Determination of amikacin stability at 1% and 3% concentrations in four topical solutions over a 56-day period

BACKGROUND: Anecdotally, amikacin has been added to compounded topical preparations for the management of canine bacterial otitis externa. However, the stability of amikacin within these solutions is unknown. HYPOTHESIS/OBJECTIVES: The purpose of this study was to determine the stability of amikacin at 10 and 30 mg/mL concentrations in four topical solutions over a 56 day period. We hypothesised that amikacin would maintain chemical stability within the various solutions. METHODS AND MATERIALS: Amikacin was formulated to 10 and 30 mg/mL (1% and 3%) concentrations within four topical solutions: tris-EDTA (TrizEDTA Aqueous Flush) (TE); 0.15% chlorhexidine gluconate and tris-EDTA (TrizCHLOR Flush) (TC); 0.9% NaCl (NA); and 0.9% NaCl + 2 mg/mL dexamethasone (ND). Samples were made in duplicate and stored at room temperature (25°C) for 0, 7,14, 21, 28 and 56 days. Amikacin content was quantified, in triplicate, by ultrahigh-performance liquid chromatography tandem mass spectrometry. RESULTS: The recovered amikacin concentrations for the 10 mg/mL solutions ranged from 10 to 13.5 mg/mL (mean 11.5 mg/mL) with the exception of NA sample 2 at Day (D)0 (9.4 mg/mL) and D7 (9.2 mg/mL). The recovered amikacin concentrations for the 30 mg/mL solutions ranged from 30 to 40.2 mg/mL (mean 35.7 mg/mL). No significant difference was seen between the amikacin concentrations at D0 compared to D56 for all solutions except 10 mg/mL TE (P \u3c 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Amikacin maintained stability within TE, TC, NA and ND over 56 days except when formulated at 10 mg/mL within TE

Doxorubicin Induces Dysregulation of AMPA Receptor and Impairs Hippocampal Synaptic Plasticity Leading to Learning and Memory Deficits

Doxorubicin (Dox) is a chemotherapeutic agent used widely to treat a variety of malignant cancers. However, Dox chemotherapy is associated with several adverse effects, including “chemobrain,” the observation that cancer patients exhibit through learning and memory difficulties extending even beyond treatment. This study investigated the effect of Dox treatment on learning and memory as well as hippocampal synaptic plasticity. Dox-treated mice (5 mg/kg weekly x 5) demonstrated impaired performance in the Y-maze spatial memory task and a significant reduction in hippocampal long-term potentiation. The deficit in synaptic plasticity was mirrored by deficits in the functionality of synaptic `α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) channels, including reduced probability of opening, decreased dwell open time, and increased closed times. Furthermore, a reduction in the AMPAR subunit GluA1 level, its downstream signaling molecule Ca(2)+/calmodulin-dependent protein kinase (CaMKII), and brain-derived neurotrophic factor (BDNF) were observed. This was also accompanied by an increase in extracellular signal regulated kinase (ERK) and protein kinase B (AKT) activation. Together these data suggest that Dox-induced cognitive impairments are at least partially due to alterations in the expression and functionality of the glutamatergic AMPAR system

A Dietary Intervention High in Green Leafy Vegetables Reduces Oxidative DNA Damage in Adults at Increased Risk of Colorectal Cancer: Biological Outcomes of the Randomized Controlled Meat and Three Greens (M3G) Feasibility Trial

Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) > 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p < 0.001) increased, while circulating 8OHdG (−8.52 ± 19.05 ng/mL, p < 0.001), fecal 8OHdG (−6.78 ± 34.86 ng/mL, p < 0.001), and TNFα (−16.95 ± 60.82 pg/mL, p < 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted