The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

Osteogenic agents, such as bone morphogenetic protein-2 (BMP-2), can stimulate the degradation as well as the formation of bone. Hence, they could impair the osteoconductivity of functionalized implant surfaces. We assessed the effects of BMP-2 and its mode of delivery on the osteoconductivity of dental implants with either a naked titanium surface or a calcium-phosphate-coated one. The naked titanium surface bore adsorbed BMP-2, whilst the coated one bore incorporated, adsorbed, or incorporated and adsorbed BMP-2. The implants were inserted into the maxillae of adult miniature pigs. The volume of bone deposited within a defined "osteoconductive" (peri-implant) space, and bone coverage of the implant surface delimiting this space, were estimated morphometrically 1-3 weeks later. After 3 weeks, the volume of bone deposited within the osteoconductive space was highest for coated and uncoated implants bearing no BMP-2, followed by coated implants bearing incorporated BMP-2; it was lowest for coated implants bearing only adsorbed BMP-2. Bone-interface coverage was highest for coated implants bearing no BMP-2, followed by coated implants bearing either incorporated, or incorporated and adsorbed BMP-2; it was lowest for uncoated implants bearing adsorbed BMP-2. Hence, the osteoconductivity of implant surfaces can be significantly modulated by BMP-2 and its mode of delivery.

Effect of thrombocytopenia on the early course of streptococcal endocarditis

Although platelets are a major factor in the pathogenesis of endocarditis, it is unclear if these cells promote or limit disease progression. To address this issue, the effects of thrombocytopenia on the early course of endovascular infection were examined. Aortic valve endocarditis was produced in rabbits by using Streptococcus sanguis M99. Thrombocytopenia was induced by intravenous administration of antiplatelet serum. Compared with controls (infected rabbits given nonimmune serum), thrombocytopenic rabbits had higher densities of streptococci within vegetations (mean log10 cfu/g, 9.78 vs. 8.11, P < .002) and a higher total number of bacteria per valve (mean log10 total cfu/valve, 8.96 vs. 7.43, P < .004). When tested for its interactions with platelets in vitro, strain M99 bound, activated, and aggregated rabbit platelets extensively and was rapidly killed by platelet microbicidal protein. These results indicate that platelets can limit disease progression in endocarditis. The host defense properties of platelets may in part be mediated by platelet microbicidal protein.

IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It exerts its cellular effects by a membrane-bound IL-6 receptor (IL-6R), or, alternatively, by forming a complex with the soluble IL-6R (sIL-6R), a process named IL-6 transsignalling. Here we investigate the role of IL-6 transsignalling in myelin basic protein (MBP)-induced EAE in the Lewis rat. In vivo blockade of IL-6 transsignalling by the injection of a specifically designed gp130-Fc fusion protein significantly delayed the onset of adoptively transferred EAE in comparison to control rats injected with PBS or isotype IgG. Histological evaluation on day 3 after immunization revealed reduced numbers of T cells and macrophages in the lumbar spinal cord of gp130-Fc treated rats. At the same time, blockade of IL-6 transsignalling resulted in a reduced expression of vascular cell adhesion molecule-1 on spinal cord microvessels while experiments in cell culture failed to show a direct effect on the regulation of endothelial adhesion molecules. In experiments including active EAE and T cell culture, inhibition of IL-6 transsignalling mildly increased T cell proliferation, but did not change severity of active MBP-EAE or regulate Th1/Th17 responses. We conclude that IL-6 transsignalling may play a role in autoimmune inflammation of the CNS mainly by regulating early expression of adhesion molecules, possibly via cellular networks at the blood-brain barrier.

Does aortic crossclamping during the cooling phase affect the early clinical outcome of acute type A aortic dissection?

OBJECTIVES: The purpose of this study is to evaluate the effects of crossclamping the ascending aorta in acute type A aortic dissection during the cooling phase for deep hypothermic arrest on early clinical outcome. METHODS: The records of 275 consecutive patients who underwent surgery for acute type A aortic dissection were reviewed. Ten patients have been excluded. Overall, 265 patients who underwent surgery under deep hypothermia and circulatory arrest in the "open technique" were divided retrospectively into two groups: those who underwent surgery with crossclamping of the ascending aorta during the cooling phase at the begin of the procedure (group 1, n = 191; 72.1 %) and those in whom the aorta was not clamped (group 2, n = 74; 27.9 %). RESULTS: Preoperative characteristics were similar in both groups. In group 1, femoral artery cannulation, composite graft repair, and aortic arch replacement were significantly more frequent. In-hospital mortality was 15.2 % in group 1 and 17.6 % in group 2 (P = not significant). Neurologic deficits were observed in 9.4% in group 1 and in 10.8% in group 2 (= not significant). There were no significant differences in clinical outcome between the two groups of patients. CONCLUSIONS: This study demonstrates that both options, aortic crossclamping or noclamping, may be used during the induction of deep hypothermia to repair acute type A aortic dissections with similar early clinical outcome. For the selection of the most appropriate technique, we recommend case by case evaluation, weighing the potential risks and benefits of aortic crossclamping.

[Experiences with the early treatment of osteogenesis imperfecta]

Between 1973 and 1988 twenty children with osteogenesis imperfecta were treated in the Department of Paediatric Surgery at the University of Berne, Switzerland. Our initial experience with the first 15 children, who had virtually no treatment during infancy and early childhood showed that they later developed severe soft tissue and skeletal deformities. Since resulting contractures and curvatures of the long bones are difficult to correct, we changed our therapeutic approach. Traditional therapy in OI was limited to the correction of bony malformations. Considering the fact, that the different elements of the locomotor system are part of a functional entity, we began early treatment combining physiotherapy and surgery.

Aerological observations in the Tropics in the Early Twentieth Century

In the first decades of the 20th century, aerological observations were for the first time performed in tropical regions. One of the most prominent endeavours in this respect was ARTHUR BERSON’s aerological expedition to East Africa. Although the main target was the East African monsoon circulation, the expedition provided also other insights that profoundly changed meteorology and climatology. BERSON observed that the tropical tropopause was much higher and colder than that over midlatitudes. Moreover, westerly winds were observed in the lower stratosphere, apparently contradicting the high-altitude equatorial easterly winds that were known since the Krakatoa eruption (‘‘Krakatoa easterlies’’). The puzzle was only resolved five decades later with the discovery of the Quasi-Biennial Oscillation (QBO). In this paper we briefly summarize the expedition of BERSON and review the results in a historical context and in the light of the current research. In the second part of the paper we re-visit BERSON’s early aerological observations, which we have digitized. We compare the observed wind profiles with corresponding profiles extracted from the ‘‘Twentieth Century Reanalysis’’, which provides global three-dimensional weather information back to 1871 based on an assimilation of sea-level and surface pressure data. The comparison shows a good agreement at the coast but less good agreement further inland, at the shore of Lake Victoria, where the circulation is more complex. These results demonstrate that BERSON’s observations are still valuable today as input to current reanalysis systems or for their validation.