OBJECTIVE: This study aimed to evaluate the treatment paradigm of a single dose of GSK-3 inhibitor administration at various time courses for the protection of the CNS from EAE.
MATERIALS AND METHODS: Effects of GSK-3 inhibition on intracellular cytokine levels were evaluated from in vitro naïve CD4+ T cell cultures. Immunized C57BL/6 female mice with MOG35-55 in conjunction with CFA and Ptx were used as a chronic inflammatory EAE disease model. Tideglusib (NP12), a Thiadiazolidinone class, selective, and non-ATP competitive GSK-3 inhibitor, was injected intraperitoneally at pre-EAE, same-day of immunization or disease onset. After 30 days post-immunization, brain, and spinal cord tissues were collected for inflammation and demyelination analysis by H&E and luxol fast blue staining, respectively, whereas cytokine profiles of the serum were assessed by cytokine beads array.
RESULTS: The inhibition of GSK-3 in CD4+ T cells increased IL-10 production. The administration of Tideglusib during pre-EAE and same-day, but not during disease onset, significantly reduced clinical symptoms and delayed disease onset. Histopathological analysis of spinal cord tissues showed a significant decline in the number of inflammatory cell infiltration with a concomitant reduction in demyelination through the blocking of GSK-3, especially during pre-EAE and sameday. Upregulation of IL-10 via GSK-3 inhibition coincided with the downregulation of cytokineassociated effector T cells, including IFN-γ, IL-9, IL-17A, IL-17F, IL-21, and IL-23. Increased IL-4 production, however, was only significant in the pre-EAE group.
CONCLUSION: The neuroprotective effects of Tideglusib against EAE are time-dependent. Downregulation of Th1 and Th17 hallmark cytokines by Tideglusib in EAE may be associated with IL-10 production.
OBJECTIVE: This study explored, assessed and compared the current status of medicines labeling, patient's counseling, and symptomatic diagnosis by general practitioners and community pharmacists.
MATERIAL AND METHODS: This study used trained Simulated Patients (SP), who participated in a scenario of common cold symptoms at private clinics and community pharmacies. SPs explored medication labeling, patients counseling and symptomatic diagnosis undertaken by general practitioners and community pharmacists. Later, study authors assessed and compared these practices. The study was conducted during June 2011 in Penang, Malaysia.
RESULTS: The study used descriptive statistics and Fisher-exact test to analyze data. Regarding patients counseling standard, among 100 visits by simulated patients, 64 (64%) from community pharmacists provided information about the medicine name, its indication, dosage and route of administration versus 17 (42.5%) general practitioners during 40 visits (p=0.024). Concerning adherence to labeling standard, for instance, only in one pharmacy visit, (1%) the pharmacist wrote the name of the patient on the medication label versus in 32 (80%) of doctors' visits, the doctors adhered to this labeling standard (p<0.001). In all doctors' visits (n=40, 100%), SPs were asked about symptoms, whereas in 87 (87%) CPs' visits, pharmacists fulfilled this counseling standard (p=0.02).
CONCLUSION: Although pharmacists showed less compliance to medicine labeling and symptomatic diagnosis compared to doctors, their counseling of patients was better. Separation will definitely contribute to more concentration of each provider on his/her roles and improve and direct the experiences and skills towards being more patient oriented.