60 research outputs found
Effects of renal-dose dopamine on renal tubular functions following coronary artery bypass grafting surgery
Assessing the Sustainability of Liquid Hydrogen for Future Hypersonic Aerospace Flight
This is the final version. Available on open access from MDPI via the DOI in this recordThis study explored the applications of liquid hydrogen (LH2) in aerospace projects, followed by an investigation into the efficiency of ramjets, scramjets, and turbojets for hypersonic flight and the impact of grey, blue, and green hydrogen as an alternative to JP-7 and JP-8 (kerosene fuel). The advantage of LH2 as a propellant in the space sector has emerged from the relatively high energy density of hydrogen per unit volume, enabling it to store more energy compared to conventional fuels. Hydrogen also has the potential to decarbonise space flight as combustion of LH2 fuel produces zero carbon emissions. However, hydrogen is commonly found in hydrocarbons and water and thus it needs to be extracted from these molecular compounds before use. Only by considering the entire lifecycle of LH2 including the production phase can its sustainability be understood. The results of this study compared the predicted Life Cycle Assessment (LCA) emissions of the production of LH2 using grey, blue, and green hydrogen for 2030 with conventional fuel (JP-7 and JP-8) and revealed that the total carbon emissions over the lifecycle of LH2 were greater than kerosene-derived fuels
Regular dipyridamole therapy produces sustained protection against cardiac ischemia–reperfusion injury: Is it time to revisit PARIS?
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It is rocket science - why dietary nitrate is hard to ‘beet’! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway
Dietary nitrate (found in green leafy vegetables, such as rocket, and in beetroot) is now recognized to be an important source of nitric oxide (NO), via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. While this pathway may now seem obvious, its realization followed a rather tortuous course over two decades. Early steps included the discovery that nitrite was a source of NO in the ischaemic heart but this appeared to have deleterious effects. In addition, nitrate-derived nitrite provided a gastric source of NO. However, residual nitrite was not thought to be absorbed systemically. Nitrite was also considered to be physiologically inert but potentially carcinogenic, through N-nitrosamine formation. In Part 1 of a two-part Review on the nitrate-nitrite-NO pathway we describe key twists and turns in the elucidation of the pathway and the underlying mechanisms. This provides the critical foundation for the more recent developments in the nitrate-nitrite-NO pathway which are covered in Part 2
Hemodynamics and renal function during administration of low-dose dopamine in severely ill patients
Cardioprotective efficacy depends critically on pharmacological dose, duration of ischaemia, health status of animals and choice of anaesthetic regimen: a case study with folic acid
Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection
The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment
An in-vitro model of ischaemia-reperfusion in murine myocardium The role of nitric oxide
Available from British Library Document Supply Centre-DSC:DXN030652 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
The dual SSTR2/5 specific somatostatin analog, AP102, does not affect glucose metabolism in diabetic ZDF rats: a comparative 14-day infusion study versus pasireotide
peer reviewe
Oleogel-S10 Phase 3 study "EASE" for epidermolysis bullosa: study design and rationale
BACKGROUND
Epidermolysis bullosa (EB) is a group of rare, genetic diseases that affect the integrity of epithelial tissues, most notably the skin. Patients experience recurrent skin wounding, with severity depending on type, sub-type, and mutation. Oleogel-S10, a formulation of birch bark extract, has demonstrated efficacy in a Phase 2 trial assessing re-epithelialization of wounds in EB. EASE (NCT03068780, EudraCT 2016-002066-32) is a randomized, Phase 3, placebo-controlled study designed to determine the efficacy of Oleogel-S10 versus placebo in patients with EB.
METHODS
EASE is a Phase 3, two-phase study comprising a 90-day, double-blind, randomized, placebo-controlled phase, followed by 24 months of open-label, single-arm follow-up. Patients with junctional EB, dystrophic EB, or Kindler syndrome and target wounds (10 - 50cm) present for > 21 days and < 9 months, are randomized in a 1:1 ratio to receive wound dressings according to local standard of care with or without Oleogel-S10. Placebo is based on the Oleogel-S10 vehicle, which is sunflower oil formulated to have a consistency indistinguishable from that of the active product. The primary endpoint of the trial, directed by the US health authority according to the required study endpoints for chronic cutaneous ulcer and burn wounds, is to compare the efficacy of Oleogel-S10 versus placebo according to the proportion of patients with complete closure of the target wound within 45 ± 7 days of treatment. Additional EB-focused endpoints include wound burden, patient-reported outcomes, and safety.
RESULTS
Results of the primary endpoint are anticipated to be available by H2 2019.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03068780 . EudraCT, 2016-002066-32. Registered on 3 March 2017
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