Perspectives of Healthcare Professionals Towards Combination Use of Oral Paracetamol and Topical Non-Steroidal Inflammatory Drugs in Managing Mild-to-Moderate Pain for Osteoarthritis in a Clinical Setting: An Exploratory Study.

Purpose: To seek indicative evidence on clinical prescription practice and perspectives regarding combined oral paracetamol (APAP) and/or topical non-steroidal anti-inflammatory drugs (NSAIDs) therapy for managing mild-to-moderate osteoarthritis (OA) pain. Participants and Methods: An exploratory qualitative study to investigate the perspectives towards using APAP and/or topical NSAIDs for OA pain management and whether current clinical practices are aligned with OA guidelines was conducted using a two-round modified Delphi methodology among three general practitioners, three orthopedists, and two pharmacists from Australia, Malaysia, and Sweden during January-June 2021. In the first round, 60-minute virtual in-depth interviews were conducted individually; in the second round, summary of the key findings was shared with the panel to seek clarity on the level of consensus (≥70% unanimity) and disagreement. Results: The healthcare professionals (HCPs) agreed that APAP was considered as a universally accepted pharmacologic for most OA patients except those with contraindications or allergies. Consensus was achieved towards APAP combination with topical NSAIDs being a safer alternative than with oral NSAIDs. However, prescription uptake of combined therapy APAP with topical NSAIDs was low among the panel due to lack of strong scientific evidence on efficacy and awareness. Differences in clinical practice across and within countries could be due to different reference sources for OA pain - clinical practice experience or local/international guidelines/medical products handbooks. Conclusion: The study suggests an opportunity to raise awareness of the suitability and potential benefits for adjuvant topical NSAIDs to APAP for effective OA pain management as well as a need for universal OA guidelines.

Enzyme system involved in the synthesis of thiamin triphosphate. I. Purification and characterization of protein-bound thiamin diphosphate: ATP phosphoryltransferase.

An enzyme system catalyzing the synthesis of thiamin triphosphate consists of an enzyme (protein-bound thiamin diphosphate:ATP phosphoryltransferase), thiamin diphosphate bound to a macromolecule as substrate, ATP, Mg2+, and a low molecular weight cofactor. This system was established by combining a purified enzyme and an essentially pure, macromolecule-bound substrate prepared from rat livers. This macromolecule was found to be a protein, and the transphosphorylation of thiamin diphosphate to thiamin triphosphate with ATP and enzyme was shown to occur on this macromolecule which binds thiamin diphosphate. Free thiamin, thiamin monophosphate, thiamin diphosphate, and thiamin triphosphate have no effect on this reaction. Thus, the overall reaction is: thiamin diphosphate-protein + ATP in equilibrium thiamin triphosphate-protein + ADP. So-called thiamin diphosphate:ATP phosphoryltransferase (EC 2.7.4.15) activity was not detected in rat brain or liver. The enzyme was extracted from acetone powder of a crude mitochondrial fraction of bovine brain cortex and purified to homogeneity with a 0.6% yield after DEAE-cellulose chromatography, a first gel filtration, hydroxylapatite chromatography, chromatofocusing, and a second gel filtration. The purified enzyme showed a single protein band on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Its molecular weight was estimated to be 103,000. The pH optimum was 7.5, and the Km was determined to be 6 X 10(-4) M for ATP. ATP was found to be the most effective phosphate donor among the nucleoside triphosphates. Amino acid analysis of the purified enzyme revealed an abundance of glutaminyl, glutamyl, and aspartyl residues. Sulfhydryl reagents inhibited the enzyme reaction. Metals such as Fe2+, Zn2+, Pb2+, and Cu2+ strongly inhibited the activity. The enzyme was unstable, and glycerol (20%) and dithiothreitol (1.0 mM) were found to preserve the enzyme activity.

The effect of juglone on cholinergic mechanisms in rat brain synaptosomes.

Juglone 5-hydroxy-1,4-napthoquinone exerts three activities on cortical synaptosomal preparations. It inhibits the release of acetylcholine and is an even more potent inhibitor of high-affinity choline transport into synaptosomes. In addition, as has already been shown by others using brain homogenates, juglone inhibits choline acetyltransferase.