Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Boron doped diamond electrode for the wastewater treatment

Electrochemical studies of diamond were started more than fifteen years ago with the first paper on diamond electrochemistry published by Pleskov. After that, work started in Japan, United States of America, France, Switzerland and other countries. Over the last few years, the number of publications has increased considerably. Diamond films have been the subject of applications and fundamental research in electrochemistry, opening up a new branch known as the electrochemistry of diamond electrodes. Here, we first present a brief history and the process of diamond film synthesis. The principal objective of this work is to summarize the most important results in the electrochemical oxidation using diamond electrodes

Cerium Compounds Coating as a Single Self-Healing Layer for Corrosion Inhibition on Aluminum 3003

The formation of cerium hydroxide was studied, and its capacity as a corrosion inhibitor on aluminum substrates was evaluated. These particles were deposited by immersing the substrate in a bath with cerium nitrate and hydrogen peroxide. Four different immersion times were used to determine the differences in behavior from low concentrations to an excess of particles on the surface. The coatings were analyzed morphologically by scanning electron microscope (SEM) and optical microscope, and chemically by energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). Electrochemical corrosion analysis was studied using cyclic potentiodynamic polarization (CPP), electrochemical impedance spectroscopy (EIS), and electrochemical noise (EN). The results show that for 2 and 5 min of immersion, there was corrosion inhibition caused by the presence of cerium Ce3+ in the coating, but with excess cerium hydroxide particles, corrosion was favored. The presence of cerium particles favors corrosion at 30 s of immersion. This is the same case at 60 min, where corrosion was favored by the excess of Ce4+ particles on the surface

Studies on a series of potent, orally bioavailable, 5-HT1 receptor ligands

A series of 5-(piperidinylethyloxy)quinoline 5-HT1 receptor ligands have been studied by elaboration of the series of dual 5-HT1-SSRIs reported previously. These new compounds display a different pharmacological profile with potent affinity across the 5-HT1A, 5-HT1B and 5-HT1D receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration