Extracorporeal Hyperoxygenation Therapy (EHT) for Carbon Monoxide Poisoning: In-Vitro Proof of Principle

Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths globally. The currently available therapy options are normobaric oxygen (NBO) and hyperbaric oxygen (HBO). While NBO lacks in efficacy, HBO is not available in all areas and countries. We present a novel method, extracorporeal hyperoxygenation therapy (EHT), for the treatment of CO poisoning that eliminates the CO by treating blood extracorporeally at elevated oxygen partial pressure. In this study, we proof the principle of the method in vitro using procine blood: Firstly, we investigated the difference in the CO elimination of a hollow fibre membrane oxygenator and a specifically designed batch oxygenator based on the bubble oxygenator principle at elevated pressures (1, 3 bar). Secondly, the batch oxygenator was redesigned and tested for a broader range of pressures (1, 3, 5, 7 bar) and temperatures (23, 30, 37 °C). So far, the shortest measured carboxyhemoglobin half-life in the blood was 21.32 min. In conclusion, EHT has the potential to provide an easily available and effective method for the treatment of CO poisoning.

Pharmacodynamics of Linezolid Plus Fosfomycin Against Vancomycin–Resistant Enterococcus faecium in a Hollow Fiber Infection Model

The optimal therapy for severe infections caused by vancomycin-resistant Enterococcus faecium (VREfm) remains unclear, but the combination of linezolid and fosfomycin may be a good choice. The 24-h static-concentration time-kill study (SCTK) was used to preliminarily explore the pharmacodynamics of linezolid combined with fosfomycin against three clinical isolates. Subsequently, a hollow-fibre infection model (HFIM) was used for the first time to further investigate the pharmacodynamic activity of the co-administration regimen against selected isolates over 72 h. To further quantify the relationship between fosfomycin resistance and bacterial virulence in VREfm, the Galleria mellonella infection model and virulence genes expression experiments were also performed. The results of SCTK showed that the combination of linezolid and fosfomycin had additive effect on all strains. In the HFIM, the dosage regimen of linezolid (12 mg/L, steady-state concentration) combined with fosfomycin (8 g administered intravenously every 8 h as a 1 h infusion) not only produced a sustained bactericidal effect of 3∼4 log10 CFU/mL over 72 h, but also completely eradicated the resistant subpopulations. The expression of virulence genes was down-regulated to at least 0.222-fold in fosfomycin-resistant strains compared with baseline isolate, while survival rates of G. mellonella was increased (G. mellonella survival ≥45% at 72 h). For severe infections caused by VREfm, neither linezolid nor fosfomycin monotherapy regimens inhibited amplification of the resistant subpopulations, and the development of fosfomycin resistance was at the expense of the virulence of VREfm. The combination of linezolid with fosfomycin produced a sustained bactericidal effect and completely eradicated the resistant subpopulations. Linezolid plus Fosfomycin is a promising combination for therapy of severe infections caused by VREfm.

Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model

Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance in the pathogen, hence necessitating the development of new treatment regimens. Drug development processes are lengthy, resource intensive, and high-risk, which have contributed to market failure as demonstrated by pharmaceutical companies limiting their antimicrobial drug discovery programmes. Pre-clinical protocols evaluating treatment regimens that can mimic in vivo PK/PD attributes can underpin the drug development process. The hollow fibre infection model (HFIM) allows for the pathogen to be exposed to a single or a combination of agents at concentrations achieved in vivo–in plasma or at infection sites. Samples taken from the HFIM, depending on the analyses performed, provide information on the rate of bacterial killing and the emergence of resistance. Thereby, the HFIM is an effective means to investigate the efficacy of a drug combination. Although applicable to a wide variety of infections, the complexity of anti-mycobacterial drug discovery makes the information available from the HFIM invaluable as explored in this review.

Chemical Plant Utility – Nitrogen System Design

The study is been conducted to understand the different techniques to separate nitrogen from atmospheric air. Separation of nitrogen takes place by following techniques: Cryogenic air separation, Pressure swing adsorption and Membrane separation technique. Cryogenic air separation operates at a very low temperature, which uses the principle of rectification to separate nitrogen at a very high purity (99.999%). Pressure swing adsorption rely on the fact that higher the pressure, more the gas is adsorbed which results in high purity (95-99.99%) of nitrogen. Membrane separation technology is the process that uses hollow fibre membranes to separate the constituent gases in air, which gives the purity in the range of 93%-99.5%. After the comparative study, it is understood that membrane separation technique is the most efficient technology based on the cost, purity, flexibility in terms of adjusting the purity, maintenance, availability; it operates without heating and therefore uses less energy than conventional thermal separation processes. Different step designs of membrane separation techniques are discussed. A Process Flow Diagram and Piping Instrumentation Diagram is been added for single step membrane separation technique. Keywords: Atmospheric air, nitrogen, Cryogenic air separation, Pressure swing adsorption, Membrane separation technique.

Grand Challenges of Perovskite and Metal Oxide-based Membrane: A Form of Dual-layer Hollow Fibre

Perovskite and metal oxides-based dual-layer hollow fibre membrane (DHF) has a high appeal as separator and catalyst for methane conversion application which operated at intermediate and high temperature. The membrane mostly fabricated via the co-extrusion followed by co-sintering method, which is quite challenging, due to the complexity to handle the barrier between layers from delamination, membrane cracking and crystal structure distortion which affects the material performance in a DHF form. This recent review clarifies the challenges in the DHF fabrication process to regulate physical and chemical properties in terms of mechanical strength, tightness, elemental distribution, and crystal structure stability. The based material of the membrane focuses on NiO-YSZ in the inner layer directly interconnected with LSCF-YSZ in the outer layer. The understanding of the challenges in DHF fabrication, will further reduce crucial errors in the fabrication process and accelerate performance improvement for application such as syngas, methanol and long-chain hydrocarbons production, and solid oxide fuel cell.