Fabrication of Net-Shape Functionally Graded Composites by Electrophoretic Deposition and Sintering: Modeling and Experimentation

It is shown that electrophoretic deposition (EPD) sintering is a technological sequence that is capable of producing net-shape bulk functionally graded materials (FGM). By controlling the shape of the deposition electrode, components of complex shapes can be obtained. To enable sintering net-shape capabilities, a novel optimization algorithm and procedure for the fabrication of net-shape functionally graded composites by EPD and sintering has been developed. The initial shape of the green specimen produced by EPD is designed in such a way that the required final shape is achieved after sintering-imposed distortions. The optimization is based on a special innovative iteration procedure that is derived from the solution of the inverse sintering problem: the sintering process is modeled in the “backward movie” regime using the continuum theory of sintering incorporated into a finite-element code. The experiments verifying the modeling approach include the synthesis by EPD of Al2O3/ZrO2 3-D (FGM) structures. In order to consolidate green parts shaped by EPD, post-EPD sintering is used. The fabricated deposits are characterized by optical and scanning electron microscopy. The experimentally observed shape change of the FGM specimen obtained by EPD and sintering is compared with theoretical predictions

Ultrastructural characteristics of glucocorticoid-induced osteoporosis

International audienc

Is androgen therapy indicated in men with osteoporosis?

Male osteoporosis is not rare, and its management is a public health issue. The clinical evaluation must include investigations for one or more etiological factors such as hypogonadism, which is found in 5% to 15% of men with osteoporosis. Gradual development of moderate hypogonadism is the most common situation, and the prevalence of hypogonadism increases with advancing age. The wealth of scientific data establishing a major role for sex hormones in growth, bone turnover, and the osteoporotic fracture risk is in striking contrast to the paucity of therapeutic trials. Androgen therapy did not consistently produce bone mass gains, and no data on potential anti-fracture effects are available. Androgen therapy was not associated with significant increases in mortality, prostate disorders, or cardiovascular events, but few data were obtained in patients older than 75 years. In practice, in a male patient with osteoporosis, a diagnosis of marked and persistent hypogonadism requires investigations for treatable causes. In patients younger than 75 years of age, androgen replacement therapy should be started, in collaboration with an endocrinologist. A history of fractures indicates a need for additional osteoporosis pharmacotherapy. The risk/benefit ratio of androgen therapy is unclear in men older than 75 years, in whom a reasonable option consists in combining fall-prevention measures, vitamin D supplementation, and a medication proven to decrease the risk of proximal femoral fractures

Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis

The finding of monoclonal gammopathy of undetermined significance (MGUS) is not infrequent during an evaluation for osteoporosis or a fracture. In most cases, the diagnosis is MGUS, whose prevalence increases with age. Although the impact of MGUS on bone mineral density, bone remodeling, and the fracture risk remains unclear, this asymptomatic hematological disorder may constitute a risk factor for osteoporosis. Furthermore, each year, 1% of patients with MGUS progress to multiple myeloma, a disease whose pathophysiology and association with bone loss and pathological fractures are increasingly well understood. Osteoporotic fractures, although probably common in myeloma patients, are less likely to be recognized. Here, we discuss the pathophysiology of myeloma and MGUS and their impact in terms of bone mineral density, osteoporotic fractures, and bone turnover markers

Is transiliac bone biopsy a painful procedure ?

Despite an increased availability of non-invasive procedures to assess bone mass, histological examination of undecalcified transiliac bone biopsies remains a very valuable tool in the diagnosis of metabolic or malignant bone disorders. Nonetheless, clinicians are sometimes reluctant to perform this “invasive” examination, arguing that it might be a painful procedure. The aim of our study was to evaluate pain and anxiety described by patients in the months following the biopsy and to characterize potential early or late side effects. A single interviewer conducted a phone survey (19 items questionnaire) in 117 patients in whom a bone biopsy had been performed by two experienced physicians, with the same material and similar anesthetic and technical procedure. The topics covered pain during or after the biopsy, anxiety, comparison of other potentially painful procedures, early or late side effects as well as global evaluation by the patients. Bone biopsy was judged as non-painful by almost 70% of patients; some discomfort was present in 25% in the following days. The procedure was described as similar as or less painful than bone marrow aspiration, venipuncture or tooth extraction. About 90% of the patients estimated that it was a quite bearable diagnostic procedure. Side effects were not serious. About 7% remembered a vasovagal episode, 47% of local bruising in the following days. There was no report of hematoma or infection. In experienced hands and adapted trephine, transiliac bone biopsy is a safe procedure that brings invaluable information in bone disorders

Elevated hepatocyte growth factor levels in osteoarthritis osteoblasts contribute to their altered response to bone morphogenetic protein-2 and reduced mineralization capacity

PURPOSE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts is involved in the progression of osteoarthritis (OA). Human osteoblasts isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin pathway, and a reduced mineralization in vitro as well as in vivo. These alterations were linked with an abnormal response to BMP-2. OA osteoblasts release factors such as the hepatocyte growth factor (HGF) that contribute to cartilage loss whereas chondrocytes do not express HGF. HGF can stimulate BMP-2 expression in human osteoblasts, however, the role of HGF and its effect in OA osteoblasts remains unknown. Here we investigated whether elevated endogenous HGF levels in OA osteoblasts are responsible for their altered response to BMP-2. METHODS: We prepared primary human subchondral osteoblasts using the sclerotic medial portion of the tibial plateaus of OA patients undergoing total knee arthroplasty, or from tibial plateaus of normal individuals obtained at autopsy. The expression of HGF was evaluated by qRT-PCR and the protein production by western blot analysis. HGF expression was reduced with siRNA technique whereas its activity was inhibited using the selective inhibitor PHA665752. Alkaline phosphatase activity (ALPase) and osteocalcin release were measured by substrate hydrolysis and EIA respectively. Canonical Wnt/β-catenin signaling (cWnt) was evaluated both by target gene expression using the TOPflash TCF/lef luciferase reporter assay and western blot analysis of β-catenin levels in response to Wnt3a stimulation. Mineralization in response to BMP-2 was evaluated by alizarin red staining. RESULTS: The expression of HGF was increased in OA osteoblasts compared to normal osteoblasts and was maintained during their in vitro differentiation. OA osteoblasts released more HGF than normal osteoblasts as assessed by western blot analysis. HGF stimulated the expression of TGF-β1. BMP-2 dose-dependently (1 to 100ng/ml) stimulated both ALPase and osteocalcin in normal osteoblasts whereas, it inhibited them in OA osteoblasts. HGF-siRNA treatments reversed this response in OA osteoblasts and restored the BMP-2 response. cWnt is reduced in OA osteoblasts compared to normal, and HGF-siRNA treatments increased cWnt in OA osteoblasts almost to normal. Smad1/5/8 phosphorylation in response to BMP-2, which is reduced in OA osteoblasts, was corrected when these cells were treated with PHA665752. The BMP-2-dependent mineralization of OA osteoblasts, which is also reduced compared to normal, was only partially restored by PHA665752 treatment whereas 28days treatment with HGF reduced the mineralization of normal osteoblasts. CONCLUSION: OA osteoblasts expressed more HGF than normal osteoblasts. Increased endogenous HGF production in OA osteoblasts stimulated the expression of TGF-β1 and reduced their response to BMP-2. Inhibiting HGF expression or HGF signaling restored the response to BMP-2 and Smad1/5/8 signaling. In addition, decreased HGF signaling partly corrects the abnormal mineralization of OA osteoblasts while increased HGF prevents the normal mineralization of normal osteoblasts. In summary, we hypothesize that sustained elevated HGF levels in OA osteoblasts drive their abnormal phenotype and is implicated in OA pathophysiology

Comparison between the Parks Medical Doppler and the Mano Médical Vet BP Doppler for recording indirect systemic blood pressure in conscious dogs

Background: The acquisition of systemic blood pressure (SBP) provides valuable information regarding cardiovascular function and tissue perfusion in human and veterinary species.Aim: To evaluate the agreement between Parks Medical Doppler (PMD) and Mano Médical Vet BP (MMVBP) Doppler for assessing SBP in conscious dogs.Methods: 40 client-owned dogs were prospectively enrolled; SBP measurements were acquired by a single operator using the PMD and then the MMVBP. The mean of five consecutive measurements for each device was classified according to target organ damage (TOD) risk scores (1: <140 mmHg; 2: 140–160 mmHg; 3: 160–180 mmHg; 4: ≥ 180 mmHg).Results: Total mean SBP for the devices was not statistically different (p = 0.77). However, the Bland–Altman analysis revealed wide limits of agreement (LoA), with MMVBP slightly underestimating SBP compared to PMD (bias = −0.6 mmHg, 95% LoA: −26.3 to 25.09). Both devices correlated well (r = 0.8269; p < 0.0001) and had identically acceptable intra-observer repeatability (coefficients of variation = 4.09% for MMVBP and 3.86% for PMD). Four dogs (10%) had a TOD score of 3 by one device but scored <3 with the other.Conclusion: A good agreement and correlation was observed between the PMD and the MMVBP, suggesting that both devices can be used interchangeably for assessment of SBP in conscious dogs. The wide LoA observed between both devices was most likely associated with intraindividual variability in SBP over time

Les effets extra-osseux de la vitamine D : faits, questions et controverses

La vitamine D a été longtemps considérée comme une hormone utile pour réguler le métabolisme phosphocalcique et la minéralisation osseuse. Depuis dix ans, la progression des connaissances fondamentales et cliniques sur son influence pluritissulaire est vertigineuse. Les auteurs passent en revue les effets biologique et clinique de la vitamine D en particulier sur le système immunitaire, les maladies auto-immunes, les infections, le cancer, le syndrome métabolique, le risque de chute, les fonctions cognitives et le fonctionnement musculaire

Extraskeletal effects of vitamin D: Facts, uncertainties, and controversies

Vitamin D was long viewed as a hormone acting chiefly to regulate calcium-phosphate metabolism and bone mineralization. Over the last decade, however, basic science and clinical researchers have produced a bewildering amount of information on the extraskeletal effects of vitamin D. This article is a review of the clinical and biological actions of vitamin D including effects on the immune system, auto-immune diseases, infections, cancer, metabolic syndrome, fall risk, cognitive function, and muscle function

Motherhood, Moral Authority and the Charismatic Matriarch in the Aftermath of Lethal Violence

Images of maternal suffering are an evocative and powerful means of communication in a world where the private grief of victims has increasingly become subject to commodification and public consumption. This article looks at the influence of bereaved mothers as symbols of respect, peace and dignity in the aftermath of violence, and as a result their persuasive presence in family activism. Drawing upon two case studies, this article explores the importance of victims’ stories in public life and, in particular, the presence of the charismatic matriarch in creating communities of solidarity, raising awareness of harms that have previously gone unheard and prompting policy change. It considers the ‘canonical’ story of the mother in public life and concludes by arguing that more attention should be paid to victims’ stories and their influence on policy-making, politics and eventually in becoming public grievances