Modulatory effect of 17ß-estradiol on myeloid cell infiltration into the male rat brain after ischemic stroke.

Ischemic stroke is the leading cause of human disability and mortality in the world. Neuroinflammation is the main pathological event following ischemia which contributes to secondary brain tissue damage and is driven by infiltration of circulating immune cells such as macrophages. Because of neuroprotective properties against ischemic brain damage, estrogens have the potential to become of therapeutic interest. However, the exact mechanisms of neuroprotection and signaling pathways is not completely understood. In the current study, 12-week-old male Wistar rats underwent an experimental ischemia by occluding the middle cerebral artery transiently (tMCAO) for 1 h. Male rats subjected to tMCAO were randomly assigned to receive 17ß-estradiol or vehicle treatment. The animals were sacrificed 72 h post tMCAO, transcardially perfused and the brains were proceeded either for TTC staining and gene analysis or for flow cytometry (CD45, CD11b, CD11c, CD40). We found that 17ß-estradiol substitution significantly reduced the cortical infarct which was paralleled by an improved Garcia test scoring. Flow cytometry revealed that CD45+ cells as well as CD45+CD11b+CD11c+ cells were massively increased in tMCAO animals and numbers were nearly restored to sham levels after 17ß-estradiol treatment. Gene expression analysis showed a reperfusion time-dependent upregulation of the markers CD45, CD11b and the activation marker CD40. The reduction in gene expression after 72 h of reperfusion and simultaneous 17ß-estradiol substitution did not reach statistical significance. These data indicate that 17ß-estradiol alleviated the cerebral ischemia-reperfusion injury and selectively suppressed the activation of the neuroinflammatory cascade via reduction of the number of activated microglia or infiltrated monocyte-derived macrophages in brain.

The concanavalin A model of acute hepatitis in mice.

The intravenous injection of the plant lectin concanavalin A (ConA) is a widely used model for acute immune-mediated hepatitis in mice. In contrast to several other models for acute hepatic damage, ConA-induced injury is primarily driven by the activation and recruitment of T cells to the liver. Hence, the ConA model has unique features with respect to its pathogenesis and important similarities to immune-mediated hepatitis in humans, such as autoimmune hepatitis, acute viral hepatitis or distinct entities of drug toxicity leading to immune activation. However, the ConA model has considerable variability, depending on the preparation of the compound, genetic background of the mice, sex, age and microbial environment of the animal facility barrier. This standard operating procedure (SOP) comprises a detailed protocol for the ConA application, including preparation of ConA working solution, handling of the animals, choice of the appropriate conditions and endpoints, as well as efficient dose-finding.

Effects of celiprolol on serum lipids in systemic hypertension.

Antihypertensive therapy with celiprolol lowers blood pressure by selectively blocking beta 1 adrenoceptors. It also exhibits vasodilatory and bronchosparing effects and is not cardiodepressive. Because many beta blockers are often suspected of adversely raising serum lipid levels, especially triglycerides, a special investigation of lipids in hypertensive subjects was performed. The preliminary findings in a series of 14 patients (average age 39.7 years) with essential hypertension (World Health Organization stages I to II) who were treated with celiprolol for a period of 6 months are presented. Serum levels of total cholesterol and low-density lipoprotein remained virtually unchanged during treatment. There was, however, a tendency for triglyceride levels to fall with celiprolol treatment, a trend that became significant after 4 weeks. Moreover, high-density lipoproteins tended to increase with treatment and were significantly increased after 2 weeks. In contrast to findings obtained with other beta-blocking agents, no increases in total serum lipids were observed during celiprolol treatment. Blood pressure values of the subjects treated decreased significantly from a mean value (measured in the upright position) of 151/99 to 131/87 mm Hg. Blood pressure values taken in the supine position were also significantly reduced. No significant changes were noted in a variety of laboratory parameters, including blood count, blood coagulation time, blood sugar concentration, liver and kidney tests, electrolyte levels and urinalysis. The significance of these results, which suggest that celiprolol is not associated with adverse changes of lipids and may even positively influence blood chemistry, is discussed.

Reduction of left ventricular hypertrophy in hypertensive patients after treatment with celiprolol.

Long-term treatment with celiprolol, a new cardioselective beta blocker, significantly reduced blood pressure in 14 patients with essential hypertension (World Health Organization stages I to II). Heart rates remained within the normal range throughout treatment and no significant side effects were observed. In 4 patients, end-systolic septum thickness was measured, and evidence was obtained that the extent of left ventricular hypertrophy was reduced. These findings indicate that celiprolol can be used for the successful long-term treatment of essential hypertension, and that such treatment reduces left ventricular hypertrophy induced by high blood pressure.