Albuminuria causes lysozymuria in rats with Heymann nephritis

Albuminuria causes lysozymuria in rats with Heymann nephritis. To determine if changes in dietary protein intake alter renal excretion of small molecular weight proteins in passive Heymann nephritis, 21 rats with passive Heymann nephritis were fed 8.5% protein for 12 days after injection with antiserum. Dietary protein intake was then increased to 40% in 10 rats (LP-HP) while 11 rats remained on 8.5% protein (LP-LP). Lysozymuria (UlysV) increased from 66.5 ±31.0 meg/day to 457.5 ± 98.0 mcg/day (P < 0.001) after five days in LP-HP, but was unchanged in LP-LP. Albuminuria (UalbV) increased only in LP-HP, from 168 ± 23 mg/day to 447 ± 45 mg/day (P < 0.001). Urinary lysozyme excretion correlated with UalbV (r = 0.737, P < 0.001), and changes in UlysV correlated with changes in UalbV (r = 0.657, P < 0.01). To determine whether the increase in UlysV was the direct effect of the change in diet, enalapril 40 mg/kg/day was administered to prevent the increase in UalbV that occurs when these rats are fed a high protein diet. Twelve rats were fed 8.5% (LP) and 10 were fed 40% protein (HP) from the time of injection with antiserum. Six LP (LPE) and five HP (HPE) received enalapril. UlysV was 873 ± 391 meg/day in HP and nearly undetectable in the other three groups. UalbV was significantly greater in HP (368 ± 60 mg/day) compared to the other three groups (114 ± 16 in LP, 136 ± 44 in HPE, 95 ± 21 in LPE). A third group of nephrotic rats, maintained on a constant diet of 21% protein had enalapril added to their drinking water. UiysV decreased from 49 ± 9 meg/day to less than 2 meg/day (P < 0.001) and UalbV decreased from 516 ± 67 to 183 ± 32 mg/day (P < 0.001). Both UlysV and UalbV remained unchanged in untreated rats. Lysozyme, an enzyme normally entirely reabsorbed by the kidney, is found in the urine of rats with passive Heymann nephritis, and increases when dietary protein intake is increased. High protein diets increase UlysV only in as much as UalbV is increased, and when UalbV is reduced by use of an angiotensin converting enzyme inhibitor in the presence of a high protein diet UlysV is reduced in a parallel fashion, suggesting that albuminuria itself decreases the capacity of the renal tubule to reabsorb lysozyme

GFR increases before renal mass or ODC activity increase in rats fed high protein diets

GFR increases before renal mass or ODC activity increase in rats fed high protein diets. Consumption of a high protein diet causes renal hypertrophy and increased glomerular filtration rate (GFR). To determine the relationship between increases in GFR, renal ornithine decarboxylase activity (ODC), arginase activity, and renal growth, dietary protein intake was increased from 8.5% to 40% in 50 male Sprague-Dawley rats (HP). Forty-one rats remained on 8.5% protein as time controls (LP). Eight to 17 animals were killed daily for measurement of kidney weight (kidney wt), ODC and arginase activities, total kidney protein and DNA content. GFR increased within the first 24 hours after the increase in dietary protein and reached a maximum within 48hrs. ODC increased from 9.7 ± 0.8 U/g to a peak of 170 ± 35 U/g at 48 hours, decreasing to a stable value of 28.6 ± 8.0 U/g at 72 hours and 25.4 ± 5.1 U/g at 168 hours, a value significantly greater than that at time zero. Arginase activity did not change. Kidney wt as percent body weight (body wt) increased after the initial increase in both GFR and in ODC activity. The peak in ODC activity corresponded with the maximum increase in GFR and preceded the increase in renal mass. After GFR stabilized, ODC activity decreased to a plateau and renal growth relative to body wt ceased. The increase in kidney weight was accompanied by a parallel increase in total kidney protein. Kidney protein/ kidney DNA ratio increased significantly by 96 hours, indicating that renal hypertrophy had occurred. The sequence of these events suggests that increasing GFR may trigger the rise in ODC activity

Novel Application of Cyclolipopeptide Amphisin: Feasibility Study as Additive to Remediate Polycyclic Aromatic Hydrocarbon (PAH) Contaminated Sediments

To decontaminate dredged harbor sediments by bioremediation or electromigration processes, adding biosurfactants could enhance the bioavailability or mobility of contaminants in an aqueous phase. Pure amphisin from Pseudomonas fluorescens DSS73 displays increased effectiveness in releasing polycyclic aromatic hydrocarbons (PAHs) strongly adsorbed to sediments when compared to a synthetic anionic surfactant. Amphisin production by the bacteria in the natural environment was also considered. DSS73’s growth is weakened by three model PAHs above saturation, but amphisin is still produced. Estuarine water feeding the dredged material disposal site of a Norman harbor (France) allows both P. fluorescens DSS73 growth and amphisin production

Literary studies and the academy

In 1885 the University of Oxford invited applications for the newly created Merton Professorship of English Language and Literature. The holder of the chair was, according to the statutes, to ‘lecture and give instruction on the broad history and criticism of English Language and Literature, and on the works of approved English authors’. This was not in itself a particularly innovatory move, as the study of English vernacular literature had played some part in higher education in Britain for over a century. Oxford University had put English as a subject into its pass degree in 1873, had been participating since 1878 in extension teaching, of which literary study formed a significant part, and had since 1881 been setting special examinations in the subject for its non-graduating women students. What was new was the fact that this ancient university appeared to be on the verge of granting the solid academic legitimacy of an established chair to an institutionally marginal and often contentious intellectual pursuit, acknowledging the study of literary texts in English to be a fit subject not just for women and the educationally disadvantaged but also for university men

Effect of genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production and renal disease in MRL/lpr mice

Terminal deoxynucleotidyl transferase (TdT) places non-template-coded nucleotides (N additions) in the VH CDR3 of T cell receptors and immunoglobulins. Amino acids coded for by N additions are important in autoantibody binding of dsDNA in lupus. We hypothesized that a genetic lack of TdT would modulate disease in lupus-prone mice. To test this hypothesis, we derived TdT-deficient MRL/lpr mice. Serum levels of anti-dsDNA antibodies and anti-dsDNA producing splenocytes were significantly lower in the TdT − versus TdT + littermates. Albuminuria, glomerular IgG deposition, and pathologic renal disease were significantly reduced in the TdT − mice. Sequence analysis of anti-dsDNA hybridomas derived from TdT − mice revealed a lack of N additions, short VH CDR3 segments, yet the presence of VH CDR3 arginines. Thus, the genetic absence of TdT reduces autoantibody production and clinical disease in MRL/lpr mice, confirming the importance of N additions in the autoimmune response in these mice

Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of inducible nitric oxide synthase

Modulation of renal disease in MRL/ lpr mice by pharmacologic inhibition of inducible nitric oxide synthase.BackgroundMRL-MPJFaslpr (MRL/lpr) mice spontaneously develop lupus-like disease characterized by immune complex glomerulonephritis and overproduction of nitric oxide (NO). Blocking NO production pharmacologically by a non-specific nitric oxide synthase (NOS) inhibitor ameliorated renal disease in MRL/lpr mice while genetically deficient inducible NOS (iNOS) mice developed proliferative glomerulonephritis similar to wild-type controls.MethodsTo clarify the role of iNOS in the pathogenesis of nephritis in MRL/lpr mice, we treated mice with two different NOS inhibitors. Either NG-monomethyl-L-arginine (L-NMMA), a nonspecific NOS inhibitor, or L-N6-(1-iminoethyl)lysine (L-NIL), an iNOS specific inhibitor, was administered in the drinking water from 10 through 22 weeks of age with disease progression monitored over time. Control mice received water alone.ResultsBoth L-NMMA and L-NIL blocked NO production effectively in MRL/lpr mice. As expected, neither L-NNMA nor L-NIL had an effect on antibody production, immune complex deposition or complement activation. Although both NOS inhibitors decreased protein excretion, L-NMMA was more effective than L-NIL. Pathologic renal disease was significantly decreased at 19 weeks in both treatment groups. At 22 weeks the L-NIL treated mice, but not the L-NMMA mice, had significantly reduced renal disease scores compared to controls.ConclusionThese results indicate that specific inhibition of iNOS blocks the development of pathologic renal disease in MRL/lpr mice