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

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

OBJECTIVETo examine the effect of acupuncture on Zhubin (KI9) in reducing alcohol craving in alcohol-dependent patients.

METHODSTwenty male alcohol-dependent patients were randomly assigned to two groups, a treatment group (10 cases, age 43.0±6.8 years) and a placebo group (10 cases, age 44.5±7.9 years). The treatment group was treated with real needle acupuncture on Zhubin (KI9) twice a week for 4 weeks, and the control group was treated with placebo needle acupuncture. Both groups were given acupuncture treatment using Park Sham Device (PSD). Alcohol craving was measured by the Visual Analogue Scale (VAS) before treatment to establish a baseline, and after 1, 2, and 4 weeks of treatment. Repeated measures ANOVA was used to determine the main and interaction effects of time and on the outcome measure (VAS).

RESULTSThere was a significant effect of time on VAS score (df=3, F=13.3, P<0.01). Main effect of group on VAS score was significant (df=1, F=10.9, P<0.01) and the time×group interaction was also significant (df=3, F=4.7, P<0.01).

CONCLUSIONSReal-needle acupuncture therapy on Zhubin (KI9) showed effectiveness in reducing alcohol craving. These results strongly suggest the usefulness of acupuncture therapy on Zhubin (KI9) in preventing a relapse in alcohol dependent patients.

Acupuncture Points ; Acupuncture Therapy ; methods ; Adult ; Alcoholism ; therapy ; Craving ; drug effects ; Ethanol ; pharmacology ; Humans ; Male ; Middle Aged ; Placebos ; Treatment Outcome

The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.
Adult ; Alcohol Drinking/*adverse effects ; Alcoholism/*drug therapy ; Capsaicin/pharmacology ; Food Preferences/*drug effects ; Humans ; Male ; Naltrexone/adverse effects/*therapeutic use ; Narcotic Antagonists/adverse effects/*therapeutic use ; Questionnaires ; Sensory System Agents/pharmacology ; Young Adult

Chronic diarrhea with a 35 kg weight loss (75 kg to 40 kg) occurred during 2 years in an alcoholic patient was diagnosed with Isospora belli infection in the Republic of Korea. The patient, a 70-year old Korean male, had been a heavy drinker for more than 30 years. He was admitted to the Seoul National University Hospital because of long-standing diarrhea and severe weight loss. He had an increased white blood cell (WBC) count with high peripheral blood eosinophilia (36.8-39.9%) and lowered protein and albumin levels but without any evidence of immunosuppression. A parasitic infection was suspected and fecal examination was repeated 3 times with negative results. Peroral endoscopy with mural biopsy was performed in the upper jejunum. The biopsy specimens revealed villous atrophy with loss of villi together with various life cycle stages of I. belli, including trophozoites, schizonts, merozoites, macrogamonts, and microgamonts. The patient was treated successfully with oral doses of trimethoprim 160-320 mg and sulfamethoxazole 800-1,600 mg daily for 4 weeks. A follow-up evaluation at 2.5 years later revealed marked improvement of body weight (68 kg), increased protein and albumin levels, and normal WBC count with low eosinophils (3.1%). This is the first clinical case of isoporiasis with demonstration of various parasitic stages in the Republic of Korea.
Aged ; Alcoholism/*complications ; Antiparasitic Agents/administration & dosage ; Diarrhea/drug therapy/*etiology/parasitology/*pathology ; Humans ; Isospora/*isolation & purification ; Isosporiasis/*diagnosis/drug therapy/parasitology/*pathology ; Male ; Republic of Korea ; Sulfamethoxazole/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage

OBJECTIVETo investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism.

METHODSIn acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium.

RESULTSCompared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P<0.05, P<0.01) and increased myocardial SOD (P<0.05, P<0.01), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity (P<0.05, P<0.01), but Na(+)-K(+)-ATPase was similar between the two groups (P>0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular.

CONCLUSIONPuerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

Alcoholism ; drug therapy ; Animals ; Cardiomyopathy, Alcoholic ; metabolism ; pathology ; prevention & control ; Ethanol ; toxicity ; Isoflavones ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley

Alcoholism ; drug therapy ; metabolism ; physiopathology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; metabolism ; Learning ; drug effects ; physiology ; Male ; Memory ; drug effects ; physiology ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism ; Superoxide Dismutase ; metabolism

Alcoholism ; complications ; Antiviral Agents ; therapeutic use ; Fatty Liver ; diagnosis ; epidemiology ; etiology ; therapy ; Hepatitis, Viral, Human ; complications ; diagnosis ; drug therapy ; Humans ; Insulin Resistance ; Interferons ; therapeutic use ; Obesity ; complications ; Risk Factors

PURPOSE: To retrospectively analyze the clinical presentations, radiographic findings, and surgical results of type I and II acute necrotizing fasciitis of the low extremity. MATERIALS AND METHODS: From April 1998 to March 2005, 13 patients who underwent surgery for the necrotizing fasciitis were reviewed. At the initial diagnosis, 6 patients were diagnosed with cellulitis and 3 patients were diagnosed correctly with necrotizing fasciitis. The underlying diseases, affected sites, official readings of MRI, the intervals between the onset of symptom and surgery, the duration of admission, and complications were investigated. RESULTS: The underlying diseases were 3 cases of diabetes, 3 cases of liver disease, 1 case of alcoholism and 1 case of cervical cancer with chemotherapy. Regarding the location of the disease, 5 cases were observed below the knees, and 8 cases were observed above the knees. Five out of 9 cases who underwent a preoperative MRI study, were diagnosed correctly as necrotizing fasciitis by the radiologist. The average period between onset of symptoms and surgery was 4.8 days. The complications were hip disarticulation in 1 case, below knee amputation in 1 case, toe amputation in 1 case, and a limited range of motion of the knee joint in 1 case. The 9 patients who healed without complications had no limitation in the range of joint motion and daily activity. CONCLUSION: Type I and II acute necrotizing fasciitis of the low extremity shows variable clinical presentations and radiological findings. Therefore, the possibility of the necrotizing fasciitis needs to be considered when dealing with patients with soft tissue infections in the low extremities.
Alcoholism ; Amputation ; Cellulitis ; Diagnosis ; Disarticulation ; Drug Therapy ; Extremities* ; Fasciitis, Necrotizing* ; Hip ; Humans ; Joints ; Knee ; Knee Joint ; Liver Diseases ; Magnetic Resonance Imaging ; Range of Motion, Articular ; Reading ; Retrospective Studies ; Soft Tissue Infections ; Toes ; Uterine Cervical Neoplasms