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

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

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

BACKGROUNDFluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP.

METHODSSeventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained.

RESULTSThe two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05).

CONCLUSIONSControlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.

Acute Disease ; Adult ; Female ; Fluid Therapy ; methods ; Humans ; Male ; Middle Aged ; Pancreatitis ; pathology ; therapy

PURPOSEIt is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs).

METHODSWe used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs.

RESULTSTotally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region.

CONCLUSIONThe altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.

Adult ; Brain Injuries, Traumatic ; cerebrospinal fluid ; genetics ; Computational Biology ; Humans ; Male ; MicroRNAs ; cerebrospinal fluid ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Unconscious (Psychology)

OBJECTIVETo investigate the effect of purple sweet potato on lipid metabolism and oxidative stress in hyperlipidemic rats.

METHODSForty male SD rats were randomly divided into 4 groups: normal control group, high-fat control group, high purple sweet potato groups, low purple sweet potato group. The rats were fed with different diets for 6w respectively.

RESULTSSerum TC, TG levels were significantly lower in high dosage group than in high-fat control group; while only serum TG was significantly lower in low dosage group than in high-fat control group, these changes started at the third week and lasted to the end of experiment. Serum LDL-C and AI levels were significantly lower in high and low dosage group than in high-fat control group, whereas, serum HDL-C was significantly higher than that in high-fat control group at w3 and lasted to the end of experiment. Serum SOD was significantly higher in high and low dosage group than in high-fat control group, whereas, serum MDA was significantly lower than that in high-fat control group at w6.

CONCLUSIONPurple sweet potato can decrease serum lipids and reduce hepatic oxidative stress in hyperlipidemic rats.

Animals ; Disease Models, Animal ; Hyperlipidemias ; metabolism ; Ipomoea batatas ; Lipid Metabolism ; Lipids ; blood ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley