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1.
Article in English | WPRIM | ID: wpr-827400

ABSTRACT

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.


Subject(s)
Humans , Collagen Type III , Genetics , Glomerular Mesangium , Kidney Diseases , Kidney Glomerulus , Proteinuria
2.
Rev. méd. Chile ; 143(2): 223-236, feb. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-742574

ABSTRACT

Prostate cancer represents the second cancer-related cause of death in North American and Chilean men. The main treatment for incurable stages of disease is surgical or pharmacological castration. However, with time and despite the addition of anti-androgens, the disease progresses to a clinical state that has been commonly referred to as “hormone refractory”. In recent years, the concept of hormone refractoriness has been challenged and replaced by “castration resistance”, acknowledging that further and optimal hormonal manipulation can be attained, beyond achieving testosterone levels at castration range. The purpose of this review is to summarize the recent therapeutic breakthroughs in the management of metastatic castrate resistant prostate cancer (mCRPC), with greater emphasis in the newer hormonal therapy agents such as Abiraterone and Enzalutamide. Future combination and sequential treatment strategies are contextualized in the current era of personalized cancer medicine and genomic characterization of prostate cancer.


Subject(s)
Animals , Rats , Angiotensin II/physiology , Fibronectins/biosynthesis , Mesangial Cells/metabolism , Plasminogen Activator Inhibitor 1/biosynthesis , Poly(ADP-ribose) Polymerases/physiology , Cells, Cultured , Fibronectins/genetics , Gene Expression Regulation, Enzymologic , Glomerular Mesangium/cytology , Glomerular Mesangium/metabolism , Glomerular Mesangium/pathology , Glomerulonephritis/genetics , Glomerulonephritis/metabolism , Glomerulonephritis/pathology , Mesangial Cells/enzymology , Mesangial Cells/pathology , Plasminogen Activator Inhibitor 1/genetics , Poly(ADP-ribose) Polymerases/biosynthesis , Poly(ADP-ribose) Polymerases/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology
3.
Article in Chinese | WPRIM | ID: wpr-346178

ABSTRACT

<p><b>OBJECTIVE</b>To study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS).</p><p><b>METHODS</b>One hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants.</p><p><b>RESULTS</b>The incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05).</p><p><b>CONCLUSIONS</b>Trace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Drug Resistance , Glomerular Mesangium , Allergy and Immunology , Glucocorticoids , Therapeutic Uses , Immunoglobulin M , Immunosuppressive Agents , Therapeutic Uses , Nephrosis, Lipoid , Drug Therapy , Allergy and Immunology , Retrospective Studies
4.
Chinese Journal of Pathology ; (12): 732-735, 2014.
Article in Chinese | WPRIM | ID: wpr-304403

ABSTRACT

<p><b>OBJECTIVE</b>To study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis.</p><p><b>METHODS</b>Five cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy.</p><p><b>RESULTS</b>The glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage.</p><p><b>CONCLUSIONS</b>Collagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.</p>


Subject(s)
Female , Humans , Basement Membrane , Metabolism , Biopsy , Collagen Type III , Genetics , Metabolism , Fluorescent Antibody Technique , Glomerular Mesangium , Metabolism , Immunohistochemistry , Kidney Diseases , Pathology , Kidney Glomerulus , Pathology , Microscopy, Electron , Prognosis , Proteinuria , Diagnosis
5.
Article in Chinese | WPRIM | ID: wpr-815455

ABSTRACT

IgA nephropathy (IgAN) is recognized as the most common immune complex related to the cause of glomerulonephritis worldwide. The disease is characterized by the predominant deposition of underglycosylated IgA1 in the mesangial area of glomeruli. Dysregulation of the immune system plays an important role in the pathogenesis of IgAN. Abnormalities restricted to T lymphocytes and/or B lymphocytes activation could be a critical causative factor in the over-production of underglycosylated IgA1.


Subject(s)
Humans , Antigen-Antibody Complex , B-Lymphocytes , Glomerular Mesangium , Glomerulonephritis, IGA , Pathology , Immunoglobulin A , Chemistry , T-Lymphocytes
6.
Chinese Medical Journal ; (24): 1755-1760, 2014.
Article in English | WPRIM | ID: wpr-248116

ABSTRACT

<p><b>BACKGROUND</b>The renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated clearly. We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines. The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).</p><p><b>METHODS</b>MCs were cultured in the medium with normal concentration glucose (group NG, 5.6 mmol/L), high concentration glucose (group HG, 25 mmol/L) and different concentrations of metformin (group M1, M2, M3). After 48-hour exposure, the supernatants and MCs were collected. The expression of NF-κB, MCP-1, ICAM-1, and TGF-β1 mRNA was analyzed by real time polymerase chain reaction. Western blotting was used to detect the expression of AMPK, phospho-Thr-172 AMPK (p-AMPK), NF-κB p65, MCP-1, ICAM-1, and TGF-β1 protein.</p><p><b>RESULTS</b>After stimulated by HG, the expression of NF-κB, MCP-1, ICAM-1, TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P < 0.05). Both genes and protein expression of NF-κB, MCP-1, ICAM-1, TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05). The expression of p-AMPK increased with the rising of metformin concentration, presenting the opposite trend, while the level of total-AMPK protein was unchanged with exposure to HG or metformin. Conlusion Metformin can suppress the expression of NF-κB, MCP-1, ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.</p>


Subject(s)
Animals , Rats , AMP-Activated Protein Kinases , Metabolism , Cells, Cultured , Glomerular Mesangium , Cell Biology , Glucose , Pharmacology , Mesangial Cells , Metabolism , Metformin , Pharmacology , NF-kappa B , Metabolism
7.
Article in Chinese | WPRIM | ID: wpr-306436

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of exendin-4 on the expression of monocyte chemoattractant protein-1 (MCP-1) and fibronectin (FN) in rat glomerular mesangial cells in vitro.</p><p><b>METHODS</b>Rat glomerular mesangial cells were divided into 5 groups, namely control group, tumor necrosis factor-α (TNF-α) group (10 ng/ml), TNF-α (10 ng/ml)+E1 (1 nmol/L exendin-4) group, TNF-α (10 ng/ml)+E5 (5 nmol/L exendin-4) group, and TNF-α (10 ng/ml)+E10 (10 nmol/L exendin-4) group. After cultured 24 h or 48 h, RNA were extracted to determine the expression of MCP-1 with real-time PCR, the supernatant were collected to determine the expression of MCP-1 and FN with ELISA.</p><p><b>RESULTS</b>Compared with control group, the cells treated with TNF-α for 24 h showed significantly increase the expression of MCP-1 and FN (P<0.01), exendin-4 significantly reduced the expression of MCP-1 and FN in TNF-α+E5 group and TNF-α+E10 group (P<0.05). After 48h incubation, the expression of MCP-1 and FN increased significantly in TNF-α group (P<0.01), which was lowered by exendin-4 in TNF-α+E1,TNF-α+E5 and TNF-α+E10 groups (P<0.05).</p><p><b>CONCLUSION</b>Exendin-4 has an intrinsic capability to concentration- and time-dependently inhibit TNF-α-induced expression of MCP-1 and FN in rat mesangial cells, suggesting the beneficial effect of exendin-4 in preventing and treating diabetic nephropathy.</p>


Subject(s)
Animals , Rats , Cells, Cultured , Chemokine CCL2 , Metabolism , Diabetic Nephropathies , Metabolism , Glomerular Mesangium , Cell Biology , Mesangial Cells , Metabolism , Peptides , Pharmacology , Tumor Necrosis Factor-alpha , Pharmacology , Venoms , Pharmacology
8.
Article in English | WPRIM | ID: wpr-267179

ABSTRACT

<p><b>OBJECTIVE</b>To study the effects and possible underlying mechanism of Qufeng Tongluo Prescription (, QFTL) on the regulation of mesangial cells (MCs) proliferation and apoptosis.</p><p><b>METHODS</b>The MCs used in this experiment have undergone five passages induced by lipopolysaccharide (LPS). Changes in the proliferation, apoptosis, cell cycle regulatory proteins and mRNA expression levels of the MCs after administration of Benazepril or QFTL were measured by methyl thiazolyl tetrazolium (MTT) reduction assay, flow cytometry, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.</p><p><b>RESULTS</b>The addition of Benazepril or QFTL serum inhibited LPS-induced MC proliferation after treatment for 24, 48 and 72 h, respectively (P<0.05 or P<0.01). Moreover, the inhibitory effect is more significant in the QFTL group at 48 h (P<0.05). Compared with the control group, LPS-induced cell proliferation decreased the number of cells in G1 phase versus cells in S and G2/M phases, while the addition of QFTL and Benazepril serum increased the ratio of cells at G1 phase (P<0.05 or P<0.01) to cells at S phase (P<0.01), implicating the cell cycle inhibition effect exerted by QFTL. LPS decreased the level of MC apoptosis, compared with the control group (P<0.05), while QFTL and Benazepril serum increased the level of MC apoptosis (P<0.01). Moreover, the difference between the QFTL group and the Benazepril group was statistically significant (P<0.01). Compared with the control group, the protein and mRNA expression levels of cylinD1, cyclin dependent kinase 2 (CDK2) and p21 were significantly increased (P<0.05 or P<0.01), p27 was decreased but with no statistical significance (P>0.05); After being treated with QFTL and Benazepril serum, the protein and mRNA expression levels of cylinD1, CDK2, p21 were decreased and p27 increased significantly (P<0.05 or P<0.01); Compared with the Benazepril group, QFTL show better effects on protein and mRNA expression levels of cylinD1, CDK2 (P<0.05 or P<0.01) and p21 protein expression (P<0.05).</p><p><b>CONCLUSION</b>QFTL inhibits MCs proliferation, promotes MCs apoptosis through an underlying mechanism of down-regulating the protein and mRNA expression levels of cylinD1, CDK2, p21 and up-regulation of the expression level of p27.</p>


Subject(s)
Animals , Male , Rats , Apoptosis , Base Sequence , Cell Cycle , Cell Cycle Proteins , Genetics , Metabolism , Cell Proliferation , DNA Primers , Drugs, Chinese Herbal , Pharmacology , Flow Cytometry , Glomerular Mesangium , Cell Biology , Metabolism , RNA, Messenger , Genetics , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
9.
Article in Chinese | WPRIM | ID: wpr-232694

ABSTRACT

<p><b>OBJECTIVE</b>To explore effects of beraprost sodium (BPS) on the metabolism of extracellular matrix (ECM) in rat mesangial cells cultured in the presence of high glucose and the possible mechanism.</p><p><b>METHODS</b>Rat mesangial cells were cultured in the presence of high glucose with or without BPS for 24 or 48 h. The levels of transforming growth factor β1 (TGFβ1), fibronectin (FN) and matrix metalloproteinase-2 (MMP-2) protein in the culture supernatants were measured by enzyme-linked immunosorbent assay, and photoshop-Smad3 was detected by Western blotting.</p><p><b>RESULTS</b>Compared with the cells in normal glucose, the cells cultured in the presence of high glucose for 24 and 48 h showed significantly increased TGFβ 1 and FN protein expression and lowered MMP-2 protein expression (P<0.01). Compared with the cells cultured in high glucose, BPS exposure at the concentration of 1, 2, and 5 µmol/L for 24 and 48 h significantly lowered TGFβ 1 protein expression (P<0.01), and at 2 and 5 µmol/L, BPS significantly decreased FN protein expression and increased MMP-2 protein expression in high glucose-induced cells (P<0.05). High glucose exposure also significantly increased the expression phosphorylated Smad3 (P<0.01), which was lowered by BPS treatment at 2 and 5 µmol/L (P<0.01).</p><p><b>CONCLUSION</b>BPS can regulate ECM metabolism in rat mesangial cells cultured in high glucose by inhibiting TGFβ 1/Smad3 pathway, suggesting the beneficial effects of BPS in preventing and treating diabetic nephropathy.</p>


Subject(s)
Animals , Rats , Cell Line , Cells, Cultured , Diabetic Nephropathies , Enzyme-Linked Immunosorbent Assay , Epoprostenol , Pharmacology , Extracellular Matrix , Metabolism , Fibronectins , Metabolism , Glomerular Mesangium , Cell Biology , Glucose , Matrix Metalloproteinase 2 , Metabolism , Mesangial Cells , Transforming Growth Factor beta1 , Metabolism
10.
Article in Chinese | WPRIM | ID: wpr-267574

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of rapamycin and 3-methyladenine on autophagy impairment, oxidative stress and premature senescence induced by high-glucose in primarily cultured rat mesangial cells.</p><p><b>METHODS</b>Rat glomerular mesangial cells (GMCs) were isolated and cultured in normal glucose, high glucose, high glucose with 3-methyladenine (3-MA), or high glucose with rapamycin. At 24 h, 72 h and 10 days of culture, the cells were examined for expression levels of autophagy markers LC3 and p62/SQSTM1, malondialdehyde (MDA) and protein carbonyl, β-galactosidase (SA-β-gal) activity and heterochromatin foci (SAHF).</p><p><b>RESULTS</b>Compared with those of normal cell culture, the cells exposed to high glucose for 72 h and 10 days showed down-regulated LC3 expression, up-regulated p62/SQSTM1 expression, elevated MDA and protein carbonyl levels, and increased SAHF formation and percentage of SA-β-gal-positive cells. These changes were reversed in GMCs exposed to high glucose and rapamycin for 72 h and 10 days, but exacerbated in cells incubated with 3-MA.</p><p><b>CONCLUSION</b>High glucose can suppress autophagic function of rat GMCs to result in oxidative damage and cell senescence. Rapamycin can attenuate autophagy impairment, oxidative damage and senescence induced by high glucose, whereas 3-MA can further aggravate high glucose-induced cell injuries in rat GMCs.</p>


Subject(s)
Animals , Male , Rats , Autophagy , Cells, Cultured , Cellular Senescence , Glomerular Mesangium , Cell Biology , Glucose , Mesangial Cells , Cell Biology , Metabolism , Oxidative Stress , Rats, Sprague-Dawley , Sirolimus , Pharmacology
11.
Chinese Journal of Pathology ; (12): 107-111, 2012.
Article in Chinese | WPRIM | ID: wpr-241984

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.</p><p><b>METHODS</b>A rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody.</p><p><b>RESULTS</b>The model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis.</p><p><b>CONCLUSION</b>FTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.</p>


Subject(s)
Animals , Male , Rats , Cell Proliferation , Connective Tissue Growth Factor , Genetics , Metabolism , Down-Regulation , Extracellular Matrix Proteins , Metabolism , Fingolimod Hydrochloride , Gene Expression , Glomerular Mesangium , Metabolism , Pathology , Glomerulonephritis, Membranoproliferative , Allergy and Immunology , Metabolism , Pathology , Immunosuppressive Agents , Pharmacology , Isoantibodies , Allergy and Immunology , Kidney Glomerulus , Metabolism , Pathology , Propylene Glycols , Pharmacology , Proteinuria , Urine , Rats, Wistar , Signal Transduction , Sphingosine , Pharmacology , Thy-1 Antigens , Allergy and Immunology , Transforming Growth Factor beta1 , Genetics , Metabolism
12.
Article in Chinese | WPRIM | ID: wpr-326660

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats.</p><p><b>METHODS</b>FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis.</p><p><b>RESULTS</b>At the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Shensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix.</p>


Subject(s)
Animals , Male , Rats , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Extracellular Matrix , Glomerular Mesangium , Glomerulosclerosis, Focal Segmental , Drug Therapy , Metabolism , Plasminogen Activator Inhibitor 1 , Metabolism , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Metabolism
13.
Rio de Janeiro; s.n; 2011. 139 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-689386

ABSTRACT

A insuficiência renal crônica (IRC) é caracterizada por alterações glomerulares secundárias aos mecanismos adaptativos ocasionados por perda de néfrons funcionantes. Alterações na hemodinâmica glomerular, proliferação celular, influxo de células inflamatórias, desequilíbrio na síntese de proteínas da matriz extracelular glomerular (MECG) e perda da seletividade de carga e/ou tamanho da membrana basal glomerular têm sido apontados como mecanismos envolvidos na expansão mesangial e conseqüente glomeruloesclerose. A participação dos hormônios sexuais na função renal e na evolução da insuficiência renal crônica tem sido sugerida. Os glicosaminoglicanos, especialmente o heparan sulfato (HS), têm sido associados à seletividade glomerular de macromoléculas. O remodelamento podocitário precoce e a proteinuria (PTN) se relacionam com a progressão da IRC. Neste contexto, o acúmulo de MECG, proliferação de miofibroblastos e PTN têm sido apontados como mediadores precoces que precedem as lesões glomerulares e túbulo-intersticiais. Neste estudo, avaliamos as alterações renais precoces (30 dias de IRC) gênero-dependentes em ratos (M) e ratas (F) Wistar submetidos à redução de 5/6 da massa renal (IRC) e à castração (c). Os animais foram divididos em 10 grupos: Controles (C) (CM, CF, CMc, CFc) e sham (CM sham, CF sham); e aqueles submetidos à nefrectomia 5/6: IRCM, IRCF, IRCMc, IRCFc. Os animais foram castrados com 5 semanas e submetidos à nefrectomia 5/6 com 7 semanas de idade. Resultados significativos mostraram que os machos com IRC apresentaram maior PTN, acompanhada de maior comprometimento mesangial, imunomarcação positiva para α-actina e maior concentração de heparan sulfato (HS) comparados com as fêmeas IRC (p<0,05). Estas alterações foram reduzidas nos machos castrados. A análise da morfologia podocitária mostrou raras regiões onde ocorreram alterações podocitárias nos grupos IRC. O conjunto de dados sugere que o hormônio masculino pode participar na manutenção...


Chronic renal failure (CRF) is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Glomerular hemodynamics alterations, cellular proliferation, inflammatory cells influx, imbalance between synthesis and degradation of the glomerular extracellular matrix (GECM) and loss of charge and/or size selectivity of the glomerular basal membrane are pointed as mechanisms leading to mesangial expansion and glomerulosclerosis. Additionally, participation of gender related hormones on renal function and progression of CRF have been suggested. We evaluated the effect of castration in renal alterations in males (M) and females (F) Wistar rats, after 30 days of 5/6 reduction of renal mass (CRF). The animals were castrated (c) at 5 weeks old and 7 weeks old 5/6 and sham nephrectomy were done. Groups: Control (C) CM, CM sham, CMc, CF, CF sham, CFc, CRFM, CRFMc, CRFF, CRFFc. CRFM group showed higher proteinuria followed by increased mesangial expansion and α-actin immunostaining. Concomitant higher concentration of heparan sulfate (HS) was also observed when compared to CRFF (p<0.05). These alterations were reduced in CRFMc group. Podocyte morphology analysis through electronic microscopy showed few disorders of foot processes in CRF groups Overall, CRFF group showed fewer alterations compared to males, and a reduction of HS was observed in association with PTN. Castration did not change this profile in female rats. Data suggest that male hormones may participate in the maintenance of the mesangial equilibrium and that PTN collaborated with the mesangial expansion process. Additionally, the higher concentration of HS in CRFM suggest that the remodeling process of the GECM, included a synthesis of de novo HS, that presented a functioning defect, compromising the glomerular filtration barrier and, ultimately corroborated with the loss of its selectivity and consequently with a higher PTN. This set of results leads us to conclude that PTN appears...


Subject(s)
Animals , Rats , Renal Insufficiency, Chronic , Kidney/physiopathology , Glomerular Mesangium , Glycosaminoglycans , Kidney Glomerulus/injuries , Myofibroblasts , Extracellular Matrix/metabolism , Nephrectomy , Proteinuria , Cell Proliferation , Rats, Wistar , Sex Factors
14.
Archives of Iranian Medicine. 2009; 12 (2): 179-181
in English | IMEMR | ID: emr-90956

ABSTRACT

Familial lecithin-cholesterol acyltransferase deficiency is an uncommon autosomal recessive disorder from a heritable defect in esterification of plasma cholesterol. In 1968, the disease was described by Gjone and Norum in Norway. Our case was a 38-year-old woman. Her disease was manifested by presence of lower extremities edema, proteinuria, corneal opacities, increased plasma cholesterol, and hemolytic anemia. Suspicion of the disease was based on renal biopsy, which revealed mesangial expansion and capillary wall widening with clusters of foamy cells in the mesangium. Immunofluorescence study was nonspecific, but specific findings of electron microscopy showed deposition of lipid in the glomerular basement membrane and mesangium. This is the first report of lecithin-cholesterol acyltransferase deficiency in Iran. The diagnosis was confirmed by a low high-density lipoprotein cholesterol concentration, decreased activity of lecithin-cholesterol acyltransferase in plasma, and positive familial history of the disease


Subject(s)
Humans , Female , Cholesterol , Esterification , Edema , Proteinuria , Corneal Opacity , Anemia, Hemolytic , Biopsy , Kidney , Fluorescent Antibody Technique , Microscopy, Electron , Glomerular Mesangium/pathology , Glomerular Basement Membrane/pathology , Lipoproteins, HDL
15.
Article in English | WPRIM | ID: wpr-98676

ABSTRACT

The aim of this study was to investigate whether green tea extract (GTE) has the protective effects on excess L-arginine induced toxicity in human mesangial cell. Human mesangial cells treated with L-arginine were cultured on Dulbecco's modified eagle medium in the presence and absence of inducible nitric oxide synthase (iNOS) inhibitor and GTE. The cell proliferation was determined by 3 (4,5-dimethylthiazol- 2-yl)-2, 5-diphengltetrqzolium bromide, a tetrazole assay. The iNOS mRNA and its protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. The concentration of nitric oxide (NO) was measured by NO enzyme-linced immuno sorbent assay kit. L-arginine significantly inhibited the proliferation of human mesangial cells, and induced the secretion of NO to the media. NO production by L-arginine was significantly suppressed by GTE and iNOS inhibitor (p<0.01). The expression level of iNOS mRNA and its protein that was significantly increased by L-arginine was decreased by iNOS inhibitor but not by GTE. GTE protected the mesangial cells from the NO-mediated cytotoxicity by scavenging the NO rather than by iNOS gene expression. Therefore, we conclude that GTE has some protective effect for renal cells against oxidative injury possibly by polyphenols contained in GTE.


Subject(s)
Humans , Antioxidants/metabolism , Arginine/metabolism , Cell Line , Cell Proliferation , Cell Survival , Flavonoids/metabolism , Glomerular Mesangium/cytology , Mesangial Cells/cytology , Nitric Oxide/chemistry , Nitric Oxide Synthase Type II/metabolism , Phenols/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tea
16.
Indian J Pathol Microbiol ; 2008 Jul-Sep; 51(3): 337-41
Article in English | IMSEAR | ID: sea-74686

ABSTRACT

Mesangioproliferative glomerulonephritis (MesPGN) consists 10% of the total renal biopsy of glomerulonephritis. Aim of the present study was to find out clinicopathological changes in MesPGN and differences between diffuse and focal variety. MesPGN was seen mostly in young adults with mean age of 28.63 years for males and 26.3 years for females. Male predominance was noted (M:F ratio - 1.4:1). About 70.83% patient presented with edema feet, followed by hypertension (29.19%), fever (16.66%), oliguria, nausea and vomiting (10.41%). Urine analysis in 50 patients revealed that 70% patients presented with nephrotic-range proteinuria, 36% patients with microscopic hematuria and 56% patients with leukocyturia. Statistically, no significant difference was found in clinical features of diffuse and focal MesPGN. Microscopic comparison between diffuse and focal variety showed that significant increase of focal glomerular basement membrane thickening, focal endothelial cell proliferation, focal smooth muscle hyperplasia, hyaline sclerosis and vasculitis was more common in diffuse variety. In focal variety, Capillary loop congestion, periglomerulitis, cloudy swelling and vacuolar degeneration in tubules were significantly more as compared to diffuse variety. Details of the clinical features, special laboratory tests and histological details revealed that diffuse variety had systemic diseases, which included Wegner's granulomatosis, microscopic polyangitis, Henoch's schonlein purpura, systemic lupus erythematosus (two cases) and one case each of Kimura's disease, pyelonephritis and tuberculosis. Only one case of focal MesPGN showed tuberculosis. Thus, our study concludes that MesPGN is an important cause of nephrotic syndrome among young adults. Secondly, search for some other diseases should be made and thirdly, if biopsy shows focal mesangial cell proliferations in minimal change glomerulonephritis (MCGN), it should be diagnosed as focal MesPGN rather than MCGN because these cases show recurrences.


Subject(s)
Adolescent , Adult , Age Factors , Child , Female , Glomerular Mesangium/pathology , Glomerulonephritis/epidemiology , Humans , Male , Middle Aged , Nephrotic Syndrome/epidemiology , Sex Factors , Urine/chemistry , Young Adult
17.
Arq. bras. endocrinol. metab ; 51(6): 901-912, ago. 2007. ilus
Article in Portuguese | LILACS | ID: lil-464281

ABSTRACT

O principal determinante da nefropatia diabética é a hiperglicemia, mas hipertensão e fatores genéticos também estão envolvidos. O glomérulo é o foco de lesão, onde proliferação celular mesangial e produção excessiva de matriz extracelular decorrem do aumento da glicose intracelular, por excesso de glicose extracelular e hiperexpressão de GLUT1. Seguem-se aumento do fluxo pela via dos polióis, estresse oxidativo intracelular, produção intracelular aumentada de produtos avançados da glicação não enzimática (AGEs), ativação da via da PKC, aumento da atividade da via das hexosaminas e ativação de TGF-beta1. Altas concentrações de glicose também aumentam angiotensina II (AII) nas células mesangiais por aumento intracelular da atividade da renina (ações intrácrinas, mediando efeitos proliferativos e inflamatórios diretamente). Portanto, glicose e AII exercem efeitos proliferativos celulares e de matriz extracelular nas células mesangiais, utilizando vias de transdução de sinais semelhantes, que levam a aumento de TGF-beta1. Nesse estudo são revisadas as vias que sinalizam os efeitos da glicose e AII nas células mesangiais em causar os eventos-chaves relacionados à gênese da glomerulopatia diabética. As alterações das vias de sinalização implicadas na glomerulopatia, aqui revisadas, suportam dados de estudos observacionais/ensaios clínicos, onde controle metabólico e anti-hipertensivo, especificamente com inibidores do sistema renina-angiotensina, têm-se mostrado importantes - e aditivos - na prevenção do início e progressão da nefropatia. Novas estratégias terapêuticas dirigidas aos eventos intracelulares descritos deverão futuramente promover benefício adicional.


The determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra- and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-beta1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-beta1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of diabetic nephropathy. New therapeutic strategies directed to the described intracellular events may give future additional benefits.


Subject(s)
Humans , Diabetic Nephropathies/etiology , Glomerular Mesangium , Hyperglycemia/complications , Angiotensin II/metabolism , Cell Proliferation/drug effects , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/physiopathology , Endothelium-Dependent Relaxing Factors/metabolism , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Glomerular Mesangium/metabolism , Glomerular Mesangium/pathology , Glomerular Mesangium/physiopathology , Glucose Transporter Type 1/metabolism , /metabolism , Hyperglycemia/metabolism , Hyperglycemia/physiopathology , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Renin-Angiotensin System/drug effects , Sclerosis/metabolism , Sclerosis/physiopathology , Transforming Growth Factor beta1/metabolism , Vasoconstrictor Agents/metabolism
18.
Indian J Pathol Microbiol ; 2007 Jul; 50(3): 511-4
Article in English | IMSEAR | ID: sea-74682

ABSTRACT

IgM nephropathy is characterised on light microscopy (LM) by variable features of normal glomeruli to mesangial hypercellularity; and immunofluorescence (IF) deposits of LgM. Our aim was to study the incidence of IgM nephropathy in adults with primary glomerular disease, with correlation to electron microscopy (EM) features. All adults presenting with proteinuria glomerular hematuria underwent renal biopsy. We excluded patients with systemic diseases and post-infectious glomerulonephritis. All the specimens were evaluated by LM, IF and EM. Our series had 146 cases. Of the 42 cases diagnosed on LM as minimal change disease, mesangial deposition of IgM was present in 11 cases. In addition there were seven cases of mesangioproliferative glomerulonephritis with mesangial IgM deposition. Thus, there were a total of 18 cases of IgM nephropathy (12.3%). Only six of these 18 cases showed typical electron dense deposits in the mesangium on EM. We feel that IgM nephropathy is probably a separate pathological entity, comprising 12.3% of all adults with primary chronic glomerulopathy. Electron dense deposits are seen in only about a third of these cases.


Subject(s)
Adolescent , Adult , Child , Female , Glomerular Mesangium/immunology , Glomerulonephritis/epidemiology , Humans , Immunoglobulin M/analysis , Incidence , Kidney/pathology , Male , Microscopy, Electron
19.
Braz. j. med. biol. res ; 40(6): 819-823, June 2007. graf, ilus
Article in English | LILACS | ID: lil-452692

ABSTRACT

Renal involvement in visceral leishmaniasis (VL) is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania) chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L.) chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L.) chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12) and from BALB/c mice (N = 24) injected intraperitoneally with 20 million L. (L.) chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L.) chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.


Subject(s)
Animals , Male , Mice , Disease Models, Animal , Glomerular Mesangium/pathology , Glomerulonephritis/pathology , Leishmania infantum , Leishmaniasis, Visceral/pathology , Glomerulonephritis/parasitology , Leishmaniasis, Visceral/complications , Mice, Inbred BALB C , Time Factors
20.
Chinese Journal of Pathology ; (12): 171-174, 2007.
Article in Chinese | WPRIM | ID: wpr-333938

ABSTRACT

<p><b>OBJECTIVE</b>To study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.</p><p><b>METHODS</b>The renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.</p><p><b>RESULTS</b>The mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.</p><p><b>CONCLUSION</b>Membranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Glomerular Basement Membrane , Allergy and Immunology , Pathology , Glomerular Mesangium , Allergy and Immunology , Pathology , Glomerulonephritis, IGA , Allergy and Immunology , Pathology , Glomerulonephritis, Membranous , Allergy and Immunology , Pathology , Immunoglobulin A , Metabolism , Immunoglobulin G , Metabolism , Kidney Glomerulus , Allergy and Immunology , Pathology , Retrospective Studies
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