Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship

Animals ; Drug Tolerance ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Morphine ; Phosphorylation ; Rats ; Signal Transduction

OBJECTIVETo evaluate the clinical results of dorsal approach and Weil osteotomy in treating the injury of the plantar plate in second metatarsophalangeal joint.

METHODSEight feet with plantar plate tear in five cases were treated by plantar plate repairment through dorsal approach and Weil osteotomy from June 2012 to December 2013. The mean age of the patients was 52 years old. All the patients were followed up for 6 to 12 months. American Orthopaedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) were used to evaluate the clinical effect.

RESULTSThe second metatarsophalangeal joint stability recovered and the pain released in all patients. Postoperative VAS was lower and AOFAS was higher than preoperative.

CONCLUSIONCombined dorsal approach and Weil osteotomy can effectively release the pian of plantar plate, stabilize the metatarsophalangeal joint, decrease the incidence rate of postoperative subluxation and anchylosis in treating plantar plate tears in the second metatarsophalangeal joint.

Female ; Humans ; Joint Instability ; surgery ; Metatarsophalangeal Joint ; injuries ; surgery ; Middle Aged ; Osteotomy ; methods ; Plantar Plate ; injuries

OBJECTIVETo evaluate clinical results of plate on the metatarsal side to reconstruction of tarsometatarsal joint dislocations secondary to diabetic charcot foot.

METHODSSeven patients (9 feet) patients with tarsometatarsal joint dislocations secondary to diabetic charcot foot were treated with plating from April 2012 to December 2014. All patients were male, and 5 cases were on the unilateral side and 2 cases were on the bilateral sides. The age of patients ranged from 45 to 52 with an average of 48 years old. The history of diabetics was from 6 to 15 years. X-ray and CT were used to evaluate fractures healing,and AOFAS was applied to estimate recovery of joint function.

RESULTSAll patients were followed up from 12 to 24 months with an average of 19 months. All incisions were healed at stage I . No infection, loosening and breakage of internal fixation, bone nonunion were found after operation. According to postoperative X-ray and CT results, the time of fracture healing ranged from 10 to 20 weeks with an average of 16 weeks. Six feet got excellent results, 2 good and 1 moderate based on AOFAS scoring.

CONCLUSIONTarsometatarsal joint dislocations secondary to diabetic charcot foot treated with plate on the metatarsal side could obtain stable fixation and got satisfied early clinical results.

Adult ; Bone Plates ; Diabetes Complications ; surgery ; Diabetes Mellitus, Type 2 ; complications ; Female ; Foot Diseases ; etiology ; surgery ; Fracture Fixation, Internal ; Humans ; Joint Dislocations ; surgery ; Male ; Metatarsal Bones ; surgery ; Middle Aged ; Tarsal Joints ; surgery

Aim To investigate the effects of new derivatives of 1H-isoindole-1,3(2H)-dione on angiogenesis in chick chorioallantoic membranes(CAM). Methods The blood vessels of CAM were calculated to determine the antiangiogenic effects of different new compounds. Results Among the 18 new derivatives of 1H-isoindole-1,3(2H)-dione , compound 1,2,3,4,11 and 13 showed significant inhibition on angiogenesis of CAM.Conculsion The 6 new derivatives of 1H-isoindole-1,3(2H)-dione screened out in this experiment may be novel angiogenesis inhibitors.

AIM: To investigate the changes of hemodynamic parameters and ECG in circulatory failure rats induced by organophosphate insecticides DDV and parathion.METHODS: Healthy Wistar male rats,weighing(320?20)g,were treated with organophosphate insecticides by ip.to induce circulatory failure.When the mean blood pressure(MBP) decreased to 45 mmHg,the changes of hemodynamic parameters and ECG were observed.RESULTS: In circulatory failure rats,SBP,DBP,MBP,HR,LVDP,IP,+dp/dtmax,-dp/dtmax,Vpm and +dp/dtmax/IP changed dramatically(P

Vascular endothelium plays an important role in regulating vascular homeostasis. Over the past years, it has become clear that endothelial dysfunction is a key event of pathophysiological changes in the initiation and progression of injuries induced by extreme environmental factors. The present review summarizes current understanding of vascular endothelial dysfunction induced by hypoxia, cold and heat, and provides the information for prevention and treatment of environmental exposure injuries.
Endothelium, Vascular ; physiopathology ; Environment ; Humans ; Hypoxia ; physiopathology ; Temperature ; Vascular System Injuries

OBJECTIVETo explore the process of refuse decomposition in hybrid bioreactor landfill.

METHODSThe bioreactor landfill was operated in sequencing of facultative-anaerobic and aerobic conditions with leachate recirculation, pH, COD, and ammonia in the leachate and pH, biodegradable organic matter (BDM), and cation exchange capacity (CEC) in refuse were detected.

RESULTSCEC increased gradually with the degradation of refuse, which was negatively correlated with BDM. COD and ammonia in the leachate was declined to 399.2 mg L(-1) and 20.6 mg N L(-1), respectively, during the 357-day operation. The respective concentrations of ammonia and COD were below the second and the third levels of current discharge standards in China.

CONCLUSIONThe refuse is relatively stable at the end of hybrid bioreactor landfill operation. Most of the readily biodegradable organic matter is mineralized in the initial phase of refuse degradation, whereas the hard-biodegradable organic matter is mainly humidified in the maturity phase of refuse degradation.

Ammonia ; analysis ; Biodegradation, Environmental ; Bioreactors ; Cations ; Hydrogen-Ion Concentration ; Methane ; analysis ; Organic Chemicals ; analysis ; Oxygen ; analysis ; Regression Analysis ; Time Factors ; Waste Disposal, Fluid ; Water Pollutants, Chemical ; isolation & purification

Objective:To summarize our experience in perioperative anesthetic management for fulminant hepatic failure (FHF)patients receiving liver transplantation.Methods:The clinical anesthetic data of 48 FHF patients receiving orthotopic liver transplantations(OLT)from January 2006 to January 2007 were retrospectively analyzed,and the anesthetic management expe- rience was summarized.General anesthesia was applied;the hemodynamics was monitored during the operation and doses of adrenaline and phenylephrine were adjusted according to the monitoring results.Blood samples were obtained before operation, before anheptic,30 min after anhepatic phase,5 min before neohepatic phase,and 5 min,30 min and 60 min after neohepatic phase for blood gas and electrolyte analysis and for determination of coagulation function;the drugs were subsequently adjusted according to analysis results.Results:All the 48 patient underwent successful anesthetic management and there was no death dur- ing opearation.The average blood loss during operation was(5 219?478)ml.Mild alkalosis,hypokalemia,hyponatrium,and hy- pocalcemia were present before operations,pH,BE and HCO_3~- were obviously reduced 30 min after anhepatic phase and in- creased 60 min after neohepatic phase.Kalemia was obviously increased 30 min following anhepatic phase and began to increase 60 min following neohepatic phase.Calium concentration was decreased at the end of preanhepatic phase(P