Fluoxetine is used widely as an antidepressant for the treatment of cancer-related depression, but has been reported to also have anti-cancer activity. In this study, we investigated the cytotoxicity of fluoxetine to human gastric adenocarcinoma cells; as shown by the MTT assay, fluoxetine induced cell death. Subsequently, cells were treated with 10 or 20 μM fluoxetine for 24 h and analyzed. Apoptosis was confirmed by the increased number of early apoptotic cells, shown by Annexin V-propidium iodide staining. Nuclear condensation was visualized by DAPI staining. A significant increase in the expression of cleaved PARP was observed by western blotting. The pan-caspase inhibitor Z-VAD-FMK was used to detect the extent of caspase-dependent cell death. The induction of autophagy was determined by the formation of acidic vesicular organelles (AVOs), which was visualized by acridine orange staining, and the increased expression of autophagy markers, such as LC3B, Beclin 1, and p62/SQSTM 1, observed by western blotting. The expression of upstream proteins, such as p-Akt and p-mTOR, were decreased. Autophagic degradation was evaluated by using bafilomycin, an inhibitor of late-stage autophagy. Bafilomycin did not significantly enhance LC3B expression induced by fluoxetine, which suggested autophagic degradation was impaired. In addition, the co-administration of the autophagy inhibitor 3-methyladenine and fluoxetine significantly increased fluoxetine-induced apoptosis, with decreased p-Akt and markedly increased death receptor 4 and 5 expression. Our results suggested that fluoxetine simultaneously induced both protective autophagy and apoptosis and that the inhibition of autophagy enhanced fluoxetine-induced apoptosis through increased death receptor expression.

Dengue viruses are single-stranded RNA viruses of the Flavivirus genus. It is a common viral infection worldwide, especially in tropical regions. Various neurological manifestations such as encephalitis, encephalopathy, meningitis, acute disseminated encephalomyelitis (ADEM) acute viral myositis, Guillain–Barré syndrome and others are increasingly reported. However, acute haemorrhagic encephalitis is a very rare presentation. Currently, there are only few previous case reports

BACKGROUND: More than 140 million people drink arsenic-contaminated groundwater. It is unknown how much arsenic exposure is necessary to cause neurological impairment. Here, we evaluate the relationship between neurological impairments and the arsenic concentration in drinking water (ACDW). PARTICIPANTS AND METHODS: A cross-sectional study design was employed. We performed medical examinations of 1867 residents in seven villages in the Thabaung township in Myanmar. Medical examinations consisted of interviews regarding subjective neurological symptoms and objective neurological examinations of sensory disturbances. For subjective neurological symptoms, we ascertained the presence or absence of defects in smell, vision, taste, and hearing; the feeling of weakness; and chronic numbness or pain. For objective sensory disturbances, we examined defects in pain sensation, vibration sensation, and two-point discrimination. We analyzed the relationship between the subjective symptoms, objective sensory disturbances, and ACDW. RESULTS: Residents with ACDW ≥ 10 parts per billion (ppb) had experienced a "feeling of weakness" and "chronic numbness or pain" significantly more often than those with ACDW < 10 ppb. Residents with ACDW ≥ 50 ppb had three types of sensory disturbances significantly more often than those with ACDW < 50 ppb. In children, there was no significant association between symptoms or signs and ACDW. CONCLUSION Subjective symptoms, probably due to peripheral neuropathy, occurred at very low ACDW (around 10 ppb). Objective peripheral nerve disturbances of both small and large fibers occurred at low ACDW (> 50 ppb). These data suggest a threshold for the occurrence of peripheral neuropathy due to arsenic exposure, and indicate that the arsenic concentration in drinking water should be less than 10 ppb to ensure human health.
Adolescent ; Adult ; Arsenic ; analysis ; toxicity ; Cross-Sectional Studies ; Dietary Exposure ; adverse effects ; Dose-Response Relationship, Drug ; Drinking Water ; adverse effects ; chemistry ; Female ; Groundwater ; chemistry ; Humans ; Male ; Middle Aged ; Myanmar ; epidemiology ; Peripheral Nervous System Diseases ; chemically induced ; epidemiology ; physiopathology ; Sensation Disorders ; chemically induced ; epidemiology ; physiopathology ; Water Pollutants, Chemical ; analysis ; toxicity ; Young Adult