The role of the complement system in innate immunity

Complement is a major component of innate immune system involved in defending against all the foreign pathogens through complement fragments that participate in opsonization, chemotaxis, and activation of leukocytes and through cytolysis by C5b-9 membrane attack complex. Bacterias and viruses have adapted in various ways to escape the complement activation, and they take advantage of the complement system by using the host complement receptors to infect various cells. Complement activation also participates in clearance of apoptotic cells and immune, complexes. Moreover at sublytic dose, C5b-9 was shown to promote cell survival. Recently it was also recognized that complement plays a key role in adaptive immunity by modulating and modifying the T cell responses. All these data suggest that complement activation constitutes a critical link between the innate and acquired immune responses.     

The role of complement activation in atherosclerosis

Atherosclerosis is a chronic inflammatory disease in which dyslipidemia, inflammation, and the immune system play an important pathogenetic role. A role in atherogenesis was demonstrated for monocyte/macrophages, complement system, and T-lymphocytes. Complement activation and C5b-9 deposition occurs both in human and experimental atherosclerosis. Complement C6 deficiency has a protective effect on diet-induced atherosclerosis, indicating that C5b-9 assembly is required for the progression of atherosclerotic lesions. The maturation of atherosclerotic lesions beyond the foam cell stage was shown to be strongly dependent on an intact complement system. C5b-9 may be responsible for cell lysis, and sublytic assembly of C5b-9 induces smooth muscle cell (SMC) and endothelial cell (EC) activation and proliferation. All these data suggest that activation of the complement system plays an important role in atherogenesis.     

Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure

OBJECTIVE: The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide. DESIGN: Prospective, controlled laboratory study. SETTING: Animal resource facilities and research laboratory. SUBJECTS: Young (2-3 months old) and aged (18-20 months old) female BALB/c mice. INTERVENTIONS: Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1beta, were assessed by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and interleukin-1beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interleukin-1beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interleukin-1beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide. CONCLUSIONS: The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality seen in the aged given an inflammatory insult.     

Force required to luxate a newly placed dental implant in bone: an in vitro pilot study

Immediate loading of newly placed dental implants is a consideration when attempting to meet patients' demands. However, immediate loading may induce implant failure to osseointegrate, particularly in the case of a patient who can generate a biting force that can reach approximately 1300 Newtons (N) in the posterior jaws. The range of biting forces that prevent osseointegration of newly placed implants is currently unknown. However, it is suspected that osseointegration may fail if an implant is luxated in bone more than 50 microm, in which case fibrous tissue will be formed instead of bone. This pilot study was focused on finding the amount of horizontal off-axial force required to move a nonosseointegrated 4.3 x 13-mm implant 50 microm. The initial data show that the amount of horizontal force required to displace such an implant by 50 microm was on the order of 150 N. Assuming that the angle between the direction of the biting force and the vertical lies between 0 degrees and 20 degrees, our data show that a 4.3 x 13-mm implant may fail to osseointegrate for biting forces that are as low as 440 N. One implication of our study is that implants having smaller diameters may move and fail to osseointegrate for even lower biting forces.     

Silicone rubber mould cast polyethylmethacrylate-hydroxyapatite plate used for repairing a large skull defect.

INTRODUCTION: Reconstruction of the cranial vault is performed for various reasons and precise repair of the defect is important. A modified method of cranioplasty is presented using three-dimensional (3D) models and polyethylmethacrylate mixed with hydroxyapatite, cast in a silicone rubber mould. PATIENT AND METHOD: A large custom made cranial implant was produced using data acquired from 3D computer tomography, rapid prototyping and cast in a silicone rubber mould. This plate was then applied to a 53 year-old man who had undergone a decompressive fronto-parieto-temporo-occipital craniotomy. The bone flap had been lost due to infection. The cranioplasty was performed at 1 year after the initial operation. RESULTS: The cranial plate fitted precisely into the defect and needed no correction at the time of surgery. The stability of the reconstruction plate was increased by the presence of thin margins allowed by silicone rubber elasticity. No complications occurred and the final functional and aesthetic results were good. CONCLUSION: The use of 3D imaging and rapid prototyping allow precise repair of large skull defects, with good aesthetic and functional results. At the same time, silicone rubber moulds permit the production of very thin details needed not only for cosmetic reasons but for reconstruction plate stability as well.     

The Potential Application of Natural Clinoptilolite-Rich Zeolite as Support for Bacterial Community Formation for Wastewater Treatment

The aim of this study was to investigate the use of natural zeolite as support for microbial community formation during wastewater treatment. Scanning electron microscopy (SEM), thermal decomposition and differential thermogravimetric curves (TGA/DGT) techniques were used for the physicochemical and structural characterization of zeolites. The chemical characterization of wastewater was performed before and after treatment, after 30 days of using stationary zeolite as support. The chemical composition of wastewater was evaluated in terms of the products of nitrification/denitrification processes. The greatest ammonium (NH₄⁺) adsorption was obtained for wastewater contaminated with different concentrations of ammonium, nitrate and nitrite. The wastewater quality index (WWQI) was determined to assess the effluent quality and the efficiency of the treatment plant used, showing a maximum of 71% quality improvement, thus suggesting that the treated wastewater could be discharged into aquatic environments. After 30 days, NH₄⁺ demonstrated a high removal efficiency (higher than 98%), while NO₃⁺ and NO₂⁺ had a removal efficiency of 70% and 54%, respectively. The removal efficiency for metals was observed as follows (%): Mn > Cd > Cr > Zn > Fe > Ni > Co > Cu > Ba > Pb > Sr. Analysis of the microbial diversity in the zeolite samples indicated that the bacteria are formed due to the existence of nutrients in wastewater which favor their formation. In addition, the zeolite was characterized by SEM and the results indicated that the zeolite acts as an adsorbent for the pollutants and, moreover, as a support material for microbial community formation under optimal conditions. Comparing the two studied zeolites, NZ1 (particle size 1–3 mm) was found to be more suitable for wastewater treatment. Overall, the natural zeolite demonstrated high potential for pollutant removal and biomass support for bacteria community growth in wastewater treatment.     

SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis

SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses. Blood samples collected from MS patients were analyzed for levels of SIRT1 and histone H3 lysine 9 (H3K9) acetylation and dimethylation. During relapses, MS patients had a lower expression of SIRT1 mRNA than did stable MS patients. In addition, there was a significant decrease in H3K9 dimethylation (H3K9me2) during relapses in MS patients when compared to stable patients (p = 0.01). Responders to GA treatment had significantly higher SIRT1 mRNA (p = 0.01) and H3K9me2 levels than did non-responders (p = 0.018). Receiver operating characteristic analysis was used to assess the predictive power of SIRT1 and H3K9me2 as putative biomarkers: for SIRT1 mRNA, the predictive value for responsiveness to GA treatment was 70% (p = 0.04) and for H3K9me2 was 71% (p = 0.03). Our data suggest that SIRT1 and H3K9me2 could serve as potential biomarkers for evaluating patients' responsiveness to GA therapy in order to help guide treatment decisions in MS.