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 investigate the effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with chronic cyclosporine A nephropathy.

METHODSMale Sprague-Dawley rats on low-salt diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000 U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy model. Masson staining was used to examine fibrin deposition. Western blotting and reversal transcription polymerase chain reaction were employed to evaluate urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene expressions, respectively.

RESULTSCsA can increase fibrin deposition and the expression of TGF-beta1 in the renal tissue, which were significantly reduced after uPA treatment (P<0.05).

CONCLUSIONContinuous low-dose uPA treatment can reduce renal interstitial fibrosis in rats possibly in association with its inhibitory effect on TGF-beta1 expression.

Animals ; Cyclosporine ; Fibrosis ; prevention & control ; Kidney ; pathology ; Kidney Diseases ; chemically induced ; drug therapy ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Urokinase-Type Plasminogen Activator ; pharmacology ; therapeutic use

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion: The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.
Anemia, Hemolytic, Autoimmune ; Antibodies, Monoclonal, Murine-Derived ; Humans ; Retrospective Studies ; Rituximab ; Splenectomy

Aged ; Creatinine ; blood ; Crystallization ; Embolism, Cholesterol ; blood ; diagnosis ; drug therapy ; Humans ; Kidney ; metabolism ; pathology ; Male

OBJECTIVETo study the effect of Shexiang Baoxin pill (SBP) on the vascular endothelial function in patients with diabetes mellitus type 2 (DM2) complicated with angina pectoris.

METHODSTwo weeks after runin, according to the randomizing table, 111 patients were divided into two groups, the XBP group (56 patients) and the control group (55 patients, treated with delayed-released isosorbide mononitrate, DRIM), they were treated for 6 months. In the treatment period, the episodes of angina attack and condition of rescue medication were recorded in the daily card, and brachial arterial changes of endothelium-dependent relaxing function before and after treatment were measured by B-ultrasonography.

RESULTSComparison between the two groups in episodes of angina attack and rescue medication were insignificantly different. In the control group, the basal value of brachial arterial inner diameter before and after treatment was 3.68 +/- 0.56 mm and 3.70 +/- 0.58 mm respectively, those before and after responsive congestion was 5.44 +/- 0.81% vs 5.68 +/- 0.83%, and those before and after taking nitroglycerin was 19.8 +/- 4.9% vs 20. +/- 5.2%, all showed insignificant difference (P > 0.05). In the SBP group, the corresponding basal value was 3.73 +/- 0.62 mm vs 3.71 +/- 0.59 mm, and those after taking nitroglycerin 18.8 +/- 4.5 % vs 19.2 +/- 5.8%, also showed insignificant difference, but those before and after responsive congestion (5.69 +/- 0.79 % vs 9.56 +/- 3.82 %) did show significant difference (P < 0.01).

CONCLUSIONXBP could improve the vascular endothelial function in patients with DM2 complicated with angina pectoris.

Aged ; Angina Pectoris ; complications ; drug therapy ; Angioplasty, Balloon, Coronary ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy

OBJECTIVETo investigate the role of integrin-linked kinase (ILK) on renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on LIK expression in mice with obstructive nephropathy.

METHODSNormal male mice were randomly divided into sham-operated group (n=20), unilateral ureteral obstruction (UUO) group (n=28), and UUO with urokinase treatment group (uPA, n=28), and UUO was induced surgically in the latter two groups. The mice were sacrificed on days l, 3, 7 and 14 after the surgery, and renal interstitial fibrosis (RIF) was graded according to the result of Masson staining. The expression of ILK in the renal tissues of the rats was examined by immunofluorescence staining and Western blotting, and the expression of E-cadherin was detected by immunohistochemistry. RT-PCR was used to examine the mRNA expressions of ILK, E-cadherin and alpha-smooth muscle actin (alpha-SMA).

RESULTSThe expressions of ILK mRNA and protein were significantly increased in UUO group, but significantly decreased by treatment with uPA (P<0.05). The expression of alpha-SMA mRNA level was significantly increased, while E-cadherin decreased in mice with UUO on day 3 after the surgery. Treatment with uPA significantly inhibited such effects (P<0.05).

CONCLUSIONILK plays an important role in renal interstitial fibrosis by mediating epithelial-mesenchymal transition. Urokinase attenuates renal tubulointerstitial fibrosis in mice with UUO possibly by inhibiting ILK expression and preventing tubular epithelial-mesenchymal transition.

Animals ; Cell Transdifferentiation ; drug effects ; Epithelial Cells ; metabolism ; pathology ; Fibrosis ; Kidney Tubules ; metabolism ; pathology ; Male ; Mesoderm ; pathology ; Mice ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; physiology ; Ureteral Obstruction ; genetics ; metabolism ; pathology ; Urokinase-Type Plasminogen Activator ; pharmacology

OBJECTIVETo identify the uptake and biological distribution of technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99mTc-GSA) in three mouse models with different degrees of hepatic injuries.

METHODSThree mouse models including hepatic fibrosis, hepatic cholestasis, and liver cancer were established. Hepatic fibrosis model was established by intraperitoneal injection of carbon tetrachloride, 0.4 ml 10%, every 48 hours for 48 days. Hepatic cholestasis model was set up by ligature of the common bile duct for 72 hours, and liver cancer model by implantation of H22 tumor cells underneath liver capsule for 10 days. On measurement, each mouse in different models and normal controls was injected with 0.1 ml (0.37 MBq)99mTc-GSA (2 microg) into vena caudalis, and 5 minutes later sacrificed by decapitation. Important organs and tissues including liver, heart, lungs, kidney, spleen, stomach, blood, bones, muscles, and intestines were taken and their different radio countings were measured. The hepatic injuries were evaluated with serum and pathological examinations.

RESULTS99mTc-GSA was concentrated in the liver in all three models and the control mice ( >40% ID x g(-1)). Compared with the control mice (90.05 +/- 10.55)% ID x g(-1), the density of 99mTc-GSA was significantly lower in the models with hepatic injuries (P < 0.001). The liver function test indicated that the injury in hepatic fibrosis model was less serious than those in the other two models. However, the concentration of 99mTc-GSA in hepatic fibrosis model [(72.20 +/- 2.13)% ID x g(-1)] was significantly higher than those in the models with cholestasis [(56.72 +/- 5.92)% ID x g(-1)] and liver cancer [(42.80 +/- 6.05)% ID x g(-1)] (P < 0.001).

CONCLUSIONS99mTc-GSA may well concentrate in liver and its concentration degree is adversely correlated with hepatic injuries. Therefore 99mTc-GSA may be clinically used as liver imaging agent. When combined with three-dimensional scanning technique, it may facilitate constructing a new three-dimensional imaging method to demonstrate the function of designed liver segments.

Animals ; Disease Models, Animal ; Female ; Humans ; Liver ; diagnostic imaging ; drug effects ; injuries ; Liver Diseases ; diagnosis ; diagnostic imaging ; Mice ; Mice, Inbred BALB C ; Radiography ; Radionuclide Imaging ; Radiopharmaceuticals ; administration & dosage ; pharmacokinetics ; Random Allocation ; Technetium Tc 99m Aggregated Albumin ; administration & dosage ; pharmacokinetics ; Technetium Tc 99m Pentetate ; administration & dosage ; pharmacokinetics

BACKGROUNDEmergence agitation is a common problem in pediatric anesthesia, especially after sevoflurane induction and maintenance anesthesia. The purpose of this study was to investigate the effect of sufentanil to reduce emergence agitation after sevoflurane anesthesia in children undergoing adenotonsillectomy compared with fentanyl.

METHODSOne hundred and five children, aged 3 - 11 years, were randomly allocated to receive normal saline (control group), sufentanil 0.2 µg/kg (S2) or fentanyl 2 µg/kg (F2) 1 minute after loss of the eyelash reflex. Anesthesia was induced and maintained with sevoflurane. Time to tracheal extubation, recovery time, Paediatric Anesthesia Emergence Delirium (PAED) scale, and emergence behavior were assessed.

RESULTSThe incidence of severe agitation was significantly lower in S2 and F2 groups vs. the control group, 4/32 and 15/34 vs. 24/34 respectively, (P = 0.002, 0.009, respectively). PAED scales were significantly different among three groups (P = 0.007), and lower in the S2 and F2 groups than in the control group (P = 0.007 and P = 0.025, respectively). And the incidence of severe agitation and the PAED scale score was significantly different between the S2 and F2 groups (P = 0.007, P = 0.019, respectively). Time to tracheal extubation and recovery time were similar in all three groups.

CONCLUSIONSAdministration of sufentanil at 0.2 µg/kg after induction of anesthesia reduced emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl. This was without delaying the recovery time or causing significant hypotension.

Adenoidectomy ; methods ; Anesthesia ; methods ; Child ; Child, Preschool ; Female ; Fentanyl ; therapeutic use ; Humans ; Male ; Methyl Ethers ; adverse effects ; therapeutic use ; Prospective Studies ; Psychomotor Agitation ; drug therapy ; etiology ; Sufentanil ; therapeutic use

PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate ; Blotting, Western ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Cell Movement ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hepatocyte Growth Factor ; Lung Neoplasms ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Protein-Tyrosine Kinases