123 research outputs found
Real-time imaging of Leishmania mexicana-infected early phagosomes: a study using primary macrophages generated from green fluorescent protein-Rab5 transgenic mice
No full textThe small GTPase Rab5 is a key regulator of endosome/phagosome maturation and in intravesicular infections marks a phagosome stage at which decisions over pathogen replication or destruction are integrated. It is currently unclear whether Leishmania-infected phagosomes uniformly pass through a Rab5(+) stage on their intracellular path to compartments with late endosomal/early lysosomal characteristics. Differences in routes and final compartments could have consequences for accessibility to antileishmanial drugs. Here, we generated a unique gfp-rab5 transgenic mouse model to visualize Rab5 recruitment to early parasite-containing phagosomes in primary host cells. Using real-time fluorescence imaging of phagosomes carrying Leishmania mexicana, we determined that parasite-infested phagosomes follow a uniform sequence of transient Rab5 recruitment. Residence in Rab5(+) compartments was much shorter compared with phagosomes harboring latex beads. Furthermore, a comparative analysis of parasite life-cycle stages and mutants deficient in lpg1, the gene encoding the enzyme required for synthesis of the dominant surface lipophosphoglycan, indicated that parasite surface ligands and host cell receptors modulate pathogen residence times in Rab5(+) phagosomes, but, as far as tested, had no significant effect on intracellular L. mexicana survival or replication. - Lippuner, C., Paape, D., Paterou, A., Brand, J., Richardson, M., Smith, A. J., Hoffmann, K., Brinkmann, V., Blackburn, C., Aebischer, T. Real-time imaging of Leishmania mexicana-infected early phagosomes: a study using primary macrophages generated from green fluorescent protein-Rab5 transgenic mice. FASEB J. 23, 483-491 (2009)</p
Kosteneffektivität einer Osteoporose-Behandlung nach systematischem Bevölkerungsscreening in der Schweiz: Auswirkungen der Preisreduktion des Alendronat-Originalpräparates
No full textManagement of fragility fractures in Switzerland: results of a nationwide survey
No full textA nationwide survey was conducted in Switzerland to assess the quality level of osteoporosis management in patients aged 50 years or older presenting with a fragility fracture to the emergency ward of the participating hospitals. Eight centres recruited 4966 consecutive patients who presented with one or more fractures between 2004 and 2006. Of these, 3667 (2797 women, 73.8 years old and 870 men, 73.0 years old in average) were considered as having a fragility fracture and included in the survey. Included patients presented with a fracture of the upper limbs (30.7%), lower limbs (26.4%), axial skeleton (19.5%) or another localisation, including malleolar fractures (23.4%). Thirty-two percent reported one or more previous fractures during adulthood. Of the 2941 (80.2%) hospitalised women and men, only half returned home after discharge. During diagnostic workup, dual x-ray absorptiometry (DXA) measurement was performed in 31.4% of the patients only. Of those 46.0% had a T-score < or =-2.5 SD and 81.1% < or =-1.0 SD. Osteoporosis treatment rate increased from 26.3% before fracture to 46.9% after fracture in women and from 13.0% to 30.3% in men. However, only 24.0% of the women and 13.8% of the men were finally adequately treated with a bone active substance, generally an oral bisphosphonate, with or without calcium / vitamin D supplements. A positive history of previous fracture vs none increased the likelihood of getting treatment with a bone active substance (36.6 vs 17.9%, ? 18.7%, 95% CI 15.1 to 22.3, and 22.6 vs 9.9%, ? 12.7%, CI 7.3 to 18.5, in women and men, respectively). In Switzerland, osteoporosis remains underdiagnosed and undertreated in patients aged 50 years and older presenting with a fragility fracture
2020 recommendations for osteoporosis treatment according to fracture risk from the Swiss Association against Osteoporosis (SVGO).
No full textCurrent guidelines from the Swiss Association against Osteoporosis (SVGO) dating from 2015 recommend therapy for men and women at increased fracture risk, specifically those with a vertebral or hip fracture; those with bone mineral density T-score <−2.5 at spine or hip; and those with a high 10-year probability of a major osteoporotic fracture as calculated by using FRAX. However no specific treatment recommendations have been made so far in our country to guide therapy according to the baseline level of risk. We now define four risk subgroup categories (imminent and very high, high, moderate, low) and propose an algorithm for osteoporosis therapy according to the level of fracture risk
Compressive strength of interbody cages in the lumbar spine: the effect of cage shape, posterior instrumentation and bone density
No full textOne goal of interbody fusion is to increase the height of the degenerated disc space. Interbody cages in particular have been promoted with the claim that they can maintain the disc space better than other methods. There are many factors that can affect the disc height maintenance, including graft or cage design, the quality of the surrounding bone and the presence of supplementary posterior fixation. The present study is an in vitro biomechanical investigation of the compressive behaviour of three different interbody cage designs in a human cadaveric model. The effect of bone density and posterior instrumentation were assessed. Thirty-six lumbar functional spinal units were instrumented with one of three interbody cages: (1) a porous titanium implant with endplate fit (Stratec), (2) a porous, rectangular carbon-fibre implant (Brantigan) and (3) a porous, cylindrical threaded implant (Ray). Posterior instrumentation (USS) was applied to half of the specimens. All specimens were subjected to axial compression displacement until failure. Correlations between both the failure load and the load at 3 mm displacement with the bone density measurements were observed. Neither the cage design nor the presence of posterior instrumentation had a significant effect on the failure load. The loads at 3 mm were slightly less for the Stratec cage, implying lower axial stiffness, but were not different with posterior instrumentation. The large range of observed failure loads overlaps the potential in vivo compressive loads, implying that failure of the bone-implant interface may occur clinically. Preoperative measurements of bone density may be an effective tool to predict settling around interbody cages
The relative importance of vertebral bone density and disc degeneration in spinal flexibility and interbody implant performance. An in vitro study
No full textAn in vitro biomechanical investigation in the human lumbar spine focuses on the functional significance of vertebral bone density and intervertebral disc degenerations
Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women
No full textIn a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures
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