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Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat
Background: Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Methods: Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. Results: The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and −3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Conclusion: Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer
A New Soldier-Producing Aphid Species, Pseudoregma baenzigeri, sp. nov., from Northern Thailand
Pseudoregma baenzigeri, sp. nov., is described from northern Thailand. This species forms dense, huge colonies on shoots of the bamboo Dendrocalamus sp., and produces many first-instar, pseudoscorpion-like soldiers. Alate sexuparae were found from the end of September to mid October. Two syrphids, Eupeodes sp. A (allied to E. confrater) and Dideoides chrysotoxoides, and the pyralid Dipha aphidivora were recorded as predators of P. baenzigeri. The aphids were also likely to be eaten by some rodents. The apterous adult, nymphs, soldier and alate sexupara of P. baenzigeri can be distinguished from those of the other congeners by the longer, conical ultimate rostral segment. A tentative key to the species of Pseudoregma living on bamboo is provided
Subacute and chronic hypersensitivity pneumonitis: Histopathological patterns and survival
Background: in hypersensitivity pneumonitis (HP), survival can be predicted on the basis of the severity of fibrosis in surgical lung biopsy, but few data are available on the influence of clinical, functional, tomographic and histologic findings on prognosis. Objectives: To describe the impact on survival. of clinical data, histological patterns, and HRCT findings in subacute/chronic HP.Methods: A retrospective analysis of 103 patients diagnosed with HP submitted to surgical lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis (n = 76).Results: the most relevant exposures were to molds and birds. Lung biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric interstitial pneumonia in 27, and nonspecific interstitial pneumonia (NSIP) in 16. By univariate analysis, several findings were predictors of mortality: older age, mate sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation during exercise, and absence of mosaic pattern/air trapping and presence of fibrosis on HRCT. By multivariate analysis, remained significant: age (p = 0.007), oxygen saturation during exercise (p = 0.003), and mosaic pattern/air trapping on HRCT (p = 0.004). Patients with NSIP had a greater survival than did those with typical histology and those with bronchiolocentric pneumonia (p = 0.033).Conclusions: A wide range of histological features are found in FIR Typical findings are seen in 45% of cases, Other common patterns are NSIP and centriacinar lesions. Survival is better in patients with NSIP and worse in those with older age, desaturation during exercise, and absence of mosaic pattern/air trapping on HRCT. (c) 2009 Etsevier Ltd. All rights reserved.Universidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilHosp Servidor Publ Estadual, Div Resp Dis, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc
Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms
<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p>
<p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p>
<p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p>
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