133 research outputs found

    Fifteen-S-hydroxyeicosatetraenoic acid (15-S-HETE) specifically antagonizes the chemotactic action and glomerular synthesis of leukotriene B4 in the rat

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    Fifteen-S-hydroxyeicosatetraenoic acid (15-S-HETE) specifically antagonizes the chemotactic action and glomerular synthesis of leukotriene B4 in the rat. In models of experimental glomerulonephritis, there is temporal concordance between the shift in the glomerular cellular infiltrate from neutrophils (PMN) to macrophages/monocytes and the suppression of glomerular leukotriene B4 (LTB4) generation. Since macrophages are a rich source of 15-lipoxygenase (15-LO) products, we investigated whether the principal product of arachidonate 15-lipoxy-genation, 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), was capable of antagonizing the proinflammatory actions of LTB4 in the rat. PMN exhibited chemotaxis to LTB4 in a dose dependent manner with an LC50 of 10-8 M. When rat neutrophils were pre-treated with 15-S-HETE, chemotaxis to LTB4 was inhibited in a dose dependent manner (maximal at 30 ”M 15-S-HETE) but, the same concentration did not inhibit chemotaxis to n-formyl-1-methionyl-1-phenylalanine (FMP). 12-S-HETE (30”M) did not inhibit chemotaxis to LTB4. Glomeruli from rats injected with nephrotoxic serum three hours earlier generated increased levels of LTB4; prior exposure of such glomeruli to 15-S-HETE totally normalized LTB4 production. The glomerular production of 15-S-HETE and LTB4 was also determined 3 hours, 72 hours and 2 weeks after administration of nephrotoxic serum. Whereas there was an early, short-lived, burst of LTB4 followed by a return to baseline levels, the production of 15-S-HETE increased steadily over the two week period and was present in amounts fivefold greater than LTB4. Thus, these studies assign a role for locally generated 15-LO derivatives in arresting LTB4-promoted PMN infiltration and suppressing LTB4 synthesis. Coupled with our previous demonstration of counterregula-tory interactions between lipoxins and cysteinyl leukotrienes, the current studies provide further support for a generalized anti-inflammatory role for 15-LO products through specific antagonism and/or inhibition of leukotriene synthesis and biologic activities

    Complement activation retards resolution of acute ischemic renal failure in the rat

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    Complement activation retards resolution of acute ischemic renal failure in the rat. We investigated the role of complement activation on the resolution of acute ischemic renal failure in the rat. Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with acute renal failure were exposed to daily zymosan infusion (an activator of the complement system), or to blood incubated with cuprophane (CUP) or polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour proteinuria on Day 3 and Day 5 following ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically. Zymosan and cuprophane exposed rats had a significant delay in the recovery of renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of zymosan-exposed rats to infusion of deferoxamine (DFO), a potent inhibitor of hydroxyl radical formation (OH‱). Infusion of DFO prior to zymosan significantly improved recovery of renal function. We also measured urinary thromboxane B2 levels in these groups of rats. While the groups of rats exposed to zymosan had the highest levels of thromboxane B2, these levels were not different between the groups exposed to zymosan alone, or to zymosan and DFO. These observations suggest a role for hydroxyl radicals in the prolongation of renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with acute renal failure

    Effect of rapid solidification and calcium additions on Sn-38 wt.%Pb-6 wt.%Sb melt-spun alloys

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    The effect of calcium additions on the structure and physical properties of melt-spun process Sn-38Pb-6Sb alloys have been experimentally investigated at a solidification rate of ~105 K/s. Structure, internal friction, elastic moduli, microhardness and electrical resistivity of the Sn-38%Pb , Sn-38%Pb -6%Sb , Sn-38%Pb -6%Sb-0.5%Ca , Sn-38%Pb -6%Sb -1%Ca , Sn-38%Pb -6%Sb -1.5%Ca , Sn-38%Pb -6%Sb -2%Ca , Sn-38%Pb -6%Sb -2.5%Ca (in wt%) rapidly solidified alloys are investigated. The results showed that the mechanical and electrical properties values are enhanced for ternary Sn-38%Pb -6%Sb alloy. The examined mechanical and electrical conductivity decreased by addition of calcium content in the studied alloys. It also leads to with increasing Ca content the SnSb inter-metallic compound (IMC) precipitates are increased in the Sn matrix. The results were explained in terms of the dislocation theory, effect of quenching rate on the produced density fluctuations in composition and the modes of interaction of crystal lattice defects

    Effect of salt intake on beat‐to‐beat blood pressure nonlinear dynamics and entropy in salt‐sensitive versus salt‐protected rats

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    Blood pressure exhibits substantial short‐ and long‐term variability (BPV). We assessed the hypothesis that the complexity of beat‐to‐beat BPV will be differentially altered in salt‐sensitive hypertensive Dahl rats (SS) versus rats protected from salt‐induced hypertension (SSBN13) maintained on high‐salt versus low‐salt diet. Beat‐to‐beat systolic and diastolic BP series from nine SS and six SSBN13 rats (http://www.physionet.org) were analyzed following 9 weeks on low salt and repeated after 2 weeks on high salt. BP complexity was quantified by detrended fluctuation analysis (DFA), short‐ and long‐range scaling exponents (αS and αL), sample entropy (SampEn), and traditional standard deviation (SD) and coefficient of variation (CV(%)). Mean systolic and diastolic BP increased on high‐salt diet (P < 0.01) particularly for SS rats. SD and CV(%) were similar across groups irrespective of diet. Salt‐sensitive and ‐protected rats exhibited similar complexity indices on low‐salt diet. On high salt, (1) SS rats showed increased scaling exponents or smoother, systolic (P = 0.007 [αL]) and diastolic (P = 0.008 [αL]) BP series; (2) salt‐protected rats showed lower SampEn (less complex) systolic and diastolic BP (P = 0.046); and (3) compared to protected SSBN13 rats, SS showed higher αL for systolic (P = 0.01) and diastolic (P = 0.005) BP. Hypertensive SS rats are more susceptible to high salt with a greater rise in mean BP and reduced complexity. Comparable mean pressures in sensitive and protective rats when on low‐salt diet coupled with similar BPV dynamics suggest a protective role of low‐salt intake in hypertensive rats. This effect likely reflects better coupling of biologic oscillators.We investigated the non‐linear dynamical properties of blood pressure variability, specifically complexity analysis and detrended fluctuation analysis (DFA), of the systolic and diastolic blood pressure time series in 9 salt sensitive and 6 protected rats. We showed that salt sensitive rats exhibit varying non linear BP dynamics compared to protected rats (smoother time series), irrespective of diet; we also showed the differential impat of salt intake on complexity and DFA metrics in both strains of rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122419/1/phy212823_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122419/2/phy212823.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122419/3/phy212823-sup-0001-SupInfo.pd

    Draft Genome Sequence of Photorhabdus luminescens Strain BA1, an Entomopathogenic Bacterium Isolated from Nematodes Found in Egypt

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    Photorhabdus luminescens strain BA1 is an entomopathogenic bacterium that forms a symbiotic association with Heterorhabditis nematodes. We report here a 5.0-Mbp draft genome sequence for P. luminscens strain BA1, with a G+C content of 42.46% and 4,250 candidate protein-coding genes

    Outcome of 2000 Cases of Phacoemulsification

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    Phacoemulsification cases performed at Fauji Foundation Hospital, Rawalpindi. Methods: This study was conducted in the Department of Ophthalmology, Fauji FoundationHospital, Rawalpindi, from October 2004 to March 2007. It comprised 2000 cases of phacoemulsification with intraocular lens (IOL) implantation which wereperformed at Fauji Foundation Hospital in two and a half years. Variables analysed included patient’s age and sex, pre-existing conditions limiting final visualacuity (VA), and type of anesthesia used. Outcome measures included intra operative and postoperative complications and final visual acuity. Results: Of the 2000 cases, there were 72% female and 28% male patients. 62% of patients were given periocular whereas 38% were operated in topical anesthesia. 15.35% of patients suffered intra operative complications. Intra operative complications were: radial tear in 5% cases, posterior capsular (PC) rent without vitreous loss in 3.45% and PC rent with vitreous loss in 4.85% of patients, iris damage in 0.83%, zonular dehiscence in 0.6% of cases, and nuclear fragment drop in 0.3% of patients. Of total patients, 91% of patients kept their appointment for 8 weeks follow up. Postoperatively corrected visual acuity after elimination of factors reducing best corrected visual acuity (BCVA) was 6/9 or better in 89% of cases. Postoperative complications were seen in 20.83% of patients, which included mild to moderate striate keratitis in 11.98%, mild to moderate anterior uveitis in 4.01%, raised intra ocular pressure (IOP) in 0.73%, wound leakage in 0.3%, ophthalmoplegia in 0.05% and endophthalmitis in 0.10% of cases. Posterior capsularopacification (PCO) was seen in 3.65% of patients in 8 weeks of followup. Post operative astigmatism was from 0 – 4.5 D. Conclusion: Phacoemulsification is much safer, predictable, relatively atraumatic procedure and it provides early rehabilitation. It is associated with more patient as well as surgeon satisfaction

    Draft Genome Sequence of Photorhabdus temperata Strain Meg1, an Entomopathogenic Bacterium Isolated from Heterorhabditis megidis Nematodes

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    Photorhabdus temperata strain Meg1 is an entomopathogenic bacterium that forms a symbiotic association with Heterorhabditis nematodes. We report here a 4.9-Mbp draft genome sequence for P. temperata strain Meg1, with a G+C content of 43.18% and containing 4,340 candidate protein-coding genes

    Regionalizing healthcare: a vision for transforming Lebanon into a regional academic hub

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    <p>Abstract</p> <p>Background</p> <p>Lebanon suffers from a large scale emigration of physicians coupled with an oversaturation of the physician job market. Lebanon is currently witnessing an expansion of its medical education capacity with the establishment of new private medical schools, raising the fears of a worsening market oversaturation.</p> <p>Discussion</p> <p>The neighboring Arabian Gulf countries are suffering from a serious shortage of clinicians and academicians. In spite of their enormous investments in educational, clinical and research collaborative initiatives with some of the most renowned North American medical schools and institutions, their ability to recruit and retain highly qualified clinicians and academicians remains a major challenge. Lebanese universities have the opportunity to establish triangular collaborations with the Gulf regional medical centers and their North American partners. They could achieve this goal by tapping into the globalized and high quality Lebanese physician workforce and consequently regionalize healthcare delivery in the Middle East.</p> <p>Summary</p> <p>By recruiting its globalized and high quality physician workforce to establish collaborations with the Gulf regional, Lebanon could become a regional "academic hub".</p

    Sector Sustainability Check: Rural Open Defecation Free (ODF) & Rural (Drinking) Water Supply Schemes (RWSS) Punjab & Sindh Provinces

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    This study focused on the behavioral sustainability of latrine use and continued functionality of rural water supply systems in ODF certified villages in the Sindh and Punjab provinces of Pakistan. Our chief role was to develop, integrate and analyze social norms measures as part of the larger sustainability check. This report presents those methods, measures and findings. PennSONG served as an associate partner in the report, working with lead partner AAN Associates (www.aanassociates.com) and associate partner Institute of Environmental Sciences and Engineering (iese.nuse.edu.pk). The study was substantially supported by the Ministry of Climate Change (MOCC), the Government of Pakistan, and UNICEF Pakistan

    Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence

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    Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy
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