Anxiety and depression in patients with multiple sclerosis: The mediating effects of perceived social support.

BACKGROUND: Social support has been identified as a buffering or intervening variable in stressful life events. Research has demonstrated that greater social support is associated with better mental health in multiple sclerosis (MS), but little is known about its links to specific aspects of mental health. We therefore investigated if and how perceived social support modulates depression, anxiety and fatigue in patients with MS. METHODS: We recruited 112 patients with MS from three French hospitals and administered a demographic and clinic interview, and self-report measures of perceived social support (Multidimensional Scale of Perceived Social Support), depression and anxiety (Hospital Anxiety and Depression Scale), and fatigue (Fatigue Severity Scale). We then analyzed the relationships between these domains using path analysis. RESULTS: The causal path model provided an excellent fit for the data (χ2 = 9.8, p = .778, standardized root mean square residual = 0.043, comparative fit index = 1.00). Results indicated that the level of social support from friends is a predictor of anxiety symptomatology. Thus, anxiety may have both a direct and an indirect impact on fatigue and depression levels. CONCLUSIONS: This study highlights the important roles played by perceived social support and anxiety in MS. These should be key pharmacological and non-pharmacological targets for optimizing patient care. (NCT 02-880-553).

2-Pyrrolinodoxorubicin and its peptide-vectorized form bypass multidrug resistance.

A well-known mechanism leading to the emergence of multidrug-resistant tumor cells is the overexpression of P-glycoprotein, which is capable of lowering intracellular drug concentrations. In the present study, we tested the capability of 2-pyrrolinodoxorubicin (p-DOX), a highly potent derivative of DOX, to bypass multidrug resistance. The accumulation, intracellular distribution and cytotoxicity of p-DOX were tested in two cell lines (K562 and A2780) and their DOX-resistant counterparts (K562/ADR and A2780/ADR). Cellular accumulation and cytotoxicity were dramatically lowered for DOX in resistant cell lines, in comparison with non-resistant cells. In contrast, cellular accumulation, intracellular distribution and cytotoxicity of p-DOX were independent of the nature of the cell lines. The p-DOX showed potent dose-dependent inhibition of cell growth against resistant cells as compared with DOX. After treatment of resistant cells with verapamil, the intracellular levels of DOX were markedly increased and consequent cytotoxicity improved. In contrast, treatment of resistant cells with verapamil did not cause any further enhancement of cell uptake or an increase in the cytotoxic effect of the derivative p-DOX, indicating that the compound bypasses the P-glycoprotein. Finally, we show that vectorization of p-DOX by a peptide vector (SynB3) which has been shown to enhance the brain uptake of DOX and to decrease its heart accumulation does not affect this property. These results indicate that p-DOX and its vectorized form are potent and effective in overcoming multidrug resistance.