Disease foci of pharmaceutical research and development as reflected in applications for International Nonproprietary Names, 1953-2022.

Objective: To evaluate trends in pharmaceutical research and development, and to correlate these trends with global medical need.

Methods: We obtained details of proposed pharmaceutical substances from 1953 to 2022 from the International Nonproprietary Names (INN) database. We used the DrugBank and Cortellis databases to obtain the INN included in approved medicines over the same period.

Edaravone N-benzyl pyridinium derivatives: BACE-1 inhibition, kinetics and in silico binding pose determination.

BACE-1 plays a pivotal role in the production of β-amyloid (Aβ) peptides, implicated in Alzheimer's Disease (AD) pathology. We previously described edaravone N-benzyl pyridinium derivatives (EBPDs) that exhibited multifunctional activity against multiple AD targets. In this study we explored the EBPDs BACE-1 inhibitory activity to potentially enhance the compounds therapeutic profile.

Calcium Modulating Effect of Polycyclic Cages: A Suitable Therapeutic Approach Against Excitotoxic-induced Neurodegeneration.

Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and functions. Excitotoxicity, characterized by calcium overload, plays a critical role in the pathophysiology of these disorders. In this review article, we explore the involvement of calcium dysregulation in neurodegeneration and neurodegenerative disorders.

Discovery and biological evaluation of an adamantyl-amide derivative with likely MmpL3 inhibitory activity.

A series of molecules containing bulky lipophilic scaffolds was screened for activity against Mycobacterium tuberculosis and a number of compounds with antimycobacterial activity were identified. The most active compound, (2E)-N-(adamantan-1-yl)-3-phenylprop-2-enamide (C1), has a low micromolar minimum inhibitory concentration, low cytotoxicity (therapeutic index = 32.26), low mutation frequency and is active against intracellular Mycobacterium tuberculosis.

Erector Spinae Plane Block With Liposomal Bupivacaine: Analgesic Adjunct in Adult Pectus Surgery.

Introduction: Pain management may be challenging in patients undergoing pectus excavatum (PE) bar removal surgery. To enhance recovery, opioid sparing strategies with regional anesthesia including ultrasound-guided erector spinae plane block (ESPB) have been implemented. The purpose of this study was to evaluate the safety and efficacy of bilateral ESPB with a liposomal bupivacaine/traditional bupivacaine mixture as part of an enhanced patient recovery pathway.

Arterial Cannulation Near-Miss During Jugular Venous Catheterization With Carotid Artery Aneurysm: A Case Report.

Central venous catheterization is a common procedure that may lead to inadvertent arterial cannulation, potentially causing bleeding, hematoma, stroke or rarely, death. In this near-miss case presentation, an aneurysmal carotid artery was misidentified with ultrasound by a junior resident, nearly leading to placement of a sheath into the artery. This case highlights arterial punctures that still occur even with ultrasound guidance.

Drug-coated balloon in the treatment of coronary bifurcation lesions: A hope or hype?

When compared to non-bifurcation lesions, percutaneous coronary intervention in coronary bifurcation lesions is technically demanding and has historically been limited by lower procedural success rates and inferior clinical results. Following the development of drug-eluting stents, dramatically better results have been demonstrated. In most of the bifurcation lesions, the provisional technique of implanting a single stent in the main branch (MB) remains the default approach.

Emergency Department Visits for Ankle Fractures Through COVID-19: An Analysis of the National Electronic Injury Surveillance System.

Background: Societal changes that occurred during the COVID-19 pandemic may have altered the epidemiology of ankle fractures. The aim of this study was to assess trends in emergency department visits for ankle fractures from 2019 to 2020 in the United States.

Methods: The National Electronic Injury Surveillance System (NEISS) database is a sample of hospitals in the United States stratified and weighted based on emergency department (ED) size, which was used to generate national estimates (NEs).

International nonproprietary names for monoclonal antibodies: an evolving nomenclature system.

Appropriate nomenclature for all pharmaceutical substances is important for clinical development, licensing, prescribing, pharmacovigilance, and identification of counterfeits. Nonproprietary names that are unique and globally recognized for all pharmaceutical substances are assigned by the International Nonproprietary Names (INN) Programme of the World Health Organization (WHO). In 1991, the INN Programme implemented the first nomenclature scheme for monoclonal antibodies.

Low-Dose Ketamine Infusion for Perioperative Pain Management in Patients Undergoing Laparoscopic Gastric Bypass: A Prospective Randomized Controlled Trial.

Introduction: Obesity is a common comorbidity seen in the perioperative setting and is associated with many diseases including cardiovascular disease and obstructive sleep apnea. Laparoscopic Roux-en-Y gastric bypass is the gold standard surgical treatment for patients whose weight is refractory to diet and exercise. Caring for these patients perioperatively presents unique challenges to anesthesiologists and is associated with an increased risk of adverse respiratory events.

Transesophageal Echocardiography in Patients With Magnetic Gastroesophageal Reflux Devices: A Report of 2 Cases.

Magnetic gastroesophageal reflux devices are becoming a common treatment option for reflux refractory to medical therapy. These devices are inserted laparoscopically with successful outcomes; however, patients may still complain of dysphagia after implantation. Echocardiographers may be hesitant to perform transesophageal echocardiography (TEE) in these patients as esophageal surgery and dysphagia represent relative contraindications to performing TEE.

Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer's disease agents.

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer's disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD's complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability.

Antimycobacterial Activity, Synergism, and Mechanism of Action Evaluation of Novel Polycyclic Amines against .

has developed extensive resistance to numerous antimycobacterial agents used in the treatment of tuberculosis. Insufficient intracellular accumulation of active moieties allows for selective survival of mycobacteria with drug resistance mutations and accordingly promotes the development of microbial drug resistance. Discovery of compounds with new mechanisms of action and physicochemical properties that promote intracellular accumulation, or compounds that act synergistically with other antimycobacterial drugs, has the potential to reduce and prevent further drug resistance.

Radical Releasing Anti-tuberculosis Agents and the Treatment of Infections - An Overview.

The treatment and management of tuberculosis (TB) is a major global concern. Approved drugs for the treatment of TB, to date, have displayed various modes of action which can be grouped into radical releasing and non-radical releasing anti-TB agents. Radical releasing agents are of special interest because they diffuse directly into the mycobacterium cell wall, interact with the host cell DNA, causing DNA strand breakages and fatal destabilization of the DNA helix inhibiting nucleic acid synthase.

Computational drug repurposing strategy predicted peptide-based drugs that can potentially inhibit the interaction of SARS-CoV-2 spike protein with its target (humanACE2).

Drug repurposing for COVID-19 has several potential benefits including shorter development time, reduced costs and regulatory support for faster time to market for treatment that can alleviate the current pandemic. The current study used molecular docking, molecular dynamics and protein-protein interaction simulations to predict drugs from the Drug Bank that can bind to the SARS-CoV-2 spike protein interacting surface on the human angiotensin-converting enzyme 2 (hACE2) receptor. The study predicted a number of peptide-based drugs, including Sar9 Met (O2)11-Substance P and BV2, that might bind sufficiently to the hACE2 receptor to modulate the protein-protein interaction required for infection by the SARS-CoV-2 virus.

4-Oxatricyclo[5.2.1.0]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC Blockers with Neuroprotective Potential.

The impact of excitotoxicity mediated by -methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes.

Design, synthesis and biological evaluation of edaravone derivatives bearing the -benzyl pyridinium moiety as multifunctional anti-Alzheimer's agents.

A series of multi-target directed edaravone derivatives bearing -benzyl pyridinium moieties were designed and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects and -benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheral anionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edaravone--benzyl pyridinium hybrid compounds were docked within the AChE active site.

Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP- and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells.

The neuroprotective effects of closed polycyclic cage molecules such as NGP1-01, memantine and amantadine have been extensively explored. These effects are mostly linked to the antagonism of the N-methyl-d-aspartate (NMDA) receptor- and the blockage of voltage gated calcium channels (VGCC). The synthesis of structurally related open and rearranged cage derivatives has been studied in depth.

A Plum Marbling Conundrum: Identification of a New Viroid Associated with Marbling and Corky Flesh in Japanese Plums.

Over the past 2 decades, fruit symptoms resembling a marbling pattern on the fruit skin or corking of the fruit flesh were observed on Japanese plums in South Africa, resulting in unmarketable fruit. The ability of high-throughput sequencing (HTS) to detect known and unknown pathogens was exploited by assaying affected and unaffected fruit tree accessions to identify the potential aetiological agent of marbling and/or corky flesh disease. In this study, it is shown that the disease is associated with a previously undescribed small RNA with typical viroid structural features.

Perioperative Management of a Patient Taking Suboxone® at the Time of Ambulatory Surgery.

In 2016, more than 11 million people reported misuse of opioids in the previous year. In an effort to combat opioid use disorder (OUD), the use of agonist/antagonist is becoming increasingly common, with more than 2.2 million patients reporting use of a buprenorphine containing medication such as Suboxone®.

The INN global nomenclature of biological medicines: A continuous challenge.

Medicines are assigned International Nonproprietary Names (INN) by the World Health Organization (WHO), pursuing the aim to increase patient safety. Following scientific developments in drug discovery and biotechnology, the number of biological medicines is constantly growing and a surge in INN applications for them has been observed. Pharmacologically active biological substances have a complex structure and mechanism of action posing new challenges in selecting names that appropriately reflect such properties.