An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models.

A Novel Sensory Wave (P25) in Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis Murine Model.

Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a murine model for multiple sclerosis. This model is characterized by chronic and progressive demyelination, leading to impairment of motor function and paralysis. While the outcomes of the disease, including impaired motor function and immunological changes, are well-characterized, little is known about the impact of EAE on the electrophysiology of the motor and sensory systems.

The centrality of PBGD expression levels on ALA-PDT efficacy.

Successful 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is dependent on efficient porphyrin synthesis in the inflicted cancer tissue, which is regulated by several enzymes. Irradiation of the tumor excites the light-sensitive porphyrins and results in ROS production and cell death. In this study we investigated the effect of the expression levels of two main enzymes in heme biosynthesis, ALA dehydratase (ALAD) and porphobilinogen deaminase (PBGD), on the capacity of K562 cells to undergo cell death following ALA-PDT.

Regulation and gene expression of heme synthesis under heavy metal exposure--review.

Environmental pollution of heavy metals is very abundant nowadays from industry, chemicals, old paints, and pipes or resulting from previous contaminants accumulating in the food chain. Most of the iron demands of the body are needed for heme synthesis and assembly, but iron is also required for Fe-S cluster proteins and other redox enzymes. Heme is an essential, iron-binding molecule used as a prosthetic group of hemoproteins or as a regulator in multiple cellular pathways.

Silencing of ALA dehydratase affects ALA-photodynamic therapy efficacy in K562 erythroleukemic cells.

Synthesis of protoporphyrin IX (PpIX) by malignant cells is essential for the success of ALA-based photodynamic therapy (PDT). Two key enzymes that were described as affecting PpIX accumulation during ALA treatment are porphobilinogen deaminase (PBGD) and ferrochelatase. Here, we show that down regulation of ALA dehydratase (ALAD) expression and activity by specific shRNA induced a marked decrease in PpIX synthesis in K562 erythroleukemic cells.