scholarly journals Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions

2020 ◽  
Vol 24 (12) ◽  
pp. 1122-1131
Author(s):  
Shuhei Naka ◽  
Kaoruko Wato ◽  
Taro Misaki ◽  
Seigo Ito ◽  
Yasuyuki Nagasawa ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Streptococcus Mutans ◽  
Intravenous Administration ◽  
Mesangial Cells ◽  
Late Phase ◽  
Control Group ◽  
Chronic Glomerulonephritis ◽  
Sprague Dawley ◽  
Mesangial Area ◽  
Specific Pathogen

Abstract Background IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Methods Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague–Dawley rats to evaluate their kidney conditions. Results The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. Conclusion Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.

scholarly journals The TLR4-MyD88-NF-κB pathway is involved in sIgA-mediated IgA nephropathy

2020 ◽  
Vol 33 (6) ◽  
pp. 1251-1261 ◽  
Author(s):  
Junjun Zhang ◽  
Yiming Mi ◽  
Ruwen Zhou ◽  
Zhangsuo Liu ◽  
Bo Huang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Mesangial Cells ◽  
Immunofluorescence Assay ◽  
Kidney Damage ◽  
Secretory Iga ◽  
Tnf Α ◽  
Mesangial Area ◽  
Enhanced Expression ◽  
Better Than

AbstractPrevious studies have shown that secretory IgA (sIgA) was critically involved in IgA nephropathy (IgAN) immune responses. Toll-like receptors (TLRs), especially TLR4 which participates in mucosal immunity, may be involved in the pathogenesis of IgAN. The purpose of this study was to investigate whether sIgA and TLR4 interact to mediate kidney damage in IgAN patients. IgAN patients with positive sIgA deposition in renal tissues were screened by immunofluorescence assay. Patient salivary sIgA (P-sIgA) was collected and purified by jacalin affinity chromatography. Salivary sIgA from healthy volunteers was used as a control (N-sIgA). Expression of TLR4, MyD88, NF-κB, TNF-α, IL-6, and MCP-1 were detected in the mesangial area of IgAN patients by immunohistochemistry, the expression levels in patients with positive sIgA deposition were higher than that with negative sIgA deposition. Human renal mesangial cells (HRMCs) were cultured in vitro, flow cytometry showed that P-sIgA bound HRMCs significantly better than N-sIgA. HRMCs were cultured in the presence of sIgA (400 μg/mL) for 24 h, compared with cells cultured with N-sIgA, HRMCs cultured in vitro with P-sIgA showed enhanced expression of TLR4, increased secretion of TNF-α, IL-6, and MCP-1, and increased expression of MyD88/NF-κB. TLR4 shRNA silencing and NF-κB inhibition both reduced the ability of HRMCs to synthesize TNF-α, IL-6, and MCP-1. Our results indicate that sIgA may induce high expression of TLR4 in HRMCs and further activate downstream signalling pathways, prompting HRMCs to secrete multiple cytokines and thereby mediating kidney damage in IgAN patients.

scholarly journals Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuhei Naka ◽  
Kaoruko Wato ◽  
Taro Misaki ◽  
Seigo Ito ◽  
Daiki Matsuoka ◽  
...  
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Mesangial Cells ◽  
Periodic Acid ◽  
Immunoglobulin A ◽  
Wide Distribution ◽  
Complement C3 ◽  
Positive Staining ◽  
Sprague Dawley ◽  
Periodic Acid Schiff

AbstractThe mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague–Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.

scholarly journals Nephroprotective effect of losartan in IgA model rat

2019 ◽  
Vol 47 (10) ◽  
pp. 5205-5215
Author(s):  
Li Xing ◽  
Er Lin Song ◽  
Xi Bei Jia ◽  
Jing Ma ◽  
Bing Li ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Tubulointerstitial Injury ◽  
Expression Levels ◽  
Losartan Group ◽  
Tgf Β1

Objective This study was performed to investigate the possible nephroprotective effects of losartan in a rat model of experimental IgA nephropathy (IgAN). Methods Thirty male Sprague–Dawley rats were randomly divided into three groups. The rats in the model group were treated with bovine serum albumin (oral gavage), lipopolysaccharide (tail vein injection), and carbon tetrachloride (subcutaneous injection); rats in the losartan group received treatments similar to those of the model group, and were orally gavaged with losartan; and rats in the control group received phosphate-buffered saline alone (both orally and intravenously). Results Losartan treatment lowered the 24-hour urinary protein, serum blood urea nitrogen, and serum creatinine levels. Proliferating mesangial cells with a variable increase in the mesangial matrix were detected in the model group, whereas injury in the losartan group was significantly attenuated. Immunohistochemistry revealed that the expression levels of transforming growth factor (TGF)-β1 and α-smooth muscle actin were significantly elevated in the model group but reduced in the losartan group. The expression levels of TGF-β1 and monocyte chemoattractant protein-1 were minimal in the control group, significantly increased in the model group, and reduced in the losartan group. Conclusion Losartan has a protective effect against tubulointerstitial injury in IgAN.

scholarly journals P0371DENTAL CARIES INDUCED BY CNM-POSITIVE STREPTOCOCCUS MUTANS DERIVED FROM IGA NEPHROPATHY PATIETNS IN RATS INDUCED GLOPERULONEPHRITIS LIKE IGA NEPHROPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yasuyuki Nagasawa ◽  
Shuhei Naka ◽  
Kaoruko Wato ◽  
Ryota Nomura ◽  
Taro Misaki ◽  
...  
Keyword(s):  
Dental Caries ◽  
Iga Nephropathy ◽  
Streptococcus Mutans ◽  
Periodic Acid ◽  
Sprague Dawley ◽  
Periodic Acid Schiff ◽  
Plaque Score ◽  
Dense Deposit ◽  
Sprague Dawley Rats ◽  
Electron Microscopy Analysis

Abstract Background and Aims IgA nephropathy (IgAN) is one of most common primary glomerulonephritis, whose pathogenesis had remained unclear. We had reported that Cnm-(+)Streptococcus mutans, a kinds of major dental caries bacteria. Cnm-(+)S. mutans had strong collagen binding ability, resulting in high pathogenicity. We reported that the prevalence of Cnm-(+)S. mutans in IgA nephropathy is significantly higher than that in control (Misaki-T et al, Clin Exp Nephrol 2015; 19:844-50), and that Cnm-(+)S. mutans in IgA nephropathy was associated with proteinuria (Misaki-T et al, Sci Rep 2016). We also reported C.rectus and S. mutans increased proteinuria synergistically (Misaki-T et al, Nephron, 2018). In this point, there is no direct evidence that Cnm-(+)S. mutans could induce IgA nephropathy. In this study, we evaluated the renal lesions in rats which had dental caries induced by Cnm-(+)S. mutans derived from IgA nephropathy patient to confirm the pathogenesis of IgA nephropathy like lesions induced by Cnm-(+)S mutans. Method Cmn-(+)S. mutans from saliva of IgA nephropathy patients was orally administrated into 4 weeks old male Sprague-Dawley rats. Addition of sugar to water had been kept during study period to develop dental carits. At week 34 after the infection, blood, urine, and kidney samples were evaluated. Kidney samples were stained by Periodic Acid-Schiff (PAS), IgA, C3. Historical evaluation by electron microscope analysis was also performed. Results At week 34, plaque score and dental caries score in infectious rats significantly elevated, compared with control rats (P&lt;0.001) (Figure 1). These findings suggested Cmn-(+)S. mutans from IgA nephropathy patients induced dental caries in rats. PAS staining revealed the significant mesangial proliferation. At week 34, the prevalence of IgA deposition in infections rats was higher than that in control rats (52.4% vs 4%), and the prevalence of C3 deposition in infectious rats was also higher than that in control rats (42% vs 11%) (Figure 2). Incidence of hematuria was also significantly higher in dental caries group than control. Electron microscopy analysis revealed high dense deposit in mesangial areas. Conclusion Cmn-(+)S. mutans from saliva of IgA nephropathy patients could induce IgA-dominant infection-associated glomerulonephritis, or IgA nephropathy.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

Effect of Green Tea and (-)-Epigallocatechin Gallate on the Pharmacokinetics of Rosuvastatin

2020 ◽  
Vol 21 (6) ◽  
pp. 471-478
Author(s):  
Shenjia Huang ◽  
Qingqing Xu ◽  
Linsheng Liu ◽  
Yicong Bian ◽  
Shichao Zhang ◽  
...  
Keyword(s):  
Green Tea ◽  
Cell Model ◽  
Hek293t Cell ◽  
Epigallocatechin Gallate ◽  
Drug Uptake ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Curve ◽  
Uptake And Transport

Background: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. Objective: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. Methods: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). Results: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). Conclusion: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.

Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy

2019 ◽  
Vol 18 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Antonio Ibarra ◽  
Erika Mendieta-Arbesú ◽  
Paola Suarez-Meade ◽  
Elisa García-Vences ◽  
Susana Martiñón ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Strategies ◽  
Chronic Phase ◽  
Motor Recovery ◽  
Neural Regeneration ◽  
Histological Evaluation ◽  
Control Group ◽  
Proof Of Concept ◽  
Sprague Dawley ◽  
Concept Study

Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.

EFFECT OF EXPERIMENTALLY INDUCED THYROIDITIS ON BIOSYNTHESIS OF THYROXINE IN RATS

1969 ◽  
Vol 62 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Colum A. Gorman ◽  
James W. Anderson ◽  
Eunice V. Flock ◽  
Charles A. Owen ◽  
Khalil G. Wakim
Keyword(s):  
Intravenous Administration ◽  
Hashimoto's Thyroiditis ◽  
Sprague Dawley ◽  
Thyroid Extract ◽  
Histologic Appearance ◽  
Gland Weight ◽  
Sprague Dawley Rats ◽  
Thyroid Glands ◽  
And Control ◽  
Experimentally Induced

ABSTRACT Thyroiditis was induced in Sprague-Dawley rats by repeated immunization with thyroid extract and Freund's adjuvant. Immunized and control animals were killed at intervals up to 6 hours after intravenous administration of 131I as iodide at 5, 8 and 10 weeks after the first injection. Radioiodinated compounds in the thyroid glands were identified chromatographically. Evidence of moderate thyroiditis was present (histologic appearance, gland weight, and protein-bound iodine-butanol-extractable iodine difference) but the rate of incorporation of radioiodide into thyroxine, the percentage of radioactivity in the gland as iodide, and the MIT/DIT ratio were not significantly different in immunized and control animals. The MIT/DIT ratio was found to vary with time after 131I administration in both immunized and control animals. These studies did not uncover a defect in organification of iodide in experimental thyroiditis similar to that described by others in humans with Hashimoto's thyroiditis.

scholarly journals Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

2021 ◽  
Vol 18 (4) ◽  
pp. 1645
Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Endurance Exercise ◽  
Field Tests ◽  
Treadmill Running ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

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