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Biomedical subjects

M Schulze

Publications and source records attributed to M Schulze.

At least 37 records · Page 2Linked to original sources

Pharmaceutical transition to non-CFC pressurized metered dose inhalers.

The production of ozone-depleting chlorofluorocarbons (CFCs) was discontinued on 1 January 1996 for all uses deemed non-essential under the Montreal Protocol. However, the use of CFCs as propellants in pressurized metered dose inhalers (pMDIs) was classed as essential, providing an exemption from the agreement. Following extensive research, the hydrofluoroalkanes (HFA) 134a and 227 were identified as the only suitable replacements for CFC propellants in pMDIs. The drug delivery of pMDIs formulated with HFA 134a as a propellant and containing either salbutamol (100 microg per actuation) or fluticasone propionate (125 and 250 microg per actuation) have been assessed for dose uniformity and particle size distribution. All of the HFA 134a pMDIs delivered doses throughout the life of the canisters that were reproducible and within specified regulatory requirements. Each of the products provided an emitted dose which was within +/- 25% of the mean value indicating accurate and consistent dosing (93, 112 and 221 microg per metered dose for the salbutamol 100 microg and fluticasone propionate 125 and 250 microg HFA 134a pMDIs, respectively). These findings were unaffected by changing the storage orientation of the pMDI or by using the device in a manner designed to simulate typical patient use. The particle size distributions of HFA 134a pMDI doses did not differ significantly from those of the corresponding CFC pMDIs. As a result of the similar pharmaceutical performance, it is unnecessary to change the label claim dose of active drug when making the transition from a CFC to an HFA 134a pMDI for salbutamol (Ventolin) and fluticasone propionate (Flixotide). A seamless transition to non-CFC pMDIs will help to maintain the confidence of patients and healthcare professionals in asthma therapy.

Aerosol Propellants↗

Regional expression of sulfatides in rat kidney: immunohistochemical staining by use of monospecific polyclonal antibodies.

Sulfatides are quantitatively prominent glycosphingolipids of rat kidney. In order to gain insight into their possible physiological significance in this organ, and their possible role in Heymann's nephritis, the main sulfatide components were localized immunohistochemically. The antibodies used recognized the sulfatides Sgal1, Stri1, Stri2, and Stet2a. Stri1 epitopes were expressed in the brush border of proximal tubuli, whereas Stri2-specific immuno staining was observed in cortical and medullar collecting ducts. Both Stri1 and Stri2 were also expressed by interstitial cells of the inner medulla. Stet2a was visualized in epithelia of the distal tubules of Henle's loop and the juxtaglomerular apparatus, including the macula densa. The mAb Sulph-I, that recognizes the SO3(-)-3Galbeta<epitope of Sgal1, seminolipid, and Slac1, prominently stained the cortical and medullar collecting ducts. No sulfatide was immuno-stained in the glomerular region. For this reason, the possibility of a direct involvement of anti-Stri1 and Stri2 antibodies in the etiology of Heymann's nephritis appears to be less likely. A strict correlation between the local sulfatide content, as analyzed by chemical estimation, and the sulfatide expression, as observed by immunohistochemical methods, may not be possible.

Animals↗

Glycosylphosphatidylinositol-specific phospholipase D in blood serum: is the liver the only source of the enzyme?

In cases of systemic inflammatory response syndrome, sepsis, and septic shock, the activity of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in serum amounts to 20 to 25% of the activity found in a healthy control group. The activity of serum GPI-PLD is positively correlated with inflammatory markers and counts of monocytes and stab cells (bands) and negatively correlated with polymorphonuclear neutrophils and lymphocytes in severe diseases. This indicates a yet unknown involvement of the inflammatory system in GPI-PLD liberation and suggests that the liver is not the only source of the plasma enzyme. Plasma was shown to contain an effective inhibitor of GPI-PLD which is soluble in organic solvents. Its concentration in capillary plasma is 20-fold higher than in venous plasma. To find possible other sources of plasma GPI-PLD besides the liver, the GPI-degrading activity was measured in different organs of the rat. Product formation was analysed using [125I]TID-labeled GPI-AP.

Alkaline Phosphatase↗

Closed reduction/percutaneous fixation of tibial plateau fractures: arthroscopic versus fluoroscopic control of reduction.

OBJECTIVE: To evaluate arthroscopic versus fluoroscopic reduction and percutaneous fixation of lateral tibial plateau fractures of AO/OTA Types 41.B1 to 41.B3. DESIGN: Prospective study. SETTING: University hospital. PATIENTS AND INTERVENTION: One hundred sixty-eight patients underwent operative treatment for a tibial plateau fracture from 1988 to 1995. Thirty-three of these patients had monocondylar fractures of the lateral plateau that were treated by percutaneous reduction and fixation techniques. In the first ten cases, arthroscopic control of reduction was used. The following twenty-three consecutive cases were treated by reduction and fixation solely under fluoroscopic control. The arthroscopy group was followed for a mean of fifty-two months and the fluoroscopy group for thirty-eight months. RESULTS: Nine of ten cases of the arthroscopy group had an excellent or good result in Rasmussen's knee score at follow-up. One patient with an unreduced anterolateral depression zone despite arthroscopic surgery required a total knee prosthesis after eighteen months. Sixteen cases in the fluoroscopy group met the follow-up criteria. Fifteen were graded good or excellent in Rasmussen's clinical score; sixteen were excellent or good in the radiological score. One patient claimed chronic medial joint line pain after a lateral split fracture and had arthroscopy revealing chondral degeneration on the medial side but had no pathological findings in the lateral compartment. No secondary meniscus or ligament surgery was performed in the follow-up period. CONCLUSIONS: Percutaneous treatment of fractures of the tibial plateau can be performed using arthroscopy as well as image intensification to control reduction of the joint surface. We were not able to demonstrate any significant benefit from arthroscopy compared with fluoroscopic reduction. Reduction under image intensification is technically easier in our practice, especially in serial fractures and multiply injured patients. We reserve arthroscopy for cases with significant ligament injuries and for children with fractures of the median eminence.

Adolescent↗

Role of xanthine oxidase in passive Heymann nephritis in rats.

Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinuria by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53 mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.

Animals↗

Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlate with clinicopathological parameters.

An extended analysis for loss of heterozygosity (LOH) on eight chromosomes was conducted in a series of 82 Wilms tumors. Observed rates of allele loss were: 9.5% (1p), 5% (4q), 6% (6p), 3% (7p), 9.8% (11q), 28% (11p15), 13.4% (16q), 8.8% (18p), and 13.8% (22q). Known regions of frequent allele loss on chromosome arms 1p, 11p15, and 16q were analyzed with a series of markers, but their size could not be narrowed down to smaller intervals, making any positional cloning effort difficult. In contrast to most previous studies, several tumors exhibited allele loss for multiple chromosomes, suggesting an important role for genome instability in a subset of tumors. Comparison with clinical data revealed a possible prognostic significance, especially for LOH on chromosome arms 11q and 22q with high frequencies of anaplastic tumors, tumor recurrence, and fatal outcome. Similarly, LOH 16q was associated with anaplastic and recurrent tumors. These markers may be helpful in the future for selecting high-risk tumors for modified therapeutic regimens.

Alleles↗

Synthesis of articular cartilage-like tissue in vitro.

Defects in mature articular cartilage do not heal without residues, and therefore they remain a challenging problem in orthopaedic surgery. Modern tissue culture techniques facilitate the synthesis of cartilage-like tissue. A requirement of retaining the phenotypic characteristics of chondrocytes in vitro is the use of three-dimensional culture techniques. Articular chondrocytes of adult rabbits were isolated and cultured on different transplantable media for several weeks. A resorbable fleece, a non-absorbable net and lyophilized dura were used. Viability was tested by immunohistochemical techniques. Deposition of extracellular matrix could be observed by electron microscopy. The phenotypical and morphological appearance of cultured chondrocytes was preserved on the resorbable polymer fleece and the lyophilized dura. Cells cultured on the non-absorbable net had a more fibroblastic appearance. The resorbable fleece is apparently most suitable in terms of viability of the cultured chondrocytes and biocompatibility. The cultured three-dimensional artificial cartilage constructs reveal a future possibility for autologous cartilage transplantation into mature cartilage defects.

Animals↗

Meningeal cells stimulate and direct the migration of cerebellar external granule cells in vitro.

The external granular layer is a secondary proliferative zone that arises from the caudolateral margin of the cerebellar ventricular zone and then spreads beneath the pial surface, eventually covering the entire cerebellar anlage. Here, both a part of the Bergmann glia and granule cells are generated. Selective destruction of the leptomeningeal cell layer during development in vivo disrupts the subpial extension of the external granular layer and the laminar deposition of its descendant cells. The mechanisms by which meningeal fibroblasts exert their controlling influence on cortical development have remained unclear but could involve diffusible factors and/or interactions mediated by direct cellular contacts. In order to test these assumptions, we have co-cultivated cerebellar slice explants with meningeal cells with and without interposition of a microfilter barrier. In this setup, meningeal cells by a diffusible factor stimulated the emigration of immature neurons exclusively from the external granular layer. This effect could also be elicited by fibroblasts from other tissues but not by nonfibroblastic cells such as, e.g., astroglia. In the Boyden chamber assay, the migration of undifferentiated neurons isolated from the external granular layer was chemotactically oriented towards the source of meningeal cell conditioned media. In comparison, neurons from the internal granular layer did not respond to this stimulus. The attraction of immature neurons towards the pial surface could (1) represent a mechanism for the establishment of (subpial) secondary proliferative zones and (2) hypothetically also play a role in the outward-directed migration of postmitotic cells, e.g., in the isocortical anlage.

Animals↗

[Spiral CT vesiculography--a new examination technique in patients with histologically verified prostate carcinoma].

PURPOSE: Development of an imaging method for detection of seminal vesicle invasion in patients with histologically proven carcinoma of the prostate. MATERIALS AND METHODS: In 24 patients with histologically proven carcinoma of the prostate we preoperatively performed an antegrade vaso-vesiculography with non-ionic, iodine-containing contrast agent followed by a spiral CT of the seminal vesicles. RESULTS: In 21 patients we achieved both a bilateral and a bulging enhancement of the seminal vesicle lumen. The method is introduced and described in detail. CONCLUSIONS: Intraductal application of contrast agent just before spiral CT results in unfold and bulging enhanced seminal vesicles. From the differentiation of the lumen, the wall, and the surrounding fat of the seminal vesicles as well as the enhanced ejaculatory ducts we expect information on tumorous infiltration in cases of histologically proven carcinomas of the prostate.

Aged↗

Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption.

BACKGROUND: Sepsis is associated with enhanced cytokine production. Here, we examined the in vitro removal of plasma cytokines during continuous plasmafiltration coupled with sorbent adsorption. METHODS: Proinflammatory (tumour necrosis factor-alpha, interleukins-1, -8) and anti-inflammatory (interleukin 1 receptor antagonist, soluble tumour necrosis factor receptor type I and II) cytokines in whole blood spiked with Escherichia coli endotoxin were determined during 2-h recirculation in the ultrafiltrate (condition A), plasma filtrate (condition B), before and after different sorbents (of the Amberlite-, Amberchrome- Ambersorb -type and charcoal). We studied the maximal adsorbing capacity, the 1% leakage test for cytokines and C3a des Arg and the adsorption of complement-dependent leukocyte chemiluminescence. Plasma proteins eluted from the resins were examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting with an anti-human alpha2-macroglobulin. RESULTS: In condition B, we observed a 40- and 121-fold % increase (vs condition A) in the removed mass and clearance of tumour necrosis factor-alpha. For all other cytokines, the removed mass and the clearance increased from 2.3- up to 6-fold. The Amberchrome but not the Amberlite or Ambersorb resins could remove the highest amount of cytokines and could reduce complement-dependent chemiluminescence. Two protein bands of approximately 400,000 D and 200,000 D were eluted only from Amberchrome resins and immunoprecipitated by anti-human alpha2-macroglobulin and anti-human C3c antibodies, respectively. CONCLUSIONS: These studies suggest an efficient removal of cytokines in continuous plasmafiltration with sorbent adsorption. The binding of alpha2-macroglobulin, a carrier of cytokines in plasma, might be a additional mechanism in the removal of cytokines from plasma.

Adsorption↗

Complexed plasma elastase as an in vivo marker for leukocyte activation in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: It has been postulated that antineutrophil cytoplasmic antibody (ANCA)-induced degranulation of primed granulocytes and monocytes is involved in the pathogenesis of ANCA-associated vasculitis. Since elastase is the major lysosomal protein released during leukocyte degranulation, we investigated cell activation in vivo in patients with ANCA-associated vasculitis by determining complexed plasma elastase levels. METHODS: Plasma elastase complexed with alpha1-antitrypsin was measured in 20 patients with ANCA-associated vasculitis, using an immunoactivation assay. In parallel, C-reactive protein (CRP) and ANCA levels were determined and clinical disease activity was assessed. RESULTS: Complexed elastase levels were significantly elevated in patients with ANCA-associated vasculitis who had not received immunosuppressive therapy (mean +/- SD 71.5 +/- 22.6 microg/liter), compared with healthy volunteers (12.2 +/- 11.4 microg/liter; P < 0.001). Elastase decreased significantly after 2 weeks (46.5 +/- 26.8 microg/liter; P < 0.01) and further after 8-10 weeks of immunosuppressive treatment (28.1 +/- 13.4 microg/liter; P < 0.02), in correlation with decreasing vasculitis activity. Concomitantly, ANCA titers and CRP levels decreased. CONCLUSION: These data support the theory that, by the release of lysosomal proteinases, leukocyte activation may be involved in the pathogenesis of ANCA-associated vasculitis. In addition, plasma elastase may be used as a marker for disease activity.

Adolescent↗

Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular chondrocyte proteoglycan synthesis.

The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA.

Adolescent↗

[Heterotopic ossifications of 5 large body joints after 105 days of intensive care with 72 days of artificial ventilation].

A 37-year-old woman had intensive care for 105 days and artificial ventilation for 72 days because of a lung transplantation and multiple postoperative complications. She developed severe heterotopic ossification of both shoulders, the right elbow and both hip joints. Owing to complete joint stiffness, she was immobilized and unable to eat or drink without help. Operative treatment was performed in two procedures. The right shoulder and right elbow were operated on first; the right hip and later the left hip were operated on after recovery from the previous surgical procedures. After 22 months, there was a good functional result; the patient took part in all activities of daily life and was pain-free. The present knowledge on heterotopic ossifications is summarized, as well as possible prophylactic measurements.

Adult↗

Activated complement C3: a potentially novel predictor of progressive IgA nephropathy.

In the search for a serologic marker of disease activity, we measured concentrations of activated C3 (actC3, that is, neoantigens developing after C3 activation on breakdown products), C4-C3 complexes and soluble C5b-9 (sC5b-9) in one or two plasma samples from adult patients with IgA nephropathy (IgAN, N = 50) or Henoch-Schönlein purpura (HSP, N = 4). As controls, 20 patients with non-immune renal disease, but comparable age, degree of proteinuria, renal dysfunction and prevalence of hypertension were studied. Compared to controls, actC3 levels were elevated in 30% of the patients with IgAN and one of the HSP patients. C4-C3 complexes were elevated in only 8% of the IgAN patients, and sC5b-9 levels were within the control range in all IgAN and HSP patients. In IgAN patients with elevated actC3 levels, proteinuria and hematuria were more pronounced than in those with normal levels. Elevated plasma concentrations of actC3 at the first presentation correlated with subsequent deterioration of renal function both in patients with initially normal and already impaired renal function (r = -0.56, N = 44, P = 0.003). The five IgAN patients with elevated actC3 on both occasions of obtaining plasma showed the most rapid loss of renal function. We conclude that mainly alternative pathway complement activation can be demonstrated in patients with IgAN and HSP. In IgAN patients the presence of complement activation is associated with more severe renal disease. Further studies are warranted to examine the clinical usefulness of actC3 as a predictor of the subsequent course of IgAN.

Adolescent↗

Tumor cell contamination of peripheral blood stem cell transplants and bone marrow in high-risk breast cancer patients.

Twenty-one high-risk patients with primary stage II/III breast cancer were treated with high-dose chemotherapy comprising etoposide, ifosfamide, carboplatin and epirubicin (VIC-E). Tumor cells of epithelial origin were analyzed using the monoclonal antibodies CK2 (IgG1) and A45-B/B3 (IgG1) against cytokeratin (CK) components in bone marrow (BM) aspirates prior to chemotherapy, and in peripheral blood stem cell transplants (PBSCT). They were separated after the first (21/21 patients) and the second cycle (16/21 patients) of induction chemotherapy with VIP-E (etoposide, ifosfamide, cisplatin, epirubicin). Preliminary results showed CK positive tumor cells in 40% (14/35) of the analyzed transplants. In 7/12 (58.3%) patients, CK positive tumor cells were detectable in BM prior to treatment. Sixteen patients were separated after the 1st and 2nd cycle of VIP-E. PBSCT of 14/16 patients were assessable for presence of CK positive tumor cells. Our preliminary results demonstrate a lower tumor cell contamination of PBSCT separated after the 2nd cycle of induction therapy (14.3%) compared to contamination after the first induction therapy (64.3%). To date, 4/21 patients have experienced a relapse, and three of these patients had tumor cell positive transplants. Due to the small patient number only a trend towards a superior relapse-free survival in the patient group with CK negative transplants can be shown by Kaplan-Meier analysis.

Adult↗

Automated biodosimetry using digital image analysis of fluorescence in situ hybridization specimens.

Fluorescence in situ hybridization (FISH) of metaphase chromosome spreads is valuable for monitoring the radiation dose to circulating lymphocytes. At low dose levels, the number of cells that must be examined to estimate aberration frequencies is quite large. An automated microscope that can perform this analysis autonomously on suitably prepared specimens promises to make practical the large-scale studies that will be required for biodosimetry in the future. This paper describes such an instrument that is currently under development. We use metaphase specimens in which the five largest chromosomes have been hybridized with different-colored whole-chromosome painting probes. An automated multiband fluorescence microscope locates the spreads and counts the number of chromosome components of each color. Digital image analysis is used to locate and isolate the cells, count chromosome components, and estimate the proportions of abnormal cells. Cells exhibiting more than two chromosomal fragments in any color correspond to a clastogenic event. These automatically derived counts are corrected for statistical bias and used to estimate the overall rate of chromosome breakage. Overlap of fluorophore emission spectra prohibits isolation of the different chromosomes into separate color channels. Image processing effectively isolates each fluorophore to a single monochrome image, simplifying the task of counting chromosome fragments and reducing the error in the algorithm. Using proportion estimation, we remove the bias introduced by counting errors, leaving accuracy restricted by sample size considerations alone.

Automation↗

Role of the complement membrane attack complex (C5b-9) in mediating experimental mesangioproliferative glomerulonephritis.

Previous studies have demonstrated that most pathologic changes in the antithymocyte serum (ATS) model of mesangioproliferative glomerulonephritis are complement-dependent. These include mesangiolysis, glomerular platelet infiltration, mesangial cell proliferation, mesangial cell production of growth factors and phenotypic change to express alpha-actin, glomerular macrophage infiltrate, mesangial matrix expansion, and proteinuria. The mechanism by which complement mediates these effects has not been defined. Because neutrophils do not participate in the ATS model, we hypothesized that the complement effects observed are consequent to glomerular cell insertion of the C5b-9 membrane attack complex of complement. This hypothesis was tested utilizing PVG rats which exhibit an absence of C6 inherited in an autosomal recessive pattern. C6 deficient (C-) PVG rat serum activated by zymosan produced normal amounts of C5a compared to normocomplementemic (C+) PVG rat controls but no C5b-9. When ATS was induced, C- PVG rats had a significant and marked reduction in mesangiolysis, platelet infiltration, mesangial cell proliferation, alpha-actin expression, macrophage infiltration, collagen IV deposition, and proteinuria compared to C+ controls. The reduction in each of these parameters was comparable to that achieved by systemic complement depletion of C+ PVG rats with cobra venom factor. These findings establish the role of C5b-9 in mediating each of the complement-dependent features of the ATS model and indicate that C5b-9 accounts for all of the complement-mediated effects observed. This study provides the first documentation of a functional role for C5b-9 in mediating a non-membranous inflammatory type of glomerular injury in vivo.

Animals↗

Beneficial effects of systemic immunoglobulin in experimental membranous nephropathy.

To test the hypothesis that systemic administration of immunoglobulin might reduce glomerular injury in membranous nephropathy through mechanisms involving inhibition of complement activation, we studied the passive Heymann nephritis (PHN) model of membranous nephropathy in rats. The daily administration of immunoglobulin goat IgG (600 mg/kg i.p.) reduced proteinuria by 52%. Quantitative immunohistochemical analysis showed that the glomerular deposition of C3c, an indicator of ongoing complement attack, and of C5b-9 was significantly decreased in the immunoglobulin treated group, while deposition of anti-Fx1A was not affected. Electron microscopic analysis demonstrated that the extent of subepithelial immune complexes did not appreciably differ between treated and control animals. Systemic complement levels were not altered by immunoglobulin treatment. These data suggest that the reduction in proteinuria that resulted from systemic immunoglobulin administration was mediated by modifying the effect of complement induced glomerular injury. This interpretation was further supported by in vitro data that documented a significant reduction in C5b-9 induced glomerular epithelial cell lysis in the presence of both goat and rat IgG. These results indicate that systemic administration of immunoglobulin can substantially reduce ongoing complement activation in the glomerulus in PHN rats and that this effect is associated with a significant reduction in glomerular injury.

Animals↗