Glucocorticoid-induced osteoporosis: clinical and therapeutic aspects.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30_50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. Glucocorticoids have direct and indirect effects on the skeleton. They impair the replication, differentiation, and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO

Volume-preserving normal forms of Hopf-zero singularity

A practical method is described for computing the unique generator of the algebra of first integrals associated with a large class of Hopf-zero singularity. The set of all volume-preserving classical normal forms of this singularity is introduced via a Lie algebra description. This is a maximal vector space of classical normal forms with first integral; this is whence our approach works. Systems with a non-zero condition on their quadratic parts are considered. The algebra of all first integrals for any such system has a unique (modulo scalar multiplication) generator. The infinite level volume-preserving parametric normal forms of any non-degenerate perturbation within the Lie algebra of any such system is computed, where it can have rich dynamics. The associated unique generator of the algebra of first integrals are derived. The symmetry group of the infinite level normal forms are also discussed. Some necessary formulas are derived and applied to appropriately modified R\"{o}ssler and generalized Kuramoto--Sivashinsky equations to demonstrate the applicability of our theoretical results. An approach (introduced by Iooss and Lombardi) is applied to find an optimal truncation for the first level normal forms of these examples with exponentially small remainders. The numerically suggested radius of convergence (for the first integral) associated with a hypernormalization step is discussed for the truncated first level normal forms of the examples. This is achieved by an efficient implementation of the results using Maple

Características tecnológicas de almidones de dos variedades de batatas (Ipomoea batatas [L.] Lam) infectadas con «encrespamiento amarillo»

El cultivo de batata se ve limitado por virosis y un complejo de siete virus, «encrespamiento amarillo» (EA), de alta incidencia en Argentina, provoca significativas disminuciones de rendimiento y calidad. En un ensayo experimental, con variedades Arapey INIA y Beauregard (sanas y enfermas con EA), se estimaron componentes de rendimiento (principalmente peso: PRC y número: NRC de raíces comerciales), rendimiento y característicastecnológicas de almidón como gelatinización y retrogradación (calorimetría diferencial de barrido) y viscosidad aparente de las pastas (analizador de viscosidad). Se analizó el comportamiento reológico de los geles de almidón, mediante resistencia a la compresión con analizador de textura, y se determinó distribución de tamaño de partícula. NRC y PRC fueron significativamente menores en plantas enfermas respecto a sanas (mermas de 81% para NRC en ambas variedades y 87% y 85,5% para PRC, en Beauregard y Arapey, respectivamente). EA no afectó al rendimiento de almidón, sin diferencias entre raíces sanas y enfermas de ambas variedades, aunque Arapey (9,00-10,05%) superó a Beauregard (6,23-8,06%). La entalpía de gelatinización del almidón resultó significativamente mayor en plantas enfermas de Beauregard que en sanas, sin diferencias en la temperatura de inicio de gelatinización entre ambos tratamientos, contrariamente a lo que sucedió en Arapey. El pico de viscosidad y la viscosidad final de los almidones fueron similares en plantas sanas y enfermas de ambas variedades, igual que la resistencia a la compresión de geles elaborados con almidones provenientes de plantas sanas y enfermas de ambos genotipos. Todas las muestras tuvieron una sola población de tamaño de partícula de almidón (rango: 5 -25 μm con pico cercano a 15 μm). En definitiva, EA no afectó la calidad tecnológica del almidón. Sin embargo, la disminución significativa de producción de raíces comerciales en plantas enfermas conllevó relevante reducción de la cantidad total de almidón por planta

Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

TEM analysis of apatite surface layers observed on zinc based glass polyalkenoate cements

peer-reviewedGlass polyalkenoate cements (GPCs) are acid base cements formed by the reaction of an aqueous solution of polyalkenoic acid, usually polyacrylic acid (PAA) with an acid degradable aluminosilicate glass. The result of the reaction is cement consisting of reacted and unreacted glass particles embedded in a polysalt matrix. In addition to these conventional GPCs, aluminium free glass polyalkenoate cements based on zinc silicate glasses (Zn-GPCs) exhibit significant potential as bone cements for several reasons. Primarily, they are formulated without the inclusion of aluminium (Al) [1] in the glass phase and thus eliminate clinical complications arising from the release of the Al3+ ion from the cement in vivo. Such complications have, in the past, included aluminium induced encephalopathy [2-5] and defective mineralisation of cancellous bone [6]. Secondly, Zn-GPCs set without a significant evolution of heat, when compared with commercial bone cements such as Spineplex ® (Stryker, Limerick, Ireland). Finally, these materials can be tailored to release clinically beneficial ions into surrounding tissues [7]. In addition to Zn, these cements have been synthesized to contain strontium (Sr) [8, 9]. Both Sr and Zn inhibit osteoclastic turnover and promote osteoblastic turnover, resulting in increased bone strength and decreased fracture risk [10-14].Acceptedpeer-reviewe

Serum IGF-1 Affects Skeletal Acquisition in a Temporal and Compartment-Specific Manner

Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks) decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 16 weeks (adulthood). Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 32 weeks (late adulthood), but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks) resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks) is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse

Materials in particulate form for tissue engineering. 2 Applications in bone

Materials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application ofmaterials in particulate formfor bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented

Laryngeal embryonal rhabdomyosarcoma in an adult - A case presentation in the eyes of geneticists and clinicians

<p>1. Abstract</p> <p>Background</p> <p>Rhabdomyosarcoma is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. For rhabdomyosarcomas (RMS) with a predilection for the head and neck, genitourinary tract, extremities, trunk, retroperitoneum, the larynx is still an unusual site. Till now only several cases of this laryngeal tumor have been described in world literature in the adult population. The entire spectrum of genetic factors underlying RMS development and progression is unclear until today. Multiple signaling pathways seem to be involved in ERMS development and progression.</p> <p>Case presentation</p> <p>In this paper we report an interesting RMS case in which the disease was located within the glottic region. We report an embryonal rhabdomyosarcoma of the larynx in 33 year-old man. After unsuccessful chemotherapy hemilaryngectomy was performed. In follow up CT no signs of recurrence were found. Recently patient is recurrence free for 62 months.</p> <p>Conclusions</p> <p>Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery.</p