Genotoxicity research takes an important place in traditional Chinese medicine safety evaluation. Genotoxicity test on traditional Chinese medicine has been paid great attention since 1970s. Currently, the most developed genotoxicity test methods included: bacterial reverse mutation test and mouse lymphoma assay which are used to detect relevant genetic changes, micronucleus test and chromosomal analysis which are used to measure chromosomal aberration, and single cell electrophoresis assay which is used to test DNA damage. This article reviews research progress on genotoxicity of traditional Chinese medicine, evaluation methods of genotoxicity, the problems and solutions on genotoxicity evaluation of traditional Chinese medicine, and new technique used in genotoxicity test.
Animals ; Biomedical Research ; Humans ; Medicine, Chinese Traditional ; adverse effects ; Mutagenicity Tests ; methods

Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug, drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years, FDA, SFDA OECD, ICH and WHO have published several guidelines on per-clinical immunotoxicity evaluation, however, no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation.
Drug Hypersensitivity ; diagnosis ; Humans ; Immune System ; drug effects ; Practice Guidelines as Topic

BACKGROUND: With the improvement of medical imaging technology, the visualization of human anatomy has been further developed; the role of three-dimensional (3D) reconstruction in medical treatment is also becoming increasingly prominent. Mimics is the most widely used medical image reconstruction software. Arigin 3D Pro is a recently developed 3D reconstructed medical software system based on 3D printing. OBJECTIVE: To study the accuracy of 3D reconstruction models obtained by using Arigin 3D Pro and Mimics with medical images. METHODS: The image data of liver, spine, knee joint and heart were selected, and the deviations of two software reconstruction models were analyzed based on the 3D model reconstructed by Mimics. Totally 10 cases of skull and 1 case of femoral comminuted fracture image data were selected and reconstructed. Each reconstruction model was measured with 10 groups of feature sizes to evaluate the differences between the two software programs. RESULTS AND CONCLUSION: Arigin 3D Pro and Mimics were used to reconstruct the liver, spine, knee and heart data. The mean ± standard deviation of model deviations were (0.93 ± 1.05), (0.36 ± 0.74), (0.45 ± 0.74), (0.18 ± 0.41) mm. It took 3 minutes and 35 minutes for Arigin 3D Pro and Mimics to reconstruct the liver model respectively, and both software reconstructed other models for less than 1 minute. There was no statistically significant difference between the feature sizes of the two software for the 3D reconstruction models of skull and femoral comminuted fracture data (P > 0.05). The 3D reconstruction model of Arigin 3D Pro is comparable to that of Mimics. For the liver model, the reconstructed time of Arigin 3D Pro is significantly shorter than that of Mimics.

OBJECTIVETo explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.

METHODSForty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.

RESULTSSignificant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.

CONCLUSIONTreatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.

Aging ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; CA1 Region, Hippocampal ; metabolism ; CA3 Region, Hippocampal ; metabolism ; Dentate Gyrus ; metabolism ; Erythropoietin ; pharmacology ; Frontal Lobe ; metabolism ; Galactose ; Humans ; Male ; Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology

OBJECTIVETo observe the distribution of hypoxia inducible factor-1alpha (HIF-1alpha) in different brain regions in aged rats and investigate the role of HIF-1alpha in the aging process of the nervous system.

METHODSThe Nissl bodies and HIF-1alpha expression in different brain regions were observed in rats aged 3 and 30 months using Nissl staining and immunohistochemical method, respectively.

RESULTSIn the 30-month-old rats, the neural cells in 4 different brain regions presented with large cell body and loose alignment, containing reduced Nissl bodies in the cytoplasm. Compared with the 3-month-old rats, the aged rats showed greater number of HIF-1alpha-positive cells in the brain (P < 0.01), and the number varied significantly between the different brain regions (P < 0.01). The CA3 region contained the greatest number of positive cells, which were fewer in the motor cortex and cerebellum.

CONCLUSIONThe capacity for protein synthesis in the neural cells is weakened but the expression of HIF-1alpha increased in aged rats, suggesting the important role that HIF-1alpha may play in the aging process of the nervous system, especially in hypomnesis.

Aging ; metabolism ; Animals ; Brain ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.

METHODSMorphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.

RESULTSOX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.

CONCLUSIONInflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.

Animals ; Cell Proliferation ; Disease Models, Animal ; Hippocampus ; cytology ; pathology ; Male ; Microglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; pathology

Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.

OBJECTIVETo observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action.

METHODSThe global cerebral ischemia-reperfusion injury model was established using the modifified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively.

RESULTS(1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged signifificantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the puerarin group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the puerarin group was up-regulated at the respective time points after ischemia reperfusion (P<0.01), reaching the peak on day 1.

CONCLUSIONSPuerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

Animals ; Apoptosis ; drug effects ; Brain Ischemia ; complications ; drug therapy ; Hippocampus ; drug effects ; pathology ; Isoflavones ; pharmacology ; therapeutic use ; Learning ; drug effects ; Memory Disorders ; complications ; drug therapy ; Models, Biological ; Protective Agents ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Reaction Time ; drug effects ; Reperfusion Injury ; complications ; drug therapy

OBJECTIVETo examine the distribution of glucose transport 3 (GLUT 3) in different brain regions of aged rats and to investigate its role in ageing process of the nervous system.

METHODSThe GLUT 3 expression in different brain regions was examined with immunohistochemical method in rats aged 3, 18 and 30 months, respectively.

RESULTSThe number of GLUT 3-positive cells varied in the different brain regions in rats of all age groups (P<0.01); the CA1 region contained the greatest number of positive cells,and fewer in the motor cortex and cerebellum. The number of GLUT 3-positive cells was reduced in the brain of aged rats (P<0.01); and the neural cells in 4 different brain regions presented with large cell body and loose alignment.

CONCLUSIONThe expression of GLUT 3 decreased in aged rats, which suggests that GLUT 3 may be involved in the ageing process of nervous system.

Aging ; metabolism ; Animals ; Brain ; metabolism ; Glucose Transporter Type 3 ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes of p38MAPK expression in a rat model of Alzheimer disease (AD).

METHODSSeventy-two adult SD rats were randomized equally into 4 groups, and a single-dose injection of Abeta25-35 (dementia group), normal saline (saline group), SB203580 (inhibitor group), or DMSO (inhibitor control group) was administered into the lateral cerebral ventricle. Y-maze tast was performed to evaluate the behavioral changes of the rats after the injections, and on days 4, 7 and 14 after the injection, p38MAPK expression in the hippocampal CA1 area was measured by means of immunohistochemistry.

RESULTSOn days 7 and 14 following Abeta25-35 injection, the training times, error number and total reaction time were significantly higher in dementia group than in saline group (P<0.05), but all these indices were significantly lowered in the inhibitor group as compared with the dementia group (P<0.05). Immunohistochemistry revealed obvious p38 expression in the dementia group 4 days after Abeta25-35 injection, which increased significantly with the passage of time (P<0.01). The gray scale in the inhibitor group was significantly higher than that in the dementia group (P<0.01).

CONCLUSIONp38MAPK activation in the hippocampal CA1 area is an event that persists during the entire course of Abeta25-35-induced AD in rats, and the inhibitor SB203580 prevents p38MAPK expression and improves the learning and memory abilities of the rats.

Alzheimer Disease ; chemically induced ; enzymology ; metabolism ; Amyloid beta-Peptides ; administration & dosage ; toxicity ; Animals ; Hippocampus ; drug effects ; enzymology ; Immunohistochemistry ; Male ; Maze Learning ; drug effects ; Peptide Fragments ; administration & dosage ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; biosynthesis