To evaluate the efficacy and safety of compound Decumbent Corydalis Rhizome (DCR) in treating patients with knee osteoarthritis (OA). Totally 79 patients with knee osteoarthritis were selected from out-patient and inpatient departments of West China Hospital and randomly divided into the test group and the control group. The test group (n = 41) was given Compound DCR with the dosage of 1.8 g · d(-1), while the control group (n = 38) was administered with diclofenac sodium with the dosage of 75 mg · d(-1). After 12 weeks of treatment, the total efficacy rates based on patients/physicians evaluation for experimental and control groups were 68.29%, 63.41% and 71.05%, 63.16%, respectively, without significant difference between the two groups. Both of the two groups showed significant improvements in the main efficacy indexes (pain on walking 20 m) and minor indexes (tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short-Form Health Survey (SF-36 ), but without significant difference in efficacy between them. The incidence of related adverse events was 24.39% in the test group and 47.37% in the control group, respectively, with significant differences between the two groups (P < 0.05). In the controlled study, compound DCR is as efficient as diclofenac sodium but more tolerable, with a good clinical application prospect.
Adult ; Aged ; Corydalis ; chemistry ; Diclofenac ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Rhizome ; chemistry ; Treatment Outcome

A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.
Asialoglycoprotein Receptor ; metabolism ; Carcinoma, Hepatocellular ; pathology ; Coumarins ; Drug Delivery Systems ; Endocytosis ; Hep G2 Cells ; drug effects ; Humans ; Lactoferrin ; pharmacology ; Liposomes ; Liver Neoplasms ; pathology ; Particle Size ; Phosphatidylethanolamines ; Polyethylene Glycols ; Thiazoles

Aorta ; pathology ; surgery ; Aortopulmonary Septal Defect ; therapy ; Balloon Occlusion ; methods ; Catheterization, Swan-Ganz ; methods ; Child ; Female ; Humans ; Pulmonary Artery ; pathology ; surgery ; Treatment Outcome

AIMTo look for new heart or kidney imaging agents. Five new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetyl glycine) isovalericamide (MVG2), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] isovalericamide (MVGT), 2-N-(2'-s-tri-phenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] isovalericamide (MVGH), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] phenyl propamide (MPGT) and 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] phenylpropamide (MPGH) were synthesized as primitive materials to explore the synthetic methods of polypeptides.

METHODS AND RESULTSAll target chelators were identified on the basis of the spectroscopic data, such as IR, 1HNMR, 13CNMR and elementary analysis. Different active esters with mercaptoacetic acid as primitive materials were used to explore the biodistribution of Technetium-99m labelling chelators in mice. The chelators were labeled with Technetium-99m and further tested for the biological activity in mice. Values given in ID which is the percentage injected dose per organ was tested to explore new heart imaging agents. The ID was determined in vivo by biodistribution study. Tc-99m complexes 0.1 mL was injected into laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 minutes post-injection, rats were sacrificed by decapitation, bled from the neck and the organs were removed. The radioactivities in various organs were determined in an automatic twin crystal gamma counter. Five new target chelators were labeled with Technetium-99m in high yield (> 95%). The bio-distribution resulted in mice indicate that 99Tcm-MVG2 has high kidney uptake, good retention, quick blood clearance and high activity ratios of kidneys to other tissues. 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT have better heart accumulation, but shorter retention, slower blood clearance and lower activity ratios of kidneys to other tissues. They were mainly metabolized through liver and kidney.

CONCLUSION99Tcm-MVG2 will be a new potential renal function imaging agent and 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT will be new potential heart function imaging agents if their structure and activity relationships are further studied.

Animals ; Chelating Agents ; chemical synthesis ; pharmacokinetics ; Kidney ; metabolism ; Mice ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Technetium ; pharmacokinetics ; Tissue Distribution

AIMTo explore the synthetic methods of polypeptides containing new heart of kidney imaging agents.

METHODS AND RESULTSFive new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-2"-N",N"-diethylethylamine) phenylpropamide (MPNE), 2-N-(2'-s-triphenylmethyl acetyl) amino-(N'-2"-N",N"-dimethylethylamine) phenylpropamide (MPNM), 2-N-(2's-triphenylmethylacetyl) amino-3-methyl-(N'-2"-N",N"-dimethylethylamine) butyramide (MVNM), 2-N-(2'-s-triphenyl methylacetyl) amino-3-methyl-(N'-2"-N",N"-diethylethylamine) butyramide (MVNE), 2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetylglycine) phenylpropamide (MPG2)--were synthesized through five steps with mercaptoacetic acid as primitive materials, all of which were identified on the basis of spectroscopic data, such as IR, 1HNMR, MS or elementary analysis. The protection of the mercapto group was improved and the relatively new reaction condition of active ester with amino acid is developed. All the chelators were labeled with Technetium-99m and their biological activities in mice given in ID values was tested to explore new heart imaging agents, where ID is the percentage injected dose per organ. The ID was determined by in vivo biodistribution study. Tc-99m complexes 0.1 mL was injected into the laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 min post-injection, rats were sacrificed by decapitation, bled from the neck and dissected. Organs were removed at dissection. The radioactivities in various organs were determined in an automatic twin crystal gamma counter.

CONCLUSIONThe bio-distribution results in mice indicate that 99Tcm-MVNM have higher heart uptake (ID = 8.40%/g, 2 min post-injection) and quicker blood clearance (ID = 4.3%/g, 60 min post-injection); 99Tcm-MPNE and 99Tcm-MPNM also have fairly high heart uptake and quick blood clearance; 99Tcm-MPG2 has better kidney accumulation and higher activity ratios of kidney to blood (about 4).

Amides ; chemical synthesis ; pharmacokinetics ; Animals ; Kidney ; metabolism ; Mice ; Molecular Structure ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Peptides ; chemical synthesis ; chemistry ; pharmacokinetics ; Sulfides ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

OBJECTIVETo study the expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction (ED).

METHODSWe established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol (DES) and treated the control rats with normal saline (n = 10) or sterilized arachis oil (n = 10). After 8 weeks, we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin (PRL) and testosterone (T) to confirm the successful construction of the prolactinoma-induced ED model. Then we determined the expression of nNOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope.

RESULTSThe prolactinoma-induced ED model was successfully established in 15 rats. The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls ([46.7 ± 15.5] vs [11.7 ± 2.4] and [12.4 ± 2.3] mg, both P < 0.05). The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups ([1,744.9 ± 304.5] vs [11.5 ± 2.4] and [10.6 ± 1.9] ng/ml, both P < 0.0l; [1.54 ± 0.46] vs [3.11 ± 1.08] and [3.04 ± 1.11] ng/ml, both P < 0.05). The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls (16.7% vs 100% and 87.5%, both P < 0.05), and so was the expression of nNOS in the penile tissue (0.024 ± 0.011 vs 0.066 ± 0.019 and 0.058 ± 0.021, both P < 0.05). Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models.

CONCLUSIONThe ultrastructural changes of the penile cavernous tissue and the reduced expression of nNOS in penile tissue may be the most important mechanisms of prolactinoma-induced ED in rats.

Animals ; Apomorphine ; Carcinogens ; Diethylstilbestrol ; Erectile Dysfunction ; etiology ; Humans ; Male ; Myocytes, Smooth Muscle ; ultrastructure ; Nitric Oxide Synthase Type I ; metabolism ; Organ Size ; Penile Erection ; Penis ; enzymology ; ultrastructure ; Pituitary Neoplasms ; chemically induced ; complications ; Prolactin ; blood ; Prolactinoma ; chemically induced ; complications ; Rats ; Rats, Wistar ; Testosterone ; blood

Wuzhuyu Tang is a classical formula for treating migraine, but its' pharmacological ingredients is unclear yet. Present study employed the everted intestinal sac model to collect the absorption samples of 10 kinds of Wuzhuyu decoction, and then analyzed the contents of 9 ingredients in Wuzhuyu Tang and absorption samples quantitatively or semi-quantitatively by HPLC-DAD method. Reserpine was used to establish the mice model of migraine, and then the contents and activities of 5-hydroxytryptamine, noradrenaline, dopamine, nitric oxide and nitricoxide synthase in brain tissues and serums were determined respectively after oral administration of Wuzhuyu Tang. Using the partial least squares regression method to correlate the total absorption quantity of 9 ingredients and pharmacodynamics. The result shows that limocitrin-3-O-beta-D-glucoside, ginsenoside Rg1 and Rb1, rutaevine, limonin, evodiamine and rutaecarpine are the main ingredients influenced the effects in absorption samples in everted intestinal sacs, especially ginsenoside Rg1, rutaevine, evodiamine and rutaecarpine among them have obvious improving effects to most pharmacodynamics index, might be the pharmacological ingredients influenced the therapeutical effects of Wuzhuyu Tang treating migraine.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Migraine Disorders ; drug therapy ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).

METHODSFrom September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.

RESULTSResponse in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.

CONCLUSIONSThe combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Drug Administration Schedule ; Epirubicin ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives

BACKGROUNDProstate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.

METHODSThe different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.

RESULTSThe growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.

CONCLUSIONNPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.

Adult ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Cluster Analysis ; Flow Cytometry ; Humans ; Immunohistochemistry ; Male ; Prostate ; cytology ; Prostatic Neoplasms ; pathology ; Stromal Cells ; cytology ; metabolism ; Tumor Cells, Cultured

OBJECTIVETo investigate the safety and efficacy of rotational atherectomy followed by drug-eluting stent implantation for treating patients with heavily calcified coronary lesions.

METHODSFrom March 1, 2010 to September 1, 2012, 65 cases with 78 heavily calcified coronary lesions which were treated with rotational atherectomy followed by drug-eluting stent implantation in Peking University People's Hospital were included, and 36 cases also underwent intravascular ultrasound to guide the rotational atherectomy procedure and drug-eluting stent implantation.All patients were followed up in hospital and post discharge. Procedure parameters, complications and major adverse cardiovascular events (cardiac death, non-fatal myocardial infarction, percutaneous coronary intervention related myocardial infarction, target vessel revascularization, recurrent angina, intra-stent restenosis and stent thrombosis) were analyzed.

RESULTSDirect rotational atherectomy was performed in 64.6%(42/65) patients, rescued rotational atherectomy in 35.4%(23/65) patients, drug-eluting stents implantation was applied to all cases after rotational atherectomy. The immediate procedural success rate was 100% (78/78). The average burr/artery ratio was 0.50 ± 0.04, the average number of burr used per case was 1.15 ± 0.36. The average burr/artery ratio was 0.52 ± 0.03 and the average number of burr used per cases was 1.19 ± 0.40 in 36 cases guided with intravascular ultrasound. Five cases (7.7%) developed complications and were treated accordingly during procedure with satisfactory results. The incidence of major adverse cardiovascular events was 13.8% (9/65) during (17.6 ± 8.5) months follow-up.

CONCLUSIONRotational atherectomy followed by drug-eluting stent implantation is a safe and efficient technique for treating heavily calcified coronary lesions.

Aged ; Atherectomy, Coronary ; methods ; Coronary Artery Disease ; surgery ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome