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

Objective To evaluate the effects of high intensity focused ultrasound (HIFU) on hepatic cancer cells spreading in blood.Methods AFP mRNA in peripheral blood of 19 patients with hepatocellular carcinoma was detected before and after HIFU therapy by RT PCR.Results ①Before HIFU therapy, 11 of 19 cases were AFP mRNA positive (57.9%), while the control group were all negative. AFP mRNA was correlated with some clinical parameters such as serum AFP level, tumor size, portal vein embolism and extrahepatic metastasis ( P 0.05). ③After one week of HIFU therapy, the AFP mRNA positive rate of the group with tumor size less than 8 cm was much lower than that of tumor size larger than 8 cm ( P

OBJECTIVE:To establish a New Vierordt method for assaying ingredients in compound fleroxacin suppositories and compound fleroxacin ear drops METHODS:New Vierordt method was applied to determination of fleroxacin and tinidazole in compound fleroxacin suppositories and fleroxacin and metronidazole in compound fleroxacin ear drops with no need of separation RESULTS:The fleroxacin and tinidazole in compound fleroxacin suppositories were detected at wavelength 286nm and 317nm respectively The average recoveries were 100 17% and 99 96% with RSDs=0 44% and 0 37% respectively The fleroxacin and metronidazole in the compound fleroxacin ear drops were detected at wavelength 286nm and 318nm respectively The average recoueries were 100 65% and 99 92% with RSDs=0 65% and 0 21% respectively CONCLUSION:The New Vierordt method can be used for quality control of the two compound preparations because of its convenience,accuracy and good repeatability and can eliminate mutual interference of two ingredients in preparations

Objective To systematically investigate the efficacy and safety of sublingual immunotherapy( SLIT) in the treatment of a-dults with seasonal allergic rhinitis( SAR) .Methods Literature was retrieved online in CNKI,CBM,VIP,Wanfang data,PubMed,EMBase, Medline,Cochrane Library,et al.After screening literature,data collection and assessment quality,randomized controlled trials relevant to our study were selected independently based on inclusion and exclusion criteria by two researchers.Statistical analyses were conducted by RevMan 5.2 software.Results A total of 13 RCTs were enrolled.The meta-analysis revealed that SLIT provided a significant improvement in aspect of reducing Symptom Scores(SS) and Medication Scores (MS)of adults with SAR,the difference had statistical significance(P<0.000 01). Compared to placebo,SLIT could increase the rate of adverse events( AEs) in the treatment of adults with SAR compared to placebo.The fre-quently reported AEs during clinical trials were oral pruritus,tongue edema,ear pruritus,throat irritation,et al.Conclusion Sublingual im-munotherapy could improve the symptoms significantly and reduce the SS and MS in the treatment of adults with SAR.And its safety could be well tolerated.

Genetic Therapy ; Mouth Neoplasms ; therapy

Purpose To evaluate the application value of volume CT perfusion (CTP) protocol with 128-slice CT scanner in patients with unilateral middle cerebral artery (MCA) stenosis or occlusion.Materials and Methods Thirty-five patients with severe unilateral MCA stenosis or occlusion who underwent cerebral volume CTP examination in Wuhan No.1 Hospital between July 2013 and December 2014 were evaluated.The volume CTP parameter maps of cerebral blood flow (CBF),cerebral blood volume (CBV),mean transit time (MTT) and time to peak (TTP) were analyzed.Meanwhile,the dynamic CT angiography (4D-CTA) images were obtained.Results In three patients,CBF,CBV and MTT were observed normal but TTP was delayed.In the other thirty-two patients,CBF in the affected side was lower than that in the contralateral side (but difference without significance:P＞0.05).The increased CBV,prolonged TTP and MTT were also detected in the affected side compared with the contralateral side (difference with significance:P＜0.05).McNemar test showed 4D-CTA and DSA diagnosis of middle cerebral artery occlusion were not significantly different (P＞0.05),and they had better consistency (Kappa=0.861,P＜0.05).Conclusion Brain volume CTP protocol with 128-slice CT scanner provides valuable information about cerebral artery abnormalities and hemodynamic changes in patients with severe stenosis or occlusion of MCA.It has great value for clinical application.

AIM: To observe the expression change of growth and differentiation factor 10 ( GDF10 ) in the spinal cord of the rats with neuropathic pain .METHODS:Male SD rats (n=60) were used.The neuropathic pain was induced by ligation of left L 5 spinal nerves of the animals .The paw withdrawal threshold was detected 1 d before surgery , and 0 d, 1 d, 3 d, 10 d and 21 d after surgery.The changes of GDF10 in the dorsal horn of L5 spinal cord were detected by immunofluorescence staining and Western blot .RESULTS:The paw withdrawal threshold of the rats with spinal nerve ligation was decreased from 1 d after surgery until 3 d with obvious difference compared with the na ve rats ( P<0.05 ) , continuously decreased until 10 d, and then stabilized at 21 d.The GDF10 was located in the cytoplasm of the neurons in the dorsal horn of L5 spinal cord detected by immunofluorescence staining .The expression of GDF10 in L5 dorsal horn de-tected by immunofluorescence staining was reduced after surgery , significantly decreased from 10 d ( P<0.05) until more than 21 d after surgery in spinal nerve ligation group compared with na ve group.GDF10 in L5 spinal cord detected at 10 d after surgery by Western blot was significantly down-regulated in spinal nerve ligation group compared with na ve group (P<0.05).CONCLUSION:Spinal nerve ligation induces the decrease in GDF 10 expression in spinal dorsal horn .The down-regulation of GDF10 may contribute to the regulation of hyperpathia caused by mechanical stimulation after the injury of spinal nerve .

The samples of experimental and control groups were obtained by 1 ∶ 1 matching method and divided into development (242 pairs) and sign (156 pairs) groups.Through a 10-month group and case type intervention,Gesell test was performed for 5 zone development quotients of large motor,fine motor,adaptability,speech and personal-social to determinate the effectiveness of interventions.Before intervention,t values of the development group were 1.07,1.42,0.78,0.62 and 1.67 while those of sign group-1.48,-1.96,1.82,1.78 and-1.73 respectively.The inter-group comparison of various developmental quotient differences had no statistical significance (P ＞ 0.05).After intervention,t values of the development group were 9.85,8.92,3.57,11.21 and 9.30 for inter-group comparison and-31.65,-36.94,-46.26,-37.56 and-49.85 for intra-group comparison.The results of sign group were 10.91,9.61,10.75,12.01 and 14.36 for inter-group comparison and-23.20,-31.75,-44.94,-33.58 and-54.58 for intra-group comparison.Between intra-group and inter-group,the comparison of the developmental quotient differences had statistical significance (P ＜ 0.01).In two experimental groups,the post-intervention developmental quotients in 5 zones are better than those pre-intervention levels.It shows that preventive intervention of infant mental health is effective.

Objective To evaluate the changes of the activation and proliferation of rat cardiac fibroblasts in infarcted and non-infarcted regions.Methods The model of myocardial infarction (AMI)was developed through the ligation of anterior descending branch of left coronary artery.After 24 hours,the survived 114 rats were randomly assigned to the following 2 groups:(1)AMI group (n=57);(2)telmisartan treatment group(n=57).And a sham-operated group(n=32)was used asa control.All groups were terminated at day 4,7,14,28,respectively(n=10,12,15,20).At the end of the study,heart rate(HR),blood pressure (BP),ventricle relative weight (ventricle weight/body weight,VW/BW) and survival rate were measured,and the activation and proliferation of fibroblast and collagen volume fraction (CVF) were assessed.Results (1)The 28 day accumulated survival rate for treatment group was lower than that for AMI group (P

The mRNA levels of adiponectin in adipose tissue and adiponectin receptor R1 in skeletal muscle of type 2 diabetic rats were examined by semi-quatitative RT-PCR.The expression of adiponectin receptor R1 was not altered in the skeletal muscle of type 2 diabetic rats as compared with normal rats.The serum adiponectin level was decreased in diabetic rats due to the decline of adiponectin mRNA level in adipose tissue and rosiglitazone improved the adiponectin deficiency.