No abstract

Acute microvascular endothelial dysfunction may occur after subarachnoid hemorrhage and contribute to microvascular spasm.

The epidemiology, clinical presentation, and treatment of infective endocarditis (IE) has significantly changed over the past few years in developed countries. However, relevant data from developing countries are different and remain scarce. The objective of this study was to evaluate the clinical presentations, treatment and outcomes of IE patients in a tertiary hospital in East China over an 8-year period. This was a retrospective observational study of consecutive cases of definite or possible IE as per the modified Duke criteria between January 2008 and December 2015. A total of 135 definite and 39 probable IE cases were identified. The mean age was 47.8 ± 15.7 years, with a male preponderance (1.9: 1). Degenerative valve disease accounted for 30.5% cases of IE, followed by congenital heart disease (29.9%) and rheumatic heart disease (14.9%). Native cardiac valves were present in 93.7% of the IE patients. Echocardiography and blood culture were performed in all patients, of whom 55.2% were found to have large vegetations (≥10 mm) and the positive rate of blood culture was 60.3%. Streptococcus remained the chief causative agent that was identified in 61.9% of culture-positive patients. Glycopeptide antibacterials and cephalosporins were the most frequently used antimicrobial drugs for IE therapy. Seventy-six (43.7%) of the IE patients were surgically treated. The mortality rate during hospital stay was 10.9%. Our data reflected clinical and microbiological profile, and treatment of IE in a tertiary hospital located in the East China.

Dexmedetomidine activated the I2 imidazoline receptor-PI3K/AKT pathway, and up-regulated HIF-1α, VEGF and RTP801 expression to protect against OGD-induced injury in rat C6 cells.

We hypothesized that activation of the central histaminergic system is required for neuroprotection induced by hypoxic preconditioning. Wild-type (WT) and histidine decarboxylase knockout (HDC-KO) mice were preconditioned by 3 hours of hypoxia (8% O 2 ) and, 48 hours later, subjected to 30 minutes of middle cerebral artery (MCA) occlusion, followed by 24 hours of reperfusion. Hypoxic preconditioning improved neurologic function and decreased infarct volume in WT or HDC-KO mice treated with histamine, but not in HDC-KO or WT mice treated with a-fluoromethylhistidine (a-FMH, an inhibitor of HDC). Laser-Doppler flowmetry analysis showed that hypoxic preconditioning ameliorated cerebral blood flow (CBF) in the periphery of the MCA territory during ischemia in WT mice but not in HDC-KO mice. Histamine decreased in the cortex of WT mice after 2, 3, and 4 hours of hypoxia, and HDC activity increased after 3 hours of hypoxia. Vascular endothelial growth factor (VEGF) mRNA and protein expressions showed a greater increase after hypoxia than those in HDC-KO or a-FMH-treated WT mice. In addition, the VEGF receptor-2 antagonist SU1498 prevented the protective effect of hypoxic preconditioning in infarct volume and reversed increased peripheral CBF in WT mice. Therefore, endogenous histamine is an essential mediator of hypoxic preconditioning. It may function by enhancing hypoxia-induced VEGF expression.

Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10–100 µmol/l. What’s more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

Highlights d Microglia display increased extensive association with neurons in complex FSs d Microglial association displaces GABAergic presynapses surrounding neuronal soma d Microglial displacement reduces neuronal excitability and seizure susceptibility d The P2Y 12 receptor mediates microglial displacement of GABAergic presynapses

Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery.