Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

Impact of an Alcohol-based hand sanitizer usage during COVID-19 pandemic on disulfiram treatment: A South Indian psychiatrist's practice experiences

Background: Alcohol-based hand sanitizer (ABHS) usage has become one of the COVID-19 pandemic-related adapted responses. Some disulfiram-ethanol reactions are reported in people who use alcohol-based hand rub/sanitizer and take Disulfiram as a treatment for their alcohol use disorders. Aim & Objective: To determine the practice experiences of psychiatrists on disulfiram prescription to alcohol use disorder victims. Methodology: A cross-sectional study on the psychiatrists to find the experiences of disulfiram prescription to their clients with alcohol use disorders during the COVID-19 pandemic. Results: Nearly 84 (51%) were reverted with a completed questionnaire. Among the respondents, 28 (33.3%) of the respondents decreased to prescribe Disulfiram, 48 (57.1%) reported that their patients stopped using ABHS due to fear of Disulfiram-Ethanol Reaction (DER), and 20 (23.8%) responders notified that their patients were expressed their worry on DER with Disulfiram and ABHS. Conclusion: Disulfiram prescribed for alcohol use disorders; treatment got peculiar experiences with the incidences of DER reported with Alcohol-based hand sanitizer. Many practitioners were scared to prescribe disulfiram due to DER with ABHS. The prevailing evidence that there is no possibility of cutaneous application of ABHS producing enough significant DER. Hence using ABHS is not a contraindication for disulfiram prescription.

Disulfiram Induced Mania — A Case Report

Disulfiram has been most widely used in patients suffering from alcohol dependence. When taken along with alcohol it can cause various side effects like flushing, drowsiness, rashes, hyperventilation, palpitations etc. Mania due to Disulfiram is an uncommon side effect and there are only a few reports of it. We hereby report a case of the development of Mania in an individual with alcohol dependence following 2 months of treatment with a therapeutic dose of Disulfiram. Before the onset of mania, the patient was abstinent from alcohol for about 2 months, which made substance-induced mania unlikely. The possible mechanism for this is the dopamine hypothesis which suggests that Disulfiram inhibits dopamine-Beta-hydroxylase which is responsible for the conversion of dopamine to Nor-adrenaline and increases the dopamine level which is responsible for psychotic and mania symptoms. This possibility of Disulfiram induced mania should be assessed whenever clinicians encounter patients with dual diagnosis, as this might change the management as such.

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

Inhibitory effect of disulfiram combined with cisplatin on triple negative breast cancer MDA-MB-231 cells and its mechanism / 吉林大学学报(医学版)

Objective: To observe the inhibitory effect of combination of disulfiram (DSF) and cisplatin (CDDP) on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells, and to explore its possible mechanism. Methods: The MDA-MB-231 cells in the logarithmic phase were divided into blank control group. DSF group. CDDP group and combination groups (60/xmol • L 1 CDDP+1. 2 and 4/imol • L ' DSF). MTT method was used to detect the survival rates of the MDA-MB-231 cells in various groups and flow cytometry was used to detect the apoptotic rates of the MDA-MB-231 cells in various groups, flow cytometry was used to detect the level of active oxygen ( ROS ) in the MDA-MB-231 cells in various groups, and Inductively Coupled Plasma-MassSpectrometry (ICP-MS) was used to detect the levels of Pt in the MDA-MB-231 cells in various groups. Results: The MTT method and flow cytometry results showed that after treated for 72 h. compared with 60/xmol • L ' CDDPgroup, the survival rates of the MDA-MB-231 cells in combination 1 group (60/xmol • L CDDP+1/xmol • L 1 DSF), combination 2 group (60/xmol • L 'CDDP+ 2/xmol • L 1 DSF) and combination 3 group (60/xmol • L 'CDDP+4/xmol • L 'DSF) were decreased ( P<0. 05). After treated for 24 h. compared with 60/x mol • L ' CDDP group and 2/x mol • L DSF group, the apoptotic rate of the MDA-MB-231 cells in combination group (60/xmol • L 'CDDP+2/xmol • L ' DSF) was increased ( P<0. 05). Compared with CDDP group, the level of ROS in the MDA-MB-231 cells in combination group (60/xmol • L 'CDDP+2/xmol • L 1 DSF) was increased (P<0. 05). The 1CP-MS results showed that compared with CDDP group, the level of Pt in the MDA-MB-231 cells in combination group (20/xmol • L 1CDDP+ 0.625/xmol • L ' DSF) was increased (P< 0.05). Conclusion: The combination of DSF and CDDP can significantly inhibit the proliferation of MDA-MB-231 cells, and its possible mechanism may be related to inhibiting the growth of tumor cells by increasing the ROS level and Pt content in the MDA-MB-231 cells.

Disulfiram combined with cooper inhibits proliferation and induces apoptosis of osteosarcoma / 中国组织工程研究

BACKGROUND: Studies have shown that disulfiram has anti-tumor activity, which can be combined with copper (Cu) ions to exert an anti-tumor effect on multiple tumors in vivo and in vitro, but the effect of disulfiram on osteosarcoma proliferation and apoptosis has not been clarified. OBJECTIVE: To investigate the effect of disulfiram combined with Cu on osteosarcoma proliferation and apoptosis and the possible mechanism in vivo and in vitro. METHODS: The study protocol was approved by the Animal Ethics Committee of Shanxi Medical University (approval No. 2017LL077). (1) In vitro study: Diethyldithiocarbamate (DDTC)-Cu (0.5, 1, 2, 3, and 5 μmol/L) was configured with Cu and DDTC which is the transformation of disulfiram after absorbed by bodies. DDTC single drug (5 μmol/L), Cu single drug (5 μmol/L) and blank control groups were set. Osteosarcoma cell lines Saos-2 and MG-63 were treated with drugs, and cell counting kit-8 assay was used to detect the inhibitory effect of DDTC-Cu at different concentrations on the proliferation of Saos-2 and MG-63 cells. Changes in Saos-2 apoptosis were measured by AnnexinV-FITC/PI staining. (2) In vivo study: A total of 10 BALB/c-nu/nu female nude mice of 4 weeks old were randomly divided into DDTC-Cu group and control group. The mixture of Saos-2 cells and Matrigel (1:1 mixed, 400 μL per mouse) was injected subcutaneously into the right back of nude mice. Two weeks after inoculation, model mice were intraperitoneally injected dexamethasone (0.5 mg/kg once every other day) in the control group, and dexamethasone (0.5 mg/kg once every other day) and DDTC-Cu complex (10 nmol/g once every other day) in the DDTC-Cu group. Xenograft tumors in each group were measured at regular intervals and tumor growth curves were drawn. Five weeks after inoculation, the animals were sacrificed under anesthesia, and tumors were completely removed. Immunohistochemistry was used to detect the expression level of ki67 protein in tumor paraffin sections. The expressions of proteins related to cell proliferation and apoptosis and JNK pathway proteins were determined by western blot analysis. RESULTS AND CONCLUSIONS: (1) In vitro study: The proliferation inhibition in the DDTC-Cu group was significantly stronger than that in the DDTC single drug, Cu single drug and blank control groups. Cell counting kit-8 results showed that DDTC-Cu inhibited osteosarcoma proliferation in a dose-dependent manner, with 50% inhibiting concentration of 0.337 μmol/L (Saos-2) and 0. 487 μmol/L (MG-63) for 24 hours, respectively. The results of flow cytometry showed that DDTC-Cu promoted Saos-2 apoptosis in a dose-dependent manner. (2) In vivo study: The tumor volume and mass of the DDTC-Cu group were smaller than those of the control group. Immunohistochemical results showed that the expression level of ki-67 protein in the DDTC-Cu group was lower than that in the control group. Western blot results showed that the expression levels of p-JNK and c-jun in the DDTC-Cu group were up-regulated. To conclude, disulfiram combined with Cu inhibits proliferation and induces apoptosis of osteosarcoma in vitro and in vivo, and its mechanism may be related with activation of JNK signaling pathway.

Synergistic effect of sertraline and disulfiram against multidrug resistant bacteria as a new alternative to drug repositioning

The repositioning of approved drugs is atopic of interest for the academy and the pharmaceutical industry. The synergistic combination of these drugs can be successful in the treatment of infections caused by resistant bacteria. This study aimed to assess the in vitro synergistic antibacterial activity of sertraline and disulfiram and their interaction with ciprofloxacin and sulfamethoxazole/trimethoprim. We determined the minimum inhibitory concentration, the minimum bactericidal concentration and the fractional inhibitory concentration index. Eighteen bacterial strains were used, being nine American Type Culture Collection reference strains and nine multidrug resistant clinical isolates. Synergy was detected between sertraline and disulfiram against a strain of Staphylococcus aureusATCC 25923 and a clinical isolate of S. aureus. When associated to sulfamethoxazole/trimethoprim and ciprofloxacin, sertraline and disulfiram showed eight synergistic events, which occurred against three different standard strains and two multidrug resistant clinical isolates. When the minimum bactericidal concentration was determined, the bactericidal activity of sertraline was enhanced with disulfiram. Our results suggest that these drugs, widely used to treat depression and chronic alcoholism, have antibacterial potential individually, in association, and combined with antimicrobials, what makes their repositioning a promising therapeutic alternative for the effective treatment of infections caused by multidrug resistant bacteria.

Clinical characteristics of elderly patients with disulfiram-like reaction : a retrospective analysis of 19 cases / 中华老年医学杂志

Objective To analyze the clinical characteristics of elderly patients with disulfiramlike reaction,in order to raise awareness of this disease.Methods Clinical data of 19 elderly patients diagnosed as disulfiram-like reaction in the emergency department of Beijing Hospital from January 2012 to March 2017 were retrospectively analyzed.Disulfiram-like reaction was diagnosed by comprehensive data of the drugs-induced disulfiram-like reaction,related clinical manifestations,auxiliary examination,treatment response,and by differential diagnosis.Results All of 19 patients were male,with one or more chronic disease,mean ± SD age were 75.6±5.1 years.Of 19 patients,16 patients were taking antibiotics,including ceftriaxone,cefoperazone sodium sulbactam,cefpropene,cefuroxime and moxifloxacin,and other patients received warfarin sodium,glimepiride and metformin before the onset of disulfiram-like reaction.Clinical manifestations of disulfiram like reaction mainly involved the cardiovascular system such as palpitation,chest distress,angina,hypotension,etc.,and might be accompanied by dizziness,facial flushing,awareness disorder,gastrointestinal hemorrhage,renal dysfunction,etc.The myocardial ischemia in ECG was observed in 13 patients,the elevated serum troponin in 3 patients,and a continuing organ dysfunction in 1 patient.Conclusions The elderly patients with disulfiram-like reaction are mainly male,with various pathogenic factors and dangerous prognosis.The symptoms of cardiovascular system are obvious,including arrhythmia,myocardial injury,heart failure,shock and other serious cardiovascular complications.

Effect of Disulfiram Combined with Copper on the Proliferation and Migration of Brain Metastases from Lung Cancer / 医药导报

Objective To investigate the effects of disulfiram combined with copper (DSF /Cu) on proliferation and migration of brain metastases from lung cancer. Methods The cell were divided into blank control group, valproate group (1.0 mmol·L-1 of valproate) , DSF /Cu (1,2,3,4,5 mg /0.17 mg) . Brain metastases from lung adenocarcinoma were incubated 72 hours.The changes of proliferative ability of cancer cells were detected by CCK-8 method, the effect of DSF /Cu on the migration ability of cancer cells was detected by Transwell chamber, and the degree of apoptosis of cancer cells was detected by Annexus V-PI double staining method. Results The ability of proliferation was significantly inhibited, the ability of migration was significantly reduced,and the rate of cell apoptosis was significantly increased in each dose group of brain metastases from lung adenocarcinoma compared with the blank control group. With the increase of DSF /Cu dose, its ability to inhibit the proliferation and migration of metastases cancer cells and induce apoptosis of metastases cancer cells has increased gradually. Conclusion DSF /Cu can inhibit the proliferation and migration of brain metastases from lung adenocarcinoma and induce apoptosis. DSF is expected to be a new method of the combined treatment of brain metastases cancer.

Epileptic Seizure Due to Disulfiram Treatment / 가정의학회지

Disulfiram has been used for the treatment of alcohol dependence for nearly 65 years and is approved by the Food and Drug Administration. It causes negative reinforcement by accumulating toxic acetaldehyde due to irreversible inhibition of aldehyde dehydrogenase. Disulfiram has very few side effects when taken without alcohol. Epileptic seizure induction is a rare side effect in therapeutic doses, and its mechanism is unknown. We present a patient with a single epileptic seizure which was thought to be due to disulfiram used in the treatment of alcohol dependence. We did not find it ethical to administer disulfiram again because the patient discontinued alcohol use and was afraid of epileptic seizures.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Knowledge, Attitude, Practices Of Disulfiram Amongst Relatives Of Patient With Alcohol Use Disorder

KAP (Knowledge, Attitude and Practice) studies are highly focused evaluations to measure changes in response to a specific intervention, usually outreach, demonstration or education. This study was conducted to assess KAP of Disulfiram amongst relatives of patients suffering from alcohol use disorder. Relatives of 100 patients diagnosed as alcohol use disorder were interviewed using a self–designed semi structured proforma. Alcohol use was documented to ascertain the pattern and dependence. On asking if “Heard about disulfiram” 38 respondents stated yes whereas 62 said no.36% said that they have used disulfiram.32% reported good experience.35% showed improved quality of life and achieved abstinence from alcohol.The present study demonstrated poor knowledge among relatives, but good attitudes toward use of disulfiram. The results suggest the need to implement an intervention strategy that reflects specific local circumstances and plan activities that are suited to the population involved.

Research progresses of the roles of disulfiram in anticancer activity and radiobiology / 中华放射医学与防护杂志

Disulfiram (DSF) has been widely used in clinical treatment of alcoholism.To date,in vivo and in vitro experiments have demonstrated that DSF has strong anti-cancer activity and could improve patient's survival,and the underlying mechanism has been elaborated.In addition,it was reported that,during radiotherapy,DSF could protect normal tissue and cells meanwhile enhance the radiosensitivity of tumor cells by forming complexes with copper ions,suppressing cancer stem cells and inhibiting ubiquitin-proteasome system activity in cancer cells.This review summarizes the completed and ongoing clinical trials of disulfiram,and its anti-tumor mechanisms and advances in radiation biology.

Disulfiram Induced Psychosis

Disulfiram is the commonly prescribed drug for the treatment of alcohol dependence. It's major metabolite (diethyldithiocarbamate) is an inhibitor of dopamine-betahydroxylase, an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis. We recommend that disulfiram should be used at the lowest effective dose, possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis.

Inhibition effect of disulfiram combined with Cu on the growth of human Burkitt lymphoma cell xenografts in nude mice / 肿瘤研究与临床

Objective To investigate the effects of disulfiram (DS) combined with Cu on the human Burkitt lymphoma cell xenografts in nude mice.Methods Burkitt lymphoma xenograft was established by subcutaneous injection of Raji cell into nude mice after 2 Gy whole body X-irradiation (1×107 Raji cells were resuspended in 200 μl saline).18 bearing tumor mice were randomly divided into control group,DS group and DS/Cu group.During the experiment,the effects of DS/Cu on the nude mice with tumors were examined,including the tumor volumes,weights and the growth curves of xenograft tumor.Histopathological examination of tumor tissue was observed with optical microscape.The protein expression levels of p-JNK and c-jun were also detected by Western blot.Results Subsequent tumor size and weight in DS or DS/Cu-treated animals were (67.71±2.15) mm3,(33.35±7.74) mm3 and (43.35±4.22) mg,(18.05±2.88) mg.One-way ANOVA analysis indicated that the tumor size and weight in DS or DS/Cu-treated animals were reduced significantly relative to tumors in vehicle-treated animals (F =27.579,P =0.000;F =16.369,P =0.000).Furthermore,multiple comparisons revealed that the DS or DS/Cu-treated animals had significantly reduced tumor size and weight compared with control animals (all P ＜ 0.05).There were significant differences in tumor size and weight between DS or DS/Cu-treated animals (both P ＜ 0.05).Tumor inhibition rates in DS or DS/Cu group were 63.48 ％ and 80.24 ％,respectively.An increase of apoptosis changes in the xenograft tumor cells in DS or DS/Cu treated mice were more significant.Westem blot showed that the p-JNK and c-jun protein expressions in the tumors were improved after the DS or DS/Cu treatment,more obvious in DS/Cu treatment.Conclusion DS/Cu can inhibit the growth of xenografts,and one possible mechanism may involve the regulation of JNK signal pathway.

Effects of DSF/Cu on surface ultrastructures and mechanical properties of human breast cancer and normal breast epithelial cells / 中国病理生理杂志

AIM: To study the effects of disulfiram/copper complex (DSF/Cu) on ultrastructures and mechan-ical properties of human breast cancer and normal breast epithelial cells by atomic force microscopy (AFM) based on the nanoscale resolution and piconewton force measurement level.METHODS: The change of cell cycle and apoptotic rate of MCF-7 cells and MCF-10A cells induced by DSF/Cu were compared by flow cytometry.The cell surface morphology, ultra-structure, height, width and roughness were detected by AFM.The effects of DSF/Cu on the hardness (Young’s modu-lus) of the 2 kinds of cells were determined by AFM with indentation technique.RESULTS: DSF/Cu significantly in-duced apoptosis of the MCF-7 cells in a dose-dependent manner, whereas had little effect on the MCF-10A cells.The cell cycle analysis showed that DSF/Cu induced G2 /M arrest in the MCF-7 cells, but led to G0 /G1 arrest in the MCF-10A cells.The AFM images showed that the MCF-7 cells shrank and showed smaller and smoother morphology, and the filopo-dia were retracted obviously, even some became into lamellipodia, or disappeared completely after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.The quantitative analysis indicated that the MCF-7 cells showed smaller width and larger height, and the root mean square roughness and average roughness were decreased significantly in a dose-dependent manner after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.However, little effect in the MCF-10A cells was observed.The biomechanics test at a single cell level demonstrated that the Young’s modulus of the MCF-7 cells and MCF-10A cells were both increased, yet the proportion increased in the MCF-7 cells was much higher than that in the MCF-10A cells after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.CONCLUSION: DSF/Cu has strong antitumor effect on breast cancer with high efficiency and low toxicity by changing the properties of the biomechanics specifically.

DSF-Cu induces apoptosis of human nasopharyngeal carcinoma CNE-2 Z cells by affecting function of mitochondria and cytoskeleton / 中国药理学通报

Aim To study the mechanism of DSF-Cu induced apoptosis of human nasopharyngeal carcinoma CNE-2 Z cells by affecting the function of mitochondria and cytoskeleton. Methods The cell cycle,the rate of apotosis,the levels of intracellular ROS and MMP in CNE-2 Z cells were tested by flow cytometry after trea-ted with different concentration of DSF-Cu. The chan-ges of the cell surface morphology, ultrastructure, cell height, width and roughness were detected by AFM. The distribution and reorganization of cytoskeleton F-actin were observed by Laser scanning confocal micro-scope. Results Cells were incubated with different concentration of DSF-Cu ( 0 ~200 nmol · L-1 ) for 24 h, the apoptotic ratio increased significantly and the treatment of DSF-Cu resulted in a concentration-de-pendent accumulation of CNE-2Z cells in G2/M phase. Furthermore,the treatment of DSF-Cu was able to in-crease the production of intracellular ROS and decrease the MMP in CNE-2Z cells. In addition,AFM imaging showed that compared to the control group,with the in-crease of DSF-Cu concentration,the CNE-2Z cells be-came smaller, cytoplasm condensed, the height in-creased,and the surface roughness reduced. Moreover, the filopodia became shorter, shrinked and even com-pletely destroyed after treated with different concentra-tion of DSF-Cu. At last,the LSCM image showed that the fluorescence intensity of F-actin networks was de-creased, then the structure was rearranged and de-stroyed obviously by treated with DSF-Cu. Conclusion DSF-Cu can induce apoptosis and arrest cell cycle at G2/M phase in CNE-2Z cell through a mitochondria-dependent pathway. Above findings highlight the appli-cations of AFM at the single cell level for the investiga-tion of antineoplastic drug in nasopharyngeal carcinoma therapy.

Encefalopatía e infarto del globus pallidum bilateral, secundarios aintoxicación con disulfiram. Reporte de caso pediátrico / Encephalopathy and bilateral globus pallidum infarction secondary to disulfiram poisoning. Case reports in pediatrics

El disulfiram (Antabuse®) es un fármaco que se usa ampliamente en pacientes con consumo crónico de alcohol,como parte del tratamiento del alcoholismo, con el fin de producir síntomas desagradables al mezclarsecon etanol, por incremento de acetaldehído. Aunque se han descrito casos de intoxicación aun sin ingesta dealcohol con dosis terapéuticas y más comúnmente por sobredosis en adultos, son pocos los casos que se handescrito en niños.Se presenta a continuación el caso de un niño con intoxicación aguda por disulfiram, quien presentó en la faseaguda somnolencia que evolucionó a estupor; concomitantemente presentó crisis convulsivas, vómito, deshidratación,rigidez, temblor distal y diaforesis; al egreso, con secuelas neurológicas severas, caracterizadas pordistonía bilateral y signos piramidales como resultado de lesión bilateral de los ganglios basales documentadapor imagenología.

Disulfiram (Antabuse ®) is a drug that is widely used in patients with chronic alcohol consumption as part of treatment for alcoholism, in order to produce unpleasant symptoms when mixed with ethanol, acetaldehyde increased.Although there have been cases of poisoning even without alcohol intake at therapeutic doses and overdose most commonly in adults, few cases have been reported in children. We present a Child with disulfiram intoxication, who presented in acute sleepiness, progressing to stupor concomitantly presented seizures, vomiting, dehydration, rigidity, tremor and sweating; in output with severe neurological sequelae characterized by bilateral dystonia and pyramidal signs as a result of bilateral basal ganglia lesion documented by imaging.

Clinical Analysis of 82 Cases of Disulfiram-like Reaction in Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational drug use in the clinic. METHODS:The cases of disulfiram-like reac-tion collected from the First Affiliated Hospital of Guangzhou University of TCM from July 1st in 2012 to June 30st in 2014,were analyzed and compared retrospectively. The epidemiological characteristics,causes,clinical characteristics and treatment methods were summarized. RESULTS:Disulfiram-like reaction mainly occurred in male(86.59%),mainly in young and middle-aged men aged 21-50 years old (78.05%). It might be induced by using cephalosporin antibiotics (as cefoperazone,cefperazone/sulbactam, etc.),nitroimidazole (as metronidazole,tinidazole,etc.),drinking or contacting beverage,food or drug containing ethanol. This reaction involved the skin and its accessories system,circulatory system,digestive system,nervous system,respiratory system, etc. Its clinical manifestations mainly were skin flush,chest tightness,shortness of breath,palpitation,nausea,vomiting,dizzi-ness,headache,etc.,occasional confusion,drowsiness,xerostomia,etc. Response to the severe disulfiram-like reaction,the foun-dation treatment combined with symptomatic treatment showed a good effect with remission of symptoms in 1 to 3 hours and no deaths. CONCLUSIONS:When the drugs with mercapto-1-methyltetrazole perssad as cephalosporin antibiotics,nitro imidazoles, etc.,are used,we should avoid drinking or taking drugs or food containing ethanol,to prevent the occurrence of disulfiram-like re-action.

Reversible Motor Neuropathy Following Disulfiram Therapy

No abstract available.