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

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

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

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

OBJECTIVETo characterize age-related cellular phenotype alterations and growth rates of human prostatic stromal cell cultures from the normal prostatic peripheral zone of young donors (PZ-young) and old donors (PZ-old).

METHODSWe isolated stromal cells from 10 donors of different ages, assessed the cellular phenotypes by immunocytostaining for prolyl-4-hydroxylase, alpha-smooth muscle actin (alpha-SMA) and desmin, and analysed the ultrastructure by transmission electron microscopy (TEM). The proliferation and apoptosis of the cells were determined by Cell Counting Kit-8 assay and flow cytometry, respectively.

RESULTSAll the stromal cells were positive for prolyl-4-hydroxylase regardless of the donors' age, while alpha-SMA and desmin positive cells increased with their age. The positive expressions of alpha-SMA and desmin were (2.56 +/- 1.81)% and (0.89 +/- 0.93)% in PZ-young, and (38.89 +/- 11.22)% and (14.89 +/- 5.97)% in PZ-old (P < 0.01). The alpha-SMA- and/or desmin-positive stromal cells were morphologically large, flat and polygonal. Ultrastructural analysis showed that the cell cultures from PZ-old were richer in rough endoplasmic reticulum and golgi complexes. The stromal cells of PZ-old had a lower growth rate than that of PZ-young (P < 0.01), but there was no significant difference in the apoptosis rate between the two groups.

CONCLUSIONCellular phenotypes of human prostate stromal cell cultures change with the increase of age from predominantly typical fibroblasts to a mixture of fibroblasts and myofibroblasts, which might responsible for the high incidence of prostate cancer in elderly men.

Adult ; Age Factors ; Aged ; Cell Proliferation ; Cells, Cultured ; Humans ; Male ; Middle Aged ; Phenotype ; Prostate ; cytology ; pathology ; Stromal Cells ; cytology ; pathology ; Urinary Bladder Neoplasms ; pathology ; Young Adult

OBJECTIVETo investigate the expression of multidrug resistance (MDR) gene-associated proteins (MRP) in gastric carcinoma, and their effects on the postoperative adjuvant chemotherapy and the prognosis of patients.

METHODSThe expressions of ToPo II, MRP, GST-pi in 99 patients with gastric carcinoma were detected by immunohistochemistry. The expression and its relationship to the pathological data were analyzed. The positive expression of MRP and GST-pi, and the negative expression of ToPo II were considered as risk factors. Patients were divided into two groups: a high risk drug-resistant group (2-3 risk factors) and the low risk drug-resistant group (0-1 risk factors). Postoperative recurrence, survival rate, and efficacy of adjuvant chemotherapy were compared between two groups.

RESULTSThe positive rate of ToPo II was 74.7%, and the expression was associated with types and differentiation of the tumor. The positive rate of GST-pi was 49.5%, and the expression was related to the gender and the differentiation. The positive rate of MRP was 40.4%, and there was no relationship between the MRP expression and the pathological finding. There were no significant differences in the recurrence, time to recurrence, and the 5-year survival rate between the positive and negative group of the three proteins (P>0.05). Recurrence was found in 25 cases(55.6%) in the high risk drug-resistant group and the mean time to recurrence was (15.2+/-8.1) months. The time to recurrence was shorter in the low risk drug-resistant group [(21.3+/-11.1) months, P<0.05] , but there was no significant difference in the recurrence rate between two groups (P>0.05). The 5-year survival rate of the high risk drug-resistant group and the low risk drug-resistant group was 44.4% and 55.6% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the high risk drug-resistant group were 45.8% and 42.9% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the low risk drug-resistant group were 70.4% and 40.7%. The survival rate of patients with chemotherapy was higher than that of the patients without chemotherapy (P<0.05).

CONCLUSIONSThe expression of ToPo II, MRP and GST-pi is associated with the efficacy of postoperative adjuvant chemotherapy. Chemotherapy appears to be more beneficial to patients with low risk drug-resistance.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Chemotherapy, Adjuvant ; DNA Topoisomerases, Type II ; metabolism ; Female ; Glutathione S-Transferase pi ; metabolism ; Humans ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Postoperative Period ; Prognosis ; Stomach Neoplasms ; diagnosis ; drug therapy ; metabolism

OBJECTIVETo analyze systematically the characteristics of occupational hazards in the foundry, and provide precise data for epidemiology studies and control of occupational hazards in the foundry.

METHODSData of airborne dust, chemical occupational hazards and physical occupational agents in environment in the foundry from 1978 to 2008 were dynamically collected. Mean concentration and intensity (geometric mean) of occupational hazards were calculated by job in different years.

RESULTSMain occupational hazards in the foundry were silica, metal fume, noise and heat stress. Silica existed in all of main jobs. The mean concentration of silica before 1986 was an extremely high level of 8.6 mg/m(3), and then remarkably dropped after 1986, with the level of 2.4 mg/m(3) from 1986 to 1989, 2.7 mg/m(3) from 1990 to 2002 and 2.7 mg/m(3) from 2003 to 2008. The trend of silica concentrations by job was consistent with that in general. Silica concentrations among jobs were significantly different, with highest level in melting (4.4 mg/m(3)), followed by cast shakeout and finishing (3.4 mg/m(3)), pouring (3.4 mg/m(3)), sand preparation (2.4 mg/m(3)), moulding (2.1 mg/m(3)) and core-making (1.7 mg/m(3)). Concentration of respirable dust in pouring was highest (2.76 mg/m(3)), followed by cast shakeout and finishing (1.14 mg/m(3)). Mean concentration of asbestos dust in melting was a relative high level of 2.0 mg/m(3). In core-making and sand preparation, there existed emission production of adhesive, with mean concentrations as followed, ammonia (5.84 mg/m(3)), formaldehyde (0.60 mg/m(3)), phenol (1.73 mg/m(3)) and phenol formaldehyde resin (1.3 mg/m(3)) also existed. Benzene and its homologues existed in cast shakeout and finishing, and the level of benzene, toluene, xylene was 0.2 mg/m(3), 0.1 mg/m(3) and 1.3 mg/m(3), respectively. In pouring and melting, there existed chemical occupational hazards, including benzo(a) pyrene, metal fume (lead, cadmium, manganese, nickel, chromium) and gas(hydrogen sulfide, phosphine, sulfur dioxide, carbon monoxide). Mean concentration of benzo(a) pyrene was a low level of 1.80 x 10(-4) microg/m(3). Physical occupational agents in the foundry were noise, heat stress and vibration. Intensity of heat stress was high in melting, pouring and cast shakeout and finishing, with the level of 30 degrees C, 29 degrees C and 26 degrees C, respectively. Noise was high in cast shakeout and finishing and core-making, with the level of 93.1 dB(A) and 89.5 dB(A), respectively. Vibration existed in core-making and cast shakeout and finishing. Compulsory postures included long standing, seating and bowing.

CONCLUSIONOccupational hazards in environment of the foundry are diversified and their concentrations exceed permissible exposure limits stipulated by the national occupational hygienic standards. High-concentrations of dust, metal fume, low-concentrations of variety of chemicals, high-intensity of noise and vibration, heat stress, and harmful compulsory posture, and so on all co-exist in the foundry. Control and protective measures should be strengthened.

Dust ; analysis ; Hazardous Substances ; analysis ; Metallurgy ; Occupational Exposure