Implication of Complement System and its Regulators in Alzheimer’s Disease

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that affects approximately 24 million people worldwide. A number of different risk factors have been implicated in AD, however, neuritic (amyloid) plaques are considered as one of the defining risk factors and pathological hallmarks of the disease. Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimer''s dementia. This review emphasizes on the dual key roles of complement system and complement regulators (CRegs) in disease pathology and progression. The particular focus of this review is on currently evolving strategies for design of complement inhibitors that might aid therapy by restoring the fine balance between activated components of complement system, thus improving the cognitive performance of patients. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of AD.Key Words: Alzheimer’s disease, neurodegeneration, inflammation, β-amyloid peptide, complement, complement regulators, CD59, complement therapeutics.     

Complement in Cancer and Cancer Immunotherapy

Recently, there has been an increase of interest in the use of biological or immune-based therapies for patients with malignancies. This has been informed by the deeper understanding of the crosstalk between the host immune system and malignant tumours, as well as the potential advantages of immunotherapy—high specificity and less toxicity compared to standard approaches. The particular emphasis of this article is on the role of the complement system in tumour growth and antibody-based cancer immunotherapy. The functional consequences from overexpression of complement regulators by tumours and the development of strategies for overcoming this are discussed in detail. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of cancer.     

Increased event-related theta activity as a psychophysiological marker of comorbidity in children with tics and attention-deficit/hyperactivity disorders

OBJECTIVE: The question as to whether coexisting tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) in children represent a combination of two independent pathologies, a separate nosologic entity manifested by both tics and hyperactivity or a phenotype subgroup of one of the two major clinical forms has received increasing attention. The aim of the present study was to classify the TD+ADHD comorbidity in the neurocognitive domain and to elucidate the neurophysiological background of TD+ADHD coexistence by analyzing event-related electroencephalographic (EEG) oscillations in the theta (3-7.5 Hz) frequency band. METHODS: Event-related potentials were recorded at 10 electrodes in 53 children (9-13 years old) from four groups (healthy controls, TD-only, ADHD-only, and combined TD+ADHD patients), while they performed an auditory selective attention task requiring a button press to a predefined target. Event-related theta oscillations were analyzed by means of time-frequency decomposition (wavelet analysis) in two latency ranges-early (0-200 ms) and late (200-450 ms). The effects of psychopathology factors (TD and ADHD) and task variables (attended channel and stimulus task relevance) on early (ETR) and late (LTR) theta responses were evaluated statistically. Theta response measures were further correlated with psychopathology scores and spontaneous theta EEG activity. RESULTS: (1) The ETR was enhanced only in comorbid children and did not differ between the control, TD-only, and ADHD-only groups. (2) The LTR was larger in children with ADHD (ADHD-only and comorbid), but this effect was mediated by the spontaneous theta EEG activity. (3) The ETR was larger to attended stimuli at frontal-central electrodes contralateral to the side of attention, to the target stimulus type at frontal locations, and at the hemisphere contralateral to the side of the response. The functional reactivity and scalp distribution of ETRs were modulated by psychopathological factors. CONCLUSIONS: In the neurocognitive domain, the TD+ADHD comorbidity can be identified as a unique nosologic entity. Both the spontaneous theta activity and late event-related theta oscillations appear as neurophysiological markers of the ADHD condition. In children, the early event-related theta oscillations may be associated with representations of relevant target features in working memory. SIGNIFICANCE: (1) A new model is proposed according to which TD+ADHD comorbidity can be classified at different levels (from neurobiological to cognitive). (2) The functional significance of stimulus-synchronized theta oscillations in children is described for the first time.     

High-pass filtering of the electrogastrogram

The recording and processing of an electrogastrogram require adequate bandpass filtering, to suppress unwanted artefacts but preserve the original signal waveform. High-pass filtering of various types of different time constants τ, filter order, analogue and digital implementation, have been used to obtain higher baseline stability and faster signal recovery after strong artefacts. Special attention should be given to possible signal amplitude and phase distortions due to high-pass filtering, which can strongly influence accurate amplitude measurements or studies of signal propagation from multichannel recordings. Synthesised and original signals are used to demonstrate the effect of high-pass filtering. The use of a first-order filter with τ=5 s is recommended for EGG studies if not especially directed to investigation of bradygastria. In the opposite case, τ=15 s should be used, and with backward filtering a full restoration of the original signal can be obtained. The same is valid for recording the electrical activity of the colon. Lower time constants (τ=5 s or less) can be applied to acquire signals from the small intestines. A radical solution is the use of a DC amplifier with controllable subtraction of the DC component.