OBJECTIVE: To prepare the slow-release complex with rifampicin (RFP)-polylactic-co-glycolic acid (PLGA)-calcium phosphate cement (CPC) (RFP-PLGA-CPC complex), and to study its physical and chemical properties and drug release properties in vitro.
 METHODS: The emulsification-solvent evaporation method was adopted to prepare rifampicin polylactic acid-glycolic acid (RFP-PLGA) slow-release microspheres, which were divided into 3 groups: a calcium phosphate bone cement group (CPC group), a CPC embedded with RFP group (RFP-CPC group), and a PLGA slow-release microspheres carrying RFP and the self-curing CPC group (RFP- PLGA-CPC complex group). The solidification time and porosity of materials were determined. The drug release experiments in vitro were carried out to observe the compressive strength, the change of section morphology before and after drug release. 
 RESULTS: The CPC group showed the shortest solidification time, while the RFP-PLGA-CPC complex group had the longest one. There was statistical difference in the porosity between the CPC group and the RFP-CPC group (P<0.05); Compared to the RFP-PLGA-CPC complex group, the porosity in the CPC group and the RFP-CPC group were significantly changed (both P<0.01). There was significant difference in the compressive strength between the RFP- PLGA-CPC complex group and the CPC group (P<0.01), while there was significant difference in the compressive strength between the RFP-CPC group and the CPC group (3 days: P<0.05; 30 and 60 days: P<0.01). The change of the compressive strength in the CPC was not significant in the whole process of degradation. The sizes of PLGA microspheres were uniform, with the particle size between 100-150 μm. The microspheres were spheres or spheroids, and their surface was smooth without the attached impurities. There was no significant change in the section gap in the CPC group after soaking for 3 to 60 days. The microstructure change in the RFP-CPC group was small, and the cross section was formed by small particles. The pores of section in the RFP-PLGA-CPC complex group increased obviously, and PLGA microspheres gradually disappeared until the 60th day when there were only empty cavities left. The RFP-PLGA-CPC complex group had no obvious drugs sudden release, and the cumulative drug release rate was nearly 95% in the 60 days. The linear fitting was conducted for the drug release behavior of the complex, which was in accordance with zero order kinetics equation F=0.168×t.
 CONCLUSION The porosity of RFP-PLGA-CPC complex is significantly higher than that of CPC, and it can keep slow release of the effective anti-tuberculosis drugs and maintain a certain mechanical strength for a long time.
Bone Cements ; pharmacokinetics ; Calcium Phosphates ; pharmacokinetics ; Compressive Strength ; Delayed-Action Preparations ; pharmacokinetics ; Dental Cements ; pharmacokinetics ; Lactic Acid ; pharmacokinetics ; Materials Testing ; Microspheres ; Polyglycolic Acid ; pharmacokinetics ; Polylactic Acid-Polyglycolic Acid Copolymer ; Porosity ; Rifampin ; administration & dosage ; pharmacokinetics

The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.
Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Lanthanum ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Parathyroid Hormone ; analysis ; Phosphates ; blood ; Pruritus ; blood ; drug therapy ; etiology ; Renal Dialysis ; adverse effects ; methods ; Treatment Outcome ; Vascular Calcification ; blood ; drug therapy

Bowel preparation is essential for successful colonoscopy examination, and the most important factor is the bowel preparation agent used. However, selection of a bowel preparation agent invariably involves compromise. Originally, bowel preparation was performed for radiologic and surgical purposes, when the process involved dietary limitations, cathartics, and enemas, which had many side effects. Development of polyethylene glycol (PEG) solution led to substantive advancement of bowel preparation; however, despite its effectiveness and safety, the large volume involved, and its salty taste and unpleasant odor reduce compliance. Accordingly, modified PEG solutions requiring consumption of lower volumes and sulfate-free solutions were developed. Aqueous sodium phosphate is more effective and better tolerated than PEG solutions; however, fatal complications have occurred due to water and electrolyte shifts. Therefore, aqueous sodium phosphate was withdrawn by the US Food and Drug Administration, and currently, only sodium phosphate tablets remain available. In addition, oral sulfate solution and sodium picosulfate/magnesium citrate are also available, and various studies have reported on adjunctive preparations, such as hyperosmolar or stimulant laxatives, antiemetics, and prokinetics, which are now in various stages of development.
Administration, Oral ; Cathartics/*administration & dosage ; Citrates/administration & dosage ; Citric Acid/administration & dosage ; Colonic Diseases/diagnosis ; Colonoscopy ; Humans ; Organometallic Compounds/administration & dosage ; Phosphates/administration & dosage ; Picolines/administration & dosage ; Polyethylene Glycols/administration & dosage

PURPOSE: Bowel cleansing is generally regarded as time-consuming and unpleasant among patients. Patients commonly state that bowel preparation provokes more discomfort than the actual colonoscopic examination. The purpose of this study was to compare two regimens of sodium phosphate (NaP) tablets versus polyethylene glycol (PEG) solution for bowel preparation in healthy Korean adults. MATERIALS AND METHODS: This was a single center, prospective, open-label, investigator-blinded, randomized, controlled-pilot study. A total of 62 healthy Korean subjects were randomly assigned to two groups (NaP vs. PEG). Efficacy, safety, and patient-related outcomes, as well as procedural parameters, were evaluated. RESULTS: Although there were no significant differences in total Ottawa bowel quality score, fluid scores and the rate of adequate bowel preparation were significantly better in the NaP group than the PEG group. Additionally, the NaP group showed better results regarding patient tolerance, satisfaction, preference, and rate of adverse events than the PEG group. Significant fluctuations in specific serum electrolytes were common and of a greater magnitude in the NaP group than the PEG group. However, these abnormalities were transient and did not result in serious complications and side effects. CONCLUSION: In this study, NaP tablets were shown to be an effective, well-tolerated, and acceptable regimen for bowel preparation. Also, our study suggests that NaP tablets may be safe and can be used as a bowel cleansing agent in healthy adults undergoing elective colonoscopy. Further multicenter, large scale studies are needed to confirm these findings.
Adult ; Asian Continental Ancestry Group ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Phosphates/*administration & dosage/therapeutic use ; Pilot Projects ; Polyethylene Glycols/*administration & dosage/therapeutic use ; Prospective Studies ; Republic of Korea ; Surface-Active Agents/*administration & dosage ; Tablets ; Therapeutic Irrigation/*methods

To develop a core-shell structure pDNA-CaPi-PLGA nanoparticles (CS-pDNA-CaPi-PLGA-NPs), calcium phosphate-pDNA nano complexes (CaPi-pDNA) were encapsulated inside of PLGA shells. The characteristics of the nanoparticles, including morphology, average particle size, zeta potential, entrapment efficiency, loading efficiency, stability in medium, pDNA protection ability from nuclease degradation, in vitro release, cytotoxicity and cell transfection were investigated and compared with the embedded structured CaPi modified PLGA nanoparticles (embedded-pDNA-CaPi-PLGA-NPs). The results showed that the obtained CS-pDNA-CaPi-PLGA-NPs were spherical in shape with an average particle size of (155 +/- 4.5) nm, zeta potentials of (-0.38 +/- 0.1) mV, entrapment efficiency of (80.56 +/- 2.5)% and loading efficiency of (1.16 +/- 0.04)%. The CS-pDNA-CaPi-PLGA-NPs were stable in the release media and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The highest gene transfection efficiency of the CS-pDNA-CaPi-PLGA-NPs in vitro reached (24.66 +/- 0.46)% (after 72 h transfection), which was significantly higher than that of free pDNA [(0.33 +/- 0.04)%, P < 0.01] and the pDNA-PLGA-NPs [(1.5 +/- 0.07)%, P < 0.01]. Besides, the transfection lasted for longer time than that of embedded-pDNA-CaPi-PLGA-NPs and the cytotoxicity of it was significantly lower than that of PEI (P < 0.01). These results indicate that CS-pDNA-CaPi-PLGA-NPs are a promising non-viral gene vector. Key words: gene delivery system; polylactic-co-glycolic acid; calcium phosphate; nanoparticle
Calcium Phosphates ; administration & dosage ; chemistry ; toxicity ; Cell Survival ; drug effects ; DNA ; administration & dosage ; chemistry ; toxicity ; Drug Carriers ; Genetic Vectors ; HEK293 Cells ; Humans ; Lactic Acid ; administration & dosage ; chemistry ; Nanoparticles ; Particle Size ; Plasmids ; genetics ; Polyglycolic Acid ; administration & dosage ; chemistry ; Transfection

OBJECTIVETo investigate the efficacy of CO2 laser combined with 32P-patch contact brachyradiotherapy for the treatment of keloids.

METHODSFrom 2001 to 2006, 121 cases with 151 keloids, which reoccurred after treatment with more than 2 methods, underwent continuous CO2 laser treatment to remove the hypertrophic scar tissue, following by ultra-pulse CO2 laser to treat the fresh granulation tissue. After wound healing, 32P-patch contact brachyradiotherapy was used for the lesion, 0.5-1 MBQ/cm2 for 72-96 hours, every 1-2 months. 2-3 treatment were applied.

RESULTSAmong the 151 keloids, good result was achieved in 111 keloids, and effective result in 40 keloids. Adverse effect included hyperpigmentation in 21 lesions and hypopigmentation in 32 lesions. The patients were followed up for 2-6 years without relapse.

CONCLUSIONCO2 laser combined with 32P-patch contact brachyradiotherapy is an effective and safe method for the treatment of recalcitrant keloids.

Adolescent ; Adult ; Female ; Humans ; Keloid ; therapy ; Lasers, Gas ; therapeutic use ; Male ; Middle Aged ; Phosphates ; administration & dosage ; therapeutic use ; Phosphorus Radioisotopes ; administration & dosage ; therapeutic use ; Transdermal Patch ; Treatment Outcome ; Young Adult

The study is to investigate the brain pharmacokinetics change of nasal tetramethylpyrazine phosphate (TMPP) pH-sensitive in situ gel in normal and model rats. Acute cerebral ischemia rat model was successfully established by middle cerebral artery occlusion (MCAO) method. Both normal and model rats were given nasal TMPP pH-sensitive in situ gel (10 mg x kg(-1)). Perfusates of brain striatum area were collected at each time point by microdialysis. The content of TMPP was determined by HPLC. The pharmacokinetics parameters were calculated by Kinetica 4.4 software at each time point of the brain drug concentration. The main pharmacokinetics parameters of TMPP were fitted with compartments 2. After nasal TMPP pH-sensitive in situ gel the values of C(max) and AUC of both components in brain showed as follows: the value of model group > that of normal group. Significant difference can be observed in the process of brain pharmacokinetics in normal and model rats after giving nasal TMPP pH-sensitive in situ gel.
Administration, Intranasal ; Animals ; Area Under Curve ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; Chromatography, High Pressure Liquid ; Gels ; Hydrogen-Ion Concentration ; Infarction, Middle Cerebral Artery ; Male ; Microdialysis ; Phosphates ; administration & dosage ; pharmacokinetics ; Pyrazines ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of administration or local application of epimedium on the fracture healing in osteoporosis rats.

METHODSEighty-two 4-month old clean female rats, 210-250 g, were randomly divided into the experimental group (n = 75) and the control group (n = 7). The bilateral ovaries were resected in the experimental group, while only little fat tissue around the ovary was resected in the control group. Ten weeks after operation the osteoporosis model was successfully established verified by bone densitometry and scanning electron microscopy (SEM). The femur fracture models were established in the rest 72 rats of the experimental group. They were randomly divided into 3 groups, 24 in each group, i.e., the calcium phosphate cement (CPC) group (Group A), the CPC-epimedium group (Group B), and the epimedium administration group (Group C). The serum alkaline phosphatase (ALP) levels of the 3 groups were determined 2, 4, 8, and 12 weeks after surgery. The vitodynamical test and observation of the histological section were performed.

RESULTSThe serum ALP levels increased to some extent in the 3 groups 2, 4, and 8 weeks after bone fracture surgery. But the increase was more obvious in Group B with statistical difference shown when compared with Group A and C (P < 0.05). The ALP level in Group B decreased to the normal range till the 12th week. The bone fracture had not completely healed in Group C and A. Their ALP levels decreased to some extent, but were still maintained to a comparatively higher level, showing statistical difference when compared with that of Group B (P < 0.05). These results were agreeable with the results of the histological observation. Better bone activity promoting results were shown in Group B. The vitodynamical test results of the femur of Group B were all higher than those of Group A and C at each time point (P < 0.05).

CONCLUSIONSLocal application of epimedium could accelerate the fracture healing in osteoporosis rats. It showed better effects when compared with oral administration at the same dose.

Alkaline Phosphatase ; blood ; Animals ; Bone Cements ; therapeutic use ; Calcium Phosphates ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Epimedium ; Female ; Fracture Healing ; drug effects ; Fractures, Bone ; drug therapy ; etiology ; Osteoporosis ; complications ; drug therapy ; Ovariectomy ; Rats

OBJECTIVETo investigate the feasibility of using calcium phosphate cement/amifostine complex as an new filling material for repairing bone defect caused by tumor resection.

METHODSCalcium phosphate cement (CPC)/cisplatin/amifostine complex was prepared at the mass ratio of 1000:2:5. The setting time, mechanical strength, and porosity of the complex were determined, and scanning electron microscopy and assessment of sustained drug release and inhibitory effect against osteosarcoma cells were carried out. The degradation of the material and new bone ingrowth were also observed in a rabbit model of femoral bone defect.

RESULTSThe setting time, strength, and porosity, appearances under scanning electron microscope, and sustained drug release properties of CPC/cisplatin/amifostine complex were identical to those of CPC, and the integration of amifostine in the complex did not affect the cytotoxicity of cisplatin against the osteosarcoma cells. Pathological evidences of the degradation of the material and new bone ingrowth into the material were observed with the passage of time following its implantation into the bone defect in rabbits.

CONCLUSIONThe CPC/cisplatin/amifostine complex can be used as a filling material for repairing bone defect caused by tumor resection and eliminating the residual tumor cells in rabbits.

Amifostine ; administration & dosage ; Animals ; Bone Cements ; therapeutic use ; Calcium Phosphates ; administration & dosage ; Cisplatin ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Female ; Femoral Neoplasms ; surgery ; therapy ; Implants, Experimental ; Male ; Osteosarcoma ; surgery ; therapy ; Porosity ; Rabbits

OBJECTIVETo observe the effective of the injectable artificial bone combined with plate fixation for reconstructing the collapse tibial plateau fracture.

METHODSFrom June 2005 to January 2008,21 cases of collapse tibial plateau fracture of type Schatzker II, III were treated by injectable calcium sulfate bone substitute combined with supportive plate reconstruction including 16 males and 5 females with an average age of 35.3 years ranging from 27 to 62 years. The disease course was from 3 to 7 days (means 4 days). According to Schatzker classification, there were 17 cases of type II, 4 of type III. All patients preoperatively underwent radiography, CT scanning and three-dimensional reconstruction in order to accurately understand the extent of fracture and fracture collapse and the shattered fragments of the flip direction. All the fracture with collapse > 3 mm, without joint degeneration were selcected for surgical treatment. The knee joint function after fracture healing and recovery were evaluated by Lysholm scoring.

RESULTSAll patients were followed-up for from 6 months to 2.5 years (means 1.5 years). The X-ray films and features of all fractures showed anatomic reduction or near anatomic reduction, except one case of grade II severe comminuted fracture occurred a high degree of loss and platform reset ineffective after 6 months. The Lysholm scoring of knee function showed that the mean score was (88.3 +/- 5.2). The results were excellent in 12 cases,good in 7 cases, fair in 2 cases.

CONCLUSIONMinimally invasive injectable calcium sulfate bone combined with plate fixation for reconstructing the collapse tibial plateau fracture of type II, III can effectively prevent the further loss after reduction, to improve the long-term results. Minimally invasive injectable calcium sulfate as an artificial bone substitute materials has good prospects for clinical application.

Adult ; Bone Plates ; Bone Substitutes ; administration & dosage ; Calcium Phosphates ; administration & dosage ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Injections ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Tibial Fractures ; surgery