Background and Purpose-Recent studies have attributed the increased infection vulnerability of patients with stroke to stroke-induced immunosuppression. We have therefore explored the immunological changes in patients with ischemic stroke. Methods-Blood from 46 patients with stroke was analyzed by fluorescent-activated cell sorter to determine leukocyte subsets. To identify changes that represent clinically relevant immunosuppression, we compared patients who developed infection within 14 days after stroke with those who did not. Results-Stroke induced a dramatic and immediate loss of T-lymphocytes, most pronounced within 12 hours after stroke onset. Only patients with subsequent infection exhibited a delay in the recovery of CD4ϩ T-lymphocyte counts. Conclusions-Our data suggest that a loss of CD4ϩ T cell function contributes to the stroke-induced immunosuppression.The CD4ϩ T cell count on the day after stroke may emerge as a predictive marker for poststroke infection allowing, early identification of patients at risk. (Stroke. 2008;39:237-241.)

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Background and Purpose— Stroke-induced immune alterations predispose patients to infections. Although the relationship between stroke and the adaptive immune system has been investigated in detail, to date it is unknown whether the innate immune system, which forms the first line of antibacterial defense, is also impaired in patients with stroke. Therefore, we investigated whether chemotaxis, phagocytosis, oxidative burst, degranulation of defensins, and NETosis in monocytes and in neutrophil granulocytes are altered in patients with stroke compared with controls. Methods— Sixty-three patients having acute ischemic stroke were recruited within 12 hours of symptom onset; blood was sampled on admission and on days 1, 3, 5, and 7. Thirty-seven age-matched controls were also recruited. Cell migration, phagocytosis, and oxidative burst of phagocytes were determined in vitro. Human neutrophil peptides 1 to 3 and serum metanephrine levels were measured by enzyme-linked immunosorbent assay, and NETosis was quantified by immunohistochemistry. Results— The key mechanisms required for bacterial killing, oxidative burst, and NETosis were significantly reduced in samples taken from patients with stroke compared with controls, whereas migration, phagocytic function, and defensin production remained unimpaired in monocytes and granulocytes from patients with stroke. Conclusions— Stroke-induced immune alterations include impairment of the first-line defense performed by specialized phagocytes against bacteria. The hypothesis that these changes enhance susceptibility to acquired infections is supported by our observation that on admission oxidative burst in monocytes was more impaired in patients with stroke with subsequent stroke-associated infections.

Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased circulating cortisol levels in those using oral contraceptives. For women taking oral contraceptives, we observed alterations in circulating phospholipid levels and elevated triglycerides and found evidence for increased glucocorticoid signalling as the transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were increased in whole blood. The effects were statistically mediated by cortisol. The associations of oral contraceptives with higher FKBP5 mRNA and altered phospholipid levels were modified by rs1360780, a genetic variance implicated in psychiatric diseases. Accordingly, the methylation pattern of FKBP5 intron 7 was altered in women taking oral contraceptives depending on the rs1360780 genotype. Moreover, oral contraceptives modified the association of circulating cortisol with depressive symptoms, potentially explaining conflicting results in the literature. Finally, women taking oral contraceptives displayed smaller hippocampal volumes than non-using women. In conclusion, the integrative analyses of different types of physiological data provided converging evidence indicating that oral contraceptives may cause effects analogous to chronic psychological stressors regarding the regulation of the HPA axis.

The study was undertaken to compare antitumor efficacy of electrochemotherapy (ECT) with cold plasma therapy (CP) in a melanoma mouse model. After melanoma implantation into the flank of C57BL/6N mice, CP by two different plasma sources (APPJ and DBD) was applied directly to the tumor surface. ECT was performed with bleomycin intravenously at a field strength of 1000 V/cm without or combined with CP. Primary endpoints were tumor growth acceleration (TGA), daily volume progression (DVP) and survival after treatment. Both plasma sources as single treatment showed a significant TGA delay, which proved less effective than ECT. CP (APPJ) combined with ECT (ECJ) significantly improved per cent mouse survival, with significant superiority compared with ECT. Plasma therapy alone albeit less effective seems a potential alternative to ECT in patients with melanoma and can be applied manifold in a session without general anaesthesia. Accordingly, CP alone and combined with ECT may serve as new option in palliative skin melanoma therapy.

Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM.

Purpose To investigate flip angle (FA)-dependent T1 bias in chemical shift-encoded fat-fraction (FF) and to evaluate a strategy for correcting this bias to achieve accurate MRI-based estimates of liver fat with optimized signal-to-noise ratio (SNR). Materials and Methods Thirty-three obese patients, 14 men/19 women, aged 57.3 ±13.9 years underwent 3 Tesla (T) liver MRI including MR-spectroscopy and four three-echo-complex chemical shift-encoded MRI sequences using different FAs (1°/3°/10°/20°). FF was estimated with R2* correction and multi-peak fat spectral modeling. The FF for each FA with and without T1 correction was compared with spectroscopy as a reference standard, using linear regression. Relative SNR of the magnitude data were assessed for each flip angle. Results The correlation between chemical shift-encoded MRI and spectroscopy was high (R2 ≍ 0.9). Without T1 correction, the agreement of both techniques showed no significant differences in slope (PFlipAngle1° = 0.385/PFlipAngle3° = 0.289) using low FA. High FA resulted in significant different slopes (PFlipAngle10°= 0.016/PFlipAngle20° = 0.014. T1 bias was successfully corrected using the T1 correction strategy (slope:PFlipAngle10° = 0.387/PFlipAngle20° = 0.440). Additionally, the use of high FA (near the Ernst angle) improved the SNR of the magnitude data (FA1 vs. FA3; respectively FA1 vs. FA10 P ≤ 0.001). Conclusion T1 bias is a strong confounder in the assessment of liver fat using chemical shift imaging with high FA. However, using a larger flip angle with T1 correction leads to higher SNR, and residual error after T1 correction is very small.