Human fetal bone cells in delivery systems for bone engineering.

The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis(®)) and collagen foams (TissueFleece(®)). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

Bone histomorphometry of broilers submitted to different phosphorus sources in growing and finisher rations

The objective of this work was to identify alterations in the histomorphology of the cortical bone tissue of broilers submitted to growing and finisher rations formulated with five different sources of phosphorus: dicalcium phosphate, simple superphosphate, triple superphosphate, monoammonium phosphate and Araxá rock phosphate. Histological images had their components segmented, and were called regions of interest (ROI). Images were analyzed through developed algorithms, using the SCILAB mathematical environment. Eleven features were considered in order to obtain a complete description of the bone images: percentage of bone by area, ROI area, ROI perimeters, ROI elongation, ROI angle and their respective standard deviations, besides entropy of ROI angles and a texture-oriented measure (lacunarity). The substitution of dicalcium phosphate in growing and finisher rations for any other tested source of phosphorus caused significant changes on the hystomorphology of the cortical broilers bones, for example: diminution of bone percentage by area, increase of lacuna area and worse matrix homogeneity. Changes were more pronounced in the Araxá rock phosphate treatments, with the highest fluorine content, than in simple superphosphate, triple superphosphate and monoammonium phosphate treatments, which were similar.

Eficacia e ineficacia de la comunicación horizontal en los movimientos sociales. Caso análisis: Oposiciones justas en Cataluña 2011

Las redes sociales están generando un amplio entramado de comunicaciones, a distintos niveles y con distintos objetivos. En este artículo analizamos un caso concreto, fruto de la observación y el seguimiento de un grupo creado para la defensa de unas oposiciones justas para el acceso a la función pública de docentes para educación secundaria. Se trata de un grupo creado como reacción a una serie de posibles irregularidades. Interesa observar tanto la creación del grupo, como las distintas fases que sigue la evolución, muy ligada a la efectividad de los procesos de comunicación, y la vinculación de estos últimos a las posibilidades de acción y resolución del conflicto que existe en la base del grupo

Immunohistochemical analysis of bone morphological protein signaling pathway in human myometrium.

We assessed by immunohistochemistry the expression of the phosphorylated (activated) form of Smad1 and 5 (P-SMAD1/5), of Noggin and of two smooth muscle cell markers (α-SMA and SM22) in a series of human myometrium samples and in a smooth muscle cell line derived from human myometrium (HUt-SMC, PromoCell, USA). Myometrium samples were removed from two cadavers (a fetus at 26weeks of gestation and a neonate) and from ten non-menopausal women who underwent hysterectomy for adenomyosis and leiomyoma. P-SMAD1/5 expression was never detected in myometrium (both normal and pathological specimens), but only as a nuclear positive staining in glandular and luminal epithelial cells in sections in which also the endometrial mucosa was present. Noggin was strongly expressed especially in myometrium and adenomyosis samples from non-menopausal patients in comparison to the neonatal and fetal myometrium specimens in which muscle cells were less positive. In more than 95% of HUt-SMCs, α-SMA and Desmin were co-expressed, indicating a pure smooth muscle phenotype. When progesterone was added to the culture medium, no P-SMAD1/5 expression was detected, whereas the expression Noggin and SM22, a marker of differentiated smooth muscle cells, increased by 3 fold (p=0.002) and 4.3 fold (p=0.001), respectively (p=0.002). Our results suggest that, in non-menopausal normal human myometrium, the BMP pathway might be inhibited and that this inhibition might be enhanced by progesterone, which increases the differentiation of smooth muscle cells (SM22 levels). These findings could help in the identification of new mechanisms that regulate uterine motility.

Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents.

OBJECTIVE: To evaluate the effects of nutrient intake and vitamin D status on markers of type I collagen formation and degradation in adolescent boys and girls. DESIGN: Cross-sectional study. SETTING: Canton of Vaud, West Switzerland. SUBJECTS: A total of 92 boys and 104 girls, aged 11-16 y. Data were collected on height, weight, pubertal status (self-assessment of Tanner stage), nutrient intake (3-day dietary record) and fasting serum concentration of 25-hydroxyvitamin D (25OHD), and markers of collagen formation (P1NP) and degradation (serum C-terminal telopeptides: S-CTX). RESULTS: Tanner stage was a significant determinant of P1NP in boys and girls and S-CTX in girls. Of the nutrients examined, only the ratio of calcium to phosphorus (Ca/P) was positively associated with P1NP in boys, after adjustment for pubertal status. 25OHD decreased significantly at each Tanner stage in boys. Overall, 15% of boys and 17% of girls were identified as being vitamin D insufficient (serum 25OHD <30 nmol/l), with the highest proportion of insufficiency at Tanner stage 4-5 (29%) in boys and at Tanner stage 3 (24%) in girls. A significant association was not found between 25OHD and either bone turnover marker, nor was 25OHD insufficiency associated with higher concentrations of the bone turnover markers. CONCLUSIONS: The marked effects of puberty on bone metabolism may have obscured any possible effects of diet and vitamin D status on markers of bone metabolism. The mechanistic basis for the positive association between dietary Ca/P ratio and P1NP in boys is not clear and may be attributable to a higher Ca intake per se, a critical balance between Ca and P intake or higher dairy product consumption. A higher incidence of vitamin D insufficiency in older adolescents may reflect a more sedentary lifestyle or increased utilisation of 25OHD, and suggests that further research is needed to define their requirements. SPONSORSHIP: Nestec Ltd and The Swiss Foundation for Research in Osteoporosis.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

CONTEXT: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk. OBJECTIVE: The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment. DESIGN, SETTING, AND PATIENTS: We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis. Intervention: A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months. MAIN OUTCOME MEASURES: Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications. RESULTS: Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index >or= 25 kg/m(2) (P = 0.02). There were no significant treatment-factor interactions for hip or nonvertebral fracture or for change in BMD. CONCLUSIONS: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.

Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength.

A role for gut hormone in bone physiology has been suspected. We evidenced alterations of microstructural morphology (trabecular and cortical) and bone strength (both at the whole-bone - and tissue-level) in double incretin receptor knock-out (DIRKO) mice as compared to wild-type littermates. These results support a role for gut hormones in bone physiology. INTRODUCTION: The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to control bone remodeling and strength. However, lessons from single incretin receptor knock-out mice highlighted a compensatory mechanism induced by elevated sensitivity to the other gut hormone. As such, it is unclear whether the bone alterations observed in GIP or GLP-1 receptor deficient animals resulted from the lack of a functional gut hormone receptor, or by higher sensitivity for the other gut hormone. The aims of the present study were to investigate the bone microstructural morphology, as well as bone tissue properties, in double incretin receptor knock-out (DIRKO) mice. METHODS: Twenty-six-week-old DIRKO mice were age- and sex-matched with wild-type (WT) littermates. Bone microstructural morphology was assessed at the femur by microCT and quantitative X-ray imaging, while tissue properties were investigated by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Bone mechanical response was assessed at the whole-bone- and tissue-level by 3-point bending and nanoindentation, respectively. RESULTS: As compared to WT animals, DIRKO mice presented significant augmentations in trabecular bone mass and trabecular number whereas bone outer diameter, cortical thickness, and cortical area were reduced. At the whole-bone-level, yield stress, ultimate stress, and post-yield work to fracture were significantly reduced in DIRKO animals. At the tissue-level, only collagen maturity was reduced by 9 % in DIRKO mice leading to reductions in maximum load, hardness, and dissipated energy. CONCLUSIONS: This study demonstrated the critical role of gut hormones in controlling bone microstructural morphology and tissue properties.

Genomic islands: tools of bacterial horizontal gene transfer and evolution.

Abstract Bacterial genomes evolve through mutations, rearrangements or horizontal gene transfer. Besides the core genes encoding essential metabolic functions, bacterial genomes also harbour a number of accessory genes acquired by horizontal gene transfer that might be beneficial under certain environmental conditions. The horizontal gene transfer contributes to the diversification and adaptation of microorganisms, thus having an impact on the genome plasticity. A significant part of the horizontal gene transfer is or has been facilitated by genomic islands (GEIs). GEIs are discrete DNA segments, some of which are mobile and others which are not, or are no longer mobile, which differ among closely related strains. A number of GEIs are capable of integration into the chromosome of the host, excision, and transfer to a new host by transformation, conjugation or transduction. GEIs play a crucial role in the evolution of a broad spectrum of bacteria as they are involved in the dissemination of variable genes, including antibiotic resistance and virulence genes leading to generation of hospital 'superbugs', as well as catabolic genes leading to formation of new metabolic pathways. Depending on the composition of gene modules, the same type of GEIs can promote survival of pathogenic as well as environmental bacteria.

Horizontal vestibulo-ocular reflex dynamics in acute vestibular neuritis and viral labyrinthitis: evidence of otolith-canal interaction.

OBJECTIVE: To evaluate the dynamic properties of the horizontal vestibulo-ocular reflex (h-VOR) in the acute stage of two common labyrinthine diseases that provoke severe attacks of vertigo with spontaneous nystagmus: vestibular neuritis (vestibular loss alone) and viral labyrinthitis (cochleovestibular loss). MATERIAL AND METHODS: Sixty-three patients were investigated: 42 were diagnosed with vestibular neuritis and 21 with viral labyrinthitis. The h-VOR function was evaluated by conventional caloric and impulsive testing. A simplified model of vestibular function was used to analyze the vestibulo-ocular response to rotational stimulation. RESULTS: The results showed a significant difference in h-VOR characteristics between the two pathologies. Patients with vestibular neuritis exhibited a strong horizontal semicircular canal deficit, but no h-VOR asymmetry between the two rotational directions. In contrast, patients with viral labyrinthitis demonstrated moderate canal paresis and a marked h-VOR deficit in rotation toward the affected ear. CONCLUSION: These findings support the hypothesis that the h-VOR dynamic asymmetry that occurs after an acute unilateral inner ear lesion is not due to canal dysfunction alone, but involves complex adaptive changes in the central VOR that may implicate the otolith system. Based on histopathologic and clinical differences in the two pathologies reported in the literature, we postulate that this otolith-canal interaction is mainly linked to the loss of saccular function.

Ultraweak photon emission in assessing bone growth factor efficiency using fibroblastic differentiation.

Photons participate in many atomic and molecular interactions and changes. Recent biophysical research has shown the induction of ultraweak photons in biological tissue. It is now established that plants, animal and human cells emit a very weak radiation which can be readily detected with an appropriate photomultiplier system. Although the emission is extremely low in mammalian cells, it can be efficiently induced by ultraviolet light. In our studies, we used the differentiation system of human skin fibroblasts from a patient with Xeroderma Pigmentosum of complementation group A in order to test the growth stimulation efficiency of various bone growth factors at concentrations as low as 5 ng/ml of cell culture medium. In additional experiments, the cells were irradiated with a moderate fluence of ultraviolet A. The different batches of growth factors showed various proliferation of skin fibroblasts in culture which could be correlated with the ultraweak photon emission. The growth factors reduced the acceleration of the fibroblast differentiation induced by mitomycin C by a factor of 10-30%. In view that fibroblasts play an essential role in skin aging and wound healing, the fibroblast differentiation system is a very useful tool in order to elucidate the efficacy of growth factors.