Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies

The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2alpha levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2alpha is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.     

Temporal relationships among immunologic alterations in a guinea pig model of thermal injury

Temporal relationships among various humoral and cellular alterations of host defense mechanisms were investigated in a guinea pig model of thermal injury during three weeks after burning. Reduction in serum concentration of C3 and fixation of C3 on Pseudomonas aeruginosa, presence of activated C3 in plasma, and elevations in levels of 6-ketoprostaglandin F1 alpha and thromboxane B2 in wound fluid were observed at 3-6 hr after burning. These alterations were accompanied by reduction in intrinsic bactericidal activity of polymorphonuclear neutrophils (PMNs) against P. aeruginosa, suppression of bactericidal activity of PMNs by serum, and decreased blood clearance of P. aeruginosa. All parameters returned to normal values by seven to nine days after burning. Proliferative responses of splenic lymphocytes to T cell mitogens were depressed at four days after burning and were maximally reduced at eight days. These data support the concept that there is a continuum of immunologic alterations resulting from thermal injury and that consumption of complement and increase in arachidonic acid metabolism are early events.     

Imidacloprid induces morphological and molecular damages on testis of lizard (Podarcis sicula)

Ecotoxicology - The insecticide imidacloprid was evaluated under laboratory conditions in the adult male Italian wall lizards (Podarcis sicula) to assess its potential toxicity. By an acute oral...     

Mixed Tumors,Myoepitheliomas, and Oncocytomas of the Soft Tissues Are Likely Members of the Same Family: A Clinicopathologic and Ultrastructural Study

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances ( epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.     

Profiling receptor tyrosine kinase activation by using Ab microarrays

Signal transduction in mammalian cells is mediated by complex networks of interacting proteins. Understanding these networks at a circuit level requires devices to measure the amounts and activities of multiple proteins in a rapid and accurate manner. Ab microarrays have previously been applied to the quantification of labeled recombinant proteins and proteins in serum. The development of methods to analyze intracellular signaling molecules on microarrays would make Ab arrays widely useful in systems biology. Here we describe the fabrication of multiplex Ab arrays sensitive to the amounts and modification states of signal transduction proteins in crude cell lysates and the integration of these arrays with 96-well microtiter plate technology to create microarrays in microplates. We apply the Ab arrays to monitoring the activation, uptake, and signaling of ErbB receptor tyrosine kinases in human tumor cell lines. Data obtained from multicolor ratiometric microarrays correlate well with data obtained by using traditional approaches, but the arrays are faster and simpler to use. The integration of microplate and microarray methods for crude cell lysates should make it possible to identify and analyze small molecule inhibitors of signal transduction processes with unprecedented speed and precision. We demonstrate the future potential of this approach by characterizing the action of the epidermal growth factor receptor inhibitor PD153035 on cells by using Ab arrays; direct scale-up to array-based screening in 96- and 384-well plates should allow small molecules to be identified with specific inhibitory profiles against a signaling network.     

Performance Assessment of Asphalt Mixture Produced with a Bio-Based Binder

Nowadays, the growing energy costs and pressing worldwide demand for petroleum-based products create a strong need to develop alternative binders deriving from green and renewable sources. Bio-binders (or bitumen added to bio-based materials) can potentially be a viable alternative for the production of bituminous mixture, promoting the circular economy as well as environmental sustainability principles without reducing the overall performance of the mixture. In this context, the current study focuses on evaluation of the effects of a bio-binder on the mechanical response of asphalt concrete (AC) produced with it. In particular, a 10% bio-oil deriving from a by-product of the paper industry has been blended with a conventional 50/70 penetration grade bitumen to obtain the bio-binder. Moreover, plain bitumen having the same consistency was chosen to produce a reference AC. Two dense-graded AC wearing courses were prepared in the laboratory according to Italian technical specifications. A mechanical characterization in terms of indirect tensile strength, indirect tensile stiffness modulus, fatigue response and permanent deformation resistance was performed on gyratory compacted specimens using both conventional and performance tests. In addition, aging and water sensitivity of the AC specimens were evaluated. Overall results highlight that the AC produced with the bio-binder did not show reduced mechanical properties and it was comparable to the reference AC regardless of aging and water conditioning. This highly encourages the use of bio-binder as a viable alternative in asphalt technology.