Redox Regulation of Pro-IL-1ß Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice.

AIMS: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. RESULTS: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/-) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of NOX2. The levels of interleukin-1ß (IL-1ß) and IL-6 in inflamed joints were higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1ß were equally effective in suppressing arthritis in wild-type mice, while IL-1ß blockade was more effective than TNFα blockade in Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1ß to its active form and this activity was suppressed by ROS. INNOVATION: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. CONCLUSION: Our results suggest that ROS act as a negative feedback to constrain IL-1ß-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.

Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson's disease.

Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the associations of vitamin D intake and outdoor activities with Parkinson's disease (PD) are still unclear, so this study is to evaluate these relationships from a case-control study in elderly Chinese. The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases. The data on dietary vitamin D and outdoor activities were collected using a food-frequency questionnaire and self-report questionnaire. Multivariable logistic regressions were used to examine the associations between dietary outdoor activities, vitamin D intake and PD. Adjustment was made for sex, age, smoking, alcohol use, education, and body mass index (BMI). Adjusted odds ratios (ORs) for PD in quartiles for outdoor physical activity were 1 (reference), 0.739 (0.413, 1.321), 0.501 (0.282, 0.891), and 0.437 (0.241, 0.795), respectively (P=0.002 for trend). Adjusted ORs for PD in quartiles for total vitamin D intake were 1 (reference), 0.647 (0.357, 1.170), 0.571 (0.318, 1.022), and 0.538 (0.301, 0.960), respectively (P=0.011 for trend). Our study suggested that outdoor activity and total vitamin D intake were inversely associated with PD, and outdoor activity seems to be more significantly associated with decreased risk for PD.

[Impacts on carotid arterial vessel and blood flow in treatment of carotid atherosclerosis with acupuncture and moxibustion].

OBJECTIVE: To assess the impacts of acupuncture and moxibustion on carotid arterial vascular structure and blood flow parameters for the patients with carotid arteriosclerosis. METHODS: Sixty-eight cases were randomized into an acupuncture-moxibustion group (35 cases) and a medication group (33 cases). In the acupuncture-moxibustion group, Renying (ST 9), Neiguan (PC 6), Zusanli (ST 36), etc. were selected, moxibustion was applied at Zusanli (ST 36). In the medication group, Enteric-coated aspirin was taken orally. The high-frequency ultrasonography was applied to detect common carotid artery (CCA), intima-media thickness (IMT), peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI) and resistance index (RI) before and after treatment for the comparative analysis. RESULTS: After treatment, in comparison between acupuncture-moxibustion group and medication group, CCA got bigger [(8.16 +/- 0.80) mm vs (7.69 +/- 0.61) mm, P < 0.01], IMT became thinner [(1.05 +/- 0.09) mm vs (1.10 +/- 0.09) mm, P < 0.05], PSV and EDV were accelerated (all P < 0.01), and PI and RI were down-regulated (P < 0.05, P < 0.01). CONCLUSION: Acupuncture and moxibustion provides a good efficacy on the improvement in carotid arteriosclerosis and blood flow in carotid artery, which contributes to the alleviation of ischemic cerebrovascular diseases and prevention from the occurrence and development of them.

[1, 25-dihydroxyvitamin D3 promotes the apoptosis of inflammatory cells in acute experimental autoimmune encephalomyelitis: experiment with rats].

OBJECTIVE: To investigate the mechanism of rapid amelioration of the pathological changes in experimental allergic encephalomyelitis (EAE) by 1, 25-dihydroxyvitamin D(3) [1, 25-(OH)(2)D(3)]. METHODS: Forty Lewis rats were immunized with myelin basic protein in complete Freud's adjuvant so as to establish ESE animal models and then randomly divided into 4 equal groups: prevention group, fed with 1, 25-(OH)(2)D(3) since day 0 for 10 days, prevention-control group fed with peanut oil for 10 days, treatment group fed with 1, 25-(OH)(2)D(3) since the appearance of EAE symptoms (generally since day 10 or 11), and treatment-control group fed with peanut oil since the appearance of EAE symptoms. The clinical symptoms were scored since immunization till day 12 when the clinical symptoms reached the maximum level. The rats were sacrificed 13 days after sensitization with their brains and spinal cords taken out to undergo pathological examination, in situ TUNEL staining for detecting apoptotic cells, and semiquantitative immunohistochemical analysis to detect the inducible NO synthase (iNOS), FasL, and tumor growth factor (TGF)-beta 1, that might involve in the signal pathway of apoptosis. Peripheral blood samples were collected to isolate mononuclear cells (MNCs). The content of nitrite in the supernatant of MNC culture was evaluated. RESULTS: The scores of clinical symptoms and the pathological changes of both the prevention and treatment groups decreased conspicuously and were significantly lower than their respective control groups (both P < 0.01). In contrast, the apoptosis indexes of the 2 1, 25-(OH)(2)D(3) administration groups were significantly higher than those of the control groups (all P < 0.01). The TUNEL positive cell rates in the brain and spinal cord of the treatment and prevention groups were all significantly higher than those of their corresponding control groups (P < 0.05, P < 0.01). The numbers of iNOS positive cells in the treatment and prevention groups were both lower than those of their corresponding control groups, which was in accord with the improvement of clinical signs and tissue lesions. The levels of nitrite in the supernatant of MNC culture of the treatment and prevention groups were higher than those of their corresponding control groups, but not significantly. CONCLUSION: Administration of 1, 25-(OH)(2)D(3) rapidly ameliorates EAE symptoms by promoting the apoptosis of inflammatory cells. The elimination of infiltrating immune cells which reverses the pathological changes in central nervous system is associated with a favorable microenvironment provided by 1, 25-(OH)(2)D(3), such as decreasing of iNOS.

Acupuncture treatment for spontaneous polyhidrosis.

OBJECTIVE: To compare the therapeutic effects of acupuncture and western medicine on spontaneous polyhidrosis. METHODS: Acupuncture at Huatuojiaji points was used to treat 30 cases of spontaneous polyhidrosis and the western medicine was used to treat 26 cases for comparison. RESULTS: The total effective rate of the former was 96.7% and that of the latter 57.7%. The difference in therapeutic effect between the two groups was significant (P<0.01). CONCLUSION: The therapeutic effect of acupuncture at Huatuojiaji points on spontaneous polyhidrosis was better than that of western medicine.

[Clinical study on acupuncture and moxibustion for treatment of plaque of carotid atherosclerosis].

OBJECTIVE: To observe effect of acupuncture and moxibustion on carotid plaque in the patient of carotid atherosclerosis due to ischemic cerebrovascular disease. METHODS: Sixty cases were randomly divided into an acup-mox group and a drug group, 30 cases in each group. Plaque of carotid atherosclerosis and quality of the plaque were investigated by color B-ultrasonography and the thickness and area of the plaque were calculated. RESULTS: The resolution rate of the plaque was 53.9% in the acup-mox group and 10.0% in the drug group with a significant difference between the two groups (P < 0.01), and with better effects on flat plaque and soft plaque. And the thickness and area of the plaque of corotid atherosclerosis were significantly reduced. CONCLUSION: Acupuncture and moxibustion can improve the plaque of corotid atherosclerosis, so as to alleviate and prevent from occurrence and development of ischemic cerebrovascular diseases.