The incidence of corpora amylacea (CA) in the optic nerve of patients with Alzheimer's disease

Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been described in normal elderly brain as well as in a number of neurodegenerative disorders. In this study, the incidence of CA in the optic nerves of Alzheimer's disease (AD) patients was compared with normal elderly controls. Samples of optic nerves (MRC Brain Bank, Institute of Psychiatry) were taken from 12 AD patients (age range 69-94 years) and 18 controls (43-82 years). Optic nerves were fixed in 2% buffered glutaraldehyde, post-fixed in osmium tetroxide, embedded in epoxy resin and then sectioned to a thickness of 2 microns. Sections were stained with toluidine blue. CA were present in all of the optic nerves examined. In addition, a number of similarly stained but more irregularly shaped bodies were present. Fewer CA were found in the optic nerves of AD patients compared with controls. By contrast, the number or irregularly shaped bodies was increased in AD. In AD, there may be a preferential decline in the large diameter fibres which may mediate the M-cell pathway. Hence, the decline in the incidence of CA in AD may be associated with a reduction in these fibres. It is also possible that the irregualrly shaped bodies are a degeneration product of the CA.

Oxidative injury induced by hypochlorous acid to Ca-ATPase from sarcoplasmic reticulum of skeletal muscle and protective effect of trolox

Hypochlorous acid (HOCl) concentration-dependently decreased ATPase activity and SH groups of pure Ca-ATPase from sarcoplasmic reticulum (SERCA) of rabbit skeletal muscle with IC(50) of 150 micromol/l and 6.6 micromol/l, respectively. This indicates that SH groups were not critical for impairment of Ca-ATPase activity. Pure Ca-ATPase activity was analysed individually with respect to both substrates, Ca(2+) and ATP. Concerning dependence of ATPase activity on HOCl (150 micromol/l) as a function of free Ca(2+) and ATP, V(max) of both dependences decreased significantly, while the affinities to individual substrates were not influenced, with the exception of the regulatory binding site of ATP. On increasing HOCl concentration, fluorescence of fluorescein-5-isothiocyanate (FITC) decreased, indicating binding of HOCl to nucleotide binding site of SERCA. A new fragment appeared at 75 kDa after HOCl oxidation of SR, indicating fragmentation of SERCA. Fragmentation may be associated with protein carbonyl formation. The density of protein carbonyl bands at 75 and 110 kDa increased concentration- and time-dependently. Trolox (250 micromol/l) recovered the Ca-ATPase activity decrease induced by HOCl, probably by changing conformational properties of the Ca-ATPase protein. Trolox inhibited FITC binding to SERCA.

Survey of influence of biomass mineral matter in thermochemical conversion of short rotation willow coppice

Short rotation willow coppice (SRC) has been investigated for the influence of K, Ca, Mg, Fe and P on its pyrolysis and combustion behaviours. These metals are the typical components that appear in biomass. The willow sample was pretreated to remove salts and metals by hydrochloric acid, and this demineralised sample was impregnated with each individual metal at the same mol g biomass (2.4 × 10 mol g demineralised willow). Characterisation was performed using thermogravimetric analysis (TGA), and differential thermal analysis (DTA) for combustion. In pyrolysis, volatile fingerprints were measured by means of pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS). The yields and distribution of pyrolysis products have been influenced by the presence of the catalysts. Most notably, both potassium and phosphorous strongly catalysed the pyrolysis, modifying both the yield and distribution of reaction products. Temperature programmed combustion TGA indicates that combustion of biomass char is catalysed by all the metals, while phosphorus strongly inhibits the char combustion. In this case, combustion rates follow the order for volatile release/combustion: P>K>Fe>Raw>HCl>Mg>Ca, and for char combustion K>Fe>raw>Ca-Mg>HCl>P. The samples impregnated with phosphorus and potassium were also studied for combustion under flame conditions, and the same trend was observed, i.e. both potassium and phosphorus catalyse the volatile release/combustion, while, in char combustion, potassium is a catalyst and phosphorus a strong inhibitor, i.e. K impregnated>(faster than) raw>demineralised»P impregnated.

Inhibition of collagen I accumulation reduces glomerulosclerosis by a Hic-5-dependent mechanism in experimental diabetic nephropathy

Glomerulosclerosis of any cause is characterized by loss of functional glomerular cells and deposition of excessive amounts of interstitial collagens including collagen I. We have previously reported that mesangial cell attachment to collagen I leads to upregulation of Hic-5 in vitro, which mediates mesangial cell apoptosis. Furthermore, glomerular Hic-5 expression was increased during the progression of experimental glomerulosclerosis. We hypothesized that reducing collagen I accumulation in glomerulosclerosis would in turn lower Hic-5 expression, reducing mesangial cell apoptosis, and thus maintaining glomerular integrity. We examined archive renal tissue from rats undergoing experimental diabetic glomerulosclerosis, treated with the transglutaminase-2 inhibitor NTU281. Untreated animals exhibited increased glomerular collagen I accumulation, associated with increased glomerular Hic-5 expression, apoptosis, and mesangial myofibroblast transdifferentiation characterized by a-smooth muscle actin (a-SMA) expression. NTU281 treatment reduced glomerular collagen I accumulation, Hic-5 and a-SMA expression, and apoptosis. Proteinurea and serum creatinine levels were significantly reduced in animals with reduced Hic-5 expression. In vitro studies of Hic-5 knockdown or overexpression show that mesangial cell apoptosis and expression of both a-SMA and collagen I are Hic-5 dependent. Together, these data suggest that there exists, in vitro and in vivo, a positive feedback loop whereby increased levels of collagen I lead to increased mesangial Hic-5 expression favoring not only increased apoptosis, but also mesangial myofibroblast transdifferentiation and increased collagen I expression. Prevention of collagen I accumulation interrupts this Hic-5-dependent positive feedback loop, preserving glomerular architecture, cellular phenotype, and function. © 2013 USCAP, Inc All rights reserved.

Mechanism of attenuation of angiotensin-II-induced protein degradation by insulin-like growth factor-I (IGF-I)

Insulin-like growth factor-I (IGF-I) has been shown to attenuate protein degradation in murine myotubes induced by angiotensin II through downregulation of the ubiquitin-proteasome pathway, although the mechanism is not known. Angiotensin II is known to upregulate this pathway through a cellular signalling mechanism involving release of arachidonic acid, activation of protein kinase Cα (PKCα), degradation of inhibitor-κB (I-κB) and nuclear migration of nuclear factor-κB (NF-κB), and all of these events were attenuated by IGF-I (13.2 nM). Induction of the ubiquitin-proteasome pathway has been linked to activation of the RNA-activated protein kinase (PKR), since an inhibitor of PKR attenuated proteasome expression and activity in response to angiotensin II and prevented the decrease in the myofibrillar protein myosin. Angiotensin II induced phosphorylation of PKR and of the eukaryotic initiation factor-2 (eIF2) on the α-subunit, and this was attenuated by IGF-I, by induction of the expression of protein phosphatase 1, which dephosphorylates PKR. Release of arachidonic acid and activation of PKCα by angiotensin II were attenuated by an inhibitor of PKR and IGF-I, and the effect was reversed by Salubrinal (15 μM), an inhibitor of eIF2α dephosphorylation, as was activation of PKCα. In addition myotubes transfected with a dominant-negative PKR (PKRΔ6) showed no release of arachidonate in response to Ang II, and no activation of PKCα. These results suggest that phosphorylation of PKR by angiotensin II was responsible for the activation of the PLA2/PKC pathway leading to activation of NF-κB and that IGF-I attenuates protein degradation due to an inhibitory effect on activation of PKR. © 2007 Elsevier Inc. All rights reserved.

Complexity of classical dynamics of molecular systems. I. Methodology

Methods for the calculation of complexity have been investigated as a possible alternative for the analysis of the dynamics of molecular systems. “Computational mechanics” is the approach chosen to describe emergent behavior in molecular systems that evolve in time. A novel algorithm has been developed for symbolization of a continuous physical trajectory of a dynamic system. A method for calculating statistical complexity has been implemented and tested on representative systems. It is shown that the computational mechanics approach is suitable for analyzing the dynamic complexity of molecular systems and offers new insight into the process.

Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia

Objective: Loss of skeletal muscle is the most debilitating feature of cancer cachexia, and there are few treatments available. The aim of this study was to compare the anticatabolic efficacy of L-leucine and the leucine metabolite β-hydroxy-β-methylbutyrate (Ca-HMB) on muscle protein metabolism, both invitro and invivo. Methods: Studies were conducted in mice bearing the cachexia-inducing murine adenocarcinoma 16 tumor, and in murine C2 C12 myotubes exposed to proteolysis-inducing factor, lipopolysaccharide, and angiotensin II. Results: Both leucine and HMB were found to attenuate the increase in protein degradation and the decrease in protein synthesis in murine myotubes induced by proteolysis-inducing factor, lipopolysaccharide, and angiotensin II. However, HMB was more potent than leucine, because HMB at 50 μM produced essentially the same effect as leucine at 1 mM. Both leucine and HMB reduced the activity of the ubiquitin-proteasome pathway as measured by the functional (chymotrypsin-like) enzyme activity of the proteasome in muscle lysates, as well as Western blot quantitation of protein levels of the structural/enzymatic proteasome subunits (20 S and 19 S) and the ubiquitin ligases (MuRF1 and MAFbx). Invivo studies in mice bearing the murine adenocarcinoma 16 tumor showed a low dose of Ca-HMB (0.25 g/kg) tobe 60% more effective than leucine (1 g/kg) in attenuating loss of body weight over a 4-d period. Conclusion: These results favor the clinical feasibility of using Ca-HMB over high doses of leucine for the treatment of cancer cachexia. © 2014 Elsevier Inc.

Novel Ni-Mg-Al-Ca catalyst for enhanced hydrogen production for the pyrolysis-gasification of a biomass/plastic mixture

A Ni-Mg-Al-Ca catalyst was prepared by a co-precipitation method for hydrogen production from polymeric materials. The prepared catalyst was designed for both the steam cracking of hydrocarbons and for the in situ absorption of CO2 via enhancement of the water-gas shift reaction. The influence of Ca content in the catalyst and catalyst calcination temperature in relation to the pyrolysis-gasification of a wood sawdust/polypropylene mixture was investigated. The highest hydrogen yield of 39.6molH2/g Ni with H2/CO ratio of 1.90 was obtained in the presence of the Ca containing catalyst of molar ratio Ni:Mg:Al:Ca=1:1:1:4, calcined at 500°C. In addition, thermogravimetric and morphology analyses of the reacted catalysts revealed that Ca introduction into the Ni-Mg-Al catalyst prevented the deposition of filamentous carbon on the catalyst surface. Furthermore, all metals were well dispersed in the catalyst after the pyrolysis-gasification process with 20-30nm of NiO sized particles observed after the gasification without significant aggregation.