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.

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 .

ObjectiveTo study the protective effects of tert-butylhydroquinone(tBHQ) on sodium arsenite (NaAsO2)-induced cytotoxicity and oxidative injuries. Methods Chang liver cells were pretreated with tBHQ[0(control), 5, 25 μmol/L]for 24 h, and then co-treated with tBHQ(5 μmol/L) together with NaAsO2[0(control),30, 40, 50, 60 μmol/L] for another 24 h, and Alamar blue reduction rates were used to evaluate cell viability,the results were expressed as the relative ratio of Alamar blue reduction rates between the experimental group and the control group. On the other hand, Chang liver cells were pretreated with tBHQ[0(control), 5, 25 μmol/L] for24 h,and then co-treated with tBHQ(5 μmol/L) together with NaAsO2[0(control), 40, 50 μmol/L] for another 24 h,and the levels of cellular reactive oxygen species(ROS) were detected by staining cells with 2',7'-dichlorofluorescin diacetate(DCFH-DA), the results were expressed as the relative ratio of mean fluorescence intensity between the experimental group and the control group. ResultsCell viability decreased dramatically by treatment with NaAsO2(30, 40, 50, 60 μmol/L), while relieved to some extent by pretreatment with 5, 25 μmol/L tBHQ, the main effects of NaAsO2 and tBHQ, as well as their interaction were all statistically significant(F =566.57, 55.09, 14.50,all P ＜ 0.05) ; the cell viability of NaAsO2(30, 40, 50, 60 μmol/L) pretreated with tBHQ(5, 25 mol/L) were 0.75 ±0.02, 0.70 ± 0.04, 0.59 ± 0.03, 0.43 ± 0.03 and 0.75 ± 0.02, 0.73 ± 0.03, 0.65 ± 0.02, 0.50 ± 0.02, respectively,all significantly higher than corresponding NaAsO2 alone groups(0.70 ± 0.03, 0.64 ± 0.03, 0.43 ± 0.03, 0.33 ±0.01, all P ＜ 0.05), the cell viability of NaAsO2(50, 60 μmol/L) pretreated with 25 μmol/L tBHQ was higher than corresponding 5 μmol/L tBHQ pretreatment groups(all P ＜ 0.05). On the other hand, 40, 50 μmol/L of NaAsO2 significantly induced hepatocellular ROS generation, while tBHQ(5, 25 μ mol/L) pretreatment significantly decreased NaAsO2-induced intracellular ROS levels, the main effects of NaAsO2 and tBHQ, as well as their interaction were all statistically significant (F =181.78, 60.55, 4.93, all P ＜ 0.05) ; the ROS levels of NaAsO2(40, 50 μ mol/L) pretreated with tBHQ(5, 25 μmol/L) were 1.87 ± 0.09, 1.80 ± 0.07 and 1.36 ± 0.11, 1.44 ± 0.12,all significantly decreased than corresponding NaAsO2 alone groups(2.30 ± 0.18, 2.18 ± 0.17, all P ＜ 0.05),the ROS levels of NaAsO2(40, 50 μmol/L) pretreated with 25 μmol/L tBHQ decreased than corresponding 5 μmol/L tBHQ pretreatment groups (all P ＜ 0.05). ConclusiontBHQ has a certain antagonism on arsenic induced cytotoxicity and oxidative injuries.

Objective To determine the effects of gutter oil on liver function,renal function and serum lipid metabolism in mice.Methods A total of 72 mice were averagely divided into 6 groups.Mice were gavaged with different dosages (5 μL/g,1 0 μL/g and 20 μL/g)of gutter oil or cooking oil every other day for continuing 8 weeks.The indexes of liver, kidney and serum lipid parameters were assayed.Results The moisture,acid value and peroxide value of the gutter oil exceeded the national standard.After continuing 8 weeks'intake of oils,alanine aminotransferase (ALT)of gutter oil group with a dosage of 5 μL/g,as well as aspartate aminotransferase (AST)of gutter oil group with a dosage of 1 0 μL/g significantly increased (P <0.05),compared with the cooking oil group.Serum creatinine (Scr)of the gutter oil groups with 3 dosages significantly increased compared with the control groups (P <0.05 ).Meanwhile,blood urea nitrogen (BUN)of gutter oil groups with a dosage of 5 μL/g and 1 0 μL/g were also significantly increased respectively(P <0.05). However,no significant differences were observed in triglyceride (TG)and total cholesterol (TC)among the groups. Conclusion Eight weeks'intake of gutter oil could cause the damage to liver and renal functions.

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
Administration, Oral ; Animals ; Arylamine N-Acetyltransferase ; genetics ; metabolism ; Caffeine ; metabolism ; urine ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Male ; Medicine, Tibetan Traditional ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

Rheum franzenbachii (called Tudahuang in local) has some similarities with R. palmatum (rhubarb) collected by "China Pharmacopoeia" and is often used as a substitute of rhubarb. Can Tudahuang simply replace rhubarb in the application or whether is there difference between Tudahuang and rhubarb, and what is the difference it is important to verify the difference and understand its proper application in the field of clinical practice. In this paper, we discussed the differences of the two herbs from the views of chemistry, efficacy and toxicity based on the author's previous research work as well as literatures, by using the major role of the rhubarb "diarrhea" as the basic point. The analysis result showed that the role of diarrhea Tudahuang was much weaker than that of rhubarb. The reason lies in the difference between the contents of combined anthraquinones component. While acute toxicity in mice of Tudahuang is stronger than that of rhubarb. Thus, Tudahuang should not simply replace rhubarb in practice.
Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; toxicity ; Humans ; Mice ; Rheum ; adverse effects ; chemistry

OBJECTIVETo analyze the clinical characteristics and antibiotic resistance in children with invasive Acinetobacter baumannii infection (IABI).

METHODSA retrospective analysis was performed on the clinical and drug sensitivity data of 52 children with IABI between January 2004 and December 2011.

RESULTSOf the 52 children with IABI, 35 (67%) were less than one year old and 35 (67%) had IABI in the summer and autumn, 19 (37%) of these children were clinically diagnosed with septicemia, 16 (31%) with urinary tract infection, and 12 (23%) with skin and soft tissue infection, and 38 (73%) of them suffered from underlying diseases. The incidence rates of hospital-acquired and community-acquired IABIs were 90% and 10% respectively; 44 cases (85%) were cured or showed improvement in symptoms, and 8 cases (15%) died. All the IAB strains isolated from these children were sensitive to amikacin, 82% of them were sensitive to imipenem, more than 70% were sensitive to fluoroquinolone and to cefoperazone/sulbactam, 13% were sensitive to cefoperazone, 8% were sensitive to aztreonam, 21% developed multidrug resistance, and 17% developed pan-drug resistance.

CONCLUSIONSIABI occurs more frequently in children under one year of age, and most children with IABI have underlying diseases. IABI mainly results in septicemia, urinary tract infection and skin and soft tissue infection and is mostly hospital-acquired. Multi-drug resistance and pan-drug resistance are severe in IAB strains.

Acinetobacter Infections ; drug therapy ; Acinetobacter baumannii ; Adolescent ; Child ; Child, Preschool ; Drug Resistance, Microbial ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; Retrospective Studies

BACKGROUNDIn-stent restenosis is a common complication after stent implantation. However, the assessment of stent lumen in computed tomography (CT) coronary angiography is limited by multiple factors. Our study aimed to evaluate the accuracy and the suspected affecting factors in diagnosing coronary in-stent restenosis by dual-source CT (DSCT) compared with coronary angiography.

METHODSOne hundred and fifteen stents in 50 patients were evaluated with DSCT before coronary angiography for the detection of coronary in-stent restenosis (≥ 50% luminal narrowing). Patency of each stent was analyzed by two independent expert radiologists blinded to the results of coronary angiography. The relationship between diagnostic accuracy and the suspected factors including age, body mass index (BMI), heart rate, variation of heart rate, radiation dose, image quality, location and stent characteristics (type, material, diameter, length and strut thickness) was assessed with both univariate and multivariate analysis. The fitting of a Logistic regression model was evaluated using a receiver operating characteristic (ROC) curve.

RESULTSMean stent diameter was (2.9 ± 0.4) mm. Sensitivity, specificity, positive and negative predictive values and accuracy of DSCT in detection of in-stent restenosis were 69.2%, 91.2%, 50.0%, 95.9%, and 88.7%, respectively. In a subgroup of stents with a diameter ≥ 3.0 mm, sensitivity, specificity, positive and negative predictive values and accuracy were 100.0%, 96.5%, 75.0%, 100.0%, and 96.8%, respectively. Stent diameter < 3.0 mm and poor image quality were associated with poor diagnostic accuracy (P < 0.05). The area under curve of ROC was 0.79.

CONCLUSIONDSCT can provide high accuracy for the assessment of in-stent restenosis in stents with a diameter = 3.0 mm, and can play an important role in ruling out in-stent restenosis.

Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Coronary Angiography ; methods ; Coronary Restenosis ; diagnosis ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; methods

OBJECTIVETo investigate the feasibility of volumetric measurement of pericardial adipose tissue (PAT) and intrathoracic adipose tissue (IAT) using coronary computed tomography angiography (CTA), and explore the characteristics of PAT and IAT distribution.

METHODSThe CTA images of 109 patients (aged 59.1∓11.7 years) with a clinical diagnosis of coronary heart disease were analyzed. The volumes of PAT and IAT were measured using the axial data from the base to the apex traced manually with the dedicated semiautomatic software program Volume. The related factors and gender difference of PAT and IAT were analyzed.

RESULTSThe pericardium was clearly defined on CTA images and the volumes of PAT and IAT were measured accurately in all the cases. The volumes of PAT and IAT were positively correlated to body weight and body mass index (BMI) but independent of age, and IAT was positive correlated to the body height. The IAT of male patients was 67% higher than that of female patients (P<0.05), whereas no such a difference was found in PAT (P<0.05).

CONCLUSIONCTA-based semiautomatic segmentation for volumetric quantification of PAT and IAT is highly accurate. The volumes of PAT and IAT are positively correlated to body weight and BMI, and PAT volume exhibits no statistical difference between male and female patients with coronary heart disease.

Adipose Tissue ; diagnostic imaging ; Aged ; Body Mass Index ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Pericardium ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

Objective To observe the effect of breathing exercise based on core strength training on nonspecific low back pain (NLBP). Methods From January to June, 2017, 60 patients with NLBP were randomly divided into control group (n=30) and ob-servation group (n=30). The control group accepted core strength training, and the observation group accepted breathing exercise in addition, for four weeks. They were assessed with Visual Analogue Scale (VAS) and Oswes-try Disability Index (ODI) before and after treatment, and their efficiency was compared. Results The scores of VAS decreased in both groups after treatment (t>4.173, P<0.001), and the scores of ODI de-creased in the observation group (t=3.875, P<0.01). The scores of both VAS and ODI were less in the observa-tion group than in the control group (t>2.595, P<0.05). The efficiency was better in the observation group than in the control group (χ2=3.874, P<0.05). Conclusion Breathing exercise based on core strength training can further improve function and relieve pain in patients with NLBP.