Glucocorticoid-induced osteoporosis: 2013 update

Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoidinduced osteoporosis (GIO). A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF) and the European Calcified Tissue Society (ECTS) published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis

Benchmark of Atucha-2 PHWR RELAP5-3D Control Rod Model by Monte Carlo MCNP5 Core Calculation

Atucha-2 is a Siemens-designed PHWR reactor under construction in the Republic of Argentina. Its geometrical complexity and peculiarities require the adoption of advanced Monte Carlo codes for performing realistic neutronic simulations. Therefore core models of Atucha-2 PHWR were developed using MCNP5. In this work a methodology was set up to collect the flux in the hexagonal mesh by which the Atucha-2 core is represented. The scope of this activity is to evaluate the effect of obliquely inserted control rod on neutron flux in order to validate the RELAP5-3DC/NESTLE three dimensional neutron kinetic coupled thermal-hydraulic model, applied by GRNSPG/UNIPI for performing selected transients of Chapter 15 FSAR of Atucha-2

Functional neural differentiation of adult hippocampus derived stem cells

Stem cells are defined by their capacity to differentiate into different phenotypes while maintaining their ability to replicate indefinitely. These characteristics depend on their intrinsic capabilities and their interaction with the cellular niche. However, stem cells isolated later in development show a restricted differentiation capability limited to the cell lineage specifically present in the tissue of origin. Using an adult, hippocampal-derived stem cell line (designated the CHIP stem cell line), I started looking at their integration once they had been implanted into hippocampal organotypic slices. This would have given me an idea of the sequential steps they follow during their integration and how this relates to what is known to happen in vivo. Knowing that in the hippocampus, they originate from the sub granular zone and develop into granule cells, I carried out an electrophysiological characterization of dentate gyrus granule cells both in organotypic and in acute slice. It became clear that the survival of stem cells after the implantation was affected by the culture medium used for the organotypic slices. Switching to a different culture medium improved the survival of the stem cells but at the same time they did not show signs of integration (e.g. dendritic-like protrusions). I therefore started looking at stem cell functional differentiation in vitro without the slice. In the CHIP stem cell line plus, in addition, in another hippocampal stem cell line (HCN95) I compared the response to two differentiation protocols. I employed several standard neuronal markers (including NeuN) in order to define their developmental status. Unlike most other studies I also used a marker for the alpha subunit of the voltage-activated sodium channel (Nav1.2) which is responsible for the generation of action potentials in mature neurons. Checking stem cell ability to fire action potentials at various time intervals, in parallel to the expression of neuronal markers, I found that Nav1.2 expression better correlates with the functional maturation of our neuronal stem cell lines when compared to NeuN. Therefore, Nav1.2 expression can be employed as reliable marker of mature neuronal phenotype

Coupling of Thermal-Hydraulics and I&C for Licensing Analyses

The BEPU (Best Estimate Plus Uncertainty) approach constitutes a valuable and, under some circumstances, an unavoidable tool to demonstrate the safety of NPP (Nuclear Power Plants). Within the licensing process of the Atucha II PHWR (Pressurized Heavy Water Reactor) the BEPU approach has been followed for issuing the Chapter 15 of the FSAR (Final Safety Analysis Report). Namely, the BEPU approach replaced the classical conservative approach. The selection of PIE (Postulated Initiating Events) and, the analysis of each PIE by best estimate models supported by uncertainty evaluation constitute key elements for BEPU. An outline of the BEPU approach is included in the paper, which, otherwise focuses on the simulation needs for Instrumentation and Control (I & C). Sample results from the analysis of PIE are included in the paper. It is demonstrated that the simulation of I&C is necessary to evaluate the safety of the concerned NPP; furthermore, the simulation shall be part of the accident analysis in Chapter 15 of FSA

Value of thrombin-antithrombin III complexes in major orthopedic surgery: relation to the onset of venous thromboembolism.

This study evaluated (a) the possible changes of plasma levels of thrombin-antithrombin III complexes during hospitalization to predict venous thromboembolism in patients undergoing elective total hip replacement and (b) the sensitivity and specificity of thrombin-antithrombin III complexes in the late incidence of deep vein thrombosis when these patients are discharged from the hospital. In 50 consecutive patients (18 men, mean age = 63 ± 8 years) a venous blood sample was obtained from each patient before surgery and postsurgery on days 5 ± 2, 9 ± 2, and 45 to evaluate the thrombin-antithrombin III complexes by the enzyme-linked immunosorbent assay as a part of a larger surveillance program. Six of 50 patients devel oped deep vein thrombosis, diagnosed by phlebography on the 45th day postsurgery. From the day before until the ninth day after surgery, mean values of the thrombin-antithrombin III complexes increased to a greater extent in patients with deep vein thrombosis than in those without, although the differences were not significant (from 14.8 ± 11.2 ng/mL to 36.2 ± 19.1 ng/mL in the former group and from 13.6 ± 3.3 ng/mL to 22.4 ± 5.1 ng/mL in the latter, p = NS). On the 45th day after surgery the mean value of the thrombin-antithrombin III com plexes reduced less in patients with deep vein thrombosis (up to 9.9 ± 1.9 ng/mL and to 25.2 ± 17.2 ng/mL, respectively, p = NS). In addition, thrombin-antithrombin III complexes re mained over the level reached on the fifth day only in the patients who developed deep vein thrombosis. On the 45th day after surgery, thrombin-antithrombin III complexes exhibited a sensitivity of 17%, a specificity of 86%, and an accuracy of 78% in differentiating the presence and absence of deep vein thrombosis as compared with phlebography. We conclude that after total hip replacement (a) serial measurement of the throm bin-antithrombin III complexes does not appear helpful in pre dicting venous thromboembolism during hospitalization, and (b) measurement of thrombin-antithrombin III complexes has a low diagnostic accuracy in diagnosing delayed deep vein thrombosis. However, the greater and persistent increase of thrombin-antithrombin III complexes level in patients who de veloped deep vein thrombosis may deserve further investiga tions

Spotlight on the Compositional Quality of Probiotic Formulations Marketed Worldwide

On the worldwide market, a great number of probiotic formulations are available to consumers as drugs, dietary supplements, and functional foods. For exerting their beneficial effects on host health, these preparations should contain a sufficient amount of the indicated living microbes and be pathogen-free to be safe. Therefore, the contained microbial species and their amount until product expiry are required to be accurately reported on the labels. While commercial formulations licensed as drugs are subjected to rigorous quality controls, less stringent regulations are generally applied to preparations categorized as dietary supplements and functional foods. Many reports indicated that the content of several probiotic formulations does not always correspond to the label claims in terms of microbial identification, number of living organisms, and purity, highlighting the requirement for more stringent quality controls by manufacturers. The main focus of this review is to provide an in-depth overview of the microbiological quality of probiotic formulations commercialized worldwide. Many incongruences in the compositional quality of some probiotic formulations available on the worldwide market were highlighted. Even if manufacturers carry at least some of the responsibility for these inconsistencies, studies that analyze probiotic products should be conducted following recommended and up-to-date methodologies

Microbiological quality and resistance to an artificial gut environment of two probiotic formulations

The quality control of probiotic products is the focus of numerous organizations worldwide. Several studies have highlighted the poor microbiological quality of many commercial probiotic formulations in terms of the identity of the contained microorganisms, viability, and purity, thus precluding the expected health benefits and representing a potential health risk for consumers. In this paper, we analyzed the contents of two probiotic formulations, one composed of an encapsulated mixture of lactobacilli and bifidobacteria, and one by a lyophilized yeast. The microorganisms contained in the products were quantified and identified using up-to-date methodologies, such as MALDI-TOF MS and metagenomic analysis. Moreover, as acid and bile tolerance is included among the criteria used to select probiotic microorganisms, in vitro tests were performed to evaluate the behavior of the formulations in conditions mimicking the harsh gastric environment and the intestinal fluids. Our results indicate the high quality of the formulations in terms of the enumeration and identification of the contained organisms, as well as the absence of contaminants. Moreover, both products tolerated the acidic conditions well, with encapsulation providing further protection for the microorganisms. A good tolerance to the simulated artificial intestinal conditions was also evidenced for both preparations

N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide (EPPTB) prevents 3-iodothyronamine (T1AM)-induced neuroprotection against kainic acid toxicity

Thyroid hormone and thyroid hormone metabolites, including 3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1), activate AKT signaling in hippocampal neurons affording protection from excitotoxic damage. We aim to explore whether the mechanism of T1AM neuroprotection against kainic acid (KA)-induced excitotoxicity included the activation of the trace amine associated receptor isoform 1 (TAAR1), one of T1AM targets. Rat organotypic hippocampal slices were exposed to vehicle (Veh) or to 5 μM kA for 24 h in the absence or presence of 0.1, 1 and 10 μM T1AM or to 0.1, 1 and 10 μM T1AM and 1 μM N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide (EPPTB), the only available TAAR1 antagonist, or to 1 μM T1AM in the absence or in the presence of 10 μM LY294002, an inhibitor of phosphoinositide 3-kinases (PI3Ks). Cell death was evaluated by measuring propidium iodide (PI) levels of fluorescence 24 h after treatment. In parallel, the expression levels of p-AKT and p-PKA were evaluated by Western blot analysis of slice lysates. The activity of mitochondrial monoamine oxidases (MAO) was assayed fluorimetrically. 24 h exposure of slices to T1AM resulted in the activation of AKT and PKA. KA exposure induced cell death in the CA3 region and significantly reduced p-AKT and p-PKA levels. The presence of 1 and 10 μM T1AM significantly protected neurons from death and conserved both kinase levels with the essential role of AKT in neuroprotection. Furthermore, EPPTB prevented T1AM-induced neuroprotection, activation of PKA and AKT. Of note, in the presence of EPPTB T1AM degradation by MAO was reduced. Our results indicate that the neuroprotection offered by T1AM depends, as for TA1, on AKT activation but do not allow to conclusively indicate TAAR1 as the target implicated. Graphical abstrac

3-iodothyronamine affects thermogenic substrates’ mobilization in brown adipocytes

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance

Efficacy of a specific rehabilitation protocol in postural control of a young woman with multiple fragility vertebral fractures: a case report

The fragility vertebral fractures have a considerable impact on an individual's health-related quality of life due to pain, limitations in activity, social participation, altered mood and balance impairment. Physiotherapy interventions may have an important role in improving quality of life, balance and reducing the fracture risk in people with osteoporotic vertebral fractures. In literature there are only a few studies that examine exercise interventions in osteoporotic populations with vertebral fracture and few studies that examine the effects on balance with instrumental measurements. In this paper we present a case of a woman with fragility vertebral fractures and a related balance impairment and the effects of a specific rehabilitation program using both clinical evaluations that instrumental measurement