Clinical Implications of Poloxamer 407 as Packing Material in an Animal Model.

BACKGROUND: Endoscopic ear surgery has recently increased, but it is still inconvenient and time-consuming to place packing material in the middle ear with one hand. Poloxamer 407 (P407) is a thermo-reversible gel that can be easily administered with one hand into the middle ear cavity in liquid form. Upon warming to body temperature, the gel form of P407 can support the graft in the target position and is known to prevent postsurgical tissue adhesion. OBJECTIVES: We aim to investigate the feasibility of P407 as packing material in an animal model. Male Hartley guinea pigs (350 and 400 g) were utilized in this study. METHOD: The animals were randomly divided into 3 groups according to the packing material: the control group, the P407 group, and the gelatin group. To assess the role of packing material on bacterial colonization, left ears were inoculated with Streptococcus pneumoniae through the tympanic membrane using a 0° endoscope. Five days after inoculation, the middle ear cavity was packed through a transbullar approach using 18% P407 or gelatin in both ears. In the control group, no ear pack was inserted. The tympanic membrane was examined every week using a 0° 1.9-mm endoscope until 6 weeks. Half of the animals in each group were sacrificed 6 weeks after placement of the packing materials. RESULTS: Compared with the absorbable gelatin sponge, the P407 group showed little inflammation or fibrosis in the tympanic membrane and middle ear mucosa regardless of bacterial inoculation. The gelatin group showed severe otorrhea or perforation until 2 weeks in the right ear (2 of 4) and the left ear (1 of 4). Even though the endoscopic findings were similar between both packing groups at 6 weeks, histological analysis showed persistent packing material, inflammatory cells, and fibrosis in the gelatin group compared to the P407 group. CONCLUSIONS: This study suggested that P407 is feasible as a packing material to handle with one hand and to prevent adhesion, especially in infected middle ear mucosa. Although there is a lack of data on how well P407 supports grafts, we suggest that P407 could be a candidate for packing material in endoscopic ear surgery.

Round-window delivery of lithium chloride regenerates cochlear synapses damaged by noise-induced excitotoxic trauma via inhibition of the NMDA receptor in the rat.

Noise exposure can destroy the synaptic connections between hair cells and auditory nerve fibers without damaging the hair cells, and this synaptic loss could contribute to difficult hearing in noisy environments. In this study, we investigated whether delivering lithium chloride to the round-window can regenerate synaptic loss of cochlea after acoustic overexposure. Our rat animal model of noise-induced cochlear synaptopathy caused about 50% loss of synapses in the cochlear basal region without damaging hair cells. We locally delivered a single treatment of poloxamer 407 (vehicle) containing lithium chloride (either 1 mM or 2 mM) to the round-window niche 24 hours after noise exposure. Controls included animals exposed to noise who received only the vehicle. Auditory brainstem responses were measured 3 days, 1 week, and 2 weeks post-exposure treatment, and cochleas were harvested 1 week and 2 weeks post-exposure treatment for histological analysis. As documented by confocal microscopy of immunostained ribbon synapses, local delivery of 2 mM lithium chloride produced synaptic regeneration coupled with corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response wave 1. Western blot analyses revealed that 2 mM lithium chloride suppressed N-methyl-D-aspartate (NMDA) receptor expression 7 days after noise-exposure. Thus, round-window delivery of lithium chloride using poloxamer 407 reduces cochlear synaptic loss after acoustic overexposure by inhibiting NMDA receptor activity in rat model.

Hidden hearing loss in patients with Charcot-Marie-Tooth disease type 1A.

The aim of this study was to investigate hidden hearing loss in patients with Charcot-Marie-Tooth disease type 1 A (CMT1A), a common inherited demyelinating neuropathy. By using pure-tone audiometry, 43 patients with CMT1A and 60 healthy controls with normal sound detection abilities were enrolled. Speech perception in quiet and noisy backgrounds, spectral ripple discrimination (SRD), and temporal modulation detection (TMD) were measured. Although CMT1A patients and healthy controls had similar pure-tone thresholds and speech perception scores in a quiet background, CMT1A patients had significantly (p < 0.05) decreased speech perception ability in a noisy background compared to controls. CMT1A patients showed significantly decreased temporal and spectral resolution (both p < 0.05). Also, auditory temporal processing of CMT1A patients was correlated with speech perception in a noisy background (r = 0.447, p < 0.01) and median motor conduction velocity (r = 0.335, p < 0.05). Therefore, we assumed that demyelination of auditory nerve in CMT1A causes defective cochlear neurotransmission, which reduces temporal resolution and speech perception in a noisy background. Because the temporal resolution test was well correlated with the degree of demyelination in auditory and peripheral motor nerves, temporal resolution testing could be performed as an additional marker for CMT1A.

Virus-mimetic polymer nanoparticles displaying hemagglutinin as an adjuvant-free influenza vaccine.

The generation of virus-mimetic nanoparticles has received much attention in developing a new vaccine for overcoming the limitations of current vaccines. Thus, a method, encompassing most viral features for their size, hydrophobic domain and antigen display, would represent a meaningful direction for the vaccine development. In the present study, a polymer-templated protein nanoball with direction oriented hemagglutinin1 on its surface (H1-NB) was prepared as a new influenza vaccine, exhibiting most of the viral features. Moreover, the concentrations of antigen on the particle surface were controlled, and its effect on immunogenicity was estimated by in vivo studies. Finally, H1-NB efficiently promoted H1-specific immune activation and cross-protective activities, which consequently prevented H1N1 infections in mice.

Intranasal distribution and clearance of thermoreversible gel in an animal model.

BACKGROUND: Poloxamer 407 (P407) has been investigated for an intranasal drug delivery system. However, there is little known about the distribution and clearance of intranasally applied P407. The purpose of this study was to evaluate the distribution and clearance time of P407 in an animal model. METHODS: Five male pigs were administered the experimental solution (18% of P407 with 0.01% of fluorescein) and the control solution (normal saline with 0.01% of fluorescein) into their right and left nasal cavity, respectively. For quantitative analysis, endoscopic images of each nasal cavity were taken immediately and at 10, 20, 30, and 60 minutes after intranasal administration. RESULTS: The experimental group showed a significantly wider distribution of fluorescein than the control group at 10, 20, and 30 minutes. The experimental group also showed a significantly higher mean intensity of fluorescein than the control group at 10, 20, and 30 minutes. The mean intensity in the control group was significantly decreased during 30 minutes but the mean intensity in the experimental group was significantly decreased during 60 minutes. CONCLUSION: A substantial amount of P407 remained in the nasal cavity for at least 30 minutes post-application.

In situ immobilized lipase on the surface of intracellular polyhydroxybutyrate granules: preparation, characterization, and its promising use for the synthesis of fatty acid alkyl esters.

Photobacterium lipolyticum M37 lipase (LipM37) was immobilized on the surface of intracellular polyhydroxybutyrate (PHB) granules in Escherichia coli. LipM37 was genetically fused to Cupriavidus necator PHA synthase (PhaC Cn ), and the engineered PHB operon containing the lip M37 -phaC Cn successfully mediated the accumulation of PHB granules (85 wt.%) inside E. coli cells. The PHB granules were isolated from the crude cell extract, and the immobilized LipM37 was comparable with the free form of LipM37 except for a favorable increase in thermostability. The immobilized LipM37 was used to synthesize oleic acid methyl ester (biodiesel) and oleic acid dodecyl ester (wax ester), and yielded 98.0 % conversion in esterification of oleic acid and dodecanol. It was suggested that the LipM37-PhaCCn fusion protein successfully exhibited bifunctional activities in E. coli and that in situ immobilization of lipase to the intracellular PHB could be a promising approach for expanding the biocatalytic toolbox for industrial chemical synthesis.