OBJECTIVE: To develop an appropriate nanostructured lipid carrier (CsA-NLC) for ocular drug delivery of cyclosporine A and its in vitro physicochemical properties and ocular irritation studies were investigated. METHODS: The melt-emulsification method was chosen to prepare CsA-NLC. The formulation was optimized by orthogonal design. The morphology of CsA-NLC was observed by transmission electron microscopy (TEM). The mean particle size and Zeta potential were measured by laser particle size analyzer. The state of drug in NLC was confirmed by DSC. Drug loading and encapsulation efficiency were determined by HPLC. Dialysis method at 34°C was employed to investigate the in vitro release of CsA-NLC. The topical ocular irritation study of CsA-NLC was made in rabbits. RESULTS: The obtained CsA- NLC was approximately spherical in shape with average particle size of (35.9 ± 0.21) nm and zeta potential of (- 13.9 ± 0.21) mV. The drug loading and encapsulation efficiency were (16.2 ± 0.09)% and (97.5 ± 0.58)%, respectively. The in vitro release of CsA-NLC was slowed down and fitted well single exponential distribution model. There was no irritation for CsA-NLC to rabbits eye. CONCLUSION: CsA-NLC with small particle sizes and high drug loading, slow release would be a promising nanocarrier for ocular drug delivery to improve drugs bioavailability. Copyright 2012 by the Chinese Pharmaceutical Association.

OBJECTIVE: To construct receptor-mediated lactoferrin-modified curcumin-loaded nanostructured lipid carriers (Lf-Cur-NLCs) and investigate its in vitro physicochemical properties and in vivo brain targeting efficiency. METHODS: Cur-NLCs were prepared by melt-emulsification method, and then lactoferrin(Lf) was adsorbed onto the surface of Cur-NLCs via electrostatic interaction to form Lf-Cur-NLCs. Lf-Cur-NLCs with different concentrations of Lf were characterized in terms of shape, diameter, Zeta potential, serum stability and in vitro release of Lf-Cur-NLCs in saline containing 1% Tween 80. Additionally, Lf-NLCs labeled with NIRD-15, a fluorescent imaging agent, were prepared with Lf at concentrations of 0.5, 1.5 and 2.0 mg · mL-1 (marked for Lf1, -NLC, Lf3-NLC, and Lf4-NLC, respectively). After iv injection in mice, living animal imaging system was used to observe the fluorescence intensity of NIRD-15 in the living animals and isolated organs to evaluate the brain targeting of Lf-NLCs. RESULTS: Cur-NLCs were spherical with average particle size of(187.5 ±4.7) nm and Zeta potential of(- 23.7 ± 2.9) mV. The average diameter of Lf-Cur-NLCs with spherical shape was between 167.8-299.9 nm. The Zeta potential was between -26.87 - -13.03 mV. When the concentration of Lf was 2.0 mg · mL-1 and the incubated time was 6 h, the adsorption of Lf at the surface of the Cur-NLCs was saturated. Lf-Cur-NLCs were stable in serum, and the release of Cur from Lf-Cur-NLCs was slowed down. Compared with NLCs, there was a strong fluorescence in the brain after iv injection of Lf-NLCs, indicating that Lf-NLCs were more effective than NLCs in brain targeting, while Lf3-NLCs were the most effective one. CONCLUSION: Lf-NLCs are constructed successfully for brain targeting via electrostatic adsorption. The established process avoids chemical synthesis in the targeting drug delivery system design. However, the ability of brain targeting of the carriers is related with the amount of Lf.

OBJECTIVE: To develop a bioadhesive nanostructured lipid carrier (P407-NLC) for ocular delivery of cyclosporine A and investigate its ocular distribution in rabbits. METHODS: Melt-emulsification method was chosen to prepare CsA-NLC. Poloxamer 407 (P407) was dissolved in borate buffer solution (pH 8.0), then added into CsA-NLC to prepare P407-NLC. The morphology of P407-NLC was observed by transmission electron microscopy (TEM). The mean particle size and Zeta potential were measured by laser particle size analyzer. The viscosity was measured by rheometer. Dialysis method was employed to investigate the in vitro release of CsA from P407-NLC at 34°C. The concentrations of CsA in ocular tissues were studied by RP-HPLC, and the pharmacokinetic parameters were calculated by linear trapezoidal method. The topical ocular irritation study of P407-NLC was carried out in rabbits. RESULTS: The obtained P407-NLC was approximately spherical in shape with average particle size of (41.2 ± 0.2) nm and Zeta potential of (-15.2 ± 0.21) mV, and P407 was coated on the appearance of NLC. P407-NLC was non-newtonian fluids. The in vitro release of CsA from P407-NLC was slowed down and fitted well with single exponential distribution model. AUC0-24h of CsA in cornea, aqueous humor and iris after ocular administration of P407-NLC containing 6.0% P407 were 10.75, 4.45 and 4.62 times higher than that of CsA oil solution, and 2.77, 1.22 and 1.54 times higher than that of CsA-NLC, respectively. MRTs in aqueous humor, cornea and iris were 3.28, 2.26 and 3.46 times higher, respectively, than that of CsA oil solution, and 1.69, 1.50 and 1.62 times higher than CsA-NLC, respectively. There was no irritation for P407-NLC to rabbit eyes. CONCLUSION: P407-NLC can be used to increase the level of CsA in ocular tissues and would be a promising nanocarrier for ocular drug delivery. Copyright 2012 by the Chinese Pharmaceutical Association.

Antibiotics, Antineoplastic ; therapeutic use ; Apoptosis ; Cell Cycle ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; Neovascularization, Pathologic ; etiology ; Phosphatidylinositol 3-Kinases ; metabolism ; Protein Kinases ; physiology ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases

OBJECTIVETo observe the clinical effect of Shugan Yiyang Capsules combined with sertraline in the treatment of premature ejaculation (PE).

METHODSWe randomly assigned 192 PE patients to receive sertraline hydrochloride 50 mg qd (control group, n = 96) or sertraline hydrochloride 50 mg qd plus Shugan Yiyang Capsules at the dose of 4 capsules tid ( combination therapy group, n = 96) , both for 6 weeks. We compared the intravaginal ejaculatory latency time (IELT) and Chinese Index of Premature Ejaculation ( CIPE) scores between the two groups of patients before and after medication and at 6 weeks after drug withdrawal.

RESULTSCompared with the baseline, the IELT was significantly increased after 6 weeks of medication in the combination therapy group ([1.41 ± 0.53] vs [6.69 ± 3.56] min, P < 0.05) and the control group ([1.43 ± 0.48] vs [5.37 ± 2.91] min, P < 0.05), and so was the CIPE score in the former (9. 80 ± 2.06 vs 21.62 ± 4.76, P < 0.05) and the latter group ([9.41 ± 1.97] vs [20.85 ± 4.83] , P < 0.05). In comparison with the pre-medication indexes, the IELT ([3.77 ± 1.63] min) and CIPE score (16.92 ± 3.37) of the combined therapy group were remarkably improved at 6 weeks after drug withdrawal (P < 0.05), but not those of the control ([1.19 ± 1.34] min and 10.59 ± 2.38, P > 0.05).

CONCLUSIONShugan Yiyang Capsules combined with sertraline have a definite and lasting effect on premature ejaculation.

Capsules ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Premature Ejaculation ; drug therapy ; Sertraline ; therapeutic use

Child ; Evidence-Based Medicine ; Humans ; Nephrotic Syndrome ; diagnosis ; etiology ; therapy ; Practice Guidelines as Topic ; Recurrence

Objective To investigated the effects of long term use of very low protein diet(VLPD,0 3 g?kg-1?d-1) treatment on patients with chronic renal insufficiency without essential amino acids(EAAs) or related ketoacids supplement.Methods Thirty seven patients with established severe chronic renal failure (CRF)[Scr(588 2?123 5)?mol/L, Ccr(9 77?3 48)ml?min-1?(1 73m2)-1]were divided into 2 groups according to their actual protein intake: 20 patients with protein intake of (0 33?0 04)g?kg-1?d-1 were used as VLPD group, while other 17 CRF patients whose protein intake was 0 6 g?kg-1?d-1 were served as low protein diet group (LPD). Results All patients in VLPD group showed good compliance to this very low protein diet,and no one presented signs of protein malnutrition during the observation. The concentrations of serum albumin and transferrin were maintained in normal ranges during the follow up period despite the transferrin levels in both groups gradually decreased as time went on. The serum concentration of transferrin was higher in VLPD patients than that in LPD patients at the end of study (P

Soluble urokinase-type plasminogen activator receptor(suPAR) , a new injury biomarker, is widely used in research of infectious diseases, cancer, cardiovascular diseases, autoimmune diseases, etc. In recent years, suPAR has been suggested to play an important role in various renal diseases. This review focuses on studies of suPAR in renal diseases and update, which will provide new clues for the diagnosis and treatment of renal diseases.

Objective To observe the expression of osteoprotegerin (OPG), receptor activator of nuclear factor κβ ligand(RANKL) and receptor activator of nuclear factor κβ (RANK) in bone tissue of rats with chronic fluorosis and to explore the relation between OPG/RANKL/RANK system and bone damage in chronic fluoride poisoning rat and the antagonism effects of Danlan Xianpeng capsule. Methods SD rats were randomly divided into six groups according to body weight (equal male and female in each group): fluorosis group, high dose drug group, medium dose drug group, low dose drug group, control group, borax group(positive control), 12 rats in each group. The control group drank tap water and the remaining 5 experimental groups consumed 50 mg/L fluoride water, and high, medium and low doses drug group took Danlan Xianpeng capsule at doses of 0.8,0.4,0.2 g/kg,borax group took borax at dose of 0.8 g/kg. OPG, RANKL, RANK protein in rat tibial metaphysis was detected by immunohistochemistry at the 6 month. Results Compared with the control group(173.79 ± 5.23, 174.17 ± 5.01,155.63 ± 7.11), the expressions of OPG, RANKL were increased and the expression of RANK was decreased in fluorosis group(156.83 ± 5.80, 157.74 ± 6.70, 173.92 ± 4.37), the difference was statistically significant (all P ＜ 0.05). Compared with the fluorosis group, the expression of OPG and RANKL were decreased and the expression of RANK was increased in high-dose drug group, middle-dose drug group(169.67±5.07, 168.08 ± 5.05,162.12 ± 4.24, 170.78 ± 5.01, 168.41 ± 7.19, 166.69 ± 5.78, all P ＜ 0.05). Compared with the borax group (167.27 ± 4.08, 167.85 ± 5.01, 166.14 ± 3.95), the expression of OPG and RANKL was increased in the low-dose drug group (163.40 ± 4.11, 159.49 ± 5.78), the expression of RANK was increased in the high-dose drug group (162.12 ± 4.24) and decreased in the low-dose drug group(171.54 ± 8.06), the difference was statistically significant (all P ＜ 0.05). Conclusions Chronic fluoride poisoning can cause increased bone turnover and enhance the activity of osteoelastic absorption by increasing RANKL. Danlan Xianpeng capsule can affect bone remodeling through the OPG/RANKL/RANK system, and antagonises bone damage caused by fluoride.

Objective To screen and analyse the dominated related factors for medical discipline construction and development,and provide evidences for the reinforcement of discipline connotation construction.Methods The candidate medical disciplines of State Key Disciplines Evaluation of 2007 were served as study subjects.Disciplines from the results of State Key Discipline Evaluation were divided into "new discipline" group(n=51),"breeding discipline" group(n=33)and "failed discipline" group(n=81).The differences between results of State Key Discipline Evaluation and corresponding data of past years(2001 to 2006)in academic team,scientific research,graduate education and lab construction were analysed by nonparametric Kruskal-Wallis test.Results There were significant differences in academic leader,state key project,prize level,graduates quality and scientific research base among the results of State Key Discipline Evaluation(P≤0.05),and the dominated factors for the unsuccessful result were lack of high-level academic leader,state key discipline,prize,gruaduates and scientific research base.Conclusion The adoption of appropriate measures for the construction of academic team,the reinforcement of scientific research and the establishment of academic achievement evaluation may help to upgrade the academic level.