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Sample records for experimental glomerulonephritis induced

  1. Experimental proliferative glomerulonephritis in the cat.

    PubMed

    Bishop, S A; Stokes, C R; Lucke, V M

    1992-01-01

    A model of chronic serum sickness was used to induce immune-complex glomerulonephritis in seven experimental cats, by daily intravenous inoculation of an increasing dose (5 to 35 mg) of human serum albumin (HSA). At week four, two of the seven animals developed anterior uveitis. At week 23, two different animals developed the subcutaneous oedema characteristic of the nephrotic syndrome (NS), whilst the other five cats appeared clinically normal. The kidneys were examined at necropsy by light microscopy and by transmission electron microscopy. The glomeruli of four animals (three with both proteinuria and uraemia, and one with proteinuria only) showed morphological changes under light microscopy. The abnormalities suggested that a diffuse mesangial proliferative glomerulonephritis (GN) had been induced in three cats and diffuse membranoproliferative GN induced in another. Ultrastructural studies revealed electron-dense deposits (immune-complexes) in six of the seven cats. Two cats without glomerular abnormalities by light microscopy had mesangial deposits and three cats with mesangial proliferative GN had deposits at mesangial, subendothelial and/or subepithelial sites. The single cat with membranoproliferative GN had deposits at mesangial, subendothelial, subepithelial and intramembranous sites. Immunohistological examination (peroxidase-antiperoxidase technique) showed that HSA and immunoglobulin (IgG and IgM) were deposited in the glomeruli of these cats. Deposits were the most dense in cats with more severe renal lesions. Deposits of IgM were most abundant. An extensive cellular infiltrate, comprising macrophages, neutrophils and plasma cells, was observed only in the four animals which showed abnormalities in glomerular ultrastructure. The disease induced in these cats thus appears to differ from the membranous nephropathy previously described in the cat and bears a close resemblance to immune complex (IC) disease in man. In view of the relatively few specific

  2. Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(IV)NC1 in Established Experimental Autoimmune Glomerulonephritis

    PubMed Central

    Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.

    2009-01-01

    Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992

  3. Glomerulonephritis

    MedlinePlus

    ... that suppress the immune system A procedure called plasmapheresis may sometimes be used for glomerulonephritis caused by ... Saunders; 2012:chap 32. Cattran DC, Reigh HN. Overview of therapy for glomerular disease. In: Taal MW, ...

  4. Th1 and Th17 Cells Induce Proliferative Glomerulonephritis

    PubMed Central

    Summers, Shaun A.; Steinmetz, Oliver M.; Li, Ming; Kausman, Joshua Y.; Semple, Timothy; Edgtton, Kristy L.; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R.

    2009-01-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1−/− mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against α3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 ± 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  5. Th1 and Th17 cells induce proliferative glomerulonephritis.

    PubMed

    Summers, Shaun A; Steinmetz, Oliver M; Li, Ming; Kausman, Joshua Y; Semple, Timothy; Edgtton, Kristy L; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R; Kitching, A Richard

    2009-12-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  6. Mesangial Localization of Immune Complexes in Experimental Canine Adenovirus Glomerulonephritis

    PubMed Central

    Wright, N. G.; Morrison, W. I.; Thompson, H.; Cornwell, H. J. C.

    1974-01-01

    Each of a group of 14 dogs was infected experimentally by an intravenous dose of canine adenovirus calculated to allow survival until the initial stages of antibody production; the kidneys of infected dogs were examined during the period of 4-14 days after administration of virus. Proliferative glomerulonephritis with localization of IgG, C3 and viral antigen in mesangial regions was demonstrated. With the electron microscope, electron dense deposits were found scattered throughout the mesangium. There was proliferation of mesangial cells, infiltration into the glomerular tuft of polymorphonuclear leucocytes and, in some cases, focal glomerular necrosis with intracapsular and tubular haemorrhage. By means of an indirect immunofluorescence test, anti-viral antibody was detected in kidney eluates; anti-kidney antibody was not present. ImagesFigs. 5-8Figs. 9-10Figs. 1-4 PMID:4375485

  7. Membranoproliferative glomerulonephritis

    MedlinePlus

    Membranoproliferative GN I; Membranoproliferative GN II; Mesangiocapillary glomerulonephritis; Membranoproliferative glomerulonephritis; Lobular GN; Glomerulonephritis - membranoproliferative; MPGN type I; MPGN type ...

  8. Glomerulonephritis-induced changes in kidney gene expression in rats

    PubMed Central

    Pavkovic, Mira; Riefke, Björn; Frisk, Anna-Lena; Gröticke, Ina; Ellinger-Ziegelbauer, Heidrun

    2015-01-01

    We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague–Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. To obtain insight into molecular processes during GN pathogenesis, mRNA expression was investigated in WKY and SD kidneys using Affymetrix's GeneChip Rat genome 230_2.0 arrays (GSE64265). The immunopathological processes during GN are still not fully understood and likely involve both innate and adaptive immunity. In the present study, several hundred mRNAs were found deregulated, which functionally were mostly associated with inflammation and regeneration. The β-chain of the major histocompatibility complex class II RT1.B (Rt1-Bb) and complement component 6 (C6) were identified as two mRNAs differentially expressed between WKY and SD rat strains which could be related to known different susceptibilities to NTS of different rat strains; both were increased in WKY and decreased in SD rats (Pavkovic et al., 2015 [1]). Increased Rt1-Bb expression in WKY rats could indicate a stronger and more persistent cellular reaction of the adaptive immune system in this strain, in line with findings indicating adaptive immune reactions during GN. The complement cascade is also known to be essential for GN development, especially terminal cascade products like C6. PMID:26697341

  9. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    PubMed

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required. PMID:19524415

  10. P2X7 Deficiency Attenuates Renal Injury in Experimental Glomerulonephritis

    PubMed Central

    Taylor, Simon R.J.; Turner, Clare M.; Elliott, James I.; McDaid, John; Hewitt, Reiko; Smith, Jennifer; Pickering, Matthew C.; Whitehouse, Darren L.; Cook, H. Terence; Burnstock, Geoffrey; Pusey, Charles D.; Unwin, Robert J.; Tam, Frederick W.K.

    2009-01-01

    The P2X7 receptor is a ligand-gated cation channel that is normally expressed by a variety of immune cells, including macrophages and lymphocytes. Because it leads to membrane blebbing, release of IL-1β, and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of inflammatory diseases. Although the P2X7 receptor is usually not detectable in normal renal tissue, we previously reported increased expression of both mRNA and protein in mesangial cells and macrophages infiltrating the glomeruli in animal models of antibody-mediated glomerulonephritis. In this study, we used P2X7-knockout mice in the same experimental model of glomerulonephritis and found that P2X7 deficiency was significantly renoprotective compared with wild-type controls, evidenced by better renal function, a striking reduction in proteinuria, and decreased histologic glomerular injury. In addition, the selective P2X7 antagonist A-438079 prevented the development of antibody-mediated glomerulonephritis in rats. These results support a proinflammatory role for P2X7 in immune-mediated renal injury and suggest that the P2X7 receptor is a potential therapeutic target. PMID:19389853

  11. Experimental glomerulonephritis in the isolated perfused rat kidney.

    PubMed Central

    Couser, W G; Steinmuller, D R; Stilmant, M M; Salant, D J; Lowenstein, L M

    1978-01-01

    The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition. Images PMID:372233

  12. Treatment of experimental mesangioproliferative glomerulonephritis with non-anticoagulant heparin: therapeutic efficacy and safety.

    PubMed

    Burg, M; Ostendorf, T; Mooney, A; Koch, K M; Floege, J

    1997-04-01

    Treatment with conventional heparin is effective in experimental mesangioproliferative glomerulonephritis. However, the long-term effects and safety of this therapy, in particular in the presence of mesangiolysis, have not been assessed. In addition, this therapy has been hampered by bleeding complications. In the present study, therefore, we investigated the long-term effects of a short course of non-anticoagulant (NA) heparin treatment in the anti-Thy 1.1 mesangioproliferative glomerulonephritis, in which early immune-mediated mesangiolysis subsequently leads to mesangial hyperproliferation. Rats received continuous ip NA-heparin or vehicle during the active mesangioproliferative phase (Days 2 to 9; early treatment) or during the early resolution phase (Days 10 to 17; late treatment). Whereas NA-heparin in the early treatment group did not affect the glomerular macrophage, lymphocyte, or platelet influx, it did lead to significantly decreased glomerular cellularity, mesangial cell proliferation, alpha-smooth muscle actin, desmin expression (ie, markers of activated mesangial cells), and matrix accumulation as well as to persistent mesangiolytic lesions including microaneurysms. Despite this latter finding, at Day 120, NA-heparin-treated rats of the early treatment group showed significantly better renal function and less proteinuria and glomerulosclerosis than vehicle-infused rats. In contrast, late therapy with NA-heparin neither accelerated resolution of the nephritis or otherwise affected the course of the disease. We conclude that transient NA-heparin therapy is effective in mesangioproliferative glomerulonephritis, both acutely and long term, when it is initiated during the active phase of the disease. Also, NA-heparin therapy is safe even in glomerular diseases accompanied by mesangiolysis. PMID:9111513

  13. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    PubMed

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an

  14. Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person.

    PubMed

    Guinault, Damien; Ribes, David; Delas, Audrey; Milongo, David; Abravanel, Florence; Puissant-Lubrano, Bénédicte; Izopet, Jacques; Kamar, Nassim

    2016-04-01

    Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) κ light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease. PMID:26682764

  15. The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis.

    PubMed

    Ooi, Joshua D; Chang, Janet; Hickey, Michael J; Borza, Dorin-Bogdan; Fugger, Lars; Holdsworth, Stephen R; Kitching, A Richard

    2012-09-25

    Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409-428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice. The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids, MPO(415-426), with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA-associated microscopic polyangiitis. PMID:22955884

  16. Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series with misleading diagnoses

    PubMed Central

    Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.

    2016-01-01

    Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161

  17. Characterization of feline glomerulonephritis associated with viral-induced hematopoietic neoplasms.

    PubMed

    Glick, A D; Horn, R G; Holscher, M

    1978-08-01

    Light, electron, and immunofluorescence microscopy on tissues from 63 domestic cats revealed that glomerulonephritis occurred in almost one third of cats with hematopoietic neoplasms of the type linked with feline leukemia virus (FeLV). Glomerular lesions were of the immune complex type with subepithelial, subendothelial, and mesangial dense deposits and reticular aggregates, similar to the nephropathy associated with systemic lupus erythematosus in humans. Evidence that the glomerular lesions may be viral-induced raises the possibility of similar pathogenetic mechanisms in human disease. PMID:677265

  18. Genetic factors influence level of proteinuria in cationic antigen-induced immune complex glomerulonephritis in the rat.

    PubMed Central

    Kato, A; Thaiss, F; Oite, T; Günther, E; Batsford, S; Vogt, A

    1985-01-01

    The influence of genetic factors on the susceptibility of the rat to cationic antigen-induced in situ immune complex glomerulonephritis was investigated. The levels of proteinuria developing in 11 inbred strains of rats differing in MHC and in genetic background varied markedly. Susceptibility was not MHC associated but resided in the genetic background. PMID:3159528

  19. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo.

    PubMed

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E; Borza, Dorin-Bogdan

    2010-09-15

    The noncollagenous (NC1) domains of alpha3alpha4alpha5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of alpha3alpha4alpha5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine alpha3alpha4alpha5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b(-/-) mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine alpha3NC1 monomer and dimer subunits but not to native alpha3alpha4alpha5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked alpha3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of alpha3alpha4alpha5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen. PMID:20709951

  20. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: Protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo 1

    PubMed Central

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan

    2010-01-01

    The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951

  1. Hydrogen Peroxide–Inducible Clone-5 Regulates Mesangial Cell Proliferation in Proliferative Glomerulonephritis in Mice

    PubMed Central

    Jamba, Ariunbold; Kondo, Shuji; Urushihara, Maki; Nagai, Takashi; Kim-Kaneyama, Joo-ri; Miyazaki, Akira; Kagami, Shoji

    2015-01-01

    Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis. PMID:25835392

  2. Influenza vaccination induced leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis.

    PubMed

    Yanai-Berar, N; Ben-Itzhak, O; Gree, J; Nakhoul, F

    2002-09-01

    Influenza vaccination is a widely accepted practice, particularly among the elderly and high-risk individuals. Minor and transitory side effects following the vaccination are common, while systemic complications are infrequently reported. We describe here a case of a patient who presented to the emergency room with arthralgia, myalgias and purpura, following influenza vaccination. Necrotizing vasculitis associated with pauci-immune glomerulonephritis was observed on kidney biopsy. With increasing use of influenza vaccination, attention should be drawn to the possible expression of systemic adverse effects such as vasculitis and glomerulonephritis. PMID:12356192

  3. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

    PubMed Central

    Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429

  4. Plasma and urine biochemical changes in cats with experimental immune complex glomerulonephritis.

    PubMed

    Bishop, S A; Lucke, V M; Stokes, C R; Gruffydd-Jones, T J

    1991-01-01

    Biochemical changes in plasma and urine were monitored in six cats before and during the induction of immune complex-mediated glomerulonephritis (ICGN) by daily intravenous administration of human serum albumin (HSA). The earliest indication of renal dysfunction in the cats was hypoalbuminaemia, which occurred as early as 13 weeks before cats developed clinical signs of renal disease. Proteinuria occurred 2 to 3 weeks before clinical disease, but was sensitive in predicting renal pathology in two cats that did not develop clinical signs of disease. In addition, increased activities of several urinary enzymes were detected in affected cats, with measurement of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase providing the earliest and most sensitive indication of renal damage. These plasma and urine measurements correlated more closely with the renal pathology, observed at postmortem, than clinical assessment of disease. It was concluded that ICGN in the cat could be diagnosed earliest by measurement of plasma protein concentration, whilst disease progress could be effectively monitored by including assays to measure urine protein and urine enzymes. PMID:1826913

  5. Acute glomerulonephritis.

    PubMed

    Yoshizawa, N

    2000-09-01

    Acute glomerulonephritis (AGN) is a representative disease of acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The prototype of AGN is acute poststreptococcal glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms that are cultured from a patient who develops AGN. Although only a limited number of M-types of streptococci have been recognized as "nephritogenic streptococci", all M-types of streptococci may have nephritogenic potential because the genes for major putative nephritogenic antigens such as SPEB and NAPIr are found to be present in all group A streptococci thus far examined. Pathogenic mechanisms for APSGN involving both humoral and cell-mediated immunity have been recently proposed. The role of humoral immunity is presumed to be mediated by the in situ formation of nephritogenic streptococcal antigen-antibody complexes and circulating immune complexes. While in the cellular immune component a role for delayed-type hypersensitivity has been suggested to contribute to the pathogenesis of APSGN. PMID:10969898

  6. Embryonic fibronectin isoforms are synthesized in crescents in experimental autoimmune glomerulonephritis.

    PubMed Central

    Nickeleit, V.; Zagachin, L.; Nishikawa, K.; Peters, J. H.; Hynes, R. O.; Colvin, R. B.

    1995-01-01

    Crescents are a severe and stereotyped glomerular response to injury that occur in several forms of glomerulonephritis that progress to renal failure. The key pathogenetic step that leads to glomerular scarring in unknown, but fibronectin (FN), the clotting system, macrophages, and proliferating parietal epithelial cells are known to participate. This study was designed to determine whether FN is synthesized locally, and in what molecular isoform, and whether cytokines known to promote FN synthesis are present in the crescent. Rats immunized with bovine glomerular basement membrane develop cellular crescents by 14 days and fibrous crescents and glomerulosclerosis by 35 days. In situ hybridization was performed with oligonucleotides specific for sequences common to all FN isoforms (total FN) or sequences specific for the alternatively spliced segments (EIIIA, EIIIB, and V). Throughout the time period (14, 21, and 35 days) all crescents and glomerular tufts contained cells with strong ISH signals for total and V+ mRNA, with the strongest signals present in large cellular crescents at day 21. In contrast, EIIIA+ and EIIIB+ mRNAs showed maximal abundance within sclerosing crescents at 35 days. Protein deposition of EIIIA+, EIIIB+, and V+ FN isoforms was confirmed by immunofluorescence with segment-specific FN antibodies. Transforming growth factor-beta and interleukin-1 beta, both known to promote FN synthesis, were found in cellular crescents (days 14 and 21) and were still present, but greatly diminished, in the sclerotic phase (day 35). In summary, EIIIA-, EIIIB-, and V+ FN mRNA plasma isoforms predominate in cellular crescents, whereas in the fibrosing stage, mainly the oncofetal EIIIA+, EIIIB+, and V+ isoforms are synthesized and accumulate. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7573372

  7. Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin.

    PubMed

    Nash, A S; Mohammed, N A; Wright, N G

    1990-11-01

    Membranous nephropathy was induced in four cats by repeated intravenous injections of 120 mg cationic bovine serum albumin (BSA, pI 9.5). All four cats developed diffuse granular deposits of IgG and C3 along the glomerular capillary walls as early as five weeks which persisted until the end of the experiment at 17 weeks. Ultrastructural studies revealed many subepithelial electron dense deposits. Two cats developed severe proteinuria and the nephrotic syndrome characterised by hypoalbuminaemia and oedema. An additional four cats received repeated injections of unmodified native BSA (pI 4.5) and remained basically normal. This is the first report of membranous nephropathy and the nephrotic syndrome in an experimental animal model which, unlike other animal models, is subject to the spontaneously occurring disease. PMID:2148430

  8. Membranous glomerulonephritis and cellular crescents induced by levamisole-adulterated cocaine abuse: a case report

    PubMed Central

    Moll-Guillen, Jose-Luis; Espí-Reig, Jordi; Blanes-Julia, Marino; García-Martínez, Ana-María; Pujol-Marco, Conrad; Hernández-Jaras, Julio

    2015-01-01

    Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use. PMID:26605317

  9. Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis.

    PubMed Central

    Tang, W W; Feng, L; Vannice, J L; Wilson, C B

    1994-01-01

    The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in

  10. Adalimumab (TNFα Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient

    PubMed Central

    Wei, S. S.; Sinniah, R.

    2013-01-01

    Adalimumab (Humira) is a tumour necrosis factor α (TNFα) inhibitor that is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, and juvenile idiopathic arthritis (Sullivan and Preda (2009), Klinkhoff (2004), and Medicare Australia). Use of TNFα inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, and sarcoidosis or sarcoid-like granulomas) (Ramos-Casals et al. (2010)). We report a patient with extensive psoriasis presenting with renal failure and seropositive lupus markers without classical lupus nephritis after 18 months treatment with adalimumab. He has renal biopsy proven IgA nephritis instead. Renal biopsy is the key diagnostic tool in patients presenting with adalimumab induced nephritis and renal failure. He made a remarkable recovery after adalimumab cessation and steroid treatment. To our knowledge, this is a unique case of a psoriasis patient presenting with seropositive lupus markers without classical lupus nephritis renal failure and had renal biopsy proven IgA glomerulonephritis after receiving adalimumab. PMID:24558628

  11. [Glomerulonephritis in dogs and cats].

    PubMed

    Reinacher, M; Frese, K

    1991-04-01

    Immunohistology and special staining of plastic sections allow diagnosis and differentiation of subtypes of glomerulonephritis in dogs. Frequency and clinical importance of these forms of glomerulonephritis vary significantly. In cats, glomerulonephritis occurs frequently in FIV-positive cats but is rare in animals suffering from persistent FeLV infection or FIP. PMID:2068715

  12. Factor VIII and glomerulonephritis.

    PubMed

    Ekberg, M; Nilsson, I M

    1975-05-17

    To find out if determination of factor VIII,which most probably is synthetised in the intima of blood-vessesls, is of value for predicting the severity of vessel damge in glomerulonephritis, factor-VIII activity, factor-VIII-related antigen, and glomerular filtration-ratewere esto,ated om 85 patients with early glomerulonephritis on admission, and in 70 of these at follow-up for up to 4 years. The levels of factor-VIII activity and factor-VIII-related antigen on admission were normal in those patients who recovered. Where renal function was impaired on admission or becaome so during follow-up, factor VIII was high. Determination of factor VIII might thus be of prognostic value in early glomerulonephritis. PMID:49471

  13. Zhen-wu-tang attenuates cationic bovine serum albumin-induced inflammatory response in membranous glomerulonephritis rat through inhibiting AGEs/RAGE/NF-κB pathway activation.

    PubMed

    Wu, Junbiao; Liu, Bihao; Liang, Chunling; Ouyang, Hui; Lin, Jin; Zhong, Yanchun; He, Yu; Zhou, Jie; Zhou, Yuan; Zhou, Jiuyao

    2016-04-01

    Zhen-wu-tang (ZWT), a traditional Chinese compound formula recorded in the Treatise on Febrile Diseases, has significant inhibitory effects on inflammatory damage and oxidative lesions in rats, but its mechanism of action remains unclear. The aim of the present study was to explore whether the anti-inflammatory and anti-oxidative effects of ZWT were mediated by the AGEs/RAGE/NF-κB signaling pathway in rats with cationic bovine serum albumin (C-BSA)-induced membranous glomerulonephritis (MGN). We found that ZWT significantly reduced the production of malondialdehyde (MDA), but enhanced the superoxide dismutase (SOD) activity. The ELISA results showed that ZWT not only reduced the serum levels of AGEs but also decreased the release of inflammatory mediators (TNF-α, IL-1β, and IL-6). Meanwhile, HE staining showed that pathological kidney injury was alleviated by ZWT. In addition, ZWT suppressed the expression of RAGE1 and NF-κB p65, as well as the nuclear translocation of NF-κB p65. The accumulation of AGEs, oxidative lesions and inflammation damage were reduced by an AGE inhibitor. Thus, the present study demonstrates that AGEs play a role in the pathogenesis of MGN and that AGE inhibition could reduce the inflammatory reactions and oxidative lesions in MGN. In general, ZWT attenuated MGN, in part, by inhibiting the AGEs/RAGE/NF-κB pathway. PMID:26851631

  14. Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis

    PubMed Central

    Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222

  15. Hypercoagulation in glomerulonephritis.

    PubMed Central

    Salem, H H; Whitworth, J A; Koutts, J; Kincaid-Smith, P S; Firkin, B G

    1981-01-01

    The clotting values of 50 patients with glomerulonephritis were examined. Three different coagulation groups were recognised: those with normal clotting values (group 1); those with high concentrations of factor VIII but otherwise normal clotting results (group 2); and patients who showed the presence of an activator of the intrinsic coagulation pathway, indicated by the presence of a short activated partial thromboplastin time or the ability of patients' plasma to shorten control clotting time in mixing studies (group 3). Patients in group 2 either had a uniform rise in all three components of the factor VIII molecule or a disproportionately higher concentration of factor-VIII-related antigen. In contrast, the level of VIII clotting activity in patients in group 3 was always higher than concentrations of either VIIIAg or VIIIWF. A significantly high incidence of thrombotic complications was observed in patients with group 3 but in none of the patients in either group 1 or group 2. Impaired renal function was more common in patients in groups 2 and 3, with higher mean serum creatinine concentrations in those with group 3. Patients with glomerulonephritis who have a short partial thromboplastin time with kaolin or who shorten control clotting time form a subgroup in whom hypercoagulation could adversely affect the course of their disease. The value of antiplatelet or anticoagulant treatment in these patients needs to be explored. PMID:6788212

  16. Membranous glomerulonephritis associated with Mycobacterium shimoidei pulmonary infection

    PubMed Central

    Kanaji, Nobuhiro; Kushida, Yoshio; Bandoh, Shuji; Ishii, Tomoya; Haba, Reiji; Tadokoro, Akira; Watanabe, Naoki; Takahama, Takayuki; Kita, Nobuyuki; Dobashi, Hiroaki; Matsunaga, Takuya

    2013-01-01

    Patient: Male, 83 Final Diagnosis: Membranous glomerulonephritis Symptoms: Producting cough Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare disease Background: Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. Case Report: An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. Conclusions: To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection. PMID:24367720

  17. Hypertension in Chronic Glomerulonephritis.

    PubMed

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  18. Comparative pathology of glomerulonephritis in animals.

    PubMed

    Slauson, D O; Lewis, R M

    1979-03-01

    Glomerulonephritis constitutes an important category of renal diseases in animals and has been recognized with increasing frequency in the last decade. We report here the comparative morphologic aspects of glomerulonephritis as a naturally occurring disease of animals. We briefly review the immunopathogenesis of glomerulonephritis. The morphology of renal lesions occurring in glomerulonephritis in dogs, cats, cattle, sheep, horses and swine has been reviewed with emphasis on the range and specificity of various glomerular lesions and on the comparison of lesions between various species. A distinction was made between glomerulonephritis as a primary disease entity and glomerulonephritis associated with other disease processes. Primary idiopathic glomerulonephritis occurred in all species but was most commonly recognized as a clinically important disease in dogs and cats. Glomerulonephritis also occurred in association with other diseases such as equine infectious anemia, chronic hog cholera, canine pyometra, dirofilariasis, feline leukemia virus infection and canine systemic lupus erythematosus. PMID:442447

  19. Membranoproliferative glomerulonephritis with essential cryoglobulinemia

    PubMed Central

    Satish, S.; Rajesh, R.; George, K.; Elango, E. M.; Unni, V. N.

    2008-01-01

    Cryoglobulinemia is an uncommon cause of renal disease and often occurs in patients with hepatitis C virus (HCV) infection. We report a case of membranoproliferative glomerulonephritis in a patient with cryoglobulinemia, which was not associated with HCV infection or any identifiable etiology. PMID:20142909

  20. Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining "post" is important in understanding and treating infection-related glomerulonephritis.

    PubMed

    Glassock, Richard J; Alvarado, Anthony; Prosek, Jason; Hebert, Courtney; Parikh, Samir; Satoskar, Anjali; Nadasdy, Tibor; Forman, John; Rovin, Brad; Hebert, Lee A

    2015-06-01

    A spate of recent publications describes a newly recognized form of glomerulonephritis associated with active staphylococcal infection. The key kidney biopsy findings, glomerular immunoglobulin A (IgA) deposits dominant or codominant with IgG deposits, resemble those of IgA nephritis. Many authors describe this condition as "postinfectious" and have termed it "poststaphylococcal glomerulonephritis." However, viewed through the prism of poststreptococcal glomerulonephritis, the prefix "post" in poststaphylococcal glomerulonephritis is historically incorrect, illogical, and misleading with regard to choosing therapy. There are numerous reports describing the use of high-dose steroids to treat poststaphylococcal glomerulonephritis. The decision to use steroid therapy suggests that the treating physician believed that the dominant problem was a postinfectious glomerulonephritis, not the infection itself. Unfortunately, steroid therapy in staphylococcus-related glomerulonephritis can precipitate severe staphylococcal sepsis and even death and provides no observable benefits. Poststreptococcal glomerulonephritis is an authentic postinfectious glomerulonephritis; poststaphylococcal glomerulonephritis is not. Making this distinction is important from the perspective of history, pathogenesis, and clinical management. PMID:25890425

  1. Pauci-Immune Crescentic Glomerulonephritis: An ANCA-Associated Vasculitis

    PubMed Central

    Syed, Rafeel; Rehman, Amina; Valecha, Gautam; El-Sayegh, Suzanne

    2015-01-01

    Rapidly progressive glomerulonephritis (RPGN) is a syndrome signified by a precipitous loss of renal function, with features of glomerulonephritis including dysmorphic erythrocyturia and glomerular proteinuria. RPGN is associated with extensive crescent formation, and, thus, the clinical term RPGN is often used interchangeably with the pathologic term crescentic glomerulonephritis (CGN). From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PICG), anti-GBM GN, and immune complex GN. PICG, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence (IF) or electron microscopy (EM). In most patients, pauci-immune CGN is a component of a systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the nomenclature ANCA-associated vasculitis (AAV). Recent research has identified several other antibodies associated with PICG, which is now understood to be a complex spectrum of disease with considerable overlap in terms of clinical phenotype and outcomes. In addition, several genetic and environmental factors have recently been implicated in the pathogenesis of this disorder. With new prognostic classifications, enhanced understanding of immunopathologic mechanisms, and novel treatment paradigms, clinical and experimental interest in PICG remains high. PMID:26688808

  2. Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis.

    PubMed

    Kanegane, Hirokazu; Vilela, Maria Marluce dos Santos; Wang, Yue; Futatani, Takeshi; Matsukura, Hiroyoshi; Miyawaki, Toshio

    2003-05-01

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4+1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS. PMID:12736807

  3. Crescentic glomerulonephritis in a child with Heiner syndrome.

    PubMed

    Yavuz, Sevgi; Karabay-Bayazıt, Aysun; Yılmaz, Mustafa; Gönlüşen, Gülfiliz; Anarat, Ali

    2014-01-01

    Heiner syndrome is a food-induced pulmonary hypersensitivity disease that predominantly affects infants. Chronic respiratory symptoms with pulmonary infiltrates on radiography, positive milk precipitins and resolution of findings upon removal of cow's milk constitute the main features. Severe cases may present with pulmonary hemosiderosis. Few renal manifestations associated with this syndrome have been reported so far. Here we report the first case of Heiner syndrome complicated by crescentic glomerulonephritis after 5 years of follow-up. PMID:26388600

  4. Membranous glomerulonephritis: a morphometric study.

    PubMed

    Paraskevakou, H; Kavantzas, N; Pavlopoulos, P M; Voudiklari, S; Zerefos, N; Papagalanis, N; Davaris, P

    2000-01-01

    Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function. PMID:10729917

  5. Glomerulonephritis

    MedlinePlus

    ... seen, including: Nerve inflammation (polyneuropathy) Signs of fluid overload, including abnormal heart and lung sounds Swelling ( edema ) ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  6. Gastric Syphilis and Membranous Glomerulonephritis.

    PubMed

    Roh, Min; Sohn, Joo Hyun; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-05-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  7. Gastric Syphilis and Membranous Glomerulonephritis

    PubMed Central

    Roh, Min; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-01-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  8. Neutrophils: game changers in glomerulonephritis?

    PubMed Central

    Mayadas, Tanya N.; Rosetti, Florencia; Ernandez, Thomas; Sethi, Sanjeev

    2010-01-01

    Glomerulonephritides represent a diverse array of diseases that have in common immune cell-mediated effector mechanisms that cause organ damage. The contribution of neutrophils to the pathogenesis of proliferative glomerulonephritis (GN) is not well recognized. Most equate neutrophils with killing pathogens and causing collateral tissue damage during acute inflammation. However, these phagocytes are endowed with additional characteristics that have been traditionally reserved for cells of the adaptive immune system. They communicate with other cells, exhibit plasticity in their responses and have the potential to coordinate and inform the subsequent immune response, thus countering the notion that they arrive, destroy and then disappear. Therefore, neutrophils, which are the first to arrive at a site of inflammation, are potential game changers in GN. PMID:20667782

  9. Skimmin, a Coumarin from Hydrangea paniculata, Slows down the Progression of Membranous Glomerulonephritis by Anti-Inflammatory Effects and Inhibiting Immune Complex Deposition

    PubMed Central

    Xin, Hongqi; Li, Yan; Zhang, Dongming; Shi, Jing; Yang, Jingzhi

    2013-01-01

    Skimmin is one of the major pharmacologically active molecules present in Hydrangea paniculata, a medical herb used in the traditional Chinese medicine as an anti-inflammatory agent. In the current study, we attempted to investigate its renoprotective activity and underlying mechanisms in a rat model of membranous glomerulonephritis induced by cationic bovine serum albumin (c-BSA). Sprague-Dawley (SD) rats were divided into five groups, including normal control, model control, Mycophenolate Mofetil-treated group, and two skimming-treated groups (15 mg/kg and 30 mg/kg). Our research showed that treatment with skimmin significantly reduced the levels of blood urea nitrogen (BUN), urinary albumin excretion (UAE), and serum creatinine (Scr) as compared with model control after experimental induction of membranous glomerulonephritis (P < 0.01). Moreover, glomerular hypercellularity, tubulointerstitial injury, and glomerular deposition of IgG were less intense after skimmin treatment. By immunochemistry analysis, we demonstrated that skimmin could significantly inhibit interleukin-1β (IL1β) and IL-6 expression (P < 0.05), reduce the loss of nephrin and podocin, and suppress the infiltration of renal interstitium by CD3-positive T cell and CD20-positive B cell. These results suggest that treatment with skimmin can significantly improve renal function and suppress the IgG deposition as well as the development of glomerular lesions in a rat model of membranous glomerulonephritis. PMID:23990847

  10. Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem

    PubMed Central

    Golgert, William A.; Appel, Gerald B.; Hariharan, Sundaram

    2008-01-01

    Background and objectives: Despite advances in prevention of acute rejection and improved short- and long-term kidney graft survival, recurrent glomerulonephritis remains problematic and poorly characterized. This study analyzed prevalence and outcome of recurrent glomerulonephritis from various registries. Design, setting, participants, & measurements: Definition, classification, and limitations in evaluating epidemiology of native and recurrent glomerulonephritis are discussed. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. Results: Analysis of data from transplant registries revealed that glomerulonephritis is an important cause of end-stage renal disease in white and pediatric recipients; however, glomerulonephritis as the cause of end-stage renal disease is not characterized well in black recipients, and many of them are perhaps labeled to have hypertensive nephrosclerosis as the cause of renal disease without renal biopsy. A systematic approach toward urinalysis after transplantation and utility of immunofluorescence and electron microscopic examination of renal biopsy tissues will identify the true prevalence of recurrent glomerulonephritis. Data on recurrent glomerulonephritis should be compiled by either using registry analysis or pooling data from multiple centers. This will provide true data on prevalence and outcome and could potentially initiate translational research studies. Conclusions: The understanding of the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as to treat individual recurrent glomerulonephritis, which can enhance long-term graft survival. PMID:18272827

  11. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Suthar, K. S.; Trivedi, H. L.

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

  12. Effect of cyclosporin on immune complex deposition in murine glomerulonephritis.

    PubMed Central

    Quinn, D G; Fennell, J S; Sheils, O; Gaffney, E F; Feighery, C F

    1991-01-01

    Chronic glomerulonephritis (GN) was induced in N/M mice by daily injections of human serum albumin (HSA). The glomerular lesion was similar to that observed in human membranous GN and was characterized by intense mesangial and capillary loop immunofluorescent staining for HSA, IgG and C3. Electron microscopic examination revealed numerous electron-dense deposits in the mesangium and along the subepithelial side of the glomerular basement membrane, the latter deposits being associated with membranous spikes. Chronically injected mice that had been treated with cyclosporin (CsA) from Day 1 had different patterns of immune complex deposition. Mesangial deposition was apparently unaltered but no subepithelial deposits or spikes were evident. In addition, only two out of 21 HSA-injected mice which began CsA treatment on Day 21 had subepithelial deposits. There was no significant difference in serum levels of HSA-specific IgG between the three groups of mice. CsA treatment would therefore appear to ameliorate the immunopathology of antigen-induced glomerulonephritis in this model without affecting serum antibody levels, and may be of therapeutic value in the treatment of human membranous GN. Images Figure 1 Figure 2 Figure 3 PMID:1828056

  13. Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.

    PubMed

    Grove, P; Neale, P H; Peck, M; Schiller, B; Haas, M

    1998-01-01

    We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present. PMID:9556416

  14. Update on endocarditis-associated glomerulonephritis.

    PubMed

    Boils, Christie L; Nasr, Samih H; Walker, Patrick D; Couser, William G; Larsen, Christopher P

    2015-06-01

    Glomerulonephritis (GN) due to infective endocarditis (IE) is well documented, but most available data are based on old autopsy series. To update information, we now present the largest biopsy-based clinicopathologic series on IE-associated GN. The study group included 49 patients (male-to-female ratio of 3.5:1) with a mean age of 48 years. The most common presenting feature was acute kidney injury. Over half of the patients had no known prior cardiac abnormality. However, the most common comorbidities were cardiac valve disease (30%), intravenous drug use (29%), hepatitis C (20%), and diabetes (18%). The cardiac valve infected was tricuspid in 43%, mitral in 33%, and aortic in 29% of patients. The two most common infective bacteria were Staphylococcus (53%) and Streptococcus (23%). Hypocomplementemia was found in 56% of patients tested and ANCA antibody in 28%. The most common biopsy finding was necrotizing and crescentic GN (53%), followed by endocapillary proliferative GN (37%). C3 deposition was prominent in all cases, whereas IgG deposition was seen in <30% of cases. Most patients had immune deposits detectable by electron microscopy. Thus, IE-associated GN most commonly presents with AKI and complicates staphylococcal tricuspid valve infection. Contrary to infection-associated glomerulonephritis in general, the most common pattern of glomerular injury in IE-associated glomerulonephritis was necrotizing and crescentic glomerulonephritis. PMID:25607109

  15. Noncongophilic fibrillary glomerulonephritis in a cat.

    PubMed

    Cavana, P; Capucchio, M T; Bovero, A; Ripanti, D; Catalano, D; Scaglione, F E; Miller, J; Blunden, T; Farca, A M

    2008-05-01

    This report describes an uncommon case of nonamyloidotic fibrillary glomerulonephritis. A 5-year-old female European cat was presented with nephrotic syndrome. Serum biochemistry and urinalysis revealed a mild increase in cholesterol, low total protein, severe hypoalbuminemia, and high proteinuria with a high protein-to-creatinine ratio. An histologic examination revealed an interstitial nephritis and a diffuse glomerulonephritis, with multifocal thickening of the Bowman's capsule. Transmission electron microscopy showed widespread fibrillary deposits in the glomerular basement membrane and in the mesangium. These fibrils ranged between 18 and 26 nm in diameter and were Congo red negative, which allowed their differentiation from amyloid. Immunohistochemistry demonstrated expression for immunoglobulin M (IgM) and immunoglobulin G (IgG) within the mesangium. Renal deposits of Congo red-negative amyloid-like fibrils have been described in humans, horses, monkeys, and dogs. This is the first report of noncongophilic fibrillary glomerulopathy in a cat. PMID:18487491

  16. Atypical membranoproliferative glomerulonephritis in a cat.

    PubMed

    Inoue, K; Kami-ie, J; Ohtake, S; Wakui, S; Machida, S; Shirota, K

    2001-07-01

    Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals. PMID:11467485

  17. Proliferative glomerulonephritis with monoclonal immunoglobulin in renal allografts

    PubMed Central

    Al-Rabadi, Laith; Francis, Jean M.; Henderson, Joel; Ghai, Sandeep

    2015-01-01

    Glomerulopathy due to dysproteinemia can have a wide spectrum of pathologic and clinical features based on specific characteristics of the abnormal protein and the response induced within the parenchymal tissue. Monoclonal immunoglobulin G (IgG) deposition can manifest as a different glomerular disease. Proliferative glomerulonephritis (GN) with monoclonal IgG deposits (PGNMID) is a unique entity mimicking immune complex GN that does not conform to any of those subtypes. IgG monoclonal granular deposition in the glomeruli with a pattern similar to immune complex disease suggested by C3 and C1q deposition should prompt consideration of PGNMID. Literature is scarce in terms of recurrence of disease in renal allografts. In this article we present the clinical–pathologic features of three cases of PGNMID in the renal allograft showing the variable course and manifestation of the disease. PMID:26613031

  18. Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

    PubMed

    Song, Jingjing; Wang, Yingwu; Liu, Chungang; Huang, Yan; He, Liying; Cai, Xueying; Lu, Jiahui; Liu, Yan; Wang, Di

    2016-04-01

    Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent. PMID:27008597

  19. Post-infectious glomerulonephritis following infective endocarditis: Amenable to immunosuppression

    PubMed Central

    Mantan, M.; Sethi, G. R.; Batra, V. V.

    2013-01-01

    Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants. PMID:24049276

  20. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits

    PubMed Central

    Larsen, Christopher P; Messias, Nidia C; Walker, Patrick D; Fidler, Mary E; Cornell, Lynn D; Hernandez, Loren H; Alexander, Mariam P; Sethi, Sanjeev; Nasr, Samih H

    2015-01-01

    The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed. PMID:26154922

  1. [Immune complex glomerulonephritis associated with pulmonary tuberculosis].

    PubMed

    Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S

    1994-01-01

    A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes. PMID:7854090

  2. CCR6 Recruits Regulatory T Cells and Th17 Cells to the Kidney in Glomerulonephritis

    PubMed Central

    Turner, Jan-Eric; Paust, Hans-Joachim; Steinmetz, Oliver M.; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans-Willi; Tiegs, Gisa; Stahl, Rolf A.K.

    2010-01-01

    T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID:20299360

  3. Fibrillary glomerulonephritis masquerading as rapidly progressive glomerulonephritis with pseudo-linear glomerular basement membrane staining.

    PubMed

    El-Husseini, Amr; Aycinena, Juan-Carlos; George, Bennet; Jennings, Stuart; Cornea, Virgilius; Sawaya, B Peter

    2015-10-01

    Fibrillary glomerulonephritis (FGN) is a rare disorder with poor renal prognosis. It is a heterogeneous disease associated with significant risk of end-stage renal disease (ESRD). Its etiology and pathogenesis have not been clearly identified. We report a case of a patient presenting with hypertensive crisis, nephrotic range proteinuria, and rapidly progressive glomerulonephritis (RPGN). The kidney biopsy demonstrates crescentic GN on light microscopy (LM) and strong pseudo-linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G on immunofluorescence (IF), suggestive of anti-GBM disease. However, circulating anti-GBM antibodies were negative. Electron microscopy (EM) revealed fibrillary deposits in the GBM, confirming the diagnosis of FGN. Review of the literature revealed very few reported similar cases. It appears that severe hypertension and heavy proteinuria, while uncommon in anti-GBM disease, are consistent findings in RPGN form of FGN. PMID:26249548

  4. Rapidly progressive glomerulonephritis due to coexistent anti-glomerular basement membrane disease and fibrillary glomerulonephritis

    PubMed Central

    Cheungpasitporn, Wisit; Zacharek, Claudia C.; Fervenza, Fernando C.; Cornell, Lynn D.; Sethi, Sanjeev; Herrera Hernandez, Loren P.; Nasr, Samih H.; Alexander, Mariam P.

    2016-01-01

    Anti-glomerular basement membrane (anti-GBM) disease is a major cause of rapidly progressive glomerulonephritis (RPGN). On the other hand, fibrillary glomerulonephritis (GN) typically presents as proteinuria, hematuria and renal insufficiency, but rarely as RPGN. Without electron microscopy, the diagnosis of fibrillary GN can be missed. We report a 68-year-old white woman who presented with RPGN with kidney biopsy demonstrating diffuse crescentic GN on light microscopy. By immunofluorescence, there was bright linear staining of the GBMs and smudgy mesangial staining for immunoglobulin G, C3, and kappa and lambda light chain. Electron microscopy revealed fibrillary deposits in the GBM and mesangium. A serum test for anti-GBM antibody was positive. To our knowledge, this is the first report of coexistence of fibrillary GN in a patient with anti-GBM disease. Electron microscopy is critical to identify the coexistence of other GN in patients presenting with crescentic GN. PMID:26798468

  5. Cryoglobulinemic Glomerulonephritis as a Presentation of Atypical Post-Infectious Glomerulonephritis

    PubMed Central

    Boumitri, Christine; Haddad, Fady G.; Rondla, Chetana; El-Sayegh, Suzanne; El-Charabaty, Elie

    2016-01-01

    Post-infectious glomerulonephritis (PIGN) usually occurs within few days to weeks following an infection. Clinical presentation is variable, but in general, it is considered a benign entity with good prognosis. It rarely requires kidney biopsy to confirm the diagnosis. We present a case of a 55-year-old, previously healthy, male who presented for worsening shortness of breath, persistent cough, and right-sided pleuritic chest pain. Initial workup revealed a right exudative effusion with empyema. Hospital course was complicated by acute kidney injury requiring renal replacement therapy with a peak creatinine of 10.2 mg/dL from a baseline of 1.18 mg/dL. On kidney biopsy, findings were compatible with a diagnosis of cryoglobulinemic glomerulonephritis or an atypical form of PIGN. While a wide variety of histopathological findings on renal biopsies have been described to complement the usual diffuse proliferative glomerulonephritis pattern, cryoglobulinemic features with negative cryoglobulin have never been reported. Our case is unique not only by having an atypical histological presentation but also by meeting the criteria of atypical PIGN with persistent hypertension and microscopic hematuria. PMID:26668683

  6. Membranoproliferative glomerulonephritis in a young cat.

    PubMed

    Asano, Tomoko; Tsukamoto, Atsushi; Ohno, Koichi; Ogihara, Kikumi; Kamiie, Junichi; Shirota, Kinji

    2008-12-01

    A 9-month-old male Japanese domestic cat showed pleural effusion, ascites, azotemia, hypoproteinemia and severe proteinuria. Histopathology of the percutaneous renal biopsy specimen revealed that all glomeruli showed intense mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls, resulting in lobular accentuation of the glomerular tufts. Frequent duplication of the capillary walls was also observed. Immunostaining for alpha-smooth muscle actin distinctly revealed mesangial interposition. Diffuse global and linear deposition of C3 and IgG was observed mostly along the peripheral capillary loops. Electron microscopy confirmed frequent circumferential mesangial interposition and subendothelial dense-deposits in the glomerulus. The glomerular lesion was consistent with human membranoproliferative glomerulonephritis type I, and might be a rare case that developed at young age. PMID:19122409

  7. Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis

    PubMed Central

    Araki, Makoto; Matsubara, Takeshi; Abe, Hideharu; Torikoshi, Kazuo; Mima, Akira; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Arai, Hidenori; Doi, Toshio

    2016-01-01

    Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis. PMID:27492138

  8. Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis.

    PubMed

    Araki, Makoto; Matsubara, Takeshi; Abe, Hideharu; Torikoshi, Kazuo; Mima, Akira; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Arai, Hidenori; Doi, Toshio

    2016-01-01

    Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis. PMID:27492138

  9. A protective role for endothelial nitric oxide synthase in glomerulonephritis.

    PubMed

    Heeringa, Peter; Steenbergen, Eric; van Goor, Harry

    2002-03-01

    In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs, suggesting a pathophysiological role for NO in the disease process. Although NO potentially could have both toxic as well as protective effects, its exact role in the pathophysiology of GN is unclear and may depend on the NOS isoform generating NO. The protective effects of NO such as prevention of leukocyte and platelet activation and adhesion have been attributed to NO generated by endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS includes the demonstration of reduced eNOS expression in experimental models of GN as well as human biopsy specimens that is mostly likely due to endothelial cell necrosis. Reduced NO production in GN also may occur through reaction of NO with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL) system. Further evidence has been provided by the observation that in several experimental models of GN, glomerular injury is exacerbated following treatment with non-selective NO inhibitors. Finally, the development of GN is severely aggravated in mice lacking a functional gene for eNOS as compared to wild-type mice, providing direct support for a protective role of eNOS-derived NO in acute GN. PMID:11849432

  10. Pathogenic mechanism of acute post-streptococcal glomerulonephritis.

    PubMed

    Nordstrand, A; Norgren, M; Holm, S E

    1999-01-01

    Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease. PMID:10680980

  11. Murine Double Minute-2 Inhibition Ameliorates Established Crescentic Glomerulonephritis.

    PubMed

    Mulay, Shrikant R; Romoli, Simone; Desai, Jyaysi; Honarpisheh, Mohammad Mohsen; Kumar, Santhosh V; Anders, Hans-Joachim; Thomasova, Dana

    2016-06-01

    Rapidly progressive glomerulonephritis is characterized by glomerular necroinflammation and crescent formation. Its treatment includes unspecific and toxic agents; therefore, the identification of novel therapeutic targets is required. The E3-ubiquitin ligase murine double minute (MDM)-2 is a nonredundant element of NF-κB signaling and the negative regulator of tumor suppressor gene TP53-mediated cell cycle arrest and cell death. We hypothesized that the MDM2 would drive crescentic glomerulonephritis by NF-κB-dependent glomerular inflammation and by p53-dependent parietal epithelial cell hyperproliferation. Indeed, the pre-emptive MDM2 blockade by nutlin-3a ameliorated all aspects of crescentic glomerulonephritis. MDM2 inhibition had identical protective effects in Trp53-deficient mice, with the exception of crescent formation, which was not influenced by nutlin-3a treatment. In vitro experiments confirmed the contribution of MDM2 for induction of NF-κB-dependent cytokines in murine glomerular endothelial cells and for p53-dependent parietal epithelial cell proliferation. To evaluate MDM2 blockade as a potential therapeutic intervention in rapidly progressive glomerulonephritis, we treated mice with established glomerulonephritis with nutlin-3a. Delayed onset of nutlin-3a treatment was equally protective as the pre-emptive treatment in abrogating crescentic glomerulonephritis. Together, the pathogenic effects of MDM2 are twofold, that is, p53-independent NF-κB activation increasing intraglomerular inflammation and p53-dependent parietal epithelial cell hyperplasia and crescent formation. We therefore propose MDM2 blockade as a potential novel therapeutic strategy in rapidly progressive glomerulonephritis. PMID:27102769

  12. Haematuria on the Spanish Registry of Glomerulonephritis

    PubMed Central

    Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel

    2016-01-01

    Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria’s overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID:26818712

  13. Eculizumab and Recurrent C3 Glomerulonephritis

    PubMed Central

    Gurkan, Sevgi; Fyfe, Billie; Weiss, Lynne; Xiao, Xue; Zhang, Yuzhou; Smith, Richard J.

    2015-01-01

    Background and objectives Hyperactivity of the alternative complement pathway is the principle defect in the C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. Design, setting, participants & measurements In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of Dense Deposit Disease (DDD) and allograft recurrence of C3 (C3GN) glomerulonephritis was treated with eculizumab every-other-week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/d at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 months and 12 months. Results Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, during therapy it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. Conclusions Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of alternative pathway remained, showing that eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients. PMID:23689905

  14. siRNA-Based Therapy Ameliorates Glomerulonephritis

    PubMed Central

    Shimizu, Hideki; Hori, Yuichi; Kaname, Shinya; Yamada, Koei; Nishiyama, Nobuhiro; Matsumoto, Satoru; Miyata, Kanjiro; Oba, Makoto; Yamada, Akira; Kataoka, Kazunori

    2010-01-01

    RNA interference by short interfering RNAs (siRNAs) holds promise as a therapeutic strategy, but use of siRNAs in vivo remains limited. Here, we developed a system to target delivery of siRNAs to glomeruli via poly(ethylene glycol)-poly(l-lysine)-based vehicles. The siRNA/nanocarrier complex was approximately 10 to 20 nm in diameter, a size that would allow it to move across the fenestrated endothelium to access to the mesangium. After intraperitoneal injection of fluorescence-labeled siRNA/nanocarrier complexes, we detected siRNAs in the blood circulation for a prolonged time. Repeated intraperitoneal administration of a mitogen-activated protein kinase 1 (MAPK1) siRNA/nanocarrier complex suppressed glomerular MAPK1 mRNA and protein expression in a mouse model of glomerulonephritis; this improved kidney function, reduced proteinuria, and ameliorated glomerular sclerosis. Furthermore, this therapy reduced the expression of the profibrotic markers TGF-β1, plasminogen activator inhibitor-1, and fibronectin. In conclusion, we successfully silenced intraglomerular genes with siRNA using nanocarriers. This technique could aid the investigation of molecular mechanisms of renal disease and has potential as a molecular therapy of glomerular diseases. PMID:20203158

  15. Metabolic Syndrome in IgA Glomerulonephritis

    PubMed Central

    Kaartinen, Kati; Syrjänen, Jaana; Pörsti, Ilkka; Harmoinen, Aimo; Huhtala, Heini; Mustonen, Jukka

    2014-01-01

    Background/Aims Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Patients and Methods Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. Results The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. Conclusion The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable. PMID:25337083

  16. Partial lipodystrophy, C3 nephritic factor and clinically inapparent mesangiocapillary glomerulonephritis.

    PubMed

    Bennett, W M; Bardana, E J; Wuepper, K; Houghton, D; Border, W A; Götze, O; Schreiber, R

    1977-05-01

    A case of partial lipodystrophy with C3 nephritic factor was found to be associated with mesangiocapillary glomerulonephritis although all clinical parameters of renal function were normal. Diagnosis of mesangiocapillary glomerulonephritis required renal biopsy. Nephriti factor obtained from this patient was immunochemically related to nephritic factor isolated from the serum of patients with typical mesangiocapillary glomerulonephritis without partial lipodystrophy. PMID:860726

  17. Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate Restores Nrf2 Activity and Ameliorates Crescentic Glomerulonephritis

    PubMed Central

    Zhou, Jason K.; Peng, Ai; Vaziri, Nosratola D.; Mohan, Chandra; Xu, Yan; Zhou, Xin J.

    2015-01-01

    Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress. PMID:25785827

  18. Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

    MedlinePlus

    ... Articles | Inside Life Science Home Page An Experimental Contact Lens to Prevent Glaucoma-Induced Blindness By Sharon Reynolds Posted January 23, 2014 An experimental contact lens design releases a glaucoma medicine at a ...

  19. Fundus changes in mesangiocapillary glomerulonephritis type II: vitreous fluorophotometry.

    PubMed Central

    Raines, M F; Duvall-Young, J; Short, C D

    1989-01-01

    We have described a complex abnormality of retinal pigment epithelium, Bruch's membrane, and choriocapillaris in mesangiocapillary glomerulonephritis (MCGN) type II. Patients with MCGN type II were examined by vitreous fluorophotometry which reveals that there is a breakdown of the blood retinal barrier (BRB) in those patients with the typical fundus lesions. The function of this barrier was calculated as a penetration ratio and was statistically greater in these patients when compared with a group of (a) normal persons, (b) patients with drusen, and (c) patients with other forms of glomerulonephritis. Images PMID:2605145

  20. The role of Th1 and Th17 cells in glomerulonephritis

    PubMed Central

    Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2015-01-01

    Context: T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Evidence Acquisitions: Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Results: Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Conclusions: Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis. PMID:25964886

  1. IL-17 Expression in the Time Course of Acute Anti-Thy1 Glomerulonephritis

    PubMed Central

    Loof, Tanja; Krämer, Stephanie; Gaedeke, Jens; Neumayer, Hans-Hellmut; Peters, Harm

    2016-01-01

    Background Interleukin-17 (IL-17) is a new pro-inflammatory cytokine involved in immune response and inflammatory disease. The main source of IL-17 is a subset of CD4+ T-helper cells, but is also secreted by non-immune cells. The present study analyzes expression of IL-17 in the time course of acute anti-thy1 glomerulonephritis and the role of IL-17 as a potential link between inflammation and fibrosis. Methods Anti-thy1 glomerulonephritis was induced into male Wistar rats by OX-7 antibody injection. After that, samples were taken on days 1, 5, 10 (matrix expansion phase), 15 and 20 (resolution phase). PBS-injected animals served as controls. Proteinuria and histological matrixes score served as the main markers for disease severity. In in vitro experiments, NRK-52E cells were used. For cytokine expressions, mRNA and protein levels were analyzed by utilizing RT-PCR, in situ hybridization and immunofluorescence. Results Highest IL-17 mRNA-expression (6.50-fold vs. con; p<0.05) was found on day 5 after induction of anti-thy1 glomerulonephritis along the maximum levels of proteinuria (113 ± 13 mg/d; p<0.001), histological glomerular-matrix accumulation (82%; p<0.001) and TGF-β1 (2.2-fold; p<0.05), IL-6 mRNA expression (36-fold; p<0.05). IL-17 protein expression co-localized with the endothelial cell marker PECAM in immunofluorescence. In NRK-52E cells, co-administration of TGF-β1 and IL-6 synergistically up-regulated IL-17 mRNA 4986-fold (p<0.001). Conclusions The pro-inflammatory cytokine IL-17 is up-regulated in endothelial cells during the time course of acute anti-thy1 glomerulonephritis. In vitro, NRK-52E cells secrete IL-17 under pro-fibrotic and pro-inflammatory conditions. PMID:27243813

  2. Hydrocarbon exposure may cause glomerulonephritis and worsen renal function: evidence based on Hill's criteria for causality.

    PubMed

    Ravnskov, U

    2000-08-01

    Many observational and experimental studies point to hydrocarbon exposure as an important pathogenic factor in glomerulonephritis. The findings have made little impact on current concepts and patient care, possibly because the hypothesis of a direct causal effect of the exposure and the hypothesis that the exposure worsens renal function have not been considered separately. This review examines these two hypotheses using Hill's criteria for causality. The results from 14 cross-sectional, 18 case-control studies, two cohort studies, 15 experiments on laboratory animals and two on human beings together with many case reports satisfy all but one of Hill's criteria for both hypotheses. Of particular importance is the finding in the case-control and follow-up studies of an association between degree of exposure and stage of renal disease, and an inverse association between degree of exposure and renal function, indicating that the most important effect of hydrocarbon exposure is its effect on renal function. End-stage renal failure may be preventable in many patients with glomerulonephritis provided a possible exposure to toxic chemicals is discontinued. PMID:10924538

  3. An immune-complex glomerulonephritis of Chinook salmon, Oncorhynchus tshawytscha (Walbaum).

    PubMed

    Lumsden, J S; Russell, S; Huber, P; Wybourne, B A; Ostland, V E; Minamikawa, M; Ferguson, H W

    2008-12-01

    Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium.Severely affected glomeruli also had expansion of the mesangium and loss of capillaries,synechiae of the visceral and parietal epithelium and mild fibrosis of Bowmans capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish. PMID:18752546

  4. Experimental evaluation of earthquake induced relay chattering

    SciTech Connect

    Bandyopadhyay, K.; Hofmayer, C.; Shteyngart, S.

    1990-01-01

    An experimental evaluation of relay performance under vibratory environments is discussed in this paper. Single frequency excitation was used for most tests. Limited tests were performed with random multifrequency inputs. The capacity of each relay was established based on a two-millisecond chatter criterion. The experimental techniques are described and the effects of parameters in controlling the relay capacity levels are illustrated with test data. A wide variation of the capacity levels was observed due to the influence of parameters related to the design of the relay and nature of the input motion. 3 refs., 15 figs.

  5. Congenital syphilis and glomerulonephritis with evidence for immune pathogenesis

    PubMed Central

    Wiggelinkhuizen, J.; Kaschula, R. O. C.; Uys, C. J.; Kuijten, R. H.; Dale, J.

    1973-01-01

    In 3 infants with congenital syphilis the dominant clinical manifestation of syphilitic kidney disease was the nephrotic syndrome. Mesangioendothelial proliferation was present in 2 cases and mixed proliferative glomerulonephritis with crescent formation in the third. The severity of the clinical and histopathological abnormalities could be related to the apparent duration of the illness. In all 3 cases immune complex deposition could be shown within and along the epithelial aspect of the glomerular basement membrane on light, electron, and immunofluorescent microscopy. These features, together with a reduced total serum haemolytic complement, suggest an immune pathogenesis of the glomerulonephritis associated with early congenital syphilis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4267344

  6. Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane.

    PubMed

    Satoh, M; Hamilton, K J; Ajmani, A K; Dong, X; Wang, J; Kanwar, Y S; Reeves, W H

    1996-10-01

    BALB/c ByJ mice develop a lupus-like syndrome characterized by anti-nRNP/Sm and Su autoantibodies and immune complex glomerulonephritis after a single i.p. pristane injection. In contrast, mercuric chloride induces anti-fibrillarin Abs only in SJL and other H-2s mice, and not in BALB/c (H-2d) mice. In the present study, the specificities of autoantibodies induced by pristane and HgCl2 were compared in SJL and BALB/c mice to examine whether these strains are "programmed" to make different sets of autoantibodies in response to nonspecific immune stimulation. Unexpectedly, the predominant autoantibodies induced by pristane in SJL mice were neither those characteristic of HgCl2-treated SJL mice nor those associated with pristane-induced disease in BALB/c mice but, rather, anti-ribosomal P, another lupus-related specificity. The autoantibodies were strongly reactive with the C-terminal 22 amino acids of the ribosomal P2 protein, indicating that they exhibited similar fine specificities to anti-P Abs in human SLE and MRL/Ipr mice. Like BALB/c mice, pristane-treated SJL mice developed severe glomerulonephritis characterized by proteinuria, mesangial proliferation, and glomerular immune complex deposits. This is the first evidence that the induction of a lupus-like syndrome by pristane is not restricted to BALB/c mice. The predominance of anti-P Abs in SJL mice contrasts sharply with the predominance of anti-nRNP/Sm and Su, in pristane-treated BALB/c mice, even though the renal lesions were similar in both strains. The data suggest that H-2s does not program mice to produce anti-fibrillarin Abs in response to nonspecific immune stimulation, arguing that autoantibody induction by pristane involves Ag-specific mechanisms. PMID:8816434

  7. Properdin and C3 Proactivator: Alternate Pathway Components in Human Glomerulonephritis

    PubMed Central

    McLean, Robert H.; Michael, Alfred F.

    1973-01-01

    Serological and immunopathological studies of human glomerulonephritis have suggested that alternate pathways of activation of the third component of complement may be important in some forms of glomerulonephritis. We have investigated the role of two alternate pathway proteins, properdin and C3 proactivator, in 22 patients with chronic membranoproliferative glomerulonephritis, 21 patients with systemic lupus erythematosus, 20 patients with acute poststreptococcal glomerulonephritis, and 19 patients with other forms of renal disease. C3 (measured at β1A), properdin, and C3 proactivator were assayed by single radial immunodiffusion. In sera with low β1A (< 2 SD), mean properdin was most significantly decreased in patients with acute poststreptococcal glomerulonephritis but was also significantly decreased in chronic membranoproliferative glomerulonephritis and in untreated systemic lupus erythematosus. Properdin levels in other renal disease, acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis with normal β1A levels were not significantly different from normal. A positive correlation between β1A and properdin levels in individual sera was present in all diseases except systemic lupus erythematosus. Serum C3 proactivator was markedly decreased in active systemic lupus erythematosus and there was a positive correlation between β1A and C3 proactivator levels in systemic lupus erythematosus and other renal diseases but not acute poststreptococcal glomerulonephritis. Properdin in fresh sera from four patients with systemic lupus erythematosus and five with chronic membranoproliferative glomerulonephritis showed increased migration toward the cathode on immunoelectrophoresis, suggesting in vivo change of the properdin molecule. The observation of reduced serum levels of properdin and C3 proactivator and altered electrophoretic migration of properdin in some patients with glomerulonephritis provide new evidence for participation of these

  8. Neural correlates of experimentally induced flow experiences.

    PubMed

    Ulrich, Martin; Keller, Johannes; Hoenig, Klaus; Waller, Christiane; Grön, Georg

    2014-02-01

    Flow refers to a positive, activity-associated, subjective experience under conditions of a perceived fit between skills and task demands. Using functional magnetic resonance perfusion imaging, we investigated the neural correlates of flow in a sample of 27 human subjects. Experimentally, in the flow condition participants worked on mental arithmetic tasks at challenging task difficulty which was automatically and continuously adjusted to individuals' skill level. Experimental settings of "boredom" and "overload" served as comparison conditions. The experience of flow was associated with relative increases in neural activity in the left anterior inferior frontal gyrus (IFG) and the left putamen. Relative decreases in neural activity were observed in the medial prefrontal cortex (MPFC) and the amygdala (AMY). Subjective ratings of the flow experience were significantly associated with changes in neural activity in the IFG, AMY, and, with trend towards significance, in the MPFC. We conclude that neural activity changes in these brain regions reflect psychological processes that map on the characteristic features of flow: coding of increased outcome probability (putamen), deeper sense of cognitive control (IFG), decreased self-referential processing (MPFC), and decreased negative arousal (AMY). PMID:23959200

  9. Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children.

    PubMed

    Hattori, M; Kurayama, H; Koitabashi, Y

    2001-07-01

    Aretrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcome of antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in children. Thirty-four ANCA-seropositive Japanese pediatric patients with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis were identified. Of these, 3 cases associated with Wegener's granulomatosis were excluded because of the small sample size. Among the 31 patients studied, 10 had a diagnosis of necrotizing crescentic glomerulonephritis alone and 21 had microscopic polyangiitis. Females predominated (87%), and the median age at onset was 12 yr. Twenty-six patients received treatment with cyclophosphamide and corticosteroids, and five patients received treatment with corticosteroids alone; 84% of patients achieved remission, and 39% of responders relapsed in a median of 24 mo. ANCA titers correlated with response to treatment and disease activity, with some exceptions. Patients were followed for a median of 42 mo (range, 3 to 96 mo). Nine of 31 patients (29.0%) progressed to end-stage renal disease, 6 (19.4%) had reduced renal function, and 15 (48.4%) had normal renal function at the last observation. One patient (3.2%) died from cytomegalovirus infection 3 mo after initiation of therapy. Life-table analysis showed 75% renal survival at 39 mo. Patients who subsequently developed end-stage renal disease (n = 9) had significantly higher average peak serum creatinine levels and more chronic pathologic lesions at diagnosis compared with patients with favorable renal outcome (n = 15). In conclusion, our clinical experience suggests that the clinical disease spectrum of ANCA-associated glomerulonephritis is similar in pediatric and adult patients, but there is a female predominance in children. PMID:11423578

  10. Cerebral venous thrombosis in a patient with acute postinfectious glomerulonephritis.

    PubMed

    Morkhandikar, S; Priyamvada, P S; Srinivas, B H; Parameswaran, S

    2016-01-01

    Thrombosis of the cerebral venous sinuses (CVT) is described in nephrotic syndrome. A 13-year-old girl was admitted with acute post-infectious glomerulonephritis (APIGN). Subsequently she developed recurrent seizures with focal neurological deficits. On evaluation, she was found to have CVT. To the best of our knowledge, this is the first report of CVT in APIGN. Identifying this complication is imperative, as timely diagnosis and treatment could be lifesaving. PMID:27194837

  11. Experimental and analytical investigation of flow through rocket pump inducer

    NASA Technical Reports Server (NTRS)

    Lakshminarayana, B.

    1974-01-01

    The characteristics of a rocket pump inducer are discussed. The effect of the pumping requirements on the blade configuration is analyzed. The effects of viscosity on blade design were determined by tests of a four bladed inducer operated in air at a flow coefficient of 0.065. The fluid properties were measured at the exit of the inducer using conventional and hot wire probes. The experimental results and the method of predicting the outlet tangential velocity and head rise are discussed.

  12. Posterior segment findings in a patient with immunotactoid glomerulonephritis

    PubMed Central

    Gupta, Aditi; Prabhu, Rangarajan Venugopal; Patel, Amit K.; Sivaraj, Ramesh

    2015-01-01

    Purpose: To present a case with posterior segment findings in a patient with cloudy corneas secondary to immunotactoid glomerulonephritis (ITG). Methods: A 57-year-old female was known to have bilateral cloudy corneas diagnosed 12 years ago secondary to immunotactoid glomerulonephritis. Clinically, fundus examination was difficult to visualise due to the density of her corneal opacities. Results: B-scan ultrasound revealed significant retino-choroidal & non-inflammatory scleral thickening. The macula also showed signs of thickening in both eyes. Optical coherence tomography (OCT) showed thinning of the inner retinal layers and significant choroidal folds in both eyes. Electrodiagnostic tests (EDT) concluded loss of retinal ganglion cells with preservation of retinal function in both eyes. Conclusion: This case widens the spectrum of findings seen in patients diagnosed with Immunotactoid Glomerulonephritis and alerts us to undertake detailed posterior segment examination where possible. Ocular coherence tomography (OCT) and B-scan ultrasonography are important adjuvants to help assess the posterior segment in patients with corneal opacities secondary to ITG.

  13. Mast cell chymase in experimentally induced psoriasis.

    PubMed

    Suttle, Mireille-Maria; Harvima, Ilkka T

    2016-06-01

    Mast cell chymase can have a pro-inflammatory or an immunosuppressive function in psoriasis, but the outcome may depend on the level of chymase activity. Therefore, mast cells showing chymase activity (Chyact ) and immunoreactivity (Chyprot ) were studied during the Köbner reaction (0 days, 2 h, 1 day, 3 days and 7 days) of psoriasis induced by the tape-stripping technique. Also, the effect of recombinant human chymase (rh-chymase) or human LAD2 mast cells (LAD2) on the (3) H-thymidine uptake of psoriatic peripheral blood mononuclear cells (PBMC) or total T cells was studied. The Chyact /Chyprot ratio tended to be higher in all time-point biopsies in the Köbner-negative (n = 10) than -positive (n = 8) group (P = 0.073), although chymase activity decreased significantly at 2 h to 1 day only in the Köbner-negative group. rh-chymase (0.05-0.5 μg/mL) stimulated to a varying extent PBMC in eight out of nine cultures, but in all cultures 5 μg/mL rh-chymase turned the stimulation towards inhibition. The effect of rh-chymase on T cells varied from stimulation to inhibition, but in 11 of 15 cultures rh-chymase, at least at 5 μg/mL, produced a change to inhibition. In co-cultures, LAD2 inhibited PBMC in the absence of soybean trypsin inhibitor (SBTI). In the presence of SBTI, LAD2 stimulated PBMC in the majority of seven cultures. In summary, the psoriatic immunopathogenesis may be promoted at low, but controlled at high, activity status of chymase. PMID:26703925

  14. Experimental background due to particle induced gas desorption in RHIC

    SciTech Connect

    Zhang,S.Y.; Trbojevic, D.

    2008-08-10

    Beam-gas collision created experimental background, i.e., singles, has affected heavy ion and polarized proton operations in Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The gas molecules in interaction region are mainly caused by the electron induced gas desorption. and the electrons are produced from the beam induced electron multipacting, or called electron cloud. The background has a dependence on the usual electron cloud related parameters, such as the bunch intensity, bunch spacing, and the solenoid field. With the RHIC upgrade plan, the experimental background may become a luminosity limiting factor. Mitigations are discussed.

  15. Experimentally induced otitis and audiogenic seizure in the mouse.

    PubMed

    Niaussat, M M

    1977-04-15

    Audiogenic seizures can be induced in genetically non-susceptible 17-day-old mice (Rb/3 strain) with various results. Priming only induces 9% of seizures, auditory insulation 3,8%, while experimental otitis leads to 79%. The hypothesis concerning disuse supersensitivity subsequent to acoustic deprivation was not confirmed by the experiment. However, modification of acoustic transmission at middle ear level induced by otitis or ear physical damage during the maturation period, exposes the upper nervous centers to intense stimulation to which the reaction is a recruiting response. PMID:862735

  16. Proliferative Glomerulonephritis with Monoclonal IgG Deposits

    PubMed Central

    Satoskar, Anjali; Markowitz, Glen S.; Valeri, Anthony M.; Appel, Gerald B.; Stokes, Michael B.; Nadasdy, Tibor; D'Agati, Vivette D.

    2009-01-01

    Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3κ (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients. PMID:19470674

  17. Monoclonal gammopathy associated membranous glomerulonephritis: A rare entity

    PubMed Central

    Gowda, K. K.; Joshi, K.; Ramachandran, R.; Nada, R.

    2015-01-01

    A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia. PMID:25684873

  18. Fibrillary glomerulonephritis associated with limited scleroderma: a case report.

    PubMed

    Nakhoul, Georges N; Simon, James F

    2016-04-01

    Fibrillary glomerulonephritis (GN) is a rare glomerular disorder that has been associated with monoclonal gammopathies, malignancies, chronic infections, and autoimmune disorders. We present the case of a 56-year-old woman with limited-type scleroderma and remote discoid lupus, evaluated for dipstick positive hematuria and preserved kidney function. Serologies were negative. Kidney biopsy revealed fibrillary GN. Her renal function and proteinuria remain stable 4 years after her initial diagnosis. This case is unusual both in its presentation and evolution, but mostly because it is the first reported case of fibrillary GN in association with limited type scleroderma. PMID:26709524

  19. Membranoproliferative glomerulonephritis: the role for laser microdissection and mass spectrometry.

    PubMed

    Jain, Deepika; Green, Jamie A; Bastacky, Sheldon; Theis, Jason D; Sethi, Sanjeev

    2014-02-01

    Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy-associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection-mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy-related glomerulonephritis. PMID:24145022

  20. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    PubMed Central

    Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  1. Rituximab therapy for primary glomerulonephritis: Report on two cases

    PubMed Central

    Fabrizi, Fabrizio; Cresseri, Donata; Fogazzi, Giovanni B; Moroni, Gabriella; Passerini, Patrizia; Martin, Paul; Messa, Piergiorgio

    2015-01-01

    The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient (hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function (he became dialysis independent with serum creatinine going back to 1.6 mg/dL) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids. PMID:26301235

  2. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.

    PubMed

    Yeturi, Supraja; Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  3. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome

    PubMed Central

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-01-01

    Abstract Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function. Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5–12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old. We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7–33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy. Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  4. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  5. The Epidermal Growth Factor Receptor Promotes Glomerular Injury and Renal Failure in Rapidly Progressive Crescentic Glomerulonephritis; the Identification of Possible Therapy

    PubMed Central

    Bollée, Guillaume; Flamant, Martin; Schordan, Sandra; Fligny, Cécile; Rumpel, Elisabeth; Milon, Marine; Schordan, Eric; Sabaa, Nathalie; Vandermeersch, Sophie; Galaup, Ariane; Rodenas, Anita; Casal, Ibrahim; Sunnarborg, Susan W; Salant, David J; Kopp, Jeffrey B.; Threadgill, David W; Quaggin, Susan E; Dussaule, Jean-Claude; Germain, Stéphane; Mesnard, Laurent; Endlich, Karlhans; Boucheix, Claude; Belenfant, Xavier; Callard, Patrice; Endlich, Nicole; Tharaux, Pierre-Louis

    2011-01-01

    Rapidly progressive glomerulonephritis (RPGN) is a clinical a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern (“crescents”) with accumulation of T cells and macrophages, and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 days after the induction of experimental RPGN. This suggests that targeting the HB-EGF/EGFR pathway could also be beneficial for treatment of human RPGN. PMID:21946538

  6. PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

  7. Elastase-induced pulmonary emphysema: insights from experimental models.

    PubMed

    Antunes, Mariana A; Rocco, Patricia R M

    2011-12-01

    Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema. PMID:22159348

  8. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  9. Crescentic glomerulonephritis in a polar bear (Ursus maritimus).

    PubMed

    Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi

    2013-11-01

    Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits. PMID:23856758

  10. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-06-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  11. [Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

    PubMed

    Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

    2014-02-26

    Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist. PMID:24665657

  12. The nephrotic syndrome in a heifer due to glomerulonephritis.

    PubMed

    Wiseman, A; Spencer, A; Petrie, L

    1980-05-01

    An 18-month-old Friesian heifer, which was admitted in November with a history of weight loss, diarrhoea and submandibular oedema, was found to have an enlarged left kidney and a massive proteinuria. Laboratory investigations revealed that there was a marked hypoalbuminaemia and that the range and the proportions of the individual proteins in the urine were almost identical to those in the serum. Consequently, the nephrotic syndrome was diagnosed. On gross and histopathological examination of the kidneys, there was evidence of pyelonephritis. However, immunofluorescence studies revealed a striking diffuse deposition of immunoglobulin in a predominantly linear pattern along the glomerular basement membranes. Abnormalities of the basement membranes. Abnormalities of the basement membranes were seen on ultrastructural examination and evidence of a flomerular protein leak was detected but changes typical of immune-complex deposition were absent. The immunofluorescence findings suggested a diagnosis of glomerulonephritis mediated by antiglomerular basement membrane antibody. PMID:7414086

  13. White-blue pyelocalyceal cyst with hydrotic glomerulonephritis

    PubMed Central

    Chaurasia, Jai Kumar; Soni, Mayank; Ahmed, Murad; Naim, Mohammed

    2013-01-01

    A 5-month-old male infant presented with a 15 day history of distension of abdomen. On clinical examination, a soft lump was palpable in the left lumbar region. Radiological findings suggested an enlarged non-functional left kidney with ureteropelvic adhesive obstruction. The left renal mass was excised and submitted for histopathological examination. The excised renal mass was cystic with its wall partly white and partly blue. Gross and histopathological findings were diagnostic of a white-blue pyelocalyceal cyst with hydrotic glomerulonephritis. This entity needs to be differentiated from a large number of other cystic diseases of the kidney. Intrauterine screening and diagnosis may be significant for a possible early intrauterine uro-laparoscopic recanalisation of the pyeloureteral obstruction to save the affected kidney. PMID:24347451

  14. Experimentally induced rodent models of type 2 diabetes.

    PubMed

    Islam, Md Shahidul; Wilson, Rachel Dorothy

    2012-01-01

    Diabetes is one of the major global public health problems and is gradually getting worse particularly in developing nations where 95% of patients are suffering from type 2 diabetes (T2D). Animal models in diabetes research are very common where rodents are the best choice of use due to being smaller in size, easy to handle, omnivorous in nature, and non-wild tranquil behavior. Normally rodent models are classified into two major classes namely: (1) genetic or spontaneously induced models and (2) non-genetic or experimentally induced models. Non-genetic models are more popular compared to genetic models due to lower cost, wider availability, easier to induce diabetes, and of course easier to maintain compared to genetic models. A number of non-genetic models have been developed in last three decades for diabetes research including adult alloxan/streptozotocin (STZ) models, partial pancreatectomy model, high-fat (HF) diet-fed models, fructose-fed models, HF diet-fed STZ models, nicotinamide-STZ models, monosodium-glutamate (MSG) induced models, and intrauterine growth retardation (IUGR) models. A T2D model should have the all major pathogenesis of the disease usually found in humans; however, none of the above-mentioned models are without limitations. This chapter comparatively evaluates most of the experimentally induced rodent models of T2D with their limitations, advantages, disadvantages, and criticality of development in order to help diabetes research groups to more appropriately select the animal models to work on their specific research question. PMID:22893406

  15. The effect of experimentally-induced subacromial pain on proprioception.

    PubMed

    Sole, Gisela; Osborne, Hamish; Wassinger, Craig

    2015-02-01

    Shoulder injuries may be associated with proprioceptive deficits, however, it is unknown whether these changes are due to the experience of pain, tissue damage, or a combination of these. The aim of this study was to investigate the effect of experimentally-induced sub-acromial pain on proprioceptive variables. Sub-acromial pain was induced via hypertonic saline injection in 20 healthy participants. Passive joint replication (PJR) and threshold to detection of movement direction (TTDMD) were assessed with a Biodex System 3 Pro isokinetic dynamometer for baseline control, experimental pain and recovery control conditions with a starting position of 60° shoulder abduction. The target angle for PJR was 60° external rotation, starting from 40°. TTDMD was tested from a position of 20° external rotation. Repeated measures ANOVAs were used to determine differences between PJR absolute and variable errors and TTDMD for the control and experimental conditions. Pain was elicited with a median 7 on the Numeric Pain Rating Scale. TTDMD was significantly decreased for the experimental pain condition compared to baseline and recovery conditions (≈30%, P = 0.003). No significant differences were found for absolute (P = 0.152) and variable (P = 0.514) error for PJR. Movement sense was enhanced for the experimental sub-acromial pain condition, which may reflect protective effects of the central nervous system in response to the pain. Where decreased passive proprioception is observed in shoulders with injuries, these may be due to a combination of peripheral tissue injury and neural adaptations that differ from those due to acute pain. PMID:25261091

  16. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease: The utility of routine staining with immunoglobulin light chains

    PubMed Central

    Gowda, K. K.; Nada, R.; Ramachandran, R.; Joshi, K.; Tewari, R.; Kohli, H. S.; Jha, V.; Gupta, K. L.

    2015-01-01

    Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009–2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy. PMID:26664209

  17. [Aplastic anemia combined with an autoimmune disease (eosinophilic fasciitis or glomerulonephritis)].

    PubMed

    Stebler, C; Tichelli, A; Gratwohl, A; Dazzi, H; Nissen, C; Steiger, U; Speck, B

    1991-06-01

    We describe 3 patients with aplastic anemia and an autoimmune disease. Two had eosinophilic fasciitis and 1 glomerulonephritis. In all patients both diseases were successfully treated by immunosuppressive therapy. Pathophysiological aspects of this association are discussed. PMID:1857945

  18. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease: The utility of routine staining with immunoglobulin light chains.

    PubMed

    Gowda, K K; Nada, R; Ramachandran, R; Joshi, K; Tewari, R; Kohli, H S; Jha, V; Gupta, K L

    2015-01-01

    Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009-2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy. PMID:26664209

  19. Necrotizing ANCA-Positive Glomerulonephritis Secondary to Culture-Negative Endocarditis

    PubMed Central

    Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura

    2015-01-01

    Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786

  20. Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings.

    PubMed Central

    Duvall-Young, J; Short, C D; Raines, M F; Gokal, R; Lawler, W

    1989-01-01

    Previously we have demonstrated a deposit in Bruch's membrane in a single case of mesangiocapillary glomerulonephritis type II. We studied a group of patients with this disease and described extensive clinical and fluorescein angiographic abnormalities, which were in marked contrast to the findings in a group of patients with other forms of glomerulonephritis. This finding contributes to our understanding of the pathophysiology of the complex of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris. Images PMID:2605144

  1. [Hypertension and primary glomerulonephritis in adults. A study of 302 cases].

    PubMed

    Seba, A; Rayane, T; Kaci, L; Haddoum, F; Benabadji, M

    1997-08-01

    The purpose of the present work was to show the place of hypertension in primary glomerulonephritis in adults. Hypertension was defined as diastolic blood pressure above 90 mmHg and renal insufficiency as serum creatinine above 135 mc mol/L. Secondary glomerulonephritis was excluded. The study was performed in 302 patients with primary glomerulonephritis biopsied between March 1994 and March 1996. They were 183 males and 119 females, aged from 16 to 63 years (mean: 29.8 years). The incidence of hypertension at the time of admission was 46.6%: 141/302 cases. The only consideration of prolonged hypertension (excluded transient hypertension of acute nephritic syndrome) shows an incidence of 31.4%: 95/302 cases (table). Frequency of hypertension (HT) in different types of primary glomerulonephritis (GN): [table: see text] The histological types observed in these cases of hypertension were represented essentially by the proliferative lesions: 73% (72/95 cases) who were grouped mainly in proliferative glomerulonephritis postinfectious and IgA nephropathy. No proliferative lesions: 24% (23/95 cases) were especially represented by focal segmental sclerosis. Renal insufficiency noted in 69 cases on 95 hypertensions was probably the result of the parallel evolution of hypertension renal lesions and those belonging to these histologic types. In conclusion, this study shows a narrow correlation between the hypertension and proliferative glomerulonephritis in our young adults population. PMID:9404432

  2. Immediate effects of chocolate on experimentally induced mood states.

    PubMed

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress. PMID:17597253

  3. Ichnocarpus frutescens Ameliorates Experimentally Induced Convulsion in Rats

    PubMed Central

    Singh, Narendra Kumar; Laloo, Damiki; Garabadu, Debapriya; Singh, Tryambak Deo; Singh, Virendra Pratap

    2014-01-01

    The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF (100, 200, and 400 mg/kg, p.o.) was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of γ-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF (200–400 mg/kg, p.o.) protected the animals in all the behavioral models used. Pretreatment of MEIF (200–400 mg/kg, p.o.) and diazepam (1.0 mg/kg, i.p.) to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin (50 mg/kg, i.p.) reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens. PMID:27379268

  4. Experimental analysis of radiation- and streaming-induced microparticle acoustophoresis

    NASA Astrophysics Data System (ADS)

    Rossi, Massimiliano; Marin, Alvaro; Kähler, Christian J.; Augustsson, Per; Laurell, Thomas; Muller, Peter B.; Barnkob, Rune; Bruus, Henrik

    2012-11-01

    We present an experimental analysis of the acoustophoretic motion of microparticles suspended in a liquid-filled acoustofluidic microchannel. This analysis intends to provide an experimental validation and support to very recent numerical and analytical models of radiation- and streaming-induced microparticle acoustophoresis (see Muller et al., Lab Chip 12, in press, 2012). For the experiments, we used a suspension of water and spherical polystyrene particles in a straight microchannel with rectangular cross section, actuated in its 1.94-MHz resonance by means of a piezoelectric transducer. The particles were labeled with a fluorescent dye and their motion was observed using an epifluorescent microscope. For the analysis, the Astigmatism Particle Tracking Velocimetry (APTV) technique was used to measure the three-dimensional trajectories and velocities of the particles with high precision and resolution (Cierpka et al., Meas Sci Technol 22, 2011). The experiments were performed for different particle sizes, ranging from 0.5- μm particles, dominated by the Stokes drag force induced by the acoustic streaming of the flow, to 5- μm particles, dominated by the acoustic radiation force. The results agree well with the analytical and numerical predictions.

  5. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

    PubMed Central

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-01-01

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  6. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

    PubMed

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-05-10

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  7. The influence of experimentally induced pain on shoulder muscle activity.

    PubMed

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul; Krogsgaard, Michael R; Nørregaard, Jesper

    2009-04-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0 degrees -105 degrees) at a speed of approximately 120 degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load

  8. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  9. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.

    PubMed

    Ariza, L; Pagès, G; García-Lareu, B; Cobianchi, S; Otaegui, P J; Ruberte, J; Chillón, M; Navarro, X; Bosch, A

    2014-08-22

    Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy. PMID:24846610

  10. Expression of alternatively spliced fibronectin variants during remodeling in proliferative glomerulonephritis.

    PubMed Central

    Barnes, J. L.; Torres, E. S.; Mitchell, R. J.; Peters, J. H.

    1995-01-01

    Fibronectin (Fn) plays an important role in tissue remodeling during embryogenesis, wound repair, and vascular disease, and is thought to regulate cellular processes such as cell adhesion, migration, proliferation, and differentiation through specialized domains within the molecule. In addition, Fn can be alternatively spliced at three regions: extradomains EIIIA, EIIIB, and a variable segment V, potentially giving rise to functionally distinct variants of the molecule. We have previously shown a sequential expression of cellular Fn first by platelets, followed by macrophages, then mesangial cells in habu snake venom-induced proliferative glomerulonephritis (Am J Pathol 145: 585-597, 1994). These studies examined the cellular sources and glomerular localization of Fn in general but did not distinguish between the various alternatively spliced isoforms. In this study, we examine by in situ hybridization and immunohistochemistry the temporal expression and cellular sources of EIIIA, EIIIB, and V in a model of proliferation glomerulonephritis that has cell migration, proliferation, and extracellular matrix synthesis as features of tissue remodeling. Macrophages were the first cells to express Fn mRNA showing an EIIIA+, EIIIB-, and V95+ pattern beginning at 8 hours after habu snake venom injection. Migrating mesangial cells at the margins of early lesions (8 and 24 hours) did not overexpress mRNA encoding these Fn variants, but immunofluorescence microscopy revealed V95 and EIIIA protein at the margins of lesions. EIIIB was absent in lesions at this time. At 48 hours and peaking at 72 hours after habu snake venom injection, mesangial cells in central aspects of glomerular lesions expressed abundant mRNA and protein for V95 and EIIIA. EIIIB mRNA and protein was slight in the mesangium at these times. Parietal epithelial cells, particularly adjacent to glomerular lesions, also expressed abundant mRNA and protein for all three variants throughout the course of the disease

  11. Expression of AIM2 is high and correlated with inflammation in hepatitis B virus associated glomerulonephritis

    PubMed Central

    2013-01-01

    Background & aims Innate immunity is the first line of defense against invasive microbial infection, and AIM2 plays an important role in this process by sensing double-stranded DNA viruses. However, the role of AIM2 in regulating the immune response to viruses in vivo, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of AIM2 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we analyzed the expression of AIM2 in HBV-GN patients in relation to the inflammatory response to HBV infection. Methods A total of 79 patients diagnosed with chronic nephritis (CN) were enrolled in this study, including 54 HBV-GN patients as the experimental group and 24 chronic glomerulonephritis (CGN) patients as the negative control group. Six patients diagnosed with chronic hepatitis B (CHB) were also enrolled as positive controls. Each CN patient received renal biopsy, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1 and IL-1β in the biopsy specimens. CHB patients received liver puncture biopsy, and immunohistochemistry was used to detect the expression of AIM2 in these specimens. Expression of AIM 2 among different groups and in relation to inflammatory factors caspase-1 and IL-1β was analyzed. Results The expression of AIM2 in HBV-GN patients (81.4%) was significantly higher than in CGN patients (4.0%). Among the HBV-GN patients, expression of AIM2 was significantly higher in the high HBV replication group than in the low HBV replication group. AIM2 expression was not correlated with age, gender, HBeAg status in serum, HBV-antigen type deposited in renal tissue or pathological type of HBV-GN. However, AIM2 levels were positively correlated with the expression of caspase-1 and IL-1β in HBV-GN patients

  12. CXCR3 Is Involved in Tubulointerstitial Injury in Human Glomerulonephritis

    PubMed Central

    Segerer, Stephan; Banas, Bernhard; Wörnle, Markus; Schmid, Holger; Cohen, Clemens D.; Kretzler, Matthias; Mack, Matthias; Kiss, Eva; Nelson, Peter J.; Schlöndorff, Detlef; Gröne, Hermann-Josef

    2004-01-01

    Chemokines play pivotal roles in the recruitment of inflammatory cells into the kidney. The chemokine receptors CXCR3 and CCR5 are expressed on activated T lymphocytes, and expression of CXCR3 by mesangial cells has been suggested. Detailed description of CXCR3 expression might form a rational basis for use as a diagnostic marker and for therapeutic CXCR3 targeting in human glomerulonephritis. We studied the expression of CXCR3 in renal biopsies by immunohistochemistry (n = 45), and real time RT-PCR (n = 78). Biopsies were from patients with IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. Furthermore, cultured human mesangial cells (HMC) were studied for CXCR3 expression, and for functional responses to the ligands CXCL10/IP-10 and CXCL9/Mig. CXCR3-positive cells were rarely found in glomerular tufts, but formed a major part of the tubulointerstitial infiltrates. Consistently, CXCR3 mRNA expression was too low to be quantified in glomerular compartments, and was not detectable in HMC. The published staining for CXCR3 of mesangial cells could be traced to cross-reactivity of an antibody for CXCR3 with a potentially related chemokine receptor as revealed by FACS analysis. Despite an absence of CXCR3 expression, mesangial cells reacted to CXCR3 ligands by proliferation and migration, which was blocked by pertussis toxin but not by an anti-CXCR3 antibody. These results indicate that HMC do not express the classical CXCR3, but may potentially express a related receptor with shared ligand specificity. By immunohistochemistry the number of CXCR3-positive cells, mainly interstitial T cells, correlated with renal function, proteinuria, and percentage of globally sclerosed glomeruli. A significant morphological and numerical correlation between CD3, CXCR3, and CCR5-positive cells indicated a CXCR3/CCR5 double-positive T cell population. No apparent difference in the CXCR3 expression pattern was found between disease entities. CXCR3 expression

  13. Mechanisms of blast induced brain injuries, experimental studies in rats.

    PubMed

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. PMID:20493951

  14. Numerical and Experimental Investigations of Tsunami-Induced Sediment Transport

    NASA Astrophysics Data System (ADS)

    Young, Y.; Xiao, H.

    2007-05-01

    As demonstrated by the 2004 Indian Ocean Tsunami, high intensity wave runup and drawdown can mobilize substantial amount of sediment deposits. The resulting erosion and scour damage can undermine building foundations, roadways, sea walls, embankments, and may even lead to eventual collapse of the coastal structure. However, most previous models ignore the effect of tsunami-induced sediment transport and scour due to the complex physics and multiple scaling issues. In this work, a numerical model is presented for the simulation of solitary waves over a uniform sloped movable bed. The depth averaged nonlinear shallow water equations (SWEs) are used to model long waves, the wave profile gradient method is used to detect wave breaking, and the effect of energy-dissipation due to wave breaking is captured as a bore collapse. The effect of sediment transport is modeled via a passive scalar and is fully coupled with the SWEs to form a complete system. New forms of the erosion and deposition fluxes are introduced to account for the effect of the flow velocity, particle fall velocity, wave profile, and pore pressure gradient. The model is validated by comparing the numerical solutions to the measured bed changes obtained from the cross-shore sediment transport experiment under breaking solitary waves conducted by (Kobayashi & Lawrence 2004). To further validate the numerical model, two sets of experimental studies are planned for 2007. The first experimental study focuses on the effect of enhanced transport due to pore pressure gradients, and will be conducted at the 30-ft long flume in the hydraulics lab at the University of Hawaii using multiple grain sizes. The second experimental study focuses on tsunami-induced sediment transport, and will be conducted at the 160-ft long tsunami wave basin at Oregon State University using fine Oregon beach sand with D50=0.20mm. The experimental setups are shown, and scaling issues for the two movable bed physical models are discussed

  15. Glomerulonephritis in a ferret with feline coronavirus infection.

    PubMed

    Fujii, Yuta; Tochitani, Tomoaki; Kouchi, Mami; Matsumoto, Izumi; Yamada, Toru; Funabashi, Hitoshi

    2015-09-01

    A male domestic ferret (Mustela putorius furo), which was purchased from outside of Japan at 13 weeks of age, was euthanized at 18 months of age because of poor health. At autopsy, the liver, spleen, and mesenteric lymph node were enlarged, and white foci were observed on the outer surface of the liver. The outer surface of the mesenteric lymph node was dark red. Histologically, granulomas were observed in the liver, spleen, bone marrow, and lymph nodes, composed mainly of aggregated epithelioid macrophages, some of which were positive to an anti-feline coronavirus (FCoV; Alphacoronavirus 1) antibody in immunohistochemistry. Mesangioproliferative glomerulonephritis was observed, and periodic acid-Schiff-positive deposits were observed along glomerular capillary walls. These deposits stained pale red with periodic acid-methenamine silver stain and red with Masson trichrome stain, and were also observed in the mesangial matrix. In affected glomeruli, glomerular capillary walls and mesangial areas were positive for anti-ferret immunoglobulin G. By electron microscopy, subepithelial and mesangial electron-dense deposits were observed consistent with immune complex deposition. The deposition of immune complexes may have been associated with FCoV infection. PMID:26319601

  16. Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis.

    PubMed

    Anand, Ananya; Krishna, Gopal G; Sibley, Richard K; Kambham, Neeraja

    2015-09-01

    We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma. PMID:25661680

  17. What is new in the management of rapidly progressive glomerulonephritis?

    PubMed

    Greenhall, George H B; Salama, Alan D

    2015-04-01

    Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease. In addition, reporting bias results in publication of cases or cohorts showing benefit for newer agents in advanced disease or RPGN, but it remains unclear how many unsuccessful outcomes in these circumstances take place. Since clinical trials specifically in RPGN are unlikely, use of biologic registries or combination of sufficient sized cohort series may provide indications of benefit outside of a clinical trial setting and should be encouraged, in order to provide some evidence for the efficacy of therapeutic regimens in RPGN and advanced renal disease. PMID:25815169

  18. De novo C3 glomerulonephritis in a renal allograft.

    PubMed

    Nahm, Ji Hae; Song, Seung Hwan; Kim, Yu Seun; Cheong, Hae-Il; Lim, Beom Jin; Kim, Beom Seok; Jeong, Hyeon Joo

    2016-01-01

    C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident. PMID:26986539

  19. Foraminiferal survival after long term experimentally induced anoxia

    NASA Astrophysics Data System (ADS)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  20. Pentamidine-induced dysglycaemia: experimental models in the rat.

    PubMed

    Assan, R; Assan, D; Delaby, J; Debussche, X; Toublanc, M

    1993-01-01

    In order to analyse further the pathophysiology of pentamidine effects on blood glucose regulation, the following experimental models were established in rats: impairment of the renal function, bile duct ligation, inhibition of the P450 cytochrome enzyme system. In otherwise intact rats, 7.5 mg/day pentamidine was well tolerated whereas doses of 15 mg/day induced severe, relapsing and eventually lethal hypoglycaemia within a few days. Induction of a renal insufficiency of graded severity by treatment with gentamycin, subtotal nephrectomy and total bilateral nephrectomy resulted in repetitive, severe (sometimes lethal) hypoglycaemia, alternating with hyperglycaemia, glucosuria and ketonuria in pentamidine-treated rats (7.5 mg/d). No long-standing insulin-dependent diabetes was observed. In the dysglycemic animals, plasma insulin levels were inappropriate to the concomitant glycaemia; no stimulation was obtained by i.v. glucose. Glucagon levels were higher than normal, suppressible by i.v. glucose, responsive to IV arginine and to hypoglycaemia. Dysglycemic events were more frequent and marked in the rats with the most severe renal functional derangement. They were more frequent in the rats treated with pentamidine mesylate than in those treated with the isethionate salt. Control uremic rats (free of pentamidine) remained euglycaemic. The islets of Langerhans displayed severe vascular congestion and degranulation and necrosis of the B cells, while the non B cells (and particularly the A cells) were intact. Exocrine pancreatitis was occasionally observed in the most severely uremic rats. In contrast with uremic rats, neither surgical ligation of choledocus, nor treatment by P450 cytochrome inhibitors (particularly ketoconazole) precipitated dysglycaemia in the pentamidine-treated rats. These experimental data: 1) strengthen the concept of inappropriate insulin release from pentamidine-lesioned islet B cells due to pentamidine accumulation; 2) indicate a predominant

  1. Glomerulonephritis associated with arteritis in marmosets infected with hepatitis A virus.

    PubMed Central

    Morita, M.; Kitajima, K.; Yoshizawa, H.; Itoh, Y.; Iwakiri, S.; Shibata, C.; Mayumi, M.

    1981-01-01

    Seven of 8 marmosets (Saguinus oedipus and Saguinus labiatus) injected i.v. with different inocula of hepatitis A virus isolated from patients in the acute phase of disease developed proliferative glomerulonephritis associated with arteritis. The glomerulonephritis was characterized by immunofluorescent and electron-dense deposits and hypercellularity. Although no antigenic component of the glomerular immune complex was detected, this glomerulonephritis and arteritis may be diagnosed morphologically as an immune complex disease. These findings show the possibility of the appearance of exohepatic disease as an immunologically mediated disease in human hepatitis A virus infection. Images Figs. 2-5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Figs. 10-15 Figs. 16-18 PMID:6452891

  2. Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies.

    PubMed

    Lionaki, Sophia; Gakiopoulou, Hara; Boletis, John N

    2016-09-01

    An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies. PMID:27356907

  3. Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis.

    PubMed

    Luo, Y-H; Kuo, C-F; Huang, K-J; Wu, J-J; Lei, H-Y; Lin, M T; Chuang, W-J; Liu, C-C; Lin, C-F; Lin, Y-S

    2007-09-01

    Streptococcal pyrogenic exotoxin B is an extracellular cysteine protease. Only nephritis-associated strains of group A streptococci secrete this protease and this may be involved in the pathogenesis of post-streptococcal glomerulonephritis. Mice were actively immunized with a recombinant protease inactive exotoxin B mutant or passively immunized with exotoxin B antibody. Characteristics of glomerulonephritis were measured using histology, immunoglobulin deposition, complement activation, cell infiltration, and proteinuria. None of the mice given bovine serum albumin or exotoxin A as controls showed any marked changes. Immunoglobulin deposition, complement activation, and leukocyte infiltration occurred only in the glomeruli of exotoxin B-hyperimmunized mice. One particular anti-exotoxin B monoclonal antibody, 10G, was cross-reactive with kidney endothelial cells and it caused kidney injury and proteinuria when infused into mice. This cross-reactivity may be involved in the pathogenesis of glomerulonephritis following group A streptococcal infection. PMID:17637712

  4. [The function of the hypophyseal-gonadal system in different variants of glomerulonephritis in children].

    PubMed

    Korovina, N A; Gavriushova, L P; Ametov, A S; Tvorogova, T M; Mumladze, E B; Toritsina, L K

    1990-01-01

    A total of 28 children with different varieties of glomerulonephritis were examined for the pituitary-gonadal system (PGS). The examination included measurements of follicle-stimulating and luteinizing hormones, prolactin, estradiol, progesterone and testosterone. To define standards of the content of the hormones under study, 45 children of the control group were examined. The relationship was analyzed between the content of hormones and the disease activity and gravity. The most active phase of glomerulonephritis was characterized by maximal alterations in the content of pituitary and gonadal hormones. The content of the latter ones appeared to be considerably changed in patients with the mixed pattern of glomerulonephritis, attesting to profound functional derangements in the PGS. The intensity of those derangements was determined by the severity of the pathological process. PMID:2259596

  5. The Effects of Experimentally Induced Adelphophagy in Gastropod Embryos

    PubMed Central

    Thomsen, Olaf; Collin, Rachel; Carrillo-Baltodano, Allan

    2014-01-01

    Adelphophagy, development where embryos grow large by consuming morphologically distinct nutritive embryos or their own normal siblings is widespread but uncommon among animal phyla. Among invertebrates it is particularly common in some families of marine gastropods and segmented worms, but rare or unknown in other closely related families. In calyptraeid gastropods phylogenetic analysis indicates that adelphophagy has arisen at least 9 times from species with planktotrophic larval development. This pattern of frequent parallel evolution of adelphophagy suggests that the embryos of planktotrophic species might be predisposed to evolve adelphophagy. Here we used embryos of three species of planktotrophic calyptraeids, one from each of three major genera in the family (Bostrycapulus, Crucibulum, and Crepidula), to answer the following 3 questions: (1) Can embryos of species with planktotrophic development benefit, in terms of pre-hatching growth, from the ingestion of yolk and tissue from experimentally damaged siblings? (2) Does ingestion of this material from damaged siblings increase variation in pre-hatching size? and (3) Does this experimentally induced adelphophagy alter the allometry between the velum and the shell, increasing morphological similarity to embryos of normally adelphophagic species? We found an overall increase in shell length and velum diameter when embryos feed on damaged siblings within their capsules. There was no detectable increase in variation in shell length or velum diameter, or changes in allometry. The overall effect of our treatment was small compared to the embryonic growth observed in naturally adelphophagic development. However each embryo in our experiment probably consumed less than one sibling on average, whereas natural adelphophages often each consume 10–30 or more siblings. These results suggest that the ability to consume, assimilate, and benefit from yolk and tissue of their siblings is widespread across calyptraeids

  6. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis.

    PubMed

    Kanojia, Deepak; Vaidya, Milind M

    2006-08-01

    Human oral cancer is the sixth largest group of malignancies worldwide and single largest group of malignancies in the Indian subcontinent. Seventy percent of premalignant cancers appear from premalignant lesions. Only 8-10% of these lesions finally turn into malignancy. The appearance of these premalignant lesions is one distinct feature of human oral cancer. At present there is dearth of biomarkers to identify which of these lesions will turn into malignancy. Regional lymph node metastasis and locoregional recurrence are the major factors responsible for the limited survival of patients with oral cancer. Paucity of early diagnostic and prognostic markers is one of the contributory factors for higher mortality rates. Cancer is a multistep process and because of constrain in availability of human tissues from multiple stages of oral carcinogenesis including normal tissues, animal models are being widely used, aiming for the development of diagnostic and prognostic markers. A number of chemical carcinogens like coal tar, 20 methyl cholanthrene (20MC), 9,10-dimethyl-1,2-benzanthracene (DMBA) and 4-nitroquinoline-1-oxide (4NQO) have been used in experimental oral carcinogenesis. However, 4NQO is the preferred carcinogen apart from DMBA in the development of experimental oral carcinogenesis. 4NQO is a water soluble carcinogen, which induces tumors predominantly in the oral cavity. It produces all the stages of oral carcinogenesis and several lines of evidences suggest that similar histological as well as molecular changes are observed in the human system. In the present review an attempt has been made to collate the information available on mechanisms of action of 4NQO, studies carried out for the development of biomarkers and chemopreventives agents using 4NQO animal models. PMID:16448841

  7. Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis.

    PubMed

    Luo, Bangwei; Jiang, Man; Yang, Xiaofeng; Zhang, Zhiyuan; Xiong, Jian; Schluesener, Hermann J; Zhang, Zhiren; Wu, Yuzhang

    2013-08-01

    Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1α (HIF-1α), HIF-2α, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods. Further, the deactivation of HIF reduced EAN-induced EPO/EPOR upregulation in EAN, suggesting the central contribution of HIF to EPO/EPOR induction. The deactivation of EPOR signalling exacerbated EAN progression, implying that endogenous EPO contributed to EAN recovery. Exogenous EPO treatment greatly improved EAN recovery. In addition, EPO was shown to promote Schwann cell survival and myelin production. In EAN, EPO treatment inhibited lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3(+)/CD4(+) regulatory T cells and decrease of IFN-γ(+)/CD4(+) Th1 cells. Furthermore, EPO inhibited inflammatory macrophage activation and promoted its phagocytic activity. In summary, our data demonstrated that EPO was induced in EAN by HIF and contributed to EAN recovery, and endogenous and exogenous EPO could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that EPO contributes to the self-recovery of EAN and could be a potent candidate for treatment of autoimmune neuropathies. PMID:23603807

  8. The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

    NASA Astrophysics Data System (ADS)

    Malatesta, M.

    The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

  9. Confabulation versus experimentally induced false memories in Korsakoff patients.

    PubMed

    Van Damme, Ilse; d'Ydewalle, Géry

    2010-09-01

    The present study focuses on both the clinical symptom of confabulation and experimentally induced false memories in patients suffering from Korsakoff's syndrome. Despite the vast amount of case studies of confabulating patients and studies investigating false memories in the Deese-Roediger-McDermott (DRM) paradigm, the nature of Korsakoff patients' confabulatory behaviour and its association with DRM false memories have been rarely examined. Hence, the first aim of the present study was to evaluate confabulatory responses in a large sample of chronic Korsakoff patients and matched controls by means of the Dalla Barba Confabulation Battery. Second, the association between (provoked) confabulation and the patients' DRM false recognition performance was investigated. Korsakoff patients mainly confabulated in response to questions about episodic memory and questions to which the answer was unknown. A positive association was obtained between confabulation and the tendency to accept unstudied distractor words as being old in the DRM paradigm. On the other hand, there was a negative association between confabulation and false recognition of critical lures. The latter could be attributed to the importance of strategic retrieval at delayed memory testing. PMID:19930792

  10. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats

    PubMed Central

    Kraemer, Bernhard; Wallwiener, Christian; Rajab, Taufiek K.; Brochhausen, Christoph; Wallwiener, Markus; Rothmund, Ralf

    2014-01-01

    Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P < 0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P < 0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P < 0.05) and group 4 (47%) (P < 0.05). There was no difference between group 3 (60%) and group 6 (P = 0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models. PMID:24809049

  11. Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.

    PubMed

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J; Sun, Deming

    2016-03-15

    Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies. PMID:26856700

  12. Albendazole therapy for experimentally induced Paragonimus kellicotti infection in cats.

    PubMed

    Dubey, J P; Hoover, E A; Stromberg, P C; Toussant, M J

    1978-06-01

    The effect of albendazole therapy was studied in 6 cats with pulmonary paragonimiasis induced by experimental inoculation of metacercariae (25/cat) of Paragonimus kellicotti. At 76 to 101 days after they were inoculated, 5 cats were administered an oral aqueous suspension of albendazole in 2 divided doses totaling 20 mg (2 cats), 50 mg (1 cat), or 100 mg (2 cats)/kg of body weight each day for 14 to 21 days. The 6th cat (control) was not administered albendazole. Nine days after cats were given the 50- and 100-mg/kg dosages, Paragonimus ova were not seen in the feces of 3 cats. There was marked reduction in ova production in the feces of the 2 cats administered 20 mg/kg of albendazole. Live flukes were not recovered from the lungs of 3 cats necropsied 4 or 5 weeks after dosing with 50 or 100 mg/kg, but the lungs of the 2 cats administered 20 mg of albendazole/kg yielded 9 and 7 apparently viable flukes. Seventeen live flukes were recovered from the control cat not treated with albendazole. In 4 noninoculated normal cats administered 20 mg (1 cat), 100 mg (1 cat), and 200 mg (2 cats) of albendazole/kg of body weight each day for 14 days, there were no gross or microscopic lesions attributable to the drug. PMID:666077

  13. Preferential effectiveness of cyclosporin in patients receiving kidney transplants after glomerulonephritis.

    PubMed

    Cats, S; Terasaki, P I; Perdue, S; Mickey, M R

    1985-03-01

    Glomerulonephritis patients transplanted with cadaver kidneys had a significantly higher one-year graft survival when immunosuppressed with cyclosporin rather than standard therapy (80% versus 59%, p less than 10(-5]. For nephrosclerosis patients the corresponding rates were 70% and 59% (p greater than 0.05); and in those with antecedent diabetes mellitus, polycystic kidney, and pyelonephritis the differences were negligible. In glomerulonephritis patients, but not in the other groups, cyclosporin was additive to the effect of transfusions and of HLA-A, B and HLA-Dr matching. PMID:2857855

  14. Protracted Clinical Course of Postinfectious Glomerulonephritis in a Previously Healthy Child

    PubMed Central

    Grøndahl, Camilla; Rittig, Søren; Povlsen, Johan Vestergaard; Kamperis, Kostantinos

    2016-01-01

    Acute postinfectious glomerulonephritis (PIGN) affects children typically after upper respiratory tract or skin infections with streptococci but can complicate the course of other infections. In children, it is generally a self-limiting disease with excellent prognosis. This paper reports a previously healthy 4-year-old boy who experienced a protracted course of PIGN with persisting episodes of gross haematuria, proteinuria, decreased complement C3c levels but normal P-creatinine levels. Due to the protracted course and the nephrotic-range proteinuria, a renal biopsy was performed 6 months after the initial presentation and the overall pathology was consistent with acute endocapillary glomerulonephritis. PMID:27226969

  15. Streptococcal Infection-related Nephritis (SIRN) Manifesting Membranoproliferative Glomerulonephritis Type I.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Yamamoto, Yasutaka; Kobayashi, Naoto; Oda, Takashi; Yamaguchi, Yutaka; Shibata, Takanori

    2016-01-01

    We herein report the case of an 18-year-old boy who developed nephrotic syndrome and hypertension after upper airway inflammation. Post-streptococcal acute glomerulonephritis was diagnosed on the basis of a high antistreptolysin O titer, hypocomplementemia, proteinuria, and microscopic hematuria. A renal biopsy was performed due to persistent proteinuria, and the pathological diagnosis was membranoproliferative glomerulonephritis (MPGN) type I. Glomeruli showed positive staining for nephritis-associated plasmin receptor (NAPlr), a nephritogenic group A streptococcal antigen, and plasmin activity was found in a similar distribution as NAPlr deposition. This rare case of streptococcal infection-related nephritis (SIRN) manifesting MPGN type I supports the histological diversity of SIRN. PMID:26984084

  16. Anticoccidial effect of mananoligosacharide against experimentally induced coccidiosis in broiler.

    PubMed

    Chand, Naila; Faheem, Hassan; Khan, Rifat Ullah; Qureshi, Muhammad Subhan; Alhidary, Ibrahim A; Abudabos, Alaeldein M

    2016-07-01

    The aim of this study was to find the effect of mananoligosacharide (MOS) in comparison with amprolium hydrochloride on performance and integrity of gut in experimentally induced coccidiosis in broiler. A total of 300, day-old male broiler chickens (Ross 308) was randomly allocated to four treatments. Each group was further divided into five replicates of 15 birds each. Group A was kept as control; group B was contaminated with Eimeria tenella, while groups C and D were infected with E. tenella and treated with MOS (0.8 g/kg feed) and anticoccidial drug, amprolium hydrochloride (12 g/100 l water), respectively. The results showed that weight gain, feed intake, and feed conversion ratio (FCR) were significantly higher (P < 0.05) in infected + MOS-treated group compared to the other groups. The result of oocyte per gram (OPG) was significantly higher (P < 0.05) in the group infected with coccidiosis during 5th, 7th, 10th, and 12th day post infection (dpi). Furthermore, the OPG was significantly lower (P < 0.05) in infected groups treated with MOS and amprolium at the studied periods (5, 7, and 10 dpi). At 12 dpi, the infected group treated with MOS showed significantly lower OPG compared to the other groups suggesting the effectiveness of MOS in comparison to amprolium. The result of pinpoint hemorrhages, thickness of cecal wall, bloody fecal contents, and mucoid contents in the cecum were significant highly (P < 0.05) in birds fed with infected oocytes. It was also noted that the differences were not significant in these parameters between amprolium and MOS-treated birds showing the effectiveness of the prebiotic agent. It was concluded from the results of the present study that MOS improved growth performance and reversed the lesions of E. tenella. PMID:27068898

  17. Experimental validation of a numerical model for subway induced vibrations

    NASA Astrophysics Data System (ADS)

    Gupta, S.; Degrande, G.; Lombaert, G.

    2009-04-01

    This paper presents the experimental validation of a coupled periodic finite element-boundary element model for the prediction of subway induced vibrations. The model fully accounts for the dynamic interaction between the train, the track, the tunnel and the soil. The periodicity or invariance of the tunnel and the soil in the longitudinal direction is exploited using the Floquet transformation, which allows for an efficient formulation in the frequency-wavenumber domain. A general analytical formulation is used to compute the response of three-dimensional invariant or periodic media that are excited by moving loads. The numerical model is validated by means of several experiments that have been performed at a site in Regent's Park on the Bakerloo line of London Underground. Vibration measurements have been performed on the axle boxes of the train, on the rail, the tunnel invert and the tunnel wall, and in the free field, both at the surface and at a depth of 15 m. Prior to these vibration measurements, the dynamic soil characteristics and the track characteristics have been determined. The Bakerloo line tunnel of London Underground has been modelled using the coupled periodic finite element-boundary element approach and free field vibrations due to the passage of a train at different speeds have been predicted and compared to the measurements. The correspondence between the predicted and measured response in the tunnel is reasonably good, although some differences are observed in the free field. The discrepancies are explained on the basis of various uncertainties involved in the problem. The variation in the response with train speed is similar for the measurements as well as the predictions. This study demonstrates the applicability of the coupled periodic finite element-boundary element model to make realistic predictions of the vibrations from underground railways.

  18. Renal tubular angiogenic dysregulation in anti-Thy1.1 glomerulonephritis.

    PubMed

    Cina, Davide P; Xu, Hui; Liu, Limin; Farkas, Laszlo; Farkas, Daniela; Kolb, Martin; Margetts, Peter J

    2011-02-01

    Peritubular vascular changes and hypoxia after glomerular injury may explain subsequent tubulointerstitial injury and fibrosis. Several studies suggested that the expected tubulointerstitial angiogenic response is actively suppressed in this setting. The mechanism of this aberrant response has not been clearly identified. We used a common model of glomerular injury in rats to assess vascular changes and to identify potential factors associated with this aberrant response. Anti-Thy1.1 antibody administration (1 or 4 weekly doses) led to a dose-dependent renal damage characterized by elevated urea and tubulointerstitial fibrosis as assessed by Picro-Sirius Red staining. We quantified peritubular capillaries using CD31 and CD34 immunohistochemistry and showed that tubular angiogenic dysregulation was associated with peritubular capillary rarefaction. Using laser capture microdissection, we demonstrated an early induction of fibrogenic and angiogenic factors in the glomeruli and a subsequent dysregulated angiogenic response in the tubulointerstitial compartment. Proximal tubules of anti-Thy1.1-treated animals had increased pigment epithelial-derived factor (PEDF) expression by immunohistochemistry. Protein taken by laser capture microdissection also showed that PEDF was upregulated. Temporally associated with PEDF expression was a transient downregulation of tubular hypoxia-inducible factor (HIF)1α. In a human proximal tubular cell culture, we show that PEDF downregulates HIF1α protein and gene expression in cells exposed to 1% oxygen. In anti-Thy1.1 glomerulonephritis, there is aberrent tubular angiogenesis associated with glomerular injury and tubulointersititial fibrosis. We showed that PEDF may be involved by downregulating HIF1α. Further work is needed to elucidate the mechanism of PEDF upregulation and action in the tubules. PMID:21048020

  19. Incidence of post-transplant glomerulonephritis and its impact on graft outcome

    PubMed Central

    An, Jung Nam; Lee, Jung Pyo; Oh, Yun Jung; Oh, Yun Kyu; Ha, Jong-won; Chae, Dong-Wan; Kim, Yon Su; Lim, Chun Soo

    2012-01-01

    Background Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. Methods Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. Results The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. Conclusion We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care. PMID:26889425

  20. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases

    PubMed Central

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989

  1. Membranous glomerulonephritis in rheumatoid arthritis unrelated to gold, D-penicillamine or other connective tissue disease.

    PubMed

    Zarza, L P; Sanchez, E N; Acin, P A; Ara, J M; Baños, J G

    1996-07-01

    We report a 58-year-old woman with classical rheumatoid arthritis (RA) who developed a membranous glomerulonephritis (MGN). She had never been treated with gold or D-penicillamine; other connective tissue diseases as well as hepatitis B were excluded. We suggest that the responsible cause of MGN is RA. PMID:8853174

  2. Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

    PubMed Central

    Peters, D. N.; Steinberg, H.; Anderson, W. I.; Hornbuckle, W. E.; Cote, P. J.; Gerin, J. L.; Lewis, R. M.; Tennant, B. C.

    1992-01-01

    Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1632459

  3. Clinical, Pathological, and Prognostic Characteristics of Glomerulonephritis Related to Staphylococcal Infection

    PubMed Central

    Wang, Si-Yang; Bu, Ru; Zhang, Qi; Liang, Shuang; Wu, Jie; Liu, Xue-Guang Zhang Shu-Wen; Cai, Guang-Yan; Chen, Xiang-Mei

    2016-01-01

    Abstract Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized. We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome. A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58 ± 17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03–8.48; P = 0.04) and age (OR 4.80; 95% CI 1.84–12.53; P = 0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82–13.18; P = 0.002) and DM (OR 3.07; 95% CI 0.98–9.59; P = 0.05) were independent risk factors for unfavorable prognosis. Glomerulonephritis related to staphylococcal infection has different features

  4. Clinical, Pathological, and Prognostic Characteristics of Glomerulonephritis Related to Staphylococcal Infection.

    PubMed

    Wang, Si-Yang; Bu, Ru; Zhang, Qi; Liang, Shuang; Wu, Jie; Liu, Xue-Guang Zhang Shu-Wen; Cai, Guang-Yan; Chen, Xiang-Mei

    2016-04-01

    Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized.We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome.A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58 ± 17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03-8.48; P = 0.04) and age (OR 4.80; 95% CI 1.84-12.53; P = 0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82-13.18; P = 0.002) and DM (OR 3.07; 95% CI 0.98-9.59; P = 0.05) were independent risk factors for unfavorable prognosis.Glomerulonephritis related to staphylococcal infection has different features than typical

  5. The Occurrence or Fibrillary Glomerulonephritis in Patients with Diabetes Mellitus May Not Be Coincidental: A Report of Four Cases

    PubMed Central

    González-Cabrera, Fayna; Henríquez-Palop, Fernando; Ramírez-Puga, Ana; Santana-Estupiñán, Raquel; Plaza-Toledano, Celia; Antón-Pérez, Gloria; Marrero-Robayna, Silvia; Ramírez-Medina, Davinia; Gallego-Samper, Roberto; Vega-Díaz, Nicanor; Camacho-Galan, Rafael; Rodríguez-Pérez, José C.

    2013-01-01

    Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45–50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed. PMID:23762079

  6. Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis.

    PubMed

    Gan, Poh-Yi; O'Sullivan, Kim M; Ooi, Joshua D; Alikhan, Maliha A; Odobasic, Dragana; Summers, Shaun A; Kitching, A Richard; Holdsworth, Stephen R

    2016-05-01

    Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4(+) effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606

  7. Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Ohtaki, Hirokazu; Matsumoto, Kei; Wada, Yukihiro; Suzuki, Taihei; Yamamoto, Yasutaka; Saito, Tomohiro; Hihara, Kei; Tachibana, Shohei; Honda, Kazuho; Shibata, Takanori

    2016-06-01

    Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSC-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. In the present study, we investigated the therapeutic effects and mechanism of MSC-CM in experimental antiglomerular basement membrane glomerulonephritis. We administered either MSC-CM or vehicle from day 0 to day 10 after the induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSC-CM on TNF-α-mediated cytokine production in cultured normal human mesangial cells, proximal tubular (HK-2) cells, human umbilical vein endothelial cells, and monocytes (THP-1 and peripheral blood mononuclear cells). Compared with vehicle treatment, MSC-CM treatment improved proteinuria and renal dysfunction. Histologically, MSC-CM-treated rats had reduced crescent formation and glomerular ED1(+) macrophage infiltration and increased glomerular ED2(+) macrophage infiltration. Increased serum monocyte chemoattractant protein (MCP)-1 levels were observed in MSC-CM-treated rats. Renal cortical mRNA expression levels of proinflammatory cytokines, such as TNF-α and IL-6, and of the T helper cell 1 cytokine interferon-γ were greatly decreased by MSC-CM treatment. In vitro, pretreatment with MSC-CM blocked TNF-α-mediated IL-8 release in normal human mesangial cells and HK-2 cells. TNF-α-mediated MCP-1 release was enhanced by pretreatment with MSC-CM in human umbilical vein endothelial cells and HK-2 cells and was strikingly enhanced in THP-1 cells. Stimulation of peripheral blood mononuclear cells with a combination of MCP-1 and IL-4 enhanced the expression of M2-associated genes compared with IL-4 alone. We demonstrated that MSC-CM had therapeutic effects in experimental antiglomerular basement membrane glomerulonephritis that were mediated through anti-inflammatory effects that were partly due to acceleration of M2 macrophage

  8. COMPARISON OF METHODS FOR EVALUATION OF EXPERIMENTALLY INDUCED EMPHYSEMA

    EPA Science Inventory

    Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH4)2SO4 or NH4NO3 aer...

  9. Induced thermoluminescence study of experimentally shock-loaded oligoclase

    NASA Technical Reports Server (NTRS)

    Ivliev, A. I.; Kashkarov, L. L.; Badjukov, D. D.

    1993-01-01

    Artificially induced thermoluminescence (TL) in oligoclase samples which were shock-loaded up to 27 GPa was measured. The essential increase of the TL sensitivity in relation to the total gamma-ray irradiation dose was observed only in samples at the 27 GPa pressure. This result can be explained by the initiation of additional radiation damages in the shocked oligoclace crystal lattice.

  10. The Effects of a Selective CK2 Inhibitor on Anti-glomerular Basement Membrane Glomerulonephritis in Rats.

    PubMed

    Shi, Junfeng; Liu, Ning; Xiao, Ying; Takei, Yoshinori; Yasue, Misato; Suzuki, Yamato; Hou, Zengye; Ohno, Hiroaki; Yamada, Masateru; Fuchi, Nobuhiro; Oshida, Keiyu; Miyamoto, Yohei; Tsujimoto, Gozoh; Hirasawa, Akira

    2015-01-01

    Protein kinase CK2 ("casein kinase II") is a protein serine/threonine kinase that plays critical roles in biological processes such as cell growth, cell cycle progression, and apoptosis. So far, we have identified that one catalytic isozyme of CK2, CK2α, is over-expressed in the kidney during the progression of glomerulonephritis (GN). Moreover, we have shown that in vivo inhibition of CK2 by administration of CK2 inhibitors was effective in the treatment of experimental GN. Hence the development of potent CK2 inhibitors should be considered in therapeutic strategies for GN. In the present study we identified compound 13, a pyrazine derivative, as a potent CK2 inhibitor. By performing enzyme kinetics analysis in vitro, we characterized the inhibition of compound 13 toward each CK2 catalytic isozyme. Furthermore, in vivo, we demonstrated that compound 13 is effective in attenuating proteinuria, decreasing the enhanced level of blood urea nitrogen and serum creatinine, and ameliorating glomerular crescent formation in an experimental GN rat model. On the other hand, cellular apoptosis was detected in the rat testis following administration of compound 13. This study provides clues for new strategies for developing applicable compounds into CK2-targeted GN treatments. PMID:26328489

  11. Experimentally induced muscle pain induces hypoalgesia in heterotopic deep tissues, but not in homotopic deep tissues.

    PubMed

    Graven-Nielsen, T; Babenko, V; Svensson, P; Arendt-Nielsen, L

    1998-03-23

    The ability of muscle pain to generate somatosensory sensibility changes is controversial. Thus, in the present study, tonic infusion of hypertonic saline (5%, 7.1 ml administered over 15 min) into the tibialis anterior (TA) muscle was used as an experimental model to induce local and referred pain. The sensibility to high-intensity pressure stimuli applied to the local pain area, referred pain area and an arm was assessed in 14 healthy volunteers. Infusion of isotonic (0.9%) saline into the other leg served as control. The subject continuously scored the pain intensity on an electronic visual analogue scale (VAS). Pressure pain threshold (PPT) was determined on the TA muscle (2 cm and 10 cm from the infusion site), at the frontal aspect of the ankle (area of referred pain) and on the arm. To minimise the skin component of the PPT, the skin covering the assessment sites was anaesthetised with an anaesthetic creme. The PPTs were obtained before and after cutaneous analgesia, 1 min and 10 min after infusion start and 10 min after the pain had disappeared. Infusion of hypertonic saline caused significantly (P<0. 05) higher VAS scores than infusion of isotonic saline. A significant (P<0.04) increase of the PPT (i.e., decreased sensibility) was found at the ankle and on the arm during muscle pain compared to the control condition. No significant differences in PPTs on the TA muscle were found during saline-induced muscle pain compared to the infusion of isotonic saline. The decrease in deep sensibility at the heterotopic sites (referred pain area and arm), but not at homotopic sites (TA muscle), probably reflected the phenomenon of diffuse noxious inhibitory control (DNIC). The inhibitory mechanism during muscle pain was shown to be effective for the deep tissue sensibility in healthy subjects. Thus, a pathologically disturbed inhibitory mechanism may result in widespread deep hyperalgesia in muscle pain patients. PMID:9518613

  12. Clinical and experimental experiences of graft-induced dyskinesia.

    PubMed

    Lane, Emma L

    2011-01-01

    Clinical trials evaluating transplantation of fetal tissue for the treatment of Parkinson's disease identified the unexpected side effect of abnormal movements in the 'off'l-DOPA state. Termed graft-induced dyskinesia (GID), various hypotheses have been put forward as to their cause but unfortunately the significant differences in clinical trial protocols and lack of a truly representative animal model has hindered the search for a conclusive basis for their appearance. Likely causative factors have been identified through careful examination of patient data and the use of amphetamine-induced dyskinesia in a rodent model of Parkinson's disease. New trials being planned in Europe hope to avoid GID, whilst maximizing on the functional benefit that can be afforded by this treatment approach but questions still remain as to the underlying mechanism. PMID:21907087

  13. Experimental Feedback Control of Flow Induced Cavity Tones

    NASA Technical Reports Server (NTRS)

    Cabell, Randolph H.; Kegerise, Michael A.; Cox, David E.; Gibbs, Gary P.

    2002-01-01

    An experimental study of the application of discrete-time, linear quadratic control design methods to the cavity tone problem is described. State space models of the dynamics from a synthetic jet actuator at the leading edge of the cavity to two pressure sensors in the cavity were computed from experimental data. Variations in model order, control order, control bandwidth, and properties of a Kalman state estimator were studied. Feedback control reduced the levels of multiple cavity tones at Mach 0.275, 0.35, and 0.45. Closed loop performance was often limited by excitation of sidebands of cavity tones, and creation of new tones in the spectrum. State space models were useful for explaining some of these limitations, but were not able to account for non-linear dynamics, such as interactions between tones at different frequencies.

  14. Comparison of methods for evaluation of experimentally induced emphysema

    SciTech Connect

    Busch, R.H.; Buschbom, R.L.; Smith, L.G.

    1984-04-01

    Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH/sub 4/)/sub 2/SO/sub 4/ or NH/sub 4/NO/sub 3/ aerosols. The most sensitive quantitative evaluation was from mean chord length (MCL) measurements on scanning electron micrographs (SEM). Four-corner and parallel-line grids provided similar results, and reducing sample size to one selected field per lobe yielded a high degree of reliability for MCL measurements. Alveolar-pore perimeter and area (also measured on SEM photographs) were increased by induced emphysema, but were not reliable indicators for degree of pulmonary involvement. Both subjective score (grading the degree of emphysema) and percentage-area-affected determinations indicated the presence of emphysema, but with less sensitivity than MCL measurements. However, these two subgross methods (performed with a dissecting microscope) provided valuable information on the distribution of pulmonary lesions; emphysema was induced in a nonuniform but consistent and progressive pattern in the two lobes of the lung studied. 23 studied.

  15. Experimental study of microwave-induced thermoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Jacobs, Ryan T.

    Microwave-Induced Thermoacoustic Imaging (TAI) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub-microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in tissue samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost alternative to MRI and early breast cancer detection methods. This work describes the implementation of a thermoacoustic experiment using a 5 kW peak power microwave source.

  16. Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

    PubMed Central

    Wang, Zheng; Guo, Qiong-Ya; Zhang, Xiao-Ju; Li, Xiao; Li, Wen-Ting; Ma, Xi-Tao; Ma, Li-Jun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis. PMID:24886817

  17. Nephrotic range proteinuria in c-ANCA-positive crescentic glomerulonephritis with linear immune deposits

    PubMed Central

    Singh, N. P.; Gulati, S.; Garg, V.; Beniwal, P.; Garg, S.

    2008-01-01

    The three broad groups of rapidly progressing glomerulonephritis are anti glomerular basement membrane (anti-GBM) disease, renal vasculitis characterized by antineutrophil cytoplasmic antibody positivity, and a heterogeneous group with granular immune deposits. Anti-GBM disease with cytoplasmic antineutrophilic antibodies (c-ANCA) positivity (type III disease) is not known to present with nephrotic syndrome. We report here a rare presentation of nephrotic syndrome in Type III disease. Larger studies are warranted to determine whether the amount and/or type of immune deposits decide the range of proteinuria. These studies are also required to elucidate the impact of immune complex deposition on renal disease in c-ANCA-positive glomerulonephritis and to outline its pathogenetic mechanism. PMID:20142931

  18. Heartworm (Dirofilaria immitis) disease and glomerulonephritis in a black-footed cat (Felis nigripes).

    PubMed

    Deem, S L; Heard, D J; LaRock, R

    1998-06-01

    A 6-yr-old, 1.36-kg, intact female black-footed cat (Felis nigripes) was presented to the Veterinary Medical Teaching Hospital, University of Florida, with a history of depression, lethargy, and anorexia. Cardiac dysfunction and renal failure were diagnosed on the basis of antemortem and postmortem findings. At necropsy, heartworms (Dirofilaria immitis), glomerulonephritis, and endometritis were present. The glomerulonephritis could have been immune mediated and may have been associated with the heartworm infection or the chronic endometritis or both. Heartworm disease should be included in the list of differential diagnoses for any exotic cat housed outdoors in an endemic heartworm region that dies peracutely or has suggestive gastrointestinal or respiratory signs. Heartworm prophylaxis and annual serologic testing in exotic cats housed outdoors in heartworm endemic regions are recommended. PMID:9732037

  19. Familial C3 glomerulonephritis associated with mutations in the gene for complement factor B.

    PubMed

    Imamura, Hideaki; Konomoto, Takao; Tanaka, Etsuko; Hisano, Satoshi; Yoshida, Yoko; Fujimura, Yoshihiro; Miyata, Toshiyuki; Nunoi, Hiroyuki

    2015-05-01

    We report the first case of familial C3 glomerulonephritis (C3GN) associated with mutations in the gene for complement factor B (CFB). A 12-year-old girl was diagnosed with biopsy-proven C3GN. Her mother had a history of treatment for membranoproliferative glomerulonephritis, and her brother had hypocomplementemia without urinary abnormalities. DNA analysis revealed heterozygosity for CFB p.S367R in the patient, mother and brother. Evaluation of the structure-function relationship supports that this mutation has gain-of-function effects in CFB. The present case suggests that CFB has an important role in the etiology of C3GN and provides a new insight into anticomplement therapy approaches. PMID:25758434

  20. Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

    PubMed

    Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

    2008-01-01

    We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353

  1. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  2. Experimental Feedback Control of Flow Induced Cavity Tones

    NASA Technical Reports Server (NTRS)

    Cabell, Randolph H.; Kegerise, Michael A.; Cox, David E.; Gibbs, Gary P.

    2005-01-01

    Discrete-time, linear quadratic methods were used to design feedback controllers for reducing tones generated by flow over a cavity. The dynamics of a synthetic jet actuator mounted at the leading edge of the cavity as observed by two microphones in the cavity were modeled over a broad frequency range using state space models computed from experimental data. Variations in closed loop performance as a function of model order, control order, control bandwidth, and state estimator design were studied using a cavity in the Probe Calibration Tunnel at NASA Langley. The controller successfully reduced the levels of multiple cavity tones at the tested flow speeds of Mach 0.275, 0.35, and 0.45. In some cases, the closed loop results were limited by excitation of sidebands of the cavity tones, or the creation of new tones at frequencies away from the cavity tones. Nonetheless, the results validate the combination of optimal control and experimentally-generated state space models, and suggest this approach may be useful for other flow control problems. The models were not able to account for non-linear dynamics, such as interactions between tones at different frequencies.

  3. Experimental distinction of Autler-Townes splitting from electromagnetically induced transparency using coupled mechanical oscillators system

    PubMed Central

    Liu, Jingliang; Yang, Hujiang; Wang, Chuan; Xu, Kun; Xiao, Jinghua

    2016-01-01

    Here we experimentally demonstrated the electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) effects in mechanical coupled pendulums. The analogue of EIT and ATS has been studied in mechanical systems and the intrinsic physics between these two phenomena are also been discussed. Exploiting the Akaike Information Criterion, we discern the ATS effect from EIT effect in our experimental results. PMID:26751738

  4. An Attempt to Reverse Performance Deficits Associated With Depression and Experimentally Induced Helplessness

    ERIC Educational Resources Information Center

    Kilpatrick-Tabak, Blair; Roth, Susan

    1978-01-01

    The learned helplessness model of depression predicts that any effective treatment for reactive depression should also reverse performance deficits associated with experimentally induced helplessness, and vice versa. This study tests that prediction with college students who were exposed to experimental manipulations designed to induce…

  5. Experimental distinction of Autler-Townes splitting from electromagnetically induced transparency using coupled mechanical oscillators system

    NASA Astrophysics Data System (ADS)

    Liu, Jingliang; Yang, Hujiang; Wang, Chuan; Xu, Kun; Xiao, Jinghua

    2016-01-01

    Here we experimentally demonstrated the electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) effects in mechanical coupled pendulums. The analogue of EIT and ATS has been studied in mechanical systems and the intrinsic physics between these two phenomena are also been discussed. Exploiting the Akaike Information Criterion, we discern the ATS effect from EIT effect in our experimental results.

  6. Effects of flunarizine on experimentally-induced convulsions in animals.

    PubMed

    Drago, F; Valerio, C; Clementi, G; Scapagnini, U

    1986-01-01

    D,L-allylglycine-induced seizures in rats were antagonized by flunarizine and other antiepileptic drugs. In this respect, the spectrum of flunarizine appears to be similar to that of diphenylhydantoin. A behavioral analysis of the effects of various drugs on amygdaloid kindled rats showed that flunarizine exerts anticonvulsive effects in this model with an ED50 of 42.8 mg/kg. Furthermore, flunarizine (1, 5, 25 and 50 mg/kg i.p.) reduced seizure parameters in rats injected with strychnine or pentetrazol. In this case, flunarizine reduced seizure intensity and increased the percentage of survival. In another study on genetically epileptic beagles, flunarizine significantly affected the REM and deep slow-wave sleep latencies. PMID:3609879

  7. Experimental Studies of Laser-Induced Breakdown in Transparent Dielectrics

    SciTech Connect

    Carr, C W

    2003-09-23

    The mechanisms by which transparent dielectrics damage when exposed to high power laser radiation has been of scientific and technological interest since the invention of the laser. In this work, a set of three experiments are presented which provide insight into the damage initiation mechanisms and the processes involved in laser-induced damage. Using an OPO (optical parametric oscillator) laser, we have measured the damage thresholds of deuterated potassium dihydrogen phosphate (DKDP) from the near ultraviolet into the visible. Distinct steps, whose width is of order K{sub b}T, are observed in the damage threshold at photon energies associated with the number of photons (3{yields}2 or 4{yields}3) needed to promote a ground state electron across the energy gap. The wavelength dependence of the damage threshold suggests that a primary mechanism for damage initiation in DKDP is a multi-photon process in which the order is reduced through excited defect state absorption. In-situ fluorescence microscopy, in conjunction with theoretical calculations by Liu et al., has been used to establish that hydrogen displacement defects are potentially responsible for the reduction in the multi-photon cross-section. During the damage process, the material absorbs energy from the laser pulse and produces an ionized region that gives rise to broadband emission. By performing a time-resolved investigation of this emission, we demonstrate both that it is blackbody in nature, and we provide the first direct measurement of the localized temperature during and following laser damage initiation for various optical materials. For excitation using nanosecond laser pulses, the plasma, when confined in the bulk, is in thermal equilibrium with the lattice. These results allow for a detailed characterization of temperature, pressure, and electron densities occurring during laser-induced damage.

  8. Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

    PubMed

    Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

    2013-11-01

    Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans. PMID:23696447

  9. Hypolipidemic effect of gypenosides in experimentally induced hypercholesterolemic rats

    PubMed Central

    2013-01-01

    Background To investigate the anti-hyperlipidemic effect of gynosaponins (GPs) in hyperlipidemic rats induced by high lipid diet. Methods Animal model of hyperlipidemia was established by high-fat and high-cholesterol diet. Rats were randomly divided into 6 groups, except the normal and model groups, rats in GPs groups were daily administered intragastrically with GPs (50, 100, and 200 mg/kg), and rats in simvastatin group were daily administered intragastrically with simvastatin (10 mg/kg). It was measured that the contents of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in the serum, TG and TC in the liver during this experiment, respectively. The left lobe of liver was observed by histopathological staining, and the immunohistochemical staining was used to observe the effects on the effect of GPs on liver functions. Results Compared with the model group, GPs groups could remarkably decrease the content of lipids, GSH-Px, SOD, CAT and MDA in the serum and TC and TG in the liver of the hyperlipidemic rats. The pathomorphological results of hepatic tissue showed that fatty degeneration and inflammatory reaction of GPs groups were lightened compared with the model group. Conclusions The results show that GPs has good effects on the treatment of hyperlipidemia induced by high lipid diet in rats. The possible anti-hyperlipidemia mechanism maybe those GPs can regulate the disorder of lipid metabolism as well as ameliorate hepatic function. PMID:24160562

  10. Histochemical changes in the testes of lead induced experimental rats.

    PubMed

    Chowdhury, A R; Rao, R V; Gautam, A K

    1986-01-01

    The experiments were performed on mature male rats divided in five groups, one control and four experimental in which the animals received 1 mg, 2 mg, 4 mg and 6 mg/kg body weight lead acetate intraperitoneally respectively, over a period of 30 days. ALA-D and lead was estimated in the blood by the use of atomic absorption spectrophotometer and ATP-ase, AMP-ase, Alk-ase were histochemically localized. Significant increase in blood and testis of lead levels along with decrease of ALA-D levels were observed. Changes in the testicular tissue were encountered. Other details concerned with the damage of the testicular tissue are discussed. PMID:3030829

  11. Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

    PubMed

    Mohiti-Asli, M; Ghanaatparast-Rashti, M

    2015-06-15

    An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. PMID:25864115

  12. The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication

    PubMed Central

    Wang, Lifen; Ye, Zhiming; Liang, Huaban; Zhang, Bin; Xu, Lixia; Feng, Zhonglin; Liu, Shuangxin; Shi, Wei

    2016-01-01

    Background: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. Method: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0.05 mg/kg/day) in combination entecavir over 24 weeks, whereas the other 19 patients only received entecavir monotherapy. Results: The probability of proteinuria remission in the Tacrolimus+entecavir group was 69 and 87% after 12 and 24 weeks, whereas was only 26 and 42%, respectively, in the entecavir group. The mean time to partial or complete remission was 18.6 weeks in the Tacrolimus+entecavir group and 34.3 weeks in the entecavir group (P<0.001). A decrease in the HBV DNA titer was observed in all patients with active HBV replication. None of the HBV carriers in the Tacrolimus+entecavir group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The Tacrolimus target trough concentration was 5-10 ng/mL. Conclusion: Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Furthermore, Tacrolimus may have a synergistic antiviral effect with entecavir.

  13. Experimental treatment of antipsychotic-induced movement disorders

    PubMed Central

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  14. Chemically induced skin carcinogenesis: Updates in experimental models (Review).

    PubMed

    Neagu, Monica; Caruntu, Constantin; Constantin, Carolina; Boda, Daniel; Zurac, Sabina; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  15. Experimental treatment of antipsychotic-induced movement disorders.

    PubMed

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  16. Experimentally induced metamorphosis in axolotls reduces regenerative rate and fidelity

    PubMed Central

    Stier, Adrian C.; Michonneau, François; Smith, Matthew D.; Pasch, Bret; Maden, Malcolm

    2014-01-01

    Abstract While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age‐matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and lead to carpal and digit malformations. Furthermore, we find evidence that metamorphic blastemal cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue‐specific changes.

  17. Flagella-induced immunity against experimental cholera in adult rabbits.

    PubMed Central

    Yancey, R J; Willis, D L; Berry, L J

    1979-01-01

    The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone. PMID:478635

  18. Chemically induced skin carcinogenesis: Updates in experimental models (Review)

    PubMed Central

    NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  19. Epithelial impedance analysis in experimentally induced colon cancer.

    PubMed Central

    Davies, R J; Joseph, R; Kaplan, D; Juncosa, R D; Pempinello, C; Asbun, H; Sedwitz, M M

    1987-01-01

    Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states. PMID:3427187

  20. Experimentally induced photosensitization in cattle with Cooperia pedunculata.

    PubMed

    Casteel, S W; Rowe, L D; Bailey, E M; Fiske, R A; Bridges, C W

    1988-04-01

    Photosensitization was induced in 2 Charolais heifers following administration of a mixture of air-dried, ground, green (75%) and dead (25%) leaves of the south Texas forb, Cooperia pedunculata, and subsequent exposure to sunlight. Plant material used in this study was collected from a pasture where natural cases of primary bovine photosensitization were occurring. Signs of photosensitization were observed in one heifer after 2 doses of plant material--10 g/kg on day 1 and 5 g/kg on day 2. Continued administration of plant material at 5 g/kg/d on days 3, 4, 7, 8, and 9 resulted in severe signs and lesions of photosensitization and death on day 23. A second heifer developed signs of mild photosensitization following administration of plant material at 1.7 g/kg/d for 4 days. This heifer recovered by day 18. Clinical and pathologic findings of this trial were consistent with the primary form of photosensitization observed in natural cases seen in cattle of south Texas exposed to this plant. PMID:3381477

  1. Experimental Investigation of Cavitation Induced Feedline Instability from an Orifice

    NASA Technical Reports Server (NTRS)

    Hitt, Matthew A.; Lineberry, David M.; Ahuja, Vineet; Frederick, Robert A,

    2012-01-01

    This paper details the results of an experimental investigation into the cavitation instabilities created by a circular orifice conducted at the University of Alabama in Huntsville Propulsion Research Center. This experiment was conducted in concert with a computational simulation to serve as a reference point for the simulation. Testing was conducted using liquid nitrogen as a cryogenic propellant simulant. A 1.06 cm diameter thin orifice with a rounded inlet was tested in an approximately 1.25 kg/s flow with inlet pressures ranging from 504.1 kPa to 829.3 kPa. Pressure fluctuations generated by the orifice were measured using a high frequency pressure sensor located 0.64 tube diameters downstream of the orifice. Fast Fourier Transforms were performed on the high frequency data to determine the instability frequency. Shedding resulted in a primary frequency with a cavitation related subharmonic frequency. For this experiment, the cavitation instability ranged from 153 Hz to 275 Hz. Additionally, the strength of the cavitation occur red as a function of cavitation number. At lower cavitation numbers, the strength of the cavitation instability ranged from 2.4 % to 7 % of the inlet pressure. However, at higher cavitation numbers, the strength of the cavitation instability ranged from 0.6 % to 1 % of the inlet pressure.

  2. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    PubMed

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-01-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders. PMID:27598124

  3. Experimental particle acceleration by water evaporation induced by shock waves

    NASA Astrophysics Data System (ADS)

    Scolamacchia, T.; Alatorre Ibarguengoitia, M.; Scheu, B.; Dingwell, D. B.; Cimarelli, C.

    2010-12-01

    Shock waves are commonly generated during volcanic eruptions. They induce sudden changes in pressure and temperature causing phase changes. Nevertheless, their effects on flowfield properties are not well understood. Here we investigate the role of gas expansion generated by shock wave propagation in the acceleration of ash particles. We used a shock tube facility consisting of a high-pressure (HP) steel autoclave (450 mm long, 28 mm in internal diameter), pressurized with Ar gas, and a low-pressure tank at atmospheric conditions (LP). A copper diaphragm separated the HP autoclave from a 180 mm tube (PVC or acrylic glass) at ambient P, with the same internal diameter of the HP reservoir. Around the tube, a 30 cm-high acrylic glass cylinder, with the same section of the LP tank (40 cm), allowed the observation of the processes occurring downstream from the nozzle throat, and was large enough to act as an unconfined volume in which the initial diffracting shock and gas jet expand. All experiments were performed at Pres/Pamb ratios of 150:1. Two ambient conditions were used: dry air and air saturated with steam. Carbon fibers and glass spheres in a size range between 150 and 210 μm, were placed on a metal wire at the exit of the PVC tube. The sudden decompression of the Ar gas, due to the failure of the diaphragm, generated an initial air shock wave. A high-speed camera recorded the processes between the first 100 μsec and several ms after the diaphragm failure at frame rates ranging between 30,000 and 50,000 fps. In the experiments with ambient air saturated with steam, the high-speed camera allowed to visualize the condensation front associated with the initial air shock; a maximum velocity of 788 m/s was recorded, which decreases to 524 m/s at distance of 0.5 ±0.2 cm, 1.1 ms after the diaphragm rupture. The condensation front preceded the Ar jet front exhausting from the reservoir, by 0.2-0.5 ms. In all experiments particles velocities following the initial

  4. Experimental investigation of the flow induced by artificial cilia.

    PubMed

    Hussong, J; Schorr, N; Belardi, J; Prucker, O; Rühe, J; Westerweel, J

    2011-06-21

    The fluid transport produced by rectangular shaped, magnetically actuated artificial cilia of 70 μm length and 20 μm width was determined by means of phase-locked Micro Particle Image Velocimetry (μPIV) measurements in a closed microfluidic chamber. The phase-averaged flow produced by the artificial cilia reached up to 130 μm s(-1) with an actuation cycle frequency of 10 Hz. Analysis of the measured flow data indicate that the present system is capable of achieving volume flow rates of V[combining dot above](cilia) = 14 ± 4 μl min(-1) in a micro channel of 0.5 × 5 mm(2) cross-sectional area when no back pressure is built up. This corresponds to an effective pressure gradient of 6 ± 1 Pa m(-1), which equals a pressure difference of 0.6 ± 0.1 mPa over a distance of 100 μm between two rows of cilia. These results were derived analytically from the measured velocity profile by treating the cilia as a thin boundary layer. While the cilia produce phase-averaged velocities of the order of O(10(2)μm s(-1)), time-resolved measurements showed that the flow field reverses two times during one actuation cycle inducing instantaneous velocities of up to approximately 2 mm s(-1). This shows that the flow field is dominated by fluid oscillations and flow rates are expected to increase if the beating motion of the cilia is further improved. PMID:21614349

  5. Predictions of Experimentally Observed Stochastic Ground Vibrations Induced by Blasting

    PubMed Central

    Kostić, Srđan; Perc, Matjaž; Vasović, Nebojša; Trajković, Slobodan

    2013-01-01

    In the present paper, we investigate the blast induced ground motion recorded at the limestone quarry “Suva Vrela” near Kosjerić, which is located in the western part of Serbia. We examine the recorded signals by means of surrogate data methods and a determinism test, in order to determine whether the recorded ground velocity is stochastic or deterministic in nature. Longitudinal, transversal and the vertical ground motion component are analyzed at three monitoring points that are located at different distances from the blasting source. The analysis reveals that the recordings belong to a class of stationary linear stochastic processes with Gaussian inputs, which could be distorted by a monotonic, instantaneous, time-independent nonlinear function. Low determinism factors obtained with the determinism test further confirm the stochastic nature of the recordings. Guided by the outcome of time series analysis, we propose an improved prediction model for the peak particle velocity based on a neural network. We show that, while conventional predictors fail to provide acceptable prediction accuracy, the neural network model with four main blast parameters as input, namely total charge, maximum charge per delay, distance from the blasting source to the measuring point, and hole depth, delivers significantly more accurate predictions that may be applicable on site. We also perform a sensitivity analysis, which reveals that the distance from the blasting source has the strongest influence on the final value of the peak particle velocity. This is in full agreement with previous observations and theory, thus additionally validating our methodology and main conclusions. PMID:24358140

  6. Generation of hydroxyl radicals during ascites experimentally induced in broilers.

    PubMed

    Arab, H A; Jamshidi, R; Rassouli, A; Shams, G; Hassanzadeh, M H

    2006-04-01

    Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the most important features of the ascites syndrome in broiler chickens. However, the mechanism of cell injury causing the pathogenesis of the syndrome is not clearly understood. Our study aimed to examine the generation of hydroxyl radicals (OH*) in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens were purchased from a local hatchery and reared in an open poultry house for 46 d. They were divided at random into three groups and ascites was induced in two groups by exposing them to low temperature or administration of triiodothyronine (T(3)). The third group served as control and was reared normally. Haematological, biochemical and pathological tests were used to determine the incidence of ascites: including total red blood cell (RBC), packed cell volume (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and ratio of right ventricular weight to total ventricular weight (RV/TV). A salicylate hydroxylation method was used to examine the generation of hydroxyl radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites, 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to detect the generation of OH*. An ascites syndrome was observed in T(3) and low-temperature treated groups, as shown by necropsy changes and increases in f RBC, PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were increased in groups experiencing ascites compared to control group. It is suggested that reactive oxygen species that is OH* ions, may be involved in the pathogenesis of the ascites syndrome in broiler chickens. PMID:16641033

  7. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    PubMed

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. PMID:26472753

  8. Experimental demonstration of population inversion driven by retroreflection-induced bichromatic adiabatic passage

    SciTech Connect

    Conde, Alvaro Peralta; Yatsenko, Leonid P.; Klein, Jens; Oberst, Martin; Halfmann, Thomas

    2005-11-15

    We present experimental data to demonstrate coherently driven population inversion by retroreflection-induced bichromatic adiabatic passage in metastable helium atoms. Complete and robust population transfer from an initial to a target state is induced by coherent interaction of the atoms in a supersonic beam with two counterpropagating and temporally delayed laser pulses of different intensities. The radiation fields intersect the atomic beam slightly tilted away from normal incidence, thereby inducing Doppler shifts of the atomic resonance between the initial and the target state. Thus the laser pulses produce a bichromatic field in the rest frame of each atom, which induces complete coherent population transfer by an adiabatic passage process.

  9. T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

    PubMed Central

    2010-01-01

    Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the

  10. Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection.

    PubMed

    Asano, Shuichi; Mizuno, Shige; Okachi, Shotaro; Aso, Hiromichi; Wakahara, Keiko; Hashimoto, Naozumi; Ito, Satoru; Kozaki, Yohei; Katsuno, Takayuki; Maruyama, Shoichi; Hasegawa, Yoshinori

    2016-01-01

    A 73-year-old woman was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection and received no treatment. Disease progression was evident one year later with the development of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) titers and systemic symptoms of a fever, polyarthritis, purpura, and rapidly progressive glomerulonephritis. Her symptoms did not improve with antibiotic treatment. A renal biopsy revealed crescentic glomerulonephritis with immunodeposition. According to these findings, she was diagnosed with ANCA-associated vasculitis (AAV) superimposed on infection-related glomerulonephritis (IRGN). Although there was a risk of aggravating an underlying infection, the combination therapy of corticosteroid and antibiotics improved AAV, IRGN, and even the lung radiological findings. To the best of our knowledge, this is the first case of AAV and IRGN secondary to pulmonary MAC infection. PMID:27580547

  11. Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

    NASA Technical Reports Server (NTRS)

    Zabrodin, O. N.

    1980-01-01

    The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration.

  12. Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis

    PubMed Central

    Wörnle, Markus; Schmid, Holger; Banas, Bernhard; Merkle, Monika; Henger, Anna; Roeder, Maximilian; Blattner, Simone; Bock, Elisabeth; Kretzler, Matthias; Gröne, Hermann-Josef; Schlöndorff, Detlef

    2006-01-01

    Hepatitis C virus (HCV) infection is frequently complicated by glomerulonephritis with immune complexes containing viral RNA. We examined the potential influence of Toll-like receptors (TLRs), specifically TLR3 recognition of viral dsRNA exemplified by polyriboinosinic:polyribocytidylic acid [poly(I:C) RNA]. Normal human kidney stained positive for TLR3 on mesangial cells (MCs), vascular smooth muscle cells, and collecting duct epithelium. Cultured MCs have low TLR3 mRNA levels with predominant intracellular protein localization, which was increased by tumor necrosis factor-α, interleukin (IL)-1β, interferon (IFN)-γ, and the TLR3 ligand poly(I:C) RNA. Poly(I:C) RNA stimulation of MCs increased mRNA and protein synthesis of IL-6, IL-1β, M-CSF, IL-8/CXCL8, RANTES/CCL5, MCP-1/CCL2, and ICAM-I; it also increased anti-proliferative and proapoptotic effects, the latter of which was decreased by inhibiting caspase-8. In microdissected glomeruli of normal and non-HCV membranoproliferative glomerulonephritis biopsies, TLR3 mRNA expression was low. In contrast TLR3 mRNA expression was significantly increased in hepatitis C-positive glomerulonephritis and was associated with enhanced mRNA for RANTES/CCL5 and MCP-1/CCL2. We hypothesize that immune complexes containing viral RNA activate mesangial TLR3 during HCV infection, thereby contributing to chemokine/cytokine release and effecting proliferation and apoptosis. Thus, TLR3 expression on renal cells, and especially MCs, may establish a link between viral infections and glomerular diseases. PMID:16436653

  13. IgA-dominant post-infectious glomerulonephritis presenting as a fatal pulmonary-renal syndrome.

    PubMed

    Saad, Marc; Daoud, Magda; Nasr, Patricia; Syed, Rafeel; El-Sayegh, Suzanne

    2015-01-01

    Over the last decades, post-infectious glomerulonephritis underwent major changes in its epidemiology, pathophysiology, and outcomes. We are reporting a case of IgA-dominant post-infectious glomerulonephritis (IgA-PIGN) presenting as a fatal pulmonary-renal syndrome. An 86-year-old Filipino man presented with worsening dyspnea, hemoptysis, and decreased urine output over 2 weeks. Past medical history is significant for hypertension, chronic kidney disease stage III, and pneumonia 3 weeks prior treated with intravenous cefazolin for methicillin-sensitive Staphylococcus aureus bacteremia. Physical examination was remarkable for heart rate of 109/min and respiratory rate of 25/min saturating 99% on 3 liters via nasal cannula. There were bibasilar rales in the lungs and bilateral ankle edema. A chest radiograph showed bibasilar opacifications. Blood work was significant for hemoglobin of 8.3 g/dL and creatinine of 9.2 mg/dL (baseline of 1.67). TTE showed EF 55%. Urinalysis revealed large blood and red blood cell casts. Kidney ultrasound showed bilateral echogenicity compatible with renal disease. Pulse methylprednisolone therapy and hemodialysis were initiated with patient's condition precluding kidney biopsy. Serology workup for rapidly progressive glomerulonephritis was negative. On day 7, the patient required mechanical ventilation; bronchoscopy showed alveolar hemorrhage and plasmapheresis was initiated. Renal biopsy revealed IgA-PIGN with endocapillary and focal extracapillary proliferative and exudative features. IgA-PIGN occurs in diabetic elderly (mean age of 60 years), 0-16 weeks after an infection mainly by Staphylococcus. However, this nondiabetic patient had normal complement IgA-PIGN with fatal pulmonary-renal syndrome. Understanding the pathogenesis and identifying the nephrotoxic bacteria species and the aberrant IgA molecule will open new insights toward prevention and treatment. PMID:26347210

  14. Acute glomerulonephritis in children of the Niger Delta region of Nigeria.

    PubMed

    McGil Ugwu, G I

    2015-09-01

    A three-year retrospective study was conducted to determine the incidence, pattern of presentation and other clinical and biochemical features as well as outcome of treatment of patients admitted with acute glomerulonephritis at the Delta State University Teaching Hospital, Oghara and GN Children's Clinic, Warri. The case notes of all the children who presented with renal diseases from January 2010 to December 2012 were retrieved and those with acute glomerulonephritis were analyzed. A total of 20 patients (13 male and seven female) with acute glomerulonephritis were seen during the three-year period under review. Twelve patients (60%) were from the low socioeconomic class, six (30%) from the middle class and only two (10%) were from the high-income group. The presentation of the illness was most common between October and January. The age range of the patients was three to 13 years, with an average age of eight years. Seventeen (85%) of the patients were in the school-going age group (>5 years to 10 years). The most common symptom/sign noted was anemia in 90% of the patients, followed by oliguria/anuria and edema seen in 80% of the patients. Seventy percent of the patients had cola-colored urine, while 55% had hypertension. Some patients gave a history suggestive of previous streptococcal infection. More patients had sore throat (25%) than skin infection (10%). All the patients had proteinuria, while 90% had hematuria. The most common complication was acute kidney injury, seen in eight (40%) of the patients, followed by hypertensive encephalopathy, which occurred in three (15%) patients. Most patients (60%) were hospitalized for one to two weeks. The outcome of the management of these patients showed 14 (70%) of the patients recovered fully while three (15%) had persistent hematuria and two (10%) had persistent proteinuria. Ninety-five percent of the patients recovered from the acute illness and one patient (5%), a boy aged nine years old, died. PMID:26354592

  15. Temporal Changes in Post-Infectious Glomerulonephritis in Japan (1976-2009)

    PubMed Central

    Usui, Joichi; Tawara-Iida, Takashi; Takada, Kenji; Ebihara, Itaru; Ueda, Atsushi; Iwabuchi, Satoshi; Ishizu, Takashi; Iitsuka, Tadashi; Takemura, Katsumi; Kawamura, Tetsuya; Kaneko, Shuzo; Sakai, Kentaro; Kai, Hirayasu; Gomibuchi, Tomoka; Nagata, Michio; Kobayashi, Masaki; Koyama, Akio; Suka, Machi; Radhakrishnan, Jai; Yamagata, Kunihiro

    2016-01-01

    Background The incidence of post-infectious glomerulonephritis (PIGN) in developed countries has decreased over the last 50 years. Here we identified the trends of the incidence of PIGN in Japan during the past four decades. Methods We explored the frequency, clinicopathological findings, and prognosis of PIGN based on 6,369 cases from the Renal Biopsy Database of our institute in the Kanto region of Japan, diagnosed histologically from 1976 to 2009. Results The numbers of PIGN cases were 131 (2.1%) in total, and 2.4%, 1.1%, 2.6% and 2.1% identified in the 1970s, 1980s, 1990s, and 2000s, respectively. Acute glomerulonephritis (AGN), including post-streptococcal glomerulonephritis (PSGN), accounted for almost all of the PIGN cases in the 1970s, but decreased to approx. 40%–50% since the 1990s. In the 1990s, Staphylococcus aureus infection-related nephritis (SARN) showed a rapid increase in rate, reaching 30%. The incidence of hepatitis C virus infection-associated GN (HCVGN) has increased since the 1990s. The average age at onset rose from 33 to 51 years over the study period. These transitions can be summarized as increases in SARN and HCVGN and decreases in PSGN and other types of AGN, since SARN and HCVGN have older onsets compared to PSGN and other AGN types. The clinicopathological features were marked for each PIGN. Regarding the prognosis, the renal death rates of both the SARN and HCVGN groups were significantly higher than those of other PIGN. Conclusion Based on our analysis of the Renal Biopsy Database, the incidence of PIGN in Japan reached its peak in the 1990s. The temporal changes in the incidence of PIGN reflected the trends in infectious diseases of each decade and the continual aging of the population, with a related higher susceptibility to infections. PMID:27286043

  16. IgA-dominant post-infectious glomerulonephritis presenting as a fatal pulmonary-renal syndrome

    PubMed Central

    Saad, Marc; Daoud, Magda; Nasr, Patricia; Syed, Rafeel; El-Sayegh, Suzanne

    2015-01-01

    Over the last decades, post-infectious glomerulonephritis underwent major changes in its epidemiology, pathophysiology, and outcomes. We are reporting a case of IgA-dominant post-infectious glomerulonephritis (IgA-PIGN) presenting as a fatal pulmonary-renal syndrome. An 86-year-old Filipino man presented with worsening dyspnea, hemoptysis, and decreased urine output over 2 weeks. Past medical history is significant for hypertension, chronic kidney disease stage III, and pneumonia 3 weeks prior treated with intravenous cefazolin for methicillin-sensitive Staphylococcus aureus bacteremia. Physical examination was remarkable for heart rate of 109/min and respiratory rate of 25/min saturating 99% on 3 liters via nasal cannula. There were bibasilar rales in the lungs and bilateral ankle edema. A chest radiograph showed bibasilar opacifications. Blood work was significant for hemoglobin of 8.3 g/dL and creatinine of 9.2 mg/dL (baseline of 1.67). TTE showed EF 55%. Urinalysis revealed large blood and red blood cell casts. Kidney ultrasound showed bilateral echogenicity compatible with renal disease. Pulse methylprednisolone therapy and hemodialysis were initiated with patient’s condition precluding kidney biopsy. Serology workup for rapidly progressive glomerulonephritis was negative. On day 7, the patient required mechanical ventilation; bronchoscopy showed alveolar hemorrhage and plasmapheresis was initiated. Renal biopsy revealed IgA-PIGN with endocapillary and focal extracapillary proliferative and exudative features. IgA-PIGN occurs in diabetic elderly (mean age of 60 years), 0–16 weeks after an infection mainly by Staphylococcus. However, this nondiabetic patient had normal complement IgA-PIGN with fatal pulmonary-renal syndrome. Understanding the pathogenesis and identifying the nephrotoxic bacteria species and the aberrant IgA molecule will open new insights toward prevention and treatment. PMID:26347210

  17. Nutrient induced type 2 and chemical induced type 1 experimental diabetes differently modulate gastric GLP-1 receptor expression.

    PubMed

    Bloch, Olga; Broide, Efrat; Ben-Yehudah, Gilad; Cantrell, Dror; Shirin, Haim; Rapoport, Micha J

    2015-01-01

    T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R) expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO) by high-energy (HE) diet and by streptozotocin (STZ) in Sprague Dawly (SD) rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis. PMID:25893200

  18. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience

    PubMed Central

    Rampelli, S. K.; Rajesh, N. G.; Srinivas, B. H.; Harichandra Kumar, K. T.; Swaminathan, R. P.; Priyamvada, P. S.

    2016-01-01

    There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36–0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04–0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022). PMID:27512296

  19. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience.

    PubMed

    Rampelli, S K; Rajesh, N G; Srinivas, B H; Harichandra Kumar, K T; Swaminathan, R P; Priyamvada, P S

    2016-01-01

    There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022). PMID:27512296

  20. Intestinal Intravascular Large B-cell Lymphoma Mimicking Ulcerative Colitis with Secondary Membranoproliferative Glomerulonephritis.

    PubMed

    Kaneyuki, Daisuke; Komeno, Yukiko; Yoshimoto, Hiroshi; Yoshimura, Naoki; Iihara, Kuniko; Ryu, Tomiko

    2016-01-01

    A 47-year-old woman with ulcerative colitis (UC) was admitted to our hospital for renal dysfunction and progressive anemia. Colonoscopy revealed intestinal lesions and pathological findings showed intravascular large B-cell lymphoma (IVLBCL). According to the polymerase chain reaction analysis of sequential rectal specimens, we concluded that she suffered from intestinal BCL, not UC. After chemotherapy, her renal function progressed to nephrotic syndrome. The pathological findings of renal biopsy specimens indicated membranoproliferative glomerulonephritis (MPGN). Chemotherapy was continued and led to the remission of BCL and MPGN. We herein describe the first case of intestinal IVLBCL mimicking UC with secondary MPGN. PMID:27580553

  1. Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

    PubMed

    Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

    2015-01-01

    We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure. PMID:25876581

  2. Renal granuloma and immunoglobulin M-complex glomerulonephritis: a case of common variable immunodeficiency?

    PubMed

    Benoit, Geneviève; Lapeyraque, Anne-Laure; Sartelet, Hervé; Saint-Cyr, Claire; Le Deist, Françoise; Haddad, Elie

    2009-03-01

    Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and recurrent bacterial infections. Granulomatous infiltrations are occasionally found in the lymphoid or solid organs of affected patients, but renal involvement is rare. We present a case of possible CVID with interstitial noncaseating granuloma and immunoglobulin (IgM)-complex glomerulonephritis with a membranoproliferative pattern and with a favorable response to corticosteroids, intravenously administered immunoglobulins (IVIGs) and rituximab. CVID must be included in the differential diagnosis of renal granuloma and should be differentiated from sarcoidosis to ensure appropriate therapy. PMID:18696117

  3. Necrotizing and crescentic glomerulonephritis with membranous nephropathy in a patient exposed to levamisole-adulterated cocaine

    PubMed Central

    Carrara, Camillo; Emili, Stefano; Lin, Mercury; Alpers, Charles E.

    2016-01-01

    Levamisole is an antihelminthic agent widely used as an adulterant of illicit cocaine recently implicated as a cause of antineutrophil cytoplasmic antibody (ANCA)–associated microscopic polyangiitis in cocaine abusers. An isolated case of membranous nephropathy (MN) associated with levamisole exposure has also been reported. We report the first case, to our knowledge, of a patient with both microscopic polyangiitis manifest as a pauci-immune necrotizing and crescentic glomerulonephritis and concurrent MN in the setting of chronic cocaine abuse and presumed levamisole exposure, raising the hypothesis that levamisole was the causative agent in the development of this rare dual glomerulopathy. PMID:26985374

  4. Nephrotic Syndrome Secondary to Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits of Lambda Light Chain

    PubMed Central

    Yun, Seongseok; Braunhut, Beth L.; Walker, Courtney N.; Bhati, Waheed; Sussman, Amy N.; Anwer, Faiz

    2014-01-01

    We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent. PMID:25136462

  5. Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2015-01-01

    Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333

  6. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    NASA Technical Reports Server (NTRS)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  7. Towards new avenues in the management of lupus glomerulonephritis.

    PubMed

    Mok, C C

    2016-04-01

    Renal involvement in systemic lupus erythematosus (SLE) carries substantial morbidity and mortality. Conventional immunosuppressive agents (cyclophosphamide and azathioprine) have suboptimal efficacy and substantial toxicity. Mycophenolate mofetil has emerged as an alternative agent for both induction and maintenance therapy in lupus nephritis because of its reduced gonadal toxicity, despite its failure to demonstrate superiority over cyclophosphamide in pivotal studies. The calcineurin inhibitor tacrolimus has equivalent efficacy to cyclophosphamide and mycophenolate mofetil for inducing remission of lupus nephritis. Although rituximab has shown promise in refractory lupus nephritis, combining rituximab with mycophenolate mofetil as initial therapy offers no additional benefit. Considerable interethnic variation is evident in the efficacy and tolerability of the various immunosuppressive regimens, which necessitates individualized treatment and comparison of the efficacy of new regimens across different ethnic groups. For example, low-dose combinations of tacrolimus and mycophenolate mofetil seem to be more effective than pulse cyclophosphamide as induction therapy in Chinese patients. The same regimen has also been used successfully to treat refractory proliferative and membranous lupus nephritis in patients of various ethnic groups. Finally, novel serum and urinary biomarkers are being validated for diagnosis, prognostic stratification and early recognition of flares in lupus nephritis. PMID:26729459

  8. Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma

    PubMed Central

    Anaele, Cyriacus Uzoma; Srisung, Weeraporn; Tomacruz, Yvette; Laski, Melvin

    2015-01-01

    Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare. PMID:26120578

  9. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

    PubMed

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-06-01

    Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  10. The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades.

    PubMed

    Woo, K-T; Chan, C-M; Mooi, C Y; -L-Choong, H; Tan, H-K; Foo, M; Lee, G S L; Anantharaman, V; Lim, C-H; Tan, C-C; Lee, E J C; Chiang, G S C; Tan, P H; Boon, T H; Fook-Chong, S; Wong, K-S

    2010-11-01

    This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries. PMID:20979946

  11. The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection

    PubMed Central

    Oda, Takashi; Yoshizawa, Nobuyuki; Yamakami, Kazuo; Sakurai, Yutaka; Takechi, Hanako; Yamamoto, Kojiro; Oshima, Naoki; Kumagai, Hiroo

    2012-01-01

    It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity. PMID:23118507

  12. CD34+ fibroblast-like cells in the interstitial infiltrates in glomerulonephritis - an immunohistochemical observation.

    PubMed

    Gluhovschi, Cristina; Potencz, Elena; Lazar, Elena; Petrica, Ligia; Bozdog, Gheorghe; Gadalean, Florica; Bob, Flaviu; Gluhovschi, Adrian; Cioca, Daniel; Velciov, Silvia

    2012-12-01

    CD34 cells in the interstitial infiltrates in glomerulonephritis (GN) could be the turning point between regenerative processes and interstitial fibrosis. The aim of our study was to assess the presence of CD34+ cells in the interstitial infiltrates in GN. A cross-sectional study of 33 patients with glomerulonephritis, mean age: 43.3 ±11.31 years, 20 male and 13 female, was conducted. Conventional stains, as well as immunohistochemistry for the CD34 antigen were employed on kidney biopsies. Strength of immunohistochemical reaction was assessed semi-quantitatively. Regarding the percentage of cases with CD34+ cells in the interstitial infiltrates out of 33 patients: cells of interstitial infiltrates were 27.3% positive. The percentage of cases showing CD34+ cells at the level of interstitial infiltrates was: 44.4% in FSGS, 14.3% in membranoproliferative GN, 28.6% in membranous nephropathy, 20% in mesangial proliferative GN, 0% in minimal change disease, and 50% in crescentic GN. With the exception of minimal change disease, CD34+ cells were found in the interstitial infiltrates in all histopathological forms of GN. Some of these cells were spindle-shaped fibroblast-like cells. As inflammation in the tubulointerstitial compartment either resolves or proceeds to fibrosis, aims at reversing this process will benefit from analyses of the interstitial infiltrates harboring CD34+ cells. PMID:23359197

  13. Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma.

    PubMed

    Anaele, Cyriacus Uzoma; Srisung, Weeraporn; Tomacruz, Yvette; Laski, Melvin

    2015-01-01

    Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare. PMID:26120578

  14. Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy

    PubMed Central

    Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea

    2016-01-01

    Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management. PMID:27293925

  15. Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy

    PubMed Central

    Khalighi, Mazdak A.; Wang, Shihtien; Henriksen, Kammi J.; Bock, Margret; Keswani, Mahima; Meehan, Shane M.; Chang, Anthony

    2016-01-01

    Background Post-infectious glomerulonephritis (PIGN) is an immune complex-mediated glomerular injury that typically resolves. Dominant C3 deposition is characteristic of PIGN, but with the emergence of C3 glomerulonephritis (C3GN) as a distinct entity, it is unclear how the pathologic similarities between PIGN and C3GN should be reconciled. Therefore, nephrologists and nephropathologists need additional guidance at the time of biopsy. Methods We studied 23 pediatric and young adult patients diagnosed with PIGN. Patients were divided into two groups, one with co-dominance between C3 and immunoglobulins and the other meeting proposed diagnostic criteria for C3GN. Clinical and pathological features were compared. Results No clinical and/or pathological features could distinguish between those with C3-co-dominant deposits and those with C3 dominance. Nearly all patients in both groups regained their baseline renal function without clinical intervention. Conclusions Although the identification of abnormalities of the alternative pathway of complement is characteristic of C3GN, testing is not widely available and the turnaround time often exceeds 1 month. Our study found that PIGN with either co-dominant or dominant C3 deposition in a cohort of young patients has excellent short-term outcomes. Close clinical observation for persistent abnormalities, such as hypocomplementemia, prolonged hematuria or proteinuria, is recommended to single out patients that may harbor intrinsic complement abnormalities. PMID:27274823

  16. A case of infectious endocarditis-associated crescentic glomerulonephritis with intracranial hemorrhage.

    PubMed

    Miyata, Eri; Nakayama, Masaru; Amano, Kazushi; Hirano, Tadashi; Uesugi, Noriko

    2010-01-01

    A 55-year-old woman was admitted to our hospital because of fever and renal impairment. The patient had undergone a tooth extraction 11 months prior to admission. Echocardiography demonstrated vegetation on the mitral valve, and Streptococcus mitis was detected on blood culture. Accordingly, infectious endocarditis (IE) was diagnosed. Renal biopsy showed crescentic glomerulonephritis. Based on the negative staining for immunoglobulins and complement components in immunofluorescence study and lack of dense deposits on electron microscopy, the renal involvement was considered to be of the pauci-immune type. Subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) developed simultaneously following commencement of antibiotic therapy. The intracranial involvement improved by conservative therapy. Antibiotic treatment resulted in gradual control of IE infection and improvement of renal function. A repeated renal biopsy, performed about 5 months after the first biopsy, showed amelioration of glomerular injury and interstitial damage. To our knowledge, our case was the second to report simultaneous developments of both SAH and SDH secondary to IE. We postulate that the glomerular injury was associated with IE. We report here a rare case of IE-associated crescentic glomerulonephritis with complications of SAH and SDH. PMID:20155718

  17. Renal infarction and immune-mediated glomerulonephritis in sheep (Ovis aries) chronically implanted with indwelling catheters.

    PubMed

    Rao, Varada P; Poutahidis, Theofilos; Marini, Robert P; Holcombe, Hilda; Rogers, Arlin B; Fox, James G

    2006-07-01

    Microbial infections are common sequelae in humans and animals implanted with long-term intravascular catheters. Understanding the pathophysiology of infectious morbidity is critical to improving quality of care in catheterized subjects. Here, we describe findings in 6 clinically healthy, male sheep implanted with indwelling aortic or cardiac catheters for 6 to 10 mo. We isolated multiple bacterial species including Serratia spp., Enterobacter agglomerans, Eschericia coli, Klebsiella oxytoca, and K. pneumoniae in aerobic cultures from catheter tips. Although sheep were clinically asymptomatic, 1 or both kidneys from all animals contained wedge-shaped infarcts of varying size and number. Microscopic examination revealed (a) marked fibrosis with mild inflammatory cell infiltrate consistent with chronic foreign body reaction around catheters; (b) moderate to severe, diffuse, subacute to chronic membranoproliferative glomerulonephritis and mild, multifocal chronic interstitial nephritis; and (c) mesangial immune-complex deposition as demonstrated by direct immunofluorescence technique. The finding of bacterial colonization of catheters together with chronic glomerulonephritis and immune-complex deposits in kidneys in clinically asymptomatic sheep underscores the need for close microbiologic monitoring of catheter implants and assessment of kidney function in animals instrumented for long-term vascular access. PMID:16884173

  18. Lutheran/basal cell adhesion molecule accelerates progression of crescentic glomerulonephritis in mice

    PubMed Central

    Huang, Jin; Filipe, Anne; Rahuel, Cécile; Bonnin, Philippe; Mesnard, Laurent; Guérin, Coralie; Wang, Yu; Le Van Kim, Caroline; Colin, Yves; Tharaux, Pierre-Louis

    2014-01-01

    Migration of circulating leukocytes from the vasculature into the surrounding tissue is an important component of the inflammatory response. Among the cell surface molecules identified as contributing to leukocyte extravasation is VCAM-1, expressed on activated vascular endothelium, which participates in all stages of leukocyte–endothelial interaction by binding to leukocyte surface expressed integrin VLA-4. However, not all VLA-4-mediated events can be linked to VCAM-1. A novel interaction between VLA-4 and endothelial Lutheran (Lu) blood group antigens and basal cell adhesion molecule (BCAM) proteins has been recently shown, suggesting that Lu/BCAM may have a role in leukocyte recruitments in inflamed tissues. Here, we assessed the participation of Lu/BCAM in the immunopathogenesis of crescentic glomerulonephritis. High expression of Lu/BCAM in glomeruli of mice with rapidly progressive glomerulonephritis suggests a potential role for the local expression of Lu/BCAM in nephritogenic recruitment of leukocytes. Genetic deficiency of Lu/BCAM attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet deposition in glomeruli. Furthermore, we found a pro-adhesive interaction between human monocyte α4β1 integrin and Lu/BCAM proteins. Thus, Lu/BCAM may have a critical role in facilitating the accumulation of monocytes and macrophages, thereby exacerbating renal injury. PMID:24429403

  19. Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

    PubMed

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V

    2016-08-01

    Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys. PMID:26791097

  20. Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.

    PubMed

    Sharma, Bhupesh; Singh, Nirmal; Singh, Manjeet

    2008-03-01

    Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions. PMID:18208924

  1. Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis

    PubMed Central

    Jirholt, Pernilla; Turesson, Olof; Wing, Kajsa; Holmdahl, Rikard; Kihlberg, Jan; Stern, Anna; Mårtensson, Inga-Lill; Henningsson, Louise; Gustafsson, Kenth; Gjertsson, Inger

    2016-01-01

    Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases. PMID:27159398

  2. Tissue factor initiates glomerular fibrin deposition and promotes major histocompatibility complex class II expression in crescentic glomerulonephritis.

    PubMed Central

    Erlich, J. H.; Holdsworth, S. R.; Tipping, P. G.

    1997-01-01

    Increased glomerular tissue factor (TF) expression is associated with glomerular fibrin deposition and renal failure in human and experimental crescentic glomerulonephritis (GN). However, the in vivo functional contribution of TF to the development of glomerular fibrin deposition, crescent formation, and renal failure in GN has not been established. The contribution of TF to fibrin deposition and renal injury was studied in a rabbit model of crescentic GN in which glomerular macrophage infiltration, augmented TF expression, and fibrin deposition are prominent. Administration of anti-TF antibody inhibited glomerular TF activity in nephritic glomeruli by 96%, without affecting macrophage accumulation or systemic indices of coagulation. Anti-TF antibody significantly reduced glomerular fibrin deposition (fibrin scores, 0.43 +/- 0.10 (treated) and 1.40 +/- 0.19 (control); P < 0.0005), crescent formation (0.33 +/- 0.05 (treated) and 1.0 +/- 0.06 (control); P < 0.0005), and development of renal failure (serum creatinine, 168 +/- 22 mumol/l (treated) and 267 +/- 35 mumol/l (control); P < 0.04). This was associated with significant reduction in proteinuria (1189 +/- 277 mg/24 hours (treated) and 2060 +/- 336 mg/24 hours (control); P < 0.03) and expression of MHC class II antigen in glomeruli (1.25 +/- 0.41 (treated) and 2.83 +/- 0.53 (control); P < 0.03) and in tubules and interstitial areas. These data demonstrate that TF is the major in vivo initiator of fibrin deposition in crescentic GN. The reduction in proteinuria and glomerular major histocompatibility class II antigen expression by TF inhibition suggests that TF may also activate other mediators that contribute to glomerular injury. Images Figure 1 PMID:9060825

  3. Four different synthetic peptides of proteolipid protein induce a distinct antibody response in MP4-induced experimental autoimmune encephalomyelitis.

    PubMed

    Recks, Mascha S; Grether, Nicolai B; van der Broeck, Franziska; Ganscher, Alla; Wagner, Nicole; Henke, Erik; Ergün, Süleyman; Schroeter, Michael; Kuerten, Stefanie

    2015-07-01

    Here we studied the autoantibody specificity elicited by proteolipid protein (PLP) in MP4-induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis (MS). In C57BL/6 (B6) mice, antibodies were induced by immunization with one of the two extracellular and by the intracellular PLP domain. Antibodies against extracellular PLP were myelin-reactive in oligodendrocyte cultures and induced mild spinal cord demyelination upon transfer into B cell-deficient J(H)T mice. Remarkably, also antibodies against intracellular PLP showed binding to intact oligodendrocytes and were capable of inducing myelin pathology upon transfer into J(H)T mice. In MP4-immunized mice peptide-specific T(H)1/T(H)17 responses were mainly directed against the extracellular PLP domains, but also involved the intracellular epitopes. These data suggest that both extracellular and intracellular epitopes of PLP contribute to the pathogenesis of MP4-induced EAE already in the setting of intact myelin. It remains to be elucidated if this concept also applies to MS itself. PMID:25959684

  4. DETECTORS AND EXPERIMENTAL METHODS: Equivalent properties of single event burnout induced by different sources

    NASA Astrophysics Data System (ADS)

    Yang, Shi-Yu; Cao, Zhou; Da, Dao-An; Xue, Yu-Xiong

    2009-05-01

    The experimental results of single event burnout induced by heavy ions and 252Cf fission fragments in power MOSFET devices have been investigated. It is concluded that the characteristics of single event burnout induced by 252Cf fission fragments is consistent to that in heavy ions. The power MOSFET in the “turn-off" state is more susceptible to single event burnout than it is in the “turn-on" state. The thresholds of the drain-source voltage for single event burnout induced by 173 MeV bromine ions and 252Cf fission fragments are close to each other, and the burnout cross section is sensitive to variation of the drain-source voltage above the threshold of single event burnout. In addition, the current waveforms of single event burnouts induced by different sources are similar. Different power MOSFET devices may have different probabilities for the occurrence of single event burnout.

  5. Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality.

    PubMed

    Botchkarev, Vladimir A; Sharov, Andrey A

    2016-03-01

    Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. PMID:26902124

  6. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  7. α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.

    PubMed

    Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio

    2016-06-01

    Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes. PMID:26749278

  8. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    PubMed

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough. PMID:1611233

  9. Protective effect of ketoconazole against experimentally induced gastric ulcers in rats.

    PubMed

    Al Moutaery, Ahmed R

    2003-01-01

    Recent studies suggest the critical role of inflammatory mediators in the genesis and healing of gastric ulcers. Ketoconazole a commonly used anti-fungal agent has a potent immunomodulatory action. The present investigation was undertaken to study the effect of ketoconazole on chemically and stress induced gastric ulcers in rats. Experimental gastric lesions in rats were induced by water immersion restraint stress, indomethacin and ethanol. Acid secretion studies were undertaken in pylorus ligated rats with and without ketoconazole. The level of myeloperoxidase (marker of neutrophil activity) non-protein sulfhydryl compounds and gastric wall mucus were measured after ethanol induced gastric lesions. Ketoconazole treatment resulted in significant protection against stress; indomethacin and ethanol induced gastric lesions in rats. Ketoconazole also dose dependently attenuated ethanol induced increase in myeloperoxidase activity and protected gastric mucosa against ethanol-induced depletion of non-protein sulfhydryl. These findings point towards the mediation of neutrophils and sulfhydryl compounds in ketoconazole induced cytoprotection. In conclusion, this study clearly shows anti-acid secretory, anti-ulcer and cytoprotective activity of ketoconazole. PMID:15686104

  10. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization

    PubMed Central

    Dominguez, Elisa; Raoul, William; Calippe, Bertrand; Sahel, José-Alain; Guillonneau, Xavier; Paques, Michel; Sennlaub, Florian

    2015-01-01

    Aims Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined. Methods and Results We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO. Conclusion Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease. PMID:26208283

  11. Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats.

    PubMed

    Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

    2014-01-01

    Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action. PMID:24753752

  12. Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats

    PubMed Central

    Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

    2014-01-01

    Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action. PMID:24753752

  13. The effect of various drugs on experimentally induced ulcers in immobilized rats

    NASA Technical Reports Server (NTRS)

    Schramm, H.

    1978-01-01

    Experiments related to the importance of functional disorders in the central nervous system in connection with stomach diseases were performed on Wistar rats. Assuming that severe mental strains may be triggering factors for such disorders, testing of the effects of different drugs on experimentally induced ulcers in these rats was done. The immobilization method described by Bonfils was used. Particular importance was placed on the sex related difference which appeared.

  14. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

    PubMed Central

    Pandurangan, Ashok Kumar; Mohebali, Nooshin; Norhaizan, Mohd Esa; Looi, Chung Yeng

    2015-01-01

    Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA. PMID:26251571

  15. Experimental pathology of local tissue damage induced by Bothrops asper snake venom.

    PubMed

    Gutiérrez, José María; Rucavado, Alexandra; Chaves, Fernando; Díaz, Cecilia; Escalante, Teresa

    2009-12-01

    Envenomations by Bothrops asper are often associated with complex and severe local pathological manifestations, including edema, blistering, dermonecrosis, myonecrosis and hemorrhage. The pathogenesis of these alterations has been investigated at the experimental level. These effects are mostly the consequence of the direct action of zinc-dependent metalloproteinases (SVMPs) and myotoxic phospholipases A(2) (PLA(2)s). SVMPs induce hemorrhage, blistering, dermonecrosis and general extracellular matrix degradation, whereas PLA(2)s induce myonecrosis and also affect lymphatic vessels. In addition, the prominent vascular alterations leading to hemorrhage and edema may contribute to ischemia and further tissue necrosis. The mechanisms of action of SVMPs and PLA(2)s are discussed in detail in this review. Venom-induced tissue damage plays also a role in promoting bacterial infection. A prominent inflammatory reaction develops as a consequence of these local pathological alterations, with the synthesis and release of abundant mediators, resulting in edema and pain. However, whether inflammatory cells and mediators contribute to further tissue damage is not clear at present. Muscle tissue regeneration after venom-induced pathological effects is often impaired, thus resulting in permanent tissue loss and dysfunction. SVMP-induced microvessel damage is likely to be responsible of this poor regenerative outcome. Antivenoms are only partially effective in the neutralization of B. asper-induced local effects, and the search for novel toxin inhibitors represents a potential avenue for improving the treatment of this serious aspect of snakebite envenomation. PMID:19303033

  16. The effect of cannabinoids on dinitrofluorobenzene-induced experimental asthma in mice.

    PubMed

    Bozkurt, Turgut Emrah; Kaya, Yesim; Durlu-Kandilci, Nezahat Tugba; Onder, Sevgen; Sahin-Erdemli, Inci

    2016-09-01

    Cannabinoids have anti-inflammatory effects and can produce bronchodilation in the airways. We have investigated the effects of cannabinoids on tracheal hyperreactivity and airway inflammation in dinitrofluorobenzene (DNFB)-induced experimental non-atopic asthma in mice. 5-hydroxytryptamine (5-HT)-induced contraction response was enhanced while carbachol- and electrical field stimulation-induced contractions, and isoprenaline-induced relaxation responses were remained unchanged in DNFB group. The increased 5-HT-induced contractions were inhibited by incubation with either atropine or tetrodotoxin. DNFB application resulted in increased macrophage number in the bronchoalveolar lavage fluid (BALF). In vivo ACEA (CB1 agonist) treatment prevented the increase in 5-HT contractions, while JWH133 (CB2 agonist) had no effect. However, neither ACEA nor JWH133 prevented the increase in macrophage number in BALF. In vitro ACEA incubation also inhibited the increase in 5-HT contraction in DNFB group. These results show that cannabinoid CB1 receptor agonist can prevent tracheal hyperreactivity to 5-HT in DNFB-induced non-atopic asthma in mice. PMID:27216000

  17. Analytical and experimental study of flow phenomena in noncavitating rocket pump inducers

    NASA Technical Reports Server (NTRS)

    Lakshminarayana, B.

    1981-01-01

    The flow processes in rocket pump inducers are summarized. The experimental investigations were carried out with air as the test medium. The major characteristics features of the rocket pump inducers are low flow coefficient (0.05 to 0.2) large stagger angle (70 deg to 85 deg) and high solidity blades of little or no camber. The investigations are concerned with the effect of viscosity not the effects of cavitation. Flow visualization, conventional and hot wire probe measurement inside and at the exit of the blade passage, were the analytical methods used. The experiment was carried out using four three and two bladed inducers with cambered blades. Both the passage and the exit flow were measured. The basic research and boundary layer investigation was carried out using a helical flat plate (of some dimensions as the inducer blades tested), and flat plate helical inducer (four bladed). Detailed mean and turbulence flow field inside the passage as well as the exit of the rotor were derived from these measurement. The boundary layer, endwall, and other passage data reveal extremely complex nature of the flow, with major effects of viscosity present across the entire passage. Several analyses were carried out to predict the flow field in inducers. These included an approximate analysis, the shear pumping analysis, and a numerical solution of exact viscous equations with approximate modeling for the viscous terms.

  18. Membranoproliferative glomerulonephritis

    MedlinePlus

    ... glomeruli. The glomeruli of the kidney help filter wastes and fluids from the blood to form urine. ... the glomerular basement membrane. This membrane helps filter wastes and extra fluids from the blood. Damage to ...

  19. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    PubMed

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. PMID:15551386

  20. Effects of nabumetone and dipyrone on experimentally induced gastric ulcers in rats.

    PubMed

    Yıldırım, Engin; Sağıroğlu, Oya; Kılıç, Fatma S; Erol, Kevser

    2013-04-01

    Nabumetone and dipyrone are non-acidic, nonsteroidal anti-inflammatory drugs. Both of them are known to have weak inhibitory effects of cyclooxygenases. Gastric side effects represent the most common adverse drug effects of the widely used nonsteroidal anti-inflammatory drugs. The gastric effects of these drugs may be comparable in experimental ulcer models. In the present study, the gastric ulcerogenic activity of nabumetone and dipyrone were investigated on stress- and diethyldithiocarbamate-induced experimental ulcer models by determining the ulcer index and gastric mucus secretion in rats. It was found that diethyldithiocarbamate increased both ulcer index and mucus secretion. Nabumetone inhibited dose-dependently the increase of diethyldithiocarbamate-induced mucus secretion. Dipyrone inhibited both stress- and diethyldithiocarbamate-induced ulcer index and mucus secretion. Nabumetone inhibited stress-induced ulcer index at 25-mg/kg dose but stimulated dose-dependently mucus secretion. These effects may be attributed to their non-acidic structures and weak inhibitory effects on gastric mucosal cyclooxygenases. PMID:23129452

  1. Effect of ranitidine on healing of experimentally induced gastric ulcers in ponies.

    PubMed

    MacAllister, C G; Sangiah, S

    1993-07-01

    Thirty young ponies were examined endoscopically for evidence of gastric ulceration. Seven ponies had noninduced gastric ulcers present at the initial examination and were eliminated from the study. In an attempt to induce gastric ulcers experimentally, flunixin meglumine (1.1 mg/kg of body weight, IM, q 8 h) was administered for 7 days to the 23 ponies with endoscopically normal gastric mucosa. During the 7 days of flunixin administration, 11 ponies developed gastric ulcers that were appropriate for study. The 11 ponies were randomly allotted to 2 groups. Group-A (n = 5) and group-B (n = 6) ponies received ranitidine (4.4 mg/kg, PO, q 8 h) and corn syrup, respectively, until ulcers healed or for a maximum of 40 days. General anesthesia was induced every 3 to 5 days for visual evaluation of ulcer healing by use of a video endoscope. The earliest complete healing of gastric lesions observed in a corn syrup-treated pony was at 17 days. At 40 days, 3 of 5 and 3 of 6 ponies of the ranitidine and corn syrup-treated groups, respectively, had healed ulcers. Results of this study indicate that: noninduced gastric ulcers may be common in young ponies, flunixin meglumine may be effective in inducing gastric ulcers for gastric healing studies in young ponies, and ranitidine (4.4 mg/kg, q 8 h) is not significantly effective in accelerating healing of experimentally induced gastric ulcers in ponies under conditions of this study. PMID:8368605

  2. Duration of Analgesia Induced by Acupuncture-Like TENS on Experimental Heat Pain

    PubMed Central

    Brochu, Marilyne; Dupuis-Michaud, Cynthia; Pagé, Catherine; Popovic, Draga; Simard, Marie-Eve

    2013-01-01

    Background. Acupuncture-like TENS (AL-TENS) is a treatment modality that can be used to temporarily reduce pain. However, there is no clear data in the literature regarding the specific duration of analgesia induced by AL-TENS. Objectives. To describe and quantify the duration and magnitude of AL-TENS analgesia on experimental heat pain in healthy subjects and verify if the duration or magnitude of analgesia induced by the AL-TENS was influenced by the duration of the application of the AL-TENS (15 versus 30 minutes). Methods. A repeated-measures, intrasubject randomized experimental design was used, where each participant was his/her own control. 22 healthy volunteers underwent heat pain stimulations with a contact thermode before (pretest) and after (posttest) AL-TENS application (15 and 30 minutes). Outcome measures included subjective pain during AL-TENS, duration, and magnitude of AL-TENS-induced analgesia. Results. Survival analysis showed that the median duration of AL-TENS analgesia was 10 minutes following the application of either 15 or 30 minutes of AL-TENS. The magnitude of analgesia following either application was comparable at all points in time (P values > 0.05) and ranged between −20% and −36% pain reduction. Conclusion. Only half of the participants still had heat-pain analgesia induced by the AL-TENS at 15 minutes postapplication. PMID:27335882

  3. Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin-33

    PubMed Central

    Shadie, A M; Herbert, C; Kumar, R K

    2014-01-01

    High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m3) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m3) concentration of ovalbumin to simulate an allergen-induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen-induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10. PMID:24730559

  4. Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon?

    PubMed

    Eisenberg, Elon; Suzan, Erica; Pud, Dorit

    2015-03-01

    Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of opioid dose escalation without adequate analgesia, true evidence in support of this notion is relatively limited. Most studies conducted in the context of acute and experimental pain, which seemingly demonstrated evidence for OIH, actually might have measured other phenomena such as acute opioid withdrawal or tolerance. OIH studies in patients with chronic pain have used various experimental pain models (such as cold pain tolerance or heat pain intensity). Therefore, the fact that they have yielded inconsistent results is hard to interpret. Thus far, with the exception of a few clinical case reports on OIH in patients with cancer pain and one prospective study in patients with chronic neuropathic pain, evidence for OIH in patients with chronic or cancer-related pain is lacking. Whether experimental pain models are necessary for establishing the clinical diagnosis of OIH, and which specific model is preferred, are yet to be determined. PMID:25128284

  5. Experimental and theoretical characterization of deep penetration welding threshold induced by 1-μm laser

    NASA Astrophysics Data System (ADS)

    Zou, J. L.; He, Y.; Wu, S. K.; Huang, T.; Xiao, R. S.

    2015-12-01

    The deep penetration-welding threshold (DPWT) is the critical value that describes the welding mode transition from the thermal conduction to the deep penetration. The objective of this research is to clarify the DPWT induced by the lasers with wavelength of 1 μm (1-μm laser), based on experimental observation and theoretical analysis. The experimental results indicated that the DPWT was the ratio between laser power and laser spot diameter (P/d) rather than laser power density (P/S). The evaporation threshold was smaller than the DPWT, while the jump threshold of the evaporated mass flux in the molten pool surface was consistent with the DPWT. Based on the force balance between the evaporation recoil pressure and the surface tension pressure at the gas-liquid interface of the molten pool as well as the temperature field, we developed a self-focusing model, which further confirmed the experimental results.

  6. Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

    PubMed

    Wegner, Alexander; Elsenbruch, Sigrid; Rebernik, Laura; Roderigo, Till; Engelbrecht, Elisa; Jäger, Marcus; Engler, Harald; Schedlowski, Manfred; Benson, Sven

    2015-10-01

    A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes. PMID:26058036

  7. Phospholipase A2 Receptor-Positive Idiopathic Membranous Glomerulonephritis with Onset at 95 Years: Case Report

    PubMed Central

    Kubota, Keiichi; Hoshino, Junichi; Ueno, Toshiharu; Mise, Koki; Hazue, Ryo; Sekine, Akinari; Yabuuchi, Junko; Yamanouchi, Masayuki; Suwabe, Tatsuya; Kikuchi, Koichi; Sumida, Keiichi; Hayami, Noriko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Akiyama, Shinichi; Maruyama, Shoichi; Ubara, Yoshifumi

    2016-01-01

    A 95-year-old woman was admitted to our hospital for evaluation of bilateral lower-limb edema persisting for 3 months. Serum creatinine was 1.55 mg/dl, and urinary protein excretion was 9.1 g/day. Renal biopsy revealed stage 1 membranous glomerulonephritis (MGN) with immunoglobulin G4-dominant staining. This patient did not have any underlying disease such as infection with hepatitis B or C virus or malignancy, and anti-phospholipase A2 receptor (PLA2R) antibody was detected in the serum. Accordingly, idiopathic MGN was diagnosed. Corticosteroid therapy was avoided, but hemodialysis was required to treat generalized edema. The patient is currently doing well. This is the oldest reported case of idiopathic MGN with positivity for anti-PLA2R antibody. PMID:27390744

  8. Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis.

    PubMed

    Mustonen, J; Pasternack, A; Helin, H; Nikkilä, M

    1985-01-01

    In an unselected series of patients with IgA glomerulonephritis, old age, high blood pressure, and high urinary protein excretion at the time of renal biopsy were found to correlate with impaired renal function, whereas sex, estimated duration of the disease, or high serum IgA levels did not. The following clinical features were favorable prognostic signs: asymptomatic proteinuria, macroscopic hematuria, and isolated microscopic hematuria. The degree of diffuse mesangial alteration and the presence of segmental glomerular lesions correlated clearly with the subsequent clinical outcome. Vascular lesions, i.e. arteriosclerosis and renal vascular deposition of C3, were most often present in patients with severe glomerulopathy. The presence of electron-dense deposits in glomerular capillary walls was also an unfavorable prognostic finding. Renal biopsy findings of interstitial infiltrates of inflammatory cells and IgA distributed along glomerular capillary walls were usually associated with extrarenal manifestations of the disease. PMID:4014321

  9. An immunohistological study of feline glomerulonephritis using the peroxidase-antiperoxidase method.

    PubMed

    Arthur, J E; Lucke, V M; Newby, T J; Bourne, F J

    1984-07-01

    Twenty-two cases of feline glomerulonephritis were investigated for the presence of immune complexes within the glomerulus using the peroxidase-antiperoxidase (PAP) method. This method was used with formalin-fixed paraffin-wax embedded tissues which were pretreated with trypsin and with frozen sections of kidney tissue. Of a total of 25 kidney specimens examined (two cats had repeated biopsies) the composition of the deposits was 23/25 IgG, 17/25 C3, 11/25 IgM and 2/25 IgA. Serial studies of two cats showed a progression of the disease from initial nephrotic syndrome to chronic renal failure. With the more severe form of the disease there was a tendency for the deposition of complement and more than one class of immunoglobulin within the glomeruli. PMID:6382492

  10. Treatment of choroidal neovascularisation secondary to membranoproliferative glomerulonephritis type II with intravitreal ranibizumab

    PubMed Central

    McCullagh, Donal; Silvestri, Giuliana; Maxwell, Alexander P

    2014-01-01

    Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by electron-dense deposits of complement components in the glomerular basement membrane and retinal pigment epithelium. Approximately, 10% of affected individuals develop serious ocular complications similar to age-related macular degeneration such as choroidal neovascularisation (CNV), which has been managed with photocoagulation or photodynamic therapy; however, these treatments can impact visual acuity. We report the case of a 42-year-old woman with MPGN II presenting with decreased visual acuity and paracentral scotoma in her left eye due to an extrafoveal choroidal neovascular membrane (growth of new vessels under the retina). The patient was successfully treated with intravitreal ranibizumab (Lucentis) with restoration of visual function. This case highlights the successful management of CNV secondary to MPGN II with the antivascular endothelial growth factor agent ranibizumab and emphasises the importance of early referral of patients with MPGN II who are reporting of visual ‘distortion’. PMID:24895384

  11. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN

    PubMed Central

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-01-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560

  12. [Autoimmune hepatitis and membranous glomerulonephritis under immune therapy in chronic hepatitis C].

    PubMed

    Paparoupa, Maria; Huy Ho, Ngoc Ahn; Schuppert, Frank

    2016-05-01

    A 63-year-old patient is evaluated for an unclear weight loss with general malaise and fatigue for several months. Serological examination reveales the first diagnosis of a hepatitis-C-virus-genotype-1b-infection with an initial viral load of 980 000 IU / ml. The duration of the infection is suggested to be more than 6 months. Because of the initially elevated anti-nuclear-antibodies (ANA) the diagnosis of an autoimmune hepatitis needs to be excluded. All other liver related autoantibodies and the immunoglobulins (Ig) IgG, IgA and IgM are normal. A liver biopsy is conducted. After a short test with non-pegylated interferon (IFN) liver enzymes remain stable and treatment with pegylated IFN-alfa-2a and ribavirin (RBV) is initiated. The patient is a "rapid viral responder" and his viral load is found under the detection limit within 4 weeks under therapy. On the 16th week, liver enzymes increase rapidly. ANA's and IgG-immunoglobulins are positive. A second lever biopsy does not confirm the diagnosis of autoimmune hepatitis and the treatment is continued under careful observation of all relevant liver parameters. 21 weeks after the initiation of the treatment, massive peripheral edema, hypoproteinemia and proteinuria are observed. The renal biopsy reveales membranous glomerulonephritis. Because of the preserved renal function, no acute immunosuppression is initiated and the treatment gets completed after overall 24 weeks. Liver and renal parameters return quickly back to normal after treatment discharge. This is the first report of a combined autoimmune reaction with development of autoimmune hepatitis and glomerulonephritis under INF and RBV antiviral therapy for a chronic hepatitis-C-infection. The occurrence of autoimmune manifestations should especially be considered in genetically susceptible individuals or those with positive autoimmunity markers. The initiation of INF for the treatment of chronic hepatitis-C-infection has to be critically evaluated since

  13. Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

    PubMed Central

    Pinto, Sergio Wyton L.; Mastroianni-Kirsztajn, Gianna; Sesso, Ricardo

    2015-01-01

    Background Scarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode. Methods In this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria. Results Comparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m2 and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C. Conclusions During the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur. PMID:25962068

  14. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN.

    PubMed

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-07-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560

  15. Anaerococcus urinomassiliensis sp. nov., isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis.

    PubMed

    Morand, A; Cornu, F; Tsimaratos, M; Lagier, J-C; Cadoret, F; Fournier, P-E; Raoult, D

    2016-09-01

    We report the main characteristics of 'Anaerococcus urinomassiliensis' strain FC4(T) (CSURP2143) that was isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis. PMID:27408746

  16. Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

    PubMed Central

    Özkardeş, Alper Bilal; Bozkurt, Birkan; Dumlu, Ersin Gürkan; Tokaç, Mehmet; Yazgan, Aylin Kılıç; Ergin, Merve; Erel, Özcan; Kılıç, Mehmet

    2015-01-01

    Objective: To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein-induced acute pancreatitis. Material and Methods: In 30 Wistar albino rats (male; 240–260 g), acute pancreatitis was induced by an intraperitoneal injection of cerulein (50 μg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained. Results: Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose-dependent manner (35% in Group 2, 75% in Group 3; p=0.048). Conclusion: Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied the specific inhibition of

  17. Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats.

    PubMed

    Devaraj, V C; Gopala Krishna, B; Viswanatha, G L; Satya Prasad, V; Vinay Babu, S N

    2011-07-01

    Raphinus sativus Linn (Cruciferae) commonly known as 'Radish' is a multipurpose herb cultivated in different parts of the world for its edible roots and leaves. The present study was aimed to evaluate the antiulcer activity of leaf extracts of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus ligation induced gastric ulcer in rats. The acute oral toxicity study revealed that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth of this dose was selected for evaluation of antiulcer activity. In acetic acid induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered significant protection against acetic acid induced ulcers when compared to control group. While in pylorus ligation induced ulcer model the ERS, EARS and AQRS showed significant protection by decreasing the ulcer index, total acidity and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to possess antiulcer property in the experimental animal models of gastric ulcers, which is consistent with the literature report in the folk medicine. PMID:23960756

  18. Effects of Guchang Capsule on Dextran Sulphate Sodium-Induced Experimental Ulcerative Colitis in Mice

    PubMed Central

    Liu, Baoshan; Liu, Tong; Wang, Xiaohong; Zheng, Xin; Wang, Hong; Ma, Lin

    2016-01-01

    Guchang capsule (GC) is a Chinese materia medica standardized product extracted from 15 Chinese traditional medical herbs and it has been clinically used in the treatment of intestinal disease. In this study, in order to extend the research of GC in intestinal disease, we were aiming to evaluate potential effects of GC on dextran sulphate sodium- (DSS-) induced murine experimental colitis and to elucidate the underlying mechanisms. GC treatment attenuated DSS-induced body weight loss and reduced the mortality. Moreover, GC treatment prevented DSS-induced colonic pathological damage; meanwhile it inhibited proinflammatory cytokines production in colon tissues. In vitro, GC significantly reduced LPS-induced proinflammatory cytokines production via inhibiting the activation of NF-κB in macrophage cells, and the expressions of several long noncoding RNAs (lncRNAs) which were reported in regulating NF-κB signaling pathway were obviously affected by adding GC into culture medium. In conclusion, our data suggested that administration of GC exhibits therapeutic effects on DSS-induced colitis partially through regulating the expression of NF-κB related lncRNAs in infiltrating immune cells. PMID:27313642

  19. Experimental rat model for alcohol-induced osteonecrosis of the femoral head

    PubMed Central

    Okazaki, Shunichiro; Nagoya, Satoshi; Tateda, Kenji; Katada, Ryuichi; Mizuo, Keisuke; Watanabe, Satoshi; Yamashita, Toshihiko; Matsumoto, Hiroshi

    2013-01-01

    Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber–DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1–24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model. PMID:24020403

  20. Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis.

    PubMed Central

    Gómez-Chiarri, M.; Ortiz, A.; González-Cuadrado, S.; Serón, D.; Emancipator, S. N.; Hamilton, T. A.; Barat, A.; Plaza, J. J.; González, E.; Egido, J.

    1996-01-01

    Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis. Images Figure 1 Figure 2 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:8546219

  1. Experimental investigations on flow induced vibration of an externally excited flexible plate

    NASA Astrophysics Data System (ADS)

    Purohit, Ashish; Darpe, Ashish K.; Singh, S. P.

    2016-06-01

    Flow-induced vibration of a harmonically actuated flexible plate in the wake of an upstream bluff body is experimentally investigated. The experiments are performed in an open-ended wind tunnel. A flexible plate trailing a bluff body is under fluid induced excitation due to the flowing fluid. The additional external excitation to the trailing plate is applied using an electro-magnetic exciter. The frequency and amplitude of the external harmonic excitation are selected as variable parameters in the experiments and their effect on the plate vibration and is investigated. To know the nature of acoustic pressure wave generated from the vibrating system, near-field acoustic pressure is also measured. A laser vibrometer, a pressure microphone and a high-speed camera are employed to measure the plate vibration, pressure signal, and instantaneous images of the plate motion respectively. The results obtained indicate that the dynamics of the plate is influenced by both the flow-induced excitation and external harmonic excitation. When frequency of the two excitations is close enough, a large vibration level and a high tonal sound pressure are observed. At higher amplitude of external excitation, the frequency component corresponding to the flow-induced excitation is found to reduce significantly in the frequency spectrum of the vibration signal. It is observed that, for certain range of excitation frequency, the plate vibration first reduces, reaches a minimum value and then increases with increase in the level of external excitation. A fair qualitative agreement of the experimental results with numerical simulation result of the past study has been noted. In addition to the experiments, the role of phase difference between the flow-induced excitation generated from the front obstacle and externally applied harmonic excitation is investigated through numerical simulations. The result obtained reveals that the final steady state vibration of the coupled system is

  2. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    PubMed

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. PMID:24632022

  3. The effect of topical metronidazole therapy on experimentally-induced periodontitis in the beagle dog.

    PubMed

    Klinge, B; Kuvatanasuhati, J; Attström, R; Kalfas, S; Edwardsson, S

    1992-10-01

    The present study was performed to assess the effect of topical metronidazole therapy on ligature-induced periodontitis in beagle dogs. 6 beagle dogs with experimentally-induced periodontitis on the mandibular 2nd, 3rd and 4th premolars were treated with metronidazole 10% dental paste 2 x daily for 4 weeks in an open placebo-controlled study using a split-mouth design. Recordings of probing pocket depth, bleeding on probing and gingival index were performed before commencement of treatment and repeated weekly during the 4-weeks treatment period. Concurrently, samples for microbiological analysis were collected from 2 of the dogs. The results demonstrated that probing pocket depth, bleeding on probing and gingival index had improved significantly in the metronidazole-treated side compared with the placebo-treated side. Black pigmented Bacteroides spp. and Spirochetes, present in all samples before treatment, were eliminated from the metronidazole-treated side after the 1st week of treatment and throughout the treatment period, whereas they were present in all samples from the placebo-treated side. The result of the present study demonstrates that topical application of metronidazole in a dental paste, improves the clinical features of the experimentally-induced periodontitis and eliminates some of the micro-organisms associated with the disease. PMID:1447390

  4. Effects of aescin on testicular repairment in rats with experimentally induced varicocele.

    PubMed

    Tian, R H; Ma, M; Zhu, Y; Yang, S; Wang, Z Q; Zhang, Z S; Wan, C F; Li, P; Liu, Y F; Wang, J L; Liu, Y; Yang, H; Zhang, Z Z; Liu, L H; Gong, Y H; Li, F H; Hu, H L; He, Z P; Huang, Y R; Li, Z

    2014-06-01

    This study was conducted to investigate the effects of aescin treatment in a rodent model treated with an experimentally induced varicocele. Experimental varicocele was induced by partial ligation of the left renal vein of rats. Aescin administration was performed daily for 4 weeks after the varicocele induction. Seven weeks later, a contrast-enhanced ultrasound was performed of the rats' testis to assess testicular blood flow. The animals were sacrificed, and H&E staining was then used to evaluate testicular pathological changes and polymorphonuclear leucocytes density. Cauda epididymal sperm counts and motility were evaluated. Blood was collected for the measurement of follicle-stimulating hormone, luteinising hormone and testosterone. Contrast-enhanced ultrasound showed that there were significant decreases in testicular blood flow in the aescin-treated groups compared with those in control varicocele group. Testicular oedema was detected in those rats treated with a varicocele but without aescin, while no oedema was found in the experimental group. H&E staining showed dysfunctional spermatogenesis in both cohorts; however, polymorphonuclear leucocytes density was significantly reduced in aescin-treated groups. There was an increase in sperm counts of the aescin-treated groups. Our study demonstrated that aescin could exert therapeutical effects on reversal of testicular lesions in varicocele rats. PMID:23682825

  5. The effect of experimentally induced sedentariness on mood and psychobiological responses to mental stress

    PubMed Central

    Endrighi, Romano; Steptoe, Andrew; Hamer, Mark

    2016-01-01

    Background Evidence suggests a link between sedentary behaviours and depressive symptoms. Mechanisms underlying this relationship are not understood, but inflammatory processes may be involved. Autonomic and inflammatory responses to stress may be heightened in sedentary individuals contributing to risk, but no study has experimentally investigated this. Aims To examine the effect of sedentary time on mood and stress responses using an experimental design. Method Forty-three individuals were assigned to a free-living sedentary condition and to a control condition (usual activity) in a cross-over, randomised fashion and were tested in a psychophysiology laboratory after spending 2 weeks in each condition. Participants completed mood questionnaires (General Health Questionnaire and Profile of Mood States) and wore a motion sensor for 4 weeks. Results Sedentary time increased by an average of 32 min/day (P = 0.01) during the experimental condition compared with control. Being sedentary resulted in increases in negative mood independent of changes in moderate to vigorous physical activity (ΔGHQ = 6.23, ΔPOMS = 2.80). Mood disturbances were associated with greater stress-induced inflammatory interleukin-6 (IL-6) responses (β = 0.37). Conclusions Two weeks of exposure to greater free-living sedentary time resulted in mood disturbances independent of reduction in physical activity. Stress-induced IL-6 responses were associated with changes in mood. PMID:26294364

  6. Experimental study to explore the 8Be-induced nuclear reaction via the Trojan horse method

    NASA Astrophysics Data System (ADS)

    Wen, Qun-Gang; Li, Cheng-Bo; Zhou, Shu-Hua; Irgaziev, Bakhadir; Fu, Yuan-Yong; Spitaleri, Claudio; La Cognata, Marco; Zhou, Jing; Meng, Qiu-Ying; Lamia, Livio; Lattuada, Marcello

    2016-03-01

    To explore a possible indirect method for 8Be induced astrophysical reactions, the 8Be=(8Be+n ) cluster structure has been studied via the Trojan horse method. For the first time a 8Be nucleus having an ultrashort lifetime is studied by the Trojan horse method and a 9Be nucleus in the ground state is used for this purpose. The 9Be nucleus is assumed to have a (8Be+n ) cluster structure and used as a Trojan horse nucleus. The 8Be nucleus acts as a participant, while the neutron is a spectator to the virtual 8Be+d →α +6Li reaction via the 3-body reaction 8Be+d →α +6Li+n . The experimental neutron momentum distribution inside 9Be has been reconstructed. The agreement between the experimental momentum distribution and the theoretical one indicates that a (8Be+n ) cluster structure inside 9Be is very likely. Therefore, the experimental study of 8Be induced reactions, for example, the measurement of the 8Be+α →12C reaction proceeding through the Hoyle state, is possible.

  7. Effect of somatosensory amplification and trait anxiety on experimentally induced orthodontic pain.

    PubMed

    Cioffi, Iacopo; Michelotti, Ambrosina; Perrotta, Stefania; Chiodini, Paolo; Ohrbach, Richard

    2016-04-01

    The perception of pain varies considerably across individuals and is affected by psychological traits. This study aimed to investigate the combined effects of somatosensory amplification and trait anxiety on orthodontic pain. Five-hundred and five adults completed the State Trait Anxiety Inventory (STAI) and the Somatosensory Amplification Scale (SSAS). Individuals with combined STAI and SSAS scores below the 20th percentile (LASA group: five men and 12 women; mean age ± SD = 22.4 ± 1.3 yr) or above the 80th percentile (HASA group: 13 men and seven women; mean age ± SD = 23.7 ± 1.0 yr) were selected and filled in the Oral Behaviors Checklist (OBC). Orthodontic separators were placed for 5 d in order to induce experimental pain. Visual analog scales (VAS) were administered to collect ratings for occlusal discomfort, pain, and perceived stress. Pressure pain thresholds (PPT) were measured. A mixed regression model was used to evaluate pain and discomfort ratings over the 5-d duration of the study. At baseline, the LASA group had statistically significantly higher PPT values for the masseter muscle than did the HASA group. During the experimental procedure, the HASA group had statistically significantly higher discomfort and pain. A significant difference in pain ratings during the 5 d of the study was found for subjects in the HASA group. Higher OBC values were statistically significantly positively associated with pain. Somatosensory amplification and trait anxiety substantially affect experimentally induced orthodontic pain. PMID:26918812

  8. Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model.

    PubMed

    Bulut, Gulay; Basbugan, Yildiray; Ari, Elif; Erten, Remzi; Bektas, Havva; Alp, Hamit Hakan; Bayram, Irfan

    2016-06-01

    This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n = 32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A + P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4 μg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A + P had lower mean fractional sodium excretion (p < 0.001) as well as higher creatinine clearance (p = 0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p = 0.035) and serum 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p < 0.001) were significantly lower; superoxide dismutase (p = 0.024) and glutathione peroxidase (p = 0.007) activities of renal tissue were significantly higher in group A + P than in group A. The mean scores of tubular necrosis (p = 0.024), proteinaceous casts (p = 0.038), medullary congestion (p = 0.035), and VEGF immunoexpression (p = 0.018) were also lower in group A + P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model. PMID:26983906

  9. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA. PMID:24048981

  10. Oral Administration of Ginseng Ameliorates Cyclosporine-Induced Pancreatic Injury in an Experimental Mouse Model

    PubMed Central

    Lim, Sun Woo; Doh, Kyoung Chan; Jin, Long; Piao, Shang Guo; Heo, Seong Beom; Zheng, Yu Fen; Bae, Soo Kyung; Chung, Byung Ha; Yang, Chul Woo

    2013-01-01

    Background This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. Methods Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2′-deoxyguanosine in serum, tissue sections, and culture media. Results Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2′-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. Conclusions The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress. PMID:24009697

  11. Antidiarrhoeal activity of leaf extract of celosia argentea in experimentally induced diarrhoea in rats.

    PubMed

    Sharma, Praveen; Vidyasagar, Gali; Singh, Sunder; Ghule, Santosh; Kumar, Bimlesh

    2010-01-01

    In order to scientifically apprise some of the anecdotal, folkloric, ethno medical uses of celosia argentea, the present study was undertaken to examine the antidiarrhoeal properties of alcoholic extract of leaves of Celosia argentea on diarrhoea by using different experimental models. Anti-diarrhoeal effect was evaluated by castor oil induced diarrhoea, charcoal meal test and PGE(2) induced diarrhoea. Loperamide (2 mg/kg) and atropine (0.1mg/kg) were used as standard drugs. Extract was used in 100 and 200 mg/kg dose. It produced dose related anti-diarrhoeal effect. Results suggest that it may act centrally and may inhibit the PGE(2) to give anti-diarrhoeal effects. Result of charcoal meal test also suggests its anti-muscarinic activity. PMID:22247831

  12. The antioxidant response induced by Lonicera caerulaea berry extracts in animals bearing experimental solid tumors.

    PubMed

    Gruia, Maria Iuliana; Oprea, Eliza; Gruia, Ion; Negoita, Valentina; Farcasanu, Ileana Cornelia

    2008-01-01

    Lonicera caerulea is a species of bush native to the Kamchatka Peninsula (Russian Far East) whose berries have been extensively studied due to their potential high antioxidant activity. The aim of our work was to investigate the in vivo effects of the antioxidant action of Lonicera caerulea berry extracts on the dynamics of experimentally-induced tumors. Our data showed that aqueous Lonicera caerulaea extracts reduced the tumor volume when administered continuously during the tumor growth and development stages, but augmented the tumor growth when the administration of extracts started three weeks before tumor grafting. Prolonged administration of Lonicera caerulaea berry extracts induced the antioxidant defense mechanism in the tumor tissues, while surprisingly amplifying the peripheral oxidative stress. PMID:18560338

  13. Boehmeria nivea Attenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

    PubMed Central

    Shin, Eun Ju; Sung, Mi Jeong; Yang, Hye Jeong; Kim, Myung Sunny; Hwang, Jin-Taek

    2014-01-01

    We examined the therapeutic effect of an ethanol extract derived from Boehmeria nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500 mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that B. nivea extract is effective in preventing colitis. PMID:25045208

  14. Protective effects of Punica granatum in experimentally-induced gastric ulcers.

    PubMed

    Alam, Mohd Sarfaraz; Alam, Mohd Aftab; Ahmad, Sayeed; Najmi, Abul Kalam; Asif, Mohd; Jahangir, Tamanna

    2010-11-01

    In the present investigation standardized aqueous methanolic extract of Punica (AMP) was used for its possible ulcer protective activity in wistar rats against different experimental models. Preliminary phytochemical screening of AMP reveals the presence of saponin, tannins, and flavonoids, which may be responsible for its activity. HPTLC finger prints of AMP showed the presence of 12 spots at different (retention factor) rf values. Oral administration of AMP (490 and 980 mg/kg bw) significantly reduced the ulcer lesion index produced by alcohol, indomethacin, and aspirin, at both doses in rats. Further, in pylorus-ligated rats AMP significantly reduces the ulcer lesions, gastric volume, and total acidity. It prevents the ulceration by increasing the pH and mucus secretion in pylorus ligated rats. The present study shows the anti-ulcer activity of AMP in experimentally-induced gastric ulcers. PMID:20846023

  15. Activity of "nonspecific pancreatic carboxylesterase" in rat serum in experimentally induced acute pancreatitis (preliminary results).

    PubMed

    Kálmán, A; Kálmán, Z; Velösy, G; Vargha, G; Vargha, G; Papp, M

    1989-01-01

    The aim of this study was to obtain more information on the serum level of "nonspecific pancreatic carboxylesterase" (PCE) in experimentally induced acute pancreatitis in rats. The effects of caerulein stimulation, hepatic duct ligation, bile-pancreatic duct ligation or the effect of retrograde injection of saline, 5% taurocholate and sunflower oil were investigated. The activity of PCE and amylase was measured in the serum, pancreatic tissue, pancreatic juice and ascitic fluid. The changes in PCE activity were greater (both in directions to increase or decrease) than that of amylase, produced by different experimental procedures. The results confirm the thesis that the serum activity of PCE is a more sensitive diagnostic method than that of amylase to detect the inflammatory process in the pancreas or the effect of obstruction of the pancreatic duct. PMID:2480696

  16. A combined experimental and numerical investigation of roughness induced supersonic boundary layer transition

    NASA Astrophysics Data System (ADS)

    Zhao, Yunfei; Liu, Wei; Xu, Dan; Gang, Dundian; Yi, Shihe

    2016-01-01

    The effect of surface roughness on boundary layer transition is of great importance to hypersonic vehicles. In this paper, both experimental and numerical methods are used to investigate the laminar-turbulent transition of a Mach 3 flat-plate boundary layer induced by isolated roughness element. Good agreements are achieved between experimental data and high-order numerical simulations. It is observed that, with increasing height of roughness, the transition tends to move forward. Two different types of transition mechanisms are found according to the height of the roughness elements. For the smallest roughness height of h=1 mm, the shear layer instability in the wake region appears to be the leading mechanism for transition to turbulence. For two larger roughness elements of h=2 mm and h=4 mm, strong unsteadiness is developed from the upstream separation zone and transition is immediately accomplished, which indicates that the absolute instability in upstream separation zone dominates the transition.

  17. The Effects of Experimentally Induced Low Back Pain on Spine Rotational Stiffness and Local Dynamic Stability.

    PubMed

    Ross, Gwyneth B; Mavor, Matthew; Brown, Stephen H M; Graham, Ryan B

    2015-09-01

    Local dynamic stability, quantified using the maximum finite-time Lyapunov exponent (λ max), and the muscular contributions to spine rotational stiffness can provide pertinent information regarding the neuromuscular control of the spine during movement tasks. The primary goal of the present study was to assess if experimental capsaicin-induced low back pain (LBP) affects spine stability and the neuromuscular control of repetitive trunk movements in a group of healthy participants with no history of LBP. Fourteen healthy males were recruited for this investigation. Each participant was asked to complete three trials (baseline, in pain, and recovery) of 35 cycles of a repetitive trunk flexion/extension task at a rate of 0.25 Hz. Local dynamic stability and the muscular contributions to lumbar spine rotational stiffness were significantly impaired during the LBP trial compared to the baseline trial (p < 0.05); however, there was a trend for these measures to recover after a 1 h rest. This study provides evidence that capsaicin can effectively induce LBP, thereby altering spine rotational stiffness and local dynamic stability. Future research should directly compare the effects capsaicin-induced LBP and intramuscular/intraligamentous induced LBP on these same variables. PMID:25663629

  18. Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats

    PubMed Central

    Noor, Neveen A; Fahmy, Heba M; Mohammed, Faten F; Elsayed, Anwar A; Radwan, Nasr M

    2015-01-01

    Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats (“EAE” group). 2- “N. sativa + EAE” group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- “EAE + N. sativa” group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE. PMID:26261504

  19. Bromocriptine induces parapoptosis as the main type of cell death responsible for experimental pituitary tumor shrinkage

    SciTech Connect

    Palmeri, Claudia Mariela Petiti, Juan Pablo; Valle Sosa, Liliana del; Gutierrez, Silvina; Paul, Ana Lucia de; Mukdsi, Jorge Humberto; Torres, Alicia Ines

    2009-10-01

    Bromocriptine (Bc) produces pituitary tumoral mass regression which induces the cellular death that was classically described as apoptosis. However, recent works have related that other mechanisms of cell death could also be involved in the maintenance of physiological and pathological pituitary homeostasis. The aim of this study was to evaluate and characterize the different types of cell death in the involution induced by Bc in experimental rat pituitary tumors. The current study demonstrated that Bc induced an effective regression of estrogen induced pituitary tumors by a mechanism identified as parapoptosis. This alternative cell death was ultrastructurally recognized by extensive cytoplasmic vacuolization and an increased cell electron density, represented around 25% of the total pituitary cells counted. Furthermore, the results obtained from biochemical assays did not correspond to the criteria of apoptosis or necrosis. We also investigated the participation of p38, ERK1/2 and PKC{delta} in the parapoptotic pathway. An important observation was the significant increase in phosphorylated forms of these MAPKs, the holoenzyme and catalytic fragments of PKC{delta} in nuclear fractions after Bc administration compared to control and estrogen treated rats. Furthermore, the immunolocalization at ultrastructural level of these kinases showed a similar distribution pattern, with a prevalent localization at nuclear level in lactotrophs from Bc treated rats. In summary, we determined that parapoptosis is the predominant cell death type involved in the regression of pituitary tumors in response to Bc treatment, and may cause the activation of PKC{delta}, ERK1/2 and p38.

  20. A proposal for the experimental detection of CSL induced random walk

    PubMed Central

    Bera, Sayantani; Motwani, Bhawna; Singh, Tejinder P.; Ulbricht, Hendrik

    2015-01-01

    Continuous Spontaneous Localization (CSL) is one possible explanation for dynamically induced collapse of the wave-function during a quantum measurement. The collapse is mediated by a stochastic non-linear modification of the Schrödinger equation. A consequence of the CSL mechanism is an extremely tiny violation of energy-momentum conservation, which can, in principle, be detected in the laboratory via the random diffusion of a particle induced by the stochastic collapse mechanism. In a paper in 2003, Collett and Pearle investigated the translational CSL diffusion of a sphere, and the rotational CSL diffusion of a disc, and showed that this effect dominates over the ambient environmental noise at low temperatures and extremely low pressures (about ten-thousandth of a pico-Torr). In the present paper, we revisit their analysis and argue that this stringent condition on pressure can be relaxed, and that the CSL effect can be seen at the pressure of about a pico-Torr. A similar analysis is provided for diffusion produced by gravity-induced decoherence, where the effect is typically much weaker than CSL. We also discuss the CSL induced random displacement of a quantum oscillator. Lastly, we propose possible experimental set-ups justifying that CSL diffusion is indeed measurable with the current technology. PMID:25563619

  1. Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats.

    PubMed

    Noor, Neveen A; Fahmy, Heba M; Mohammed, Faten F; Elsayed, Anwar A; Radwan, Nasr M

    2015-01-01

    Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats ("EAE" group). 2- "N. sativa + EAE" group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- "EAE + N. sativa" group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE. PMID:26261504

  2. Ameliorative potential of fluoxetine/raloxifene combination on experimentally induced breast cancer.

    PubMed

    Kabel, Ahmed M; Elkhoely, Abeer A

    2016-04-01

    Breast cancer is one of the most common types of malignancies in females worldwide. Targeting the estrogen receptors alone with raloxifene (RAL) reduces the incidence of estrogen receptor positive tumors. Fluoxetine (FLX) is one of selective serotonin reuptake inhibitors that was proven to have anticancer properties. Our aim was to detect the effects of RAL/FLX combination on experimentally induced breast cancer. Eighty female Wistar rats were divided into four equal groups: 7,12-Dimethyl Benzanthracene (DMBA) induced breast cancer group, DMBA+RAL, DMBA+FLX and DMBA+RAL+FLX. Tumor volume, tissue malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and transforming growth factor beta1 (TGF-β1) were determined in the tumor tissues. Parts of the tumor were subjected to histopathological examination. RAL or FLX alone or in combination induced significant increase in tumor CAT and SOD with significant decrease in tumor volume, tissue MDA, TNF-α, IL-6 and TGF-β1 and alleviated the histopathological and immunohistochemical changes compared to DMBA group. In conclusion, RAL/FLX combination had a better effect than each of RAL or FLX alone against DMBA-induced breast cancer in rats which may represent a new therapeutic modality for management of breast cancer. PMID:26881735

  3. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. PMID:26794590

  4. A proposal for the experimental detection of CSL induced random walk.

    PubMed

    Bera, Sayantani; Motwani, Bhawna; Singh, Tejinder P; Ulbricht, Hendrik

    2015-01-01

    Continuous Spontaneous Localization (CSL) is one possible explanation for dynamically induced collapse of the wave-function during a quantum measurement. The collapse is mediated by a stochastic non-linear modification of the Schrödinger equation. A consequence of the CSL mechanism is an extremely tiny violation of energy-momentum conservation, which can, in principle, be detected in the laboratory via the random diffusion of a particle induced by the stochastic collapse mechanism. In a paper in 2003, Collett and Pearle investigated the translational CSL diffusion of a sphere, and the rotational CSL diffusion of a disc, and showed that this effect dominates over the ambient environmental noise at low temperatures and extremely low pressures (about ten-thousandth of a pico-Torr). In the present paper, we revisit their analysis and argue that this stringent condition on pressure can be relaxed, and that the CSL effect can be seen at the pressure of about a pico-Torr. A similar analysis is provided for diffusion produced by gravity-induced decoherence, where the effect is typically much weaker than CSL. We also discuss the CSL induced random displacement of a quantum oscillator. Lastly, we propose possible experimental set-ups justifying that CSL diffusion is indeed measurable with the current technology. PMID:25563619

  5. A proposal for the experimental detection of CSL induced random walk

    NASA Astrophysics Data System (ADS)

    Bera, Sayantani; Motwani, Bhawna; Singh, Tejinder P.; Ulbricht, Hendrik

    2015-01-01

    Continuous Spontaneous Localization (CSL) is one possible explanation for dynamically induced collapse of the wave-function during a quantum measurement. The collapse is mediated by a stochastic non-linear modification of the Schrödinger equation. A consequence of the CSL mechanism is an extremely tiny violation of energy-momentum conservation, which can, in principle, be detected in the laboratory via the random diffusion of a particle induced by the stochastic collapse mechanism. In a paper in 2003, Collett and Pearle investigated the translational CSL diffusion of a sphere, and the rotational CSL diffusion of a disc, and showed that this effect dominates over the ambient environmental noise at low temperatures and extremely low pressures (about ten-thousandth of a pico-Torr). In the present paper, we revisit their analysis and argue that this stringent condition on pressure can be relaxed, and that the CSL effect can be seen at the pressure of about a pico-Torr. A similar analysis is provided for diffusion produced by gravity-induced decoherence, where the effect is typically much weaker than CSL. We also discuss the CSL induced random displacement of a quantum oscillator. Lastly, we propose possible experimental set-ups justifying that CSL diffusion is indeed measurable with the current technology.

  6. Postinfectious glomerulonephritis secondary to Erythrovirus B19 (Parvovirus B19): case report and review of the literature.

    PubMed

    Marco, Helena; Guermah, Imane; Matas, Lurdes; Hernández, Alba; Navarro, Maruja; Lopez, Dolores; Bonet, Josep

    2016-04-01

    A previously healthy 32-yearold woman developed arterial hypertension, proteinuria, and hematuria (nephritic syndrome) with normal renal function and was diagnosed with post-infectious glomerulonephritis secondary to parvovirus B19 infection. The renal biopsy showed endocapillary glomerulonephritis, with positive IgG, C3, and C1q immunoreactivity in the capillary walls and ultrastructural evidence of subendothelial deposits. The diagnosis of parvovirus B19 infection was confirmed by IgG/IgM serological positivity and parvovirus DNA demonstration in both peripheral blood and kidney tissue. Glomerular involvement improved spontaneously. To be noted are the atypical signs and symptoms of our patient who, unlike previously reported cases, failed to show fever, skin rash, or affected relatives. PMID:26833301

  7. Proteomics and glomerulonephritis: A complementary approach in renal pathology for the identification of chronic kidney disease related markers.

    PubMed

    L'Imperio, Vincenzo; Smith, Andrew; Chinello, Clizia; Pagni, Fabio; Magni, Fulvio

    2016-04-01

    Glomerulonephritis (GN) is one of the most common origins of chronic kidney disease and its careful evaluation is crucial for prognostic and therapeutic purposes, with the renal biopsy still playing a central role for the diagnosis. However, due to its invasiveness, it is not devoid of complications and many investigations have focused on identifying biomarkers for chronic kidney diseases using less-invasive and easy-to-collect samples, such as urine and blood. In this context, proteomics has played a crucial role in determining the molecular changes related to disease progression and early pathological glomerular modifications. Here, we report a review of selected literature for each GN, based on selected works published in the last 10 years, showing how these approaches have generated clinically relevant findings in the study of glomerulonephritis. We also describe several proteomic strategies, highlighting their technical advantages and limitations, future perspectives for proteomic applications in the study of GNs, and their possible application in routine practice. PMID:26642820

  8. Experimental Study of a Single-Coil Induced-Electromotive-Force Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Matthews, Clarence W.; Cuddihy, William F.

    1961-01-01

    An experimental study was made of a single-coil induced-electromotive-force plasma accelerator which used a capacitor discharge for the driving force. A strong shock was observed from the first pulse with a velocity of 10(exp 6) centimeters per second. This shock was followed by three or four discharges which produced plasmoids moving at about 5 x 10(exp 6) centimeters per second. The efficiency of the accelerator was estimated to be about 3 percent in the production of the high-velocity plasmoids. Suggestions are made for the improvement of this type of accelerator.

  9. Experimental Study of the Cross Sections of {alpha}-Particle Induced Reactions on 209Bi

    SciTech Connect

    Hermanne, A.; Tarkanyi, F.; Takacs, S.; Szucs, Z.

    2005-05-24

    Alpha particle induced reactions for generation of 211At used in therapeutic nuclear medicine and possible contaminants were investigated with the stacked foil activation technique on natural bismuth targets up to E{alpha}=39 MeV. Excitation functions for the reactions 209Bi({alpha},2n)211At, 209Bi({alpha},3n)210At, 209Bi({alpha},x) 210Po obtained from direct alpha emission measurements and gamma spectra from decay products are compared with earlier literature values. Thick target yields have been deduced from the experimental cross sections.

  10. Renal interstitial mast cell count is significantly higher in membranoproliferative glomerulonephritis than in class IV lupus nephritis.

    PubMed

    Kaczmarczyk, Karolina; Musiał, Jacek; Soja, Jerzy; Kuźniewski, Marek; Gala-Błądzińska, Agnieszka; Białas, Magdalena; Okoń, Krzysztof

    2015-06-01

    Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; in LN class IV morphologic lesions may be similar to the lesions in primary membranoproliferative glomerulonephritis (MPGN). The aim of the study was to compare the counts of tryptase-positive and chymase-positive mast cells between LN class IV and MPGN. The material consisted of 61 renal biopsies: 32 with lupus nephritis class IV, and 29 with membranoproliferative glomerulonephritis. Chymase- and tryptase-positive cells were stained by immunohistochemistry and subsequently counted. The mean count of chymase-positive mast cells was 21.94 for the whole group, 12.66 for LN class IV and 32.18 for MPGN. The mean count of tryptase-positive cells was 34.94 hpf for the entire group, 22.98 for LN class IV and 48. 13 for MPGN. The differences between lupus nephritis and membranoproliferative glomerulonephritis were significant both for chymase- and tryptase-positive cells. Both chymase-positive MC counts and tryptase-positive MC counts correlated with relative interstitial volume (RIV) (R=0.35 and R=0.28, respectively) and with creatinine level (R=0.35 and R=0.43, respectively). There was also a significant correlation between age, creatinine level and RIV (R=0.28 and R=0.26, respectively). PMID:26247528

  11. Fibrillary glomerulonephritis with small fibrils in a patient with the antiphospholipid antibody syndrome successfully treated with immunosuppressive therapy

    PubMed Central

    Javaid, Muhammad M; Denley, Helen; Tagboto, Senyo

    2007-01-01

    Background Fibrillary glomerulonephritis is a rare cause of progressive renal dysfunction, often leading to the need for dialysis within a few years. The role of immunosuppressive treatment is still uncertain although this has been tried with variable success. Case presentation A 56 year old woman with the antiphospholipid antibody syndrome (IgM anticardiolipin antibodies) was seen in the nephrology clinic with haematuria, proteinuria, and worsening renal function. A renal biopsy demonstrated a mesangial proliferative glomerulonephritis on light microscopy and smaller fibrils (10.6–13.8 nm in diameter) than is usual for fibrillary glomerulonephritis (typically 18–22 nm) on electron microscopy. Amyloidosis was excluded following detailed evaluation. On account of rapidly worsening renal failure she was started on cyclophosphamide and prednisolone which led to the partial recovery and stabilization of her renal function. Conclusion This case highlights the need for routine electron microscopy in native renal biopsies, where the differential diagnosis is wide and varied and the light and immunofluorescence microscopic findings may be non specific. PMID:17490479

  12. A Computational and Experimental Study of Nonlinear Aspects of Induced Drag

    NASA Technical Reports Server (NTRS)

    Smith, Stephen C.

    1996-01-01

    performance of the split-tip wing was also investigated by wing tunnel experiments. Induced drag was determined from force measurements by subtracting the estimated viscous drag, and from an analytical drag-decomposition method using a wake survey. The experimental results confirm the computational prediction.

  13. TNF-α Involvement in Insulin Resistance Induced by Experimental Scorpion Envenomation

    PubMed Central

    Ait-Lounis, Aouatef; Laraba-Djebari, Fatima

    2012-01-01

    Background Scorpion venom induces systemic inflammation characterized by an increase in cytokine release and chemokine production. There have been few experimental studies assessing the effects of scorpion venom on adipose tissue function in vivo. Methodology/Principal Findings To study the adipose tissue inflammation (ATI) induced by Androctonus australis hector (Aah) venom and to assess possible mechanisms of ATI, mice (n = 6, aged 1 month) were injected with Aah (0.45 mg/kg), toxic fraction of Aah (FTox-G50; 0.2 mg/kg) or saline solution (control). Inflammatory responses were evaluated by ELISA and cell sorting analyses in adipose tissue 45 minutes and 24 hours after injection. Quantitative real-time PCR was used to assess the regulation of genes implicated in glucose uptake. The titers of selected inflammatory cytokines (IL-1β, IL-6 and TNF-α) were also determined in sera and in insulin target tissues. The serum concentration of IL-1β rose 45 minutes after envenomation and returned to basal level after 24 hours. The pathophysiological effects of the venom after 24 hours mainly involved M1-proinflammatory macrophage infiltration in adipose tissue combined with high titers of IL-1β, IL-6 and TNF-α. Indeed, TNF-α was strongly induced in both adipose tissue and skeletal muscle. We studied the effects of Aah venom on genes implicated in insulin-stimulated glucose uptake. Insulin induced a significant increase in the expression of the mRNAs for hexokinase 2 and phosphatidylinositol 3-kinase in both skeletal muscle and adipose tissue in control mice; this upregulation was completely abolished after 24 hours in mice envenomed with Aah or FTox-G50. Conclusions/Significance Our findings suggest that Aah venom induces insulin resistance by mechanisms involving TNF-α-dependent Map4k4 kinase activation in the adipose tissue. PMID:22816003

  14. RNase L contributes to experimentally induced type I diabetes onset in mice

    PubMed Central

    Zeng, Chun; Yi, Xin; Zipris, Danny; Liu, Hongli; Zhang, Lin; Zheng, Qiaoyun; Krishnamurthy, Malathi; Jin, Ge; Zhou, Aimin

    2014-01-01

    The cause of type I diabetes continues to be a focus of investigation. Studies have revealed that interferon (IFN)-α in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type I diabetes. However, how IFN-α contributes to the onset of type I diabetes is obscure. In this study, we found that 2-5A dependent RNase L (RNase L), an IFN-α-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type I diabetes. By using RNase L deficient, rat insulin promoter (RIP)-B7.1 transgenic mice which are more vulnerable to environmental harmful factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin (STZ), a drug which can artificially induce type I-like diabetes in experimental animals. Immunohistochemical staining showed that the population of infiltrated CD8+ T-cells was remarkably reduced in the islets of RNase L deficient mice, suggesting that RNase L may contribute to type I diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas in induced conditions. Our findings provide new insight into the molecular mechanism underlying β-cells destruction and may suggest novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L. PMID:25287058

  15. [Characterization of an experimental model of monosodium- glutamate-induced convulsions in the amphibian Bufo spp].

    PubMed

    Alfaro, F; Blas, O; Gutiérrez-Padilla, R; Feria-Velasco, A

    1990-01-01

    In previous reports, Feria-Velasco et al. characterized an experimental model of convulsions in rats induced by monosodium glutamate (MSG) with evaluation of the motor behavior and neurochemical parameters. In the present work, MSG injected in toads (Bufo spp) reproduced the model of convulsions with some peculiarities. The electrocorticographic recordings in toads after MSG injection were similar to those obtained in rats after administration of convulsant agents. Most of the toads injected with MSG (81.8%) showed convulsions preceded by an episode of stereotyped movements and signs of hyperexcitability. Latency for convulsions and frequency of convulsive episodes were similar to what has been reported in rats injected with MSG. However, the duration of convulsive period was larger than that seen in rats, and no deaths were recorded in toads. The peculiar feature of amphibia regarding their cerebral structures and their blood-brain barrier (BBB) make the amphibian model, an interesting and valuable one in studying experimentally induced convulsions, as well as the role of BBB in these phenomena. PMID:1669233

  16. Experimental investigation of flow induced dust acoustic shock waves in a complex plasma

    NASA Astrophysics Data System (ADS)

    Jaiswal, S.; Bandyopadhyay, P.; Sen, A.

    2016-08-01

    We report on experimental observations of flow induced large amplitude dust-acoustic shock waves in a complex plasma. The experiments have been carried out in a Π shaped direct current glow discharge experimental device using kaolin particles as the dust component in a background of Argon plasma. A strong supersonic flow of the dust fluid is induced by adjusting the pumping speed and neutral gas flow into the device. An isolated copper wire mounted on the cathode acts as a potential barrier to the flow of dust particles. A sudden change in the gas flow rate is used to trigger the onset of high velocity dust acoustic shocks whose dynamics are captured by fast video pictures of the evolving structures. The physical characteristics of these shocks are delineated through a parametric scan of their dynamical properties over a range of flow speeds and potential hill heights. The observed evolution of the shock waves and their propagation characteristics are found to compare well with model numerical results based on a modified Korteweg-de-Vries-Burgers type equation.

  17. Brugia malayi abundant larval transcript 2 protein treatment attenuates experimentally-induced colitis in mice.

    PubMed

    Khatri, Vishal; Amdare, Nitin; Yadav, Ravi Shankar; Tarnekar, Aaditya; Goswami, Kalyan; Reddy, Maryada Venkata Rami

    2015-11-01

    Helminths are known to modulate host's immunity by suppressing host protective pro-inflammatory responses. Such immunomodulatory effects have been experimentally shown to have therapeutic implications in immune mediated disorders. In the present study, we have explored a filarial protein i.e. Brugia malayi recombinant abundant larval transcript 2 (rBmALT2) for its therapeutic effect in dextran sodium sulfate (DSS) induced colitis in mouse model. The immunomodulatory activity of rBmALT-2 was initially confirmed by demonstrating that it suppressed the lipopolysaccharide (LPS) induced nitric oxide synthesis and down-regulated the expression of pro-inflammatory cytokines in vitro by peritoneal exudate cells of mice. Treatment with rBmALT2 reduced severity of colitis associated with significant reduction in weight loss, disease activity, colon damage, mucosal edema and histopathological score including myeloperoxidase activity in colon tissues. rBmALT2 was comparatively more effective in attenuation of colitis when used in the preventive mode than when used for curative purpose. The therapeutic effect of rBmALT2 was found to be associated with downregulation of IFN-γ, IL-6, IL-17 and upregulation of IL-10 cytokines. These results provide strong experimental evidence that BmALT2 could be a potential alternative therapeutic agent in colitis. PMID:26669016

  18. Experimental Gingivitis Induces Systemic Inflammatory Markers in Young Healthy Individuals: A Single-Subject Interventional Study

    PubMed Central

    Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar

    2013-01-01

    Objectives We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Background Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. Methods 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. Results The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, P<0.0001). This local inflammation was associated with a systemic increase in hsCRP (0.24 mg/L, P = 0.038), IL-6 (12.52 ng/L, P = 0.0002) and MCP-1 (9.10 ng/l, P = 0.124) in peripheral blood samples between baseline and day 21, which decreased at day 42. Monocytes showed an enhanced adherence to endothelial cells and increased foam cell formation after oxLDL uptake (P<0.050) at day 21 of gingivitis. Conclusions Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http

  19. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis.

    PubMed

    Stangou, M; Bantis, C; Skoularopoulou, M; Korelidou, L; Kouloukouriotou, D; Scina, M; Labropoulou, I T; Kouri, N M; Papagianni, A; Efstratiadis, G

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17-67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25-80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  20. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

    PubMed Central

    Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  1. Experimental tonic hand pain modulates the corticospinal plasticity induced by a subsequent hand deafferentation.

    PubMed

    Mavromatis, N; Gagné, M; Voisin, J I A V; Reilly, K T; Mercier, C

    2016-08-25

    Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. Sixteen healthy subjects participated in two experimental sessions (Pain, No Pain) in which transcranial magnetic stimulation was used to assess corticospinal excitability in two forearm muscles (flexor carpi radialis and flexor digitorum superficialis) before (T0, T10, T20, and T40) and after (T60 and T75) inflation of a cuff around the wrist. The cuff was inflated at T45 in both sessions and in the Pain session capsaicin cream was applied on the dorsum of the hand at T5. Corticospinal excitability was significantly greater during the Post-inflation phase (p=0.002) and increased similarly in both muscles (p=0.861). Importantly, the excitability increase in the Post-inflation phase was greater for the Pain than the No-Pain condition (p=0.006). Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase (p=0.030) but no difference during the Pre-inflation phase (p=0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations. PMID:27291642

  2. Assessing potential abiotic and biotic complications of crayfish-induced gravel transport in experimental streams

    NASA Astrophysics Data System (ADS)

    Statzner, Bernhard; Peltret, Odile

    2006-03-01

    Biogeomorphology adds the element "biological dynamics" (of populations or communities) to chemical and physical geomorphic factors and thus complicates the framework of geomorphic processes. Such biological complications of the animal-induced transport of solids in streams should be particularly important in crayfish, as crayfish affect this transport through their overall activity and intraspecific aggression levels, which could be modified by shelter availability or the establishment of dominance hierarchies among individuals not knowing each other. Using experimental streams, we tested these hypotheses by measuring how shelter availability or residential crayfish group invasion by unknown individuals affected the impact of the crayfish Orconectes limosus on the (i) transport of gravel at baseflow (during 12 experimental days); (ii) sediment surface characteristics (after 12 days); and (iii) critical shear stress causing incipient gravel motion during simulated floods (after 12 days). The two potentially important factors shelter availability or residential group invasion negligibly affected the crayfish impact on gravel sediments, suggesting that habitat unfamiliarity (a third potentially important factor affecting crayfish activity) should increase the crayfish-induced sediment transport. Because habitat unfamiliarity is associated with sporadic long-distance migrations of a few crayfish individuals, this third factor should play a minor role in real streams, where crayfish biomass should be a key factor in relations with crayfish effects on sediments. Therefore, we combined the results of this study with those of previous crayfish experiments to assess how crayfish biomass could serve in modelling the gravel transport. Crayfish biomass explained 47% of the variability in the baseflow gravel transport and, in combination with the coefficient of variation of the bed elevation and algal cover, 72% of the variability in the critical gravel shear stress. These

  3. Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle.

    PubMed

    Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Riou, Mickaël; Zohari, Siamak; Comtet, Loic; Olofson, Ann-Sophie; Gélineau, Robert; Martin, Guillaume; Elvander, Marianne; Blomqvist, Gunilla; Zientara, Stéphan; Valarcher, Jean Francois

    2014-11-20

    Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. PMID:25312275

  4. Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Stormanns, Eva R.; Recks, Mascha S.; Kuerten, Stefanie

    2015-01-01

    Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Limited availability of human tissue underscores the importance of animal models to study the pathology of MS. Methods Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord. Results B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. In addition, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation. Conclusions Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute

  5. Numerical and experimental studies of drying and shrinkage induced microcracking in concrete

    NASA Astrophysics Data System (ADS)

    Jankovic, D.

    2007-12-01

    The aim of this research is to investigate moisture flow in cement paste and Interface Transition Zone, around aggregate, as well as associated shrinkage induced strains, and subsequent microcracking. Two coupled methods are used: numerical simulations and experiments. The moisture flow is numerically simulated by Lattice Gas Automata, while drying experiments are performed in Environmental Scanning Electron Microscope (ESEM) in order to determine drying deformations and shrinkage coefficient. The moisture movement simulation by Lattice Gas Automata, a type of cellular automata, involves different drying collision rules, which results in different density (moisture content) at each node. Special attention is given to the effect of the presence of aggregate particles on the moisture flow in concrete, which are considered rigid obstacles. The shrinkage deformation is considered a linear function of the moisture content if the relative humidity, RH does not exceed 40%. The calculated moisture gradient from the numerical analysis and an assumed shrinkage coefficient are used to calculate drying shrinkage induced strains and stresses using the basic equations. To determine the drying shrinkage coefficient for the RH range 100% to 20%, new experimental techniques of drying in ESEM are used. Small paste samples are cast in a specially developed mould with 2 mm thickness and afterwards carefully grounded and polished to a thickness of required 1 mm. The used variables in the tests are: various cement types, w/c ratio, sample age and curing conditions. Drying shrinkage displacements and strains are determined in order to calculate the drying shrinkage coefficient. These experimentally obtained values of the coefficient are compared with the literature data and used in numerical simulations of shrinkage induced strains, stresses and cracking in drying concrete.

  6. Numerical and experimental investigation of natural flow-induced vibrations of flexible hydrofoils

    NASA Astrophysics Data System (ADS)

    Chae, Eun Jung; Akcabay, Deniz Tolga; Lelong, Alexandra; Astolfi, Jacques Andre; Young, Yin Lu

    2016-07-01

    The objective of this work is to present combined numerical and experimental studies of natural flow-induced vibrations of flexible hydrofoils. The focus is on identifying the dependence of the foil's vibration frequencies and damping characteristics on the inflow velocity, angle of attack, and solid-to-fluid added mass ratio. Experimental results are shown for a cantilevered polyacetate (POM) hydrofoil tested in the cavitation tunnel at the French Naval Academy Research Institute (IRENav). The foil is observed to primarily behave as a chordwise rigid body and undergoes spanwise bending and twisting deformations, and the flow is observed to be effectively two-dimensional (2D) because of the strong lift retention at the free tip caused by a small gap with a thickness less than the wall boundary layer. Hence, the viscous fluid-structure interaction (FSI) model is formulated by coupling a 2D unsteady Reynolds-averaged Navier-Stokes (URANS) model with a two degree-of-freedom (2-DOF) model representing the spanwise tip bending and twisting deformations. Good agreements were observed between viscous FSI predictions and experimental measurements of natural flow-induced vibrations in fully turbulent and attached flow conditions. The foil vibrations were found to be dominated by the natural frequencies in absence of large scale vortex shedding due to flow separation. The natural frequencies and fluid damping coefficients were found to vary with velocity, angle of attack, and solid-to-fluid added mass ratio. In addition, the numerical results showed that the in-water to in-air natural frequency ratios decreased rapidly, and the fluid damping coefficients increased rapidly, as the solid-to-fluid added mass ratio decreases. Uncoupled mode (UM) linear potential theory was found to significantly over-predict the fluid damping for cases of lightweight flexible hydrofoils, and this over-prediction increased with higher velocity and lower solid-to-fluid added mass ratio.

  7. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    PubMed Central

    Mohd Sairazi, Nur Shafika; Sirajudeen, K. N. S.; Asari, Mohd Asnizam; Muzaimi, Mustapha; Mummedy, Swamy; Sulaiman, Siti Amrah

    2015-01-01

    Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration. PMID:26793262

  8. An experimental setup to characterize MR switched gradient-induced potentials.

    PubMed

    Fokapu, Odette; El-Tatar, Aziz

    2013-06-01

    We have developed an experimental setup as an in vitro research tool for studying the contamination of electrophysiological signals (EPS) by MRI environment; particularly, when due to the switched gradient-induced potentials. The system is composed of: 1) a MRI compatible module for the transmission of the EPS into the MRI tunnel, 2) a gelatin-based tissue-mimicking phantom, placed inside the tunnel, in which EPS is injected, 3) a detection module composed of a five input channel MRI compatible transmitter placed inside the tunnel, allowing an on-site pre-amplification of the bio-potentials and their transmission, via an optical fiber cable, to a four filtered output per channel receiver (350 Hz, 160 Hz, 80 Hz, and 40 Hz, for a total of 20 channels) placed in the control room, and 4) a signal processing algorithm used to analyze the generated induced potentials. A set of tests were performed to validate the electronic performances of the setup. We also present in this work an interesting application of the setup, i.e., the acquisition and analysis of the induced potentials with respect of the slice orientation for a given MRI sequence. Significant modifications of the time and frequency characteristics were observed with respect to axial, coronal or sagittal orientations. PMID:23853335

  9. [Protective effects of S-adenosylmethionine against CCl4 - and ethanol-induced experimental hepatic fibrosis].

    PubMed

    Zhang, F; Gu, J-X; Zou, X-P; Zhuge, Y-Z

    2016-01-01

    In this study the effects of S-adenosylmethionine (SAM) on experimental hepatic fibrotic rats induced by carbon tetrachloride (CCl(4)) and ethanol and the relevant potential mechanisms were explored. Hepatic fibrotic rat models were established with CCl(4) diluted in olive oil being drunk with 10% ethanol in water. SAM was used both for prevention and treatment. Histological evaluation was carried out by hematoxylin-eosin (HE) and Masson staining of hepatic samples. Serum biochemical assays showed that alanine aminotransferase (ALT) was increased and albumin (ALB) was decreased by CCl(4) and ethanol, and both effects were suppressed by preventing and treating use of SAM. The model control rats got significantly higher scores in fatty degeneration, lobular inflammation, and hepatocyte ballooning. A significant improvement was observed in the SAM-prevented rats and SAM-treated rats, which was consistent with the change of fibrosis scoring in each group. Smad3 was induced by CCl(4) and ethanol in the model control group, which was significantly down regulated by SAM. SAM reduced both total Smad3 and phospho-Smad3 in vitro. SAM had a protective effect on hepatic fibrosis in rats induced by CCl(4) combined with ethanol and the down-regulation of activity and expression of Smad3 were involved in the potential mechanisms. PMID:27239849

  10. Evaluation of anti-urolithiatic activity of Pashanabhedadi Ghrita against experimentally induced renal calculi in rats

    PubMed Central

    Gupta, Sanjay Kumar; Baghel, Madhav Singh; Bhuyan, Chaturbhuja; Ravishankar, B.; Ashok, B. K.; Patil, Panchakshari D.

    2012-01-01

    Population in an industrialized world is afflicted by urinary stone disease. Kidney stones are common in all kinds of urolithiasis. One distinguished formulation mentioned by Sushruta for management of Ashmari (urolithiasis) is Pashanabhedadi Ghrita (PBG), which is in clinical practice since centuries. Validation of drug is the requirement of time through the experimental study. In this study, trial of PBG has been made against ammonium oxalate rich diet and gentamicin injection induced renal calculi in albino rats. The calculi were induced by gentamicin injection and ammonium oxalate rich diet. Test drug was administered concomitantly in the dose of 900 mg/kg for 15 consecutive days. Rats were sacrificed on the 16th day. Parameters like kidney weight, serum biochemical, kidney tissue and histopathology of kidney were studied. Concomitant treatment of PBG attenuates blood biochemical parameters non-significantly, where as it significantly attenuated lipid peroxidation and enhanced glutathione and glutathione peroxidase activities. It also decreased crystal deposition markedly into the renal tubules in number as well as size and prevented damage to the renal tubules. The findings showed that PBG is having significant anti-urolithiatic activities against ammonium oxalate rich diet plus gentamicine injection induced urolithiasis in rats. PMID:23723654

  11. Experimental Gestational Diabetes Mellitus Induces Blunted Vasoconstriction and Functional Changes in the Rat Aorta

    PubMed Central

    Tufiño, Cecilia; Villanueva-López, Cleva; Ibarra-Barajas, Maximiliano; Bracho-Valdés, Ismael; Bobadilla-Lugo, Rosa Amalia

    2014-01-01

    Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e−) vessels. Losartan reduced GDM but not SD e− vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations. PMID:25610861

  12. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

    SciTech Connect

    Giavazzi, R.; Garofalo, A.; Bani, M.R.; Abbate, M.; Ghezzi, P.; Boraschi, D.; Mantovani, A.; Dejana, E. )

    1990-08-01

    This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-(125I)odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies.

  13. Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition.

    PubMed

    Guo, Wenjie; Hu, Shasha; Elgehama, Ahmed; Shao, Fenli; Ren, Ren; Liu, Wen; Zhang, Wenjing; Wang, Xinlei; Tan, Renxiang; Xu, Qiang; Sun, Yang; Jiao, Ruihua

    2015-10-01

    In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases. PMID:26320672

  14. Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

    PubMed Central

    Settles, Erik W.; Moser, Lindsey A.; Harris, Tajie H.

    2014-01-01

    A chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondii infection can prevent Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondii antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. berghei infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-γ). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-γ levels compared to those of mock-treated mice, suggesting that reductions in IFN-γ at the time of ECM onset protected against lethality. Using IL-10- and IL-12βR-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein, mediates protection from ECM-associated pathology potentially through early induction of IFN-γ and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM. PMID:24396042

  15. Analytical and Experimental Characterization of Gravity Induced Deformations In Subscale Gossamer Structures

    NASA Technical Reports Server (NTRS)

    Johnston, John D.; Blandino, Joseph R.; McEvoy, Kiley C.

    2004-01-01

    The development of gossamer space structures such as solar sails and sunshields presents many challenges due to their large size and extreme flexibility. The post-deployment structural geometry exhibited during ground testing may significantly depart from the in-space configuration due to the presence of gravity-induced deformations (gravity sag) of lightly preloaded membranes. This paper describes a study carried out to characterize gravity sag in two subscale gossamer structures: a single quadrant from a 2 m, 4 quadrant square solar sail and a 1.7 m membrane layer from a multi-layer sunshield The behavior of the test articles was studied over a range of preloads and in several orientations with respect to gravity. An experimental study was carried out to measure the global surface profiles using photogrammetry, and nonlinear finite element analysis was used to predict the behavior of the test articles. Comparison of measured and predicted surface profiles shows that the finite dement analysis qualitatively predicts deformed shapes comparable to those observed in the laboratory. Quantitatively, finite element analysis predictions for peak gravity-induced deformations in both test articles were within 10% of measured values. Results from this study provide increased insight into gravity sag behavior in gossamer structures, and demonstrates the potential to analytically predict gravity-induced deformations to within reasonable accuracy.

  16. Aloe vera gel protects liver from oxidative stress-induced damage in experimental rat model.

    PubMed

    Nahar, Taslima; Uddin, Borhan; Hossain, Shahdat; Sikder, Abdul Mannan; Ahmed, Sohel

    2013-01-01

    Aloe vera is a semi-tropical plant of Liliaceae family which has a wide range of applications in traditional medicine. In the present study, we sought to investigate the heptaoprotective potential of Aloe vera gel as a diet supplement. To achieve this goal, we have designed in vitro and in vivo experimental models of chemical-induced liver damage using male Sprague-Dawley rat. In the in vitro model, its effect was evaluated on Fenton's reaction-induced liver lipid peroxidation. Co-incubation with gel significantly reduced the generation of liver lipid peroxide (LPO). Next, to see the similar effect in vivo, gel was orally administered to rats once daily for 21 successive days. Following 1 hour of the last administration of gel, rats were treated with intra-peritoneal injection of CCl4. Dietary gel showed significant hepatoprotection against CCl4-induced damage as evident by restoration of liver LPO, serum transaminases, alkaline phosphatase, and total bilirubin towards near normal. The beneficial effects were pronounced with the doses used (400 and 800 mg/kg body weight). Besides, we did not observe any significant drop in serum albumin, globulin as well as total protein levels of gel-administered rats. Histopathology of the liver tissue further supported the biochemical findings confirming the hepatoprotective potential of dietary gel. PMID:23652643

  17. Effects of Schizolobium parahyba Extract on Experimental Bothrops Venom-Induced Acute Kidney Injury

    PubMed Central

    Martines, Monique Silva; Mendes, Mirian M.; Shimizu, Maria H. M.; Melo Rodrigues, Veridiana; de Castro, Isac; Filho, Sebastião R. Ferreira; Malheiros, Denise M. A. C.; Yu, Luis; Burdmann, Emmanuel A.

    2014-01-01

    Background Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI. Methodology Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score). Principal Findings BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. Conclusion SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR. PMID:24551041

  18. Diet shifts and population dynamics of estuarine foraminifera during ecosystem recovery after experimentally induced hypoxia crises

    NASA Astrophysics Data System (ADS)

    Brouwer, G. M.; Duijnstee, I. A. P.; Hazeleger, J. H.; Rossi, F.; Lourens, L. J.; Middelburg, J. J.; Wolthers, M.

    2016-03-01

    This study shows foraminiferal dynamics after experimentally induced hypoxia within the wider context of ecosystem recovery. 13C-labeled bicarbonate and glucose were added to the sediments to examine foraminiferal diet shifts during ecosystem recovery and test-size measurements were used to deduce population dynamics. Hypoxia-treated and undisturbed patches were compared to distinguish natural (seasonal) fluctuations from hypoxia-induced responses. The effect of timing of disturbance and duration of recovery were investigated. The foraminiferal diets and population dynamics showed higher fluctuations in the recovering patches compared to the controls. The foraminiferal diet and population structure of Haynesina germanica and Ammonia beccarii responded differentially and generally inversely to progressive stages of ecosystem recovery. Tracer inferred diet estimates in April and June and the two distinctly visible cohorts in the test-size distribution, discussed to reflect reproduction in June, strongly suggest that the ample availability of diatoms during the first month of ecosystem recovery after the winter hypoxia was likely profitable to A. beccarii. Enhanced reproduction itself was strongly linked to the subsequent dietary shift to bacteria. The distribution of the test dimensions of H. germanica indicated that this species had less fluctuation in population structure during ecosystem recovery but possibly reproduced in response to the induced winter hypoxia. Bacteria seemed to consistently contribute more to the diet of H. germanica than diatoms. For the diet and test-size distribution of both species, the timing of disturbance seemed to have a higher impact than the duration of the subsequent recovery period.

  19. Evaluation of anti-urolithiatic activity of Pashanabhedadi Ghrita against experimentally induced renal calculi in rats.

    PubMed

    Gupta, Sanjay Kumar; Baghel, Madhav Singh; Bhuyan, Chaturbhuja; Ravishankar, B; Ashok, B K; Patil, Panchakshari D

    2012-07-01

    Population in an industrialized world is afflicted by urinary stone disease. Kidney stones are common in all kinds of urolithiasis. One distinguished formulation mentioned by Sushruta for management of Ashmari (urolithiasis) is Pashanabhedadi Ghrita (PBG), which is in clinical practice since centuries. Validation of drug is the requirement of time through the experimental study. In this study, trial of PBG has been made against ammonium oxalate rich diet and gentamicin injection induced renal calculi in albino rats. The calculi were induced by gentamicin injection and ammonium oxalate rich diet. Test drug was administered concomitantly in the dose of 900 mg/kg for 15 consecutive days. Rats were sacrificed on the 16(th) day. Parameters like kidney weight, serum biochemical, kidney tissue and histopathology of kidney were studied. Concomitant treatment of PBG attenuates blood biochemical parameters non-significantly, where as it significantly attenuated lipid peroxidation and enhanced glutathione and glutathione peroxidase activities. It also decreased crystal deposition markedly into the renal tubules in number as well as size and prevented damage to the renal tubules. The findings showed that PBG is having significant anti-urolithiatic activities against ammonium oxalate rich diet plus gentamicine injection induced urolithiasis in rats. PMID:23723654

  20. Acute experimentally induced neck pain does not affect fatigability of the peripheral biceps brachii muscle.

    PubMed

    Hung, Laurie Y; Maracle, Emmalee; Srbely, John Z; Brown, Stephen H M

    2014-10-01

    Evidence has shown that upper limb muscles peripheral to the cervical spine, such as the biceps brachii, can demonstrate functional deficits in the presence of chronic neck pain. However, few studies have examined how neck pain can affect the fatigability of upper limb muscles; therefore we were motivated to investigate the effects of acutely induced neuropathic neck pain on the fatigability of the biceps brachii muscle during isometric contraction to exhaustion. Topical capsaicin was used to induce neck pain in 11 healthy male participants. Surface EMG signals were recorded from the biceps brachii during an isometric elbow flexion fatigue task in which participants held a weight equivalent to 30% of their MVC until exhaustion. Two experimental sessions, one placebo and one capsaicin, were conducted separated by two days. EMG mean power frequency and average normalized activation values were calculated over the course of the fatigue task. In the presence of pain, there was no statistically significant effect on EMG parameters during fatigue of the biceps brachii. These results demonstrate that acutely induced neuropathic neck pain does not affect the fatigability, under the tested conditions, of the biceps brachii. PMID:24718930

  1. Independent associations of urine neutrophil gelatinase–associated lipocalin and serum uric acid with interstitial fibrosis and tubular atrophy in primary glomerulonephritis

    PubMed Central

    Lertrit, Amornpan; Worawichawong, Suchin; Vanavanan, Somlak; Chittamma, Anchalee; Muntham, Dittapol; Radinahamed, Piyanuch; Nampoon, Aumporn; Kitiyakara, Chagriya

    2016-01-01

    The degree of interstitial fibrosis and tubular atrophy (IFTA) is one of the strongest prognostic factors in glomerulonephritis (GN). In experimental models, high serum uric acid (UA) could contribute to IFTA through direct effects on the renal tubules, but the significance of this process has not been evaluated in patients. Urine neutrophil gelatinase–associated lipocalin (NGAL) is produced by renal tubules following acute or chronic damage. We investigated the relationship between UA and NGAL excretion in primary GN and tested whether these biomarkers are independently associated with IFTA. Urine and blood were collected from patients on the day of kidney biopsy. IFTA was assessed semi-quantitatively. Fifty-one patients with primary GN were enrolled. NGAL/creatinine correlated significantly with proteinuria but not with glomerular filtration rate (GFR). By contrast, UA correlated with GFR but not with proteinuria. NGAL/creatinine did not correlate with UA. Both NGAL/creatinine and UA increased with the severity of IFTA. By multivariate analysis, GFR, NGAL/creatinine, and UA were independently associated with moderate-to-severe IFTA. Combining UA and NGAL/creatinine with classical predictors (proteinuria and GFR) tended to improve discrimination for moderate-to-severe IFTA. Findings that UA was unrelated to urinary NGAL excretion suggest that the two biomarkers reflect different pathways related to the development of IFTA in primary GN. Both NGAL/creatinine and UA were independently associated with moderate-to-severe IFTA. PMID:27143950

  2. Spectroscopic evaluation of painted layer structural changes induced by gamma radiation in experimental models

    NASA Astrophysics Data System (ADS)

    Manea, Mihaela M.; Moise, Ioan V.; Virgolici, Marian; Negut, Constantin D.; Barbu, Olimpia-Hinamatsuri; Cutrubinis, Mihalis; Fugaru, Viorel; Stanculescu, Ioana R.; Ponta, Corneliu C.

    2012-02-01

    The degradation of cultural heritage objects by insects and microorganisms is an important issue for conservators, art specialists and humankind in general. Gamma irradiation is an efficient method of polychrome wooden artifacts disinfestation. Color changes and other modifications in the physical chemical properties of materials induced by gamma irradiation are feared by cultural heritage responsible committees and they have to be evaluated objectively and precisely. In this paper FTIR and FT-Raman spectroscopy methods were used to investigate the structural changes in some experimental models of tempera paint layers on wood following 11 kGy gamma irradiation at two dose rates. Radiation chemistry depends on the particular pigment, matrix formed by protein, resin (in case of varnished samples) and water presence. For the majority of painted layer in experimental models very small spectral variations were observed. Small changes in the FTIR spectra were observed for the raw sienna experimental model: for the higher dose rate the egg yolk protein oxidation peaks and the CH stretching bands due to lipids degradation products increased.

  3. Radiating plasma species density distribution in EUV-induced plasma in argon: a spatiotemporal experimental study

    NASA Astrophysics Data System (ADS)

    van der Horst, R. M.; Beckers, J.; Osorio, E. A.; van de Ven, T. H. M.; Banine, V. Y.

    2015-12-01

    In this contribution we experimentally study temporally and spatially resolved radiating plasma species density distribution in plasma induced by irradiating a low pressure argon gas with high energy photons with a wavelength of 13.5 nm, i.e. extreme ultraviolet (EUV). This is done by recording the optical emission spatially and temporally resolved by an iCCD camera as a function of the argon gas pressure. Our experimental results show that the emission intensity, i.e. density of radiating plasma species, depends quadratically on the gas pressure. The linear term is due to photoionization and simultaneous excitation by EUV photons, the quadratic term due to electron impact excitation by electrons generated by photoionization. The decay of radiating plasma species can be divided into two phases. At time scales shorter than 10 μs (first phase), the decay is governed by radiative decay of radiating plasma species. At longer time scales (second phase, >10 μs), the decay is dominated by diffusion and subsequent de-excitation at the wall. The experimental decay and expansion during this phase corresponds well with a simplified diffusion model. In order to gain more insight in this exotic type of plasma, we compare the electron density from previous measurements with the results obtained here.

  4. Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model

    PubMed Central

    Lewis, S. Rochelle; Ellison, Siobhan P.; Dascanio, John J.; Lindsay, David S.; Gogal, Robert M.; Werre, Stephen R.; Surendran, Naveen; Breen, Meghan E.; Heid, Bettina M.; Andrews, Frank M.; Buechner-Maxwell, Virginia A.; Witonsky, Sharon G.

    2014-01-01

    Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both. PMID:26464923

  5. Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.

    PubMed

    Lewis, S Rochelle; Ellison, Siobhan P; Dascanio, John J; Lindsay, David S; Gogal, Robert M; Werre, Stephen R; Surendran, Naveen; Breen, Meghan E; Heid, Bettina M; Andrews, Frank M; Buechner-Maxwell, Virginia A; Witonsky, Sharon G

    2014-01-01

    Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5-1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both. PMID:26464923

  6. Urinary Thrombin: A Novel Marker of Glomerular Inflammation for the Diagnosis of Crescentic Glomerulonephritis (Prospective Observational Study)

    PubMed Central

    Kitamoto, Yasunori; Arizono, Kenji; Fukui, Hiroyoshi; Tomita, Kimio; Kitamura, Hiroshi; Taguma, Yoshio; Imamura, Takahisa

    2015-01-01

    Background Crescentic glomerulonephritis (CresGN), an uncommon rapidly progressive disease, is characterized by severe glomerular inflammation with fibrin deposition. The lack of specific CresGN biomarkers delays diagnosis and threatens life. Because fibrin deposits in CresGN glomeruli indicate thrombin generation, we hypothesized that thrombin is excreted in urine and is a specific CresGN biomarker. Methods We measured urinary thrombin activity in 200 untreated patients (17 with CresGN, 183 with primary glomerulonephritis) and controls (8 patients with healed CresGN, 11 with nephrosclerosis, and 10 with tubulointerstitial nephritis, and 66 healthy volunteers). CresGN types included 15 pauci-immune and 2 immune complex. We assessed the diagnostic accuracy of thrombinuria in 169 patients with hematuria and proteinuria. Renal biopsy tissues were immunostained for tissue factor and fibrin. We analyzed the relationship of thrombinuria to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, glomerular fibrin deposition, antineutrophil cytoplasmic antibodies (ANCAs), and C-reactive protein (CRP). We studied changes in thrombin activities after glucocorticoid treatment in 12 patients with thrombinuria. Results The highest thrombinuria occurrence was in CresGN (70.6%), followed by membranoproliferative glomerulonephritis (41.7%), IgA nephropathy (9.2%), and acute glomerulonephritis (0%). More than 75% of patients with nonproliferative glomerulonephritis manifested no thrombinuria. No controls had thrombinuria. Thrombinuria showed high CresGN specificity (90.1%) and moderate sensitivity (70.6%) and was detected in 4 of 7 patients with ANCA-negative CresGN. In CresGN, thrombinuria was associated with fibrin deposition in glomerular extracapillary tissue, where monocytes/macrophages expressed tissue factor. Thrombinuria in CresGN was unrelated to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, and

  7. Numerical and experimental studies of coupling-induced phase shift in resonator and interferometric integrated optics devices.

    PubMed

    Tobing, L Y M; Tjahjana, L; Darmawan, S; Zhang, D H

    2012-02-27

    Coupling induced effects are higher order effects inherent in waveguide evanescent coupling that are known to spectrally distort optical performances of integrated optics devices formed by coupled resonators. We present both numerical and experimental studies of coupling-induced phase shift in various basic integrated optics devices. Rigorous finite difference time domain simulations and systematic experimental characterizations of different basic structures were conducted for more accurate parameter extraction, where it can be observed that coupling induced wave vector may change sign at the increasing gap separation. The devices characterized in this work were fabricated by CMOS-process 193 nm Deep UV (DUV) lithography in silicon-on-insulator (SOI) technology. PMID:22418385

  8. Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis

    PubMed Central

    Nascimento, Daniele Carvalho; Sônego, Fabiane; Castanheira, Fernanda Vargas e Silva; Melo, Paulo Henrique; Scortegagna, Gabriela Trentin; Silva, Rangel Leal; Barroso-Sousa, Romualdo; Souto, Fabrício Oliveira; Pazin-Filho, Antonio; Figueiredo, Florencio; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2016-01-01

    Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are

  9. Correlation Between Stereoacuity and Experimentally Induced Graded Monocular and Binocular Astigmatism

    PubMed Central

    Puthran, Neelam; Gagal, Bhavna

    2016-01-01

    Introduction Stereopsis, the highest grade of binocular single vision, is affected by various factors, such as mis-alignment of visual axes, refractive errors especially anisometropia and astigmatism, both of which may result in amblyopia. There are very few studies in literature regarding the relationship between stereoacuity and refractive errors, especially astigmatism. Aim The present study was conducted to determine the correlation between stereoacuity and experimentally induced graded astigmatism in emmetropes. Materials and Methods A randomized study was conducted on 2000 individuals of either gender, between the ages of 8-35 years, at tertiary care centre attached to a medical college during the period of August 2012 to August 2014, All subjects were emmetropic with normal binocular single vision. Participants were randomly divided into four groups of 500 individuals each. Two groups were subjected to induced myopic astigmatism, either uni-ocularly or binocularly, using + 1.0 D and + 2.0 D cylinders at varying axes i.e., 450, 900 and 1800. Similarily, the remaining two groups were subjected to induced hypermetropic astigmatism, using - 1.0 D and - 2.0D cylinders at varying axes i.e. 450, 900 and 1800. Near stereoacuity was determined by the Titmus Fly Stereo Test, both before and after induction of astigmatism. Statistical analysis was done using paired t-test and ANOVA. Results The mean stereoacuity in emmetropes was 28.81±4.97 seconds of arc. There was a decrease in stereoacuity with increase in dioptric power of astigmatism (p<0.001). Oblique astigmatism reduced the stereoacuity maximally, while stereoacuity was least affected at 180o axis. Hypermetropic astigmatism caused more deterioration in stereoacuity than myopic astigmatism. A gross reduction in stereoacuity was noted in induced monocular astigmatism as against binocular astigmatism. Conclusion This study suggests that stereoacuity is significantly affected by even minor degrees of monocular or

  10. Spontaneous and experimental glycoprotein storage disease of goats induced by Ipomoea carnea subsp fistulosa (Convolvulaceae).

    PubMed

    Armién, A G; Tokarnia, C H; Peixoto, P Vargas; Frese, K

    2007-03-01

    Spontaneous and experimental poisoning with the swainsonine-containing and calystegine-containing plant Ipomoea carnea subsp fistulosa is described. Three of 8 goats presenting with emaciation, weakness, symmetrical ataxia, posterior paresis, proprioceptive deficits, abnormal posture, abnormal postural reaction, and muscle hypertonia were necropsied. I fistulosa was suspected to be the cause of the neurologic disease in all cases. An experiment was conducted to confirm the diagnosis using 12 goats and diets containing 3 different concentrations of the plant. All goats fed I fistulosa developed neurological signs that were similar to those observed in the spontaneous intoxication. Muscle atrophy and pallor were the only macroscopic changes observed in spontaneous and in experimental intoxication. Histological lesions of spontaneous and experimental animals were similar. The most prominent lesion was cytoplasmic vacuolation in neurons of the central and the autonomous nervous system, pancreatic acinar cells, hepatocytes, Kupffer cells, follicular epithelial cells of the thyroid gland, and macrophages of the lymphatic tissues. Neuronal necrosis, axonal spheroids formation, and astrogliosis were additionally observed in the brain. Ultrastructurally, the cytoplasmic vacuoles consisted of distended lysosomes surrounded by a single-layered membrane. Nonreduced end-rests or sequence of alpha-Man, alpha-Glc, beta(1-4)-GlcNAc, and NeuNAc on lysosomal membrane were revealed by lectin histochemistry. Samples of plants used in the experimental trial contained swainsonine and calystegine and their intermediary derivate. We conclude that I fistulosa induces a glycoprotein storage disease primarily based on the inhibition of the lysosomal alpha-mannosidase by the alkaloid swainsonine. PMID:17317794

  11. Combined optical coherence tomography and optical coherence elastography for glomerulonephritis classification

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Mohammadzai, Qais; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Chang, Anthony; Mohan, Chandra; Larin, Kirill V.

    2016-03-01

    Acute Glomerulonephritis caused by anti-glomerular basement membrane disease has a high mortality due to delayed diagnosis. Thus, an accurate and early diagnosis is critical for preserving renal function. Currently, blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution. Optical coherence tomography (OCT) is a noninvasive imaging technique that provides superior spatial resolution (micron scale) as compared to ultrasound and CT. Pathological changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signal, such as optical attenuation and speckle variance. Moreover, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, we utilized OCT to detect the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, classification accuracy using only optical metrics was clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improved from 76% to 95%. These results show that OCT combined with OCE can be potentially useful for nephritis detection.

  12. Long-term follow-up of atypical membranoproliferative glomerulonephritis: are steroids indicated?

    PubMed

    Fujita, Teruo; Nozu, Kandai; Iijima, Kazumoto; Kamioka, Ichiro; Yoshiya, Kunihiko; Tanaka, Ryojiro; Hamahira, Kiyoshi; Nakanishi, Koichi; Yoshikawa, Norishige; Matsuo, Masafumi

    2006-02-01

    Atypical membranoproliferative glomerulonephritis (MPGN) has been reported to have a good prognosis when treated with corticosteroids. However, this recommendation is based on uncontrolled trials and is associated with many complications. The purpose of our study is to determine whether steroid therapy is indicated for atypical MPGN. The cases of seven patients with atypical MPGN are reported in this study. Urinary abnormalities of five of them were detected by urine screening at school, of two because of macrohematuria. Hypocomplementemia was noted in six patients. All but one patient were treated without corticosteroids, and five with angiotensin-converting enzyme inhibitors (ACEI) and/or the Chinese herbal medicine Sairei-to (TJ-114). One patient recovered spontaneously from proteinuria and was therefore not treated, and one who developed severe proteinuria during observation was treated with corticosteroids. After an average follow-up period of 10.0 years, five patients showed normal urinary findings, one had hematuria and one proteinuria. At the most recent follow-up, the renal function of all patients remained within the normal range, and serum C3 had returned to normal levels in five out of six. These findings suggest that the indication of steroid therapy for atypical MPGN should be re-examined, since most of the patients with atypical MPGN seem to have an excellent prognosis without treatment with corticosteroids. PMID:16247645

  13. Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls

    PubMed Central

    Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou

    2015-01-01

    Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483

  14. Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls.

    PubMed

    Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou

    2015-01-01

    Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction-chromatography- mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483

  15. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report

    PubMed Central

    Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  16. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report.

    PubMed

    Vitaliti, Giovanna; Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  17. Differentiating Glomerular Inflammation from Fibrosis in A Bone Marrow Chimera for Rat Anti-GBM Glomerulonephritis

    PubMed Central

    Zhou, Cindy; Lou, Kristie; Tatum, Kiana; Funk, Jeremiah; Wu, Jean; Bartkowiak, Todd; Kagan, David; Lou, Yahuan

    2015-01-01

    Background Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end stage disease. This study investigated how these two phases were controlled. Methods Using a rat anti-glomerular basement membrane (GBM) GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. Results LEW’s BM to WKY (WKYLEW) chimeras with or without co-transfer of host WKY’s T cells were GN-resistant. On the other hand, WKY’s BM to LEW (LEWWKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEWWKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM derived non-T cell populations. However, unlike WKY rats, LEWWKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Conclusion Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEWWKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation. PMID:26337665

  18. Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis.

    PubMed

    O'Sullivan, Kim M; Lo, Camden Y; Summers, Shaun A; Elgass, Kirstin D; McMillan, Paul J; Longano, Anthony; Ford, Sharon L; Gan, Poh-Yi; Kerr, Peter G; Kitching, A Richard; Holdsworth, Stephen R

    2015-11-01

    Myeloperoxidase (MPO) is an important neutrophil lysosomal enzyme, a major autoantigen, and a potential mediator of tissue injury in MPO-ANCA-associated vasculitis (MPO-AAV) and glomerulonephritis. Here we examined MPO deposition in kidney biopsies from 47 patients with MPO-AAV. Leukocyte accumulation and fibrin deposition consistent with cell-mediated immunity was a major feature. Tubulointerstitial macrophage, CD4+ and CD8+ T-cell, and neutrophil numbers correlated with low presenting eGFR. MPO was not detected in kidneys from patients with minimal change or thin basement membrane disease, but was prominent in glomerular, periglomerular, and tubulointerstitial regions in MPO-AAV. Extracellular MPO released from leukocytes was pronounced in all MPO-AAV patients. Similar numbers of neutrophils and macrophages expressed MPO in the kidneys, but colocalization studies identified neutrophils as the major source of extracellular MPO. Extraleukocyte MPO was prominent in neutrophil extracellular traps in the majority of patients; most of which had traps in half or more glomeruli. These traps were associated with more neutrophils and more MPO within glomeruli. Glomerular MPO-containing macrophages generated extracellular trap-like structures. MPO also localized to endothelial cells and podocytes. The presence of the most active glomerular lesions (both segmental necrosis and cellular crescents) correlated with intraglomerular CD4+ cells and MPO+ macrophages. Thus, cellular and extracellular MPO may cause glomerular and interstitial injury. PMID:26176828

  19. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis.

    PubMed

    Beck, Laurence; Bomback, Andrew S; Choi, Michael J; Holzman, Larry B; Langford, Carol; Mariani, Laura H; Somers, Michael J; Trachtman, Howard; Waldman, Meryl

    2013-09-01

    Glomerulonephritis (GN) is an important cause of morbidity and mortality in patients of all ages throughout the world. Because these disorders are relatively rare, it is difficult to perform randomized clinical trials to define optimal treatment for many of the specific glomerulopathies. In the absence of high-grade evidence to guide the care of glomerular diseases, in June 2012, KDIGO (Kidney Disease: Improving Global Outcomes) published an international clinical guideline for GN. The Work Group report represents an important review of the literature in this area and offers valid and useful guidelines for the most common situations that arise in the management of patients with glomerular disease. This commentary, developed by a panel of clinical experts convened by the National Kidney Foundation, attempts to put the GN guideline into the context of the US health care system. Overall, we support the vast majority of the recommendations and highlight select areas in which epidemiological factors and medical practice patterns in this country justify modifications and adjustments in order to achieve favorable outcomes. There remain large gaps in our knowledge of the best approaches to treat glomerular disease and we strongly endorse an expanded clinical research effort to improve the health and long-term outcomes of children and adults with GN. PMID:23871408

  20. Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy

    SciTech Connect

    Donadio, J.V. Jr.; Anderson, C.F.; Mitchell, J.C.; Holley, K.E.; Ilstrup, D.M.; Fuster, V.; Chesebro, J.H.

    1984-05-31

    Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of /sup 51/Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m/sup 2/ of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.

  1. Clinical and Immunologic Characteristics of Patients With ANCA-Associated Glomerulonephritis Combined With Membranous Nephropathy

    PubMed Central

    Zou, Rong; Liu, Gang; Cui, Zhao; Chen, Min; Zhao, Ming-Hui

    2015-01-01

    Abstract The concurrent antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) and membranous nephropathy (MN) have been increasingly documented, mainly in case studies and case series; however, the differences of clinical and pathologic characteristics as well as outcomes between ANCA-GN patients with and without MN remain unclear. The current study investigated the clinical and immunologic features of patients with combined ANCA-GN and MN in a large cohort. Twenty-seven of 223 patients had combined ANCA-GN and MN; they had significantly higher levels of initial serum creatinine, higher Birmingham Vasculitis Activity Score and poorer renal outcome than ANCA-GN patients without MN (P < 0.05). ANCA-GN patients with MN could recognize the light chain of myeloperoxidase more frequently than those without MN (P < 0.05). The prevalence of circulating anti-PLA2R antibodies and glomerular PLA2R deposits was significantly lower in patients with combined ANCA-GN and MN than that in patients with idiopathic MN (P < 0.05). Compared with the idiopathic MN patients, the patients with combined ANCA-GN and MN had significantly higher recognition frequency of immunoglobulin (Ig) G2 and IgG3, and significantly lower recognition frequency of IgG4 (P < 0.05). Patients with combined ANCA-GN and MN had distinct clinical features and a different pathogenesis of MN. PMID:26376387

  2. Renal parenchymal resistance in patients with biopsy proven glomerulonephritis: Correlation with histological findings.

    PubMed

    Gigante, Antonietta; Barbano, Biagio; Di Mario, Francesca; Rosato, Edoardo; Simonelli, Marzia; Rocca, Anna Rachele; Conti, Fabrizio; Ceccarelli, Fulvia; Giannakakis, Konstantinos; Valesini, Guido; Cianci, Rosario

    2016-09-01

    Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis (P <0.01, r = 0.26), conversely a negative correlation exists between glomerular filtrate rate and percentage of glomerular sclerosis(P <0.0001, r = -0.35). The percentage of glomerular sclerosis correlate positively with pulsatile index (PI) (P <0.05, r = 0.21) and renal resistive index (RI) (P <0.05, r = 0.20). The percentage of crescents correlates positively with PI(P <0.05, r = 0.21) and RI (P <0.05, r = 0.20). Classifying arteriolosclerosis in four groups according to a severity scale, from absence to severe, PI (P <0.05) and RI (P <0.01) were significantly different. In the post hoc analysis, the median values of PI and RI are significantly different in patients with severe arteriolosclerosis than others. Ultrasound examination is a non-invasive diagnostic technique used on patients with suspected or established renal disease. Our study shows a close correlation between kidney function, ultrasound parameters, and histological findings. Measurement of renal parenchymal resistance by ultrasound could be used in association with biopsy and glomerular function for the evaluation of renal damage in patients with glomerulonephritis. PMID:27091839

  3. The interstitial expression of alpha-smooth muscle actin in glomerulonephritis is associated with renal function

    PubMed Central

    Novakovic, Zana Saratlija; Durdov, Merica Glavina; Puljak, Livia; Saraga, Marijan; Ljutic, Dragan; Filipovic, Tomislav; Pastar, Zvonimir; Bendic, Antonia; Vukojevic, Katarina

    2012-01-01

    Summary Background In a healthy kidney, contractile protein alpha-smooth muscle actin (ASMA) is immunohistochemically strongly expressed only in the blood vessels, while in pathological conditions it can be visualized in glomerular mesangial cells and interstitial myofibroblasts. The aim of this study was to explore the possible correlation between expression of ASMA in glomerulonephritis (GN) and indicators of renal function. Material/Methods We analyzed expression of ASMA in percutaneous renal biopsy of 142 adult and pediatric patients with GN and its correlation with blood pressure, serum creatinine, creatinine clearance and 24-hour urine protein at the time of biopsy. Immunoexpression of ASMA was analyzed quantitatively using computer-assisted morphometric analysis. Relative surface of ASMA expression in all glomeruli and interstitium was calculated for each patient. Results In adults and children, greater expression of ASMA in interstitium was associated with higher serum creatinine and reduced creatinine clearance. Conversely, greater ASMA expression in glomeruli was associated with normal or decreased serum creatinine in adults and increased creatinine clearance in children. In children, correlation was found between high blood pressure and ASMA expression in interstitium. Conclusions We confirmed that interstitial expression of ASMA is associated with reduced renal function at time of biopsy. The connection of ASMA expression in glomeruli with lower serum creatinine and normal or increased creatinine clearance suggests a favorable role of this phenotypic change in glomerular filtration rate; further investigation is needed. PMID:22460095

  4. Recurrence of ANCA-negative renal-limited pauci-immune glomerulonephritis in the renal allograft

    PubMed Central

    Rajkumar, Venkatesh; Gowda, Kiran Krishne; Jha, Vivekanand; Kohli, Harbir Singh; Kumar, Vivek; Ramachandran, Raja

    2013-01-01

    Renal transplantation is the treatment of choice for end-stage renal disease (ESRD) due to pauci-immune crescentic glomerulonephritis (PICGN). A small subgroup of patients with PICGN are anti-neutrophil cytoplasmic antibody (ANCA) negative. We report a case of a patient with ANCA-negative renal-limited form of PICGN who developed ESRD despite treatment. He underwent live-related renal allograft transplantation after 12 months on haemodialysis. In the eighth post-transplant month, he developed graft dysfunction, which on evaluation turned out to be a graft recurrence of the basic disease in the form of PICGN. He received treatment with methylprednisolone, cyclophosphamide and plasmapheresis. However, his renal functions did not improve and he developed graft loss in the 11th post-transplant month and was started on continuous ambulatory peritoneal dialysis. We report a rare recurrence of renal-limited PICGN in the allograft. Patients with PICGN undergoing renal transplantation should be followed up carefully, and an early biopsy should be performed in the case of graft dysfunction to deal with this potentially graft-threatening complication. PMID:26064517

  5. Outcome of glomerulonephritis in live-donor renal transplant recipients: A single-centre experience

    PubMed Central

    Akl, Ahmed Ibrahim; Adel, Hany; Rahim, Mona Abdel; Wafa, Ehab Wahba; Shokeir, Ahmed A.

    2015-01-01

    Objectives To investigate the frequency and risk factors affecting the incidence of post-transplantation glomerulonephritis (GN) and the impact of GN on the survival of the graft and the patient. Patients and methods Patients were classified based on histological findings into three groups. Graft survival was ascertained using the Kaplan–Meier method and significance calculated using log-rank tests. For multivariate analysis the Cox model was used. Results Transplant glomerulopathy was the most prevalent glomerular disease in our series followed by recurrent GN and lastly de novo GN. In all, 50% of the de novo GN group had diabetes. The worst graft outcomes were in the recurrent GN group (P = 0.044). Multivariate analysis revealed ageing of the graft and mammalian target of rapamycin (mTOR) immunosuppression as risk factors for development of GN. While, the age of the recipient and donor, anti-lymphocyte globulin induction therapy, and acute rejection were risk factors for poor graft outcomes. Conclusions GN is an important issue after transplantation. Tracking the incidence and progression of histological findings in the graft may help to guide proper management and improve graft outcome. PMID:26609451

  6. Experimental study of the water jet induced by underwater electrical discharge in a narrow rectangular tube

    NASA Astrophysics Data System (ADS)

    Koita, T.; Zhu, Y.; Sun, M.

    2016-05-01

    This paper reports an experimental investigation on the effects of explosion depth and tube width on the water jet induced by an underwater electrical discharge in a narrow rectangular tube. The water jet formation and bubble structure were evaluated from the images recorded by a high-speed video camera. Two typical patterns of jet formation and four general patterns of bubble implosion were observed, depending on the explosion depth and tube width. The velocity of the water jet was calculated from the recorded images. The jet velocity was observed to depend on not only the explosion depth and energy, but also on the tube width. We proposed an empirical formula defining the water jet velocity in the tube as a function of the tube width and explosion depth and energy.

  7. Evaluation of some coagulation parameters in hepatic coccidiosis experimentally induced with Eimeria stiedai in rabbits.

    PubMed

    Cam, Y; Cetin, E; Iça, A; Atalay, O; Cetin, N

    2006-05-01

    The objective of this study was to evaluate some coagulation parameters in hepatic coccidiosis experimentally induced with Eimeria stiedai in rabbits. Fourteen healthy New Zealand rabbits were equally divided into two groups. One group received no treatment, the other group was orally inoculated with 40 000 sporulated oocysts of E. stiedai in a 1 ml inoculum using a catheter. At day 24 after inoculation, blood samples were collected into sodium citrate-containing tubes to evaluate some coagulation parameters. Although statistically not significant, infected rabbits had prolonged prothrombin time and activated partial thromboplastin time compared with rabbits in the control group. A significant reduction (P < 0.05) was observed in the level of fibrinogen of infected rabbits compared with that of the controls. A slight decrease in thrombocyte counts of infected rabbits was not statistically significant. PMID:16629990

  8. Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies.

    PubMed

    Jensen, V F H; Bøgh, I B; Lykkesfeldt, J

    2014-03-01

    Insulin-induced hypoglycaemia (IIH) is a major acute complication in type 1 as well as in type 2 diabetes, particularly during intensive insulin therapy. The brain plays a central role in the counter-regulatory response by eliciting parasympathetic and sympathetic hormone responses to restore normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from experimental studies on nondiabetic IIH, this review outlines the central mechanisms behind the counter-regulatory response to IIH, as well as cerebral adaption to avoid sequelae of cerebral neuroglycopaenia, including seizures and coma. PMID:24428753

  9. High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens

    NASA Astrophysics Data System (ADS)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Gazzotti, Valeria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The aims of this study was the safety and the efficacy of High Intensity Laser Therapy (HILT) on chronic degenerative tenosynovitis. We have effectuated the histological evaluation and seroassay (C reactive protein) on 18 chickens affect by chronic degenerative tenosynovitis experimentally induced. We have been employed a Nd:YAG laser pulsed wave; all irradiated subjects received the same total energy (270 Joule) with a fluence of 7,7 J/cm2 and intensity of 10,7 W/cm2. The histological findings revealed a distinct reduction of the mineralization of the choral matrix, the anti-inflammatory effect of the laser, the hyperplasia of the synoviocytes and ectasia of the lymphatic vessels.

  10. The use of airborne imaging spectrometer data to determine experimentally induced variation in coniferous canopy chemistry

    NASA Technical Reports Server (NTRS)

    Swanberg, Nancy A.; Matson, Pamela A.

    1987-01-01

    It was experimentally determined whether induced differences in forest canopy chemical composition can be detected using data from the Airborne Imaging Spectrometer (AIS). Treatments were applied to an even-aged forest of Douglas fir trees. Work to date has stressed wet chemical analysis of foilage samples and correction of AIS data. Plot treatments were successful in providing a range of foliar N2 concentrations. Much time was spent investigating and correcting problems with the raw AIS data. Initial problems with groups of drop out lines in the AIS data were traced to the tape recorder and the tape drive. Custom adjustment of the tape drive led to recovery of most missing lines. Remaining individual drop out lines were replaced using average of adjacent lines. Application of a notch filter to the Fourier transform of the image in each band satisfactorily removed vertical striping. The aspect ratio was corrected by resampling the image in the line direction using nearest neighbor interpolation.

  11. An explanation for experimental observations of harmonic cyclotron emission induced by fast ions

    SciTech Connect

    Chen, K.R.; Horton, W.; Van Dam, J.W.

    1993-09-01

    An explanation, supported by numerical simulations and analytical theory, is given for the harmonic cyclotron emission induced by fast ions in tokamak plasmas - particular, for the emission observed at low harmonics in deuterium-deuterium md deuterium-tritium experiments in the Joint European Tokamak. We show that the first proton harmonic is one of the highest spectral peaks whereas the first alpha is weak. We also compare the relative spectral amplitudes of different harmonics. Our results axe consistent with the experimental observations. The simulations verify that the instabilities are caused by a weak relativistic mass effect. Simulation that a nonuniform magnetic field leads to no appreciable change in the growth and saturation amplitude of the waves.

  12. An experimental investigation of vortex-induced vibration with nonlinear restoring forces

    NASA Astrophysics Data System (ADS)

    Mackowski, A. W.; Williamson, C. H. K.

    2013-08-01

    We experimentally examine the amplitude of a bluff body undergoing vortex-induced vibration (VIV) supported by linear and various nonlinear structural forces. This investigation is made possible by our Cyber-Physical Fluid Dynamics force-feedback technique; using it, we can impose arbitrary nonlinear restoring forces on a circular cylinder in our water channel. For the range of nonlinearities examined, detailed analysis allows one to understand and predict the response of the nonlinear structural system using knowledge of a standard, linear VIV system. We also present a case study examining the potential of nonlinear springs to aid in a VIV-based energy harvesting device. Appropriate choices of the spring's nonlinearity allow the hypothetical energy harvester to operate at high performance over a much larger range of Reynolds number than a standard system.

  13. Anti-arthritic effect of eugenol on collagen-induced arthritis experimental model.

    PubMed

    Grespan, Renata; Paludo, Marcia; Lemos, Henrique de Paula; Barbosa, Carmem Patrícia; Bersani-Amado, Ciomar Aparecida; Dalalio, Marcia Machado de Oliveira; Cuman, Roberto Kenji Nakamura

    2012-01-01

    This study was designed to test the efficacy of eugenol, a compound obtained from the essential oil of cloves (Syzygium aromaticum) in collagen-induced arthritis (CIA), a well characterized murine model of rheumatoid arthritis. Macroscopic clinical evidence of CIA manifests first as periarticular erythema and edema in the hind paws. Treatment with eugenol starting at the onset of arthritis (day 25) ameliorated these clinical signs of CIA. Furthermore, eugenol inhibited mononuclear cell infiltration into the knee joints of arthritic mice and also lowered the levels of cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ and tumor growth factor (TGF)-β) within the ankle joints. Eugenol treatment did not affect the in vitro cell viability as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, eugenol ameliorates experimental arthritis and could be useful as a beneficial supplement in treating human arthritis. PMID:23037170

  14. Experimental investigation of a supersonic swept ramp injector using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J.; Hollo, Steven D.; Mcdaniel, James C.

    1990-01-01

    Planar measurements of injectant mole fraction and temperature have been conducted in a nonreacting supersonic combustor configured with underexpanded injection in the base of a swept ramp. The temperature measurements were conducted with a Mach 2 test section inlet in streamwise planes perpendicular to the test section wall on which the ramp was mounted. Injection concentration measurements, conducted in cross flow planes with both Mach 2 and Mach 2.9 free stream conditions, dramatically illustrate the domination of the mixing process by streamwise vorticity generated by the ramp. These measurements, conducted using a nonintrusive optical technique (laser-induced iodine fluorescence), provide an accurate and extensive experimental data base for the validation of computation fluid dynamic codes for the calculation of highly three-dimensional supersonic combustor flow fields.

  15. Nanolesions induced by heavy ions in human tissues: Experimental and theoretical studies

    PubMed Central

    Bleicher, Marcus; Burigo, Lucas; Herrlitz, Maren; Krämer, Michael; Mishustin, Igor; Müller, Iris; Natale, Francesco; Pshenichnov, Igor; Schramm, Stefan; Taucher-Scholz, Gisela; Wälzlein, Cathrin

    2012-01-01

    Summary The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively. PMID:23019551

  16. Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants

    PubMed Central

    Jain, Gyan Chand; Jangir, Ram Niwas

    2014-01-01

    Today diabetes mellitus has emerged as a major healthcare problem throughout the world. It has recently broken the age barrier and has been diagnosed in younger people also. Sustained hyperglycemia is associated with many complications including male reproductive dysfunctions and infertility. Numerous medicinal plants have been used for the management of the diabetes mellitus in various traditional system of medicine and in folklore worldwide as they are a rich source of bioactive phytoconstituents, which lower blood glucose level and/or also act as antioxidants resulting in the amelioration of oxidative-stress-induced diabetic complications. The present review describes the ameliorative effects of medicinal plants or their products, especially on male reproductive dysfunctions, in experimental diabetic animal models. PMID:25125884

  17. Scoliosis in rats with experimentally-induced hemiparkinsonism: dependence upon striatal dopamine denervation.

    PubMed Central

    Herrera-Marschitz, M; Utsumi, H; Ungerstedt, U

    1990-01-01

    Rats suffering from experimental hemiparkinsonism induced by a unilateral injection of 6-hydroxydopamine into the left area ventralis tegmenti showed a strong ipsilateral deviation and scoliosis-like skeletal deformity. The rats often showed single rotatory curves affecting the thoracic and lumbar regions, although cases with multiple curves were also found. The severity of the scoliosis was closely related to a decrease in extracellular striatal dopamine measured with microdialysis and to the development of postsynaptic dopamine receptor supersensitivity, functionally evaluated with rotational behaviour elicited with apomorphine. Indeed, rats with the strongest dopamine depletion (greater than 95%) and the strongest rotational responses showed the sharpest spinal deviation and skeletal deformity. These findings agree with the clinical observations that scoliosis occurs in patients with Parkinson's disease and its direction is correlated with the side of the major signs and symptoms of parkinsonism. Images PMID:2303830

  18. Experimental studies of collective excitations of a BEC in light-induced gauge fields

    NASA Astrophysics Data System (ADS)

    Li, Chuan-Hsun; Niffenegger, Robert; Blasing, David; Olson, Abraham; Chen, Yong P.

    2015-05-01

    We present our experimental studies of collective modes including spin dipole mode and scissors mode of a 87Rb Bose-Einstein condensate (BEC) in the presence of Raman light-induced gauge fields and synthetic spin-orbit coupling (SOC). By Raman dressing the mf spin states within the F =1 manifold, we engineer atoms' energy-momentum dispersion to create synthetic SOC, and spin dependent synthetic electric and magnetic fields. We have used spin dependent synthetic electric fields to make two BECs with different spins oscillate and collide in the optical trap. We have studied the effects of SOC on both the momentum damping and thermalization behaviors of the BECs when undergoing such spin dipole oscillations. We have also used spatially dependent synthetic electric fields to excite the scissors mode, which has been used as a probe for superfluidity. We have investigated the effects of the synthetic gauge fields and SOC on the measured scissors mode.

  19. Efficacy and safety of albendazole against experimentally induced Fasciola hepatica infections in goats.

    PubMed

    Foreyt, W J

    1988-01-01

    Forty 8-week-old goats were allocated to five groups of equal size to determine the optimal dosage of albendazole against experimentally induced 14-week-old Fasciola hepatica infections. Albendazole suspension given orally at 5.0, 7.5, 10.0 and 15 mg kg-1 of body weight was 73.3, 88.2, 88.3 and 95.9% effective, respectively, when compared to untreated controls. Mean number of F. hepatica in the untreated control goats was 75.4. No signs of toxicity were observed. When albendazole was given to eight, 8-week-old goats orally at 75 mg kg-1 (five times the optimal dosage), no signs of toxicity were observed. PMID:3347986

  20. Autoantibody profile in the experimental model of scleroderma induced by type V human collagen

    PubMed Central

    Callado, Maria R M; Viana, Vilma S T; Vendramini, Margarete B G; Leon, Elaine P; Bueno, Cleonice; Velosa, Ana P P; Teodoro, Walcy R; Yoshinari, Natalino H

    2007-01-01

    The aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (Anti-Scl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175 000 and 220 000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. Conclusion: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc. PMID:17442023

  1. Angiopoietin-2 enhances survival in experimental sepsis induced by multidrug-resistant Pseudomonas aeruginosa.

    PubMed

    Tzepi, Ira-Maria; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Tsaganos, Thomas; Claus, Ralf A; Vaki, Ilia; Pelekanou, Aimilia; Kotsaki, Antigone; Tziortzioti, Vassiliki; Topouzis, Stavros; Bauer, Michael; Papapetropoulos, Andreas

    2012-11-01

    Levels of circulating angiopoietin-2 (Ang-2) increase in sepsis, raising the possibility that Ang-2 acts as a modulator in the sepsis cascade. To investigate this, experimental sepsis was induced in male C57BL6 mice by a multidrug-resistant isolate of Pseudomonas aeruginosa; survival was determined along with neutrophil tissue infiltration and release of proinflammatory cytokines. Survival was significantly increased either by pretreatment with recombinant Ang-2 2 h before or treatment with recombinant Ang-2 30 min after bacterial challenge. Likewise, Ang-2 pretreatment protected against sepsis-related death elicited by Escherichia coli; however, Ang-2 failed to provide protection in lipopolysaccharide (LPS)-challenged mice. The survival advantage of Ang-2 in response to P. aeruginosa challenge was lost in tumor necrosis factor (TNF)-deficient mice or neutropenic mice. Infiltration of the liver by neutrophils was elevated in the Ang-2 group compared with saline-treated animals. Serum TNF-α levels were reduced by Ang-2, whereas those of interleukin (IL)-6 and IL-10 remained unchanged. This was accompanied by lower release of TNF-α by stimulated splenocytes. When applied to U937 cells in vitro, heat-killed P. aeruginosa induced the secretion of IL-6 and TNF-α; low levels of exogenous TNF-α synergized with P. aeruginosa. This synergistic effect was abolished after the addition of Ang-2. These results put in evidence a striking protective role of Ang-2 in experimental sepsis evoked by a multidrug-resistant isolate of P. aeruginosa attributed to modulation of TNF-α production and changes in neutrophil migration. The protective role of Ang-2 is shown when whole microorganisms are used and not LPS, suggesting complex interactions with the host immune response. PMID:22859861

  2. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    PubMed Central

    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  3. Bacillus cereus Induces Permeability of the Blood Ocular Barrier During Experimental Endophthalmitis

    PubMed Central

    Moyer, A. L.; Ramadan, R. T.; Novosad, B.; Astley, R.; Callegan, M. C.

    2010-01-01

    Purpose The purpose of this study was to determine to what extent blood retina barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. Methods Mice were intravitreally injected with 100 CFU B. cereus and eyes were analyzed at specific times postinfection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the RPE. Results B. cereus-induced leakage of albumin and fibrin into the aqueous and vitreous humor by 8 h postinfection. BRB permeability occurred as early as 4 h and increased 13.30-fold compared to uninfected controls by 8 h. Production of proinflammatory cytokines IL-6, MIP-1α, IL-1β, and KC increased over the course of infection. In the retina, ZO-1 disruption begins by 4 h, followed by decreasing occludin and ZO-1 expression at 4 and 8 h, respectively. Tubulin condensation and RPE65 degradation occurred by 12 h. A quorum sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Both wild-type and mutant B. cereus sterile supernatants induced blood ocular barrier permeability similarly to that of wild-type infection. Conclusions These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 h postinfection. Disruption of tight junctions at the level of the RPE may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability. PMID:19264886

  4. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord.

    PubMed

    Oji, Satoru; Nicolussi, Eva-Maria; Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  5. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  6. Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria

    PubMed Central

    Spaccapelo, Roberta; Janse, Chris J.; Caterbi, Sara; Franke-Fayard, Blandine; Bonilla, J. Alfredo; Syphard, Luke M.; Di Cristina, Manlio; Dottorini, Tania; Savarino, Andrea; Cassone, Antonio; Bistoni, Francesco; Waters, Andrew P.; Dame, John B.; Crisanti, Andrea

    2010-01-01

    Plasmodium parasites lacking plasmepsin 4 (PM4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion, have only a modest decrease in the asexual blood-stage growth rate; however, PM4 deficiency in the rodent malaria parasite Plasmodium berghei results in significantly less virulence than that for the parental parasite. P. berghei Δpm4 parasites failed to induce experimental cerebral malaria (ECM) in ECM-susceptible mice, and ECM-resistant mice were able to clear infections. Furthermore, after a single infection, all convalescent mice were protected against subsequent parasite challenge for at least 1 year. Real-time in vivo parasite imaging and splenectomy experiments demonstrated that protective immunity acted through antibody-mediated parasite clearance in the spleen. This work demonstrates, for the first time, that a single Plasmodium gene disruption can generate virulence-attenuated parasites that do not induce cerebral complications and, moreover, are able to stimulate strong protective immunity against subsequent challenge with wild-type parasites. Parasite blood-stage attenuation should help identify protective immune responses against malaria, unravel parasite-derived factors involved in malarial pathologies, such as cerebral malaria, and potentially pave the way for blood-stage whole organism vaccines. PMID:20019192

  7. Foraminiferal survival after long-term in situ experimentally induced anoxia

    NASA Astrophysics Data System (ADS)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-11-01

    Anoxia was successfully induced in four benthic chambers installed at 24 m depth on the northern Adriatic seafloor from 9 days to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerTM Green method was applied and calcareous and agglutinated foraminifera were analyzed. Numerous individuals were found living at all sampling times and at all sampling depths (to 5 cm), supported by a ribosomal RNA analysis that revealed that certain benthic foraminifera were active after 10 months of anoxia. The results show that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulfides. However, foraminiferal standing stocks decrease with sampling time in an irregular manner. A large difference in standing stock between two cores sampled under initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after one month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in cores sampled after 2 months of anoxia to then attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulfides but rather due to a continuous diminution of labile organic matter.

  8. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus.

    PubMed

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  9. Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy.

    PubMed

    Bonnet, Benjamin; Vigneron, James; Levacher, Béatrice; Vazquez, Thomas; Pitoiset, Fabien; Brimaud, Faustine; Churlaud, Guillaume; Klatzmann, David; Bellier, Bertrand

    2016-07-01

    Regulatory T cells (Tregs) are pivotal for maintenance of immune self-tolerance and also regulate immune responses to exogenous Ags, including allergens. Both decreased Treg number and function have been reported in allergic patients, offering new therapeutic perspectives. We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (ld-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of ld-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in ld-IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that ld-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases. PMID:27259854

  10. Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

    PubMed Central

    Martinez, María del Carmen; Ruspini, Silvina Fernanda; Afonso, Susana Graciela; Meiss, Roberto; Buzaleh, Ana Maria

    2015-01-01

    The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or ursodeoxycholic (URSO). The administration of Gris alone increased the activities of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST), as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris. PMID:25945334

  11. Critical role of activation induced cytidine deaminase in experimental autoimmune encephalomyelitis.

    PubMed

    Sun, Yonglian; Peng, Ivan; Senger, Kate; Hamidzadeh, Kajal; Reichelt, Mike; Baca, Miriam; Yeh, Ronald; Lorenzo, Maria N; Sebrell, Andrew; Dela Cruz, Christopher; Tam, Lucinda; Corpuz, Racquel; Wu, Jiansheng; Sai, Tao; Roose-Girma, Merone; Warming, Søren; Balazs, Mercedesz; Gonzalez, Lino C; Caplazi, Patrick; Martin, Flavius; Devoss, Jason; Zarrin, Ali A

    2013-03-01

    Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE. PMID:23167594

  12. Critical role of activation induced cytidine deaminase in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    2013-01-01

    Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE. PMID:23167594

  13. Exploring the electron density in plasma induced by EUV radiation: I. Experimental study in hydrogen

    NASA Astrophysics Data System (ADS)

    van der Horst, R. M.; Beckers, J.; Osorio, E. A.; Astakhov, D. I.; Goedheer, W. J.; Lee, C. J.; Ivanov, V. V.; Krivtsum, V. M.; Koshelev, K. N.; Lopaev, D. V.; Bijkerk, F.; Banine, V. Y.

    2016-04-01

    Plasmas induced by EUV radiation are unique since they are created without the need of any discharge. Moreover, it is essential to characterize these plasmas to understand and predict their long term impact on highly delicate optics in EUV lithography tools. In this paper we study plasmas induced by 13.5 nm EUV radiation in hydrogen gas. The electron density is measured temporally resolved using a non-invasive technique known as microwave cavity resonance spectroscopy. The influence of the EUV pulse energy and gas pressure on the temporal evolution of the electron density has been explored over a parameter range relevant for industry. Our experimental results show that the maximum electron density is in the order of 1014 m-3 and depends linearly on the EUV pulse energy. Furthermore, the maximum electron density depends quadratically on the pressure; the linear term is caused by photoionization and the quadratic term by subsequent electron impact ionization. The decay of the plasma is governed by ambipolar diffusion and, hence, becomes slower at elevated pressures. Similarities and differences of the same processes in argon are highlighted in this paper.

  14. Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

    PubMed

    Bolat, D; Oltulu, F; Uysal, A; Kose, T; Gunlusoy, B; Yigitturk, G; Turk, N S; Turan, T

    2016-09-01

    To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. PMID:27373273

  15. Prevention of chemically induced diabetes mellitus in experimental animals by virgin argan oil.

    PubMed

    Bellahcen, Said; Mekhfi, Hassane; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Hakkou, Abdelkader; Aziz, Mohammed; Bnouham, Mohamed

    2012-02-01

    The argan tree plays an important socioeconomic and ecologic role in South Morocco. Moreover, there is much evidence for the beneficial effects of virgin argan oil (VAO) on human health. Thus, this study investigated whether administering VAO to rats can prevent the development of diabetes. VAO extracted by a traditional method from the almonds of Argania spinosa (2 mL/kg) was administered orally (for 7 consecutive days) to rats before and during intraperitoneal alloxan administration (75 mg/kg for 5 consecutive days). An alloxan diabetic-induced untreated group and treated by table oil were used as control groups. Body mass, blood glucose and hepatic glycogen were evaluated. In the present study, subchronic treatment with VAO at a dose of 2 mL/kg, before the experimental induction of diabetes, prevented the body mass loss, induced a significant reduction of blood glucose and a significant increase of hepatic glycogen level (p < 0.001) compared with the untreated diabetic group. In conclusion, the present study shows that argan oil should be further investigated in a human study to clarify its possible role in reducing weight loss in diabetics, and even in inhibiting the development or progression of diabetes. This antidiabetic effect could be due to the richness of VAO in tocopherols, phenolic compounds and unsaturated fatty acids. PMID:21584872

  16. Antistressor activity of Ocimum sanctum (Tulsi) against experimentally induced oxidative stress in rabbits.

    PubMed

    Jyoti, S; Satendra, S; Sushma, S; Anjana, T; Shashi, S

    2007-01-01

    Fresh leaves of Ocimum sanctum (O. sanctum) were evaluated for antistress activity against experimentally induced oxidative stress in albino rabbits. Animals of the test group received supplementation of 2 g fresh leaves of O. sanctum per rabbit for 30 days. Anemic hypoxia was induced chemically by injecting the rabbits with 15 mg sodium nitrite per 100 g body weight intraperitoneally. Results indicated that O. sanctum administration blunted the changes in cardiorespiratory (BP, HR, RR) parameters in response to stress. A significant (p < 0.01) decrease in blood sugar level was observed after 30 days of dietary supplementation of O. sanctum leaves. Significant increase (p < 0.05) in the levels of enzymatic (superoxide dismutase) and nonenzymatic (reduced glutathione) antioxidants was observed in the test group after the treatment with O. sanctum. Oxidative stress led to a lesser depletion of reduced glutathione (28.80%) and plasma superoxide dismutase (23.04%) in O. sanctum-treated rabbits. The results of this study suggest that the potential antistressor activity of O. sanctum is partly attributable to its antioxidant properties. PMID:17922070

  17. Role of vascular endothelial growth factor signaling in Schistosoma-induced experimental pulmonary hypertension

    PubMed Central

    2014-01-01

    Abstract There is significant evidence that Th2 (T helper 2)-mediated inflammation supports the pathogenesis of both human and experimental animal models of pulmonary hypertension (PH). A key immune regulator is vascular endothelial growth factor (VEGF), which is produced by Th2 inflammation and can itself contribute to Th2 pulmonary responses. In this study, we interrogated the role of VEGF signaling in a murine model of schistosomiasis-induced PH with a phenotype of significant intrapulmonary Th2 inflammation, vascular remodeling, and elevated right ventricular pressures. We found that VEGF receptor blockade partially suppressed the levels of the Th2 inflammatory cytokines interleukin (IL)-4 and IL-13 in both the lung and the liver after Schistosoma mansoni exposure and suppressed pulmonary vascular remodeling. These findings suggest that VEGF positively contributes to schistosomiasis-induced vascular inflammation and remodeling, and they also provide evidence for a VEGF-dependent signaling pathway necessary for pulmonary vascular remodeling and inflammation in this model. PMID:25006448

  18. Experimental peritonitis induced by oral administration of indomethacin in Mongolian gerbils

    PubMed Central

    Lee, Jin-Uk

    2006-01-01

    The possibility of inducing peritoneal inflammation in three murine species (gerbils, rats and mice) via the oral administration of indomethacin was investigated with the overall aim of developing an experimental animal model for human peritonitis. Gerbils given high doses of indomethacin at a rate of 30 mg and 40 mg/kg body weight showed swelling of the abdomen, depression and dyspnea within 4 days after the treatment. The severity of the clinical symptoms increased with time. The animals were confirmed as having developed peritonitis based on the pathological features including inflammation of the peritoneum, and fibrinous adhesion of the abdominal organs in the abdominal cavity. The severity of peritonitis increased with increasing dose of indomethacin, and was not related to the gender of the animal. On the other hand, peritoneal inflammation did not develop in the rats and mice even at high doses. Therefore, the administration of 30 mg/kg body weight of indomethacin is an effective and simple method of inducing peritonitis in 5-week-old Mongolian gerbils. The animal peritonitis model used in this study can be used as an effective tool for examining potential therapeutic compounds for preventing peritoneal damage during peritonitis, and provide insight into the pathophysiology of peritonitis. PMID:16645338

  19. Antitussive effect of naringin on experimentally induced cough in Guinea pigs.

    PubMed

    Gao, Sen; Li, Peibo; Yang, Hongliang; Fang, Siqi; Su, Weiwei

    2011-01-01

    The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels. PMID:20645246

  20. Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice.

    PubMed

    Yang, Yang; He, Jiao; Suo, Yuan; Zheng, Zongwei; Wang, Jingjing; Lv, Le; Huo, Chuanchuan; Wang, Ziye; Li, Jing; Sun, Wenji; Zhang, Yongmin

    2016-07-01

    Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60mg/kg) and sulfasalazine (500mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1β, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice. PMID:27179450

  1. Induced current electrical impedance tomography system: experimental results and numerical simulations.

    PubMed

    Zlochiver, Sharon; Radai, M Michal; Abboud, Shimon; Rosenfeld, Moshe; Dong, Xiu-Zhen; Liu, Rui-Gang; You, Fu-Sheng; Xiang, Hai-Yan; Shi, Xue-Tao

    2004-02-01

    In electrical impedance tomography (EIT), measurements of developed surface potentials due to applied currents are used for the reconstruction of the conductivity distribution. Practical implementation of EIT systems is known to be problematic due to the high sensitivity to noise of such systems, leading to a poor imaging quality. In the present study, the performance of an induced current EIT (ICEIT) system, where eddy current is applied using magnetic induction, was studied by comparing the voltage measurements to simulated data, and examining the imaging quality with respect to simulated reconstructions for several phantom configurations. A 3-coil, 32-electrode ICEIT system was built, and an iterative modified Newton-Raphson algorithm was developed for the solution of the inverse problem. The RMS norm between the simulated and the experimental voltages was found to be 0.08 +/- 0.05 mV (<3%). Two regularization methods were implemented and compared: the Marquardt regularization and the Laplacian regularization (a bounded second-derivative regularization). While the Laplacian regularization method was found to be preferred for simulated data, it resulted in distinctive spatial artifacts for measured data. The experimental reconstructed images were found to be indicative of the angular positioning of the conductivity perturbations, though the radial sensitivity was low, especially when using the Marquardt regularization method. PMID:15005319

  2. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

    SciTech Connect

    Constantinou, Maria A.; Theocharis, Stamatios E.; Mikros, Emmanuel . E-mail: mikros@pharm.uoa.gr

    2007-01-01

    Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.

  3. Experimentally Induced Pulpal Lesion and Substance P Expression: Effect of Ketoprofen—A Preliminary Study

    PubMed Central

    Abbate, Gian Marco; Sacerdote, Paola; Amodeo, Giada; Mangano, Alessandro; Levrini, Luca

    2016-01-01

    Objectives. To evaluate substance P (SP) and the effect of ketoprofen administration, a nonsteroidal anti-inflammatory drug (NSAID), on SP in the pulp of upper third molars with experimentally induced pulpal lesion. Materials and Methods. A sample of 20 young systemically healthy adults of both sexes, nonsmokers, with a healthy upper third molar to extract for orthodontic purposes, was selected. Prior to the procedure, an inflammatory process was generated by mechanical exposure of the pulp. After 15 minutes, the pulp was collected using a sterile barbed broach. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into two groups: group 1 received a dose of ketoprofen 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration. The patients were asked to complete a diary on the postoperative pain. Results. No statistically significant difference could be detected in SP expression between the two groups. In group 1, pain manifestation was significantly delayed in comparison with group 2. Conclusions. Preventive administration of ketoprofen did not significantly affect the pulpal levels of SP but resulted in a significantly postponed manifestation of pain after extraction. PMID:27034673

  4. Naturally occurring and experimentally induced castor bean (Ricinus communis) poisoning in ducks

    USGS Publications Warehouse

    Jensen, W.I.; Allen, J.P.

    1981-01-01

    Castor bean (Ricinus communis) poisoning accounted for the death of several thousand ducks in the Texas panhandle in the fall and winter months of 1969-1971. Signs of intoxication resembled those of botulism, except for mucoid, blood-tinged excreta. The most common lesions were severe fatty change in the liver, widely distributed internal petechial hemorrhages or ecchymoses, and catarrhal enteritis. Nearly intact castor beans were found in the stomach of one duck during field necropsy. Fragments of seed coat resembling castor bean were found in the stomachs of 10 of 14 ducks examined in the laboratory. Clinical signs and postmortem lesions observed in wild ducks were induced experimentally in mallards (Anas platyrhynchos) by force-feeding intact castor beans. Toxicity titrations were erratic, but the LD50 appeared to be between three and four seeds. The mouse toxicity test, used to detect Clostridium botulinum toxin in the blood serum of intoxicated ducks, was negative in every case. Hemagglutination and precipitin tests generally failed to detect castor bean in extracts of excreta or intestinal contents of experimentally intoxicated ducks.

  5. Acid-induced changes in DOC quality in an experimental whole-lake manipulation

    SciTech Connect

    Donahue, W.F.; Schindler, D.W.; Page, S.J.; Stainton, M.P.

    1998-10-01

    Fluorescence analyses of archived water samples were used to typify dissolved organic carbon (DOC) quality in experimentally acidified lakes and reference lakes at the Experimental Lakes Area, in northwestern Ontario. Carbon-specific DOC fluorescence (CSF) during peak acidification was 40--50% of that for a high-DOC reference lake and similar to a low-DOC reference lake. Reference lakes showed similar but smaller decreases in CSF during several years of prolonged drought in the late 1980s. During the 1990s, recovery from acidification resulted in increased CSF, whereas reference lakes remained unchanged during the same time period. In addition to causing decreased [DOC], acidification causes changes in fluorescence-peak geometry that indicate a switch in DOC quality from allochthonous to autochthonous-like during acidification. The acid-induced change in DOC quality was likely due to increased chemical oxidation or precipitation of the UV-absorbent aromatic portions of allochthonous DOC molecules, leaving more UV-transparent aliphatic chains. The change in the nature of DOC following acidification and drought may have an important role in physical, biological, and chemical processes within these lakes. With recovery from acidification, DOC quality has also recovered.

  6. Experimental investigation of flow-induced vibration interference between two circular cylinders

    NASA Astrophysics Data System (ADS)

    Assi, G. R. S.; Meneghini, J. R.; Aranha, J. A. P.; Bearman, P. W.; Casaprima, E.

    2006-08-01

    This paper presents experimental results concerning flow-induced oscillations of circular cylinders arranged in tandem. New measurements on the dynamic response oscillations of an isolated cylinder and flow interference of two cylinders are shown. Preliminary flow visualization employing a PIV system is also shown. The models are mounted on an elastic base fitted with flexor blades and instrumented with strain gauges. The base is fixed on the test-section of a water channel facility. The flexor blades possess a low-damping characteristic (ζ≃0.008 0.0109) and they are free to oscillate only in the cross-flow direction. The Reynolds number of the experiments is from 3000 to 13000, and reduced velocities, based on natural frequency in still water, vary up to 12. The interference phenomenon on VIV is investigated by conducting experiments in which the upstream cylinder is maintained fixed and the downstream one is mounted on the elastic base. The results for an isolated cylinder are in accordance with other measurements found in the literature for m≃2 and 8. For the tandem arrangement and m≃2, the trailing cylinder oscillation presents what previous researchers have termed interference galloping behaviour for a centre-to-centre gap spacing ranging from 2D to 5.6D. These initial results validate the experimental set-up and lead the way for future work, including tandem, staggered and side-by-side arrangements with the two cylinders free to move.

  7. Prediction of Symptom Change in Placebo Versus No-Treatment Group in Experimentally Induced Motion Sickness.

    PubMed

    Horing, Bjoern; Weimer, Katja; Muth, Eric R; Enck, Paul

    2015-09-01

    The long-standing question of who responds to placebo and who does not is of great theoretical and clinical relevance and has received increasing attention in recent years. We therefore performed a post hoc analysis of one of our previously published studies on placebo responses (PRs). In the analysis, fourteen potential predictors for the PR on experimentally induced motion sickness in 32 healthy volunteers were explored using moderated multiple regression. Generalized self-efficacy, generalized self, internal locus of control and cognitive flexibility were significantly associated with symptom improvement in the placebo group, as compared to the untreated control group. Notably, the directions of the associations were such that the "unfavorable" side of the constructs (e.g. low self-efficacy) predicted a higher PR. Instead, the "favorable" side predicted symptom improvement in the control group. Results fit well with prior research into psychological influences on motion sickness. Although PRs in motion sickness are not well established, it is suggested to include the identified constructs in future research involving motion sickness-related symptoms such as nausea and vertigo. Concerning PRs in general, the results may have implications for clinical as well as experimental research on other symptoms and disorders, such as pain or depression. PMID:25912825

  8. Experimentally Induced Pulpal Lesion and Substance P Expression: Effect of Ketoprofen-A Preliminary Study.

    PubMed

    Abbate, Gian Marco; Sacerdote, Paola; Amodeo, Giada; Mangano, Alessandro; Levrini, Luca

    2016-01-01

    Objectives. To evaluate substance P (SP) and the effect of ketoprofen administration, a nonsteroidal anti-inflammatory drug (NSAID), on SP in the pulp of upper third molars with experimentally induced pulpal lesion. Materials and Methods. A sample of 20 young systemically healthy adults of both sexes, nonsmokers, with a healthy upper third molar to extract for orthodontic purposes, was selected. Prior to the procedure, an inflammatory process was generated by mechanical exposure of the pulp. After 15 minutes, the pulp was collected using a sterile barbed broach. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into two groups: group 1 received a dose of ketoprofen 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration. The patients were asked to complete a diary on the postoperative pain. Results. No statistically significant difference could be detected in SP expression between the two groups. In group 1, pain manifestation was significantly delayed in comparison with group 2. Conclusions. Preventive administration of ketoprofen did not significantly affect the pulpal levels of SP but resulted in a significantly postponed manifestation of pain after extraction. PMID:27034673

  9. Experimentally induced life-history evolution in a killifish in response to the introduction of guppies.

    PubMed

    Walsh, Matthew R; Reznick, David N

    2011-04-01

    Life-history theory predicts that increased predation on juvenile age/size-classes favors delayed maturation and decreased reproductive investment. Although this theory has received correlative support, experimental tests in nature are rare. In 1976 and 1981, guppies (Poecilia reticulata) were transplanted into localities that previously only contained a killifish, Rivulus hartii. This situation presents an opportunity to experimentally test this life-history prediction because guppies prey upon young Rivulus. We evaluated the response to selection in Rivulus by measuring phenotypic and genotypic divergence between introduction and upstream "control" localities that lack guppies. Contrary to expectations, Rivulus from the introduction sites evolved earlier maturation and increased reproductive investment within 25 years. Such evolutionary changes parallel previous investigations on natural communities of Rivulus, but do not comply with predictions of age/size-specific theory. Guppies also caused reduced densities and increased growth rates of Rivulus, which are hypothesized indirect effects of predation. Additional life-history theories show that changes in density and growth can interact with predator-induced mortality to alter the predicted trajectory of evolution. We discuss how these latter frameworks improve the fit between theory and evolution in Rivulus. PMID:21062280

  10. Modeling and experimental verification of thermally induced residual stress in RF-MEMS

    NASA Astrophysics Data System (ADS)

    Somà, Aurelio; Mubasher Saleem, Muhammad

    2015-05-01

    Electrostatically actuated radio frequency microelectromechanical systems (RF-MEMS) generally consist of microcantilevers and clamped-clamped microbeams. The presence of residual stress in these microstructures affects the static and dynamic behavior of the device. In this study, nonlinear finite element method (FEM) modeling and the experimental validation of residual stress induced in the clamped-clamped microbeams and the symmetric toggle RF-MEMS switch (STS) is presented. The formation of residual stress due to plastic deformation during the thermal loading-unloading cycle in the plasma etching step of the microfabrication process is explained and modeled using the Bauschinger effect. The difference between the designed and the measured natural frequency and pull-in voltage values for the clamped-clamped microbeams is explained by the presence of the nonhomogenous tensile residual stress. For the STS switch specimens, three-dimensional (3D) FEM models are developed and the initial deflection at zero bias voltage, observed during the optical profile measurements, is explained by the residual stress developed during the plasma etching step. The simulated residual stress due to the plastic deformation is included in the STS models to obtain the switch pull-in voltage. At the end of the simulation process, a good correspondence is obtained between the FEM model results and the experimental measurements for both the clamped-clamped microbeams and the STS switch specimens.

  11. Experimentally-induced Increases in Early Gesture Lead to Increases in Spoken Vocabulary

    PubMed Central

    LeBarton, Eve Sauer; Goldin-Meadow, Susan; Raudenbush, Stephen

    2014-01-01

    Differences in vocabulary that children bring with them to school can be traced back to the gestures they produce at 1;2, which, in turn, can be traced back to the gestures their parents produce at the same age (Rowe & Goldin-Meadow, 2009b). We ask here whether child gesture can be experimentally increased and, if so, whether the increases lead to increases in spoken vocabulary. Fifteen children aged 1;5 participated in an 8-week at-home intervention study (6 weekly training sessions plus follow-up 2 weeks later) in which all were exposed to object words, but only some were told to point at the named objects. Before each training session and at follow-up, children interacted naturally with caregivers to establish a baseline against which changes in communication were measured. Children who were told to gesture increased the number of gesture meanings they conveyed, not only during training but also during interactions with caregivers. These experimentally-induced increases in gesture led to larger spoken repertoires at follow-up. PMID:26120283

  12. Inability of two topical treatments to influence the course of experimentally induced dermatophytosis in cats.

    PubMed

    DeBoer, D J; Moriello, K A

    1995-07-01

    An experimental model of dermatophytosis was used to compare the efficacy of 2 topical antifungal treatments against Microsporum canis infection in cats. Infection was established in 24 cats by topical application of 10(5) M canis macroconidia to the skin of the lateral part of the abdomen under an occlusive bandage. Three groups of 6 cats each then were treated twice weekly for 18 weeks with chlorhexidine shampoo and dip, detergent shampoo vehicle only, or glyceryl monolaurate shampoo. Six cats were left untreated as controls. The experimentally induced infections strongly resembled naturally developing infections of moderate to severe nature. Signs of infection peaked in severity at 5 weeks after inoculation, then gradually resolved over 7 to 16 additional weeks. Dermatophytes were consistently isolated on culture for at least 8 weeks of treatment. Mycologic cure (defined as lack of dermatophyte isolation on 3 successive weekly cultures) was attained in 8 cats at the end of 18 weeks of treatment. Infections appeared to resolve at equivalent rates in all groups of cats, including controls. Consistent or meaningful significant differences in variables such as lesion size, clinical sign score, or total infection score were not found between treated and control groups. Our study revealed that this topical treatment regimen with chlorhexidine or glyceryl monolaurate is ineffective against M canis infection in cats. PMID:7601693

  13. Innate immune response in experimentally induced bovine intramammary infection with Staphylococcus simulans and S. epidermidis

    PubMed Central

    2011-01-01

    Coagulase-negative staphylococci (CNS) are in several countries the most common bacteria isolated in subclinical mastitis. To investigate the innate immune response of cows to infections with two common mastitis-causing CNS species, Staphylococcus epidermidis and Staphylococcus simulans, experimental intramammary infection was induced in eight cows using a crossover design. The milk somatic cell count (SCC), N-acetyl-β-D-glucosaminidase (NAGase) activity, milk amyloid A (MAA), serum amyloid A (SAA) and proinflammatory cytokines interleukin (IL)-1β, IL-8, and tumor necrosis factor α (TNF-α) were determined at several time points before and after challenge. All cows became infected and showed mild to moderate clinical signs of mastitis. The spontaneous elimination rate of the 16 infections was 31.3%, with no difference between species. Infections triggered a local cytokine response in the experimental udder quarters, but cytokines were not detected in the uninfected control quarters or in systemic circulation. The innate local immune response for S. simulans was slightly stronger, with significantly higher concentrations of IL-1β and IL-8. The IL-8 response could be divided into early, delayed, or combined types of response. The CNS species or persistency of infection was not associated with the type of IL-8 response. No significant differences were seen between spontaneously eliminated or persistent infections. PMID:21414189

  14. Experimental optic neuritis induced by the microinjection of lipopolysaccharide into the optic nerve.

    PubMed

    Aranda, Marcos L; Dorfman, Damián; Sande, Pablo H; Rosenstein, Ruth E

    2015-04-01

    Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve which leads to retinal ganglion cell (RGC) loss, and visual dysfunction. We investigated the ability of a single microinjection of bacterial lipopolysaccharide (LPS) directly into the optic nerve to induce functional and structural alterations compatible with ON. For this purpose, optic nerves from male Wistar rats remained intact or were injected with vehicle or LPS. The effect of LPS was evaluated at several time points post-injection in terms of: i) visual pathway and retinal function (visual evoked potentials (VEPs) and electroretinograms, (ERGs), respectively), ii) anterograde transport from the retina to its projection areas, iii) consensual pupil light reflex (PLR), iv) optic nerve histology, v) microglia/macrophage reactivity (by Iba-1- and ED1-immunostaining), vi) astrocyte reactivity (by glial fibrillary acid protein-immunostaining), vii) axon number (by toluidine blue staining), vii) demyelination (by myelin basic protein immunoreactivity and luxol fast blue staining), viii) optic nerve ultrastructure, and ix) RGC number (by Brn3a immunoreactivity). LPS induced a significant and persistent decrease in VEP amplitude and PLR, without changes in the ERG. In addition, LPS induced a deficit in anterograde transport, and an early inflammatory response consisting in an increased cellularity, and Iba-1 and ED1-immunoreactivity in the optic nerve, which were followed by changes in axonal density, astrocytosis, demyelination, and axon and RGC loss. These results suggest that the microinjection of LPS into the optic nerve may serve as a new experimental model of primary ON. PMID:25687552

  15. Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

    NASA Astrophysics Data System (ADS)

    Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

    2015-08-01

    Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new

  16. Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions

    PubMed Central

    2013-01-01

    Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group. PMID:24308772

  17. Experimental and Numerical Study of Laser-Induced Forward Transfer Printing of Liquids

    NASA Astrophysics Data System (ADS)

    Brown, Matthew S.

    Laser-induced forward transfer (LIFT) is an emerging high-resolution printing technique, which can deposit a wide range of fluid materials without a nozzle. In this process, a pulsed laser initiates the highly directed expulsion of fluid from a thin donor ink film onto a confined region of an acceptor substrate. Despite being validated as a versatile technique for printing devices, the fundamental mechanisms of the deposition process are still not fully understood. Further investigation of the laser-induced ejection dynamics is necessary in order to motivate new ways in which to optimize and control the printing process. Additionally, the LIFT configuration presents a unique laboratory in which to study novel regimes of fluid dynamics. This thesis presents an in-depth study of the LIFT printing process using a balance of experimental measurement and computational modeling. In the first part, time-resolved imaging is used to investigate the mechanisms responsible for the laser-induced ejection of ink. Fluid ejections driven by a rapidly expanding gas cavity within the ink film are observed and analyzed within the context of similar work on cavitation bubble formation, revealing that the unique geometry and size scale of LIFT invokes novel flow behavior. An alternative mechanism is also observed in which the fluid is ejected by the rapid formation of blister on a polymer layer adjacent to the ink film. The dynamics of the blister expansion and associated ink ejection are analyzed as a function of system properties and processing parameters. In the second part, a computational model of the blister-actuated ejection process is developed and used to study the novel regime of free-surface jetting from thin liquid films. The model is first validated against experimental results. It is then used to develop a fundamental understanding of the ejection process as well as conduct a detailed parametric study on the influence of system parameters on printing performance. These

  18. The effect of spinal manipulative therapy on experimentally induced pain: a systematic literature review

    PubMed Central

    2012-01-01

    Background Although there is evidence that spinal manipulative therapy (SMT) can reduce pain, the mechanisms involved are not well established. There is a need to review the scientific literature to establish the evidence-base for the reduction of pain following SMT. Objectives To determine if SMT can reduce experimentally induced pain, and if so, if the effect is i) only at the level of the treated spinal segment, ii) broader but in the same general region as SMT is performed, or iii) systemic. Design A systematic critical literature review. Methods A systematic search was performed for experimental studies on healthy volunteers and people without chronic syndromes, in which the immediate effect of SMT was tested. Articles selected were reviewed blindly by two authors. A summary quality score was calculated to indicate level of manuscript quality. Outcome was considered positive if the pain-reducing effect was statistically significant. Separate evidence tables were constructed with information relevant to each research question. Results were interpreted taking into account their manuscript quality. Results Twenty-two articles were included, describing 43 experiments, primarily on pain produced by pressure (n = 27) or temperature (n = 9). Their quality was generally moderate. A hypoalgesic effect was shown in 19/27 experiments on pressure pain, produced by pressure in 3/9 on pain produced by temperature and in 6/7 tests on pain induced by other measures. Second pain provoked by temperature seems to respond to SMT but not first pain. Most studies revealed a local or regional hypoalgesic effect whereas a systematic effect was unclear. Manipulation of a “restricted motion segment” (“manipulable lesion”) seemed not to be essential to analgesia. In relation to outcome, there was no discernible difference between studies with higher vs. lower quality scores. Conclusions These results indicate that SMT has a direct local/regional hypoalgesic effect on

  19. Electroacupuncture-Induced Attenuation of Experimental Epilepsy: A Comparative Evaluation of Acupoints and Stimulation Parameters

    PubMed Central

    Kang, Xuezhi; Shen, Xueyong; Xia, Ying

    2013-01-01

    The efficacy of electroacupuncture (EA) on epilepsy remains to be verified because of previous controversies that might be due to the complexity of the effects induced by different acupoints and stimulation approaches adopted. Therefore, we investigated the effects of EA on epilepsy to determine the specific acupoints and optimal stimulation parameters in this work. Experimental epilepsy was induced by injecting kainic acid to the lateral cerebral ventricle of adult male SD rats. EA with a low-frequency (10 Hz/1 mA) or high-frequency (100 Hz/1 mA) current was applied to the epileptic model for 30 minutes starting at 0.5 hour after the injection. Four pairs of acupoints were tested, that is, Shuigou (DU26) + Dazhui (DU14), Jinsuo (DU8) + Yaoqi (EXB9), Neiguan (PC6) + Quchi (LI11), and Fenglong (ST40) + Yongquan (KI1). We found that (1) low- or high-frequency EA at different acupoints reduced epileptic seizures (P < 0.05 versus the control) with an exception of low-frequency EA at Neiguan (PC6) and Quchi (LI11); (2) low-frequency EA induced a better effect at Fenglong (ST40) plus Yongquan (KI1) than that of the other acupoints (P < 0.05); (3) there is no significant difference in the effects of high-frequency EA at these acupoints; and (4) the high-frequency EA elicited a greater effect than that of low-frequency EA in all groups (P < 0.05), with an exception at Jinsuo (DU8) + Yaoqi (EXB9). The EA-induced attenuation appeared 1–1.5 hours after EA with no appreciable effect in the first hour after EA in either the EEG or the behavioral tests. We conclude that EA attenuation of epileptic seizures is dependent on the stimulation parameters and acupoints and that the delay in appearance of the EA effect could be a reflection of the time required by the EA signal to regulate neural function in the central nervous system. PMID:23589718

  20. Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background

    PubMed Central

    ROBSON, M G; COOK, H T; PUSEY, C D; WALPORT, M J; DAVIES, K A

    2003-01-01

    Antibody-mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q-deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv × C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed-strain 129/Sv × C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice. PMID:12930357

  1. Association of Retinoid X Receptor Alpha Gene Polymorphism with Clinical Course of Chronic Glomerulonephritis.

    PubMed

    Grzegorzewska, Alicja E; Ostromecki, Grzegorz; Zielińska, Paulina; Mostowska, Adrianna; Niemir, Zofia; Polcyn-Adamczak, Magdalena; Pawlik, Magdalena; Sowińska, Anna; Jagodziński, Paweł P

    2015-01-01

    BACKGROUND Vitamin D (VD), VD binding protein, VD receptor (VDR), and retinoids are involved in pathogenesis of chronic glomerulonephritis (ChGN). We aimed to compare distribution of VD pathway gene polymorphisms in ChGN patients showing glomerular filtration rate (GFR) category 1-3, GFR category 5D, and healthy controls in order to elucidate the role of VD-related polymorphisms in the course of ChGN. MATERIAL AND METHODS GFR category 1-3 ChGN patients (n=195), GFR category 5D ChGN patients (n=178), and controls (n=751) underwent testing for polymorphisms of genes encoding VD binding protein (GC, rs2298849, rs7041, rs1155563), VDR (VDR, rs2228570, rs1544410), and retinoid X receptor alpha (RXRA, rs10776909, rs10881578, rs749759). RESULTS Among GFR 1-3 subjects possessing TT genotype of RXRA rs10776909, 75% of patients had nephrotic syndrome, and 37.5% had glomerular hyperfiltration defined as GFR >140 ml/min/1.73 m2, and, consequently, serum creatinine was lower in these patients compared to the remaining subjects (0.67±0.26 vs. 0.94±0.34, P=0.014). In GFR category 5D ChGN patients, frequencies of RXRA rs10776909 allele T (25% vs. 19%) and CT+TT (46% vs. 34%) were higher compared to frequencies of respective variants in controls (Ptrend=0.004, Pgenotype=0.008). CONCLUSIONS RXRA rs10776909 allele T is specifically involved in the pathogenesis of ChGN. This risk allele may be also associated with worse clinical course of ChGN. PMID:26610845

  2. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    PubMed

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease. PMID:26971743

  3. A Case of Fibrillary Glomerulonephritis Associated with Thrombotic Microangiopathy and Anti-Glomerular Basement Membrane Antibody

    PubMed Central

    Momose, Akishi; Nakajima, Taku; Chiba, Shigetoshi; Kumakawa, Kenjirou; Shiraiwa, Yasuo; Sasaki, Nobuhiro; Watanabe, Kazuo; Kitano, Etsuko; Hatanaka, Mitiyo; Kitamura, Hajime

    2015-01-01

    We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction. Laboratory data revealed normocytic-normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia, increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative results for both direct and indirect Coombs tests. Based on these results, we diagnosed TMA. Assays conducted several days later indicated a disintegrin-like and metalloprotease with a thrombospondin motif 13 (ADAMTS13) activity of 31.6%, and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day, and mild convulsions developed. Based on magnetic resonance imaging of the head, the patient was diagnosed with reversible posterior leukoencephalopathy syndrome. Hypertension persisted despite administration of multiple antihypertensive agents, and the patient experienced a sudden generalized seizure. Computed tomography of the head showed multiple cerebral hemorrhages. However, his blood pressure subsequently decreased and the platelet count increased. TMA remitted following 36 plasma exchange sessions, but renal function was not restored, and maintenance hemodialysis was continued. The patient was discharged on the 119th day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM antibody were closely related. PMID:25873933

  4. Systematic experimental study on a highly efficient terahertz source based on two-color laser-induced air plasma

    NASA Astrophysics Data System (ADS)

    Xie, Jun; Fan, Wen-Hui; Chen, Xu

    2016-05-01

    In this paper, highly efficient terahertz radiation generated by two-color femtosecond laser-induced air plasma is reported. A number of variables that can obviously influence terahertz generation and detection have been investigated systematically. The dependence on experimental parameters, including pulse energy, the rotation angle of beta-barium boron oxide (BBO) crystal, the distance between BBO crystal and laser-induced plasma, focal length, chopper frequency, and detection angle are presented, and the optimal values of these parameters have also been obtained experimentally. Finally, a highly efficient terahertz source has been achieved and can be utilized to carry out further investigation on terahertz sensing, spectroscopy, and imaging.

  5. Experimental and predicted cavitation performance of an 80.6 deg helical inducer in high temperature water

    NASA Technical Reports Server (NTRS)

    Kovich, G.

    1972-01-01

    The cavitating performance of a stainless steel 80.6 degree flat-plate helical inducer was investigated in water over a range of liquid temperatures and flow coefficients. A semi-empirical prediction method was used to compare predicted values of required net positive suction head in water with experimental values obtained in water. Good agreement was obtained between predicted and experimental data in water. The required net positive suction head in water decreased with increasing temperature and increased with flow coefficient, similar to that observed for a like inducer in liquid hydrogen.

  6. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. PMID:24373522

  7. IgA-dominant acute poststreptococcal glomerulonephritis with concomitant rheumatic fever successfully treated with steroids: a case report

    PubMed Central

    Rus, Rina R; Toplak, Nataša; Vizjak, Alenka; Mraz, Jerica; Ferluga, Dušan

    2015-01-01

    There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases. PMID:26718763

  8. IgA-dominant acute poststreptococcal glomerulonephritis with concomitant rheumatic fever successfully treated with steroids: a case report.

    PubMed

    Rus, Rina R; Toplak, Nataša; Vizjak, Alenka; Mraz, Jerica; Ferluga, Dušan

    2015-12-01

    There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases. PMID:26718763

  9. Focal mesangial-sclerosing glomerulonephritis and acute-spontaneous infectious canine hepatitis: structural, immunohistochemical and subcellular studies.

    PubMed

    Hervás, J; Gómez-Villamandos, J C; Pérez, J; Carrasco, L; Sierra, M A

    1997-06-01

    The glomerular alterations observed in a dog with acute spontaneous infectious canine hepatitis (ICH) are described. Histologic changes of the glomeruli were enlargement of the mesangium with presence of intranuclear inclusion bodies and without proliferation of mesangial cells. Electron microscopy revealed adenovirus replication sites in glomerular mesangial cells and in endothelial cells of glomerular capillaries, as well as a focal mesangial-sclerosing glomerulonephritis associated with electron dense deposits which were closely related with extracellular ICH viral particles and immunohistochemically reactive for immunoglobulin (Ig) G, IgA, IgM and C3c complement components. PMID:9239835

  10. Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation

    PubMed Central

    2016-01-01

    Background Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. Methodology and Principal Findings The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Conclusion Taken together, these findings

  11. Mesangial proliferative glomerulonephritis with acute tubule interstitial nephritis leading to acute kidney injury in influenza A (H1N1) infection

    PubMed Central

    Kute, V. B.; Vanikar, A. V.; Shah, P. R.; Gumber, M. R.; Patel, H. V.; Trivedi, H. L.

    2014-01-01

    Respiratory complications and renal failure are the leading causes for morbidity and mortality due to influenza (H1N1) virus infection. There has been limited information on histopathology of H1N1 influenza-related acute kidney injury (AKI). We describe AKI with H1N1 infection in a 52-year-old female. Renal biopsy showed mesangial proliferative glomerulonephritis with acute tubule interstitial nephritis. Her condition improved rapidly with oseltamivir, fluid replacement, steroid and dialysis. Our case suggests that H1N1 infection may have a causative link to the development of mesangial proliferative glomerulonephritis with acute tubulointerstitial nephritis. PMID:24701045

  12. A new experimental model of acid- and endotoxin-induced acute lung injury in rats.

    PubMed

    Puig, F; Herrero, R; Guillamat-Prats, R; Gómez, M N; Tijero, J; Chimenti, L; Stelmakh, O; Blanch, L; Serrano-Mollar, A; Matthay, M A; Artigas, A

    2016-08-01

    The majority of the animal models of acute lung injury (ALI) are focused on the acute phase. This limits the studies of the mechanisms involved in later phases and the effects of long-term treatments. Thus the goal of this study was to develop an experimental ALI model of aspiration pneumonia, in which diffuse alveolar damage continues for 72 h. Rats were intratracheally instilled with one dose of HCl (0.1 mol/l) followed by another instillation of one dose of LPS (0, 10, 20, 30, or 40 μg/g body weight) 2 h later, which models aspiration of gastric contents that progresses to secondary lung injury from bacteria or bacterial products. The rats were euthanized at 24, 48, and 72 h after the last instillation. The results showed that HCl and LPS at all doses caused activation of inflammatory responses, increased protein permeability and apoptosis, and induced mild hypoxemia in rat lungs at 24 h postinstillation. However, this lung damage was present at 72 h only in rats receiving HCl and LPS at the doses of 30 and 40 μg/g body wt. Mortality (∼50%) occurred in the first 48 h and only in the rats treated with HCl and LPS at the highest dose (40 μg/g body wt). In conclusion, intratracheal instillation of HCl followed by LPS at the dose of 30 μg/g body wt results in severe diffuse alveolar damage that continues at least 72 h. This rat model of aspiration pneumonia-induced ALI will be useful for testing long-term effects of new therapeutic strategies in ALI. PMID:27317688

  13. Anti-Thymocyte Globulin Induces Neoangiogenesis and Preserves Cardiac Function after Experimental Myocardial Infarction

    PubMed Central

    Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

    2012-01-01

    Rationale Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Objective Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. Methods and Results AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. Conclusions These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI. PMID:23284885

  14. Electromagnetically induced absorption in detuned stub waveguides: a simple analytical and experimental model.

    PubMed

    Mouadili, A; Boudouti, E H El; Soltani, A; Talbi, A; Djafari-Rouhani, B; Akjouj, A; Haddadi, K

    2014-12-17

    We give an analytical and experimental demonstration of a classical analogue of the electromagnetic induced absorption (EIA) in a simple photonic device consisting of two stubs of lengths d1 and d2 grafted at the same site along a waveguide. By detuning the lengths of the two stubs (i.e. δ = d(2) - d(1)) we show that: (i) the amplitudes of the electromagnetic waves in the two stubs can be written following the two resonators model where each stub plays the role of a radiative resonator with low Q factor. The destructive interference between the waves in the two stubs may give rise to a sharp resonance peak with high Q factor in the transmission as well as in the absorption. (ii) The transmission coefficient around the resonance induced by the stubs can be written following a Fano-like form. In particular, we give an explicit expression of the position, width and Fano parameter of the resonances as a function of δ. (iii) By taking into account the loss in the waveguides, we show that at the transmission resonance, the transmission (reflection) increases (decreases) as a function of δ. Whereas the absorption goes through a maximum around 0.5 for a threshold value δth which depends on the attenuation in the system and then falls to zero. (iv) We give a comparison between the phase of the determinant of the scattering matrix, the so-called Friedel phase and the phase of the transmission amplitude. (v) The effect of the boundary conditions at the end of the resonators on the EIA resonance is also discussed. The analytical results are obtained by means of the Green's function method, whereas the experiments are carried out using coaxial cables in the radio-frequency regime. These results should have important consequences for designing integrated devices such as narrow-frequency optical or microwave filters and high-speed switches. PMID:25406973

  15. Intrinsic and induced regulation of the age-associated onset of spontaneous experimental autoimmune encephalomyelitis.

    PubMed

    Zhang, Hong; Podojil, Joseph R; Luo, Xunrong; Miller, Stephen D

    2008-10-01

    Multiple sclerosis is characterized by perivascular CNS infiltration of myelin-specific CD4(+) T cells and activated mononuclear cells. TCR transgenic mice on the SJL background specific for proteolipid protein (PLP)(139-151) develop a high incidence of spontaneous experimental autoimmune encephalomyelitis (sEAE). We examined the intrinsic mechanisms regulating onset and severity of sEAE. CD4(+) T cells isolated from the cervical lymph nodes, but not spleens, of diseased 5B6 transgenic mice are hyperactivated when compared with age-matched healthy mice and produce both IFN-gamma and IL-17, indicating that the cervical lymph node is the initial peripheral activation site. The age-associated development of sEAE correlates with a decline in both the functional capacity of natural regulatory T cells (nTregs) and in PLP(139-151)-induced IL-10 production and a concomitant increase in IL-17 production. Anti-CD25-induced inactivation of nTregs increased the incidence and severity of sEAE. Conversely, induction of peripheral tolerance via the i.v. injection of PLP(139-151)-pulsed, ethylcarbodiimide-fixed APCs (PLP(139-151)-SP) inhibited the development of clinical disease concomitant with increased production of IL-10 and conversion of Foxp3(+) Tregs from CD4(+)CD25(-) progenitors. These data indicate that heterogeneous populations of Tregs regulate onset of sEAE, and that induction of peripheral tolerance can be exploited to prevent/treat spontaneous autoimmune disease. PMID:18802066

  16. Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia

    PubMed Central

    Chou, Hsiu-Chu; Li, Yuan-Tsung; Chen, Chung-Ming

    2016-01-01

    Background: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. Methods: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on Gestational Days 20 and 21. Human MSCs (3×105 and 1×106 cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×105 cells), LPS+RA+MSC (1×106 cells), LPS+O2+NS, LPS+O2+MSC (3×105 cells), and LPS+O2+MSC (1×106 cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14. Results: Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin-6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively. Conclusion: Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression. PMID:27158330

  17. Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis.

    PubMed

    Balaji, C; Muthukumaran, J; Nalini, N

    2014-12-01

    Sinapic acid (SA) is a naturally occurring phenolic acid found in various herbal plants which is attributed with numerous pharmacological properties. This study was aimed to investigate the chemopreventive effect of SA on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Rats were treated with DMH injections (20 mg kg(-1) bodyweight (b.w.) subcutaneously once a week for the first 4 consecutive weeks and SA (20, 40 and 80 mg kg(-1) b.w.) post orally for 16 weeks. At the end of the 16-week experimental period, all the rats were killed, and the tissues were evaluated biochemically. Our results reveal that DMH alone treatment decreased the levels/activities of lipid peroxidation by-products such as thiobarbituric acid reactive substances, conjugated dienes and antioxidants such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione in the intestine and colonic tissues which were reversed on supplementation with SA. Moreover, the activities of drug-metabolizing enzymes of phase I (cytochrome P450 and P4502E1) were enhanced and those of phase II (glutathione-S-transferase, DT-diaphorase and uridine diphosphate glucuronosyl transferase) were diminished in the liver and colonic mucosa of DMH alone-treated rats and were reversed on supplementation with SA. All the above changes were supported by the histopathological observations of the rat liver and colon. These findings suggest that SA at the dose of 40 mg kg(-1) b.w. was the most effective dose against DMH-induced colon carcinogenesis, and thus, SA could be used as a potential chemopreventive agent. PMID:24532707

  18. Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction.

    PubMed

    Kucharekova, M; Schalkwijk, J; Van De Kerkhof, P C M; Van De Valk, P G M

    2002-06-01

    In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in

  19. Amelioration of Cisplatin-Induced Experimental Peripheral Neuropathy by a Small Molecule Targeting p75NTR

    PubMed Central

    Friesland, Amy; Weng, Zhiying; Duenas, Maria; Massa, Stephen M.; Longo, Frank M.; Lu, Qun

    2014-01-01

    Cisplatin is an effective and widely used first-line chemotherapeutic drug for treating cancers. However, many patients sustain cisplatin-induced peripheral neuropathy (CIPN), often leading to a reduction in drug dosages or complete cessation of treatment altogether. Therefore, it is important to understand cisplatin mechanisms in peripheral nerve tissue mediating its toxicity and identify signaling pathways for potential intervention. Rho GTPase activation is increased following trauma in several models of neuronal injury. Thus, we investigated whether components of the Rho signaling pathway represent important neuroprotective targets with the potential to ameliorate CIPN and thereby optimize current chemotherapy treatment regimens. We have developed a novel CIPN model in the mouse. Using this model and primary neuronal culture, we determined whether LM11A-31, a small-molecule, orally bioavailable ligand of the p75 neurotrophin receptor (p75NTR), can modulate Rho GTPase signaling and reduce CIPN. Von Frey filament analysis of sural nerve function showed that LM11A-31 treatment prevented decreases in peripheral nerve sensation seen with cisplatin treatment. Morphometric analysis of harvested sural nerves revealed that cisplatin-induced abnormal nerve fiber morphology and the decreases in fiber area were alleviated with concurrent LM11A-31 treatment. Cisplatin treatment increased RhoA activity accompanied by the reduced tyrosine phosphorylation of SHP-2, which was reversed by LM11A-31. LM11A-31 also countered the effects of calpeptin, which activated RhoA by inhibiting SHP-2 tyrosine phosphatase. Therefore, suppression of RhoA signaling by LM11A-31 that blocks proNGF binding to p75NTR or activates SHP-2 tyrosine phosphatase downstream of NGF receptor enhances neuroprotection in experimental CIPN in mouse model. PMID:25277379

  20. Tracking anti-fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: an insight.

    PubMed

    Shiha, Gamal E; Abu-Elsaad, Nashwa M; Zalata, Khaled R; Ibrahim, Tarek M

    2014-10-01

    The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have promising antifibrotic activity in experimental models of liver fibrosis. The aim of the present study was to investigate new pathways underlying this beneficial effect. Hepatic injury was induced in male Wistar rats by intraperitoneal injection of CCl4 for 12 weeks. During the last 8 weeks of treatment, rats were also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/kg nilotinib. At the end of treatment, effects on fibrosis were assessed by measuring serum fibrotic markers and profibrogenic cytokines, as well as by histopathological examination. Possible anti-inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of α-smooth muscle actin, transforming growth factor (TGF)-β1 antibodies and platelet-derived growth factor receptor β (PDGFRβ) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly (P < 0.05) decreased all serum fibrotic markers measured, but 20 mg/kg of either nilotinib or imatinib had limited effects. At all doses tested, nilotinib significantly (P < 0.05) decreased the CCl4 -induced increases in tissue inflammatory cytokines. Furthermore, 5 and 10 mg/kg nilotinib significantly decreased TGF-β1 levels and tissue expression of its antibody, as well expression of PDGFRβ. In conclusion, low doses (5 and 10 but not 20 mg/kg) of nilotinib, rather than imatinib, can control hepatic fibrosis by regulating levels of proinflammatory cytokines, primarily interleukin (IL)-1 and IL-6. Nilotinib also controls the signalling pathways of profibrogenic cytokines by lowering TGF-β1 levels and decreasing expression of PDGFRβ. PMID:25115651

  1. Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

    PubMed Central

    Son, Dong Ju; Lee, Gyung Rak; Oh, Sungil; Lee, Sung Eun; Choi, Won Sik

    2015-01-01

    This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy)-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy)-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone’s phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives—5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin—were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP) enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes. PMID:25781220

  2. Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups.

    PubMed

    Bailey, Zachary S; Hubbard, W Brad; VandeVord, Pamela J

    2016-01-01

    Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma. PMID:27604716

  3. System dynamic instabilities induced by sliding contact: A numerical analysis with experimental validation

    NASA Astrophysics Data System (ADS)

    Brunetti, J.; Massi, F.; Saulot, A.; Renouf, M.; D`Ambrogio, W.

    2015-06-01

    Mechanical systems present several contact surfaces between deformable bodies. The contact interface can be either static (joints) or in sliding (active interfaces). The sliding interfaces can have several roles and according to their application they can be developed either for maximizing the friction coefficient and the energy dissipation (e.g. brakes) or rather to allow the relative displacement at joints with a maximum efficiency. In both cases the coupling between system and local contact dynamics can bring to system dynamics instabilities (e.g. brake squeal or squeaking of hip prostheses). This results in unstable vibrations of the system, induced by the oscillation of the contact forces. In the literature, a large number of works deal with such kind of instabilities and are mainly focused on applied problems such as brake squeal noise. This paper shows a more general numerical analysis of a simple system constituted by two bodies in sliding contact: a rigid cylinder rotating inside a deformable one. The parametrical Complex Eigenvalue Analysis and the transient numerical simulations show how the friction forces can give rise to in-plane dynamic instabilities due to the interaction between two system modes, even for such a simple system characterized by one deformable body. Results from transient simulations highlight the key role of realistic values of the material damping to have convergence of the model and, consequently, reliable physical results. To this aim an experimental estimation of the material damping has been carried out. Moreover, the simplicity of the system allows for a deeper analysis of the contact instability and a balance of the energy flux among friction, system vibrations and damping. The numerical results have been validated by comparison with experimental ones, obtained by a specific test bench developed to reproduce and analyze the contact friction instabilities.

  4. Parameters Optimization of Laser-Induced Breakdown Spectroscopy Experimental Setup for the Case with Beam Expander

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Zhang, Lei; Fan, Juanjuan; Li, Yufang; Gong, Yao; Dong, Lei; Ma, Weiguang; Yin, Wangbao; Jia, Suotang

    2015-11-01

    Improvement of measurement precision and repeatability is one of the issues currently faced by the laser-induced breakdown spectroscopy (LIBS) technique, which is expected to be capable of precise and accurate quantitative analysis. It was found that there was great potential to improve the signal quality and repeatability by reducing the laser beam divergence angle using a suitable beam expander (BE). In the present work, the influences of several experimental parameters for the case with BE are studied in order to optimize the analytical performances: the signal to noise ratio (SNR) and the relative standard deviation (RSD). We demonstrate that by selecting the optimal experimental parameters, the BE-included LIBS setup can give higher SNR and lower RSD values of the line intensity normalized by the whole spectrum area. For validation purposes, support vector machine (SVM) regression combined with principal component analysis (PCA) was used to establish a calibration model to realize the quantitative analysis of the ash content. Good agreement has been found between the laboratory measurement results from the LIBS method and those from the traditional method. The measurement accuracy presented here for ash content analysis is estimated to be 0.31%, while the average relative error is 2.36%. supported by the 973 Program of China (No. 2012CB921603), National Natural Science Foundation of China (Nos. 61475093, 61127017, 61178009, 61108030, 61378047, 61275213, 61475093, and 61205216), the National Key Technology R&D Program of China (No. 2013BAC14B01), the Shanxi Natural Science Foundation (Nos. 2013021004-1 and 2012021022-1), the Shanxi Scholarship Council of China (Nos. 2013-011 and 2013-01), and the Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi, China

  5. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    PubMed Central

    Mohan, Surapaneni Krishna; Veeraraghavan, Vishnu Priya; Jainu, Mallika

    2015-01-01

    Objective(s): Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. Materials and Methods: The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. Results: The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid. PMID:26557974

  6. Experimental study on impact-induced seismic wave propagating through quartz sand simulating asteroid regolith

    NASA Astrophysics Data System (ADS)

    Matsue, Kazuma; Arakawa, Masahiko; Yasui, Minami; Matsumoto, Rie; Tsujido, Sayaka; Takano, Shota; Hasegawa, Sunao

    2015-08-01

    Introduction: Recent spacecraft surveys clarified that asteroid surfaces were covered with regolith made of boulders and pebbles such as that found on the asteroid Itokawa. It was also found that surface morphologies of asteroids formed on the regolith layer were modified. For example, the high-resolution images of the asteroid Eros revealed the evidence of the downslope movement of the regolith layer, then it could cause the degradation and the erasure of small impact crater. One possible process to explain these observations is the regolith layer collapse caused by seismic vibration after projectile impacts. The impact-induced seismic wave might be an important physical process affecting the morphology change of regolith layer on asteroid surfaces. Therefore, it is significant for us to know the relationship between the impact energy and the impact-induced seismic wave. So in this study, we carried out impact cratering experiments in order to observe the seismic wave propagating through the target far from the impact crater.Experimental method: Impact cratering experiments were conducted by using a single stage vertical gas gun set at Kobe Univ and a two-stage vertical gas gun set at ISAS. We used quartz sands with the particle diameter of 500μm, and the bulk density of 1.48g/cm3. The projectile was a ball made of polycarbonate with the diameter of 4.75mm and aluminum, titan, zirconia, stainless steel, cupper, tungsten carbide projectile with the diameter of 2mm. These projectiles were launched at the impact velocity from 0.2 to 7km/s. The target was set in a vacuum chamber evacuated below 10 Pa. We measured the seismic wave by using a piezoelectric uniaxial accelerometer.Result: The impact-induced seismic wave was measured to show a large single peak and found to attenuate with the propagation distance. The maximum acceleration of the seismic wave was recognized to have a good relationship with the normalized distance x/R, where x is the propagation distance

  7. Investigation of the indulgence cycles hypothesis of suppression on experimentally induced visual intrusions in dysphoria.

    PubMed

    Williams, Alishia D; Moulds, Michelle L

    2007-11-01

    Within the thought control literature, Wegner [(1989). White bears and other unwanted thoughts: Suppression, obsession, and the psychology of mental control. New York, NY, USA: Penguin Press.] referred to the combined initial suppression and expression phases of thought control as an indulgence cycle which results in the rebound effect typically observed in suppression studies. According to Ironic Process Theory [Wegner, (1994). Ironic processes of mental control. Psychological Review, 101, 34-52.], this rebound leads to further attempts to suppress that are difficult due to the target thought's hyperaccessibility, resulting in a secondary rebound effect owing to a positive feedback system of indulgence cycles. The current study investigated (i) the effects of repeated suppression and opportunities for expression by using a method to index the frequency, duration, and associated levels of distress of an experimentally induced visual intrusion, and (ii) whether any observed effects were differentially linked to depressive symptomatology in an analogue sample of low and high dysphoric participants. Results supported a secondary rebound effect in those participants most successful at suppressing target intrusions. The findings offer an important extension to the emerging literature on the management of intrusive memories in depression. PMID:17692285

  8. Experimental study on the onset of cavitation induced by an impact

    NASA Astrophysics Data System (ADS)

    Kiyama, Akihito; Kurihara, Chihiro; Tagawa, Yoshiyuki

    2015-11-01

    We study reasonable expression for predicting the onset of cavitation induced by an impact experimentally. A liquid-filled test tube is dropped and impacts a floor, followed by the emergence of cavitation bubbles inside a liquid. As floor materials, a metal and a resin are chosen. As a wetting liquid, gas-saturated silicone oil was used. Experiments are conducted at room temperature. The condition for cavitation occurrence for a resin floor cannot be described by the typical velocity measured by high-speed imaging, temporal resolution and spatial resolution of which are respectively O(10) μs and O(100) μm. We investigate sudden acceleration at the impact using an accelerometer. Its temporal resolution is O(1) ns, much smaller than that of high-speed imaging. The time history of acceleration for the resin floor is more moderate and peak acceleration is smaller than that for the metal floor. Based on these findings, we discuss the reasonable description of the criterion for the onset of cavitation bubbles, applicable for various floors. JSPS KAKENHI Grant Number 26709007.

  9. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU)

    PubMed Central

    Zhao, Ronglan; Liang, Dongchun; Sun, Deming

    2016-01-01

    Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP) functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU). Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs), T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases. PMID:27196432

  10. Illusions and Delusions: Relating Experimentally-Induced False Memories to Anomalous Experiences and Ideas

    PubMed Central

    Corlett, Philip R.; Simons, Jon S.; Pigott, Jennifer S.; Gardner, Jennifer M.; Murray, Graham K.; Krystal, John H.; Fletcher, Paul C.

    2009-01-01

    The salience hypothesis of psychosis rests on a simple but profound observation that subtle alterations in the way that we perceive and experience stimuli have important consequences for how important these stimuli become for us, how much they draw our attention, how they embed themselves in our memory and, ultimately, how they shape our beliefs. We put forward the idea that a classical memory illusion – the Deese–Roediger–McDermott (DRM) effect – offers a useful way of exploring processes related to such aberrant belief formation. The illusion occurs when, as a consequence of its relationship to previous stimuli, a stimulus that has not previously been presented is falsely remembered. Such illusory familiarity is thought to be generated by the surprising fluency with which the stimulus is processed. In this respect, the illusion relates directly to the salience hypothesis and may share common cognitive underpinnings with aberrations of perception and attribution that are found in psychosis. In this paper, we explore the theoretical importance of this experimentally-induced illusion in relation to the salience model of psychosis. We present data showing that, in healthy volunteers, the illusion relates directly to self reported anomalies of experience and magical thinking. We discuss this finding in terms of the salience hypothesis and of a broader Bayesian framework of perception and cognition which emphasizes the salience both of predictable and unpredictable experiences. PMID:19956402

  11. Numerical and experimental study of the thermal stress of silicon induced by a millisecond laser

    SciTech Connect

    Wang Xi; Qin Yuan; Wang Bin; Zhang Liang; Shen Zhonghua; Lu Jian; Ni Xiaowu

    2011-07-20

    A spatial axisymmetric finite element model of single-crystal silicon irradiated by a 1064 nm millisecond laser is used to investigate the thermal stress damage induced by a millisecond laser. The transient temperature field and the thermal stress field for 2 ms laser irradiation with a laser fluence of 254 J/cm{sup 2} are obtained. The numerical simulation results indicate that the hoop stresses along the r axis on the front surface are compressive stress within the laser spot and convert to tensile stress outside the laser spot, while the radial stresses along the r axis on the front surface and on the z axis are compressive stress. The temperature of the irradiated center is the highest temperature obtained, yet the stress is not always highest during laser irradiation. At the end of the laser irradiation, the maximal hoop stress is located at r=0.5 mm and the maximal radial stress is located at r=0.76 mm. The temperature measurement experiments are performed by IR pyrometer. The numerical result of the temperature field is consistent with the experimental result. The damage morphologies of silicon under the action of a 254 J/cm{sup 2} laser are inspected by optical microscope. The cracks are observed initiating at r=0.5 mm and extending along the radial direction.

  12. A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

    PubMed Central

    Saha, Indraneel; Das, Joydeep; Maiti, Biswaranjan

    2015-01-01

    Objectives. Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Methods. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Results. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level. Conclusion. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes. PMID:25695047

  13. Mitigation of DMBA-induced mammary carcinoma in experimental rats by antiangiogenic property of Kalpaamruthaa.

    PubMed

    Sathish, Sivaprakasam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2011-06-01

    Extra cellular matrix (ECM) and basement membrane (BM) are important layers that regulate cell structure, cell migration, and cellular proliferation. Degradation of both ECM and BM mediated by proteases favors the tumor invasion and promotes angiogenesis. Female Sprague-Dawley rats weighing 180 ± 10 g were categorized into 6 groups. Group-1 animals served as vehicle control. Group-2 to Group-4 animals were administered with 7,12-dimethylbenz(a)anthracene (25 mg/rat dissolved in olive oil, orally) on day 1 of experimental period to induce mammary carcinoma. (After 90 days, mammary carcinoma was confirmed by histopathological examination). Group-3 and Group-4 rats were subsequently treated with Semecarpus anacardium nut milk extract (SA) and Kalpaamruthaa (KA), respectively. Group-5 and Group-6 animals served as drug control for SA and KA, respectively. Pro-angiogenic factors like proteases, cyclooxygenase-2, and vascular endothelial growth factor were elevated in tumor-bearing animals and decreased in SA- and KA-supplemented rats. Increased levels of these angiogenic factors in tumor-bearing rats indicate the progression of mammary tumor. The decreased levels of these angiogenic in SA- and KA-treated rats may be due to the ameliorative effect of phenolic compounds such as flavonoids, tannins, and other compounds present in the drug. PMID:22432686

  14. Use of laparoscopy for diagnosing experimentally induced acute pancreatitis in dogs

    PubMed Central

    Kim, Hyun-wook; Oh, Ye-in; Choi, Ji-hye; Kim, Dae-yong

    2014-01-01

    Diagnosis of acute pancreatitis in dogs remains a significant challenge despite the development of advanced diagnostic methodologies. Visual inspection and pancreas biopsy using laparoscopy are generally considered to be procedures free of complications when conducted on healthy animals. However, the usefulness of laparoscopy for diagnosing acute pancreatitis has not been assessed. In the present study, the efficacy of laparoscopy for diagnosing acute pancreatitis in dogs was evaluated in animals with experimentally induced acute pancreatitis. Gross appearance of the pancreatic area was examined by laparoscopy to survey for the presence of edema, adhesions, effusion, pseudocysts, hemorrhage, and fat necrosis. Laparoscopic biopsy was performed and the histopathologic results were compared to those of pancreatic samples obtained during necropsy. The correlation between laparoscopy and histopathologic findings of the pancreas was evaluated. The presence of adhesions, effusion, and hemorrhage in the pancreatic area observed by laparoscopy significantly correlated with the histopathologic results (p < 0.05). There was no significant relationship between the histopathologic and laparoscopic biopsy findings. Results of this study suggested that laparoscopic evaluation of gross lesions has clinical significance although the laparoscopic biopsy technique has some limitations. This method combined with additional diagnostic tools can be effective for diagnosing acute pancreatitis in dogs. PMID:24962411

  15. Experimental investigation of ultraviolet laser induced plasma density and temperature evolution in air

    SciTech Connect

    Thiyagarajan, Magesh; Scharer, John

    2008-07-01

    We present measurements and analysis of laser induced plasma neutral densities and temperatures in dry air by focusing 200 mJ, 10 MW high power, 193 nm ultraviolet ArF (argon fluoride) laser radiation to a 30 {mu}m radius spot size. We examine these properties that result from multiphoton and collisional cascade processes for pressures ranging from 40 Torr to 5 atm. A laser shadowgraphy diagnostic technique is used to obtain the plasma electron temperature just after the shock front and this is compared with optical emission spectroscopic measurements of nitrogen rotational and vibrational temperatures. Two-color laser interferometry is employed to measure time resolved spatial electron and neutral density decay in initial local thermodynamic equilibrium (LTE) and non-LTE conditions. The radiating species and thermodynamic characteristics of the plasma are analyzed by means of optical emission spectroscopy (OES) supported by SPECAIR, a special OES program for air constituent plasmas. Core plasma rotational and vibrational temperatures are obtained from the emission spectra from the N{sub 2}C-B(2+) transitions by matching the experimental spectrum results with the SPECAIR simulation results and the results are compared with the electron temperature just behind the shock wave. The plasma density decay measurements are compared with a simplified electron density decay model that illustrates the dominant three-and two-body recombination terms with good correlation.

  16. Experimental investigation of ultraviolet laser induced plasma density and temperature evolution in air

    NASA Astrophysics Data System (ADS)

    Thiyagarajan, Magesh; Scharer, John

    2008-07-01

    We present measurements and analysis of laser induced plasma neutral densities and temperatures in dry air by focusing 200 mJ, 10 MW high power, 193 nm ultraviolet ArF (argon fluoride) laser radiation to a 30 μm radius spot size. We examine these properties that result from multiphoton and collisional cascade processes for pressures ranging from 40 Torr to 5 atm. A laser shadowgraphy diagnostic technique is used to obtain the plasma electron temperature just after the shock front and this is compared with optical emission spectroscopic measurements of nitrogen rotational and vibrational temperatures. Two-color laser interferometry is employed to measure time resolved spatial electron and neutral density decay in initial local thermodynamic equilibrium (LTE) and non-LTE conditions. The radiating species and thermodynamic characteristics of the plasma are analyzed by means of optical emission spectroscopy (OES) supported by SPECAIR, a special OES program for air constituent plasmas. Core plasma rotational and vibrational temperatures are obtained from the emission spectra from the N2C-B(2+) transitions by matching the experimental spectrum results with the SPECAIR simulation results and the results are compared with the electron temperature just behind the shock wave. The plasma density decay measurements are compared with a simplified electron density decay model that illustrates the dominant three-and two-body recombination terms with good correlation.

  17. Induced Cannibalism in Experimental Populations of the Forensic Indicator Chrysomya putoria Wiedemann (Diptera: Calliphoridae).

    PubMed

    Botteon, V W; Fernandes, F S; Godoy, W A C

    2016-04-01

    We analyzed the behavior of third-instars of Chrysomya putoria as potential cannibals in experimental populations. Cannibalism rates were evaluated in three settings observed for 3, 6, 9, and 24 h, placing injured and uninjured larvae of C. putoria together. Our data heavily support that C. putoria larvae behave as cannibals when induced by a wound in another larva, and also after starving for 24 h. The probability of cannibalism increased as a function of time, both in no-choice and in choice experiments evidencing that time is a determining factor for cannibalism induction in C. putoria. However, the treatment combining injured with uninjured larvae showed the highest probability of cannibalism. These results suggest that C. putoria larvae may cannibalize under scarcity of food over long time or the presence of injured larvae. This study is useful to understand the behavior of C. putoria feeding on ephemeral substrates such as carrion or corpses and brings relevant and significant contribution to population ecology of blowflies and also forensic entomology. PMID:26698866

  18. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    NASA Astrophysics Data System (ADS)

    Kavanagh, J. N.; Currell, F. J.; Timson, D. J.; Holzscheiter, M. H.; Bassler, N.; Herrmann, R.; Prise, K. M.; Schettino, G.

    2010-10-01

    Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offer a further enhancement due to their annihilation at the end of the path. The work presented here aimed to establish and validate an experimental procedure for the quantification of plasmid and genomic DNA damage resulting from antiproton exposure. Immunocytochemistry was used to assess DNA damage in directly and indirectly exposed human fibroblasts irradiated in both plateau and Bragg peak regions of a 126 MeV antiproton beam at CERN. Cells were stained post irradiation with an anti- γ-H2AX antibody. Quantification of the γ-H2AX foci-dose relationship is consistent with a linear increase in the Bragg peak region. A qualitative analysis of the foci detected in the Bragg peak and plateau region indicates significant differences highlighting the different severity of DNA lesions produced along the particle path. Irradiation of desalted plasmid DNA with 5 Gy antiprotons at the Bragg peak resulted in a significant portion of linear plasmid in the resultant solution.

  19. Experimental evidence for drought induced alternative stable states of soil moisture

    PubMed Central

    Robinson, David. A.; Jones, Scott B.; Lebron, Inma; Reinsch, Sabine; Domínguez, María T.; Smith, Andrew R.; Jones, Davey L.; Marshall, Miles R.; Emmett, Bridget A.

    2016-01-01

    Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction. PMID:26804897

  20. Modeling and simulation of organophosphate-induced neurotoxicity: Prediction and validation by experimental studies.

    PubMed

    Greget, Renaud; Dadak, Selma; Barbier, Laure; Lauga, Fabien; Linossier-Pierre, Sandra; Pernot, Fabien; Legendre, Arnaud; Ambert, Nicolas; Bouteiller, Jean-Marie; Dorandeu, Frédéric; Bischoff, Serge; Baudry, Michel; Fagni, Laurent; Moussaoui, Saliha

    2016-05-01

    Exposure to organophosphorus (OP) compounds, either pesticides or chemical warfare agents, represents a major health problem. As potent irreversible inhibitors of cholinesterase, OP may induce seizures, as in status epilepticus, and occasionally brain lesions. Although these compounds are extremely toxic agents, the search for novel antidotes remains extremely limited. In silico modeling constitutes a useful tool to identify pharmacological targets and to develop efficient therapeutic strategies. In the present work, we developed a new in silico simulator in order to predict the neurotoxicity of irreversible inhibitors of acetyl- and/or butyrylcholinesterase (ChE) as well as the potential neuroprotection provided by antagonists of cholinergic muscarinic and glutamate N-methyl-d-aspartate (NMDA) receptors. The simulator reproduced firing of CA1 hippocampal neurons triggered by exposure to paraoxon (POX), as found in patch-clamp recordings in in vitro mouse hippocampal slices. In the case of POX intoxication, it predicted a preventing action of the muscarinic receptor antagonist atropine sulfate, as well as a synergistic action with the non-competitive NMDA receptor antagonist memantine. These in silico predictions relative to beneficial effects of atropine sulfate combined with memantine were recapitulated experimentally in an in vivo model of POX in adult male Swiss mice using electroencephalic (EEG) recordings. Thus, our simulator is a new powerful tool to identify protective therapeutic strategies against OP central effects, by screening various combinations of muscarinic and NMDA receptor antagonists. PMID:27108687

  1. Experimental characterization of fire-induced response of rigid polyurethane foam

    SciTech Connect

    Chu, T.Y.; Gill, W.; Moore, J.W.; Hobbs, M.L.; Gritzo, L.A.; Moya, J.L.

    1995-12-31

    Reported is the result of an experimental investigation of fire-induced response of a 96 kg/m{sup 3} closed cell rigid polyurethane foam. The specimen is 0.37 m in diameter, and 152 mm thick, placed in a cylindrical test vessel. The fire condition is simulated by heating the bottom of the test vessel to 1283 K using a radiant heat source. Real-time x-ray shows that the degradation process involves the progression of a charring front into the virgin material. The charred region has a regular and graded structure consisting of a packed bubble outer layer and successive layers of thin shells. The layer-to-layer permeability appears to be poor. There are indications that gas vents laterally. The shell-like structure might be the result of lateral venting. Although the foam degradation process is quite complicated, the in-depth temperature responses in the uncharted foam appear to be consistent with steady state ablation. The measured temperature responses are well represented by the exponential distribution for steady state ablation. An estimate of the thermal diffusivity of the foam is obtained from the ablation model. The experiment is part of a more comprehensive program to develop material response models of foams and encapsulants.

  2. Experimental evidence for drought induced alternative stable states of soil moisture.

    PubMed

    Robinson, David A; Jones, Scott B; Lebron, Inma; Reinsch, Sabine; Domínguez, María T; Smith, Andrew R; Jones, Davey L; Marshall, Miles R; Emmett, Bridget A

    2016-01-01

    Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction. PMID:26804897

  3. Experimental evidence for drought induced alternative stable states of soil moisture

    NASA Astrophysics Data System (ADS)

    Robinson, David. A.; Jones, Scott B.; Lebron, Inma; Reinsch, Sabine; Domínguez, María T.; Smith, Andrew R.; Jones, Davey L.; Marshall, Miles R.; Emmett, Bridget A.

    2016-01-01

    Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction.

  4. Hazard of CO₂ laser-induced airway fire in laryngeal surgery: experimental data of contributing factors.

    PubMed

    Stuermer, Konrad Johannes; Ayachi, Stefan; Gostian, Antoniu-O; Beutner, Dirk; Hüttenbrink, Karl-Bernd

    2013-09-01

    In carbon dioxide (CO2) laser surgery of the larynx, the potentially dangerous combination of laser-induced heat in an oxygen-enriched atmosphere typically occurs when jet ventilation is used or due to an insufficiently blocked endotracheal tube. Until now, no limitations for safe oxygen concentrations or laser intervals have been established. The aim of this study was to investigate and quantify the factors that may contribute to an airway fire in laryngeal laser surgery. Fat, muscle and cartilage were irradiated with a CO2 laser at 2, 4, 6 and 8 W in five different oxygen concentrations with and without smoke exhaustion. The time to ignition was recorded for each different experimental setup. Fat burnt fastest, followed by cartilage and muscle. The elevation of laser energy or oxygen concentration reduced the time to inflammation of any tissue. The elevation of oxygen by 10 % increases the risk of inflammation more than the elevation of laser power by 2 W. Under smoke exhaustion, inflammation and burning occurred delayed or were even inhibited at lower oxygen concentrations. Lasing in more than 50 % oxygen is comparatively dangerous and can cause airway fire in less than 5 s, especially when laser energies of more than 5 W are applied. In equal or lower than 50 % oxygen, an irradiation interval of 5 s can be considered a comparatively safe time limit to prevent inflammation in laryngeal laser surgery. Smoke exhaustion should always be applied. PMID:23636479

  5. An Experimental Study of Roughness-Induced Instabilities in a Supersonic Boundary Layer

    NASA Technical Reports Server (NTRS)

    Kegerise, Michael A.; King, Rudolph A.; Choudhari, Meelan; Li, Fei; Norris, Andrew

    2014-01-01

    Progress on an experimental study of laminar-to-turbulent transition induced by an isolated roughness element in a supersonic laminar boundary layer is reported in this paper. Here, the primary focus is on the effects of roughness planform shape on the instability and transition characteristics. Four different roughness planform shapes were considered (a diamond, a circle, a right triangle, and a 45 degree fence) and the height and width of each one was held fixed so that a consistent frontal area was presented to the oncoming boundary layer. The nominal roughness Reynolds number was 462 and the ratio of the roughness height to the boundary layer thickness was 0.48. Detailed flow- field surveys in the wake of each geometry were performed via hot-wire anemometry. High- and low-speed streaks were observed in the wake of each roughness geometry, and the modified mean flow associated with these streak structures was found to support a single dominant convective instability mode. For the symmetric planform shapes - the diamond and circular planforms - the instability characteristics (mode shapes, growth rates, and frequencies) were found to be similar. For the asymmetric planform shapes - the right-triangle and 45 degree fence planforms - the mode shapes were asymmetrically distributed about the roughness-wake centerline. The instability growth rates for the asymmetric planforms were lower than those for the symmetric planforms and therefore, transition onset was delayed relative to the symmetric planforms.

  6. Experimental investigation on vortex-induced vibration of steel catenary riser

    NASA Astrophysics Data System (ADS)

    Fan, Yu-ting; Mao, Hai-ying; Guo, Hai-yan; Liu, Qing-hai; Li, Xiao-min

    2015-10-01

    Steel catenary riser (SCR) is the transmission device between the seabed and the floating production facilities. As developments move into deeper water, the fatigue life of the riser can become critical to the whole production system, especially due to the vortex-induced vibration (VIV), which is the key factor to operational longevity. As a result, experimental investigation about VIV of the riser was performed in a large plane pool which is 60 m long, 36 m wide and 6.5 m deep. Experiments were developed to study the influence of current speed and seabed on VIV of SCR. The results show that amplitudes of strain and response frequencies increase with the current speed both in cross-flow (CF) and in-line (IL). When the current speed is high, multi-mode response is observed in the VIV motion. The amplitudes of strain in IL direction are not much smaller than those in CF direction. The seabed has influence on the response frequencies of riser and the positions of damage for riser.

  7. Experimental Study of Overtopping Induced Landslide Dam Break Flow and Two Layer Two Phase Mixture Model

    NASA Astrophysics Data System (ADS)

    Liu, L.; Duan, J. G.; Zhong, D.; Zhang, H.

    2013-12-01

    A series of experiments were conducted to investigate flood flow generated by the failure of landslide dams due to overtopping. These experiments aim to quantify the influences of inflow discharge, downstream slope, width of dam crest, dam height, and dam material on the flood flow. Images from high-speed cameras are used to determine the profiles of dam body and flow discharge during the failure processes. Results showed that the water level in the upstream reservoir and the erosion of dam body are the dominant factors affecting the downstream flood flow. A physical-based model is established to calculate the arriving time and the peak discharge of dam break flow using two phase mixture model. Both analytical and numerical solutions were derived for the model. The modelling results were verified using data from this and several other laboratory experimental datasets. The agreement between the calculated and measured data showed the applicability of the proposed model for predicting the peak discharge of overtopping induced dam break flow.

  8. Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance.

    PubMed

    Piaggio, Eliane; Mars, Lennart T; Cassan, Cécile; Cabarrocas, Julie; Hofstätter, Maria; Desbois, Sabine; Bergereau, Emilie; Rötzschke, Olaf; Falk, Kirsten; Liblau, Roland S

    2007-05-29

    Immunotherapy by using multimerized self-peptides has demonstrated a clear protective effect on experimental models of autoimmune diseases. However, the mechanisms involved remain ill-defined. Here we have evaluated the therapeutic efficacy of multimerized self-peptides at the effector phase of autoimmune diabetes and examined their mechanisms of action. Diabetes was induced in rat insulin promoter-hemagglutinin (HA) mice expressing HA in pancreatic beta-cells by adoptive transfer of HA(110-119)-specific T helper 1 cells. Complete protection was provided by low doses of the HA 4-mer consisting of four covalently linked linear HA(107-119) peptides. In vivo, the 4-mer appeared to act directly on the pathogenic HA-specific T helper 1 cells and indirectly by activation/recruitment of lymphocytes with regulatory properties so that mice became resistant to a second transfer of diabetogenic T cells. This effect was associated with a recruitment of Foxp3(+) CD4 T cells around islets. Moreover, we show that dominant protection from autoimmunity was transferable by spleen cells, and that development of this regulatory population was crucially dependent on the lymphocytes from treated rat insulin promoter-HA mice. Thus, immunotherapy using multimerized epitopes emerges as a promising strategy in view of the current identification of self-epitopes that are major targets of the pathogenic CD4 T cell response in autoimmune diseases. PMID:17517665

  9. Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance

    PubMed Central

    Piaggio, Eliane; Mars, Lennart T.; Cassan, Cécile; Cabarrocas, Julie; Hofstätter, Maria; Desbois, Sabine; Bergereau, Emilie; Rötzschke, Olaf; Falk, Kirsten; Liblau, Roland S.

    2007-01-01

    Immunotherapy by using multimerized self-peptides has demonstrated a clear protective effect on experimental models of autoimmune diseases. However, the mechanisms involved remain ill-defined. Here we have evaluated the therapeutic efficacy of multimerized self-peptides at the effector phase of autoimmune diabetes and examined their mechanisms of action. Diabetes was induced in rat insulin promoter-hemagglutinin (HA) mice expressing HA in pancreatic β-cells by adoptive transfer of HA110–119-specific T helper 1 cells. Complete protection was provided by low doses of the HA 4-mer consisting of four covalently linked linear HA107–119 peptides. In vivo, the 4-mer appeared to act directly on the pathogenic HA-specific T helper 1 cells and indirectly by activation/recruitment of lymphocytes with regulatory properties so that mice became resistant to a second transfer of diabetogenic T cells. This effect was associated with a recruitment of Foxp3+ CD4 T cells around islets. Moreover, we show that dominant protection from autoimmunity was transferable by spleen cells, and that development of this regulatory population was crucially dependent on the lymphocytes from treated rat insulin promoter-HA mice. Thus, immunotherapy using multimerized epitopes emerges as a promising strategy in view of the current identification of self-epitopes that are major targets of the pathogenic CD4 T cell response in autoimmune diseases. PMID:17517665

  10. [A study of epidermal alterations induced by PCDF on experimental carcinogenesis].

    PubMed

    Hirose, R; Hori, M; Toyoshima, H; Shukuwa, T; Udono, M; Yoshida, H

    1991-05-01

    An effect of 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as a promoter on a course of experimental skin carcinogenesis in mice by chemicals 20-methylcholanthrene (MC) has been proved by our previous studies. Details of ultrastructural epidermal alterations induced by MC and PCDF were observed and an attempt to differentiate benign tumor from malignant one in which a combined application of MC and PCDF on mice skin resulted was done electron microscopically. Four significant findings as follows were detected. First of all even the epidermal cells without tumor had some atypicality. Secondly both of benign tumor and normal-appeared skin without tumor had giant and round-shaped keratohyalin granules (KHGs) which show a tendency of less keratinization. Thirdly cytoplasmic projections of epidermal cells increased in number and sparse tonofilaments scattered in the cytoplasm of benign tumor. This is also an appearance of mucous metaplasia of keratinocytes as well as the form of KHGs mentioned above. Finally benign tumor had thick horny cells including numerous lipid droplets, and that is a sign of acceleration of epidermal turn over. Since epidermal cells have little chance to be exposed to carcinogens when they quickly keratinize, they rarely form a cancer. When epidermal cells have such tendency as less keratinization or more keratinization, they are supposed to be less sensitive to any stimuli of carcinogens, and consequently they incline to be benign tumor instead of malignant one. PMID:1916594

  11. Protective effects of D-002 on experimentally induced gastroesophageal reflux in rats

    PubMed Central

    Zamora, Zullyt; Molina, Vivian; Mas, Rosa; Ravelo, Yazmin; Perez, Yohany; Oyarzabal, Ambar

    2014-01-01

    AIM: To investigate the effects of beeswax alcohols (D-002) on the esophageal damage induced by gastroesophageal reflux (GER) in rats. METHODS: Sixty male rats were randomized into six groups (10 rats/group): a negative control and five groups with experimentally induced GER: a positive vehicle control, three treated with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10 mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER was produced by simultaneous ligation of the pyloric end and the forestomach. Esophageal lesions index (ELI), gastric secretion volume and acidity, and esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were measured. Statistical significance was considered at P < 0.05. RESULTS: As compared to the negative control, the positive control group exhibited increased ELI (5.2 ± 0.33 vs 0 ± 0, P = 0.0003), gastric secretion volume (2.69 ± 0.09 vs 0.1 ± 0.0, P = 0.0003) and acidity (238 ± 19.37 vs 120.0 ± 5.77, P = 0.001), and esophageal concentrations of MDA (2.56 ± 0.1 vs 1.76 ± 0.28, P = 0.001) and SH groups (1.02 ± 0.05 vs 0.56 ± 0.08, P = 0.0003). D-002 (25, 100 and 200 mg/kg) reduced ELI (3.36 ± 0.31, 2.90 ± 0.46 and 2.8 ± 0.23, respectively) vs the positive control (5.2 ± 0.33) (P = 0.004; P = 0.002; P = 0.001, respectively). There were no significant changes in acidity with D-002 treatment, and only the highest dose reduced the volume of the gastric secretion (1.92 ± 0.25) vs the positive control (2.69 ± 0.09, P = 0.013). D-002 (25, 100 and 200 mg/kg) lowered the esophageal MDA (2.05 ± 0.16, 1.98 ± 0.22 and 1.93 ± 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH group concentration (0.87 ± 0.06, 0.79 ± 0.08 and 0.77 ± 0.06, respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 ± 0.10 and 1.02 ± 0.05, respectively). Omeprazole decreased ELI (2.54 ± 0.47), gastric secretion volume (1.97 ± 0.14) and acidity

  12. Heat-induced evaporation in the shallow subsurface: Experimental and modeling investigation

    NASA Astrophysics Data System (ADS)

    Smits, K. M.; Cihan, A.; Sakaki, T.; Illangasekare, T. H.

    2009-12-01

    The simultaneous movement of liquid water, water vapor and heat in the shallow subsurface below the land-atmosphere interface plays a critical role in determining the mass and energy fluxes between the soil surface and the atmosphere in many agricultural and engineering practices. In arid and semiarid regions, temperature gradients can be very large and the transfer of water due to temperature fluctuations and evaporative conditions may have a significant effect on soil water distributions. Although it is widely recognized that liquid water, water vapor and heat are closely coupled, their mutual interactions are rarely considered in most soil water modeling efforts or in practical application. The validation of numerical models that are designed to capture these processes is difficult due to the inherent complexities of the problem and the scarcity of laboratory data with accurately known hydraulic and thermal parameters, thus limiting the testing and refinement of heat and water transfer theory. In this work, we first developed a long column apparatus equipped with a network of recent sensor technologies. Data were then generated under well-controlled transient heat boundary conditions with a goal of validating the coupled heat-mass transport model and assessing fundamental processes. The objectives of this work were to (1) develop an experimental setup in order to generate precision data (2) develop and implement a fully coupled numerical model to solve for heat, liquid water and water vapor flux (3) determine the key model parameters and processes in order to find the simplest mathematical relationship that best describes the experimental system. For this experimental investigation, very uniform sand was used to minimize particle segregation during packing and achieve as uniform packing as possible. Water saturation, capillary pressure, temperature, relative humidity and column weight were continuously monitored. Evaporation was induced at the soil surface by

  13. Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients.

    PubMed

    Parto, K; Kallajoki, M; Aho, H; Simell, O

    1994-04-01

    Lysinuric protein intolerance is an autosomal recessive disease caused by defective transport of cationic amino acids. Of the 38 lysinuric protein intolerance patients diagnosed in Finland since 1965, four pediatric patients have died. We describe the clinical courses and autopsy findings for these patients. All patients developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, three of the patients had pulmonary alveolar proteinosis and one had cholesterol granulomas. Three patients had a clinically obvious renal insufficiency, but all four showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. The bone marrow of three patients was hypercellular, but the amount of megakaryocytes was decreased in two cases. Amyloid was present in the lymph nodes and the spleen. Bone specimens showed osteoporosis. We conclude that pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. They are also at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids. PMID:8163273

  14. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice.

    PubMed

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-03-15

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  15. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice

    PubMed Central

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-01-01

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  16. Analytical and experimental study of mean flow and turbulence characteristics inside the passages of an axial flow inducer

    NASA Technical Reports Server (NTRS)

    Gorton, C. A.; Lakshminarayana, B.

    1974-01-01

    The effort conducted to gather additional understanding of the complex inviscid and viscid effects existing within the passages of a three-bladed axial flow inducer operating at a flow coefficient of 0.065 is summarized. The experimental investigations included determination of the blade static pressure and blade limiting streamline angle distributions, and measurement of the three components of mean velocity, turbulence intensities and turbulence stresses at locations inside the inducer blade passage utilizing a rotating three-sensor hotwire probe. Applicable equations were derived for the hotwire data reduction analysis and solved numerically to obtain the appropriate flow parameters. Analytical investigations were conducted to predict the three-dimensional inviscid flow in the inducer by numerically solving the exact equations of motion, and to approximately predict the three-dimensional viscid flow by incorporating the dominant viscous terms into the exact equations. The analytical results are compared with the experimental measurements and design values where appropriate.

  17. Experimental Study on the Vortex-Induced Vibration of Towed Pipes

    NASA Astrophysics Data System (ADS)

    HONG, S.; CHOI, Y. R.; PARK, J.-B.; PARK, Y.-K.; KIM, Y.-H.

    2002-01-01

    We experimentally attempted to understand the vibration characteristics of a flexible pipe excited by vortex shedding. This has been extensively studied in the previous decades (for example, see Sarpkaya 1979 Journal of Applied Mechanics46, 241-258; Price et al. 1989 Eighth International Conference on Offshore Mechanics and Arctic Engineering, The Hague-March 19 -23, 447-454; Yoerger et al. 1991 Journal of Offshore Mechanics and Arctic Engineering, Transaction of Engineers113, 117-127; Grosenbaugh et al. 1991Journal of Offshore Mechanics and Arctic Engineering, Transaction of Engineers113 , 199-204; Brika and Laneville 1992 Journal of Fluid Mechanics250, 481-508; Chakrabarti et al. 1993 Ocean Engineering20, 135-162; Jong 1983 Ph.D. Dissertation, Department of Ocean Engineering, M. I. T.; Kimet al. 1986 Journal of Energy Resources Technology, Transactions of American Society of Mechanical Engineers108, 77-83). However, there are still areas that need more study. One of them is the relation between spatial characteristics of a flow-induced vibrating pipe, such as its length, the distribution of wave number, and frequency responses. A non-linear mechanism between the responses of in-line and cross-flow directions is also an area of interest, if the pipe is relatively long so that structural modal density is reasonably high. In order to investigate such areas, two kinds of instrumented pipe were designed. The instrumented pipes, of which the lengths are equally 6 m, are wound with rubber and silicon tape in different ways, having different vortex-shedding conditions. One has uniform cross-section of diameter of 26·7 mm, and the other has equally spaced four sub-sections, which are composed of different diameters of 75·9, 61·1, 45·6 and 26·7 mm. Both pipes are towed in a water tank (200 m×16 m×7 m) so that they experienced different vortex-shedding excitations. Various measures were obtained from the towing experiment, including frequency responses, the time

  18. Experimental animal models for studies on the mechanisms of blast-induced neurotrauma.

    PubMed

    Risling, Mårten; Davidsson, Johan

    2012-01-01

    A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments

  19. The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis.

    PubMed

    Pedersen, Niels C; Liu, Hongwei; Gandolfi, Barbara; Lyons, Leslie A

    2014-11-15

    Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP

  20. Experimental investigation of flow-induced vibration on isolated and tandem circular cylinders fitted with strakes

    NASA Astrophysics Data System (ADS)

    Korkischko, I.; Meneghini, J. R.

    2010-05-01

    The effect of varying the geometric parameters of helical strakes on vortex-induced vibration (VIV) is investigated in this paper. The degree of oscillation attenuation or even suppression is analysed for isolated circular cylinder cases. How a cylinder fitted with strakes behaves when immersed in the wake of another cylinder in tandem arrangement is also investigated and these results are compared to those with a single straked cylinder. The experimental tests are conducted at a circulating water channel facility and the cylindrical models are mounted on a low-damping air bearing elastic base with one degree-of-freedom, restricted to oscillate in the transverse direction to the channel flow. Three strake pitches (p) and heights (h) are tested: p=5, 10, 15d, and h=0.1, 0.2, 0.25d. The mass ratio is 1.8 for all models. The Reynolds number range is from 1000 to 10 000, and the reduced velocity varies up to 21. The cases with h=0.1d strakes reduce the amplitude response when compared to the isolated plain cylinder, however the oscillation still persists. On the other hand, the cases with h=0.2, 0.25d strakes almost completely suppress VIV. Spanwise vorticity fields, obtained through stereoscopic digital particle image velocimetry (SDPIV), show an alternating vortex wake for the p=10d and h=0.1d straked cylinder. The p=10d and h=0.2d cylinder wake has separated shear layers with constant width and no roll-up close to the body. The strakes do not increase the magnitude of the out-of-plane velocity compared to the isolated plain cylinder. However, they deflect the flow in the out-of-plane direction in a controlled way, which can prevent the vortex shedding correlation along the span. In order to investigate the wake interference effect on the strake efficiency, an experimental arrangement with two cylinders in tandem is employed. The centre-to-centre distance for the tandem arrangement varies from 2 to 6. When the downstream p=10d and h=0.2d cylinder is immersed in the

  1. Experimental Animal Models for Studies on the Mechanisms of Blast-Induced Neurotrauma

    PubMed Central

    Risling, Mårten; Davidsson, Johan

    2012-01-01

    A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments

  2. CT and MRI of experimentally induced mesenteric ischemia in a porcine model

    SciTech Connect

    Klein, H.M.; Seggewib, C.; Weghaus, P.; Kamp, M.; Guenther, R.W.

    1996-03-01

    Our goal was to assess the value of CT and MRI for the detection of bowel wall changes in experimentally induced mesenteric ischemia. In 18 female pigs. a percutaneous embolization of the superior mesenteric artery was performed with buthyl-2-cyanoacrylate and Lipoidal (1:1) (experimental group). In six animals, only diagnostic imaging and histologic evaluation were performed (control group). CT was carried out 3, 6, and 12 h after occlusion. Incremental CT (1 s scan time, 5 mm slice thickness, 7 mm increment, 120 kV/290 mAs) and spiral CT (slice thickness 5 mm, pitch 1.5, 120 kV/165 mA) were performed pre and post contrast injection (Somatom Plus/ Siemens). Serial CT was carried out after intravenous contras