Abstract Pulsatility of the brain has been hypothesised to be linked to intracranial pressure (ICP), although the nature of this relationship remains poorly understood. We used a low‐level expiratory resistance manoeuvre to characterise brain tissue pulsation (BTP) responses in a pilot healthy volunteer study. BTPs were measured using a transcranial tissue Doppler ultrasound prototype in 10 healthy volunteers at rest and during the manoeuvre. Measurements of mean arterial pressure (MAP), pulse pressure (PP), and heart rate (HR) were also recorded. One‐way repeated‐measures ANOVA compared changes between baseline, each phase of the manoeuvre, and recovery. Bulk BTP amplitude increased significantly during the initial phase compared with baseline ( P = 0.004). A non‐significant decrease was observed as the manoeuvre continued, with values decreasing below baseline during the late phase, followed by an increase above baseline during recovery. HR increased significantly during the late phase ( P = 0.015). No significant changes were observed in MAP or PP. Bulk BTP amplitude demonstrated a dynamic response during low‐level expiratory resistance, characterised by an initial increase followed by a non‐significant decrease over the remainder of the manoeuvre. The physiological mechanisms underlying these observations remain uncertain. Future studies incorporating direct ICP measurements and complementary physiological monitoring are needed to clarify the relationship between BTPs and intracranial dynamics.
Abstract Although the impact of obesity on the action of insulin has been studied extensively, little is known about how obesity affects the action of its counter‐regulatory hormone, glucagon. The purpose of this study was to determine whether diet‐induced obesity alters in vivo glucagon responsiveness, independent of insulin action. To study diet‐induced obesity, C57BL/6J male mice were fed a normal chow diet or a Western diet for 16 weeks. Glucagon responsiveness was determined by assessing the blood glucose response to glucagon (25 µg/kg) while insulin secretion was inhibited by octreotide (1 mg/kg). Body composition was assessed by nuclear magnetic resonance spectroscopy. Insulin sensitivity was assessed by an insulin‐assisted glucose tolerance test. As expected, the Western diet resulted in an increase in adiposity and a decrease in insulin sensitivity. Contrary to our initial hypothesis, diet‐induced obesity increased glucagon responsiveness, as evidenced by significantly higher blood glucose levels following glucagon administration, resulting in a greater area under the curve in mice fed a Western diet compared with mice fed a normal chow diet. In a preclinical model of obesity and insulin resistance, our study indicates that the glycaemic response to glucagon is enhanced when insulin secretion is inhibited with octreotide, arguing against the idea of impaired glucagon responsiveness. Future studies can use this approach to identify alterations in glucagon signalling that might explain the enhanced glucose response to glucagon.
Creatine is among the most extensively studied and widely used nutritional supplements in sports and exercise science. Over the past two decades, however, interest has expanded well beyond skeletal muscle, driven by growing recognition of the central role played by the creatine-phosphocreatine system in cerebral bioenergetics. Experimental evidence indicates that creatine contributes to neuronal energy homeostasis, mitochondrial function, membrane stability and potentially neuroprotection. This has fuelled growing enthusiasm for the idea that creatine supplementation might enhance cognitive function and benefit individuals with compromised cerebral metabolism. Yet, despite strong physiological plausibility, clinical findings remain inconsistent and often difficult to interpret. In this review, it is argued that the gap between proposed mechanisms and available clinical evidence reflects two distinct challenges: biological constraints on cerebral creatine availability after supplementation, and persistent methodological weaknesses in the clinical literature. We contend that the central challenge for the coming decade is not to identify new mechanisms of creatine action in the brain, but to establish, unequivocally, whether measurable changes in cerebral bioenergetics translate into meaningful cognitive benefit - whether as enhanced performance in healthy individuals or as clinically significant improvement in patient populations.
Abstract Electronic cigarettes generate an aerosol by heating an e‐liquid based on propylene glycol (PG) and/or glycerin (VG), with or without nicotine and flavourings. Their acute respiratory effects, particularly with respect to asthma, remain poorly defined. We exposed ovalbumin‐sensitised female BALB/c mice, which were subsequently challenged with ovalbumin (‘asthmatic’) or saline (‘non‐asthmatic’), to one of four e‐cigarette aerosols (PG or VG, each with 0 or 12 mg/mL nicotine) for 30 s. Airway resistance ( R aw ), tissue damping ( G ) and tissue elastance ( H ) were measured once/minute for 60 min using the forced oscillation technique. A second e‐cigarette aerosol was given at the 30‐min mark. Bronchoalveolar lavage (BAL) was taken for assessment of cellular inflammation. Group sizes were 4–9 mice ( n = 53 for lung mechanics and 57 for BAL). All aerosols acutely increased R aw , G and H , and excipient was the dominant determinant. VG produced substantially larger increases than PG across most parameters and exposures ( P < 0.0001, except airway resistance after the first exposure, P = 0.0569), responses approximately doubled after a second exposure, and allergic sensitisation augmented the repeated‐exposure mechanical response. Nicotine was not required for these effects and, where significant, attenuated them. In BAL, granulocytic inflammation was confined to asthmatic mice and was greater with VG than PG. Acute e‐cigarette aerosol exposure is not innocuous; e‐liquid composition, especially the excipient, is a key determinant of acute respiratory effects independent of nicotine.
