Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS

The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal standard. The biological samples were extracted using Strata-X-C SPE cartridges and separated on C<sub>8</sub> column (50 x 3 mm, 3 µm), and methanol: 0.1% formic acid (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for D<sub>8</sub>-imatinib on mass spectrometer. The method was linear in the concentration range of 1-1500 ng/250 µl in spiked human plasma samples and limit of quantification was 5 ng/mL. Inter-day and intra-day variations in spiked human plasma spiked with 50, 250 and 500 ng /mL were less than 3.16%. The repeatability and reproducibility and other parameters of the methods were also validated. The method was employed for the analysis of the imatinib in human plasma and bone marrow samples. The drug levels in bone marrow and plasma samples were correlated to the degree of cytogenetic response. No significant difference of imatinib level between blood and bone marrow in IM-treated patients dosed to steady state was observed

Mechanical behavior of osteoporotic bone at sub-lamellar length scales

Osteoporosis is a disease known to promote bone fragility but the effect on the mechanical properties of bone material, which is independent of geometric effects, is particularly unclear. To address this problem, micro-beams of osteoporotic bone were prepared using focused ion beam (FIB) microscopy and mechanically tested in compression using an atomic force microscope (AFM) while observing using in situ electron microscopy. This experimental approach was shown to be effective at measuring the subtle changes in the mechanical properties of bone material required to evaluate the effects of osteoporosis. Osteoporotic bone material was found to have lower elastic modulus and increased strain to failure when compared to healthy bone material, while the strength of osteoporotic and healthy bone was similar. A mechanism is suggested based on these results and previous literature that indicates degradation of the organic material in osteoporosis bone is responsible for resultant mechanical properties

Relação coronal do implante com a crista óssea

Introdução: A reabilitação com implantes nas últimas décadas tem evoluído tendo em vista a obtenção de melhores resultados ao nível mecânico/funcional, mas também a nível estético. A relação coronal dos implantes com crista óssea é um dos pontos que tem sido estudado. Objectivo: Realizar uma revisão sobre a relação coronal dos implantes com a crista óssea, com objectivo de responder à seguinte questão “A posição sub-crestal dos implantes em relação à crista óssea é vantajosa?”. Para tal vão ser estudados alguns dos factores que podem influenciar esta decisão. Metodologia: Realizou-se pesquisa bibliográfica recorrendo às bases de dados da “MEDLINE/Pubmed”, “SciELO”, “Science Direct”, “B-on”, “Google Academic” e repositórios de várias universidades portuguesas e estrangeiras, com as palavras-chave: “Bone Cells” ”Bone remodeling”, “Bone Crest”, “Osseointegration”, “Implant Placement”, “Biologic Width” e “Platform Switching”,”Implant Placement Depth” e “Morse Cone”, tendo sido estas associadas entre si. Também foi realizada pesquisa manual em livros dos vários temas estudados. Conclusão: A colocação de implantes ao nível sub-crestal ainda apresenta alguma controvérsia, mas obedecendo a alguns factores, como a utilização de um implante e pilar específicos, pode tornar- se algo muito vantajoso numa perspectiva futura.Introduction: The rehabilitation using implants has evolved in the last decades with the purpose of obtaining better results at a mechanical/functional level but also at the aesthetic. The coronal relation between the implants and the bone crest is one of the points that have been more studied. Aim: Perform a revision about the coronal relation of the implants and the bone crest, with the goal to answer the following question “Is the sub-crest position of implants with the bone crest an advantage?”. For this, some factors that might influence this decision will be studied. Methodology: The bibliographic research was made using the data bases of “MEDLINE/Pubmed”, “SciELO”, “Science Direct”, “B-on”, “Google Academic” and the repositories of several Portuguese and foreign universities, using the following key-words:“Bone Cells” ”Bone remodeling”, “Bone Crest”, “Osseointegration”, “Implant Placement”, “Biologic Width” e “Platform Switching” e “Morse Cone”, and associating with each other. There were also used several books about the different subjects studied in this research. Conclusion: The implant placement at a sub-crestal level still presents some controversy, but following some factors, as using specific implant and abutment, it may become something very advantageous in a future perspective

A chondroblastic osteosarcoma of the coronoid process mimicking a fragmented coronoid process in a dog

A 6-year-old Rhodesian Ridgeback was presented with a 1.5 year history of right forelimb lameness. Clinical, radiological and computed tomographic findings suggested the presence of fragmented medial coronoid process. A subtotal coronoidectomy was performed and, due to the atypical appearance of the medial coronoid process on imaging and at surgery, histopathology of the fragments was performed which revealed chondroblastic OS. Ten months after surgery, the dog was re-presented with the same clinical signs and the radiographic changes were suggestive of a recurrence of the OS. Palliative therapy was instigated at the owner's request. Thirty months after surgery of the neoplasm, the dog was presented with dyspnea. Thoracic radiographs showed lesions consistent with lung metastases. Euthanasia was requested by the owner, who declined post-mortem examination

The Clinical Significance of Subclinical Thyroid Dysfunction.

Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's ag

Higher fracture prevalence and smaller bone size in patients with hEDS/HSD-a prospective cohort study

Increased fracture risk in patients with Ehlers-Danlos syndromes has been reported, but the reasons for it are incompletely understood. We aimed to investigate possible determinants of this increased risk and found that hEDS/HSD patients present with a cortical bone size deficit compared with control subjects, possibly related to lower mechanical loading. Introduction The Ehlers-Danlos syndromes (EDS) comprise a group of heritable connective tissue disorders caused by defects in the biosynthesis, secretion, and/or organization of fibrillar collagens which might impair bone strength. Our aim was to compare fracture prevalence, volumetric and areal bone mineral density (BMD), bone geometry, muscle size and the muscle-bone interaction, body composition and longitudinal changes therein between patients with hypermobile EDS (hEDS) or hypermobility spectrum disorder (HSD), and healthy control subjects. Methods Cross-sectional data comprised 39 female hEDS/HSD patients (age 41 +/- 11 years) and 43 age-matched controls. After 8 years, 27 hEDS/HSD and 17 control subjects were re-evaluated. Tibial trabecular and cortical volumetric BMD, bone mineral content (BMC), cortical bone geometry, and lower leg muscle cross-sectional area (CSA) were measured using pQCT. Body composition, areal BMD, and BMC were determined by DXA. Results At baseline, patients with hEDS/HSD presented with a smaller cortical bone area, smaller cortical thickness and muscle CSA, and a higher fracture prevalence than control subjects (all p < 0.05). No differences in areal or volumetric BMD were found. Longitudinally, muscle CSA decreased in both groups and muscle density decreased in the hEDS/HSD group (p < 0.001) whereas all bone parameters remained unchanged. Conclusion hEDS/HSD patients have a cortical bone size deficit compared with controls, possibly contributing to their increased fracture risk. They presented with decreased muscle CSA but normal bone/muscle area ratio, suggesting that this bone size deficit is likely secondary to decreased mechanical loading. Further, there were no arguments for accelerated bone loss in hEDS/HSD subjects

Chronology and Demography: How Many People Lived in a Mega-Site?

Since the discovery of the huge dimensions of Trypillia BIVCI mega-sites, estimations about their population size have mainly resulted magnitudes which are as extraordinary for European prehistory as the dimensions of the sites themselves. A variety of population calculations is known, usually (e.g. for Taljanky and Maidanetske) focusing on around 7500-25,000 inhabitants per site (Shmaglij, 1982; Shmaglij & Videiko, 1987; Kruts, 1989; Ohlrau, 2015). A basic assumption for these population estimations is the contemporaneity of the majority of houses in each megasite, which might be problematic. Also, for the reconstruction of the overall population density in the Southern Buh and Dnipro Interfluve, the question of the contemporaneity, or alternatively a sequential appearance, of mega-sites is very important. In many views, the mega-sites Nebelivka-Dobrovody-Taljanky-Maidanetske are described as a chronological sequence of about 15,000 people, moving after about fifty years from one site to the next, at a distance of about 20 km (Kruts, 1989). In other views, a contemporary existence of some of the mega-sites is supposed (MUller et al, in print). In such an argumentation, no less than about 30,000 people were projected as living contemporarily in mega-sites of the Volodymyrivsko-Tomashivska group

Functionally heterogeneous porous scaffold design for tissue engineering

Most of the current tissue scaffolds are mainly designed with homogeneous porosity which does not represent the spatial heterogeneity found in actual tissues. Therefore engineering a realistic tissue scaffolds with properly graded properties to facilitate the mimicry of the complex elegance of native tissues are critical for the successful tissue regeneration. In this work, novel bio-mimetic heterogeneous porous scaffolds have been modeled. First, the geometry of the scaffold is extracted along with its internal regional heterogeneity. Then the model has been discretized with planner slices suitable for layer based fabrication. An optimum filament deposition angle has been determined for each slice based on the contour geometry and the internal heterogeneity. The internal region has been discritized considering the homogeneity factor along the deposition direction. Finally, an area weight based approach has been used to generate the spatial porosity function that determines the filament deposition location for desired biomimetic porosity. The proposed methodology has been implemented and illustrative examples are provided. The effective porosity has been compared between the proposed design and the conventional homogeneous scaffolds. The result shows a significant error reduction towards achieving the biomimetic porosity in the scaffold design and provides better control over the desired porosity level. Moreover, sample designed structures have also been fabricated with a NC motion controlled micro-nozzle biomaterial deposition system