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*

OBJECTIVES: Bone mineral density (BMD) and fragility fracture (FF) have high heritability, but few data exist on impact of other factors on families with fracture history. We aimed to evaluate predictors of FF and low BMD, in patients with family history of FF. METHODS: This was a retrospective study on patients undergoing dual energy X-ray absorptiometry at a district general hospital (DGH), 2004–2016. Parameters recorded (in addition to standard dual energy X-ray absorptiometry parameters): age, smoking, alcohol, corticosteroids, aromatase inhibitors, Depo-Provera, hormone replacement therapy, rheumatoid arthritis, polymyalgia rheumatica, breast or prostate cancer, coeliac disease, and fracture site. Logistic regression was used to model fracture risk and site, and linear regression for impact of factors on L1–4 and femoral BMD. Factor analyses with polychoric correlation matrices and calculation of Eigenvalues were applied to determine association between fracture sites and associated risk factors. RESULTS: A total of 6053 patients were included, 91.1% female. 2094 had sustained at least one FF. Smoking, alcoholism, increased age, height, and fat mass increased FF risk. Sites analysed: femur, tibia/fibula, humerus, forearm, ribs, and vertebrae. Alcoholism, and increasing tissue thickness and fat mass significantly increased FF risk. Decreased right femoral and vertebral BMD increased overall FF risk. CONCLUSIONS: Our study confirms the effect of certain factors on vertebral BMD, but suggests a differential effect on the upper and lower spine, as well as in the dominant and nondominant hip. Different sites of fracture are associated with different risk factors, the most common sites of fracture being the peripheral long bones and vertebrae.
Absorptiometry, Photon ; Adrenal Cortex Hormones ; Alcoholism ; Aromatase Inhibitors ; Arthritis, Rheumatoid ; Bone Density ; Breast ; Female ; Femur ; Forearm ; Hip ; Hormone Replacement Therapy ; Hospitals, General ; Humans ; Humerus ; Linear Models ; Logistic Models ; Medroxyprogesterone Acetate ; Osteoporosis ; Parents ; Polymyalgia Rheumatica ; Prostatic Neoplasms ; Retrospective Studies ; Ribs ; Risk Factors ; Smoke ; Smoking ; Spine

For patients with newly diagnosed type 2 diabetes mellitus (T2DM), lifestyle modifications including medical nutrition therapy, weight control, physical activity, smoking cessation, and avoidance of alcohol abuse should be initiated. Metformin must be considered as the first-line oral glucose-lowering therapy, but other drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, thiazolidinediones, glucagon-like peptide 1 receptor agonists, sulfonylureas, glinides, α-glucosidase inhibitors, and insulin can be considered based on patient circumstances. If the initial HbA1c level of a patient is ≥ 7.5% or the HbA1c target is not achieved within three months of initiating monotherapy, dual combination therapy can be considered. If the HbA1c target is not achieved within 3 months of initiating dual therapy, a third agent with a complementary mechanism of action can be added for triple combination therapy. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of SGLT-2 inhibitors in T2DM patients with cardiovascular risk factors have been incorporated into the updated recommendations.
Alcoholism ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Glucagon-Like Peptide 1 ; Humans ; Hypoglycemic Agents ; Insulin ; Life Style ; Metformin ; Motor Activity ; Nutrition Therapy ; Risk Factors ; Smoking Cessation ; Thiazolidinediones

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

INTRODUCTIONMany alcohol-related problems often go undetected and untreated. In Singapore, no epidemiological studies have been done in general hospitals on alcohol use disorders (AUD), i.e. alcohol dependence and abuse (DSM-IV-TR). Such findings are useful in planning AUD liaison services. In this study, we aim to estimate the prevalence of AUD among non-psychiatric inpatients and to determine the rates of identification and intervention rendered by medical staff.

MATERIALS AND METHODSNon-psychiatric medical and surgical wards inpatients aged 21 years and above were recruited over a 3-month period. The Alcohol Use Disorders Identification Test (AUDIT) was used to screen for AUD and the MINI International Neuropsychiatric Interview (MINI English Version 5.0.0) was administered to diagnose AUD if the AUDIT score was 8 or above. Case notes were independently reviewed for AUD identification and if interventions were offered during admissions.

RESULTSA total of 5599 inpatients were screened, of which 673 (12%) completed the screening using the AUDIT, and of these, 154 (2.8% of total sample) were positive for AUDIT. In this group, 107 were diagnosed with AUD. The estimated prevalence was 1.9% (approximately 400 cases per year per hospital). The medical staff identified only 25 (23.4%) cases of AUD, out of which, majority of them (76%) were rendered interventions.

CONCLUSIONThe rate of AUD identification by medical staff was low. Of those identified, majority were given interventions. Thus, the training of health care staff to identify AUD together with the implementation of brief interventions should be considered.

Adult ; Aged ; Alcoholism ; diagnosis ; epidemiology ; therapy ; Female ; Hospitalization ; Hospitals, General ; Humans ; Male ; Mass Screening ; utilization ; Mental Health Services ; Middle Aged ; Prevalence ; Referral and Consultation ; Singapore ; epidemiology ; Young Adult

Rhabdomyolysis is defined as a skeletal muscle injury with release of muscle cell constituents into the plasma. It can occur in various diseases and conditions, including muscle strain, drug or alcohol abuse, connective tissue disease, excess exercise, or following surgery. Only one case of rhabdomyolysis has ever been associated with liposuction in Korea. We experienced a case of rhabdomyolysis that developed after liposuction surgery. The patient was a 39-year-old woman presenting with abdominal pain 1 day after liposuction. She was treated with general supportive care, including massive hydration and absolute bed rest. Renal replacement therapy was performed due to pulmonary edema. She, finally, recovered fully. Acute kidney injury caused by liposuction-induced rhabdomyolysis is a rare disease. Therefore, we present this case with a review of the literature.
Abdominal Pain ; Acute Kidney Injury* ; Adult ; Alcoholism ; Bed Rest ; Connective Tissue Diseases ; Female ; Humans ; Korea ; Lipectomy* ; Muscle Cells ; Muscle, Skeletal ; Plasma ; Pulmonary Edema ; Rare Diseases ; Renal Replacement Therapy ; Rhabdomyolysis*

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