As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

AIM:To observe the effects of transection of right cervical sympathetic trunk(TCST)on inflam-matory response and expression of high mobility group box 1(HMGB1)and TLR4/NF-κB signaling pathway in the rats af-ter acute myocardial infarction(AMI).METHODS: AMI model was established by ligation of left anterior descending coronary artery in SD rats,then the model rats were randomly divided into MI group and MI +TCST group.MI+TCST model was performed by transection of right cervical sympathetic trunk after left anterior descending coronary artery ligation. The rats in MI group and MI+TCST group were divided into 1,3,7,14 and 28 d subgroups,and another sham operation group threading without ligation, with 8 rats in above each group.After modeling for 4 weeks, the cardiac function was measured by echocardiography.All rats were killed to harvest the hearts for mesuring cardiac hypertrophy index.The myo-cardial tissue close to infarction was observed with HE staining.The relative mRNA expression levels of HMGB1, tumor necrosis factor α(TNF-α)and interleukin(IL)-6 at different time points were detected by real-time PCR.The protein ex-pression of HMGB1 and TLR4 at different time points after AMI was determined by Western blot.The effect of transection of right cervical sympathetic trunk on the expressions of HMGB 1 and TLR4/NF-κB signaling pathway was also analyzed. RESULTS:Compared with the MI group,left ventricular ejection fraction(LVEF)and left ventricular shorterning fraction (LVFS)were significantly higher(P<0.05),left ventricular end-diastole dimension(LVEDd),left ventricular end-sys-tole dimension(LVESd)and cardiac hypertrophy index were significantly lower(P<0.05), and the mRNA levels of HMGB1,TNF-αand IL-6 decreased significantly in MI +TCST group(P<0.05).Western blot results revealed that the protein expression level of HMGB1 increased in the infarct border zone at 3 d,and reached its peak at 7 d,then gradually decreased,and at 28 d after MI in MI group was still significantly higher than that in sham group(P<0.05).The protein expression of TLR4 was consistent with that of HMGB1.Transection of right cervical sympathetic trunk reduced protein ex-pression of HMGB1 and TLR4/NF-κB signaling pathway-related proteins(P<0.05).CONCLUSION: Transection of right cervical sympathetic trunk improves ventricular remodeling and maintaining cardiac function.The mechanism may be related to inhibiting HMGB1/TLR4/NF-κB signaling pathway to reduce inflammatory response.

Micromotion and fretting damages at the dental implant/bone interface are neglected for the limitation of check methods, but it is particularly important for the initial success of osseointegration and the life time of dental implant. This review article describes the scientific documentation of micromotion and fretting damages on the dental implant/bone interface. The fretting amplitude is less than 30 µm in vitro and the damage in the interface is acceptable. While in vivo, the micromotion's effect is the combination of damage in tissue level and the real biological reaction.
Biomechanical Phenomena ; Bone and Bones ; anatomy & histology ; physiology ; Dental Implants ; Humans ; Mechanical Phenomena ; Movement ; Osseointegration ; physiology ; Stress, Mechanical ; Surface Properties

The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF-α levels in notoginseng total saponin preparation middle-dose group and high-dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-α, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree.
Anaphylaxis ; chemically induced ; Animals ; Capillary Permeability ; drug effects ; Cytokines ; blood ; Dose-Response Relationship, Drug ; Drug Hypersensitivity ; etiology ; Mice ; Mice, Inbred ICR ; Panax notoginseng ; adverse effects ; chemistry ; Saponins ; adverse effects

OBJECTIVETo investigate the effects of a new anticoagulant, annexin V derivative (AND) on anticoagulation and antithrombosis.

METHODSHigh and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bolus injections followed by half the respective AND doses by iv infusion over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was put into femoral artery to induce endothelial denudation 15 min after IV bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The femoral arteries were collected and the thrombi were stripped off for measuring their lengths, wet and dry weights.

RESULTSAnticoagulation parameters: APTT at 15 min after iv bolus in AND group was significantly longer than that in group 4 (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3 were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The dry weight in high-dose AND group was remarkably lighter than that in low-dose group (P = 0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4 (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group than in group 4 (P < 0.05), but not in 3.

CONCLUSIONAND is an effective anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs at 15 min after IV bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.

Animals ; Annexin A5 ; administration & dosage ; pharmacology ; Anticoagulants ; administration & dosage ; pharmacology ; Blood Coagulation ; drug effects ; Disease Models, Animal ; Fibrinogen ; analysis ; Humans ; Injections, Intravenous ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Rabbits ; Random Allocation ; Thrombin Time ; Thrombosis ; prevention & control

Amino Acids ; metabolism ; Animals ; Dose-Response Relationship, Radiation ; Hippocampus ; metabolism ; radiation effects ; Male ; Microwaves ; adverse effects ; Neurons ; radiation effects ; ultrastructure ; Rats ; Rats, Wistar ; Synapses ; radiation effects ; ultrastructure

Aged ; Humans ; Male ; Urinary Diversion ; adverse effects ; Urinary Fistula ; diagnosis ; etiology

OBJECTIVETo investigate the maturation of individual bones on the hand and wrist in children with central precocious puberty (CPP) and idiopathic short stature (ISS).

METHODSHand and wrist films of 25 children with CPP, 29 children with ISS and 21 normal controls were evaluated by conventional Greulich-Pyle (GP) atlas method and individual bone assessment method, in which all twenty bones of the hand and wrist were evaluated based on GP atlas, including 2 radius and ulna, 7 carpal bones, 11 metacarpal and phalangeal bones, the average bone age (BA) was calculated. The differences in groups were analyzed by independent samples t test. The differences between the two methods were analyzed by paired sample t test. The differences between BA and chronological age (CA) were analyzed by ROC with SPSS 17.0.

RESULTSCompared with the normal control group, the advance of BA in the CPP group was 0.70-2.26 y (1.48 ±0.78) by the GP atlas method, while that was 0.28-2.00 y(1.14 ±0.86) by the individual bone evaluation method. In all twenty bones, the advance of metacarpal and phalangeal BA was the greatest [0.34-2.06 y(1.2±0.86)]. In the ISS group,the delay of BA was 0.47-2.91 y(-1.69±1.22) by the GP atlas method, while that was 0.48-2.50 y (-1.49±1.01) by individual bone evaluation method.The delay of carpal BA was the greatest [0.59-2.73 y(-1.66±1.07)] in all twenty bones. In the ISS group and the normal control group, there were no statistic differences between the two methods. In the CPP group, statistic difference was found between two methods. There were no statistic differences for the areas under ROC curves between two methods.

CONCLUSIONThe advance of metacarpal and phalangeal BA is the greatest in CPP group and the delay of carpal BA is the greatest in ISS group.Both methods provide diagnostic information for bone age in CPP and ISS children.

Age Determination by Skeleton ; methods ; Carpal Bones ; diagnostic imaging ; Case-Control Studies ; Child ; Dwarfism ; diagnostic imaging ; Female ; Hand ; diagnostic imaging ; Humans ; Male ; Puberty, Precocious ; diagnostic imaging

Objective:To discuss the management principles and skills for treatment of intractable ureterostenosis under ureteroscope.Methods:Our management experience on 19 patients with intractable ureteral stenosis was retrospectively analyzed.The 19 cases included urological TB-caused multiple ureteral stenosis,oncothlipsis to ureters from intestinal tract or gynecology,restenosis 3 months to 12 years after pelviureteric junction plasty,operative site stenosis after ureterolithotomy. double ureter back flow accompanied by stenosis,ureter imperforation after renal parenchyma lithotomy without placing double"J",ureter imperforation 3 months after extracorporeal shock-wave lithotripsy due to ureterolith,tubal bladder stoma stenosis after renal transplantation,restenosis after tubal bladder stoma due to distal ureterostenosis,and so on.All the patients were treated under ureteroscope.The management methods included:the Wolf 8/9.8 CH12?and Wolf 6/7.6 CH5?ureteroscope was used as a dilator to dilate the stenoses:balloon expanding under ureteroscope was used to dilate the stenoses;the ureter pliers was used to expand the stenoses to different directions;the cold knife was used to open the stenoses;if the diameter of stenoses were smaller than the that of the ureteroscopes,F4.5 or F3 double"J"tubes were inserted guided by a wire under ureteroscope; and 2 or 3 weeks later,a larger tube or two tubes were introduced into the stenoses already dilated partly by the former tube. Results:Ureteroscopic method failed in treating 2 patients in our group and succeeded in treating all the other patients.The outcomes of patient were fine during 9 months to 3 years'follow-up.Conclusion:It is difficult to treat patients with intractable ureterostenoses.With good experience in manipulation of ureteroscope,the flexible application of several techniques according to the different conditions of different patients can guarantee successful treatment in most patients.

This study is to investigate the treatment of YinQiaojiedu soft capsule for influenza virus A/PR8/34 (H1N1) infection. The model of pneumonia was established by dropping influenza virus into the nose of normal mice, and the lung index and death rate were observed. Real time RT-PCR and Western blotting technique were used to detect the virus load and the relative expression of M1 protein in lungs of mice on the 1st, 3rd, 5th and 7th day after infection. The results showed that YinQiaojiedu soft capsule in 1 g x kg(-1) and 0.5 g x kg(-1) dose groups can decrease the lung index significantly on the 3rd, 5th and 7th day after being infected (P < 0.05, P < 0.01), and the number of death in the two groups of animals decreased significantly. YinQiaojiedu soft capsule in 1 g x kg(-1) dose group can decreased virus load at each time point, and lower it in 0.5 g x kg(-1) dose group at the 3rd, 5th and 7th day (P < 0.05, P < 0.01). YinQiaojiedu soft capsule can decrease the relative expression of M1 protein in lungs of mice, 1 g x kg(-1) and 0.5 g x kg(-1) dose groups are significantly lower in expression of M1 protein compared with model group at the 3rd and 7th day (P < 0.05, P < 0.01). It can be concluded that YinQiaojiedu soft capsule exerts antiviral effects against influenza virus by downregulating expression of virus load and M1 protein.
Animals ; Antiviral Agents ; administration & dosage ; pharmacology ; Capsules ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Influenza A Virus, H1N1 Subtype ; Lung ; metabolism ; virology ; Male ; Mice ; Mice, Inbred ICR ; Orthomyxoviridae Infections ; drug therapy ; metabolism ; virology ; Pneumonia ; metabolism ; virology ; Viral Load ; drug effects ; Viral Matrix Proteins ; metabolism