188 research outputs found
Effects of hypertension and anti-hypertensive treatment on Aβ plaque load, Aβ–synthesising and –degrading enzymes in frontal cortex
Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses
Development of an ethogram for hutch-housed dairy calves and determination of factors influencing their behaviour
Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model
The effects of a single whole-body cryotherapy exposure on physiological, performance and perceptual responses of professional academy soccer players following repeated sprint exercise
In professional youth soccer players, the physiological, performance and perceptual effects of a single whole body cryotherapy (WBC) session performed shortly after repeated sprint exercise were investigated. In a randomized, counter-balanced and crossover design, 14 habituated English Premier League academy soccer players performed 15 x 30 m sprints (each followed by a 10 m forced deceleration) on two occasions. Within 20 min of exercise cessation, players entered a WBC chamber (Cryo: 30 s at -60°C, 120 s at -135°C) or remained seated (Con) indoors in temperate conditions (~25°C). Blood and saliva samples, peak power output (countermovement jump) and perceptual indices of recovery and soreness were assessed pre-exercise and immediately, 2 h and 24 h post exercise. When compared to Con, a greater testosterone response was observed at 2 h (+32.5 ± 32.3 pg·ml-1, +21%) and 24 h (+50.4 ± 48.9 pg·ml-1, +28%) post-exercise (both P=0.002) in Cryo (trial x treatment interaction: P=0.001). No between trial differences were observed for other salivary (cortisol and testosterone/cortisol ratio), blood (lactate and Creatine Kinase), performance (peak power output) or perceptual (recovery or soreness) markers (all trial x treatment interactions: P>0.05); all of which were influenced by exercise (time effects: all P<0.05). A single session of WBC performed within 20 min of repeated sprint exercise elevated testosterone concentrations for 24 h but did not affect any other performance, physiological or perceptual measurements taken. While unclear, WBC may be efficacious for professional soccer players during congested fixture periods
Antibacterial and antibiofilm potency of XF drugs, impact of photodynamic activation and synergy with antibiotics.
With increasing incidence of antimicrobial resistance, there is an urgent need for novel and effective antibacterials. Destiny Pharma plc have developed a series of porphyrin-based XF drugs, some with dual mechanisms of antibacterial action. An innate mechanism acts through binding to the outer bacterial membrane and a separate, light-activated, photodynamic (PD) mechanism, acts via the generation of reactive oxygen species. This study aimed to assess the innate and PD associated antibacterial activity of XF drugs against planktonic bacteria, their biofilms and combinational effects with conventional antibiotics. Minimum inhibitory concentrations (MICs) were determined for 3 XF drugs against 114 bacterial isolates. MICs for XF-73 and XF-70 were determined (± PD). DPD-207 was designed to not exhibit PD action due to its structure. XF-drugs (± PD) were further assessed for synergy with conventional antibiotics (using a checkerboard assay) and antibiofilm activity against susceptible strains. XF drugs were innately active against all tested Gram-positive isolates. PD action significantly increased bacterial susceptibility to XF-73 and XF-70 for all Gram-positive isolates. Generally, the XF drugs exhibited higher MICs against Gram-negative isolates, however PD significantly enhanced potency, particularly for XF-70. XF-73 and XF-70 exhibited synergy with ertapenem against a methicillin resistant Staphylococcus aureus (MRSA) strain (± PD) and XF-73 with polymyxin B (± PD) against Pseudomonas aeruginosa. No antagonism was seen between the XF drugs and any of the 5 antibiotics tested. The antibiofilm effect of XF drugs was also observed for all Staphylococcus isolates tested. Generally, PD did not enhance activity for other bacterial isolates tested with the exception of XF-73 against Acinetobacter baumannii biofilms. XF drugs exhibited significant antimicrobial activity against Gram-positive bacteria, with PD enhancement of bacterial susceptibility. Additionally, XF drugs displayed synergy with conventional antibiotics and demonstrated antibiofilm effects
Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes:Divergent effects of multifunctional enzymes
There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), and angiotensin-converting enzyme (ACE) reduce Aβ levels and protect against cognitive impairment in mouse models of AD. In post-mortem human brain tissue we have found that the activity of these Aβ-degrading enzymes rise with age and increases still further in AD, perhaps as a physiological response that helps to minimize the build-up of Aβ. ECE-1/-2 and ACE are also rate-limiting enzymes in the production of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors, increases in the levels of which are likely to contribute to reduced blood flow in AD. This review considers the possible interdependence between Aβ-degrading enzymes, ischemia and Aβ in AD: ischemia has been shown to increase Aβ production both in vitro and in vivo, whereas increased Aβ probably enhances ischemia by vasoconstriction, mediated at least in part by increased ECE and ACE activity. In contrast, NEP activity may help to maintain cerebral perfusion, by reducing the accumulation of Aβ in cerebral blood vessels and lessening its toxicity to vascular smooth muscle cells. In assessing the role of Aβ-degrading proteases in the pathogenesis of AD and, particularly, their potential as therapeutic agents, it is important to bear in mind the multifunctional nature of these enzymes and to consider their effects on other substrates and pathways
Coccolithophores: Functional Biodiversity, Enzymes and Bioprospecting
Emiliania huxleyi is a single celled, marine phytoplankton with global distribution. As a key species for global biogeochemical cycling, a variety of strains have been amassed in various culture collections. Using a library consisting of 52 strains of E. huxleyi and an ‘in house’ enzyme screening program, we have assessed the functional biodiversity within this species of fundamental importance to global biogeochemical cycling, whilst at the same time determining their potential for exploitation in biocatalytic applications. Here, we describe the screening of E. huxleyi strains, as well as a coccolithovirus infected strain, for commercially relevant biocatalytic enzymes such as acid/alkali phosphodiesterase, acid/alkali phosphomonoesterase, EC1.1.1-type dehydrogenase, EC1.3.1-type dehydrogenase and carboxylesterase
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