Recently traditional Chinese medicine (TCM)-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury (DILI) is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.
Animals ; Biomarkers, Pharmacological ; metabolism ; Biopsy ; methods ; Chemical and Drug Induced Liver Injury ; diagnosis ; metabolism ; pathology ; Early Diagnosis ; Humans ; Liver ; drug effects ; pathology ; Medicine, Chinese Traditional ; adverse effects ; Rats

Objective To examine how ischemic time under common temperature affects acute rejection by using a rat vascularized skin transplantation model.Methods Vascularized groin flaps were transplanted from BN to Lewis rats with 1,2,3 and 4 h of ischemic time (Isc-1 h,2 h,3 h,4 h groups) under common temperature,and the allografts in each group were evaluated daily.Groin flaps were transplanted from Lewis to Lewis rats as control group.Biopsy samples taken from the each group on the postoperative day 2-8 were graded for signs of acute rejection.Biopsy samples taken from each group on the postoperative day 6 were stained for chemokine receptor CXCR3.Results When the ischemia time was 1,2,3 and 4 h,the survival time of the grafts was (9.0 ± 1.2),(8.6 ±1.1),(8.8 ± 1.3),and (7.0 ± 0.8) days respectively.The survival time in Isc-4 h group was significantly shorter than in other groups (P＜0.05).Histological evaluation showed acceleration of activated lymphocyte infiitration in the Isc-4 h group as compared with other g.roups.Furthermore,the proportion of CXCR3 positive cells in the Isc-4 h group was (50.1 ± 8.4) ％,significantly higher than that in the other groups on the day 6 after transplantation.Conclusion When ischemic time was over 3 h,the immune response is accelerated.The acceleration is associated with the higher expression of CXCR3 in the infiltrated cells.

Objective To understand acute rejection differences between untreated recipients and rapmycin-treated recipients in a rat free flap allotransplantation model. Methods Brown groin free flaps were transplanted to Lewis recipients. In the treated group, recipients were treated with rapamycin at the dose of 4 mg/kg every day from day 0 to day 14 after transplantation. In the untreated group, recipients didn't receive any treatment. Allografts were evaluated clinically and histologically. Results Allografts in the treated group showed epidermolysis as sign of rejection.Rejection sign of untreated grafts was ischemic necrosis of whole skin. In histological evaluation, the treated grafts showed "band-like" lymphocytes infiltration in the upper dermis when rejection occurred, while the untreated grafts showed thrombosis in the subdermal vessels. Conclusion The differences between the two groups implied that embolization may be responsible for the rejection of free flap allotransplantation in rat model.

Background Ginkgolide B (GB) has been proved to have neuroprotective and anti-apoptotic effects and can effectively inhibit apoptosis of retinal photoreceptor cells.But the high hydrophobic feature and low bioavailability of GB limit its clinical application.Self microemulsifying drug delivery system (SMEDDS) can effectively improve the infusibility drug dissolution and bioavailability in the retina.Objective This study was to investigate the pharmacokinetics and drug-time change of GB-loaded SMEDDS in retina.Methods Eighty SD rats were randomized into 2 groups,2.5％ GB(40 mg/kg) of SMEDDS or GB suspension(0.1％ DMSO dissolve) were gastrically given respectively in two groups.The rats were sacrificed and retinas were isolated 15,30,45 minutes and 1 hour,2,4,8,12 hours to prepare the retinal suspension.The content of GB in retina was assayed with high performance liquid chromatography-electrospray ionization-(1) (1)ss spectrum (HPLC-ESI-MS) and contrasted with standard curve.Practical drug dynamics program 3p87 was used to detect the pharmacokinetics parameters.The maximal content(Cmax,mg/g),time to peak (Tmax,h),clearance ratio (Ke/h),high-life period (t1/2) and area under the concentration-time curve(AUC0-∞,mg/(g · h)) of GB in various time points in retina after a single oral dose were calculated and compared between two groups.Results The standard curve was obtained over the concentration range of 1-32 mg/L with a linear regression equation,Y =0.0732X + 0.056 (r =0.992).A similar content-time curve was seen between GB suspension group and GB-SMEDDS group.The GB content was higher in GB-SMEDDS group than that in GB suspension group from 30 minutes through 12 hours after administration of drugs.The Cmax of GB-SMEDDS group and GB suspension group were(15.83±1.84) mg/g and(2.65±0.10) mg/g,the AUC0-∞ were(15.30±0.11)mg/(g· h)and(6.42±0.19)mg/(g · h).Conclusions HPLC-ESI-MS is proved to be a rapid,accurate,sensitive and suitable method for pharmocokinetic study of GB.SMEDDS can raise the concent of GB in retina,and it probably improve the bioavailability of GB.

The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines.
China ; epidemiology ; Drug Evaluation ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Product Surveillance, Postmarketing

Post-marketing evaluation is a process which evaluate the risks and benefits of drug clinical application comprehensively and systematically, scientific and systematic results of post-marketing evaluation not only can provide data support for clinical application of traditional Chinese medicine, but also can be a reliable basis for the supervision department to develop risk control measures. With the increasing demands for treatment and prevention of disease, traditional Chinese medicine has been widely used, and security issues are also exposed. How to find risk signal of traditional Chinese medicine in the early stages, carry out targeted evaluation work and control risk timely have become challenges in the development of traditional Chinese medicine industry.
Drug Evaluation ; methods ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Traditional Chinese medicine Polygoni Multiflori Radix is dried roots of Polygonaceae Polygortum multiflorum Thunb. Its clinical application records were first discovered in literatures of the Tang dynasty. The origins, efficacy, toxicity, processing and taboos of Polygoni Multiflori Radix have been discussed in many ancient herb literatures. In recent years, with the increase in the public awareness in health, Polygoni Multiflori Radix admits preparations have been more widely applied in the treatment and prevention of diseases. However, there have been more and more reports about Polygoni Multiflori Radix induced liver injury, the safety of Polygoni Multiflori Radix has increasingly attracted attention of the society. In this paper, the authors summarized and analyzed the toxicity and medication risk factors of Polygoni Multiflori Radix recorded in ancient herb literatures, and proposed that more attention shall be given to the effect of the planting and processing methods on the components and toxicity of Polygoni Multiflori Radix in safety studies, which provides clues for the further studies.
China ; Drugs, Chinese Herbal ; adverse effects ; history ; History, Ancient ; Humans ; Medicine in Literature ; Medicine, Chinese Traditional ; history ; Polygonum ; adverse effects ; Risk Assessment

The renal toxicity and mutagenicity of aristolochic acid (AA) as well as its carcinogenicity on upper urinary tract transitional epithelial cells have been widely known. Since 2003, drug regulatory departments have successively cancelled the quality standards for AA-containing medicines such as Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolchiae Fangchi Radix, and adopted measures for strengthening regulation and revising package insert or quality standards for other AA-containing medicines, including Aristolochia Cinnabarina Radix, Aristolochiae Fructus, Aristolochiae Mollissimae Herba, in order to control its safety risk. In recent years, domestic and foreign studies on AA have mainly involved action mechanism and clinical performance of AA toxicity, early-stage diagnosis and treatment method. In this paper, authors gave a brief summary and evaluation on risk factors for using AA-containing medicines, and offered measures and suggestions for preventing and controlling AA toxicity.
Animals ; Aristolochia ; adverse effects ; chemistry ; Aristolochic Acids ; analysis ; therapeutic use ; toxicity ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; toxicity ; Humans

Objective To investigate the epidemiology of bacterial infections after liver transplantation and anaIyze the antimi- crobial susceptibility of major pathogens to provide reference for clinical therapy.Methods A retrospective survey was conduc ted in 174 patients who underwent liver transplantation during 2001 and 2004.Identification and susceptibility of pathogens were assayed by Microscan Walkaway 40 Automatic System.Results Infection was identified in 59.8% of the 174 patients after liver transplantation.A total of 218 non-duplicate strains were isolated.Most infections were caused by single pathogen.The infection was frequently identified in respiratory tract,biliary tract,blood stream or intra-abdominal cavity.The top 5 patho- gens were Acinetobacter baumannii,Staphylococcus aureus,Pseudomonas aeruginosa,Stenotrophomonas maltophilia and Escherichia coli.Gram-negative bacilli were usually resistant to multiple antimicrobial agents,but less resistant to piperacillin- tazobactam or imipenem.Most of S.aureus isolates were methicillin-resistant,which were susceptible to vancomyein.Conclu- sions Pathogens of postoperative infections in liver transplantation recipients are mostly multi-drug resistant.The microbiologi- cal surveillance is important for guiding clinical therapy.