RESUMO
BACKGROUND: Multimodal rheumatologic complex treatment (MRCT) is based on an acute inpatient treatment concept for patients with clinically relevant functional impairments and exacerbation of pain, which are caused by rheumatic and musculoskeletal diseases. Patients with axial spondylarthritis (axSpA) including ankylosing spondylarthritis (AS) often suffer from such health problems. Regular movement exercises and physical therapy measures are an important pillar of treatment management. The ASAS Health Index (ASAS-HI) can be used to document the global functional ability and health of axSpA patients. The selectivity of the ASAS HI for nonpharmacological treatment changes has so far not yet been proven. OBJECTIVE: Evaluation of the MRCT and ASAS HI for nonpharmacological treatment measures of patients with axSpA carried out in the Ruhr Area Rheumatism Center. The primary endpoint was an improvement of the ASDAS≥ 1.1. It was assumed that >â¯25% of the patients would achieve this threshold. METHODS: Consecutively included patients with active axSpA and relevant functional impairments received inpatient treatment for 14 days during MRCT. On days 1 (V1) and 14 (V2) all patients completed questionnaires on pain (NRS), disease activity (BASDAI, ASDAS) and function (BASFI, ASAS HI). The clinical examination was carried out using BASMI and measurement of Creactive protein (CRP) at both times. RESULTS: The 66 prospectively included patients had an average age of 47.2 years (SD 14.2 years), a duration of symptoms of ca. 20 years, 65.3% were male, 75% were positive for HLA B27 and CRP was elevated in 41.3%. The disease activity at V1 was elevated: BASDAI 5.6 (1.8), ASDAS 3.1 (0.9), whereas functional ability and mobility were reduced: BASFI 3.5 (1.8), BASMI 5.6 (2.1), ASAS-HI 8.4 (3.4). During the course the global patient verdict improved (NRS 0-10) from 6.9 (1.7) at V1 to 4.8 (1.8) at V2 and the pain from 6.9 (1.9) to 4.7 (2.0) (all pâ¯< 0.001). The disease activity also decreased at V2: BASDAI 4.1 (1.9), ASDAS 2.4 (1.0), function and mobility were also improved: BASFI 4.3 (2.4), BASMI 2.7 (1.6), ASAS HI 6.5 (3.8) (all pâ¯< 0.001). CONCLUSION: In this study the effectiveness of a 2week MRCT according to OPS 8-983.1 with respect to important patient-centered outcomes (PCO) could be proven and the results of previous studies could be confirmed. In this context ASAS-HI was also sensitive to change.
RESUMO
Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD) and could initiate dopaminergic neuronal degeneration. Nevertheless, experimental glutathione depletion does not result in preferential toxicity to dopaminergic neurons either in vivo or in vitro. Moreover, dopaminergic neurons in culture are preferentially resistant to the toxicity of glutathione depletion, possibly owing to differences in cellular glutathione peroxidase (GPx1) function. However, mesencephalic cultures from GPx1-knockout and wild-type mice were equally susceptible to the toxicity of glutathione depletion, indicating that glutathione also has GPx1-independent functions in neuronal survival. In addition, dopaminergic neurons were more resistant to the toxicity of both glutathione depletion and treatment with peroxides than nondopaminergic neurons regardless of their GPx1 status. To explain this enhanced antioxidant capacity, we hypothesized that tetrahydrobiopterin (BH(4)) may function as an antioxidant in dopaminergic neurons. In agreement, inhibition of BH(4) synthesis increased the susceptibility of dopaminergic neurons to the toxicity of glutathione depletion, whereas increasing BH(4) levels completely protected nondopaminergic neurons against it. Our results suggest that BH(4) functions as a complementary antioxidant to the glutathione/glutathione peroxidase system and that changes in BH(4) levels may contribute to the pathogenesis of PD.
