Decreased levels of insulin-like growth factor-1 and vascular endothelial growth factor relevant to the ossification disturbance in femoral heads spontaneous hypertensive rats.

Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p<0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR

Accuracy and complications using computer-designed stereolithographic surgical guides for oral rehabilitation by means of dental implants: a review of the literature

Background: In the last decade several stereolithographic guided surgery systems were introduced to the market. In this context, scientific information regarding accuracy of implant placement and surgical and prosthodontical complications is highly relevant as it provides evidence to implement this surgical technique in a clinical setting. Purpose: To review data on accuracy and surgical and prosthodontical complications using stereolithographical surgical guides for implant rehabilitation. Material and Methods: PubMed database was searched using the following keywords: “three dimensional imaging,”“image based surgery,” “flapless guided surgery,” “customized drill guides,” “computer assisted surgery,” “surgical template,” and “stereolithography.” Only papers in English were selected. Additional references found through reading of selected papers completed the list. Results: In total 31 papers were selected. Ten reported deviations between the preoperative implant planning and the postoperative implant locations. One in-vitro study reported a mean apical deviation of 1.0 mm, three ex vivo studies a mean apical deviation ranging between 0.6 and 1.2 mm. In six in vivo studies an apical deviation between 0.95 and 4.5 mm was found. Six papers reported on complications mounting to 42% of the cases when stereolithographic guided surgery was combined with immediate loading. Conclusion: Substantial deviations in three-dimensional directions are found between virtual planning and actually obtained implant position. This finding and additionally reported postsurgical complications leads to the conclusion that care should be taken whenever applying this technique on a routine basis

A Femtomol Range FRET Biosensor Reports Exceedingly Low Levels of Cell Surface Furin: Implications for the Processing of Anthrax Protective Antigen

Furin, a specialized endoproteinase, transforms proproteins into biologically active proteins. Furin function is important for normal cells and also in multiple pathologies including malignancy and anthrax. Furin is believed to cycle between the Golgi compartment and the cell surface. Processing of anthrax protective antigen-83 (PA83) by the cells is considered thus far as evidence for the presence of substantial levels of cell-surface furin. To monitor furin, we designed a cleavage-activated FRET biosensor in which the Enhanced Cyan and Yellow Fluorescent Proteins were linked by the peptide sequence SNSRKKR↓STSAGP derived from anthrax PA83. Both because of the sensitivity and selectivity of the anthrax sequence to furin proteolysis and the FRET-based detection, the biosensor recorded the femtomolar levels of furin in the in vitro reactions and cell-based assays. Using the biosensor that was cell-impermeable because of its size and also by other relevant methods, we determined that exceedingly low levels, if any, of cell-surface furin are present in the intact cells and in the cells with the enforced furin overexpression. This observation was in a sharp contrast with the existing concepts about the furin presentation on cell surfaces and anthrax disease mechanism. We next demonstrated using cell-based tests that PA83, in fact, was processed by furin in the extracellular milieu and that only then the resulting PA63 bound the anthrax toxin cell-surface receptors. We also determined that the biosensor, but not the conventional peptide substrates, allowed continuous monitoring of furin activity in cancer cell extracts. Our results suggest that there are no physiologically-relevant levels of cell-surface furin and, accordingly, that the mechanisms of anthrax should be re-investigated. In addition, the availability of the biosensor is a foundation for non-invasive monitoring of furin activity in cancer cells. Conceptually, the biosensor we developed may serve as a prototype for other proteinase-activated biosensors

Evaluation of computer-assisted virtual treatment planning and template-guided surgery in dental implant treatment

One of the newly introduced concepts in implant dentistry is computer-guided surgery. The development of 3D implant planning software and imaging technology provide clinicians with 3D information of patients bony structures. Furthermore, the combination of such image technologies and the CAD/CAM technology allows fabrication of surgical templates and implant supported prostheses preoperatively based on the virtual treatment planning. However, whether the new method can offer patients as successful and reliable treatment as the conventional methods has not yet been shown scientifically. The general aim of this thesis was to evaluate computer-assisted virtual treatment planning and template-guided implant surgery. Study I and Study II aimed to evaluate the clinical performance, including survival rates, complications, soft tissue conditions, and marginal bone changes following the template-guided surgery in combination with immediate loading of a prefabricated prosthesis. In Study III and Study IV, the aim was to verify the accuracy of virtually planned and template-guided implant surgery. Patients with edentulous maxilla, mandible or both, consecutively treated using the NobelGuide and Teeth-in-an-Hour were included in this project. In Study I, survival rates and complications during the follow-up period were investigated. The results showed that survival rates of implants and prostheses were lower compared to those following conventional treatment protocols. Furthermore, complications occurred in as many as 42 % of the treated cases. Most observed complications were related to this specific technique or hardware. Study II assessed soft tissue conditions and marginal bone changes at ≥ 1 year follow-up. A pressure-like-ulcer was one of the most frequently observed complications during the follow-up period. Although the mean marginal bone loss after functional loading in Study II was within the range of other reports presenting mean bone loss data after immediate loading, our patients showed a wide range of bone loss at several sites, where the bone loss was greater than commonly used successful level (< 1.5 mm after 1 year of prosthesis connection). Study III and IV showed that there were significant differences between virtually planned implant positions and the clinically placed implant positions. In Study III, the accuracy was assessed by matching the implant planning data based on the pre-operative CT scan and the post-operative CT scan from ≥ 1 year follow-up. In this matching method, patient movement during CT scan was one of the main factors that contributed to the deviations. In Study IV, we developed a novel method. In this method, two plaster models were compared, one created from the surgical template and the other made from impressions on copings attached to the implants in patients at ≥ 1-year follow-up. The matching procedure, best-fit alignment, might have led to the smaller deviations compared to the results of CT matching method. In the guided-surgery technique used in these studies, the surgery including prosthesis connection was completed within 30 - 45 minutes, with minimal surgical trauma in the majority of individuals. In addition, the patients post-operative discomfort such as pain and swelling was almost negligible in successfully treated cases. However, the results in the present studies imply that the method of computer-assisted treatment and template-guided surgery must still be regarded as being in an exploratory phase. Further investigations regarding the clinical performance and products as well assessments from the patient s viewpoint will lead to more optimal results and improvement of the system

Kirenol Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Differentiation of Th1 and Th17 Cells and Inducing Apoptosis of Effector T Cells

Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis. Our findings implicate kirenol as a useful agent for the treatment of MS