NADPH-Independent Fluorescent Probe for Live-Cell Imaging of Heme Oxygenase-1.

Heme oxygenase-1 (HO-1) catalyzes heme degradation on the consumption of NADPH and molecular oxygen. As an inducible enzyme, HO-1 is highly induced in various disease states, including cancer. Currently, two fluorescent probes for HO-1 have been designed based on the catalytic activity of HO-1, in which the probes serve as a substrate, so NADPH is required to enable the detection.

Potent BODIPY-based photosensitisers for selective mitochondrial dysfunction and effective photodynamic therapy.

The development of new and improved mitochondria-targeting photosensitisers (PSs) for photodynamic therapy (PDT) remains highly desirable, due to the critical role the mitochondria play in maintaining healthy cellular function. Here, we report the design, synthesis, photophysical properties and biological characterisation of a series of di-iodinated BODIPY-based PSs, BODIPY-Mito-I-n, for mitochondria-targeted PDT applications. Six BODIPY-Mito-I-n analogues were synthesised in good yields, with fast reaction times of between 30 and 60 min under mild conditions.

Mitochondria-targeting biocompatible fluorescent BODIPY probes.

An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-, for mitochondria-targeted fluorescence imaging applications.

Familial hepatic rupture in vascular Ehlers-Danlos syndrome in pregnancy with atypical thromboses.

This case highlights the importance of genetic testing over fibroblast testing and presents the first published thromboelastometry data in vascular Ehlers-Danlos syndrome.

Critical illness aspects of heatstroke: A hot topic.

Heatstroke represents the most severe end of the heat illness spectrum, and is increasingly seen in those undergoing exercise or exertion ('exertional heatstroke') and those exposed to high ambient temperatures, for example in heatwaves ('classical heatstroke'). Both forms may be associated with significant thermal injury, leading to organ dysfunction and the need for admission to an intensive care unit. The process may be exacerbated by translocation of bacteria or endotoxin through an intestinal wall rendered more permeable by the hyperthermia.

Enzyme-activated probes in optical imaging: a focus on atherosclerosis.

Enzyme-activated probes enable complex biological processes to be studied in real-time. A wide range of enzymes are modulated in diseases, including cancer, inflammatory diseases and cardiovascular disease, and have the potential to act as vital diagnostic and prognostic biomarkers to monitor and report on disease progression. In this perspective article, we discuss suitable design characteristics of enzyme-activated fluorescent probes for and optical imaging applications.

Exercise hyperthermia induces greater changes in gastrointestinal permeability than equivalent passive hyperthermia.

Hyperthermia and exertional heat illness increase gastrointestinal (GI) permeability, although whether the latter is only via hyperthermia is unclear. The aim of this pilot study was to determine whether different changes in GI permeability, characterized by an increased plasma lactulose:rhamnose concentration ratio ([L:R]), occurred in exercise hyperthermia in comparison to equivalent passive hyperthermia. Six healthy adult male participants (age 25 ± 5 years, mass 77.

A fluorescent probe for the discrimination of oxidation states of palladium.

Palladium-based catalysts are widely used in pharmaceutical industries, which can sometimes cause palladium contamination in pharmaceutical drug manufacture. It is important to separately quantify the different oxidation states of palladium (Pd and Pd) in pharmaceuticals as they react with scavengers differently. Although palladium sensors have been under intense investigation, oxidation state differentiators are very rare.

A Coumarin-Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1.

Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases.

Effect of a fever in viral infections - the 'Goldilocks' phenomenon?

Acute infections, including those due to Coronaviridae and other viruses, often stimulate a febrile response. A mild fever appears to improve outcome; it appears to diminish viral replication by several mechanisms, including virion entry into host cells and genome transcription, and improving host defence mechanisms against the pathogen. However, a fever may also damage host cellular and tissue function and increase metabolic demands.

Association between collapse and serum creatinine and electrolyte concentrations in marathon runners: a 9-year retrospective study.

Objective: Abnormal biochemical measurements have previously been described in runners following marathons. The incidence of plasma sodium levels outside the normal range has been reported as 31%, and the incidence of raised creatinine at 30%. This study describes the changes seen in electrolytes and creatinine in collapsed (2010-2019 events) and noncollapsed (during the 2019 event) runners during a UK marathon.

The efficacy of steroids in reducing morbidity and mortality from extreme hyperthermia and heatstroke-A systematic review.

Severe hyperthermia from classical or exertional heatstroke, or from drug ingestion or other noninfective pyrogens, is associated with a high mortality and morbidity. A systemic pro-inflammatory response occurs during heatstroke, characterized by elevated cytokines with endotoxemia from elevated lipopolysaccharide (LPS) levels. Corticosteroids reduce LPS and cytokine levels, suggesting that they may improve outcome.

Hematoma Resolution In Vivo Is Directed by Activating Transcription Factor 1.

Rationale: The efficient resolution of tissue hemorrhage is an important homeostatic function. In human macrophages in vitro, heme activates an AMPK (AMP-activated protein kinase)/ATF1 (activating transcription factor-1) pathway that directs Mhem macrophages through coregulation of HO-1 (heme oxygenase-1; ) and lipid homeostasis genes.

Objective: We asked whether this pathway had an in vivo role in mice.

The efficacy of antibiotics in reducing morbidity and mortality from heatstroke - A systematic review.

Severe hyperthermia, for example, classical heatstroke or exertional heatstroke from heatwaves or exercise respectively, or from drug ingestion or other non-infective pyrogens, is associated with a high mortality and morbidity, which may be chronic or permanent. Abolition of lipopolysaccharide, from gram-negative intestinal bacteria translocating into the systemic circulation via an intestinal wall rendered permeable from the hyperthermia, reduces the adverse effects, suggesting that antibiotics against the intestinal bacteria may have a similar effect. A systematic review searching Embase, MEDLINE and PubMed from the earliest date available until 2019 was conducted, according to PRISMA guidelines.

APTRA-Based Luminescent Lanthanide Complexes Displaying Enhanced Selectivity for Mg.

A series of three europium(III) complexes has been created in which an APTRA moiety has been integrated into the sensitising chromophore (APTRA=o-aminophenol-N,N,N-triacetate). The constitutionally isomeric complexes EuL and EuL feature the APTRA unit linked to a metal-bound pyridine ring through an alkynyl unit, differing according to the disposition of the APTRA substituents relative to the C≡C unit (para-N and para-O). In EuL , the APTRA ring is directly bonded to the Eu-coordinated pyridine (para-O).

Tuning Mg(II) Selectivity: Comparative Analysis of the Photophysical Properties of Four Fluorescent Probes with an Alkynyl-Naphthalene Fluorophore.

Four alkynyl-1-naphthyl fluorophores have been synthesised with tri- or pentadentate ligating groups suited to the binding of magnesium. Their photophysical and binding properties for magnesium, calcium and zinc ions have been assessed using absorption, emission and excitation spectroscopy. Each compound has a pK value between 6.

Death from Kratom toxicity and the possible role of intralipid.

We present the case of a 26-year-old man who was brought into our emergency department in cardiorespiratory arrest, having taken Kratom 24 h previously. Despite multi-organ support, he deteriorated and died from cardiorespiratory failure and hypoxic brain damage 12 h later. Lipid emulsion was given, with significant temporary improvement in the cardiorespiratory failure.

Review of management in cardiotoxic overdose and efficacy of delayed intralipid use.

We present the case of a 51-year-old woman admitted to our intensive care unit following an intentional overdose of a calcium channel antagonist and a beta blocker. The resultant hypotension was reversed with glucagon, noradrenaline, calcium and high-dose insulin. Despite these interventions, she remained vasoplegic and received a delayed, standard dose of intralipid.

Enhanced selectivity for Mg with a phosphinate-based chelate: APDAP versus APTRA.

o-Aminophenol-N,N,O-triacetate, known as APTRA, is one of the most well-established ligands for targeting magnesium ions but, like other aminocarboxylate ligands, it binds Ca much more strongly than Mg. The synthesis of an O-phosphinate analogue of APTRA is reported here, namely o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate, referred to as APDAP. Metal binding studies monitored using UV-visible spectroscopy show that the affinity of APDAP for Ca is reduced by over two orders of magnitude compared to APTRA, and for Zn by over three orders of magnitude, whereas the affinity for Mg is attenuated to a much lesser extent, by a factor of only about 7.

Solvent polarity and oxygen sensitivity, rather than viscosity, determine lifetimes of biaryl-sensitised terbium luminescence.

In a macrocyclic terbium complex incorporating a biaryl sensitiser, the observed variation of emission lifetime is shown to be determined by the solubility of oxygen in the solvent system and the relative energy of the chromophore excited state, rather than any dependence on solvent viscosity.