Clinic choice of long or short segment pedicle screw-rod fixation in the treatment of thoracolumbar burst fracture: From scan data to numerical study.

Based on computerized tomography scanning images of human lumbar vertebrae, finite element (FE) analysis is performed to predict the stress of pedicle screws, rods, and fractured vertebra as well as the displacement of fractured vertebra after internal fixation treatment of thoracolumbar burst fracture. A three-dimensional FE model of L1-L5 lumbar vertebrae with L3 burst fracture has been established and four fixation methods, namely, short segment cross- and trans-injured vertebrae, long segment cross- and trans-injured vertebrae fixations, have been adopted to perform posterior pedicle fixation. The stress distributions of the screws, rods, and fractured vertebra and the total deformation of the fractured vertebra are investigated under six different physiological motions. From the view of the stress on the screw-rod system and the deformation of the fractured vertebral body, the long segment cross-injured vertebra fixation has the best mechanical performance, followed by the long segment trans-injured vertebra fixation, and then the short segment fixation trans-injured vertebra. The short segment fixation cross-injured vertebra performs the worst. Among the six motions, the forward flexion movement has the greatest impact on the screw-rod system and the fractured vertebra. However, the rotation motion greatly affects the stress of the screw in the long segment fixation. This indicates that the longer the fixed segment is, the more susceptible it is to human rotation. Thus, for patients with severe fracture, the long segment cross-injured vertebra is preferred. On the contrary, the short segment trans-injured vertebra fixation is optimal.

Chemical constituents of Viscum coloratum (Kom.) Nakai and their cytotoxic activities.

A new diarylheptanoid, (1 R,2S,3S,5S)-2,3-dihydroxy-3',3''-dimethoxy-4'-de-O-methylcentrolobine (1) and a new bisabolane-type sesquiterpenoid, (1 R,7S)-1,12,13-trihydroxybisabola-3,10-diene (2), together with nineteen known compounds (3-21) were isolated from the EtOH extract of the stems and branches of Viscum coloratum (Kom.) Nakai. Their structures were elucidated by extensive analysis of 1 D and 2 D NMR spectra and from the HRESIMS. All the compounds were evaluated for their cytotoxic activity against eight human tumor cell lines.

Polydopamine-based nanospheres as nanoplatforms to kill Staphylococcus aureus and to promote wound healing by photothermal therapy.

Bacterial infections have always been a threat when it comes to public health accounting for increased morbidity and mortality rates around the world. For the first time, Polydopamine is often used as an ocular surface drug delivery medium to treat some ocular surface diseases based on its good tissue affinity. Mesoporous polydopamine nanospheres (MPDA NPs) under photothermal therapy (PTT) are demonstrated as efficient therapeutic nanoplatforms for Staphylococcus aureus (S. aureus) infection and wound healing. MPDA NPs were found to exhibit excellent photothermal performance, significantly causing an increase in temperature within a short period of NIR-I exposure (808 nm, 1 W cm-2, 6 min). The MPDA NPs under the NIR irradiation remarkably eliminated S. aureus in vitro. Moreover, these synergistic effects turnouts to be phenomenal in vivo, effectively killing and healing S. aureus-infected abscesses in mice. These revealed the combined effect of the intrinsic antibacterial activity of MPDA NPs enhanced upon NIR-I exposure. Hence, MPDA NPs under NIR-I could prove excellent therapeutic nanoplatforms for bacteria-related infections and other biomedical applications.

SPARC Levels Modulate the Capacity of Mitomycin to Inhibit the Proliferation of Human Tenon's Capsule Fibroblasts.

PURPOSE: To evaluate the role of SPARC in the antiproliferation effect of MMC on human Tenon's fibroblasts (HTF). METHOD: Sixteen PACG patients aged 59 ± 10 years (31-72 years), including 6 males and 10 females, were recruited. Tenon tissue was harvested during filtering surgery. Cell density was evaluated after MMC application with different concentrations and application times, by which the optimized MMC application modality was determined. MMC, si-SPARC, or SPARC protein was used when needed to evaluate the cell densities under different conditions, by which the role of SPARC in MMC-mediated antifibrotic process was identified. RESULTS: Considering that the cell densities, as well as SPARC expression on mRNA and protein levels, are relatively stable when the MMC concentration is higher than 0.02% and exposure time longer than 90 s, we chose the MMC application pattern with 0.02% and 90 s as an optimized pattern for the downstream work. Compared to control, the si-SPARC and MMC downregulated the SPARC protein by 91% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (P < 0.01) and 65% (. CONCLUSION: This study demonstrates that in HTF, (1) MMC downregulates the expression of SPARC in protein and mRNA levels; (2) SPARC depletion has synergistic effect on the antifibrotic effect of MMC; and (3) reactive oxygen species are the possible mediator in the antifibrotic effect of MMC and si-SPARC.

A novel lipid prodrug strategy for sustained delivery of hexadecyloxypropyl 9-[2-(phosphonomethoxy)ethyl]guanine (HDP-PMEG) on unwanted ocular proliferation.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease and there is no effective pharmacological measure to prevent PVR development. The difficulty comes from lack of potent antiproliferative agent and lack of sustained delivery to cover high-risk time window for PVR to develop. Lipid prodrug of PMEG, hexadecyloxypropyl 9-[(2-phosphonomethoxy)ethyl]guanine (HDP-PMEG), was prepared and was evaluated as a pharmacological adjuvant to surgical management of PVR. A dose-escalation study determined that the highest nontoxic dose for intravitreal use in pigmented rabbits was 3 µg per eye. The genotoxicity of HDP-PMEG was harnessed as a perioperative preventative measure against PVR in a rabbit eye model while the sustained intravitreal pharmacological effect was evaluated on a laser-induced fibrovascular model in rat eye. After intravitreal 3 µg, HDP-PMEG particles in the rabbit vitreous was visible for at least 6 weeks. A single 50-min intravitreal infusion of HDP-PMEG demonstrated significant inhibition of PVR formation when compared with the eyes infused with only BSS (BSS vs. HDP-PMEG: estimate = 1.14, OR = 3.1, p = .027). A single intravitreal 104 ng (equivalent to 3 µg for rabbit eye) of HDP-PMEG significantly inhibit laser-induced fibrovascular proliferation in rat eye by 55% (least square mean pixel, BSS = 4763569.5 vs. HDP-PMEG = 2148129.7, p < .0001, generalized estimating equation [GEE]). Retinal fluorescein angiography showed the odds for BSS intervened eyes to have higher-rated FA leaking grades were 38.5 times compared with HDP-PMEG treated eyes (p < .0001, GEE). Our study results indicate that single intravitreal HDP-PMEG may be a promising ocular drug delivery as a perioperative intervention to prevent PVR reoccurrence following primary surgical management.

Relation of Serum and Vitreous Concentrations of Fetuin-A with Diabetic Retinopathy.

BACKGROUND: Fetuin-A, a liver-derived glycoprotein, is correlated with diabetes. The aim of the present investigation was to evaluate serum and vitreous concentrations of fetuin-A in patients with diabetic retinopathy (DR). MATERIAL AND METHODS: We randomly selected 224 diabetic patients and 68 control subjects for this study. RESULTS :There were markedly higher serum and vitreous fetuin-A concentrations in proliferative diabetic retinopathy (PDR) patients than in the other three groups. NPDR patients exhibited elevated vitreous fetuin-A concentrations compared with patients without DR. However, no significant differences in serum fetuin-A concentrations were observed between NPDR patients and patients without DR. In addition, there were significantly lower concentrations of serum and vitreous fetuin-A in control subjects compared with the other three groups. CONCLUSIONS: The occurrence and severity of DR is correlated with serum and vitreous fetuin-A concentrations.

[Characteristic of ocular safety profile of triamcinolone made in China].

OBJECTIVE: To characterize the safety profile of triamcinolone acetonide made in China (Transton) and triamcinolone acetonide acetate (Tongyong) for their ocular application. METHODS: Experimental study. In vitro cell viability assay was performed on 3 types of human ocular cells to evaluate the cytotoxicity of the simulated vitreal concentrations (from a 1:15 dilution as if injected into 1.5 ml of rabbit vitreous to 1:50 dilution as if injected into 5 ml of human vitreous) of Transton and Tongyong using MTT method.In vivo 28 guinea pigs, randomly divided into four groups, were used for evaluating either intravitreal 6 µl of the two types of triamcinolone suspension or 18 µl of their supernatant. Following the injections, the eyes were monitored by biomicroscopy, ophthalmoscopy, tonometry, electroretinography, and histology. The Dunnett's test was used to analyze in vitro cell viability. Paired sample t-test and Generalized Estimating Equations (GEE) were respectively used to compare electroretinography data and intraocular pressure between experimental eyes and the control eyes. RESULTS: The undiluted supernatant of Transton and Tongyong was toxic to human scleral fibroblasts when compared with their control groups (MTT values = 0.046 ± 0.036 and 0.044 ± 0.05 versus 0.367 ± 0.106 and 0.413 ± 0.128) (P < 0.01) or with the BSS group (0.368 ± 0.106 and 0.441 ± 0.137) (P < 0.01). 1:15 or greater dilution of supernatant of Transton and Tongyong did not show cytotoxicity on cultured human retinal pigment epithelium cells or Müller cell (P > 0.05), but 1:15 dilution of Tongyong supernatant showed cytotoxicity on the Müller cells (MTT value = 0.366 ± 0.062 versus 0.417 ± 0.042 for BSS) (P = 0.03). In vivo, neither intravitreal 6 µl (0.25 mg, equivalent to 4 mg in 0.1 ml for human eyes) of the suspension nor 18 µl (equivalent resultant preservative concentration to intravitreal 4 mg in 0.1 ml for rabbit eyes) of the supernatant of Transton and Tongyong showed ocular toxicity. CONCLUSION: The equivalent dose (6 µl) to 4 mg in 0.1 ml intravitreal suspension for human eye or equivalent resultant preservative concentration to 0.1 ml intravitreal suspension for rabbit eye is found safe in guinea pig eyes.

Different intravitreal properties of three triamcinolone formulations and their possible impact on retina practice.

PURPOSE: We sought to better characterize the intravitreal profile of different triamcinolone formulations. METHODS: The study was performed in vitro and in vivo. Kenalog-40, Triesence, and Transton were characterized for ocular pharmacokinetics, particle size, crystallinity, and dissolving kinetics in vitreous following an intravitreal injection into 12 rabbit eyes. The relationship of free drug levels in the aqueous and vitreous was investigated through a dual-probe microdialysis and liquid chromatography tandem mass spectrometry. RESULTS: Triesence had the most uniform particle size distribution (mean 11.51 µm) and Kenalog-40 had the largest particle sizes (mean 18.86 µm). Triesence and Kenalog-40 had 100% crystallinity, while Transton had 89% crystallinity. Triesence had a slower dissolution in vitreous than that of Kenalog-40, and Transton had the fastest dissolution, though their solubility was very similar. Following a 1.2 mg intravitreal injection in the rabbit eye, Triesence had a significantly lower ocular free drug level than Kenolog-40 (P = 0.025) and Transton (P = 0.007). Quantitative dual-probe microdialysis revealed that the aqueous free triamcinolone (Kenolog-40) was less than 1% of the vitreous free triamcinolone during the first few hours, and this percentage increased to 26.8% at 2 weeks and was 11.7% at 3 weeks following an intravitreal injection. CONCLUSIONS: Triesence demonstrated a significantly slower dissolution profile and lower free drug level in the vitreous than the other preserved triamcinolone, which may translate into a longer therapeutic duration and lower rate of drug-associated complications.

Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.

Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.

Can graphene oxide cause damage to eyesight?

As graphene becomes one of the most exciting candidates for multifunctional biomedical applications, contact between eyes and graphene-based materials is inevitable. On the other hand, eyes, as a special organ in the human body, have unique advantages to be used for testing new biomedical research and development, such as drug delivery. Intraocular biocompatible studies on graphene-related materials are thus essential. Here, we report our recent studies on intraocular biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in vivo. The successful preparation of GO nanosheets was confirmed using atomic force microscopy, contact angle analyzer, Fourier transform infrared spectroscopy, and Raman spectroscopy. The influence of GO on human retinal pigment epithelium (RPE) cells in terms of the cell morphology, viability, membrane integrity, and apoptosis was investigated using various techniques, including optical micrography, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little influence on cell morphology, but the change was visible after long-time culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO solutions and less than 8% LDH release, although a small amount of apoptosis (1.5%) was observed. In vitro results suggested good biocompatibility of GO to RPE cells with slight adverse influence, on the cell viability and morphology in long-time periods, along with aggregation of GO. Thus, some further studies are needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected eyes showed few changes in eyeball appearance, intraocular pressure (IOP), eyesight, and histological photos. Our results suggested that GO did not cause any significant toxicity to the cell growth and proliferation. Intravitreal injection of GO into rabbits' eyes did not lead to much change in the eyeball appearance, IOP, electroretinogram, and histological examination.

Further characterization of ocular safety profile of commercially available preserved and preservative-free triamcinolone acetonide.

PURPOSE: To characterize the safety profile of triamcinolone acetonide (TA) for intraocular application. METHODS: In vitro cell viability assay was performed on 2 types of human ocular cells to evaluate the cytotoxicity of the simulated different vitreal concentrations (from a 1:15 dilution as if injected into 1.5 mL of rabbit vitreous to 1:50 dilution as if injected into 5 mL of human vitreous) of preservative and excipient (supernatant) from Kenalog-40. In vivo 35 guinea pigs were used for evaluating either a dose of intravitreal triamcinolone acetonide (Kenalog-40 and Triesence) or the supernatant of Kenalog-40. The animal eyes were monitored by biomicroscopy, ophthalmoscopy, tonometry, electroretinography, and histology. RESULTS: A ≥ 1:15 dilution of triamcinolone acetonide supernatant from Kenalog-40 did not show cytotoxicity on cultured human pigment epithelial (retinal pigment epithelium) cells or Müller cells. In vivo, neither intravitreal 6 µL (0.248 mg, equivalent to 4 mg in 0.1 mL for human eyes) nor 18 µL (0.744 mg, equivalent to 4 mg in 0.1 mL for rabbit eyes and equivalent to 12 mg in 0.1 mL for human eyes) of triamcinolone acetonide suspension showed ocular toxicity. No significant difference was noted between Kenalog-40 and Triesence clinically and histopathologically. CONCLUSION: The equivalent triamcinolone acetonide doses to 0.1 mL (4 or 12 mg) intravitreal injection for human eye were found safe in guinea pig eyes. No significant difference was noted for 0.1 mL intravitreal injection between Kenalog-40 and Triesence.

[Differential expression and significance of complement C4b and transthyretin in proliferative vitreoretinopathy].

OBJECTIVE: To investigate the differential expression of complement C4b and transthyretin in proliferative vitreoretinopathy (PVR). METHODS: It was a controlled experimental study. Human vitreous samples of 5 patients with PVR were analyzed by using two-dimensional gel electrophoresis and mass spectrometry, and the results were compared with those from normal control vitreous obtained from donor eyes. An in vivo model of PVR was created by intravitreous injection of cultured rabbit retinal pigment epithelial (RPE) cells. The vitreous of PVR models were analyzed by enzyme linked immunosorbent assay (ELISA) to confirm the proteomic results from the PVR patients. RESULTS: Seventy nine various proteins were expressed differently between PVR and normal vitreous, among which nine up-regulated proteins including complement C4b, transthyretin (TTR), and 7 albumins were identified by mass spectrometry. The up-regulation of complement C4b and TTR in PVR patients was also confirmed by ELISA. The concentration of complement C4b and TTR in normal vitreous were (20.18 ± 1.97) mg/L and (88.58 ± 8.84) mg/L respectively, in PVR patients were (38.1 ± 5.79) mg/L and (112.57 ± 6.89) mg/L respectively, difference significantly between these two groups (C4b: t = 11.54, TTR:t = 9.24; P < 0.05). CONCLUSIONS: Differences of complement C4b and TTR expression were observed between PVR and normal vitreous. These results have lead to the assumption that there is a connection between elevated concentrations of both complement C4b and TTR and the pathogenesis of PVR and further studies on the functions of these proteins are required.

Antiproliferative property of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) for unwanted ocular proliferation.

PURPOSE: To investigate the safety and inhibitory effects of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) on ocular cell proliferation and collagen matrix contraction. METHODS: For the antiproliferation studies, various ocular cell monolayers were exposed to HDP-PMEG, PMEG, 5-fluorouracil (5-FU), and daunorubicin (DNB). For the collagen contraction studies, retinal pigment epithelium (RPE) cells seeded onto type I collagen lattices were exposed for a single 5- or 50-min period to various concentrations of HDP-PMEG or 5-FU. For the cytotoxicity study, trypan blue exclusion tests were performed using a human Müller cell line. Cytotoxicity was determined up to 4 days after treatment. RESULTS: The proliferation of RPE cells, scleral fibroblasts, vessel endothelial cells, and ocular melanoma cells can all be significantly inhibited by HDP-PMEG. Its inhibitory effects on those cells were uniformly stronger than that of 5-FU. Contraction of the collagen matrix containing RPE cells was significantly inhibited by HDP-PMEG and by 5-FU at concentrations of 20 µM and 2,000 µM, respectively, as compared with controls (p<0.05). The safety profile of HDP-PMEG was significantly better than 5-FU and daunorubicin. The ocular therapeutic index is 1,100 for HDP-PMEG, 17.2 for 5-FU, and 1.25 for daunorubicin. CONCLUSIONS: HDP-PMEG possesses a significant inhibitory effect on the proliferation of RPE, retinal glial cells, scleral fibroblasts, and ocular melanoma cells. HDP-PMEG is also genotoxic and may be used as a single short application for the modulation of unwanted ocular proliferation.