Acceptance of the extracare program by Beta interferon-treated patients with multiple sclerosis: results of the explore study.

BACKGROUND: To gain full benefit from disease-modifying therapies such as interferon ß-1b, patients with multiple sclerosis (MS) need to adhere to treatment in the long term. Treatment adherence requires high patient satisfaction with treatment and care. OBJECTIVES: Our aim was to evaluate the satisfaction of patients with MS receiving interferon ß-1b Extavia with the patient care program Extracare. Efficacy and safety of treatment were evaluated as secondary objectives. METHODS: In this prospective, noninterventional 1-year study, data on the satisfaction of 174 patients with MS with Extracare were obtained by questionnaires. Disability and symptom severity as well as patients' reported activity limitations, quality of life, and fatigue were recorded. RESULTS: We observed high levels of patients' satisfaction with MS nurses, telephonic care, and information provided by Extracare (values ≤ 1.53 on a Likert scale ranging from 1 [very good] to 6 [insufficient]). Patient reported quality of life (Patient Reported Indices for MS QoL) improved from 11.82 ± 11.36 at baseline to 9.74 ± 10.94 at the end of the study (p = .02), whereas clinical parameters of disease progression remained unchanged. Rate of adverse events was as expected. CONCLUSIONS: This study provides the basis for further improvements of care programs to increase treatment adherence of patients with MS.

Additivity, antagonism, and synergy in arsenic trioxide-induced growth inhibition of C6 glioma cells: effects of genistein, quercetin and buthionine-sulfoximine.

Arsenic trioxide (ATO) induces clinical remission in acute promyelocytic leukemia and growth inhibition in various cancer cell lines in vitro. Recently, genistein and quercetin were reported to potentiate ATO-provoked apoptosis in leukemia and hepatocellular carcinoma cells. Genistein acted via enhanced ROS generation and quercetin via glutathione depletion. Searching for potential strategies for the treatment of malignant gliomas in this study the capacity of these flavonoids to sensitize rat C6 astroglioma cells for the cytotoxic action of ATO was investigated. ATO inhibited cell growth in a concentration- and time-dependent manner. This effect was accompanied neither by enhanced radical generation nor lipid peroxidation and was not attributed to apoptosis. ATO treatment concentration-dependently increased glutathione levels. Genistein enhanced radical generation. Combined with ATO it inhibited cell growth additively. Additivity was also obtained after cotreatment with ATO and H2O2. Quercetin acted antagonistically on ATO-induced growth inhibition. Quercetin increased glutathione levels. In contrast, buthionine-sulfoximine (BSO) depleted cellular glutathione and acted synergistically with ATO. In conclusion, in C6 cells neither genistein nor quercetin are suited as sensitizing agent, in contrast to BSO. Depletion of cellular glutathione content rather than an increase of ROS generation plays a central role in the enhancement of ATO-toxicity in C6 cells.

Cytoprotective activity against peroxide-induced oxidative damage and cytotoxicity of flavonoids in C6 rat glioma cells.

The aim of this study was to investigate the relationship between cytoprotective and cytotoxic activities of selected plant flavonoids in C6 glioma cells. Apigenin, kaempferol, luteolin, and quercetin were cytotoxic at low µM concentrations (LOECs: 5-20 µM), whereas myricetin was less toxic (LOEC>20 µM). Cytotoxicity was not due to H(2)O(2) generation from flavonoids in culture medium. Quercetin, luteolin, and kaempferol protected the cells from peroxide-induced cytotoxicity. Concentration-effect curves for cytoprotection had a biphasic shape. In contrast, apigenin and myricetin did not exhibit any cytoprotective activity. The first three compounds also inhibited cellular lipid peroxidation induced by CHP, while the latter were ineffective. Importantly, concentrations of luteolin and kaempferol protecting cells under oxidative stress were identical to those causing cell damage under normal conditions. Only in case of quercetin there was a narrow range of concentrations protecting cells without being cytotoxic to non-stressed cells. Thus, even for flavonoids with a high antioxidant capacity in cell-free systems the cytoprotective selectivity (LOEC(cytotox)/LOEC(cytoprot)) was very low or even absent. These results should be taken into account when the prophylactic or therapeutic application of flavonoids as antioxidants is discussed.

TLR2-, TLR4- and Myd88-independent acquired humoral and cellular immunity against Salmonella enterica serovar Typhimurium.

Toll-like receptors (TLR) are central to pathogen recognition by the innate immune system. However, their role in the generation of acquired immunity is less clear. Using experimental Salmonella enterica serovar Typhimurium (ST) infection of mice, we determined the role of TLR2, TLR4 and of the TLR adaptor protein Myeloid differentiation factor 88 (MyD88) in the generation of specific T- and B-cell responses against this pathogen. When infected with an attenuated ST strain, mice deficient in TLR4, TLR2 plus TLR4 or MyD88 suffered from exacerbated bacterial burden and delayed clearance. However, all mutant mice not only survived infection but also generated normal antibody responses. Compared to wild-type mice, TLR2+4 deficient mice displayed even enhanced CD4(+) T(H)1 and CD8(+) T cell responses. In contrast, T-cell responses in TLR2 deficient and MyD88 deficient mice were similar to those observed in wild-type controls. Overall, T- and B-cell responses were functional and provided protection against a challenge infection with virulent ST. Our results demonstrate that in the ST infection model, MyD88 as well as TLR2 and TLR4 were largely dispensable for the induction of protective acquired immunity.