OBJECTIVETo observe the intervention of Shenkangling Decoction (SD) on the renal injury of primary nephrotic syndrome (PNS) children patients of Shen deficiency blood stasis syndrome (SDBSS) and to explore its mechanism.

METHODSTotally 65 PNS children patients were randomly assigned to the combined group (33 cases, treated by SD +Western medicine) and the Western medicine group (32 cases, treated by Western medicine). Meanwhile, 30 healthy children were recruited as the healthy control group from the medical examination center. Those in the Western medicine group were treated with prednisone (5 mg per tablet) at the daily dose of 1.5 -2.0 mg/kg till two weeks after their urine protein turned to negative. Then the dosage was reduced once daily per every other day. The therapeutic course lasted for more than 1 year. For those with no effect of prednisone or partial effect, cyclophosphamide intravenous pulse therapy was additionally applied for 2 successive days per week, a total of 6 times, or they took cyclosporine A. Patients in the combined group additionally took SD while starting treatment of prednisone. SD was decocted in water for oral dose, once daily, taken in two portions until 2 months after prednisone was discontinued. Efficacy was evaluated based on serum levels of chemotactic factor CXCL16, disintegrin metalloproteinase 10 ( ADAM10 ), disintegrin metalloproteinase 17 (ADAM17), albumin (ALB), total cholesterol (TC), and 24-h urine protein excretion (UPE) detected by ELISA before and after treatment.

RESULTSCompared with before treatment in the same group, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE were significantly lower in the two treatment groups (P <0. 01). Compared with the control group, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE significantly increased, and the serum ALB level decreased in the two treatment groups (P <0.01). Compared with the Western medicine group at the same time point, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE significantly decreased in the combined group. The 1 -year recurrence rate and the recurrence times decreased in the combined group (P <0.01). The complete remission rate increased in the combined group (P <0.01).

CONCLUSIONSD could effectively improve the clinical prognosis of PNS children patients possibly by reducing the release of inflammatory mediators such as CXCL16, ADAM10, and ADAM17, decreasing UPE and the TC level, and elevating the serum ALB level.

Child ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Nephrotic Syndrome ; drug therapy ; Prednisone ; Syndrome

OBJECTIVETo observe the effect of Fengshi No. 1 (FS1) in treating patients with active stage of rheumatoid arthritis (RA).

METHODSPatients with RA were randomly divided into two groups, the 40 patients in the treated group were treated with combined therapy of methotrexate (MTX), sulfasalazine (SSZ) and FS1, and the 20 in the control groups were treated with MTX and SSZ alone.

RESULTSIn the treated group, the total effective rate was 97.5%, the clinical controlled and markedly effective rate 95.0% and the occurrence rate of side-toxic reaction 10.0%, as compared with those in the control group, 60.0%, 20.0% and 45.0% respectively, the difference was significant (chi 2 = 11.91, 32.23 and 7.67 respectively, all P < 0.01). The effect in the treated group was superior to that in the control group in abating joint swelling and pain, improving function of joint, reducing immune indices and ameliorating iconographic features (P < 0.01 or P < 0.05).

CONCLUSIONFS1 not only has the effects of anti-inflammation, analgesis, regulating immune reaction, but also could retard the occurring of bone destruction, reduce the toxic-side effects of MTX and SSZ.

Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Phytotherapy ; Sulfasalazine ; therapeutic use

Objective To explore the efficacy and tolerability of sorafenib in combination with interferon-α-2b for Chinese patients with metastatic renal cell carcinoma. Methods Seventeen pa-tients with unreseetable metastatic renal cell carcinoma were enrolled and received sorafenib in combi-nation with interferon-α-2b. Sorafenib was continuously given at the dose of 400 mg twice per day, in-terferon-α-2b 300 MIU subscutaneously once per day for 5 d each week, until disease progression or intolerable toxieities occurred. Tumor responses were evaluated every two months by response evalua-tion criteria in solid tumor. Results The median treatment duration was 120(51-442)d. All 17 pa-tients were evaluable for efficacy and safety. Five patients achieved partial responses (PR), 1 uncon-firmed PR,9 stable diseases. Two patients had progressed diseases. The overall response rate was 29%(5/17)with the disease control rate of 88%(15/17). Due to short-time follow up, the median progression free and overall survival time were not yet available. The common side effects included: fever 82%(14/17), diarrhea 82%(14/17), hand-foot syndrome 71%(12/17), asthenia 65%(11/17), rash 53%(9/17), alopecia 41% (7/17), mucosities 41% (7/17), hypertension 29% (5/17), anorexia 24% (4/17), hoarseness 24% (4/17), myalgia 24 % (4/17), nausea/vomiting 12 % (2/17) and headach/ dizzle 12%(2/17). Eleven (65%) out of 17 patients developed neutropenia, 5(29%) thrombocytope-nia and 5 (29%)anemia. Four(24%) out of 17 patients had abnormally elevated ALT/AST. Conclu-sion Sorafenib in combination with interferon-α-2b for metastatic renal cell carcinoma improves re-sponse rate with manageable toxicity.

Objective To research the significanec of genes bel-2 and bax in chondrocyte apoptosis in experimental osteoarthritis in rabbits.Method Twelve New Zealand rabbits divided into two groups at random:model group and control group.Model group with osteoarthritis was duplicated by immobilizing with gypsum at extension position in right hind limb of rabbits.Rabbits of model group were executed after 6 weeks and chondrocytes were taken.Positive expression rate of bcl-2 and bax mRNA was measured by immunohisto- chemistry and Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL).Results Positive expression rate of mRNA in bel-2 and bax of model group was obviously more than control group(P＜0.05).According to immunohistochemistry,and grey grade of positive expression of protein in bcl-2 and bax of chondrocytes in model group was lower and positive expression rate was gigher compared with control group (P＜0.05,P＜0.01).bcl-2 and bax of model group were lower than control group(P＜0.05).Conclusion Genes bcl-2 and bax participate and thus accelerate chondrocyte apoptosis of osteoarthritis together.

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Design ; Humans ; Organophosphonates ; chemical synthesis ; pharmacology

To investigate the inhibitory effect of Pluronic on P-glycoprotein (P-gp) drug efflux pump, Caco-2 cells and animal models were established to study the influence of Pluronic on celiprolol transport across Caco-2 cell monolayer and intestinal mucous membrane with verapamil set as a positive control. Drug concentration was measured by HPLC and the apparent permeability coefficient (P(app)), absorption rate constant (k(a)) and the effective permeability coefficient (P(eff)) were calculated. P(app) of basolateral to apical side and apical to basolateral side was (2.10 +/- 0.13) x 10(-6) and (0.333 +/- 0.018) x 10(-6) cm x s(-1), respectively. Transports of celiprolol across Caco-2 cell monolayer were influenced by both verapamil and Pluronic. The absorption constants (k(a)) of celiprolol at duodenum, jejunum, ileum, and colon were (0.09 +/- 0.03), (0.14 +/- 0.04), (0.11 +/- 0.03) and (0.05 +/- 0.02) h(-1), k(a) of celiprolol in verapamil group were (0.14 +/- 0.03), (0.24 +/- 0.02), (0.25 +/- 0.03) and (0.23 +/- 0.02) h(-1), and k(a) of celiprolol in Pluronic group were (0.13 +/- 0.02), (0.22 +/- 0.02), (0.22 +/- 0.03) and (0.20 +/- 0.03) h(-1), respectively. Pluronic showed significant effect on inhibiting P-gp of Caco-2 cell and intestinal mucosa in rats.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Biological Transport ; drug effects ; Caco-2 Cells ; Celiprolol ; pharmacokinetics ; Excipients ; Humans ; Intestinal Absorption ; drug effects ; Intestinal Mucosa ; metabolism ; Jejunum ; metabolism ; Male ; Permeability ; Poloxamer ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

P-glycoprotein (P-gp) located in the apicalmembranes of intestinal absorptive cells is an energy-dependent efflux pump which can reduce the bioavailability of a wide range of substrate drugs. There is increasingly interest in enhancing the bioavailability of these molecules by inhibiting intestinal P-gp. A classification of excipient inhibitors of intestinal P-gp nonionic surfactants, poly (ethylene glycol), derivates of beta-cyclodextrin and thiolated chitosan will be presented and then the inhibition mechanism will be discussed. Compared with traditional P-gp inhibitor, excipient inhibitors appear to have minimal nonspecific pharmacological activity, thus potential side effects can be mostly avoided. These excipient inhibitors, which hold the promise of replacing the traditional ones, will be extensively employed to significantly improve the intestinal absorption of poorly soluble and absorbed drugs as a result of P-gp inhibition, and thus to enhance the bioavailability of these drugs. However, the further studies of both the mechanism and clinical application are urgently needed.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; pharmacokinetics ; Animals ; Biological Availability ; Chitin ; analogs & derivatives ; pharmacology ; Excipients ; pharmacology ; Glycerol ; analogs & derivatives ; pharmacology ; Humans ; Intestinal Absorption ; drug effects ; Polyethylene Glycols ; pharmacology ; Surface-Active Agents ; pharmacology ; beta-Cyclodextrins ; pharmacology

Our previous finding showed that down-regulation of CD3ζ gene was detected in patients with chronic myeloid leukemia (CML). In order to further elucidate the feature of T cell immune status in the signal transduction in CML patients, the expression patterns of all 4 CD3 genes were characterized in peripheral blood of patients, the expression levels of CD3γ, δ, ε and ζ chain genes were detected by real time qPCR with SYBR Green I staining in peripheral blood mononuclear cells (PBMNCs) from 17 cases of de novo CML patients in chronic phase and 17 cases of healthy individuals, the ß₂-microglobulin gene was used as an internal reference, and the mRNA expression level of each CD3 gene was evaluated by the 2(-ΔCt) x 100% method. The results showed that the median expression levels of CD3γ, δ and ε genes (2.344%, 0.515% and 3.516%) in CML patients were not significantly different from healthy individuals (p = 0.072, p = 0.190, p = 0.615, respectively), while the expression level of CD3ζ gene in PBMNCs from CML patients (0.395%) was lower than that from healthy individuals (1.538%) (p < 0.001). The expression patterns of 4 CD3 genes in proper order were CD3ε > CD3γ > CD3δ > CD3ζ in CML group, in contrast, the expression patterns were presented as CD3γ > CD3ε > CD3ζ > CD3δ in healthy group. It is concluded that the present study characterized the expression pattern of CD3γ, δ, ε and ζ chain genes in CML patients, lower expression of CD3ζ is the feature of TCR signal transduction immunodeficiency and the expression patterns of 4 CD3 genes are changed in CML patients.
Adolescent ; Adult ; Aged ; CD3 Complex ; genetics ; metabolism ; Case-Control Studies ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; genetics ; Lymphocyte Count ; Male ; Middle Aged ; Signal Transduction ; T-Lymphocytes ; metabolism ; Young Adult

OBJECTIVETo investigate the effect of chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 on liver metastasis of human colon cancer.

METHODSExpression of CXCR4 in different colon cancer cell lines and SDF-1 in different tissues were detected by using Western-blot technique. Effect of SDF-1 and anti-CXCR4 monoclonal antibody (McAb) on proliferation and migration of HT-29 cells were measured using MTT methods. Model mimicking liver metastasis of human colon cancer was established by injecting HT-29 cells intrasplenically into BALB/C nude mice. Mice were randomly divided into AMD3100 treated group and control group. Liver metastatic rate and tumor foci were measured 7 weeks after.

RESULTSHT-29 cells expressed higher level of CXCR4 protein, and liver tissue expressed higher level of SDF-1 protein. Compared with the control, SDF-1 could significantly induced the proliferation and migration of the HT-29 cells, and anti-CXCR4 McAb could inhibited both functions of SDF-1. The liver metastasis rate in the control group was 100%, and it was 40% in the AMD3100 treating group (P < 0.05). The mean liver metastasis number also significantly decreased by AMD3100 (7.8 +/- 2.6 vs 22.4 +/- 8.6, P < 0.05).

CONCLUSIONSSDF-1/CXCR4 biological axis play an important role in liver metastasis of human colon cancer. Arrest of CXCR4 can inhibit liver metastasis of colon cancer through blocking cell proliferation and migration induced by SDF-1.

Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12 ; metabolism ; physiology ; Colonic Neoplasms ; metabolism ; pathology ; HT29 Cells ; Humans ; Liver Neoplasms, Experimental ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptors, CXCR4 ; metabolism ; physiology ; Xenograft Model Antitumor Assays

PURPOSE: Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. MATERIALS AND METHODS: CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. RESULTS: Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). CONCLUSION: Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP.
Animals ; Antioxidants/pharmacology ; Ascorbic Acid/*pharmacology ; Hyaluronic Acid/blood ; Laminin/blood ; Male ; Organotin Compounds ; Oxidative Stress/drug effects ; Pancreas/*drug effects/pathology ; Pancreatic Diseases/blood/chemically induced/*prevention & control ; Rats ; Rats, Sprague-Dawley