As an integral part of translational medicine,translational toxicology is intended to apply the results of toxicological studies to the prevention of diseases and the harmful effects on organisms. As far as drug safety evaluation is concerned,translational work is focused on developing more sensitive and specific translational safety biomarkers. Previous research focused on indicators of the liver and kidney,cardiovascular damage in the early stage,and detection of early-stage cancer. MicroRNA is hot sphere of research and considered a potential biomarker. Translational toxicology requires multi-discipli-nary and multi-agency communication and cooperation. The approach adopted by the Predictive Safety Testing Consortium is relatively perfect and is worth learnikng from.

· AIM: To observe the effect of tetrandrine (Ted) eye drops of different concentrations on corneal graft and on allograft rejection in rats.64 SD rats and they were then randomly divided into 3,5, 10g/L tetrandrine eye drops-treated and control groups. At different times postoperatively, neovascularization and inflammation of corneal graft were observed using slit-lamp microscopy, HE staining, light microscopy and microphoto-analysis.lymphocytes and mononuclear-macrophages. Corneal neovascularization and inflammation were significantly inhibited in the 5g/L Tet-treated group (P ＜0.05),compared with control group at 7, 14, 21, 28d postoperatively.bubble appeared when the graft was treated with tetrandrine of higher concentration (10g/L), but 5g/L Tet eye drops significantly inhibited corneal allograft rejection in rats without serious side-effects.

OBJECTIVETo investigate the migration of fluorescent dye PKH26-labeled BM-MSC in the Alzheimer's model rats.

METHODSNormal human bone marrow extracted for isolation of BM-MSC was cultured in vitro. The 5th passaged BM-MSC was labeled with PKH26, and observed under a fluorescence microscope for PKH26 labeling efficiency, and using flow cytometry BM-MSC surface markers was checked. The PKH26 labeled BM-MSC injected into the tail vein of the normal control group and AD animal model group, 14 days after finding the PKH26-labeled BM-MSC cells in the rat hippocampus using fluorescence microscopy. Using the Morris water maze experiment comparison of AD model and BM-MSC transplantation group of spatial learning and memory ability.

RESULTSTFlow cytometry showed BM-MSC surface markers CD73 and CD105 were positive. In vitro, PKH26-labeled rate of BM-MSC was 100 %. The Morris water maze experiment comparison of BM-MSC transplantation group and AD group of animals, BM-MSC transplantation group at 13, 14 days of spatial learning and memory ability than AD animal group had significantly improved. 14 days after BM-MSCs in rat hippocampus could be found which were PKH26-positive, consistent with DAPI staining. PKH26-positive cells in animal models of AD were significantly more than those in the normal control group.

CONCLUSIONBM-MSC in AD rats not only migrates through the blood-brain barrier, but also mainly survives in the hippocampus of AD rats, and it can improve AD rat model of learning disabilities.

Alzheimer Disease ; pathology ; Animals ; Bone Marrow Cells ; cytology ; Cell Movement ; Cells, Cultured ; Disease Models, Animal ; Humans ; Injections, Intravenous ; Male ; Mesenchymal Stromal Cells ; cytology ; Organic Chemicals ; Rats ; Rats, Sprague-Dawley

0.05).However,A-waves were recorded in 7 patients who were with normal F-waves.Conclusion The occur- rence of A-waves,especially of multiple type,in the ulnar and median nerves might be helpful for the early diagnosis of Guillain-Barr?Syndrome.

The epieardial adipose tissue in 210 subjects with or without metabolic syndrome (MS) was measured by echocardiography.The thickness of epicardial adipose tissue in male with MS group was significantly greater than that in men without MS [(9.10?3.59) mm vs (6.82?3.00) mm,P

OBJECTIVEThis study aimed to investigate the feature of D(L)CO (Diffusion Lung Capacity for Carbon Monoxide) in CHF (left ventricular heart failure) patients, underlying pathophysiological mechanism and clinical significance.

METHODSWe retrospectively studied the D(L)CO, pulmonary ventilation function, cardiopulmonary exercise testing and related clinical information in severer HF patients.

RESULTSPeak VO2 severely decreased to 34 ± 7 percentage of predicted(%pred) and anaerobic threshold to 48 ± 11%pred in all patients. D(L)CO moderately decreased to 63 ± 12%pred and there were 25 patients lower than 80%pred. FVC, FEV1, FEV1/FVC and TLC were 75 ± 14%pred, 71 ± 17%pred, 97 ± 11%pred, and 79 ± 13%pred, which indicated borderline or mild restrictive ventilatory dysfunction. The decrease of D(L)CO was more severe than those of TLC, FEV1 and FVC.

CONCLUSIONFor patients with severe CHF, cardiopulmonary exercise function is extremely limited, D(L)CO generally moderately declines and ventilation function is merely mildly limited. D(L)CO is the parameter for cardiopulmonary coupling, reflecting limitation of the cardiovascular dysfunction while without ventilatory limit.

Blood Gas Analysis ; Heart Failure ; physiopathology ; Humans ; Respiratory Function Tests ; Retrospective Studies ; Ventricular Dysfunction, Left ; physiopathology

Objective To explore the effect of resveratrol ( Rev) as an antioxidant on oxidative damage to HepaRG cells induced by troglitazone ( Tro).Methods Cells were divided into five groups: control ( RPMI 1640 only with 0.1%DMSO), Tro(50 μmol/L), Tro(50 μmol/L) +Rev(15 μmol/L), Tro(50 μmol/L) +Rev(7.5 μmol/L) and Tro (50 μmol/L)+Rev(3.75 μmol/L) groups.MTT assay was performed to detect the viability of Rev-treated, Tro-treated and Rev with 50 μmol/L Tro-treated HepaRG cells.After 48 hours, the level of reactive oxygen species (ROS) and lipid oxidation ( malondialdehyde , MDA ) , degree of apoptosis , total antioxidant capacity , activity of hydrogenperoxidase (catalase, CAT), glutathione peroxidase (GSH-px) and superoxide dismutase(SOD)of these groups were identified. Results Tro could obviously cause HepaRG cells to produce oxidative stress .Compared with control group ,ROS and lipid peroxidation ( MDA) levels and the rate of apoptosis and necrosis in Tro-treated group were significantly increased ( P<0.05),total antioxidant capacity greatly reduced (P<0.05),and the activity of CAT,GSH-px and SOD was decreased (P<0.05).After adding various concentrations of Rev interaction , ROS and MDA production volume decreased (P < 0.05), and the apoptosis and necrosis rate correspondingly declined (P<0.05).Total antioxidant capacity of the cells and the activity of the three antioxidant enzymes were increased (P<0.05), and there was a dose-dependent relationship. Conclusion Tro can cause HepaRG cells to produce significant oxidative stress while Rev can significantly improve the oxidative damage of Tro to HepaRG cells .

Objective Pemetrexed and β-elemene can inhibit the growth of tumor cells .This study was to investigate the effect of pemetrexed combined with β-elemene on the proliferation and apoptosis of cervical cancer HeLa cells. Methods Cervical cancer HeLa cells were treated with pemetrexed at the concentrations of 38, 76, 152, 228, and 304μg/mL, and at 24 and 48 hours of treatment subjected to MTT for detection of their proliferation .The experiment included four groups , with the cells treated with β-elemene ( 125μg/mL) , pemetrexed ( 76 μg/mL ) , β-elemene ( 125 μg/mL ) +pemetrexed (76μg/mL), and nothing (blank control) for 24 hours, followed by determination of their proliferation and apoptosis by MTT and flow cytometry, respectively. Results Pemetrexed at 38, 76, 152 and 228μg/mL inhibited the proliferation of the HeLa cells in a concentration-dependent manner, with the inhibition rates of (7.24 ±3.78), (7.94 ±4.37), (11.10 ±2.86) and (15.88 ± 3.38)%at 24 hours, and (16.69 ±0.95), (22.54 ±1.53), (24.48 ±0.92) and (25.54 ±3.61)%at 48 hours, both with statis-tically significant differences between any two groups (P<0.05).Significant differences were also found in the proliferation rate of the same concentration of pemetrexed at the two time points (P<0.05).The combination of pemetrexed and β-elemene showed an inhibi-tion rate of (49.95 ±5.76)%at 24 hours, remarkably higher than (24.36 ±5.59)%in theβ-elemene group and (10.69 ±1.37)%in the pemetrexed group (P<0.01). Conclusion Pemetrexed combined with β-elemene can significantly inhibit the proliferation and synergistically accelerate the apoptosis of HeLa cells .

OBJECTIVETo investigate the effects and mechanisms of Wuling mycelia on seizure development and learning ability induced by pentylenetetrazole-kindling epilepsy in rats.

METHODSSD rats were randomly divided into four groups: pentylenetetrazole-kindling model group (model group), low dose Wuling mycelia (0.3 g*kg(-1)) group (LD-WM group), high dose Wuling mycelia (0.6 g*kg(-1)) group (HD-WM group) and control group. The rats were intraperitoneal injected with a subconvulsive dose (35 mg*kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for 12 times. Wuling mycelia was intragastrically applied 30 min before pentylenetetrazole injection. An 8-arm radial maze ( 4 arms baited) was used to measure the learning ability. Histamine was measured by chemical fluorometric enzyme immunoassay.

RESULTSCompared with the model group, the kindling stage of LD-WM group degraded significantly after 7th injection, the latency to the onset of myoclonic jerks (LTMJ) and the latency to the onset of generalized seizures (LTGS) prolonged after the 6th and 7th injection, respectively (P<0.05). The kindling stage of HD-WM group also degraded markedly after the 6th to 8th injection, and the LTMJ and the LTGS extended after the 8th to 9th and 6th injection, respectively (P<0.05). Compared with the control group, the frequency of working memory error (WME) and reference memory error (RME) of the model group in the 8-arm radial maze increased through 3-d training (P<0.05). The memory tests showed that the impairment induced by pentylenetetrazole was partially reversed by Wuling mycelia. Compared with the control group, brain histamine contents (hippocampus, cortex, thalamus and hypothalamus) were significantly lower in model group (P<0.05). But compared with the model group, hippocampal histamine contents in LD-WM group and hippocampal, thalamic and hypothalamic histamine contents in HD-WM group were elevated (P<0.05).

CONCLUSIONWuling mycelia can delay the kindling and ameliorate the ability of learning in rats with pentylenetetrazole-induced epilepsy and the enhancement of neuronal histamine activity may be one of possible mechanisms.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Epilepsy ; chemically induced ; metabolism ; prevention & control ; Hippocampus ; metabolism ; Histamine ; metabolism ; Kindling, Neurologic ; drug effects ; Learning ; drug effects ; Male ; Pentylenetetrazole ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the clinical symptom and effect of arthroscopic treatment of symptomatic anterior cruciate ligament (ACL) cysts of the knee.

METHODSClinical data from 12 symptomatic ACL cysts patients from January 2005 to December 2010 were retrospectively analyzed,including 8 males and 4 females,with an average age of (33.7±9.5) years old (ranged, 19 to 53 years old). The locations were the left knee in 5 cases and the right knee in 7 cases. The disease duration ranged from 3 to 48 months,with a mean of (15.8±13.2) months. All cysts were arthroscopically resected. Range of motion was measured preoperatively and postoperatively, and Lysholm scoring system was used to evaluate the knee function.

RESULTSAll the incisions healed by first intention, and no complications occurred. Twelve patients were followed up for an average of (32.3±6.6) months(ranged, 24 to 48 months). The symptoms of arthralgia,swelling and interlocking of the affected knees disappeared. There was no recurrence during the follow-up. There were significant differences in the range of motion and Lysholm score between pre-operation and post-operation.

CONCLUSIONArthroscopic surgery, showing its advantages of minimal invasion and rapid recovery,is an effective measure in the treatment of ACL cysts.

Adult ; Anterior Cruciate Ligament ; physiopathology ; surgery ; Arthroscopy ; methods ; Cysts ; physiopathology ; surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Range of Motion, Articular