| 1. |
- Omar, Omar, et al.
(författare)
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In vivo gene expression in response to anodically oxidized versus machined titanium implants.
- 2010
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 92:4, s. 1552-1566
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Tidskriftsartikel (refereegranskat)abstract
- A quantitative polymerase chain reaction technique (qPCR) in combination with scanning electron microscopy was applied for the evaluation of early gene expression response and cellular reactions close to titanium implants. Anodically oxidized and machined titanium miniscrews were inserted in rat tibiae. After 1, 3, and 6 days the implants were unscrewed and the surrounding bone was retrieved using trephines. Both the implants and bone were analyzed with qPCR. A greater amount of cells, as indicated with higher expression of 18S, was detected on the oxidized surface after 1 and 6 days. Significantly higher osteocalcin (at day 6), alkaline phosphatase (at days 3 and 6), and cathepsin K (at day 3) expression was demonstrated for the oxidized surface. Higher expression of tumor necrosis factor-alpha (at day 1) and interleukin-1beta (at days 1 and 6) was detected on the machined surfaces. SEM revealed a higher amount of mesenchymal-like cells on the oxidized surface. The results show that the rapid recruitment of mesenchymal cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation, constitute biological mechanisms for osseointegration, and high implant stability associated with anodically oxidized implants. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.
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| 2. |
- Omar, Omar, et al.
(författare)
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Integrin and chemokine receptor gene expression in implant-adherent cells during early osseointegration.
- 2010
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3, s. 969-80
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of early cellular recruitment and interaction to titanium implants are not well understood. The aim of this study was to investigate the expression of pro-inflammatory cytokines, chemokines and adhesion markers during the first 24 h of implantation. Anodically oxidized and machined titanium implants were inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and analyzed with quantitative polymerase chain reaction. Immunohistochemistry and scanning electron microscopy revealed different cell types, morphology and adhesion at the two implant surfaces. A greater amount of cells, as indicated by higher expression of small subunit ribosomal RNA (18S), was detected on the oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was detected at the oxidized surfaces. Significantly higher tumor necrosis factor-alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for the machined surface. It is concluded that material surface properties rapidly modulate the expression of receptors important for the recruitment and adhesion of cells which are crucial for the inflammatory and regenerative processes at implant surfaces in vivo.
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| 3. |
- Omar, Omar, et al.
(författare)
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Interfacial gene expression and stability of oxidized and machined titanium implants
- 2010
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Ingår i: European Association for Osseointegration 19th Annual Scientific Meeting, Glasgow, UK, 6-9 October, 2010.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In previous studies, combination of experimental model and gene expression analysis showed that from 3 hours to 6 days of implantation, significant differences in expression of genes denoting for cellular recruitment, inflammation, bone formation and bone resorption were seen at the interfaces of screw-shaped oxidized and machined titanium implants. It was concluded that the modulation of gene expression in favor of osteogenic differentiation and downregulation of the pro-inflammatory responses might explain the improved osseointegration of the oxidized implant surfaces. However, as a major condition, the developed bone-implant interface needs to be mechanically stable in order to fulfill the requirements of osseointegration The aim of the current study was to combine in vivo interfacial gene expression model with torque analysis in order to determine how molecular and cellular events taking place at the different titanium implants are related to the biomechanical properties of the interface. Anodically oxidized and machined titanium miniscrews were inserted in tibiae of 6 rats. Each rat received two oxidized implants in one tibia and two machined implants in the opposite tibia. After 28 days, the implants were removed using torque measuring equipment. The torque was registered and the implants completely removed and analyzed with quantitative polymerase chain reaction (n=12). Wilcoxon signed rank test was used to analyze the statistical differences of biomechanical and gene expression results between the two implant types. In addition, similar oxidized and machined titanium miniscrews were characterized topographically, chemically and ultrastructurally using profilometry, Auger electron microscopy and cross-sectioning electron microscopy, respectively. For chemical and topographical analyses, 3 implants from each type were analyzed. The measurements were made on flanks, tops, and valleys of two nonadjacent threads giving a total of 18 measurements for each implant type. Topographical comparisons were performed using one-way ANOVA followed by Bonferroni’s test. The biomechanical evaluation demonstrated 190% increase in torque values for the oxidized implants as compared to the machined ones. At the same time (28d), oxidized implants showed significantly higher expression of Runt-related transcription factor 1, osteocalcin, and tartrate resistant acid phosphatase. On the other hand higher expression of tumor necrosis factor-α and interleukin-1β was detected on the machined surfaces. Surface characterization procedures revealed major differences in the physico-chemical properties of the implant surfaces. In conclusion, the favorable cellular and molecular events at the oxidized implants were in parallel with significantly stronger bone anchorage during osseointegration
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| 4. |
- Omar, Omar
(författare)
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Mechanisms of Osseointegration: Experimental Studies on Early Cellular and Molecular Events in vivo
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The early cellular and molecular activities determining the early tissue response and bone formation at bone/implant interface are not fully understood. The general aim of the current thesis was to develop a model for studying the early molecular and cellular activities in different bone types, and in response to different implant surface properties. The studies were performed by analyzing gene expression of implant-adherent cells using a sampling procedure and subsequent qPCR. The developed model was combined with histology and immunohistochemistry to study cellular relations and early tissue organization at the interface with the implant, governing the early structural basis of osseointegration. The ultimate aim was to determine the strength of the early formed bone/implant interface, by measuring the removal torque forces, and thereby to correlate the results with the degree of inflammation, bone formation and bone resorption, as measured by a gene expression panel. The evaluation time for the studies ranged between 3 hours up 28 days from implantation. The present studies provided a combination of gene expression, morphological, and biomechanical data. The present results demonstrated biological differences between cortical and trabecular bone types, both in the normal steady-state condition and in response to biomaterial. During steady-state conditions, bone with trabecular architecture expressed higher level of bone turnover markers compared to cortical bone, while the latter had a higher inflammatory constitutive expression. The response to anodically oxidized titanium implants was different in trabecular and cortical bone sites after 3 days of implantation. Early differences in gene expression in cells associated with different implant materials can be detected as early as 3 hours after implantation. Higher level of osteogenic activity indicated by significantly higher expression of mesenchymal stem cell recruitment and adhesion markers and higher expression of markers for coupled bone formation and resorption, were found at oxidized surfaces. A higher expression of CXCR4 homing receptor for stem cells, and the integrins, αv, β1 and β2 were detected in cells at oxidized surfaces. On the other hand, higher proinflammatory activity was detected at the machined surfaces, as exemplified by the expression of TNF-α and IL-1β. Scanning electron microscopy and immunohistochemical analysis confirmed the presence of both inflammatory monocytes/macrophages and mesenchymal stem cells at the implant surfaces with predominance of the mesenchymal cells on the oxidized surfaces. Gene expression analyzed on the screw level provided additional information in comparison with that of surrounding bone. The rapid recruitment and adhesion of mesenchymal stem cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation correlated with higher stability of the oxidized implants. In conclusion, the combination of the in vivo experimental model, qPCR and morphological and biomechanical techniques provided hitherto unexplored opportunities to analyze in detail the mechanisms of osseointegration. A major conclusion of the studies is that material surface properties elicit early, significant differences in gene expression in interfacial cells. This observation is important in order to understand the mechanisms behind osseointegration and the role of material surface properties. Furthermore, this knowledge is essential for the ability to design the material and biological conditions for optimal tissue regeneration in association with implanted medical devices.
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| 5. |
- Palmquist, Anders, 1977, et al.
(författare)
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Titanium oral implants - surface characteristics, interface biology and clinical outcome
- 2010
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 7:S.5, s. S515-27
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Tidskriftsartikel (refereegranskat)abstract
- Bone-anchored titanium implants have revolutionized oral healthcare. Surface properties of oral titanium implants play decisive roles for molecular interactions, cellular response and bone regeneration. Nevertheless, the role of specific surface properties, such as chemical and phase composition and nanoscale features, for the biological in vivo performance remains to be established. Partly, this is due to limited transfer of state-of-the-art preparation techniques to complex three-dimensional geometries, analytical tools and access to minute, intact interfacial layers. As judged by the available results of a few randomized clinical trials, there is no evidence that any particular type of oral implant has superior long-term success. Important insights into the recruitment of mesenchymal stem cells, cell-cell communication at the interface and high-resolution imaging of the interface between the surface oxide and the biological host are prerequisites for the understanding of the mechanisms of osseointegration. Strategies for development of the next generation of material surface modifications for compromised tissue are likely to include time and functionally programmed properties, pharmacological modulation and incorporation of cellular components.
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| 6. |
- Amir, Omar A., 1963-
(författare)
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Biology, ecology and anthropogenic threats of Indo-Pacific bottlenose dolphins in east Africa
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the biology, ecology and anthropogenic threats of Indo-Pacific bottlenose dolphins (Tursiops aduncus) off Zanzibar, Tanzania, based on research conducted and samples collected between 2000 and 2008. Distribution and occurrence are described based on incidental catches (bycatch) in gillnet fisheries. Biology and ecology are examined by ageing and studying the reproductive biology and stomach contents of collected specimens. The composition of organohalogen compounds is determined in blubber samples, and assessment and mitigation of bycatch are conducted using observers onboard fishing vessels. Fisheries bycatch data showed that Indo-Pacific bottlenose dolphins occur year round in all areas around Zanzibar. Sexual maturity was attained between 7 and 8 years and body length 190-200 cm in females and at 16 years and body length 213 cm in males. The gestation period was estimated to be 12.3 months, with calving occurring throughout the year, peaking November-March and with an interval of 2.7 years. The estimated pregnancy rate was between 0.10 and 0.58 depending on methods used. Stomach contents revealed a relatively large number of prey species, but that only a few small- and medium-sized neritic fish and cephalopods contribute substantially to the diet. Estimates of total annual bycatch were >9% which is not considered sustainable. An experiment showed that pingers can be a short term mitigation measure to reduce bycatch of dolphins in both drift- and bottom set gillnets. Methoxylated polybrominated diphenyl ethers (Meo-BDEs) were found at higher concentrations than anthropogenic organic pesticides (OCPs), with only traces of polychlorinated biphenyls (PCBs) detected. This study reveals the magnitude and apparent susceptibility of Indo-Pacific bottlenose dolphins off Zanzibar to anthropogenic threats, especially fisheries bycatch, and it is clear that immediate conservation and management measures are needed to reduce bycatch.
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| 7. |
- Buchser, William J., et al.
(författare)
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Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology
- 2010
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Ingår i: Molecular Systems Biology. - : Nature Publishing Group. - 1744-4292 .- 1744-4292. ; 6, s. 391-
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Tidskriftsartikel (refereegranskat)abstract
- Development and regeneration of the nervous system requires the precise formation of axons and dendrites. Kinases and phosphatases are pervasive regulators of cellular function and have been implicated in controlling axodendritic development and regeneration. We undertook a gain-of-function analysis to determine the functions of kinases and phosphatases in the regulation of neuron morphology. Over 300 kinases and 124 esterases and phosphatases were studied by high-content analysis of rat hippocampal neurons. Proteins previously implicated in neurite growth, such as ERK1, GSK3, EphA8, FGFR, PI3K, PKC, p38, and PP1a, were confirmed to have effects in our functional assays. We also identified novel positive and negative neurite growth regulators. These include neuronal-developmentally regulated kinases such as the activin receptor, interferon regulatory factor 6 (IRF6) and neural leucine-rich repeat 1 (LRRN1). The protein kinase N2 (PKN2) and choline kinase alpha (CHKA) kinases, and the phosphatases PPEF2 and SMPD1, have little or no established functions in neuronal function, but were sufficient to promote neurite growth. In addition, pathway analysis revealed that members of signaling pathways involved in cancer progression and axis formation enhanced neurite outgrowth, whereas cytokine-related pathways significantly inhibited neurite formation.
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| 8. |
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| 9. |
- Carlsson, Gunnar E, 1930, et al.
(författare)
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The future of complete dentures in oral rehabilitation. A critical review.
- 2010
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Ingår i: J Oral Rehabil. ; 37, s. 143-156
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Forskningsöversikt (refereegranskat)abstract
- Based on available investigations and current trends in oral rehabilitation published in the dental literature, an attempt is made to describe the possible future role of complete dentures. For edentulous patients, complete dentures have for long been the only prosthodontic treatment option. Whereas a large number of edentulous patients report satisfaction with denture usage, a smaller number are unable to adapt; for such patients, sophistication of clinical and technical processes or quality of denture supporting tissues, appear to have little influence on patient-perceived outcomes. Since the 1980s, osseointegrated dental implants have dramatically improved the therapeutic possibilities, especially so for maladaptive patients. Those able to access such treatment can expect significant improvements in oral functional status and quality of life. While there is a downward trend in edentulism in several countries, it is region-specific, confirming the overriding influence of socioeconomic factors on health status. In most societies, despite ageing populations, the need for complete dentures is not likely to reduce in the near future. Whereas a two- or even a one-implant overdenture for the edentulous mandible is increasingly regarded as a minimum standard of care in many developed countries, its routine prescription for the majority in the world who are disadvantaged is unrealistic; for them, even ‘low-tech’ therapies like conventional dentures are beyond their reach. Improving the conventional management of edentulous patients is a necessity, and requires a keener focus by researchers, educators and clinicians in the developed world on the needs of populations with fewer resources.
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| 10. |
- Fiz-Palacios, Omar, et al.
(författare)
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The uneven phylogeny and biogeography of Erodium (Geraniaceae) : radiations in the Mediterranean and recent recurrent intercontinental colonization
- 2010
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Ingår i: Annals of Botany. - : Oxford University Press (OUP). - 0305-7364 .- 1095-8290. ; 106:6, s. 871-884
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The genus Erodium is a common feature of Mediterranean-type climates throughout the world, but the Mediterranean Basin has significantly higher diversity than other areas. The aim here is to reveal the biogeographical history of the genus and the causes behind the evolution of the uneven distribution. Methods Seventy-eight new nrITS sequences were incorporated with existing plastid data to explore the phylogenetic relationships and biogeography of Erodium using several reconstruction methods. Divergence times for major clades were calculated and contrasted with other previously published information. Furthermore, topological and temporal diversification rate shift analyses were employed using these data. Key Results Phylogenetic relationships among species are widely congruent with previous plastid reconstructions, which refute the classical taxonomical classification. Biogeographical reconstructions point to Asia as the ancestral area of Erodium, arising approx. 18 MYA. Four incidences of intercontinental dispersal from the Mediterranean Basin to similar climates are demonstrated. Increases in diversification were present in two independent Erodium lineages concurrently. Two bursts of diversification (3 MYA and 0·69 MYA) were detected only in the Mediterranean flora.Conclusions Two lineages diverged early in the evolution of the genus Erodium: (1) subgenus Erodium plus subgenus Barbata subsection Absinthioidea and (2) the remainder of subgenus Barbata. Dispersal across major water bodies, although uncommon, has had a major influence on the distribution of this genus and is likely to have played as significant role as in other, more easily dispersed, genera. Establishment of Mediterranean climates has facilitated the spread of the genus and been crucial in its diversification. Two, independent, rapid radiations in response to the onset of drought and glacial climate change indicate putative adaptive radiations in the genus.
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