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Selected AbstractsBlood,brain barrier impairment with enhanced SP, NK-1R, GFAP and Claudin-5 expressions in experimental cerebral toxocariasisPARASITE IMMUNOLOGY, Issue 10 2008C.-W. LIAO SUMMARY Infection by Toxocara canis in humans may cause cerebral toxocariasis (CT). Appreciable numbers of T. canis larvae cross the blood,brain barrier (BBB) to invade the brain thus causing CT. In the present studies, we evaluated the BBB permeability and BBB injury as assessed by the cerebral Evans blue (EB) concentration as well as by pathological changes and glial fibrillary acidic protein (GFAP) expression in T. canis -infected mice monitored from 3 days (dpi) to 8 weeks post-infection (wpi). The vasodilation neuropeptides, the expressions of substance P (SP) and its preferred binding neurokinin-1 receptor (NK-1R) as well as claudin-5 of tight-junction proteins associated with BBB impairment were also assessed by Western blotting and reverse-transcriptase polymerase chain reaction. Results revealed that BBB permeability increased as evidenced by a significantly elevated EB concentration in brains of infected mice. BBB injury appeared due to enhanced GFAP protein and mRNA expressions from 4 to 8 wpi. Leukocytes might have been unrelated to BBB impairment because there was no inflammatory cell infiltration despite T. canis larvae having invaded the brain; whereas markedly elevated SP protein and NK-1R mRNA expressions concomitant with enhanced claudin-5 expression seemed to be associated with persistent BBB impairment in this experimental CT model. [source] A reappraisal of the histologic findings of pigmented pretibial patches of diabetes mellitusJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2004Gregory M. Houck Background:, Pigmented pretibial patches (PPPs) are the most common cutaneous alterations in diabetes mellitus, found in up to 50% of diabetic patients. They classically present as flat-topped, dull-red papules on the pretibial areas, later becoming hyperpigmented and atrophic. Little is known regarding the pathogenesis of these lesions, and the histopathologic findings have been regarded as non-specific. Methods:, We investigated the clinical and pathologic attributes of a series of 12 diabetic patients with PPP in an effort to discern any specific histologic attributes compared to normal skin removed from diabetic patients with cutaneous carcinoma. Results:, All cases of PPP showed hyaline microangiopathy, all patients showed extravasated erythrocytes and/or hemosiderin deposits, and 10 patients showed an appreciable number of perivascular plasma cells. The average number of plasma cells per vascular plexus was 2.2. Control specimens removed from five diabetic patients showed hyaline microangiopathy, and three showed extravasated erythrocytes and hemosiderin. One patient showed a single vascular plexus with two plasma cells, p = 0.01. Conclusion:, The presence of increased dermal perivascular plasma cells in the appropriate clinical context might be an important and under-recognized clue for PPP. The pathogenic significance of this finding is unknown. [source] Old and emerging therapies in chronic hepatitis C: an updateJOURNAL OF VIRAL HEPATITIS, Issue 1 2008M. Deutsch Summary., The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response currently defined as undetectable HCV-RNA in peripheral blood determined with the most sensitive polymerase chain reaction technique 24 weeks after the end of treatment. This goal is practically equivalent with eradication of HCV infection and cure of the underlying HCV-induced liver disease. The current standard in hepatitis C treatment consists in combination regimens of pegylated interferon-, (Peg-INF-,) with Ribavirin (RBV). Such treatment schemes are quite successful in patients with HCV genotypes 2 and 3 infections achieving HCV eradication rates of 75,90%. However, they are much less effective in patients with genotypes 1 and 4 infections with eradication rates ranging between 45% and 52%. Moreover, they have several, and sometimes severe, adverse effects and contraindications, further limiting their efficacy and applicability in an appreciable number of patients with chronic HCV-induced liver disease. Therefore, the need for improvement of existing therapies and for development of new effective, safe and tolerable drugs is a matter of great clinical relevance and importance. In this article, recent improvements in the current standard of therapy with IFN-, and RBV in various subsets of patients with chronic hepatitis C and in the clinical development of new emerging drugs, particularly small molecules, will be reviewed and commented. The article is divided in two main parts: (i) improvements in the standard combination therapies and schemes of approved Peg-INF-, with RBV and expectations from new interferons, interferon inducers and alternatives to RBV; (ii) new drugs for HCV in clinical development focusing mostly on specific inhibitors of HCV and less so on other drugs including immune therapies. [source] Genetical genomics in livestock: potentials and pitfallsANIMAL GENETICS, Issue 2006C. Haley Summary Genetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false-positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed. [source] Pit membrane remnants in perforation plates of Hydrangeales with comments on pit membrane remnant occurrence, physiological significance and phylogenetic distribution in dicotyledonsBOTANICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2004SHERWIN CARLQUIST FLS Perforation plates from ten species of seven genera of Hydrangeales sensu Thorne were studied using scanning electron microscopy (SEM). The presence of pit membranes in perforations ranges from abundant, as in Carpenteria and Hydrangea, to minimal, as in Deutzia, Escallonia and Philadelphus. Abnormally great pit membrane presence may result from the presence of secondary compounds that inhibit lysis, as in Quintinia serrata; such interference with the natural lysis process may or may not be evident from coarseness and irregularity of pit membrane surface and of threads composing the pit membrane remnants. The presence of pit membrane remnants in perforation plates is hypothesized to be a symplesiomorphy, found in a fraction of dicotyledons with scalariform perforation plates (but still in an appreciable number of species). Pit membrane remnant presence may represent incomplete lysis of primary wall material (cellulose microfibrils) in species that occupy highly mesic habitats, where such impedance in the conductive stream does not have an appreciable negative selective value. This physiological interpretation of pit membrane remnants in perforations is enhanced by the phylogenetic distribution as well as the strongly mesic ecological preferences of species that exemplify this phenomenon in dicotyledons at large. Families with pit membrane presence in perforations are scattered throughout phylogenetic trees, but they occur most often in basal branches of major clades (superorders) or as basal branches of orders within the major clades. Further study will doubtless reveal other families and genera in which this phenomenon occurs, although it is readily detected only with SEM. Phylogenetic stages in the disappearance of pit membrane remnants from perforation plates are described, ranging from intact pit membranes except for presence of pores of various sizes, to presence of membrane remnants only at lateral ends of perforations and in one or two perforations (arguably pits) at the transition between a perforation plate and subadjacent lateral wall pitting. Developmental study of the mechanism and timing of lysis of pit membranes in perforations, and assessment of the role of the conductive stream in their removal, are needed to enhance present understanding of vessel evolution. © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society, 2004, 146, 41,51. [source] |