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.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

OBJECTIVE: To compare the clinical efficacy between auricular point sticking combined with transcutaneous electrical acupoint stimulation (TEAS) and nicotine patch for smoking cessation. METHODS: Two hundred patients who voluntarily quit smoking were randomly divided into a combination group and a nicotine patch group, 100 cases in each group. In the combination group, auricular point sticking (Shenmen [TF₄], Neifenmi [CO₁₈], Pizhixia [AT₄], Jiaogan [AH_6a], etc., once every other day) combined with TEAS（Lieque [LU 7] and Zusanli [ST 36], with continuous wave, 20 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day) were applied. In the nicotine patch group, nicotine patch was applied. Both groups were treated for 8 weeks. The immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and in follow-up of 16 weeks after treatment in the two groups were compared; before treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the degree of nicotine dependence was evaluated by using Fagerström test for nicotine dependence (FTND); 1 week into treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the withdrawal symptoms and smoking craving were evaluated by using Minnesota nicotine withdrawal scale (MNWS); the safety and compliance (dropped off rate and treatment completeness) were evaluated in the two groups. RESULTS: There was no statistical significance of the differences in the immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and during follow-up between the two groups (P>0.05). The FTND scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those before treatment (P<0.01); the FTND score during follow-up in the combination group was lower than the nicotine patch group (P<0.05). The MNWS scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those 1 week into treatment (P<0.05); the changes of MNWS scores 8 weeks into treatment and during follow-up in the combination group were greater than the nicotine patch group (P<0.05, P<0.01). There were no serious adverse reactions in either group. Eight weeks into treatment and during follow-up, the dropped off rates were all 16.0% (16/100) in the combination group, which were 20.0% (20/100) and 23.0% (23/100) in the nicotine patch group, there was no statistical significance of the differences in the two groups (P>0.05). There was no significant difference in treatment completeness between the two groups (P>0.05). CONCLUSION Auricular point sticking combined with TEAS could effective decrease the degree of nicotine dependence, improve withdrawal symptoms in smokers, its effect is superior to nicotine patch.
Humans ; Smoking Cessation ; Tobacco Use Disorder ; Acupuncture Points ; Administration, Cutaneous ; Nicotine ; Substance Withdrawal Syndrome/drug therapy*

The purpose of this study was to investigate the effects of α₂ adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α₂ adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α₂ adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use* ; Alcoholism/drug therapy* ; Animals ; Dexmedetomidine/therapeutic use* ; Hippocampus/metabolism* ; Male ; Norepinephrine ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2/metabolism* ; Substance Withdrawal Syndrome/drug therapy* ; Yohimbine/pharmacology*

Alcohol use disorder is a kind of chronic illness that is difficult to treat. The disorder often recurs easily and patients visit the outpatient clinic while intoxicated. Therefore, is often too difficult to treat all people of concern, i.e., the caregiver, patient, and doctor, due to the frequent helpless and hopeless relapse. If the patient has severe withdrawal symptoms or poor physical condition, it is very difficult to maintain treatment at an outpatient clinic. On the other hand, many patients abstain or reduce drinking and go on to live a sober life by outpatient-based management. In addition, psychosocial treatment techniques and efficient medications are available at the level of a psychiatric outpatient clinic. Under the scope and limitations of outpatient-based approaches, patients with alcohol use disorder can develop a new life called ‘recovery’ with the help of psychiatrists, by the way of motivating changes, correcting cognitive errors, establishing effective coping skills, utilizing external resources actively, and facilitating healthy roles with their families.
Adaptation, Psychological ; Alcoholism ; Ambulatory Care Facilities ; Caregivers ; Chronic Disease ; Drinking ; Drug Therapy ; Hand ; Humans ; Outpatients ; Psychiatry ; Psychotherapy ; Recurrence ; Substance Withdrawal Syndrome

OBJECTIVE: To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai tablet combined with buprenorphine in the treatment of patients with acute withdrawal syndrome of mild heroin dependence. METHODS: A total of 150 patients with mild heroin dependence were recruited, and were randomly assigned to a Ji-Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50) and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before and 1 h or 2 h after medication each day. The total withdrawal symptoms scores and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the following measures: baseline of treatment, drug side effects after the treatment, vital signs (blood pressure, heart rate, and respiration rate), laboratory examination (routine blood and urine tests and the liver and kidney function tests), and electrocardiograms. RESULTS: A total of 142 mild heroin dependence patients performed the experiments (including 48 in the Ji-Tai tablet group, 48 in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The scores of baseline withdrawal symptoms were 43.520±19.786, 42.640±17.648 and 47.100±24.450, respectively, with no significant differences among the 3 groups (all P>0.05 ). During the 10-day treatment, the reduction rate of acute withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores and the anxiety symptoms scores declined from day 0 to day 10, there was also no significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not affect vital signs such as blood pressure, heart rate, and respiration rate. CONCLUSION Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no effect on acute withdrawal symptoms of mild heroin dependence.
Anxiety ; Buprenorphine ; therapeutic use ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Heroin Dependence ; drug therapy ; Humans ; Substance Withdrawal Syndrome ; drug therapy ; Tablets

BACKGROUNDWe previously demonstrated that the aqueous extract of the Schizandra chinensis fruit (AESC) ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity. In the present study, we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol (a metabolite of norepinephrine) in different brain regions during ethanol withdrawal in rats.

METHODSMale Sprague-Dawley rats were treated with 3 g/kg of ethanol (20%, w/v) or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal. During withdrawal, rats were given AESC (100 mg × kg(-1)× d(-1) or 300 mg × kg(-1)× d(-1), P.O.) once a day for three days. Thirty minutes after the final dose of AESC, the anxiogenic response was evaluated using an elevated plus maze, and the plasma corticosterone levels were examined by radioimmunoassay. Meanwhile, the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography.

RESULTSRats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior, which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion, which were greatly attenuated by doses of AESC in a dose-dependent manner. The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus, while not significantly altering them in the hippocampus. Similar to the results from the elevated plus maze test, the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner.

CONCLUSIONSThese results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.

Animals ; Anxiety ; drug therapy ; etiology ; Behavior, Animal ; drug effects ; Ethanol ; adverse effects ; Fruit ; chemistry ; Male ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Schisandra ; chemistry ; Substance Withdrawal Syndrome ; drug therapy

This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group (n=41) were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group (n=42) were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05). It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.
Administration, Oral ; Adult ; Dietary Supplements ; Drug Therapy, Combination ; methods ; Female ; Heroin Dependence ; diagnosis ; therapy ; Humans ; Male ; Neurotransmitter Agents ; administration & dosage ; Placebo Effect ; Single-Blind Method ; Substance Withdrawal Syndrome ; diagnosis ; drug therapy ; therapy ; Treatment Outcome

The treatment of benzodiazepine withdrawal is difficult, and the search continues for substances that can reduce craving and the risk of relapse. Here, we report three cases of benzodiazepine addicts with histories of unsuccessful withdrawal attempts who experienced marked reductions in craving and improved relapse prognoses under add-on administration of agomelatine. These cases demonstrate a possible area of use for the antidepressant agomelatine in the treatment of benzodiazepine withdrawal and addiction. The extent to which this effect is due to the anti-craving effects of agomelatine, or its profile of receptor activation, should be further investigated in larger clinical and experimental studies.
Acetamides ; therapeutic use ; Adult ; Antidepressive Agents ; therapeutic use ; Behavior, Addictive ; Benzodiazepines ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Hypnotics and Sedatives ; adverse effects ; Lorazepam ; adverse effects ; Male ; Middle Aged ; Substance Withdrawal Syndrome ; drug therapy ; Substance-Related Disorders ; drug therapy ; Time Factors ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of slow anti-epileptic drug (AED) taper protocol and a rescue benzodiazepine protocol in video-electroencephalography (video-EEG) monitoring for presurgical evaluation of epilepsy.

METHODSSixty-two of 109 patients with refractory focal epilepsy underwent pre-surgical video-EEG monitoring with a slow AEDs taper protocol and a rescue benzodiazepine protocol. Seizures were recorded by video-EEG in 56 patients. The time to the first seizure, duration of monitoring, incidence of 4-h and 24-h seizure clustering, secondarily generalized tonic-clonic seizures (sGTCS), status epilepticus, falls and cardiac asystole were evaluated.

RESULTSA total of 191 seizures were recorded in the 56 cases, and the diagnostic efficiency of video-EEG was 90.3%. The mean time to the first seizure was 2.4 days and the time to conclude video-EEG monitoring averaged 6.8 days. Eight (12.9%) patients had 4-h clusters and 24 (38.7%) had 24-h clusters. Seizure clusters were more frequent in extra temporal epilepsy than in temporal lobe epilepsy. While 19 sGTCS were recorded in 15 patients (26.8%), status epilepticus did not occur and no seizure was complicated by cardiac asystole. Epileptic falls with no significant injuries occurred in 4 patients.

CONCLUSIONSeizure clustering is common during presurgical video-EEG monitoring, but serious adverse events are rare with a slow AED tapering and a rescue benzodiazepine protocols. These two protocols are effective and save in presurgical video-EEG monitoring for refractory focal epilepsy.

Adolescent ; Adult ; Anticonvulsants ; adverse effects ; therapeutic use ; Electroencephalography ; methods ; Epilepsy ; diagnosis ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; methods ; Substance Withdrawal Syndrome ; diagnosis ; prevention & control ; Video Recording ; Young Adult

OBJECTIVE: To explore the change and impact factors of craving for heroin in patients after 6 month methadone maintenance treatment (MMT). METHODS: The questionnaire of craving for heroin was used to measure the level of craving for heroin when patients just entered the study and were treated for 6 months. The influence of MMT on craving in patients were analyzed. RESULTS: The total score and score for other factors decreased except the factor "self-control" after MMT. The craving for high dose patients decreased significantly after 6 month treatment (P<0.05). The degree of craving for heroin in males and females all decreased after MMT, but no significant difference was shown (P>0.05). The craving degree for heroin in patients with long drug use was higher than that of patients with short drug use. After the treatment, the improvement of craving was more significant for the long drug users. CONCLUSION MMT can decline the craving for heroin in drug users. Dosage for methadone and gender may be the risk factors of craving change.
Adult ; China ; Female ; Heroin Dependence ; drug therapy ; psychology ; rehabilitation ; Humans ; Male ; Methadone ; therapeutic use ; Substance Withdrawal Syndrome ; drug therapy ; psychology ; Surveys and Questionnaires ; Young Adult