A Comparative Analysis of Local Anesthetics: Injection Associated Pain and Duration of Anesthesia.

BACKGROUND: Local anesthesia administration is frequently the most painful step of dermatologic surgery. Identification of an anesthetic that minimizes infiltration pain and toxicity while maximizing duration of action would improve both patient satisfaction and procedural safety. This study compared eight local anesthetic solutions to identify the composition that minimizes infiltration pain, maximizes duration of effect, and minimizes amount of local anesthetic needed. METHODS: In a double-blinded study, thirty subjects were injected with eight local anesthetic solutions of varied concentrations of lidocaine, epinephrine, benzyl alcohol, and sodium bicarbonate. Infiltration pain was rated by subjects using a visual analog scale and duration of anesthesia was assessed by needle prick sensation every 15 minutes. RESULTS: Solutions 2, 7, and 8, were significantly less painful (P<0.001), though not statistically different from each other. Two of the three solutions were buffered 10:1 with sodium bicarbonate. Additionally, two of the three contained notably decreased concentrations of lidocaine, 0.091% and 0.083%, than traditionally used in practice. The use of benzyl alcohol did not result in a reduction of reported pain. The duration of action was equal among the solutions regardless of anesthetic concentration. CONCLUSIONS: A solution of 0.091% lidocaine with epinephrine 1:1,100,000 and 0.82% benzyl alcohol reduces medication dose while ensuring maximum patient comfort and, theoretically, increases shelf life. While considered off-label, clinically effective dermal anesthesia may be obtained at a lower concentration of lidocaine and epinephrine than is commonly used, aiding conservative use of local anesthetic, particularly during times of national shortage. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.5183 Citation: Moses A, Klager S, Weinstein A, et al. A comparative analysis of local anesthetics: Injection associated pain and duration of anesthesia. J Drugs Dermatol. 2023;22(4):364-368. doi:10.36849/JDD.5183.

The potential of dietary treatment in patients with glycogen storage disease type IV.

There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initiated this observational study to assess the outcomes of medical diets, which limit the accumulation of glycogen. Clinical, dietary, laboratory, and imaging data for 15 GSD IV patients from three centres are presented. Medical diets may have the potential to delay or prevent liver transplantation, improve growth and normalize serum aminotransferases. Individual care plans aim to avoid both hyperglycaemia, hypoglycaemia and/or hyperketosis, to minimize glycogen accumulation and catabolism, respectively. Multidisciplinary monitoring includes balancing between traditional markers of metabolic control (ie, growth, liver size, serum aminotransferases, glucose homeostasis, lactate, and ketones), liver function (ie, synthesis, bile flow and detoxification of protein), and symptoms and signs of portal hypertension.

Notalgia paresthetica: treatment review and algorithmic approach.

Background: Notalgia paresthetica (NP) is a sensory neuropathy of the back characterized by a well demarcated, hyperpigmented macule or patch located medial or inferior to the scapulae. Symptoms include localized pruritus and pain, and the clinical course consists of remissions and relapses. It can be an underrecognized and difficult disease to treat since conventional treatments for pruritus in inflammatory dermatosis have variable efficacy. There are a variety of treatment modalities, but strong evidence to suggest the superiority of any one treatment is lacking.Objective: This review describes the treatments that have been used for NP in the literature and evaluates their level of evidence with respect to their efficacy. We also present a treatment algorithm based on our analysis.Materials and methods: MEDLINE search was performed using the terms 'notalgia,' 'paresthetica,' and 'treatment.' All resulting articles have been included in this review.Results: Treatment options include topical agents (capsaicin, tacrolimus, anesthetic cream, and amitriptyline/ketamine), systemic agents (gabapentin, oxcarbazepine, and amitriptyline), procedural modalities (botulinum toxin A and narrowband UVB), and physical therapy.Conclusions: Treatment should begin with topical agents or physical therapy, then systemic agents, and finally procedural modalities. We recommend combining treatment options with physical therapy for sustained treatment response.

Improving the pharmacokinetic and CYP inhibition profiles of azaxanthene-based glucocorticoid receptor modulators-identification of (S)-5-(2-(9-fluoro-2-(4-(2-hydroxypropan-2-yl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanamido)-N-(tetrahydro-2H-pyran-4-yl)-1,3,4-thiadiazole-2-carboxamide (BMS-341).

An empirical approach to improve the microsomal stability and CYP inhibition profile of lead compounds 1a and 1b led to the identification of 5 (BMS-341) as a dissociated glucocorticoid receptor modulator. Compound 5 showed significant improvements in pharmacokinetic properties and, unlike compounds 1a-b, displayed a linear, dose-dependent pharmacokinetic profile in rats. When tested in a chronic model of adjuvant-induced arthritis in rat, the ED50 of 5 (0.9 mg/kg) was superior to that of both 1a and 1b (8 and 17 mg/kg, respectively).

A novel role for the immunophilin FKBP52 in copper transport.

FK506-binding protein 52 (FKBP52) is an immunophilin that possesses peptidylprolyl cis/trans-isomerase (PPIase) activity and is a component of a subclass of steroid hormone receptor complexes. Several recent studies indicate that immunophilins can regulate neuronal survival and nerve regeneration although the molecular mechanisms are poorly understood. To investigate the function of FKBP52 in the nervous system, we employed a yeast two-hybrid strategy using the PPIase domain (domain I) as bait to screen a neonatal rat dorsal root ganglia cDNA expression library. We identified an interaction between FKBP52 domain I and Atox1, a copper-binding metallochaperone. Atox1 interacts with Menkes disease protein and Wilson disease protein (WD) and functions in copper efflux. The interaction between FKBP52 and Atox1 was observed in both glutathione S-transferase pull-down experiments and when proteins were ectopically expressed in human embryonic kidney (HEK) 293T cells and was sensitive to FK506. Interestingly, the FKBP52/Atox1 interaction was enhanced when HEK 293T cells were cultured in copper-supplemented medium and decreased in the presence of the copper chelator, bathocuproine disulfate, suggesting that the interaction is regulated in part by intracellular copper. Overexpression of FKBP52 increased rapid copper efflux in (64)Cu-loaded cells, as did the overexpression of WD transporter. Taken together, our present findings suggest that FKBP52 is a component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity.