This study provides a new method for quantifying the cyclotide kalata B1 in both plasma and brain homogenate. Cyclotides are ultra-stable peptides with three disulfide bonds that are interesting from a drug development perspective as they can be used as scaffolds. In this study we describe a new validated LC-MS/MS method with high sensitivity and specificity for kalata B1. The limit of quantifi...

Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS pat...

Human African trypanosomiasis (HAT), a neglected tropical disease, is fatal without treatment. Pentamidine, a cationic diamidine, has been used to treat first-stage (hemolymphatic) HAT since the 1940s, but it is ineffective against second-stage (meningoencephalitic, or central nervous system [CNS]) infection. Novel diamidines (DB75, DB820, and DB829) have shown promising efficacy in both mouse ...

Brain derived neurotrophic factor (BDNF) seems to be involved in regulation of synaptic plasticity and neurogenesis. BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether BDNF plasma concentration was ass...

Awake adult rats were given a solution of [9,10-3H]palmitate ([3H]PAM) by gavage. The appearance of radiolabel in plasma lipid fractions was monitored by thin-layer chromatography at fixed intervals thereafter. At 2 h, the rats were killed by microwave irradiation and radioactivity in whole brain and individual brain phospholipids was determined. In plasma, esterified [3H]PAM was mainly associa...

There is interest in pharmacologic preconditioning for end-organ protection by targeting the HIF system. This can be accomplished by inhibition of prolyl 4-hydroxylase (PHD). GSK360A is an orally active PHD inhibitor that has been previously shown to protect the failing heart. We hypothesized that PHD inhibition can also protect the brain from injuries and resulting behavioral deficits that can...

This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results from clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on metaanalytical approaches, important components of the Lund concept are based on physiological mechanisms...

In contrast to the wealth of information available concerning the response of plasma atrial natriuretic peptide to changes in pressure and volume status and to inhibition of endopeptidase 24.11, very little is known of possible concomitant effects on brain natriuretic peptide. The effects of change in posture, pressor infusions of angiotensin II, or inhibition of endopeptidase 24.11 were docume...

background: recent studies have shown that oxidative stress (os) is the most important indicator in the pathogenesis of alzheimer's disease (ad), but the results in previous studies are conflicting. this study aimed to assess the plasma levels of 8-hydroxy-2'-deoxyguanosine (8-ohdg) as dna oxidative damage marker and total antioxidant capacity (tac) in patients with ad versus control ...