OBJECTIVETo investigate the effects of prednisone on the expressions of FAK and Pyk2 in the kidneys of rats with adriamycin-induced nephritis.

METHODSThirty SD rats were randomized into normal control group, adriamycin-induced nephritic model group, and prednisone treatment group (n=10). Prednisone was administered at 10 mg/kg once daily in nephritic rats starting since the 7th day after adriamycin injection. Twenty-four-hour proteinuria was measured in the rats at different time points, and renal tissue histology was examined using transmission electron microscope. The expression levels of Pyk2, FAK and nephrin mRNA in the renal tissue were detected tested by RT-PCR, and the protein expressions of FAK, Pyk2, phosphorylated Pyk2 and phosphorylated FAK-Tyr397 were detected by Western blotting; immunohistochemistry was used for detecting nephrin protein expression in the kidney.

RESULTSCompared with the normal control group, the rats with adriamycin-induced nephritis showed significantly increased proteinuria (P<0.01), which was obviously lowered by prednisone treatment (P<0.01). Transmission electron microscopy revealed extensive fusion of the foot processes of the podocytes in the model group. Prednisone treatment promoted nephrin expression in the kidney (P<0.05). Compared with the control group, the model and prednisone treated groups showed significantly lowered nephrin mRNA expression (P<0.01) but increased FAK mRNA expression (P<0.01), but prednisone-treated group had a higher nephrin mRNA expression than the model group (P<0.05). The model group exhibited significantly increased expressions of FAK total and phosphorylated proteins, P-FAK/FAK, and P-Pyk2/Pyk2 (P<0.01), which were all lowered in the treatment group (P<0.01). Correlation analysis suggested that the expressions of FAK mRNA, FAK, pFAK, Pyk2 mRNA and pPyk2/Pyk2 were positively correlated with proteinuria (r=0.819, 0.750, 0.838, 0.762, 0.934, respectively, P<0.01).

CONCLUSIONSAdriamycin increases phosphorylated FAK and Pyk2 expressions to mediate kidney injury in rats. Prednisone inhibits Pyk2 and FAK activation, decreases proteinuria, and alleviates podocyte lesions to protect the glomerular filtration barrier.

Animals ; Doxorubicin ; Focal Adhesion Kinase 2 ; metabolism ; Kidney ; metabolism ; pathology ; Kidney Glomerulus ; Membrane Proteins ; metabolism ; Nephritis ; chemically induced ; drug therapy ; Podocytes ; pathology ; Prednisone ; pharmacology ; Proteinuria ; drug therapy ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis.

METHODSFemale albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected.

RESULTSKidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased.

CONCLUSIONSThe obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).

Animals ; Female ; Isoantibodies ; toxicity ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; metabolism ; Nephritis ; chemically induced ; surgery ; Rats

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.
Adult ; Anti-Inflammatory Agents/therapeutic use ; Antirheumatic Agents/therapeutic use ; Antithyroid Agents/*adverse effects/therapeutic use ; Blister/chemically induced/pathology ; Drug Therapy, Combination ; Female ; Graves Disease/diagnosis/drug therapy ; Humans ; Hydroxychloroquine/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Lupus Erythematosus, Systemic/chemically induced/*diagnosis/drug therapy ; Lupus Nephritis/diagnosis/drug therapy ; Methimazole/*adverse effects/therapeutic use ; Mycophenolic Acid/analogs & derivatives/therapeutic use ; Prednisolone/therapeutic use ; Skin/pathology

A 51-yr-old female was referred to our outpatient clinic for the evaluation of generalized edema. She had been diagnosed with idiopathic thrombocytopenic purpura (ITP). She had taken no medicine. Except for the ITP, she had no history of systemic disease. She was diagnosed with systemic lupus erythematosus. Immunosuppressions consisting of high-dose steroid were started. When preparing the patient for discharge, a generalized myoclonic seizure occurred at the 47th day of admission. At that time, the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome. Brain MRI and EEG showed brain atrophy without other lesion. The seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit. The patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone, insulin glargine and nateglinide. The patient remained asymptomatic under maintenance therapy with deflazacort and without insulin or medication for blood sugar control.
Edema ; Epilepsies, Myoclonic/complications/drug therapy ; Female ; Humans ; Hyperglycemia/*chemically induced ; Immunosuppression ; Insulin/therapeutic use ; Lupus Nephritis/*complications/drug therapy ; Middle Aged ; Prednisolone/administration & dosage/*adverse effects/therapeutic use ; Purpura, Thrombocytopenic, Idiopathic/complications/*drug therapy

Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.
Acute Kidney Injury ; chemically induced ; Animals ; Anti-Infective Agents ; adverse effects ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Antineoplastic Agents ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Nephritis, Interstitial ; chemically induced ; Renal Insufficiency ; chemically induced

OBJECTIVETo investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A (CsA)-induced nephropathy.

METHODSMale SD rats were fed on low salt diet (0.05% sodium) for 7 days and randomized into 4 groups for treatment with CsA, CsA+continuous low-dose uPA (U2), intermittent CsA+ high-dose uPA (U6) or vehicle (control group). In the former 3 groups, the rats were subjected to daily intragastric administration of CsA (25 mg/kg) for 4 weeks to establish CsA-induced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator (uPA) and transforming growth factor-beta1 (TGF-beta 1).

RESULTSFour weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine (Scr), blood urea nitrogen (BUN) and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-beta1 expression in the renal tissue, which were significantly reduced in U2 group (P<0.05) but not in U6 group (P>0.05).

CONCLUSIONContinuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number of macrophages and TGF-beta1 expression in the renal tissue.

Animals ; Chronic Disease ; Cyclosporine ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Macrophages ; drug effects ; metabolism ; pathology ; Male ; Nephritis ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; biosynthesis ; Urokinase-Type Plasminogen Activator ; therapeutic use

OBJECTIVETo study the urinary protein patterns of nephropathy mice induced by dextran and the effects of aquesous extract of Fructus Corni (AEFC) and Radix Astragali (AERA).

METHODNephropathy model was established by administrated with dextran to mice. Some of the dextran treated mice were given AERA (20 g x kg(-1) x d(-1)) as AERA group, other mice were given AEFC (10 g x kg(-1) x d(-1)) as AEFC group. Some of the dextran treated mice were given water as model group, some normal mice as normal control group. After a 12 weeks' treatment, 24 hour urine of four groups was collected, respectively. Each urinary sample was divided into two parts, one was non-concentrated urine sample, another was used as concentrated urine sample. Two kinds of urinary sample of four groups were analyzed with microfluidic chips on Agilent 2100 Bioanalyzer instrument.

RESULTEach group's urinary protein patterns were obtained, more than 20 proteins were were detected. Compared with normal group, about five kinds of protein were found in urinary sample of model group, among which M > 43 x 10(3) proteins were increased. Compared with model group, significant treated-related protein's kind and quantitative changes in AERA treated group and AEFC group were found. Urinary protein kinds were reduced, especially certain the proteins (M > 50 x 10(3)) were significantly decreased approach to normal patterns. Non-concentrated urine samples' protein pattern mainly included were proteins (M=29, 32, 43, 52, 68, 76 x 10(3) and concentrated urine samples mainly included the proteins (M=22, 24, 32, 46 x 10(3)).

CONCLUSIONAERA and AEFC could reduce the urinary protein and made protein pattern different, which showed that radix astragali and fructus corni could play an important role in protecting renal function of nephropathy mice and finding the target protein markers related to AERA and AEFC effects on nephropathy mice.

Animals ; Astragalus membranaceus ; chemistry ; Cornus ; chemistry ; Dextrans ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Kidney ; drug effects ; physiopathology ; Male ; Mice ; Microfluidic Analytical Techniques ; methods ; Nephritis ; chemically induced ; metabolism ; urine ; Plants, Medicinal ; chemistry ; Proteinuria ; urine ; Proteomics ; methods

OBJECTIVETo investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN).

METHODSTwenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan containing aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 microg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr).

RESULTSThe level of Scr an d serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were significantly increased compared with control (P < 0.05).

CONCLUSIONPGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.

Adult ; Alprostadil ; therapeutic use ; Aristolochic Acids ; adverse effects ; Creatinine ; blood ; Female ; Follow-Up Studies ; Hemoglobins ; metabolism ; Humans ; Kidney ; pathology ; Male ; Middle Aged ; Nephritis, Interstitial ; chemically induced ; drug therapy ; pathology

OBJECTIVEFollowing the former report, we continue to observe the chronic renal tubular-interstitial injury induced by Radix Aristolochiae Fangchi Extract(RAFE) in rats in order to understand whether RAFE in different doses causes the renal tubular-interstitial injury or not.

METHODRAFE at the dose of 25.0 mg x kg(-1) x d(-1), 120.0 mg kg(-1) x d(-1) and 200.0 mg x kg(-1) x d(-1) and aristolochic acid (AA, 10.0 mg x kg(-1) d(-1)) was interruptedly administrated by gastric tube for 22 w and 4 w durg withdrawal. Blood, urine and kidney were taken out respectively in 17 w, 22 w and 26 w to measure the indexes of renal function. The morphology of kidney was observed, and Masson staining of kidney were made respectively to compare RAFE groups with AA group.

RESULTPathological changes of renal tissue forms were as follows: All RAFE groups and AA group could develop the pathological process of renal tubular injury-chronic renal interstitial fibrosis. The pathologic changes of RAFE were similar with AA.

CONCLUSIONRAFE at all doses administrated interruptedly by gastric tube above 13 w caused chronic renal tubulo-interstitium fibrosis. The renal injury in functions and tissue forms in rats were similar with AA closely. The results showed that AA was the main toxic composition of RAFE.

Animals ; Aristolochia ; chemistry ; toxicity ; Aristolochic Acids ; isolation & purification ; toxicity ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; toxicity ; Female ; Fibrosis ; blood ; chemically induced ; pathology ; Kidney Tubules ; pathology ; Male ; Nephritis, Interstitial ; blood ; chemically induced ; pathology ; Plant Roots ; chemistry ; toxicity ; Plants, Medicinal ; chemistry ; toxicity ; Proteinuria ; chemically induced ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Aristolochic Acids ; adverse effects ; Chronic Disease ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; chemistry ; Female ; Humans ; Male ; Middle Aged ; Nephritis, Interstitial ; blood ; chemically induced ; pathology