Tolerogenic effect of fiber tract injury: reduced EAE severity following entorhinal cortex lesion

Despite transient, myelin-directed adaptive immune responses in regions of fiber tract degeneration, none of the current models of fiber tract injuries evokes disseminated demyelination, implying effective mechanisms maintaining or re-establishing immune tolerance. In fact, we have recently detected CD95L upregulation accompanied by apoptosis of leukocytes in zones of axonal degeneration induced by entorhinal cortex lesion (ECL), a model of layer-specific axonal degeneration. Moreover, infiltrating monocytes readily transformed into ramified microglia exhibiting a phenotype of immature (CD86+/CD80−) antigen-presenting cells. We now report the appearance of the axonal antigen neurofilament-light along with increased T cell apoptosis and enhanced expression of the pro-apoptotic gene Bad in cervical lymph nodes after ECL. In order to test the functional significance of such local and systemic depletory/regulatory mechanisms on subsequent immunity to central nervous system antigens, experimental autoimmune encephalomyelitis was induced by proteolipid protein immunization 30 days after ECL. In three independent experiments, we found significantly diminished disease scores and infiltrates in lesioned compared to sham-operated SJL mice. This is consistent with a previous meta-statistical analysis (Goodin et al. in Neurology 52:1737–1745, 1999) rejecting the O-hypothesis that brain trauma causes or exacerbates multiple sclerosis. Conversely, brain injuries may involve long-term tolerogenic effects towards brain antigens. Leman Mutlu, Christine Brandt, Jon D. Laman, and Ingo Bechmann have contributed equally.     

The relationship between the severity of erectile dysfunction and aortic stiffness

Aortic stiffness increases in patients with erectile dysfunction (ED) but it is not known whether aortic stiffness affects the degree of ED. In the present study, we aimed to determine whether there is any relationship between aortic stiffness and the severity of ED. Patients with ED were divided into 3 groups according to the International Index of Erectile Function (IIEF) scores. Mild ED was named as group 1, moderate ED as group 2 and severe ED as group 3. The values of fasting blood glucose (FBG), serum lipid values, total testosterone (T. tes), and free testosterone (F tes) were recorded. Aortic stiffness was determined by pulse wave velocity (PWV) and augmentation index (AIX) measurements. The mean or median values of the laboratory parameters among the groups were similar (p > .05). No statistical difference was found between the groups in terms of AIX value (p = .386). Mean PWV values were calculated as 7.26, 8.30 and 8.78 in group 1, group 2 and group 3 respectively. PWV values were significantly different between groups (p < .0001). PWV values were found to be increased with increasing severity of erectile dysfunction.     

Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea

Background

Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA.

Methods

Of 60 patients, 10 patients had mild OSA (AHI 5–14), 10 moderate (AHI 15–29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured.

Results

Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention.

Conclusions

Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.