Twelve Tips for Inclusive Practice in Healthcare Settings.

This paper outlines practical tips for inclusive healthcare practice and service delivery, covering diversity aspects and intersectionality. A team with wide-ranging lived experiences from a national public health association's diversity, equity, and inclusion group compiled the tips, which were reiteratively discussed and refined. The final twelve tips were selected for practical and broad applicability. The twelve chosen tips are: (a) beware of assumptions and stereotypes, (b) replace labels with appropriate terminology, (c) use inclusive language, (d) ensure inclusivity in physical space, (e) use inclusive signage, (f) ensure appropriate communication methods, (g) adopt a strength-based approach, (h) ensure inclusivity in research, (i) expand the scope of inclusive healthcare delivery, (j) advocate for inclusivity, (k) self-educate on diversity in all its forms, and (l) build individual and institutional commitments. The twelve tips are applicable across many aspects of diversity, providing a practical guide for all healthcare workers (HCWs) and students to improve practices. These tips guide healthcare facilities and HCWs in improving patient-centered care, especially for those who are often overlooked in mainstream service provision.

A Review of Nanomaterials with Different Dimensions as Lubricant Additives.

Lubricant additives can effectively enhance the performance and environmental adaptability of lubricants and reduce the energy loss and machine wear caused by friction. Nanomaterials, as important additive materials, have an essential role in the research and development of new lubricants, whose lubrication performances and mechanisms are not only related to their physical and chemical properties, but also influenced by the geometric shape. In this paper, the friction reduction and antiwear performances of nanomaterials as lubricant additives are first reviewed according to the classification of the dimensions, and their lubrication mechanisms and influence rules are revealed. Second, the recent research progress of composite nanomaterials as lubrication additives is introduced, focusing on their synergistic mechanism to improve the lubrication performance further. Finally, we briefly discuss the challenges faced by nanoadditives and provide an outlook on future research. The review expects to provide new ideas for the selection and development of lubricant additives to expand the application of nanoadditives.

Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium.

Metformin is a traditional anti-hyperglycemic medication that has recently been shown to benefit vascular complications of diabetes via an anti-inflammatory mechanism other than glycemic control. This study aims to test the hypothesis that metformin suppresses diabetic retinopathy (DR) associated intraocular inflammation. Human vitreous from control and proliferative diabetic retinopathy (PDR) patients with or without long-term metformin treatment (> 5 years) were collected for multiple inflammatory cytokines measurements with a cytokine array kit. The vast majority of the measurable cytokines in PDR vitreous has a lower level in metformin group than non-metformin group. Although the p values are not significant due to a relatively small sample size and large deviations, the 95% confidence interval (CI) for the mean difference between the two groups shows some difference in the true values should not be neglected. Using quantitative ELISA, soluble intercellular adhesion molecule -1 (ICAM-1) and monocyte chemoattractant protein -1 (MCP-1) presented with significantly lower concentrations in metformin group versus non-metformin group. Metformin group also has significantly less up-regulated cytokines and diminished positive correlations among the cytokines when compared to non-metformin group. Possible role of AMP-activated protein kinase (AMPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in metformin's anti-inflammatory effects were studied in human retinal vascular endothelial cells (hRVECs) cultured in normal glucose (NG) and high glucose (HG) conditions. Metformin inhibited HG-induced ICAM-1, IL-8, and MCP-1 via AMPK activation, whereas pharmacological AMPK inhibition had no effect on its inhibition of NF-κB p65, sICAM-1, and tumor necrosis factor-α (TNF-α). Metformin-induced suppression of the inflammatory cytokines could also be mediated through its direct inhibition of NF-κB, independent of AMPK pathway. This is a proof-of-concept study that found metformin treatment was associated with reduced inflammatory responses in vitreous of diabetes patients and retinal vascular endothelial cells, supporting the rationale for using metformin to treat DR at an early stage.

Investigation into Friction and Wear Characteristics of 316L Stainless-Steel Wire at High Temperature.

The damping performance of metal rubber is highly correlated with the tribological properties of the internal metal wires. In this paper, the friction and wear characteristics of 316L stainless-steel wire are investigated under different temperatures, loads, crossing angles, and working strokes. Results show that the friction coefficient increases from 0.415 to 0.635 and the wear depth increases from 34 µm to 51 µm, with the temperature rising from 20 °C to 400 °C. High temperature will soften metal materials and promote the oxidation of metal. Softened materials can be easily sheared and removed under friction action, resulting in high wear depth. However, when a continuous oxide film with high hardness is formed under higher temperature, the oxide film can work as a wear-resisting layer to prevent further wear of the wire to a certain degree. At the same temperature, the loads, crossing angles, and working strokes change the wear resistance by affecting the surface stress, debris removal efficiency, etc., and high temperature will aggravate this change. The results pave the way for the design and selection of materials for high-temperature metal rubber components.

Association of Metformin Treatment with Reduced Severity of Diabetic Retinopathy in Type 2 Diabetic Patients.

PURPOSE: To evaluate effects of long-term metformin on the severity of diabetic retinopathy (DR) in high-risk type 2 diabetic (T2D) patients. METHODS: A retrospective chart review study was conducted involving 335 DR patients with T2D ≥ 15 years from 1990 to 2013. The severity of DR was determined by Early Treatment Diabetic Retinopathy Study scale. The associations between metformin and DR severity were evaluated. Comparison with stratification for the use of sulfonylurea and insulin was performed to identify possible confounding effects. RESULTS: Severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy (SNPDR/PDR) was more often diagnosed in nonmetformin users (67/142, 47%) versus metformin users (48/193, 25%) (p < 0.001), regardless of gender and race of the patients. The odds ratio of metformin associated with SNPDR/PDR was 0.37 in all cases (p < 0.001), 0.35 in sulfonylurea use cohort (p < 0.05), 0.45 in nonsulfonylurea use cohorts (p < 0.01), and 0.42 in insulin use cohort (p < 0.01). Insulin users had a higher rate of SNPDR/PDR. Metformin had no influence on the occurrence of clinical significant diabetic macular edema. CONCLUSIONS: Long-term use of metformin is independently associated with a significant lower rate of SNPDR/PDR in patients with type 2 diabetes ≥ 15 years.

APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats.

APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebral artery occlusion (MCAo) and treated with either PBS or APX3330 (10mg/kg, oral gavage) starting at 24h after MCAo, and daily for 14 days. Rats were sacrificed at 14 days after MCAo and, blood brain barrier (BBB) permeability, ischemic lesion volume, immunohistochemistry, cell death assay, Western blot, real time PCR, and angiogenic ELISA array were performed. Compared to PBS treatment, APX3330 treatment of stroke in T1DM rats significantly improves neurological functional outcome, decreases lesion volume, and improves BBB integrity as well as decreases total vessel density and VEGF expression, while significantly increases arterial density in the ischemic border zone (IBZ). APX3330 significantly increases myelin density, oligodendrocyte number, oligodendrocyte progenitor cell number, synaptic protein expression, and induces M2 macrophage polarization in the IBZ of T1DM stroke rats. Compared to PBS treatment, APX3330 treatment significantly decreases plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 and matrix metalloproteinase 9 (MMP9) and receptor for advanced glycation endproducts expression in the ischemic brain of T1DM stroke rats. APX3330 treatment significantly decreases cell death and MMP9 and PAI-1 gene expression in cultured primary cortical neurons subjected to high glucose and oxygen glucose deprivation, compared to untreated control cells. APX3330 treatment increases M2 macrophage polarization and decreases inflammatory factor expression in the ischemic brain as well as promotes neuroprotective and neurorestorative effects after stroke in T1DM rats.

Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo.

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p<0.05). Several inflammatory molecules upregulated by tumor necrosis factor-α in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFκB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8). Further, metformin significantly decreased retinal leukocyte adhesion (p<0.05) in streptozotocin-induced diabetic mice. Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFκB p65 and IL-8. Our findings support the notion that metformin has considerable anti-angiogenic and anti-inflammatory effects on retinal vasculature. Metformin could be potentially used for the purpose of treating diabetic retinopathy in addition to blood glucose control in diabetic patients.

Modeling the response of a quartz crystal microbalance under nanoscale confinement and slip boundary conditions.

Nanorheology and boundary slip play an important role in the micro/nanofluidics, and micro/nano-electromechanical systems, especially for research on DNA, proteins and polymers. Herein, a nanoscale confinement structure, called a nanocell, is established by assembling a parallel plate on the quartz crystal microbalance (QCM) chip to study the nanorheology of liquids and the boundary slip on the interface. The corresponding analytical models are established and verified experimentally with high consistency. We reveal that the responses of QCM with the nanocell assembled are dependent on the nanocell confinement thickness, the acoustic impedance of the nanocell lid (parallel plate), as well as the boundary slip on the interface. A critical influence thickness of the assembled nanocell d = 2δ is indicated, above which the assembly of a nanocell has no influence on the QCM response. And the interfacial boundary slip results in obvious decreases of relative frequency shift and relative half-bandwidth variation. We find that adopting a nanocell lid with the same acoustic impedance as the tested liquids will evidently simplify the experimental analysis. In the paper, the nanocell provides an effective method to investigate the nanorheology of confined liquids and the interfacial boundary slip, and the established models offer a theoretical basis for the analysis of the nanocell-assembled QCM response.

Intraocular penetration of systemic antibiotics in eyes with penetrating ocular injury.

PURPOSE: To determine whether penetrating scleral or corneal injury can enhance intraocular penetration of systemic moxifloxacin, vancomycin, and ceftazidime. METHODS: Thirty rabbits were divided into 3 groups for each antibiotic and then further subdivided to receive either scleral or corneal injury to the right eye. The left eye served as a control. Intravenous antibiotics were given following injury, and eyes were subsequently enucleated. Vitreous antibiotic concentration was determined by high-performance liquid chromatography analysis. Plasma concentration was measured for comparison. RESULTS: Intravitreal moxifloxacin concentration was unchanged by injury. Minimum inhibitory concentration (MIC90) was achieved in the vitreous against the most common gram-positive endophthalmitis-causing organisms. Intravitreal vancomycin levels were not enhanced by injury and did not reach the MIC90 for gram-positive organisms commonly causing intraocular infection. Intravitreal ceftazidime was increased in the injured eyes, 67% and 73% higher in scleral and corneal injury eyes. It reached MIC90 of many gram-negative bacteria. CONCLUSIONS: Intravitreal antibiotic penetration of systemic antibiotics with or without penetrating ocular injury varies depending on the antibiotic. For prevention or treatment of gram-positive-bacteria-causing endophthalmitis, intravitreal vancomycin is necessary and provides the most reliable coverage. Systemic ceftazidime can be used for many gram-negative bacteria, but intravitreal injection is recommended for better coverage, especially for more-potent organisms. Systemic moxifloxacin can be considered for most gram-positive and -negative infections due to its excellent intraocular penetration and broad coverage, but the patient's previous history of its topical use and increasing resistance patterns must be considered.

Suppression of choroidal neovascularization through inhibition of APE1/Ref-1 redox activity.

PURPOSE: The redox function of APE1/Ref-1 is a key regulator in pathological angiogenesis, such as retinal neovascularization and tumor growth. In this study, we examined whether inhibition of APE1/Ref-1 redox function by a small molecule inhibitor E3330 suppresses experimental choroidal neovascularization (CNV) in vitro and in vivo. METHODS: Primate choroid endothelial cells (CECs) received treatment of 0 to 100 µM E3330 alone or cotreatment of E3330 and 500 µg/mL anti-VEGF antibody bevacizumab. Choroid endothelial cell angiogenic function was examined by cell proliferation, migration, and tube formation assays. The effects of E3330 on NF-κB and STAT3 signaling pathways were determined by reporter gene assay, Western blot, and ELISA. Laser-induced CNV mouse model was used to test the effects of E3330 in vivo. Potential toxicity of E3330 was evaluated by TUNEL assay. RESULTS: The E3330 of 25 to 100 µM dose-dependently suppressed CEC proliferation, migration, and tube formation, in the absence of noticeable cell toxicity. Lower doses of E3330 (10-20 µM) reduced the transcriptional activity of NF-κB and STAT3 without affecting protein phosphorylation of both molecules. At the same time, E3330 downregulated MCP-1 production in CECs. The antiangiogenic effect of E3330 was comparable and additive to bevacizumab. The E3330 effectively attenuated the progression of laser-induced CNV in mice after a single intravitreal injection. CONCLUSIONS: The APE1/Ref-1 redox function regulates multiple transcription factors and inflammatory molecules, and is essential for CEC angiogenesis. Specific inhibition of APE1/Ref-1 redox function with E3330 may represent a promising novel treatment for wet AMD.

Inhibition of APE1/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo.

This study examines the role of APE1/Ref-1 in the retina and its potential as a therapeutic target for inhibiting retinal angiogenesis. APE1/Ref-1 expression was quantified by Western blot. The role of APE1/Ref-1 redox function in endothelial cell in vitro angiogenesis was examined by treating retinal vascular endothelial cells (RVECs) with APX3330, a small molecule inhibitor of APE1/Ref-1 redox activity. In vitro methods included a proliferation assay, a transwell migration assay, a Matrigel tube formation assay, and a Real-Time Cell Analysis (RTCA) using the xCELLigence System. In vivo functional studies of APE1/Ref-1 were carried out by treating very low density lipoprotein (VLDL) receptor knockout mice (Vldlr(-/-)) with intravitreal injection of APX3330, and subsequent measurement of retinal angiomatous proliferation (RAP)-like neovascularization for one week. APE1/Ref-1 was highly expressed in the retina and in RVECs and pericytes in mice. APX3330 (1-10 µM) inhibited proliferation, migration and tube formation of RVECs in vitro in a dose-dependent manner. Vldlr(-/-) RVECs were more sensitive to APX3330 than wild-type RVECs. In Vldlr(-/-) mice, a single intravitreal injection of APX3330 at the onset of RAP-like neovascularization significantly reduced RAP-like neovascularization development. APE1/Ref-1 is expressed in retinal vascular cells. APX3330 inhibits RVEC angiogenesis in vitro and significantly reduces RAP-like neovascularization in Vldlr(-/-) mice. These data support the conclusion that APE1/Ref-1 redox function is required for retinal angiogenesis. Thus, APE1/Ref-1 may have potential as a therapeutic target for treating neovascular age-related macular degeneration and other neovascular diseases.

Loss of VLDL receptor activates retinal vascular endothelial cells and promotes angiogenesis.

PURPOSE: The very low-density lipoprotein receptor (VLDLR) knockout (vldlr(-/-)) mouse has been identified as a model for retinal angiomatous proliferation with subretinal neovascularization (SNV) evolving from retinal vessels. The effects of VLDLR on the angiogenic functions of retinal vascular endothelial cells (RVECs) in vivo and in vitro were examined. METHODS: Immunofluorescent staining of markers for activated endothelial cells was performed with CD105 and CD106 antibodies. Proliferation, tube formation, and migration assays were carried out in RVECs isolated from wild-type and vldlr(-/-) mice to assess the angiogenic functions in vitro. The effect of VLDLR blockage on wild-type RVEC proliferation was also examined. RESULTS: The expression of CD105 and CD106 was significantly upregulated in the retinas of adult vldlr(-/-) mice, especially at lesion sites. An intense CD105 signal was found in the inner retinas of vldlr(-/-) mice starting at postnatal day 14, before the onset of SNV. In vitro proliferation assays revealed a significantly enhanced (approximately 20%-100%) growth rate in vldlr(-/-) RVECs compared with that in the wild-type RVECs. The formation of capillary-like structures in vldlr(-/-) RVECs was approximately 3 to 11 times greater than in wild-type RVECs. Migration of vldlr(-/-) RVECs was 1.3 to 3.7 times that of wild-type. VLDLR blockage using a receptor-associated protein or neutralizing anti-VLDLR antibodies significantly enhanced the proliferation rate in wild-type RVECs by more than 200% and 30%, respectively. CONCLUSIONS: VLDLR is a potent endogenous inhibitor that negatively regulates the angiogenic properties of RVECs. Loss of VLDLR activates RVECs and significantly enhances angiogenesis in vivo and in vitro.

Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1.

The DNA base excision-repair pathway is responsible for the repair of DNA damage caused by oxidation/alkylation and protects cells against the effects of endogenous and exogenous agents. Removal of the damaged base creates a baseless (AP) site. AP endonuclease1 (Ape1) acts on this site to continue the BER-pathway repair. Failure to repair baseless sites leads to DNA strand breaks and cytotoxicity. In addition to the repair role of Ape1, it also functions as a major redox-signaling factor to reduce and activate transcription factors such as AP1, p53, HIF-1alpha, and others that control the expression of genes important for cell survival and cancer promotion and progression. Thus, the Ape1 protein interacts with proteins involved in DNA repair, growth-signaling pathways, and pathways involved in tumor promotion and progression. Although knockdown studies with siRNA have been informative in studying the role of Ape1 in both normal and cancer cells, knocking down Ape1 does not reveal the individual role of the redox or repair functions of Ape1. The identification of small-molecule inhibitors of specific Ape1 functions is critical for mechanistic studies and translational applications. Here we discuss small-molecule inhibition of Ape1 redox and its effect on both cancer and endothelial cells.

Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model's retinal angiomatous proliferation.

PURPOSE: Very-low-density lipoprotein receptor (VLDLR) in knockout mice (vldlr(-/-)) has been reported to induce subretinal neovascularization. Therefore, VLDLR expression in the wild-type mouse retina was investigated and the retinal angiogenic process in vldlr(-/-) mice was characterized. METHODS: VLDLR expression in the retina and in purified retinal vascular endothelial cells (RECs) and retinal pigment epithelial (RPE) cells was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Angiogenic evolution in vldlr(-/-) mice was examined by fundus fluorescein angiography, histology, double-staining of FITC-dextran perfusion and elastin immunohistochemistry, isolectin staining, and confocal fluorescence microscopy. RESULTS: VLDLR mRNA was detected in the wild-type mouse retina and in purified RECs and RPE cells. The VLDLR protein was localized in the RPE layer, vessels in the ganglion cell layer, and around the outer limiting membrane of the retina. The retinal pathogenic process in vldlr(-/-) mice recapitulates key features of retinal angiomatous proliferation (RAP) in humans, a subtype of neovascular age-related macular degeneration (AMD). These include neovascular growth originating from retinal vessels and progressing to the subretinal space with intraretinal, subretinal, and choroidal angiogenic stages, RPE disruption and Bruch membrane exposure, retinal-choroidal anastomosis, subsequent photoreceptor degeneration, RPE hyperplasia, and subretinal fibrosis at the end stage. CONCLUSIONS: VLDLR is expressed in the wild-type mouse retina, especially in RECs and RPE cells. The vldlr(-/-) mouse exhibits histologic and angiographic characteristics of RAP and is a reproducible animal model facilitating studies of the molecular mechanisms of RAP.

Differential regulation of glutamate receptor-mediated BDNF mRNA expression in the cerebellum and its defects in stargazer mice.

Activity-dependent regulation of BDNF expression plays important roles in synaptic plasticity and neuronal function. We have investigated glutamate receptor-mediated regulation of BDNF expression in the cerebellum of wild-type and stargazer (stg) mice. Both in vivo and in vitro studies revealed that BDNF response kinetics in the cerebellum were much delayed with reversed sensitivity to NMDA versus non-NMDA agonist exposures significantly different from those in the cortex and hippocampus of wild-type mice. In stg mice, the severely impaired BDNF expression was restricted to the cerebellum while responses in the forebrain were intact. A selective failure of BDNF mRNA response to AMPA stimulation, but not NMDA, was evident in cultured stg cerebellar granule cells. These results demonstrate that BDNF expression is differentially regulated with region-specific kinetics. It indicates that the BDNF expression defect in the stg cerebellum is attributable to the AMPA receptor defect caused by the stargazin mutation.

BDNF transgene improves ataxic and motor behaviors in stargazer mice.

The stargazer (stg) mouse exhibits severe cerebellar ataxia, abnormal motor behavior, and absence epilepsy. Selective failure of cerebellar brain-derived neurotrophic factor (BDNF) expression is one of the molecular defects in stg mutant. To determine the in vivo effect of BDNF replacement on cerebellar function, we generated a double mutant line of stg-BDNF mice by crossbreeding BDNF-overexpressing transgenics with stg mutants. Significant upregulation of BDNF mRNA and protein levels was confirmed in the double mutant cerebellum. Gross examination showed less severe ataxia with normal cerebellar cytoarchitecture in stg-BDNF mice than the original stg mice. Behavioral characterization of stg-BDNF mice revealed significantly improved performance in swimming test and footprint analysis compared to stg mice. These results provide in vivo evidence for the correlation of the cerebellar BDNF levels to the ataxia and motor behaviors of stg mice.

Lack of spontaneous ocular neovascularization and attenuated laser-induced choroidal neovascularization in IGF-I overexpression transgenic mice.

Robust IGF-I overexpression induces ocular angiogenesis in mice. To investigate the effect of subtle IGF-I overexpression, we examined the ocular phenotype of IGF-II promoter-driven IGF-I transgenic mice. Despite 2.5-fold elevation of IGF-I mRNA in the retina and 29 and 52% increase of IGF-I protein in the retina and aqueous humor, respectively, no ocular abnormality was observed in these transgenics. This was correlated with unaltered VEGF mRNA levels in the transgenic retina. The transgene was also associated with an attenuated laser-induced choroidal neovascularization. Differential expression levels and pattern of IGF-I gene may underlie the different retinal phenotypes in different transgenic lines.

Stargazin mutation impairs cerebellar synaptogenesis, synaptic maturation and synaptic protein distribution.

Stargazin mutation results in absence epilepsy and cerebellar ataxia in stargazer (stg) mice. We have previously discovered defects of AMPA receptor function, failure of BDNF expression and immature morphology specifically in the cerebellar cortex of stg mice. To further characterize the nature of synaptic abnormalities, we examined the ultrastructure of cerebellar granule cell output synapses and measured the expression levels of several synaptic proteins in different brain regions of stg mutant. Electron microscopic examination revealed a number of immature features in the molecular layer of the mutant cerebellar cortex, including the presence of desmosoid plaques, concentric profiles of parallel fibers, smaller presynaptic terminal and fewer synaptic vesicles. Quantitative measurement showed a significantly lower number of synapses and smaller area of presynaptic terminals in adult stg cerebellum when compared with age-matched wildtype. Immunoblotting analysis of the SNARE proteins revealed selective reduction of the levels of synaptobrevin and synaptophysin in synaptosomes from stg cerebellum. The expression levels of synapsins were not altered in stg cerebellum, but showed a significant upregulation in stg cerebral cortex and hippocampus. Our results suggest that, despite the relatively normal gross morphology of cerebellum, stargazin mutation results in abnormal ultrastructure of cerebellar synapses, and stargazin-induced regional failure of BDNF expression may be responsible for abnormal SNARE protein distribution and partially attributes to the defects in the synaptic ultrastructure.

Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models.

PURPOSE: To determine whether moxifloxacin can be used safely as an intraocular antibiotic, retinal safety of intravitreal moxifloxacin was studied with electroretinography (ERG) and histopathology in animal models. METHODS: Moxifloxacin was injected into mouse eyes at intravitreal concentrations of 5 to 500 microg/mL and into rabbit eyes at 150 microg/mL. As the control, the vehicle was injected into the fellow eyes of each animal. Four weeks after injection, ERG recordings were performed, and animal eyes were processed for histologic examination. RESULTS: ERG studies showed no significant difference between control and moxifloxacin-injected eyes at any dose in either the mouse or rabbit model. Histologic examination revealed no retinal abnormality in mice at 5 to 100 microg/mL or in rabbits at 150 microg/mL intravitreal moxifloxacin. In mice at 500 microg/mL, occasional focal retinal necroses were observed, suggesting isolated retinal toxicity at this concentration of moxifloxacin. CONCLUSIONS: Intravitreal moxifloxacin, up to 100 microg/mL in mice or 150 microg/mL in rabbits, caused no ERG or retinal histologic abnormality. These results indicate that moxifloxacin is a safe intravitreal antibiotic in mouse and rabbit animal models. If proven safe and efficacious by further study in humans, intravitreal injection of moxifloxacin could be considered as an alternative to currently used antibiotics in selected patients with resistance or allergy to the more traditional antibiotics.

Intravitreal voriconazole: an electroretinographic and histopathologic study.

BACKGROUND: Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds. OBJECTIVE: To determine whether voriconazole could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis. METHODS: Retinal toxicity of voriconazole was examined in a rodent animal model. Voriconazole solutions were serially diluted and injected intravitreally into the eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 microg/mL, 10 microg/mL, 25 microg/mL, 50 microg/mL, and 500 microg/mL (n = 3 for each concentration group). Saline was injected into the fellow eyes of all animals as controls. Three weeks after injections, electroretinograms were measured, and eyes were subsequently enucleated for histologic examination. RESULTS: In electroretinographic studies, maximum scotopic b-wave, intensity needed for half saturation, and saturated a-wave amplitude were measured. There was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups. Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25 microg/mL of intravitreal voriconazole. In the eyes with 50 microg/mL and 500 microg/mL of voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 microg/mL of voriconazole. CONCLUSIONS: Our results demonstrate that intravitreal voriconazole of up to 25 microg/mL [corrected] causes no electroretinographic change or histologic abnormality in rat retinas. This indicates that voriconazole is a safe antifungal agent for intravitreal injection in rodents and may be used in the treatment of human fungal endophthalmitis following further study.