Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with avail...Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.展开更多
The consumption of a mixture of leafy vegetables has always been a practice anchored in the dietary habits of the people of Brazzaville. The objective of this study was to evaluate the acute and subacute toxicities of...The consumption of a mixture of leafy vegetables has always been a practice anchored in the dietary habits of the people of Brazzaville. The objective of this study was to evaluate the acute and subacute toxicities of the aqueous extract of the recipe based on three leafy vegetables (Amaranthus hybridus L., Spinacia oleracea, Brassica campestris L.) in laboratory rodents. The aqueous extract of the food recipe was administered orally using a cannula. Regarding acute toxicity, the administration of single doses of 5000 and 10,000 mg/kg to mice had no significant effects on behavior. On the other hand, weight loss was significantly (**p < 0.01) compared to control mice (1 mL/100g). The results on subacute toxicity showed that daily administration of the aqueous extract of the food recipe at a dose of 1000 mg/kg for 21 days in rats resulted in a non-significant weight gain, and caused changes in some biochemical parameters including HDL-cholesterol levels, blood sugar levels and ALAT activity.展开更多
Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic canc...Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.展开更多
Rice brown planthopper (BPH) (Nilaparvata lugens Stal, ) which occurs 4 generations within one year in Jiangsu Province has become a serious pest and causes loss of yield on rice every year in this region. The contact...Rice brown planthopper (BPH) (Nilaparvata lugens Stal, ) which occurs 4 generations within one year in Jiangsu Province has become a serious pest and causes loss of yield on rice every year in this region. The contact toxicities of imidacloprid and methamidophos to rice BPH were tested by means of immerse topical application method and a field trial from 1993 to 1994. A randomized complete design was laid out in 6 treatments with three replications.展开更多
AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or seve...AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.展开更多
OBJECTIVE： To assess toxicities of the air in Chinese medicine clinics polluted by moxa-burning smoke due to moxibustion-derived burning products （MBP）. METHODS： Both acute and chronic toxicity studies were conduc...OBJECTIVE： To assess toxicities of the air in Chinese medicine clinics polluted by moxa-burning smoke due to moxibustion-derived burning products （MBP）. METHODS： Both acute and chronic toxicity studies were conducted. For the acute toxicity study, five groups of Wistar rats （n = 16/group, male： female = 1 ： 1） were exposed to five different concentrations （95%, 90%, 85%, 80% and 75%, respectively） of MBP for 2 h. For the chronic toxicity study, another three groups of male rats （n = 21/group） were ex- posed to MBP in three concentrations （10%, 40% and 70%, respectively） and one control group ex- posed to clean air 20 min/d for 144 d. Routine ex- aminations were performed and analyzed by analy- sis of variance and dose-response relationship. RESULTS： In the acute toxicity study, the number of dead rats in the 95%, 90%, 85%, 80% and 75% groups were 16, 13, 7, 6 LDS0 of 86.274% after or and 3, respectively, with during the 2 h exposure. In the chronic toxicity study, MBP exposure induced a decline in activity of the rats. Rats in the 10% group showed no signs of toxicity, while those in the 40% MBP group showed toxicity effects on the body weights （P 〈 0.05） and lung. Rats in the 70% MBP group also presented with reversible damage in the blood coagulation system （P 〈 0.05）. CONCLUSION： Exposure to 10% MBP, which is equivalent to 27.45 mg/m^3 was under the critical threshold for male rats＇safety. Exposure to MBP above that limit induced lung damage. MBP in clinics need to be reduced to a safe level with enhanced ventilation.展开更多
In this paper we take photobacterium phosphoreum （T3） as the experimental bacteria, and determine the half-inhibitory concentration （-1gEC50） against the photobacterium phosphoreum of 16 halogenated benzenes. Usin...In this paper we take photobacterium phosphoreum （T3） as the experimental bacteria, and determine the half-inhibitory concentration （-1gEC50） against the photobacterium phosphoreum of 16 halogenated benzenes. Using B3LYP method of DFT in the Gaussian 03 program, we obtain the structural and thermodynamic descriptors of 16 halogenated benzenes by fully-optimized calculation at the 6-311G＊＊ level. Taking the structural and thermodynamic descriptors as theoretical descriptors, the 2D QSAR model （R2 = 0.983） was established, which can be utilized to predict -lgEC50 of halogenated benzene according to the corrected linear solvation energy theory based on the experimental data of-lgECs0. In addition, the relationship between the toxicity and 3D spatial structure of the compound is studied by comparing the molecular similarity index analysis （CoMSIA） of 3D-QSAR method. By cross validation, the correlation coefficient q2 of CoMSIA model is 0.687, and the conventional correlation coefficient R2 = 0.958. The model is stable and reliable with great predictive ability. The 3D-QSAR model shows that the toxicity of halogenated benzene compound is mainly affected by the characteristics of hydrophobie field of the substituted halogens.展开更多
The occurrence, toxicities, and ecological risks of five heavy metals（Pb, Cu, Cd, Zn and Ni） in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the ...The occurrence, toxicities, and ecological risks of five heavy metals（Pb, Cu, Cd, Zn and Ni） in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates（tubificid and chironomid）.The correlations between toxicity of sediment and the sediment quality guidelines（SQGs）derived previously were evaluated. There were significant correlations（p 〈 0.0001） between the observed toxicities and the total risk quotients of the heavy metals based on SQGs,indicating that threshold effect level（TEL） and probable effect level（PEL） were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides（AVS） and simultaneously extracted metals（SEM）,such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover,the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake.展开更多
Polychlorinated biphenyls(PCBs)with different chlorine substitution patterns often coexist in e-waste-processing sites.However,the single and combined toxicity of PCBs to soil organisms and the influence of chlorine s...Polychlorinated biphenyls(PCBs)with different chlorine substitution patterns often coexist in e-waste-processing sites.However,the single and combined toxicity of PCBs to soil organisms and the influence of chlorine substitution patterns remain largely unknown.Herein,we evaluated the distinct in vivo toxicity of PCB28(a trichlorinated PCB),PCB52(a tetrachlorinated PCB),PCB101(a pentachlorinated PCB),and their mixture to earthworm Eisenia fetida in soil,and looked into the underlining mechanisms in an in vitro test using coelomocytes.After a 28-days exposure,all PCBs(up to 10 mg/kg)were not fatal to earthworms,but could induce intestinal histopathological changes and microbial community alterations in the drilosphere system,along with a significant weight loss.Notably,pentachlorinated PCBs with a low bioaccumulation ability showed greater inhibitory effects on the growth of earthworm than lowly chlorinated PCBs,suggesting that bioaccumulation was not the main determinant of chlorine substitution-dependent toxicity.Furthermore,in vitro assays showed that the highly chlorinated PCBs induced a high-percentage apoptosis of eleocytes in the coelomocytes and significantly activated antioxidant enzymes,indicating that the distinct cellular vulnerability to lowly/highly chlorinated PCBs was the main contributor to the PCBs toxicity.These findings emphasize the specific advantage of using earthworms in the control of lowly chlorinated PCBs in soil due to their high tolerance and accumulation ability.展开更多
AIMTo compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives.METHODSIn a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a ...AIMTo compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives.METHODSIn a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm<sup>2</sup>/d) compared in each group using Kruskal-Wallis tests.RESULTSThere were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm<sup>2</sup>/d (levofloxacin group), 5.52±1.68 mm<sup>2</sup>/d (gatifloxacin group), and 4.40±1.30 mm<sup>2</sup>/d (moxifloxacin group), P=0. 003.CONCLUSIONWithout the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.展开更多
Acute toxicities of potassium permanganate, formalin, and Lugol’s iodine solution to a commonly occurred marine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of...Acute toxicities of potassium permanganate, formalin, and Lugol’s iodine solution to a commonly occurred marine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of the results highlighted the close relationships between doses of the medicines and mortalities of the organisms, thus providing a capability to predict toxicity effects from the dose. Toxic effects of the medicines on the ciliates were described in the present paper, and the median lethal concentrations (LC 50 values) were given. Results of measurements indicated that 2 h-LC 50 and 12 h-LC 50 values of formalin on P. coronatum were 59.00×10 -6 and 43.57×10 -6, while those of Lugol’s solutions were 90.13 and 67.84×10 -6 respectively. The tolerance of P. coronatum to formalin is apparently lower than that to Lugol’s iodine solution and potassium permanganate is a suitable medicine to kill ciliates in short time.展开更多
This study showed Iethal concentrations (LC) of copper for Peneaus penicillatus at various stages ofits Iife cycle were 1000μg/L for nauplii, 1000μg/L for Zoea I, 2000μg/L for Zoea Il, 2500μg/Lfor Zoea III, 3000μ...This study showed Iethal concentrations (LC) of copper for Peneaus penicillatus at various stages ofits Iife cycle were 1000μg/L for nauplii, 1000μg/L for Zoea I, 2000μg/L for Zoea Il, 2500μg/Lfor Zoea III, 3000μg/L for Mysis I, II and III and that for almost 100% mortality for postlarvae was3000μg/L. For cadmium LC were 100μg/L for nauplii, 500μg/L for Zoea l, 1000μg/L forZoea II, 2000μg/L for Zoea III, 2500μg/L for Mysis I and 3500μg/L for Mysis II, III andpostlarvae. For tmixture of both metals, LC were 400μg/L for nauplii, 1000 μg/L for nauplii, 1000μg/L for Zoea I,2000μg/L for Zoea II and 3000μg/L for Mysis I, II, III and post larvae.展开更多
Objective:To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine.Methods:The plantain-based diet at 50%,25% and 12.5% were prepared from the basal diet by substi...Objective:To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine.Methods:The plantain-based diet at 50%,25% and 12.5% were prepared from the basal diet by substituting the corn starch with plantain fruit pulp flour at different percentages.Wistar rats were fed plantain-based diet in varying concentrations ranging from 12.5% to 50% of the basal diet for 21 days before or after atrazine treatment in a two-phase experiment:preventive and therapeutic phases.The therapeutic model(n=35)had seven groups with 5 rats each,including the control,atrazine,atrazine recovery,atrazine plus plantain-based diet 50%,25%,12.5%,and atrazine plus quercetin groups.The preventive model(n=30)had six groups of 5 rats,consisting of the control,atrazine,50%,25%,12.5% plantain-based diet plus atrazine,and quercetin plus atrazine groups.Gonadal hormones(testosterone,luteinizing hormone and follicle-stimulating hormone),sperm parameters(sperm motility,viability,morphology and concentration),and testicular function indices(protein,cholesterol,glycogen,acid phosphatase,alkaline phosphatase and lactate dehydrogenase)were measured.Results:The gonadal hormones,sperm characteristics,and testicular function indices of the rat testis decreased significantly in the atrazine group alongside degeneration of the histoarchitecture.However,plantain-based diet restored the gonadal hormone concentrations,semen parameters,and testicular function indices in both the preventive and therapeutic models.Conclusions:Treatment with plantain-based diet protects against rat testicular toxicity caused by atrazine via the modulation of gonadal hormones,sperm quality,testicular function index as well as histoarchitecture of rat testes.展开更多
Nanoliposome is a useful dosage form to increase solubility and absorption of simvastatin(SMV), and consequently improves its therapeutic effects. However, in vivo toxicity of SMV could also be elevated accompanied by...Nanoliposome is a useful dosage form to increase solubility and absorption of simvastatin(SMV), and consequently improves its therapeutic effects. However, in vivo toxicity of SMV could also be elevated accompanied by the absorption enhancement, which is a decisive factor for the clinical application of SMV nanoliposome(SMV-Lipo), but has not been studied systematically and reported so far. In this study, organ toxicity of SMV-Lipo was evaluated in mice in the presence and absence of isoproterenol and compared to those of free SMV. Results demonstrated that compared to free SMV, the SMV-Lipo administrated at an equal dose of 25 mg/kg/d led to severe myocardiotoxicity, hepatotoxicity at baseline and more pronounced liver injury with elevation of alanine aminotransferase. In addition, muscular adverse effect was also observed in SMV-Lipo treated group but not in SMV group. Pharmacokinetic studies revealed that compared to free SMV, the SMV-Lipo administration significantly improved the plasma SMV concentration, and the oral bioavailability was 6.5 times of free SMV. Notably, when the dosage of free SMV increased to 50 mg/kg/d, yielding the comparable plasma concentration as SMV-Lipo given at 25 mg/kg/d, the myocardiotoxicity was observed in free SMV treated mice as well, which further confirmed that the enhanced absorption of SMV by the nanoliposomal formulation resulted in more severe myocardiotoxicity than the equal dose of free SMV.展开更多
Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,anim...Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.展开更多
AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 t...AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.展开更多
Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security o...Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.展开更多
BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy.Prophylactic actions are recommended,but routine clinical manageme...BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy.Prophylactic actions are recommended,but routine clinical management of these toxicities and their impact on quality of life remain unknown.AIM To assess the dermatological toxicities reported after panitumumab initiation,their impact on the quality of life and the clinical practices for their management.METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer.The incidence of dermatological toxicities,clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up.RESULTS Overall,229 patients(males,57.6%;mean age,66.2 years)were included.At day 15,59.3%of patients had dermatological toxicity;the rate peaked at month 2(74.7%)and decreased at month 6(46.5%).The most frequent dermatological toxicities were rash/acneiform rash,xerosis and skin cracks.At least one preventive treatment was administered to 65.9%of patients(oral antibiotics,84.1%;emollients,75.5%;both,62.9%).The rates of patients who received at least one curative treatment peaked at month 2(63.4%)and decreased at month 6(44.8%).The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score.The rates of topical corticosteroids administration and visits to specialists were low.CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up.Nevertheless,their clinical management could be optimized with a better adherence to current recommendations.The impact of skin toxicities on patient’s quality of life appeared to be limited.展开更多
[Objectives]This study was conducted to investigate the analgesic effects and acute toxicities of Bidens alba (L.) DC.[Methods]The alcohol extract of B.alba (L.) DC was extracted and separated with petroleum ether and...[Objectives]This study was conducted to investigate the analgesic effects and acute toxicities of Bidens alba (L.) DC.[Methods]The alcohol extract of B.alba (L.) DC was extracted and separated with petroleum ether and chloroform successively.The acute toxicities of the two extracts on mice were measured,and then the analgesic effects were measured with writhing pain model induced by acetic acid.[Results]No mice died when the crude dosages of B.alba (L.) DC from petroleum ether extract and chloroform extract were 5 016 and 5 100 mg/kg,respectively.When the petroleum ether extract was 60.0 mg/kg,the percentage of twisted mice induced by acetic acid was 40%,the analgesic rate was 77.5%,and the time of the first writhing was (294.0±165.8) s;when the chloroform extract was 20.0 mg/kg,the percentage of twisted animals was 55.6%,the analgesic rate was 51.5%,and the time of the first writhing was (273.8 ±153.4) s;and when the chloroform extract was 4.0 mg/kg,the percentage of twisted animals was 40%,and the analgesic rate was 62.1%,and the time of the first writhing was (370.6±231.3) s.[Conclusions]The petroleum ether extracts and chloroform extracts of B.alba (L.) DC have good analgesic effects and no acute toxicities.展开更多
Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metaboli...Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.展开更多
基金supported by grants from the National Natural Science Foundation of China(82200212)and(81902934).
文摘Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.
文摘The consumption of a mixture of leafy vegetables has always been a practice anchored in the dietary habits of the people of Brazzaville. The objective of this study was to evaluate the acute and subacute toxicities of the aqueous extract of the recipe based on three leafy vegetables (Amaranthus hybridus L., Spinacia oleracea, Brassica campestris L.) in laboratory rodents. The aqueous extract of the food recipe was administered orally using a cannula. Regarding acute toxicity, the administration of single doses of 5000 and 10,000 mg/kg to mice had no significant effects on behavior. On the other hand, weight loss was significantly (**p < 0.01) compared to control mice (1 mL/100g). The results on subacute toxicity showed that daily administration of the aqueous extract of the food recipe at a dose of 1000 mg/kg for 21 days in rats resulted in a non-significant weight gain, and caused changes in some biochemical parameters including HDL-cholesterol levels, blood sugar levels and ALAT activity.
文摘Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.
文摘Rice brown planthopper (BPH) (Nilaparvata lugens Stal, ) which occurs 4 generations within one year in Jiangsu Province has become a serious pest and causes loss of yield on rice every year in this region. The contact toxicities of imidacloprid and methamidophos to rice BPH were tested by means of immerse topical application method and a field trial from 1993 to 1994. A randomized complete design was laid out in 6 treatments with three replications.
基金Supported by The Health Research Council of New Zealand
文摘AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.
基金Supported by the National Natural Science Foundation of China:effect of Moxibustion on"Longevity Gene"SIRT1 Regulation in Aged Mice(No.81403449)NSFC Project:effect of Moxibustion and its Therapeutic Factors on Mitochondrial Energy Metabolism and Apotosis Pathyway in APP/PS1Transgenic Alzheimer's Disease Mouse Model(No.8157-4068)National Program on Key Basic Research Project(973 Program):the Study of Components and Mecha-nisms of Artemisia and the Product and Moxibustion and Safety Evaluation(No.2009CB522906)
文摘OBJECTIVE： To assess toxicities of the air in Chinese medicine clinics polluted by moxa-burning smoke due to moxibustion-derived burning products （MBP）. METHODS： Both acute and chronic toxicity studies were conducted. For the acute toxicity study, five groups of Wistar rats （n = 16/group, male： female = 1 ： 1） were exposed to five different concentrations （95%, 90%, 85%, 80% and 75%, respectively） of MBP for 2 h. For the chronic toxicity study, another three groups of male rats （n = 21/group） were ex- posed to MBP in three concentrations （10%, 40% and 70%, respectively） and one control group ex- posed to clean air 20 min/d for 144 d. Routine ex- aminations were performed and analyzed by analy- sis of variance and dose-response relationship. RESULTS： In the acute toxicity study, the number of dead rats in the 95%, 90%, 85%, 80% and 75% groups were 16, 13, 7, 6 LDS0 of 86.274% after or and 3, respectively, with during the 2 h exposure. In the chronic toxicity study, MBP exposure induced a decline in activity of the rats. Rats in the 10% group showed no signs of toxicity, while those in the 40% MBP group showed toxicity effects on the body weights （P 〈 0.05） and lung. Rats in the 70% MBP group also presented with reversible damage in the blood coagulation system （P 〈 0.05）. CONCLUSION： Exposure to 10% MBP, which is equivalent to 27.45 mg/m^3 was under the critical threshold for male rats＇safety. Exposure to MBP above that limit induced lung damage. MBP in clinics need to be reduced to a safe level with enhanced ventilation.
基金supported by the National Natural Science Foundation of China(20977046, 20737001) the Natural Science Foundation of Zhejiang Province(2007Y507280)
文摘In this paper we take photobacterium phosphoreum （T3） as the experimental bacteria, and determine the half-inhibitory concentration （-1gEC50） against the photobacterium phosphoreum of 16 halogenated benzenes. Using B3LYP method of DFT in the Gaussian 03 program, we obtain the structural and thermodynamic descriptors of 16 halogenated benzenes by fully-optimized calculation at the 6-311G＊＊ level. Taking the structural and thermodynamic descriptors as theoretical descriptors, the 2D QSAR model （R2 = 0.983） was established, which can be utilized to predict -lgEC50 of halogenated benzene according to the corrected linear solvation energy theory based on the experimental data of-lgECs0. In addition, the relationship between the toxicity and 3D spatial structure of the compound is studied by comparing the molecular similarity index analysis （CoMSIA） of 3D-QSAR method. By cross validation, the correlation coefficient q2 of CoMSIA model is 0.687, and the conventional correlation coefficient R2 = 0.958. The model is stable and reliable with great predictive ability. The 3D-QSAR model shows that the toxicity of halogenated benzene compound is mainly affected by the characteristics of hydrophobie field of the substituted halogens.
基金supported by the Ministry of Science and Technology(No.2012ZX07501-003-04)the National Natural Science Foundation of China(NSFC)(Nos.21325730,21577067,46103095)
文摘The occurrence, toxicities, and ecological risks of five heavy metals（Pb, Cu, Cd, Zn and Ni） in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates（tubificid and chironomid）.The correlations between toxicity of sediment and the sediment quality guidelines（SQGs）derived previously were evaluated. There were significant correlations（p 〈 0.0001） between the observed toxicities and the total risk quotients of the heavy metals based on SQGs,indicating that threshold effect level（TEL） and probable effect level（PEL） were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides（AVS） and simultaneously extracted metals（SEM）,such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover,the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake.
基金This work was supported by the National Key Research and Development Program of China(No.2017YFA0207003)the National Natural Science Foundation of China(No.21777139).
文摘Polychlorinated biphenyls(PCBs)with different chlorine substitution patterns often coexist in e-waste-processing sites.However,the single and combined toxicity of PCBs to soil organisms and the influence of chlorine substitution patterns remain largely unknown.Herein,we evaluated the distinct in vivo toxicity of PCB28(a trichlorinated PCB),PCB52(a tetrachlorinated PCB),PCB101(a pentachlorinated PCB),and their mixture to earthworm Eisenia fetida in soil,and looked into the underlining mechanisms in an in vitro test using coelomocytes.After a 28-days exposure,all PCBs(up to 10 mg/kg)were not fatal to earthworms,but could induce intestinal histopathological changes and microbial community alterations in the drilosphere system,along with a significant weight loss.Notably,pentachlorinated PCBs with a low bioaccumulation ability showed greater inhibitory effects on the growth of earthworm than lowly chlorinated PCBs,suggesting that bioaccumulation was not the main determinant of chlorine substitution-dependent toxicity.Furthermore,in vitro assays showed that the highly chlorinated PCBs induced a high-percentage apoptosis of eleocytes in the coelomocytes and significantly activated antioxidant enzymes,indicating that the distinct cellular vulnerability to lowly/highly chlorinated PCBs was the main contributor to the PCBs toxicity.These findings emphasize the specific advantage of using earthworms in the control of lowly chlorinated PCBs in soil due to their high tolerance and accumulation ability.
文摘AIMTo compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives.METHODSIn a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm<sup>2</sup>/d) compared in each group using Kruskal-Wallis tests.RESULTSThere were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm<sup>2</sup>/d (levofloxacin group), 5.52±1.68 mm<sup>2</sup>/d (gatifloxacin group), and 4.40±1.30 mm<sup>2</sup>/d (moxifloxacin group), P=0. 003.CONCLUSIONWithout the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.
基金This work is supported by the Natural Science Foundation of China(No.40206021).
文摘Acute toxicities of potassium permanganate, formalin, and Lugol’s iodine solution to a commonly occurred marine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of the results highlighted the close relationships between doses of the medicines and mortalities of the organisms, thus providing a capability to predict toxicity effects from the dose. Toxic effects of the medicines on the ciliates were described in the present paper, and the median lethal concentrations (LC 50 values) were given. Results of measurements indicated that 2 h-LC 50 and 12 h-LC 50 values of formalin on P. coronatum were 59.00×10 -6 and 43.57×10 -6, while those of Lugol’s solutions were 90.13 and 67.84×10 -6 respectively. The tolerance of P. coronatum to formalin is apparently lower than that to Lugol’s iodine solution and potassium permanganate is a suitable medicine to kill ciliates in short time.
文摘This study showed Iethal concentrations (LC) of copper for Peneaus penicillatus at various stages ofits Iife cycle were 1000μg/L for nauplii, 1000μg/L for Zoea I, 2000μg/L for Zoea Il, 2500μg/Lfor Zoea III, 3000μg/L for Mysis I, II and III and that for almost 100% mortality for postlarvae was3000μg/L. For cadmium LC were 100μg/L for nauplii, 500μg/L for Zoea l, 1000μg/L forZoea II, 2000μg/L for Zoea III, 2500μg/L for Mysis I and 3500μg/L for Mysis II, III andpostlarvae. For tmixture of both metals, LC were 400μg/L for nauplii, 1000 μg/L for nauplii, 1000μg/L for Zoea I,2000μg/L for Zoea II and 3000μg/L for Mysis I, II, III and post larvae.
文摘Objective:To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine.Methods:The plantain-based diet at 50%,25% and 12.5% were prepared from the basal diet by substituting the corn starch with plantain fruit pulp flour at different percentages.Wistar rats were fed plantain-based diet in varying concentrations ranging from 12.5% to 50% of the basal diet for 21 days before or after atrazine treatment in a two-phase experiment:preventive and therapeutic phases.The therapeutic model(n=35)had seven groups with 5 rats each,including the control,atrazine,atrazine recovery,atrazine plus plantain-based diet 50%,25%,12.5%,and atrazine plus quercetin groups.The preventive model(n=30)had six groups of 5 rats,consisting of the control,atrazine,50%,25%,12.5% plantain-based diet plus atrazine,and quercetin plus atrazine groups.Gonadal hormones(testosterone,luteinizing hormone and follicle-stimulating hormone),sperm parameters(sperm motility,viability,morphology and concentration),and testicular function indices(protein,cholesterol,glycogen,acid phosphatase,alkaline phosphatase and lactate dehydrogenase)were measured.Results:The gonadal hormones,sperm characteristics,and testicular function indices of the rat testis decreased significantly in the atrazine group alongside degeneration of the histoarchitecture.However,plantain-based diet restored the gonadal hormone concentrations,semen parameters,and testicular function indices in both the preventive and therapeutic models.Conclusions:Treatment with plantain-based diet protects against rat testicular toxicity caused by atrazine via the modulation of gonadal hormones,sperm quality,testicular function index as well as histoarchitecture of rat testes.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81770268)the National Basic Research Program of China(No.2015CB932100).
文摘Nanoliposome is a useful dosage form to increase solubility and absorption of simvastatin(SMV), and consequently improves its therapeutic effects. However, in vivo toxicity of SMV could also be elevated accompanied by the absorption enhancement, which is a decisive factor for the clinical application of SMV nanoliposome(SMV-Lipo), but has not been studied systematically and reported so far. In this study, organ toxicity of SMV-Lipo was evaluated in mice in the presence and absence of isoproterenol and compared to those of free SMV. Results demonstrated that compared to free SMV, the SMV-Lipo administrated at an equal dose of 25 mg/kg/d led to severe myocardiotoxicity, hepatotoxicity at baseline and more pronounced liver injury with elevation of alanine aminotransferase. In addition, muscular adverse effect was also observed in SMV-Lipo treated group but not in SMV group. Pharmacokinetic studies revealed that compared to free SMV, the SMV-Lipo administration significantly improved the plasma SMV concentration, and the oral bioavailability was 6.5 times of free SMV. Notably, when the dosage of free SMV increased to 50 mg/kg/d, yielding the comparable plasma concentration as SMV-Lipo given at 25 mg/kg/d, the myocardiotoxicity was observed in free SMV treated mice as well, which further confirmed that the enhanced absorption of SMV by the nanoliposomal formulation resulted in more severe myocardiotoxicity than the equal dose of free SMV.
基金financially supported by Vice-Chancellery for Research and Technology,Isfahan University of Medical Sciences(Grant No.399187).
文摘Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.
基金Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR00165 through our institution’s Center for Clinical and Translational Science(in part)
文摘AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.
文摘Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.
文摘BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy.Prophylactic actions are recommended,but routine clinical management of these toxicities and their impact on quality of life remain unknown.AIM To assess the dermatological toxicities reported after panitumumab initiation,their impact on the quality of life and the clinical practices for their management.METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer.The incidence of dermatological toxicities,clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up.RESULTS Overall,229 patients(males,57.6%;mean age,66.2 years)were included.At day 15,59.3%of patients had dermatological toxicity;the rate peaked at month 2(74.7%)and decreased at month 6(46.5%).The most frequent dermatological toxicities were rash/acneiform rash,xerosis and skin cracks.At least one preventive treatment was administered to 65.9%of patients(oral antibiotics,84.1%;emollients,75.5%;both,62.9%).The rates of patients who received at least one curative treatment peaked at month 2(63.4%)and decreased at month 6(44.8%).The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score.The rates of topical corticosteroids administration and visits to specialists were low.CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up.Nevertheless,their clinical management could be optimized with a better adherence to current recommendations.The impact of skin toxicities on patient’s quality of life appeared to be limited.
基金Supported by Special Fund for Scientific and Technological Development of Guangdong Province(2017A020225023)President Fund of Guangdong Academy of Agricultural Sciences(201627)Special Research Fund for Medical and Health of Huadu District of Guangzhou City(17-HDWS-037)
文摘[Objectives]This study was conducted to investigate the analgesic effects and acute toxicities of Bidens alba (L.) DC.[Methods]The alcohol extract of B.alba (L.) DC was extracted and separated with petroleum ether and chloroform successively.The acute toxicities of the two extracts on mice were measured,and then the analgesic effects were measured with writhing pain model induced by acetic acid.[Results]No mice died when the crude dosages of B.alba (L.) DC from petroleum ether extract and chloroform extract were 5 016 and 5 100 mg/kg,respectively.When the petroleum ether extract was 60.0 mg/kg,the percentage of twisted mice induced by acetic acid was 40%,the analgesic rate was 77.5%,and the time of the first writhing was (294.0±165.8) s;when the chloroform extract was 20.0 mg/kg,the percentage of twisted animals was 55.6%,the analgesic rate was 51.5%,and the time of the first writhing was (273.8 ±153.4) s;and when the chloroform extract was 4.0 mg/kg,the percentage of twisted animals was 40%,and the analgesic rate was 62.1%,and the time of the first writhing was (370.6±231.3) s.[Conclusions]The petroleum ether extracts and chloroform extracts of B.alba (L.) DC have good analgesic effects and no acute toxicities.
文摘Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.
