In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.     

Real-time ocular artifact suppression using recurrent neural network for electro-encephalogram based brain-computer interface

The paper presents an adaptive noise canceller (ANC) filter using an artificial neural network for real-time removal of electro-oculogram (EOG) interference from electro-encephalogram (EEG) signals. Conventional ANC filters are based on linear models of interference. Such linear models provide poorer prediction for biomedical signals. In this work, a recurrent neural network was employed for modelling the interference signals. The eye movement and eye blink artifacts were recorded by the placing of an electrode on the forehead above the left eye and an electrode on the left temple. The reference signal was then generated by the data collected from the forehead electrode being added to data recorded from the temple electrode. The reference signal was also contaminated by the EEG. To reduce the EEG interference, the reference signal was first low-pass filtered by a moving averaged filter and then applied to the ANC. Matlab Simulink was used for real-time data acquisition, filtering and ocular artifact suppression. Simulation results show the validity and effectiveness of the technique with different signal-to-noise ratios (SNRs) of the primary signal. On average, a significant improvement in SNR up to 27 dB was achieved with the recurrent neural network. The results from real data demonstrate that the proposed scheme removes ocular artifacts from contaminated EEG signals and is suitable for real-time and short-time EEG recordings.     

Expression of collagen, interstitial collagenase, and tissue inhibitor of metalloproteinases-1 in restenosis after carotid endarterectomy.

Extracellular matrix is the principal component of the fibrous caps of atherosclerotic plaques and intimal hyperplastic lesions of reconstructed arteries. Interstitial collagen form an important part of the matrix, and the balance between collagen synthesis and degradation by interstitial collagenase (matrix metalloproteinase-1, MMP-1) may determine whether plaques rupture or vessels develop stenosis. We examined type I procollagen gene expression in human atherosclerotic and restenotic carotid arteries using in situ messenger RNA (mRNA) hybridization and the expression of MMP-1 and its endogenous inhibitor (tissue inhibitor of metalloproteinases-1, TIMP-1) by immunohistochemistry. Compared with normal arteries, atherosclerotic plaques bed increased expression of immunoreactive MMP-1 and TIMP-1 with modest increase of type 1 procollagen mRNA. Early restenotic lesions (< 1.5 years) contained abundant type I procollagen mRNA but little immunoreactive MMP-1 and TIMP-1. Late restenotic lesions (> 4 years) resembled atheroma and exhibited increased immunoreactive MMP-1 and TIMP-1 as well as abundant type I procollagen mRNA. Compared with atherosclerotic plaques, type I procollagen is increased and MMP-1 is decreased in early restenotic lesions. MMP-1 and TIMP-1 expressions are upregulated in lesions with a clear atheroma. These findings suggest that the balance between proteolysis and matrix synthesis may influence both the stability of atheromatous plaques and the development of restenotic lesions.     

Effect of Acute Pain on Splenic NK Cell Activity,Lymphocyte Proliferation and Cytokine Production Activities

Various types of physical and physiological stress in animals have been shown to affect their humoral and cell-mediated immune responses. The present study was designed to investigate the possible influence of acute pain on the immune system. BALB/c mice were exposed to an increasing number of heat shocks using a Tail Flick apparatus; an equal number of control mice received no shock treatments. After each of the regimens was completed, the spleen of each mouse was recovered and various cell populations isolated to assess: the proliferative response to phytohemagglutinin by lymphocytes; cytotoxic activities of natural killer (NK) cells; and, the production of select important cytokines by splenic lymphocytes. The results indicated that NK cell activity and proliferation of lymphocytes were significantly (p < 0.001) increased due to the shock regimens after only a single day's rounds of stimulation (i.e., 3 rounds of ≈12 equally time-spaced shocks/hr with 30–45 min gap between rounds). After 2 and 3 days' rounds of stimulations, no significant changes were detected in the proliferative response of isolated lymphocytes; conversely, the activity of NK cells remained significantly elevated compared to the controls hosts' cells, even on the second day of stimulation but not on the third. Regarding effects on cytokines, no significant changes were detected in the amount of Interferon-γ (IFNγ) and Interlukin-10 (IL-10) produced by lymphocytes obtained from the spleens of any of the shocked mice. These results could suggest that certain acute stressors might actually strengthen a host's immunological reactivity and, possibly, result in an enhanced capacity to resist pathogens that might infect the body.