Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Determination of the Mineral Composition of the Pulp and Evaluation of the Acute Toxicity of the Seeds of Carica papaya L. Consumed in Lubumbashi and Kinshasa in the Democratic Republic of the Congo

This work aimed, on the one hand, to determine the mineral and phytochemical composition of Carica papaya in order to guarantee the food safety of consumers and on the other hand, to evaluate the acute toxicity of papaya seeds. The papayas were bought at the Mzée market in Lubumbashi and Selembao in Kinshasa. Fruit sampling was done according to the ISO 7002 standard on agricultural and food products;the papayas were firm, mature, and without stains or physical damage. The analysis results of the papaya pulp showed both for the samples from the city of Lubumbashi and for the city province of Kinshasa that it contains respectively 85.87% and 84.46% water, 0.59% and 0.53% ash content. The mineral evaluation of our two samples presented a potassium content of 200 ± 8 mg, magnesium 13.12 ± 3 mg, calcium 22.15 ± 2 mg, sodium 3 mg ± 0.5 for the sample from Lubumbashi and 192.32 ± 8 mg of potassium, 14.458 ± 3 mg of magnesium, 20.58 ± 2 mg of calcium and 3.58 ± 0.5 mg of sodium for the sample from Kinshasa in macroelements. Concerning the trace elements, after analysis, we found zinc content (0.29 ± 0.1 mg and 0.12 ± 0.1 mg), copper (0.02 ± 0.01 mg and 0.14 ± 0.01 mg), and iron (2.22 ± 0.5 mg and 2.04 ± 0.5 mg) respectively for Lubumbashi and Kinshasa. The chemical screening indicates the presence of alkaloids, saponosides, tannins catechics, flavonoids and anthocyanins in the palm wine and ethanolic extract of the seeds of Carica papaya and an absence of cyanogenic glycosides and gallic tannins. With mild toxicity, the seeds of the fruit of Carica papaya L. can be used with moderate risk by the population.

Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Study on the Acute Toxicity and Genetics Toxicity of Bensulfuronk-methyl on Danio rerio

[Objective] The aim was to study the effect of bensulfuron-methyl herbicide on acute toxicity and genetics toxicity of Danio redo. [ Method] Median lethal concentration was calculated by acute toxicity test, and analyzing the herbicide whether existing in potential toxicity to aquatic organisms or not. Based on the study of acute toxicity, genetics toxicity was carried out, by calculating the micronucleus rate to judge bensulfuron-methyl herbicide whether existing in potential toxicity or not. [ Result ] The LD5o （24 h and 48 h） of bensulfuron-methyl herbicide are 0.698 ml/L and 0.637 ml/L respectively, the safe concentration was 0.159 ml/L. The results on the effects of micronucleus （MN） in erythrocytes of Danio redo induced by bensulfuron-methyl at different times and different concentrations showed that the MN rate of control group was 0.010 3%, the highest MN rate of experimental group reached to 0. 372%, it also indicated that bensulfuron-methyl herbicide had genetics toxicity to Danio redo. At the same detection time, there was dose-effect relationship of MN rate in erythrocytes between treatment and control groups with different concentrations. In the same treatment group, the MN rate in erythrocytes reached to peak value at 24 h, and decreased at 48 h and 72 h with the infection time was prolonged. [ Conclusion ] The study provides some basis for scientifically selecting and reasonably using herbicide.

Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.

Toxicity Tests of Soil Contaminated by Recycling of Scrap Plastics

The present investigation studied the toxicity of soil contaminated by untreated discharge from a factory that recycles used plastics. The nearby agricultural areas and freshwater fish ponds were polluted with high concentrations of Cu, Ni, and Mn. Water extracts from the contaminated soil retarded root growth of Brassica chinensis (Chinese white cabbage) and Cynodon dactylon (Bermuda grass) where their seeds were obtained commercially. The contaminated populations of C. dactylon, Panicum repen (panic grass), and Imperata cylindrica (wooly grass) were able to withstand higher concentrations of Cu. Ni, and Mn, especially C. dactylon, when compared with their uncontaminated counterparts. 1990 Academic Press, Inc.

The Sub Acute Toxicity Evaluation of <i>Stereospermum kunthianum</i>Aqueous Methanolic Stem Bark Extract

Stereospermum kunthianum (Bignoniaceae) is a plant widely used for health benefits. A safety profile evaluation (acute toxicity study) of the plant extract is critical, in a step to the systematic pharmacognostic study of this plant. Thirty-two (32) rats were randomly selected and divided into four groups labelled 1 to 4 with the initial weights of the rats recorded. The animals in group 1 served as control and were administered distilled water, while those in Groups 2, 3 and 4 received 100, 200, and 400 mg/kg respectively, of the Stereospermum kunthianum aqueous methanolic stem bark extract daily. The results indicated no deaths, no observable clinical signs of toxicity, no obvious stress or changes in physical appearance or behaviour in the rats. This general picture of safety is further supported by the multiple comparison post hoc test (Turkey’s) of, the organs weights, the renal (electrolyte, urea and creatinine), the haematological parameters (RBC, HB, PCV, MCV, MCH, MCHC, and Platelet), and the hepatic enzymes (AST and ALT), that all showed the control group to be insignificantly different from the extract treated groups. In conclusion, the extract was deduced to be safe on oral administration for 28 days and it also showed a hepatoprotective quality.

Estimation of Acute Toxicity of Ammonium Sulphate to the Fresh Water Catfish,Heteropneustes fossilis——Ⅰ.Analysis of LC_(50) Values Determined by Various Methods

The acute toxic effects of ammonium sulphate to fresh-water catfish, Heteropneustes fossilis (H.fossilis) have been studied by determining LC50 values with 95% confidence limits, by the graphic method, the logistic method, the Spearman and Karber method and the trimmed Spearman-Karber method. The trimmed Spearman-Karber method was found the most ideal for ammonium salt toxicity test. The flaws in the trimmed Spearman-Karber method are also discussed.

Experimental Study on Acute Toxicity of Yusheng Xiaoyang Lotion in Mice

[Objective] This study was carried out to provide toxicological basic data for the development and research of Yushen Xiaoyang Lotion.[Method]SPF SD mice, half male and half female, were divided into a blank control group and a Yusheng Xiaoyang Lotion group randomly. The percutaneous acute toxicity of Yusheng Xiaoyang Lotion was observed by one time limited dose method, and ap-parent sign changes and death condition of mice after administration of the drug were recorded. After the test, all the animals were weighed and subjected to gross anatomy, and if there were abnormal phenomena, further histopathological examina-tion of should be done. Animals died during the test should be subjected to anato-my. [Result] All the mice survived and exhibited normal behavior,glossy hair and increase of body weight in accordance with growth law.No local and systematic toxicity responses on skin were observed. In visual observation after dissection, no pathologic changes on heart, liver, spleen, lung and kidney were observed. There were no significant differences in body weight between the Yusheng Xiaoyang Lo-tion group and the blank control group before administration,the 7th d after adminis-tration and the 14th after administration （P〉0.05）. [Conclusion] In the transdermaldrug delivery acute toxicity test of Yusheng Xiaoyang Lotion on mice, no obvious toxic responses were observed under the total dose of 89.70 g/kg （equivalent to 120 times of the clinical daily dose for adults）.

Structural Characterization and Acute Toxicity Prediction of Substituted Aromatic Compounds by Using Molecular Vertexes Correlative Index

A molecular structural characterization （MSC） method called molecular vertexes correlative index （MVCI） was used to describe the structures of 30 substituted aromatic compounds. Through multiple linear regression （MLR） and stepwise multiple regression （SMR）, a quantitative structure-toxicity relationship （QSTR） model with 4 variables was obtained. The correlation coefficient （R） of the model was 0.9467. Through partial least-squares regression （PLS）, another QSTR model with 5 principal components was obtained. The correlation coefficient （R） of the model was 0.9518. Both models were evaluated by performing the cross-validation with the leave-one-out （LOO） procedure and the Cross-Validation （CV） correlation coefficients （Rcv） were 0.9208 and 0.9214, respectively. The results suggested good stability and predictability of the models, and the molecular vertexes correlative index could successfully describe the structures of the substituted aromatic compounds.

Holographic quantitative structure-activity relationship for prediction acute toxicity of benzene derivatives to the guppy(poecilia reticulata)

Holographic quantitative structure activity relationship(HQSAR) is an emerging QSAR technique with the combined application of molecular hologram, which encoded the frequency of occurrence of various molecular fragment types, and the subsequent partial least squares(PLS) regression analysis. In this paper, the acute toxicity data to the guppy( poecilia reticulata) for a series of 56 substituted benzenes, phenols, aromatic amines and nitro aromatics were subjected and this resulted in a model with a high predictive ability. The influence of fragment size and fragment distinction parameters on the quality of HQSAR model was investigated. The robustness and predictive ability of the model were also validated by leave one out (LOO) cross validation procedure and external testing data set.

Quantitative Correlation of Chromatographic Retention and Acute Toxicity for Alkyl(1-phenylsulfonyl) Cycloalkane Carboxylates and Their Structural Parameters by DFT

Twenty eight alkyl(1-phenylsulfonyl) cycloalkane carboxylates were computed at the B3LYP/6-31G* level. Based on linear solvation energy theory, two quantitative correlation equations of the molecular structures of alkyl(1-phenylsulfonyl) cycloalkane carboxylate com- pounds to their chromatographic retention (capacity factor lgKW) and the toxicity for photo- bacterium phosphoreum (–lgEC50) were developed by using the molecular structural parameters as theoretical descriptors (r2 = 0.9501, 0.9488). The two quantitative correlation equations were consequently cross validated by leave-one-out (LOO) validation method with q2 of 0.9113 and 0.9281, respectively. The result showed that the two equations achieved in this work by B3LYP/6-31G* are both more advantageous than those from AM1, and can be used to predict the lgKW and –lgEC50 of congeneric organics.

Predicting the Acute Toxicity of Aromatic Amines by Linear and Nonlinear Regression Methods

In current paper, a quantitative structure-activity relationship （QSAR） study was performed for the prediction of acute toxicity of aromatic amines. A set of 56 compounds was randomly divided into a training set of 46 compounds and a test set of 10 compounds. The electronic and topological descriptors computed by the Scigress package and Dragon software were used as predictor variables. Multiple linear regression （MLR） and support vector machine （SVM） were utilized to build the linear and nonlinear QSAR models, respectively. The obtained models with five descriptors show strong predictive ability. The linear model fits the training set with R2 = 0.71, with higher SVM values of R2 = 0.77. The validation results obtained from the test set indicate that the SVM model is comparable or superior to that obtained by MLR, both in terms of prediction ability and robustness.

QSARS for Acute Toxicity of Halogenated Benzenes to Bacteria in Natural Waters

Objective To measure the acute toxicity of halogenated benzenes to bacteria in natural waters and to study quantitative relationships between the structure and activity of chemicals. Methods The concentration values causing 50% inhibition of bacteria growth （24h-IC50） were determined according to the bacterial growth inhibition test method. The energy of the lowest unoccupied molecular orbital and the net charge of carbon atom of 20 halogenated benzenes were calculated by the quantum chemical MOPAC program. Results The logl/IC50 values ranged from 4.79 for 2,4-dinitrochlorobenzene to 3.65 for chlorobenzene. A quantitative structure-activity relationship model was derived from the toxicity and structural parameters： logl/IC50 =-0.531（ELUMO）＋1.693（Qc）＋0.163（logP）＋3.375. This equation was found to fit well （r^2=0.860, s=0.106）, and the average percentage error was only 1.98%. Conclusion Halogenated benzenes and alkyl halogenated benzenes are non-polar narcotics, and have hydrophobicity-dependent toxicity. The halogenated phenols and anilines exhibit a higher toxic potency than their hydrophobicity, whereas 2,4-dinitrochlorobenzene is electrophile with the halogen acting as the leaving group.

Quantitative Correlation of the Acute Toxicity of Phenylthio-carboxylates with Their Structural and Thermodynamic Parameters by DFT Calculation

Phenylthio-carboxylates were computed at the B3LYP/6-31G* level with DFT method. Based on linear solvation energy theory, the structural parameters were firstly taken as theoretical descriptors, and the corresponding linear solvation energy relationship (LSER) equation (r = 0.8989) to the toxicity of photobacterium phosphoreum (–lgEC50) was thus obtained. Then the structural and thermodynamic parameters were taken as theoretical descriptors, and as a result the other corresponding correlation equation (r = 0.9274) relating to –lgEC50 was provided. The two equations achieved in this work by B3LYP/6-31G* are both more advantageous than that from AM1.

A novel respirometer for biological toxicity tests

A respirometer has been developed for microbial toxicity tests. The respirometer is based on luminescence quenching by molecular oxygen. The oxygen sensing film consists of luminescent ruthenium complex adsorbed on amorphous fumed silica and immobilized inside silicone rubber. The luminescence intensity depends on the oxygen concentration of sample in contact with sensing film. The inhibition effect of heavy metals on the respiration rate of microorganisms can be evaluated by monitoring the luminescence intensity of the sensing film. The toxicity of Cu 2+ , Zn 2+ , Ni 2+ , Cr 3+ , Pb 2+ and Hg 2+ on activated sludge was tested using the respirometer. The results indicated that the proposed method was sensitive to the heavy metals tested in this experiment. It was feasible to use the respirometer for microbial toxicity tests.

In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

Objective:To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata(T.paniculata)ethanolic extract in Sprague Dawley rats.Methods:The solvent extracts(hexane,ethyl acetate and ethanol)of T.paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed.The oral acute toxicity was evaluated using ethanolic extract of T.paniculata.Results:Ethyl acetate and elhanolic extracts showed more phytochemicals,whereas highest DPPH scavenging activity was found in ethanolic extract.In an acute toxicity study,T.paniculata ethanolic extract was orally administered(1000 mg/kg body weight)to rats and observed for72 h for any toxic symptoms and the dose was continued up to 14 d.On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters.We did not observe any behavioral changes in test groups in comparison with their controls.Also,there were no significant alterations in biochemical,hematological(hemoglobin content and blood cells count)and liver function parameters such as serum glutamate pyruvate transaminase,serum glutamate oxaloacetate transaminase,alkaline phosphatase,total proteins,albumin and bilirubin levels between T.paniculata ethanolic extract treated and normal control groups.Conclusions:Together our results demonstrated that T.paniculala ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy(HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0 Mx. The patients received3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity.RESULTS: The acute radiation induced skin toxicity was as following: grade Ⅰ 27.6%, grade Ⅱ 7.8% and grade Ⅲ 2.6%. No significant correlation was noted between toxicity grading and chemotherapy(P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively(P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions(P = 0.47, χ2test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse.CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.

Large-scale Purification and Acute Toxicity of Hygromycin B PhoSphotransferase

Objective To provide the acute toxicity data of hygromycin B phosphotransferase （HPT） using recombinant protein purified from E. coli. Methods Recombinant HPT protein was expressed and purified from E. coli. To exclude the potential adverse effect of bacteria protein in recombinant HPT protein, bacterial control plasmid was constructed, and bacteria control protein was extracted and prepared as recombinant HPT protein. One hundred mice, randomly assigned to 5 groups, were administrated 10 g/kg, 5 g/kg, or 1 g/kg body weight of HPT or 5 g/kg body weight of bacterial control protein or phosphate-buffered saline （PBS） respectively by oral gavage. Results All animals survived with no significant change in body weight gain throughout the study. Macroscopic necropsy examination on day 15 revealed no gross pathological lesions in any of the animals. The maximum tolerated dose （MTD） of HPT was 10 g/kg body weight in mice and could be regarded as nontoxic. Conclusion HPT protein does not have any safety problems to human health.