Sensitive and Rapid determination of Trientine and N1-Acetyl Trientine in Human Plasma by LC-MS/MS for bioequivalence study

A simple and robust method for simultaneous determination of Trientine and N1-Acetyl Trientine in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. The analyte and internal standard were extracted from 200 μL plasma by liquid phase extraction. Chromatographic analysis was carried out on column Xtimate, C18 (4.6 x 50 mm) 5 μm with a flow rate of 1 mL/min, at 40˚C temperature. An isocratic elution method was applied using (A) Acetonitrile - 80% and (B) 10mM Ammonium Acetate in water - 20%.  Detection and quantitation was done by multiple reactions monitoring in positive ionization with Q3 LCMS-8050, Shimadzu. Mass parameters 1035.45/1030.55 m/z and 855.15/859.50 m/z on a triple quadrupole mass spectrometer were chosen for analysis of Trientine and N1-Acetyl Trientine. Linearity was established in human plasma covering the concentration range 10.009 ng/mL to 1000.571 ng/mL for Trientine and 10.009 ng/mL to 1000.628 ng/mL for N1-Acetyl Trientine. Correlation coefficient was consistently greater than 0.99 for Trientine and N1-Acetyl Trientine using Trientine-D4 and N1-Acetyl Trientine Trihydrochloride D4 as internal standards. Different parameters such as linearity, range, precision, accuracy, ruggedness and robustness, limit of detection (LOD) and limit of quantification (LOQ) were used for a full validation of this method. The results were found to be acceptable as per the guidelines of International Conference on Harmonization (ICH), CDER, EMA1,2,3,4,5. The developed and validated method was successfully applied to estimate Trientine and N1-Acetyl Trientine in a bioequivalence study in healthy human volunteers. Assay reproducibility was checked by reanalysis of samples near the Cmax and the elimination phase in the pharmacokinetic profile of the drug. Keywords: Trientine and N1-Acetyl Trientine, LC-MS/MS, Validation, ICH

Variants of Tribulus species – a scientific study through DNA RAPD – molecular characterization

Gokshura a well-known drug in Ayurveda which is extensively used in many disease conditions like dysuria, asthma, diabetes, cough, oedema, cardiac disorders etc. Tribulus terrestris (Family – Zygophyllaceae) is an official source of Gokshura as per API. Five species of genus Tribulus are found throughout India with a slight morphological difference. In this study, three different species of Tribulus genus from different regions were subjected for molecular characterization by RAPD method. Analysis showed that three different samples gave clearly similar banding pattern with each of the random primers used and 80% similarity between the three samples were observed when the results were subjected to band scoring and analysis with clustering. Even through the micromorpholgical observations showed differentiating characters in mature carpels and intrastaminal glands of the selected species

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

EVALUATION OF A DRUG UTILIZATION PATTERN AND USE OF POTENTIALLY INAPPROPRIATE MEDICATIONS AMONG GERIATRIC PATIENTS ADMITTED TO A MEDICAL INTENSIVE CARE UNIT OF A TERTIARY CARE TEACHING HOSPITAL: Drug utilization and PIMs among geriatrics

Background: Elderly account for the majority of total drug usage due to multiple comorbidities, which increases the risk of irrational prescribing, drug-drug interactions, and adverse drug reactions (ADRs). The potentially inappropriate medications whose risks may outweigh their benefits can increase the risk of developing ADRs by many times. This study aimed to evaluate a drug utilization pattern and the use of potentially inappropriate medications in geriatric patients admitted to a medical intensive care unit (MICU) of a tertiary care teaching hospital. Methods: A prospective, observational study was conducted among geriatric patients admitted to a MICU of a tertiary care teaching hospital. The data relevant to study variables were collected in a pre-designed case record form. Evaluation of a drug utilization pattern was carried out using WHO core drug prescribing indicators, and the use of potentially inappropriate medications among patients was evaluated using the Beers criteria 2019. Results: The average duration of stay in MICU per patient was 6.98 ± 1.82 days. Hypertension and diabetes mellitus were the two most common co-morbidities found in the geriatric patients. Average 10.29 ± 3.46 drugs were prescribed per patient. Average 0.77 ± 0.08 antibiotics were prescribed per patient. Nearly half of the drugs were prescribed in the form of parenteral formulations. About 14.6% of the prescribed drugs were found to be potentially inappropriate according to Beer’s criteria 2019. Conclusion: The majority of the drug classes were prescribed to geriatric patients for the appropriate indications. Prescribing potentially inappropriate medications to geriatric patients was common. The Beers criteria have not yet found their way into mainstream clinical practice

Three-Dimensional Co(II)/Cd(II) Metal–Organic Frameworks: Luminescent Cd-MOF for Detection and Adsorption of 2,4,6-Trinitrophenol in the Aqueous Phase

Sensing and adsorption of hazardous and explosive nitroaromatic compounds using metal–organic frameworks (MOFs) have been a promising research field in the current scenario due to environmental concerns and homeland security. Here, we report two mixed ligand MOFs {[Co₂(SDB)₂­(TIB)­(H₂O)]­(H₂O)­(1,4-dioxane)₂}_<i>n</i> (<b>CP1</b>) and {[Cd₃(SDB)₃(TIB)]­(H₂O)₂­(1,4-dioxane)­(G)_<i>x</i>}_<i>n</i> (<b>CP2</b>) (where SDB = 4,4′-sulfonyldibenzoate, TIB = 1,3,5-tris­(imidazol-1-ylmethyl) benzene, and G = guest solvent molecules) synthesized by a hydrothermal method and the application of <b>CP2</b> as an adsorbent and sensing material for 2,4,6-trinitrophenol (TNP). Both MOFs are characterized by various physicochemical techniques including single crystal X-ray analysis, and the crystal structures of <b>CP1</b> and <b>CP2</b> revealed that both MOFs are 3D frameworks composed of trimeric metal clusters linked by SDB ligand further coordinated through the imidazole nitrogen of the TIB moiety. Taking advantage of d¹⁰ transition metal present in the case of <b>CP2</b>, the recognition of nitroaromatics has been investigated engaging this fluorescent material. The photoluminescence property of <b>CP2</b> revealed that significant and sensitive fluorescence quenching was observed toward TNP in the aqueous phase from different pools of NACs with a detection limit up to 35 ppb. Plausible accounts for the fluorescence quenching and <b>CP2</b> as a column chromatographic filler for the adsorption of TNP from water have also been demonstrated

azyx-1 is a new gene that overlaps with zyxin and affects its translation in C. elegans, impacting muscular integrity and locomotion.

Overlapping genes are widely prevalent; however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novel zyx-1 overlapping gene, azyx-1, with distinct regulatory functions in Caenorhabditis elegans. We observed conservation of alternative open reading frames (ORFs) overlapping the 5' region of zyxin family members in several animal species, and find shared sites of azyx-1 and zyxin proteoform expression in C. elegans. In line with a standard ribosome scanning model, our results support cis regulation of zyx-1 long isoform(s) by upstream initiating azyx-1a. Moreover, we report on a rare observation of trans regulation of zyx-1 by azyx-1, with evidence of increased ZYX-1 upon azyx-1 overexpression. Our results suggest a dual role for azyx-1 in influencing zyx-1 proteoform heterogeneity and highlight its impact on C. elegans muscular integrity and locomotion