Passive permeability assay of doxorubicin through model cell membranes under cancerous and normal membrane potential conditions.

Doxorubicin is an anti-cancer drug that is important for breast cancer therapy. In this study, the effects of the membrane potential of breast cancer cells (-30 mV) and normal breast epithelial cells (-60 mV) on doxorubicin (DOX) permeability was studied. To achieve this goal, black lipid membranes (BLMs) as a model cell membrane were formed with DPhPC phospholipids in a single aperture of a Teflon sheet by the Montal and Mueller method. The presence of the BLM was characterized by capacitive measurements. The measured specific capacitance of 0.6 µF/cm2 after applying the Montal and Mueller method, confirming the presence of a BLM in the aperture. In addition, the very low current leakage of the BLM (9-24 pA) and ClyA-protein channel insertion in the BLM indicate the compactness, high quality, and thickness of 3-5 nm of the BLM. Afterwards, the permeability of doxorubicin through the BLM was studied at defined cell conditions (37 °C and pH 7.4), as well as cancerous and healthy epithelial-cell membrane potentials (-30 mV and -60 mV, respectively). The results show a slow DOX penetration within the first few hours, which increases rapidly with time. The initial slow penetration can be attributed to an electrostatic interaction between doxorubicin and DPhPC molecules in the model cell membrane. Furthermore, a MTT assay on MCF-10A and MCF-7 under different concentrations of doxorubicin confirmed that the cancerous MCF-7 cell line is more resistant to doxorubicin in comparison with the non-cancerous MCF-10A. Such studies highlight important strategies for designing and tuning the interaction efficacy of novel pharmaceuticals at molecular level.

Diagnostic stability in patients with first-episode psychosis.

OBJECTIVE: To examine the short-term stability of Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) and International Classification of Diseases (10th revision; ICD-10) diagnoses in a group of patients with first-episode psychosis. METHOD: Sixty patients with first-episode psychosis admitted consecutively to Roozbeh Hospital, Tehran, were sampled; their illnesses could not be attributed to any medical or substance-induced conditions. Patients were assessed at the time of discharge from the hospital, and at 3, 6 and 12 month intervals following admission. At each visit, two psychiatrists made consensus DSM-IV and ICD-10 diagnoses, based on all available information. Stability was discerned as the consistency between diagnoses at the time of discharge and at 12 month follow up. RESULTS: Forty-eight patients completed follow up. Affective psychotic disorders and schizophrenia in both classification systems were highly stable. In addition, all patients with DSM-IV brief psychotic disorder and ICD-10 acute and transient psychotic disorders remained the same at follow up. CONCLUSIONS: Affective psychoses and schizophrenia, in line with previous findings, remained stable. Diagnoses of brief psychoses were highly stable as well; this could reflect a non-relapsing course of acute brief psychoses, especially in developing countries.