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.     

An electrophysiological investigation of discourse coherence in healthy adults

This study used event-related potentials (ERPs) to investigate discourse-coherence processing. Because there are scant data on ERP indices of discourse coherence in typical adults, it is important to study a non-clinical population before examining clinical populations. Twelve adults listened to a story with sentences in a coherent versus incoherent order. Sequences of nonsense syllables served as a control. ERPs in the 200–400?ms time window, reflecting phonological and lexical processing, and in the 600–900?ms time window, reflecting later discourse processing for integration, were investigated. Results revealed a right anterior and posterior positivity that was greater for coherent than for incoherent discourse during the 600–900?ms time window. These findings point to an index of discourse coherence and further suggest that ERPs can be used as a clinical tool to study discourse-processing disorders in populations with brain damage, such as aphasia and traumatic brain injury.     

Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis

Hepatitis C virus (HCV) has chronically infected a large number of patients, leading to the development of steatosis, cirrhosis and, ultimately, hepatocellular carcinoma. The pathogenesis of HCV has not been fully explained, although steatosis is considered to contribute greatly to liver fibrosis progression, modulating host-cell lipid metabolism. Suspected underlying molecular mechanisms include interactions between HCV proteins and intracellular lipid metabolic pathways. Recent studies have suggested that the nucleocapsid of HCV (core) acts as a pathogenic factor involved in lipid droplet accumulation, changes in lipogenic gene expression and/or the activity of lipogenic proteins in a genotype-specific manner. In this review, we have tried to summarize the current knowledge regarding HCV-induced steatosis and the regulation of expression of host genes and receptors that aid in the viral life cycle and promote liver diseases.     

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.     

Dual behavior of HCV Core gene in regulation of apoptosis is important in progression of HCC

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can lead to HCC (Hepatocelluar carcinoma) via oxidative stress, steatosis, insulin resistance, fibrosis and liver cirrhosis. Apoptosis is essential for the control and eradication of viral infections. In acute HCV infection, enhanced hepatocyte apoptosis is significant for elimination of viral pathogen. In case of chronic HCV, down regulation of apoptosis and enhanced cell proliferation not only causes HCV infection persistency in the majority of patients. However, the impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. Regulation of apoptosis in hepatocytes by HCV Core is so important in progression of HCC. This review focuses on the dual character of HCV Core on regulation of apoptosis and progression of HCC.     

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.