, mineral composition, and glycosaminoglycan concentration. There were no differences in OC concentrations because of treatment (p = 0.12), and CO calves had lower DPD concentrations than SS calves (p = 0.01), but the OC-to-DPD ratio was not different between treatments (p = 0.98). No differences in bone architecture or mechanical properties were detected. SZA supplementation increased cortical bone (p = 0.0002) and articular cartilage (p = 0.05) aluminum content. Glycosaminoglycan concentrations were not different in synovial fluid or cartilage. Supplementation of SZA appeared to alter the rate of bone turnover without altering bone strength. Aluminum concentrations in the bone and cartilage increased, which may be a concern, although the long-term consequences of such remain to be determined.


Asunto(s)
Remodelación Ósea/efectos de los fármacos , Suplementos Dietéticos , Huesos del Metacarpo/metabolismo , Zeolitas/farmacología , Aluminio/metabolismo , Aminoácidos/metabolismo , Animales , Cartílago Articular/metabolismo , Cartílago Articular/patología , Bovinos , Suplementos Dietéticos/efectos adversos , Glicosaminoglicanos/metabolismo , Huesos del Metacarpo/patología , Osteocalcina/metabolismo , Líquido Sinovial/metabolismo , Zeolitas/efectos adversos
20.
Vet Radiol Ultrasound ; 48(5): 460-6, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17899983

RESUMEN

The aims of this study were to establish the frequency of occurrence, intensity and symmetry of focal increased radiopharmaceutical uptake in the dorsoproximal aspect of the diaphysis of the proximal phalanx; to determine if this focal increased radiopharmaceutical uptake was related to age, height, gender, breed, bodyweight, or discipline of the horse, and if there was any relationship with lameness. Scintigraphic images from 690 horses were analyzed subjectively and objectively. Age, breed, discipline, height, weight, gender, and lame limb(s) or reasons for presentation were recorded for all horses. Univariate and multivariable logistic regression was performed to identify associations between available variables and focal increased radiopharmaceutical uptake. Focal increased radiopharmaceutical uptake was present in 17% of forelimbs and 7% of hindlimbs. It occurred most frequently in the forelimbs of older, taller, and heavier warmblood and warmblood cross dressage horses, and the hindlimbs of older, taller, and heavier showjumpers and dressage horses. It was usually bilaterally symmetrical and was not associated with lameness.


Asunto(s)
Caballos/anatomía & histología , Huesos del Metacarpo/metabolismo , Huesos Metatarsianos/metabolismo , Radiofármacos/farmacocinética , Medronato de Tecnecio Tc 99m/farmacocinética , Animales , Femenino , Miembro Anterior/diagnóstico por imagen , Miembro Anterior/metabolismo , Miembro Posterior/diagnóstico por imagen , Miembro Posterior/metabolismo , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Huesos Metatarsianos/diagnóstico por imagen , Cintigrafía/veterinaria , Reproducibilidad de los Resultados
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