Adsorption of paracetamol on activated charcoal in the presence of dextropropoxyphene hydrochloride, N-acetylcysteine and sorbitol

Paracetamol, an over the counter analgesic and antipyretic drug, causes hepatic and renal tubular necrosis at higher doses ingested accidentally, or intentionally. The situation worsens clinically upon the ingestion of product containing paracetamol and dextropropoxyphene. In paracetamol poisoning, activated charcoal is used to adsorb the drug from the gastrointestinal tract, sorbitol to remove charcoaldrug complexes and N-acetylcysteine to reduce the drug and its metabolites from systemic circulation. Activated charcoal being non-specific adsorbent may adsorb other chemical moieties from the intestine as well as antidotes. Therefore, the present study aimed to investigate the adsorption of paracetamol on activated charcoal in presence of dextropropoxyphene hydrochloride, N-acetylcysteine and sorbitol. Paracetamol was combined separately with dextropropoxyphene hydrochloride, N-acetylcysteine and sorbitol. These mixtures were combined with varying amounts of activated charcoal to evaluate the in vitro adsorption of paracetamol using Langmuir Isotherm. Paracetamol adsorption was 96.6 % at charcoal-drug ratio (6:1) while only 2 % higher in 8:1 and 2.9 % in 10:1. The binding constant (K2), maximum adsorption capacity per gram of activated charcoal for paracetamol alone and in presence of dextropropoxyphene hydrochloride, N-acetylcysteine and sorbitol was found to be 366, 339, 313 and 355 mg/g, respectively. The results of the present study indicate that except sorbitol other investigated substances significantly reduce the adsorption of paracetamol on activated charcoal, which may be compensated by increasing the concentration of activated charcoal.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Inducing Drought Tolerance in Wheat through Exopolysaccharide-Producing Rhizobacteria

Wheat is the main staple food in the world, so it is the backbone of food security. Drought not only affects growth and development but also ultimately has a severe impact on the overall productivity of crop plants. Some bacteria are capable of producing exopolysaccharides (EPS) as a survival mechanism, along with other metabolites, which help them survive in stressful conditions. The present study was conducted with the aim of inducing drought stress tolerance in wheat through EPS-producing plant growth-promoting rhizobacteria (PGPR). In this regard, a series of laboratory bioassays were conducted with the aim to isolating, characterizing, and screening the EPS-producing PGPR capable of improving wheat growth under limited water conditions. Thirty rhizobacterial strains (LEW1–LEW30) were isolated from the rhizosphere of wheat. Ten isolates with EPS-producing ability were quantitatively tested for EPS production and IAA production ability. Four of the most efficient EPS-producing strains (LEW3, LEW9, LEW16, and LEW28) were evaluated for their drought tolerance ability along with quantitative production of EPS and IAA under polyethylene glycol (PEG-6000)-induced drought stress. The jar experiment was conducted under gnotobiotic conditions to examine the drought-tolerant wheat genotypes, and two wheat varieties (Johar-16, and Gold-16) were selected for further experiments. The selected varieties were inoculated with EPS-producing rhizobacterial strains and grown under control conditions at different stress levels (0, 2, 4, and 6% PEG-6000). The strain LEW16 showed better results for improving root morphology and seedling growth in both varieties. The maximum increase in germination, growth parameters, percentage, root diameter, root surface area, and root colonization was recorded in Johar-16 by inoculating LEW16 at 6% PEG-6000. Plant growth-promoting traits were tested on the top-performing strains (LEW3, LEW9, and LEW16). Through 16S rRNA sequencing, these strains were identified as Chryseobacterium sp. (LEW3), Acinetobacter sp. (LEW9), and Klebsiella sp. (LEW16), and they showed positive results for phosphorous and zinc solubilization as well as hydrogen cyanide (HCN) production. The partial sequencing results were submitted to the National Center for Biotechnology Information (NCBI) under the accession numbers MW829776, MW829777, and MW829778. These strains are recommended for their evaluation as potential bioinoculants for inducing drought stress tolerance in wheat

Inducing Drought Tolerance in Wheat through Exopolysaccharide-Producing Rhizobacteria

Wheat is the main staple food in the world, so it is the backbone of food security. Drought not only affects growth and development but also ultimately has a severe impact on the overall productivity of crop plants. Some bacteria are capable of producing exopolysaccharides (EPS) as a survival mechanism, along with other metabolites, which help them survive in stressful conditions. The present study was conducted with the aim of inducing drought stress tolerance in wheat through EPS-producing plant growth-promoting rhizobacteria (PGPR). In this regard, a series of laboratory bioassays were conducted with the aim to isolating, characterizing, and screening the EPS-producing PGPR capable of improving wheat growth under limited water conditions. Thirty rhizobacterial strains (LEW1–LEW30) were isolated from the rhizosphere of wheat. Ten isolates with EPS-producing ability were quantitatively tested for EPS production and IAA production ability. Four of the most efficient EPS-producing strains (LEW3, LEW9, LEW16, and LEW28) were evaluated for their drought tolerance ability along with quantitative production of EPS and IAA under polyethylene glycol (PEG-6000)-induced drought stress. The jar experiment was conducted under gnotobiotic conditions to examine the drought-tolerant wheat genotypes, and two wheat varieties (Johar-16, and Gold-16) were selected for further experiments. The selected varieties were inoculated with EPS-producing rhizobacterial strains and grown under control conditions at different stress levels (0, 2, 4, and 6% PEG-6000). The strain LEW16 showed better results for improving root morphology and seedling growth in both varieties. The maximum increase in germination, growth parameters, percentage, root diameter, root surface area, and root colonization was recorded in Johar-16 by inoculating LEW16 at 6% PEG-6000. Plant growth-promoting traits were tested on the top-performing strains (LEW3, LEW9, and LEW16). Through 16S rRNA sequencing, these strains were identified as Chryseobacterium sp. (LEW3), Acinetobacter sp. (LEW9), and Klebsiella sp. (LEW16), and they showed positive results for phosphorous and zinc solubilization as well as hydrogen cyanide (HCN) production. The partial sequencing results were submitted to the National Center for Biotechnology Information (NCBI) under the accession numbers MW829776, MW829777, and MW829778. These strains are recommended for their evaluation as potential bioinoculants for inducing drought stress tolerance in wheat

Controllably Biodegradable Hydroxyapatite Nanostructures for Cefazolin Delivery against Antibacterial Resistance

Multidrug resistance (MDR) is a global threat posed by continuously evolving microbial resistance against currently available antimicrobial agents. In this study, we synthesized hydroxyapatite-based porous nanocarriers with pH-dependent biodegradation, using cefazolin (CFZ) as cargo drug against MDR E. coli, S. aureus, and P. aeruginosa. Oval-shaped porous hydroxyapatite nanoparticles (opHANPs) were synthesized via core-shell method. Field emission scanning electron microscopy revealed that the average length and width of opHANPs were found to be similar to 90 and similar to 110 nm, respectively with monodispersed size and morphology. The encapsulation efficiency (EE) of CFZ was observed to be dependent on the initial concentration of the drug (EE, 41.37-92.40% with 300-2000 mu g/mL of CFZ). Brunauer-Emmett-Teller specific surface area and pore width of opHANPs were 166.73 m(2)/g and 3.3 nm, respectively, indicating hierarchal pore distribution. The pH-responsive drug release was observed from CFZ-loaded opHANPs (CFZ@opHANPs). An enhanced drug-releasing behavior was observed at lower pH (4.5, 2.5, and 1.5). The study of release kinetics revealed that at pH 7.4, drug release is due to anomalous diffusion, while at lower pH, the drug release followed fickian diffusion model. Cytotoxic and hemolytic studies showed biocompatibility of CFZ@opHANPs with HepG2 and red blood cells. The growth kinetic study and colony-forming unit assay showed the superior antibacterial potential of CFZ@opHANPs, in contrast to carrier or CFZ alone, against MDR E. coli, S. aureus, and P. aeruginosa strains