Despite methodological limitations in the existing literature, there was a small, significant association between perceived discrimination and hypertension. Future studies should consider ambulatory nighttime blood pressure, which may more accurately capture daily variation attributable to experienced racial discrimination. Perceived discrimination may partly explain racial health disparities.

Introduction Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central α2A and imidazoline type 1 receptors while activation of peripheral α2B–adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance (SVR). In this randomized, prospective, clinical study we attempted to quantify the short-term hemodynamic effects resulting from a rapid IV bolus administration of dexmedetomidine in pediatric cardiac transplant patients. Methods Twelve patients, aged ≤10 years of age, weighing ≤40kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or IV induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1mcg/kg) and rocuronium (1mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure and thermodilution-based cardiac output, a rapid IV dexmedetomidine bolus of either 0.25mcg/kg or 0.5mcg/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 min and 5 mins. Results There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure and systemic vascular resistance all increased at 1 minute after rapid IV bolus for both doses, and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, CVP and pulmonary vascular resistance did not change significantly. HR decreased at 1 min for both doses and was, within the 0.5 mcg/kg group, the only hemodynamic variable still changed from baseline at the 5 min time point Conclusion Rapid IV bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system there is a larger percent increase in the diastolic pressures than the systolic pressures, and furthermore these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.

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Two treatable component causes of participation, walking capacity and mood, were identified; of these, only excellent walking capacity could be considered a sufficient cause.

Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood-brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor’s increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity. The effect of replacing phenylalanine’s carboxylic acid with a tetrazole, acylsulfonamide and hydroxamic acid (HA) bioisostere was examined. Compounds were tested for their ability to be LAT1 substrates using both cis-inhibition and trans-stimulation cell assays. As HA-Phe demonstrated weak substrate activity, its structure-activity relationship (SAR) was further explored by synthesis and testing of HA derivatives of other LAT1 amino acid substrates (i.e. Tyr, Leu, Ile, and Met). The potential for a false positive in the trans-stimulation assay caused by parent amino acid was evaluated by conducting compound stability experiments for both HA-Leu and the corresponding methyl ester derivative. We concluded that HA’s are transported by LAT1. In addition, our results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site.