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Sample records for corneal damage induced

  1. Ketamine/Xylazine-Induced Corneal Damage in Mice.

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    Demelza Koehn

    Full Text Available We have observed that the commonly used ketamine/xylazine anesthesia mix can induce a focally severe and permanent corneal opacity. The purpose of this study was to establish the clinical and histological features of this deleterious side effect, its sensitivity with respect to age and anesthesia protocol, and approaches for avoiding it.Young C57BL/6J, C57BLKS/J, and SJL/J mice were treated with permutations of anesthesia protocols and compared using slit-lamp exams, optical coherence tomography, histologic analyses, and telemetric measurements of body temperature.Ketamine/xylazine induces corneal damage in mice with a variable frequency. Among 12 experimental cohorts, corneal damage associated with ketamine/xylazine was observed in 9 of them. Despite various treatments to avoid corneal dehydration during anesthesia, the frequency of corneas experiencing damage among responding cohorts was 42% (26% inclusive of all cohorts, which is significantly greater than the natural prevalence (5%. The damage was consistent with band keratopathy. It appeared as a white or gray horizontal band located proximal to the pupil and was positive for subepithelial calcium deposition with von Kossa stain.The sum of our clinical and histological observations is consistent with ketamine/xylazine-induced band keratopathy in mice. This finding is relevant for mouse studies involving the eye and/or vision-dependent behavioral assays, which would both be prone to artifact without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of yohimbine is suggested as a practical means of avoiding this complication.

  2. In vivo and in vitro evaluation of corneal damage induced by 1573 nm laser radiation

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    Courant, D.; Chapel, C. [CEA Fontenay-aux-Roses (DSV/DRR/SRBF), 92 (France). Dept. de Radiobiologie et de Radiopathologie; Pothier, C. [DGA-DCE/CTA/LOT, 94 - Arcueil (France); Sales, N. [CEA Fontenay-aux-Roses (DSV/DRM/SNV), 92 (France)

    2006-07-01

    Recent developments in laser technology have originated a variety of infrared laser sources between 1500-1700 nm called as 'eye-safe' which are gaining widespread use in industry, medicine and military applications. This spectral region has been called 'eye safe' because the cornea and aqueous humor absorb sufficient radiation to prevent nearly all potentially damaging radiation from reaching the retina whereas the lens does not absorb this spectral range and remains undamaged. However, in providing protection for the deeper layers of the eye, the cornea itself is susceptible to thermal damage. Previous studies, performed at 1540 nm with exposures less than 1 s, are inconsistent in the quantity of energy required to cause corneal damage. The purpose of this study was first, to determine the threshold damage exposure (E.D.{sub 50}) on rabbit cornea induced by a 3 ns single pulse emitted at 1573 nm, using clinical observations and histology and to compare the results to the limit values recommended by I.C.N.I.R.P. guidelines or international standards. Secondly, it was suggested to investigate the cellular effects of infrared radiation with biochemical techniques on cell cultures in order to specify a cellular damage threshold and a better understanding of the laser - tissue interaction and the corneal injury. The minimal damage criterion was defined by a shallow, very small depression of the epithelial surface with a mild fluorescein staining. The E.D.{sub 50} obtained with corneal beam diameter of 400 mm is 26.6 J.cm{sup -2}. The corresponding radiant exposure, calculated with the 1 mm aperture diameter recommended by I.C.N.I.R.P. guidelines or standards, is 4.3 J.cm{sup -2}. In vitro experiments have been carried out on primary keratocytes and H.T. 1080 epithelial cell line, using an expanded beam of 3.5 mm diameter on plates or Lab Tek holders. Cells were irradiated with 10 Hz pulse ratio frequency during 1, 2 or 3 s. The S A

  3. The Protective Role of Hyaluronic Acid in Cr(VI-Induced Oxidative Damage in Corneal Epithelial Cells

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    Wei Wu

    2017-01-01

    Full Text Available Cr(VI exposure could produce kinds of intermediates and reactive oxygen species, both of which were related to DNA damage. Hyaluronan (HA has impressive biological functions and was reported to protect corneal epithelial cells against oxidative damage induced by ultraviolet B, benzalkonium chloride, and sodium lauryl sulfate. So the aim of our study was to investigate HA protection on human corneal epithelial (HCE cells against Cr(VI-induced toxic effects. The HCE cell lines were exposed to different concentrations of K2Cr2O7 (1.875, 3.75, 7.5, 15.0, and 30 μM or a combination of K2Cr2O7 and 0.2% HA and incubated with different times (15 min, 30 min, and 60 min. Our data showed that Cr(VI exposure could cause decreased cell viability, increased DNA damage, and ROS generation to the HCE cell lines. But incubation of HA increased HCE cell survival rates and decreased DNA damage and ROS generation induced by Cr(VI in a dose- and time-dependent manner. We report for the first time that HA can protect HCE cells against the toxicity of Cr(VI, indicating that it will be a promising therapeutic agent to corneal injuries caused by Cr(VI.

  4. In vitro ultraviolet–induced damage in human corneal, lens, and retinal pigment epithelial cells

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    Youn, Hyun-Yi; McCanna, David J.; Sivak, Jacob G.; Jones, Lyndon W.

    2011-01-01

    Purpose The purpose was to develop suitable in vitro methods to detect ocular epithelial cell damage when exposed to UV radiation, in an effort to evaluate UV-absorbing ophthalmic biomaterials. Methods Human corneal epithelial cells (HCEC), lens epithelial cells (HLEC), and retinal pigment epithelial cells (ARPE-19) were cultured and Ultraviolet A/Ultraviolet B (UVA/UVB) blocking filters and UVB-only blocking filters were placed between the cells and a UV light source. Cells were irradiated w...

  5. Genoprotective effect of hyaluronic acid against benzalkonium chloride-induced DNA damage in human corneal epithelial cells

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    Wu, Han; Zhang, Huina; Wang, Changjun; Wu, Yihua; Xie, Jiajun; Jin, Xiuming; Yang, Jun

    2011-01-01

    Purpose The aim of this study was to investigate hyaluronic acid (HA) protection on cultured human corneal epithelial cells (HCEs) against benzalkonium chloride (BAC)-induced DNA damage and intracellular reactive oxygen species (ROS) increase. Methods Cells were incubated with different concentrations of BAC with or without the presence of 0.2% HA for 30 min. DNA damage to HCEs was examined by alkaline comet assay and by immunofluorescence microscopic detection of the phosphorylated form of histone variant H2AX (γH2AX) foci. ROS production was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cell apoptosis was determined with annexin V staining by flow cytometry. Results HA significantly reduced BAC-induced DNA damage as indicated by the tail length (TL) and tail moment (TM) of alkaline comet assay and by γH2AX foci formation, respectively. Moreover, HA significantly decreased BAC-induced ROS increase and cell apoptosis. However, exposure to HA alone did not produce any significant change in DNA damage, ROS generation, or cell apoptosis. Conclusions BAC could induce DNA damage and cell apoptosis in HCEs, probably through increasing oxidative stress. Furthermore, HA was an effective protective agent that had antioxidant properties and could decrease DNA damage and cell apoptosis induced by BAC. PMID:22219631

  6. Alterations in corneal nerves following crack cocaine use mimic diabetes-induced nerve damage

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    Whitney L Stuard

    2017-03-01

    Full Text Available The use of in vivo confocal microscopy (IVCM is rapidly emerging as an important clinical tool to evaluate changes in corneal sensory nerves as a surrogate measure for diabetic peripheral neuropathy. Commonly used metrics to document and grade the severity of diabetes and risk for diabetic peripheral neuropathy include nerve fiber length, density, branching and tortuosity. In addition to corneal nerves, thinning of the retinal fiber layer has been shown to correlate with the severity of diabetic disease. Here, we present a case report on a pre-diabetic 60-year-old native American woman with abnormal corneal nerve morphology and retinal nerve fiber layer thinning. Her past medical history was positive for illicit substance abuse. IVCM showed a decrease in nerve fiber density and length, in addition to abnormally high levels of tortuosity. OCT revealed focal areas of reduced retinal nerve fiber layer thickness that were asymmetric between eyes. This is the first report of abnormally high levels of tortuosity in the corneal sub-basal nerve plexus in a patient with a past history of cocaine abuse. It also demonstrates, for the first time, that illicit substance abuse can have long-term adverse effects on ocular nerves for years following discontinued use of the drug. Studies using IVCM to evaluate changes in corneal nerve morphology in patients with diabetes need to consider a past history of illicit drug use as an exclusionary measure.

  7. Brm inhibits the proliferative response of keratinocytes and corneal epithelial cells to ultraviolet radiation-induced damage.

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    Nur Mohammad Monsur Hassan

    Full Text Available Ultraviolet radiation (UV from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm-/- mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm-/- mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm-/-, Trp53+/-, and particularly the Brm-/- Trp53+/- mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm-/- Trp53+/+ and Brm-/- Trp53+/- mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm-/- mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis.

  8. Corneal Biomechanical Findings in Contact Lens Induced Corneal Warpage

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    Letafatnejad, Mojgan; Beheshtnejad, Amir Hooshang; Ghaffary, Seyed Reza; Hassanpoor, Narges; Yaseri, Mehdi

    2016-01-01

    Purpose. To evaluate the difference in biomechanical properties between contact lens induced corneal warpage and normal and keratoconic eyes. Method. Prospective observational case control study, where 94 eyes of 47 warpage suspicious and 46 eyes of 23 keratoconic patients were included. Warpage suspected cases were followed until a definite diagnosis was made (warpage, normal, or keratoconus). Results. 44 eyes of 22 patients had contact lens related corneal warpage. 46 eyes of 23 people were diagnosed as nonwarpage normal eyes. 46 eyes of 23 known keratoconus patients were included for comparison. The mean age of the participants was 23.8 ± 3.8 years, and 66.2% of the subjects were female. The demographic and refractive data were not different between warpage and normal groups but were different in the keratoconus group. The biomechanical properties (corneal hysteresis or CH and corneal resistance factor or CRF) were different with the highest value in the warpage group followed by normal and keratoconus groups. CRF was 10.08 ± 1.75, 9.23 ± 1.22, and 7.38 ± 2.14 and CH was 10.21 ± 1.57, 9.59 ± 1.21, and 8.69 ± 2.34 in the warpage, normal, and keratoconus groups, respectively. Conclusion. Corneal biomechanics may be different in people who develop contact lens induced warpage. PMID:27688908

  9. Infectious Keratitis: Secreted Bacterial Proteins That Mediate Corneal Damage

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    Mary E. Marquart

    2013-01-01

    Full Text Available Ocular bacterial infections are universally treated with antibiotics, which can eliminate the organism but cannot reverse the damage caused by bacterial products already present. The three very common causes of bacterial keratitis—Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae—all produce proteins that directly or indirectly cause damage to the cornea that can result in reduced vision despite antibiotic treatment. Most, but not all, of these proteins are secreted toxins and enzymes that mediate host cell death, degradation of stromal collagen, cleavage of host cell surface molecules, or induction of a damaging inflammatory response. Studies of these bacterial pathogens have determined the proteins of interest that could be targets for future therapeutic options for decreasing corneal damage.

  10. Emodin ameliorates lipopolysaccharides-induced corneal inflammation in rats

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    Guo-Ling; Chen; Jing-Jing; Zhang; Xin; Kao; Lu-Wan; Wei; Zhi-Yu; Liu

    2015-01-01

    · AIM: To investigate the effect of emodin on pseudomonas aeruginosa lipopolysaccharides(LPS)-induced corneal inflammation in rats.· METHODS: Corneal infection was induced by pseudomonas aeruginosa LPS in Wistar rats. The inflammation induced by LPS were examined by slit lamp microscope and cytological checkup of aqueous humor.Corneal tissue structure was observed by hematoxylin and eosin(HE) staining. The activation of nuclear factor kappa B(NF-κB) was determined by Western blot.Messenger ribonucleic acid(m RNA) of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1(ICAM-1) in LPS-challenged rat corneas were measured with reverse transcription-polymerase chain reaction(RT-PCR).· RESULTS: Typical manifestations of acute corneal inflammation were observed in LPS-induce rat model,and the corneal inflammatory response and structure were improved in rats pretreated with emodin. Treatment with emodin could improve corneal structure, reduce corneal injure by reducing corneal inflammatory response. Emodin could inhibit the decreasing lever of inhibitor of kappa B alpha(IкBα) express, and the m RNA expression of TNF-α and ICAM-1 in corneal tissues was also inhibited by emodin. The differences were statistically significant between groups treated with emodin and those without treatment(P <0.01).·CONCLUSION: Emodin could ameliorate LPS-induced corneal inflammation, which might via inhibiting the activation of NF-κB.

  11. Ocular histopathological changes after eyeball enucleation induced by corneal trauma

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    2001-01-01

    Objective: To observe the ocular histopathological changes aftereyeball enucleation induced by corneal trauma.Methods: Light microscopic examination was done on 117 eyeball specimens enucleated after corneal trauma (18 with corneal fissure and 99 with corneal perforating trauma).Results: Acute, subacute or chronic inflammatory changes, and fibrous membrane formation were observed in well-closed corneal wounds, whereas inflammation, atrophy and scar were observed in the focal tissues. But at the late period, secondary glaucoma, retinal detachment, endophthalmitis and eyeball atrophy resulted in blindness. Corneal fistula was observed in those with inadequate cure of wounds caused by ingrowth of corneal epithelium, embedment of iris and vitreous body, and large area of centrally located tissue deficiency of the corneal. A high incidence of endophthalmitis was noted due to the presence of corneal fistula. Severe inflammation was observed in the anterior segmental tissues with fibrous infiltration in the anterior chamber, which might result in rapid destruction of the eyeballs.Conclusions: Ocular pathology varies with the difference of the position, form, size and closing conditions of the corneal laceration after trauma.

  12. Cataract surgery in a patient with severe chronic iritis and corneal endothelial damage.

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    Yasukawa, T; Suga, K; Yokoo, N; Asada, S

    1998-07-01

    We report a patient with broad anterior synechias and corneal endothelial damage. The patient had chronic iritis and cataracts secondary to chronic iritis in both eyes. Because the right eye had broad anterior synechias and severe corneal endothelial damage, extracapsular cataract extraction and intraocular lens implantation were performed through the basal iris. Good postoperative visual acuity was obtained. The cornea showed little trauma from the surgery and remained clear 36 months postoperatively.

  13. Production of Hypoxia-induced Corneal Edema in Aged Eyes

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    Alan K. Cheung; Andrew W. Siu; Digby W. Cheung; Edwin C. Mo

    2004-01-01

    Purpose:Corneal thickness assessment is a common clinical procedure applied in corneal and contact lens care. This study aims to investigate the effect of age on hypoxiainduced corneal swelling.Methods:Eighteen male subjects were equally divided into the younger [(23.7±0.8) and older [(74.4±2.5) years old]groups.Each subject wore a thick soft contact lens (uniform thickness of 0.3 mm) on the left cornea. With the contact lens in place, the baseline central corneal thickness was measured using a specially designed photo-pachometer. The lens was then patched behind the closed eyelids, producing an extremely hypoxic stress to the cornea. The change in central corneal thickness was monitored every 20 minutes with momentary disruptions to the hypoxic stress over the next 2 hours. The increase in thickness was taken as an index of corneal edema. The rate of change in corneal thickness, as derived from a non-linear mathematical model, was compared between groups. Results:The corneal thickness of both age groups increased significantly with time (P<0.000 1 ). The mean corneal swelling constant for the older subjects was 16.5 × 10-3 (S.E.M. = 2.65 × 10-3) and the value for the younger subjects was 46.5 × 10-3 (S.E.M. = 3.25× 10-3). The difference was statistically significant (P < 0.000 1 ).Conclusion:Aging cornea has a slower hypoxia-induced edema response compared with the younger group. Whether it is caused by a decreased corneal lactate production or an increased resistance to physical expansion deserves further investigation. Eye Science2004;20:1-5.

  14. Q-switched erbium:YAG laser corneal trephination: thermal damage in corneal stroma and cut regularity of nonmechanical Q-switched erbium:YAG laser corneal trephination for penetrating keratoplasty.

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    Stojkovic, M; Seitz, B; Langenbucher, A; Viestenz, A; Viestenz, A; Hofmann-Rummelt, C; Schlötzer-Schrehardt, U; Küchle, M; Naumann, G O H

    2004-01-01

    To assess stromal thermal damage and cut regularity induced by nonmechanical Q-switched Er:YAG laser corneal trephination for penetrating keratoplasty. Corneal trephination was performed in 80 enucleated porcine eyes by Q-switched (2.94-microm) Er:YAG laser, along with donor and recipient masks made of metal or ceramic. All combinations of 0.65- or 0.96-mm spot diameter and 45- or 50-mJ/pulse energy setting were used with each of the masks at a 5-Hz repetition rate. Corneas were processed for histologic examinations. Stromal thermal damage was quantified on PAS-stained slides, and cut regularity was assessed semiquantitatively on a scale from 0 (regular) to 3 (highly irregular). Transmission electron microscopy and scanning electron microscopy were performed on selected specimens. The least thermal damage (mean +/- SD = 6.2 +/- 0.7 microm) was found in the donor ceramic group with 50-mJ/pulse energy and 0.65-mm spot diameter, while the best regularity of the cut (1.2 +/- 0.4) was found in the donor ceramic group with 45-mJ pulse energy and 0.65-mm spot diameter. Thermal damage was less pronounced in donor than in recipient corneas (P trephination for nonmechanical penetrating keratoplasty, reproducible high cut regularity and low concomitant thermal damage were observed. This is an encouraging finding in the search for a nonmechanical trephine for penetrating keratoplasty combining high precision and low cost.

  15. Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells

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    Jing Zhong

    2016-01-01

    Full Text Available Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.

  16. Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells.

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    Zhong, Jing; Deng, Yuqing; Tian, Bishan; Wang, Bowen; Sun, Yifang; Huang, Haixiang; Chen, Ling; Ling, Shiqi; Yuan, Jin

    2016-01-01

    Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.

  17. Change in corneal curvature induced by surgery

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    G. van Rij (Gabriel)

    1987-01-01

    textabstractThe first section deals with the mechanisms by which sutures, incisions and intracorneal contact lenses produce a change in corneal curvature. To clarify the mechanisms by which incisions and sutures produce astigmatism, we made incisions and placed sutures in the corneoscleral limbus of

  18. Ceramide-induced apoptosis in rabbit corneal fibroblasts.

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    Kim, Tae-im; Pak, Jhang Ho; Tchah, Hungwon; Lee, Seung-ah; Kook, Michael S

    2005-01-01

    To evaluate the effect of various ceramides on the apoptosis of corneal fibroblasts and to determine the pathway on which they act. Corneal fibroblasts isolated and cultured from New Zealand white rabbits were exposed to various concentrations of ceramide types II and VI and phytoceramide types II and VI, and their apoptotic response was evaluated using an LDH assay and Hoechst and Annexin V staining. Corneal fibroblasts were preincubated with various concentrations of the CPP32-like protease inhibitor Z-VAD-FMK, the caspase-8 inhibitor IETD-CHO, and the caspase-9 inhibitor Z-LEHD-FMK before treatment with ceramide, and apoptotic response was assayed by LDH assay. In addition, cells treated with ceramide or phytoceramide were stained with an antibody to cytochrome c. At concentrations of 20 microM and higher, all 4 ceramides increased fibroblast apoptotic response significantly after 12 hours. Hoechst staining showed shrinkage of the cytoplasm, formation of apoptotic bodies, and nuclear fragmentation after ceramide exposure, and Annexin V staining showed small vesicles around the cell membrane. The CPP32-like protease inhibitor reduced the apoptotic response to all 4 ceramides. The specific caspase-8 inhibitor reduced the apoptotic response to ceramide type VI and phytoceramide types II and VI, whereas the specific caspase-9 inhibitor significantly reduced the apoptotic response to phytoceramide types II and VI. Following exposure to ceramides, corneal fibroblasts stained positively with antibody to cytochrome c. Ceramide induced apoptosis in cultured corneal fibroblasts. This apoptosis involved the caspase cascade and the mitochondrial pathway.

  19. Characterization of corneal damage from Pseudomonas aeruginosa infection by the use of multiphoton microscopy

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    Chang, Yu-Lin; Chen, Wei-Liang; Lo, Wen; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2010-11-01

    Using multiphoton autofluorescence (MAF) and second harmonic generation (SHG) microscopy, we investigate the morphology and the structure of the corneal epithelium and stroma collagen of bovine cornea following injection of Pseudomonas aeruginosa. We found that corneal epithelial cells are damaged and stromal collagen becoming increasingly autofluorescent with time. We also characterized infected cornea cultured for 0, 6, 12, and 24 h by quantitative ratiometric MAF to SHG index (MAFSI) analysis. MAFSI results show that the destruction of the stromal collagen corresponds to a decrease in SHG intensity and increase of MAF signal with time.

  20. Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

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    Ryuhei Hayashi

    Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

  1. Analysis of human transforming growth factor β-induced gene mutation in corneal dystrophy

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    李杨; 孙旭光; 任慧媛; 董冰; 王智群; 孙秀英

    2004-01-01

    Background Corneal dystrophy is a group of inherited blinding diseases of the cornea. This study was to identify the mutations of the keratoepithelin (KE) gene for proper diagnosis of corneal dystrophy. Methods Three families with corneal dystrophy were analysed. Thirteen individuals at risk for corneal dystrophy in family A, the proband and her son in family B, and the proband in family C were examined after their blood samples were obtained. Mutation screening of human transforming growth factor β-induced gene (BIGH3 gene) was performed. Results Five individuals in family A were found by clinical evaluation to be affected with granular corneal dystrophy and carried the BIGH3 mutation W555R. However, both probands in families B and C, also diagnosed with granular corneal dystrophy, harboured the BIGH3 mutation R124H. Conclusion Molecular genetic analysis can improve accurate diagnosis of corneal dystrophy.

  2. Hypocellular scar formation or aberrant fibrosis induced by an intrastromal corneal ring: a case report

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    Ramkumar Hema L

    2011-08-01

    Full Text Available Abstract Introduction Intrastromal corneal rings or segments are approved for the treatment of myopia and astigmatism associated with keratoconus. We describe a clinicopathological case of intrastromal corneal rings. For the first time, the molecular pathological findings of intrastromal corneal rings in the cornea are illustrated. Case presentation A 47-year-old African-American man with a history of keratoconus and failure in using a Rigid Gas Permeable contact lens received an intrastromal corneal ring implant in his left eye. Due to complications, penetrating keratoplasty was performed. The intrastromal corneal ring channels were surrounded by a dense acellular (channel haze and/or hypocellular (acidophilic densification collagen scar and slightly edematous keratocytes. Mild macrophage infiltration was found near the inner aspect of the intrastromal corneal rings. Molecular analyses of the microdissected cells surrounding the intrastromal corneal ring channels and central corneal stroma revealed 10 times lower relative expression of IP-10/CXCL10 mRNA and two times higher CCL5 mRNA in the cells surrounding the intrastromal corneal ring, as compared to the central corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by macrophages, endothelial cells and fibroblasts. Conclusion An intrastromal corneal ring implant can induce hypocellular scar formation and mild inflammation, which may result from aberrant release of fibrosis-related chemokines.

  3. Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide.

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    Kimura, Kazuhiro; Morita, Yukiko; Orita, Tomoko; Haruta, Junpei; Takeji, Yasuhiro; Sonoda, Koh-Hei

    2013-04-17

    TNF-α disrupts the barrier function of cultured human corneal epithelial (HCE) cells. We investigated the effects of the cytoprotective drug rebamipide on this barrier disruption by TNF-α as well as on corneal epithelial damage in a rat model of dry eye. The barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance. The distribution of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, and the p65 subunit of nuclear factor-κB (NF-κB) was determined by immunofluorescence microscopy. Expression of junctional proteins as well as phosphorylation of the NF-κB inhibitor IκB-α and myosin light chain (MLC) were examined by immunoblot analysis. A rat model of dry eye was developed by surgical removal of exorbital lacrimal glands. Rebamipide inhibited the disruption of barrier function as well as the downregulation of ZO-1 expression, and the disappearance of ZO-1 from the interfaces of neighboring HCE cells induced by TNF-α. It also inhibited the phosphorylation and downregulation of IκB-α, the translocation of p65 to the nucleus, the formation of actin stress fibers, and the phosphorylation of MLC induced by TNF-α in HCE cells. Treatment with rebamipide eyedrops promoted the healing of corneal epithelial defects as well as attenuated the loss of ZO-1 from the surface of corneal epithelial cells in rats. Rebamipide protects corneal epithelial cells from the TNF-α-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton. Rebamipide is, thus, a potential drug for preventing or ameliorating the loss of corneal epithelial barrier function associated with ocular inflammation.

  4. Induced astigmatism after diamond burr superficial keratectomy for recurrent corneal erosion.

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    Yoo, Janie H; Choi, David M

    2009-11-01

    To report a case of induced astigmatism after diamond burr superficial keratectomy (DBSK) for recurrent corneal erosion (RCE). Case report. Review of clinical findings in a 54-year-old women with ocular history of a scleral buckling procedure for a retinal detachment from blunt trauma and phacoemulsification with intraocular lens placement. The patient presented with RCE after trauma with a mascara brush to the OD and was treated with DBSK. Postoperatively, she developed significant astigmatism. In the third postoperative week after the DBSK procedure, the patient reported of worsening vision. On corneal topography, the patient was found to have 4 diopters of induced astigmatism. The astigmatic error was followed closely by serial corneal topography; a gradual decrease in the amount of astigmatism occurred over the course of 30 weeks. Forme fruste keratoconus was suspected in the patient's contralateral eye, based on corneal topographic analysis. Induced corneal astigmatism is a previously undescribed complication that can occur after DBSK. It is unclear whether the induced astigmatism in our patient was caused by the DBSK procedure alone or whether the patient had decompensated structural integrity from forme fruste keratoconus or blunt corneal trauma or both. The authors recommend that corneal topographic analysis be appropriately considered before DBSK for RCE and that corneal astigmatism be seen as a potential complication of the procedure.

  5. Derivation of Corneal Keratocyte-Like Cells from Human Induced Pluripotent Stem Cells

    Science.gov (United States)

    Naylor, Richard W.; McGhee, Charles N. J.; Cowan, Chad A.; Davidson, Alan J.; Holm, Teresa M.; Sherwin, Trevor

    2016-01-01

    Corneal diseases such as keratoconus represent a relatively common disorder in the human population. However, treatment is restricted to corneal transplantation, which only occurs in the most advanced cases. Cell based therapies may offer an alternative approach given that the eye is amenable to such treatments and corneal diseases like keratoconus have been associated specifically with the death of corneal keratocytes. The ability to generate corneal keratocytes in vitro may enable a cell-based therapy to treat patients with keratoconus. Human induced pluripotent stem cells (hiPSCs) offer an abundant supply of cells from which any cell in the body can be derived. In the present study, hiPSCs were successfully differentiated into neural crest cells (NCCs), the embryonic precursor to keratocytes, and then cultured on cadaveric corneal tissue to promote keratocyte differentiation. The hiPSC-derived NCCs were found to migrate into the corneal stroma where they acquired a keratocyte-like morphology and an expression profile similar to corneal keratocytes in vivo. These results indicate that hiPSCs can be used to generate corneal keratocytes in vitro and lay the foundation for using these cells in cornea cell-based therapies. PMID:27792791

  6. Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops.

    Science.gov (United States)

    Nagai, Noriaki; Yoshioka, Chiaki; Tanino, Tadatoshi; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    We investigated the protective effects of mannitol on corneal damage caused by benzalkonium chloride (BAC), which is used as a preservative in commercially available timolol maleate eye drops, using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constant (kH), as well as cell viability, were higher following treatment with 0.005% BAC solution containing 0.5% mannitol than in the case BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without mannitol. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.5% mannitol was significantly higher than that for eyes instilled with timolol maleate eye drops without mannitol, and the addition of mannitol did not affect the corneal penetration or IOP reducing effect of the timolol maleate eye drops. A preservative system comprising BAC and mannitol may provide effective therapy for glaucoma patients requiring long-term treatment with anti-glaucoma agents.

  7. Corneal Biomechanical Parameters and Asymmetric Visual Field Damage in Patients with Untreated Normal Tension Glaucoma

    Science.gov (United States)

    Li, Bai-Bing; Cai, Yu; Pan, Ying-Zi; Li, Mei; Qiao, Rong-Hua; Fang, Yuan; Tian, Tian

    2017-01-01

    Background: High intraocular pressure (IOP) and low central corneal thickness (CCT) are important validated risk factors for glaucoma, and some studies also have suggested that eyes with more deformable corneas may be in higher risk of the development and worsening of glaucoma. In the present study, we aimed to evaluate the association between corneal biomechanical parameters and asymmetric visual field (VF) damage using a Corvis-ST device in patients with untreated normal tension glaucoma (NTG). Methods: In this observational, cross-sectional study, 44 newly diagnosed NTG patients were enrolled. Of these, 31 had asymmetric VF damage, which was defined as a 5-point difference between the eyes according to the Advanced Glaucoma Intervention Study scoring system. Corneal biomechanical parameters were obtained using a Corvis-ST device, such as time from start until the first and second applanation is reached (time A1 and time A2, respectively), cord length of the first and second applanation (length A1 and length A2, respectively), corneal speed during the first and second applanation (velocity A1 and velocity A2, respectively), time from start until highest concavity is reached (time HC), maximum amplitude at the apex of highest concavity (def ampl HC), distance between the two peaks at highest concavity (peak dist HC), and central concave curvature at its highest concavity (radius HC). Results: Time A1 (7.19 ± 0.28 vs. 7.37 ± 0.41 ms, P = 0.010), length A1 (1.73 [1.70–1.76] vs. 1.78 [1.76–1.79] mm, P = 0.007), length A2 (1.58 [1.46–1.70] vs. 1.84 [1.76–1.92] mm, P < 0.001), peak dist HC (3.53 [3.08–4.00] vs. 4.33 [3.92–4.74] mm, P = 0.010), and radius HC (6.20 ± 0.69 vs. 6.59 ± 1.18 mm, P = 0.032) were significantly lower in the worse eyes than in the better eyes, whereas velocity A1 and def ampl HC were significantly higher (0.156 [0.149–0.163] vs. 0.145 [0.138–0.152] m/s, P = 0.002 and 1.19 ± 0.13 vs. 1.15 ± 0.13 mm, P = 0.005, respectively

  8. The Preliminary Experimental Study of Induced Differentiation of Embryonic Stem Cells into Corneal Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Ling Yu; Jian Ge; Zhichong Wang; Bing Huang; Keming Yu; Chongde Long; Xigu Chen

    2001-01-01

    Purpose:To study preliminarily induced differentiation of embryonic stem cells intocorneal epithelial cells in vitro.Methods: Murine embryonic stem cells were co-cultured with Rabbit limbal cornealepithelial cells in Transwell system to induce differentiation. Mophological andimmunohistochemical examination were implemented.Results: The induced cells from embryonic stem cells have an epithelial appearance.The cells formed a network and were confluent into film gradually after beingco-cultured with rabbit limbal corneal epithelial cells for 24 ~ 96 hours. The cells rangedmosaic structure and localized together with clear rim. Most of the cells showedpolygonal appearance. Transmission electron microscope showed lots of microvilli on thesurface of induced cells and tight junctions between them. These epithelial-like cellsexpressed the corneal epithelial cell specific marker cytokeratin3/cytokeratinl2.Conclusion: The potential mechanism of the differentiation of murine embryonic stemcells into corneal epithelial cells induced by limbal corneal epithelial cell-derivedinducing activity is to be further verified.

  9. Vorinostat: a potent agent to prevent and treat laser-induced corneal haze.

    Science.gov (United States)

    Tandon, Ashish; Tovey, Jonathan C K; Waggoner, Michael R; Sharma, Ajay; Cowden, John W; Gibson, Daniel J; Liu, Yuanjing; Schultz, Gregory S; Mohan, Rajiv R

    2012-04-01

    This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro. Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measure its efficacy. Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (Prabbit eyes in vivo screened 4 weeks after PRK. Vorinostat reduced TGFβ1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation. Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia. Copyright 2012, SLACK Incorporated.

  10. Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts.

    Science.gov (United States)

    Zhou, Hongyan; Kimura, Kazuhiro; Orita, Tomoko; Nishida, Teruo; Sonoda, Koh-Hei

    2012-06-28

    To examine the effect of medroxyprogesterone 17-acetate (MPA) on interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts. Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels with or without MPA. Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression or activity of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) was evaluated by immunoblot analysis or gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. MPA inhibited IL-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. MMP expression and activation as well as TIMP expression in corneal fibroblasts exposed to IL-1β were also inhibited by MPA. MPA had no effect on cell proliferation or viability. MPA inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK. IL-1β-induced MMP expression and activation as well as collagen degradation were also blocked by the p38 MAPK inhibitor SB203580. MPA inhibited MMP expression and thereby suppressed collagen degradation by corneal fibroblasts induced by IL-1β. Furthermore, inhibition of p38 MAPK phosphorylation by MPA may contribute to its inhibition of collagen degradation.

  11. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans.

    Science.gov (United States)

    Mazzotta, Cosimo; Balestrazzi, Angelo; Traversi, Claudio; Baiocchi, Stefano; Caporossi, Tomaso; Tommasi, Cristina; Caporossi, Aldo

    2007-05-01

    To assess ultrastructural stromal modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus. This was a second-phase prospective nonrandomized open study in 10 patients with progressive keratoconus treated by riboflavin-UVA-induced cross-linking of corneal collagen and assessed by means of Heidelberg Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal microscopy. The eye in the worst clinical condition was treated for each patient. Treatment under topical anesthesia included corneal deepithelization (9-mm diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500 solution at 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment. Rarefaction of keratocytes in the anterior and intermediate stroma, associated with stromal edema, was observed immediately after treatment. The observation at 3 months after the operation detected keratocyte repopulation in the central treated area, whereas the edema had disappeared. Cell density increased progressively over the postoperative period. At approximately 6 months, keratocyte repopulation was complete, accompanied by increased density of stromal fibers. No endothelial damage was observed at any time. Reduction in anterior and intermediate stromal keratocytes followed by gradual repopulation has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy after riboflavin-UVA-induced corneal collagen cross-linking.

  12. Corneal Confocal Microscopy: A Non-Invasive Surrogate Marker of Small Nerve Fibre Damage and Repair in Patients with Small Fibre Neuropathy

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    M Tavakoli

    2005-10-01

    Full Text Available Aim: ‘Painful neuropathy’ is presumed to be secondary to small fibre damage from a variety of causes. Methods to detect, characterize and quantify small fibre damage are time consuming and highly variable (QST’s, or invasive (skin or nerve biopsy. We have recently shown that corneal nerve damage assessed using corneal confocal microscopy is an accurate surrogate marker for somatic nerve damage in patients with diabetic neuropathy. We have now assessed corneal nerve morphology in patients with painful neuropathy who had been labelled as having ‘small fibre neuropathy’. Methods: 30 patients aged 60 + 13 with ‘small fibre neuropathy’ and 12 age-matched control subjects underwent assessment of the Neuropathy Deficit Score in the lower limb (NDS, Neuropathy Symptom Profile (NSP, Electrophysiology, QST for thermal perception and corneal confocal microscopy (CCM. CCM quantified corneal nerve morphology: nerve fibre density (NFD, nerve branch density (NBD, nerve fibre length (NFL, nerve fibre tortuosity (NFT. Results: According to the results obtained for “neuropathy severity assessment” including NDS, NSP, electrophysiology and QST data , a significance reduction in corneal nerve NFD (P< 0.0001, NBD (P< 0.0001, NFL (P< 0.0001 and no statistical significant changes in tortuosity was shown. Discussion: Corneal confocal microscopy offers a rapid, non-invasive, and reiterative technique to accurately detect, and quantify nerve damage in patients with ‘small fibre neuropathy’.

  13. Clinical applications of corneal confocal microscopy

    Directory of Open Access Journals (Sweden)

    Mitra Tavakoli

    2008-06-01

    Full Text Available Mitra Tavakoli1, Parwez Hossain2, Rayaz A Malik11Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; 2University of Southampton, Southampton Eye Unit, Southampton General Hospital, Southampton, UKAbstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy, and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.Keywords: corneal confocal microscopy, cornea, infective keratitis, corneal dystrophy, neuropathy

  14. Role of nuclear factor-kappaB in interleukin-1-induced collagen degradation by corneal fibroblasts.

    Science.gov (United States)

    Lu, Ying; Fukuda, Ken; Li, Qin; Kumagai, Naoki; Nishida, Teruo

    2006-09-01

    The proinflammatory cytokine interleukin (IL)-1 is implicated in corneal ulceration. The role of nuclear factor (NF)-kappaB in the IL-1-induced degradation of collagen by corneal fibroblasts that underlies corneal ulceration was investigated. Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen with or without IL-1 and sulfasalazine, an inhibitor of NF-kappaB activation. Collagen degradation was assessed from the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The release of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) into culture supernatants was examined by immunoblot analysis and gelatin zymography, and the cellular abundance of MMP and TIMP mRNAs was determined by reverse transcription and real-time polymerase chain reaction analysis. The phosphorylation and degradation of the NF-kappaB-inhibitory protein IkappaB-alpha were examined by immunoblot analysis. The subcellular localization and DNA binding activity of the p65 subunit of NF-kappaB were evaluated by immunofluorescence analysis and with a colorimetric assay, respectively. The transactivation activity of NF-kappaB was assessed with a reporter gene assay. Sulfasalazine inhibited IL-1-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner. It also inhibited the stimulatory effects of IL-1 on the synthesis or activation of various MMPs in a concentration-dependent manner. IL-1 induced the phosphorylation and degradation of IkappaB-alpha, the nuclear translocation and up-regulation of the DNA binding activity of the p65 subunit of NF-kappaB, and the activation of NF-kappaB in a manner sensitive to sulfasalazine. These results suggest that NF-kappaB contributes to the IL-1-induced degradation of collagen by corneal fibroblasts and is therefore a potential therapeutic target for treatment of corneal ulcers.

  15. Murine Corneal Inflammation and Nerve Damage After Infection With HSV-1 Are Promoted by HVEM and Ameliorated by Immune-Modifying Nanoparticle Therapy

    Science.gov (United States)

    Edwards, Rebecca G.; Kopp, Sarah J.; Ifergan, Igal; Shui, Jr-Wen; Kronenberg, Mitchell; Miller, Stephen D.; Longnecker, Richard

    2017-01-01

    Purpose To determine cellular and temporal expression patterns of herpes virus entry mediator (HVEM, Tnfrsf14) in the murine cornea during the course of herpes simplex virus 1 (HSV-1) infection, the impact of this expression on pathogenesis, and whether alterations in HVEM or downstream HVEM-mediated effects ameliorate corneal disease. Methods Corneal HVEM levels were assessed in C57BL/6 mice after infection with HSV-1(17). Leukocytic infiltrates and corneal sensitivity loss were measured in the presence, global absence (HVEM knockout [KO] mice; Tnfrsf14−/−), or partial absence of HVEM (HVEM conditional KO). Effects of immune-modifying nanoparticles (IMPs) on viral replication, corneal sensitivity, and corneal infiltrates were measured. Results Corneal HVEM+ populations, particularly monocytes/macrophages during acute infection (3 days post infection [dpi]) and polymorphonuclear neutrophils (PMN) during the chronic inflammatory phase (14 dpi), increased after HSV-1 infection. Herpes virus entry mediator increased leukocytes in the cornea and corneal sensitivity loss. Ablation of HVEM from CD45+ cells, or intravenous IMP therapy, reduced infiltrates in the chronic phase and maintained corneal sensitivity. Conclusions Herpes virus entry mediator was expressed on two key populations: corneal monocytes/macrophages and PMNs. Herpes virus entry mediator promoted the recruitment of myeloid cells to the cornea in the chronic phase. Herpes virus entry mediator–associated corneal sensitivity loss preceded leukocytic infiltration, suggesting it may play an active role in recruitment. We propose that HVEM on resident corneal macrophages increases nerve damage and immune cell invasion, and we showed that prevention of late-phase infiltration of PMN and CD4+ T cells by IMP therapy improved clinical symptoms and mortality and reduced corneal sensitivity loss caused by HSV-1. PMID:28114589

  16. Corneal alterations induced by topical application of commercial latanoprost, travoprost and bimatoprost in rabbit.

    Science.gov (United States)

    Chen, Wensheng; Dong, Nuo; Huang, Caihong; Zhang, Zhenhao; Hu, Jiaoyue; Xie, Hui; Pan, Juxin; Liu, Zuguo

    2014-01-01

    Prostaglandin (PG) analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK) was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT), rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier integrity of corneal

  17. Corneal alterations induced by topical application of commercial latanoprost, travoprost and bimatoprost in rabbit.

    Directory of Open Access Journals (Sweden)

    Wensheng Chen

    Full Text Available Prostaglandin (PG analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT, rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin and adherens-junction (E-cadherin, β-catenin proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier

  18. Effects of 4-methylumbelliferone and high molecular weight hyaluronic acid on the inflammation of corneal stromal cells induced by LPS.

    Science.gov (United States)

    Li, Fang; Hao, Peng; Liu, Guangjie; Wang, Weiyi; Han, Ruifang; Jiang, Zhixin; Li, Xuan

    2017-03-01

    To investigate the effects of hyaluronic acid (HA) on the inflammation of corneal fibroblasts induced by lipopolysaccharide (LPS). Primary rabbit corneal keratocytes were isolated with collagenase. The keratocytes were cultured in a serum-containing medium to induce corneal fibroblasts, which represented the wound repair phenotype of corneal keratocytes. Corneal fibroblasts were treated with LPS with or without 4-methylumbelliferone (4-MU) / high molecular weight hyaluronic acid (HMWHA). The gene expression was evaluated via real-time PCR, immunofluorescence, and western blot. The release of inflammatory cytokines and HA was determined by ELISA. Three types of hyaluronan synthase (HAS) were detected in corneal fibroblasts. LPS stimulation caused the up-regulation of HAS1 and HAS2 expression in corneal fibroblasts. LPS-induced HAS2 expression was significantly inhibited by 4-MU, and accompanied by decreased HA release by the corneal fibroblasts. In the corneal fibroblasts, 4-MU reduced the LPS-stimulated up-regulation of inflammatory cytokines including IL-1, IL-6, IL-8, TNF-α, and also attenuated the LPS-induced up-regulation of inflammatory related receptors including TLR2, TLR4, CD44, and CXCR1. HMWHA treatment resulted in a significant decline in the expression of IL-6, IL-8, TLR4, and CXCR1 responded to LPS stimulation. Consistent with mRNA expression of level, the up-regulation of the release of IL-6 and IL-8 induced by LPS in corneal fibroblasts was significantly attenuated by 4-MU and HMWHA. The LPS-induced expression of IL-8 and its receptor CXCR1 at both the mRNA and protein level were significantly attenuated by 4-MU and HMWHA. The inhibitor of HA synthesis 4-MU, and HMWHA successfully reduced LPS-induced inflammation in corneal fibroblasts. The mechanism might be via the inhibition of LPS-induced TLR4 up-regulation.

  19. The graft of autologous adipose-derived stem cells in the corneal stromal after mechanic damage.

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    Xiao-Yun Ma

    Full Text Available This study was designed to explore the feasibility of using autologous rabbit adipose derived stem cells (rASCs as seed cells and polylactic-co-glycolic acid (PLGA as a scaffold for repairing corneal stromal defects. rASCs isolated from rabbit nape adipose tissue were expanded and seeded on a PLGA scaffold to fabricate cell-scaffold constructs. After 1 week of cultivation in vitro, the cell-scaffold complexes were transplanted into corneal stromal defects in rabbits. In vivo, the autologous rASCs-PLGA constructed corneal stroma gradually became transparent without corneal neovascularization after 12 weeks. Hematoxylin and eosin staining and transmission electron microscopy examination revealed that their histological structure and collagen fibril distribution at 24 weeks after implantation were similar to native counterparts. As to the defect treated with PLGA alone, the stromal defects remained. And scar tissue was observed in the untreated-group. The implanted autologous ASCs survived up to 24 weeks post-transplantation and differentiated into functional keratocytes, as assessed by the expression of aldehyde-3-dehydrogenase1A1 (ALDH1A1 and cornea-specific proteoglycan keratocan. Our results revealed that autologous rASCs could be one of the cell sources for corneal stromal restoration in diseased corneas or for tissue engineering of a corneal equivalent.

  20. Dexamethasone inhibition of IL-1-induced collagen degradation by corneal fibroblasts in three-dimensional culture.

    Science.gov (United States)

    Lu, Ying; Fukuda, Ken; Liu, Yang; Kumagai, Naoki; Nishida, Teruo

    2004-09-01

    Corticosteroids regulate the functions of inflammatory cells. The purpose of the present study was to investigate the effect of dexamethasone on collagen degradation by corneal fibroblasts, an underlying cause of corneal ulceration. Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen and in the absence or presence of IL-1beta or dexamethasone. The extent of collagen degradation was determined by measurement of the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was evaluated by immunoblot analysis, gelatin zymography, and reverse transcription and real-time polymerase chain reaction. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was assessed by immunoblot analysis. Dexamethasone inhibited IL-1beta-induced collagen degradation by corneal fibroblasts in a dose-dependent manner. Both the synthesis and activation of MMPs and the expression of TIMPs were inhibited by dexamethasone, as was the activity of plasmin in culture supernatants. Dexamethasone also inhibited the IL-1beta-induced phosphorylation of the MAPKs extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not that of p38. Dexamethasone exerted multiple effects on the MMP-TIMP system in corneal fibroblasts and thereby inhibited IL-1beta-induced collagen degradation by these cells. Inhibition of the IL-1beta-induced activation of ERK and JNK may contribute to these effects of dexamethasone. Copyright Association for Research in Vision and Ophthalmology

  1. Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

    Science.gov (United States)

    Sari, Esin Sogutlu; Yazici, Alper; Aksit, Hasan; Yay, Arzu; Sahin, Gözde; Yildiz, Onur; Ermis, Sitki Samet; Seyrek, Kamil; Yalcin, Betul

    2015-01-01

    To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats. Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA. The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

  2. Corneal alternations induced by topical application of benzalkonium chloride in rabbit.

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    Wensheng Chen

    Full Text Available Benzalkonium chloride (BAC is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF. The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo.

  3. Corneal Alternations Induced by Topical Application of Benzalkonium Chloride in Rabbit

    Science.gov (United States)

    Chen, Wensheng; Li, Zhiyuan; Hu, Jiaoyue; Zhang, Zhenhao; Chen, Lelei; Chen, Yongxiong; Liu, Zuguo

    2011-01-01

    Benzalkonium chloride (BAC) is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC) in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF). The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR) were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo. PMID:22022526

  4. Inhibition by rebamipide of cytokine-induced or lipopolysaccharide-induced chemokine synthesis in human corneal fibroblasts.

    Science.gov (United States)

    Fukuda, Ken; Ishida, Waka; Tanaka, Hiroshi; Harada, Yosuke; Fukushima, Atsuki

    2014-12-01

    The dry-eye drug rebamipide has mucin secretagogue activity in and anti-inflammatory effects on corneal epithelial cells. Corneal stromal fibroblasts (transdifferentiated keratocytes) function as immune modulators in the pathogenesis of chronic ocular allergic inflammation and in innate immune responses at the ocular surface. The possible anti-inflammatory effects of rebamipide on human corneal stromal fibroblasts were examined. Serum-deprived cells were incubated for 1 h with rebamipide and then for various times in the additional absence or presence of cytokines or bacterial lipopolysaccharide (LPS). The release of chemokines into culture supernatants was determined with ELISAs. The intracellular abundance of chemokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor κB (NFκB) inhibitor IκBα was detected by immunoblot analysis. Rebamipide suppressed the release of interleukin (IL)-8 and the upregulation of IL-8 mRNA induced by tumour necrosis factor α (TNF-α) or LPS in corneal fibroblasts. It also inhibited eotaxin-1 (CCL-11) expression at the protein and mRNA levels induced by the combination of TNF-α and IL-4. In addition, rebamipide attenuated the degradation of IκBα induced by TNF-α or LPS. Rebamipide inhibited the synthesis of chemokines by corneal fibroblasts in association with suppression of NFκB signalling. Rebamipide may therefore prove effective for the treatment of corneal stromal inflammation associated with allergy or bacterial infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Aligned Fibrous Scaffold Induced Aligned Growth of Corneal Stroma Cells in vitro Culture

    Institute of Scientific and Technical Information of China (English)

    GAO Yan; YAN Jing; CUI Xue-jun; WANG Hong-yan; WANG Qing

    2012-01-01

    To investigate the contribution of fibre arrangement to guiding the aligned growth of corneal stroma cells,aligned and randomly oriented fibrous scaffolds of gelatin and poly-L-lactic acid(PLLA) were fabricated by electrospinning.A comparative study of two different systems with corneal stroma cells on randomly organized and aligned fibres were conducted.The efficiency of the scaffolds for inducing the aligned growth of cells was assessed by morphological observation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT) assay.Results show that the cells cultured on both randomly oriented and aligned scaffolds maintained normal morphology and well spreading as well as long term proliferation.Importantly,corneal stroma cells grew high orderly on the aligned scaffold,while the cells grew disordered on the randomly oriented scaffold.Moreover,the cells exhibited higher viability in aligned scaffold than that in randomly oriented scaffold.These results indcate that electrospinng to prepare aligned fibrous scaffolds has provided an effective approach to the aligned growth of corneal stroma cells in vitro.Our findings that fiber arrangement plays a crucial role in guiding the aligned growth of cells may be helpful to the development of better biomaterials for tissue engineered cornea.

  6. Ambient fine particulate matters induce cell death and inflammatory response by influencing mitochondria function in human corneal epithelial cells.

    Science.gov (United States)

    Park, Eun-Jung; Chae, Jae-Byoung; Lyu, Jungmook; Yoon, Cheolho; Kim, Sanghwa; Yeom, Changjoo; Kim, Younghun; Chang, Jaerak

    2017-11-01

    Ambient fine particulate matter (AFP) is a main risk factor for the cornea as ultraviolet light. However, the mechanism of corneal damage following exposure to AFP has been poorly understood. In this study, we first confirmed that AFP can penetrate the cornea of mice, considering that two-dimensional cell culture systems are limited in reflecting the situation in vivo. Then, we investigated the toxic mechanism using human corneal epithelial (HCET) cells. At 24h after exposure, AFP located within the autophagosome-like vacuoles, and cell proliferation was clearly inhibited in all the tested concentration. Production of ROS and NO and secretion of pro-inflammatory cytokines were elevated in a dose-dependent manner. Additionally, conversion of LC3B from I-type to II-type and activation of caspase cascade which show autophagic- and apoptotic cell death, respectively, were observed in cells exposed to AFP. Furthermore, AFP decreased mitochondrial volume, inhibited ATP production, and altered the expression of metabolism-related genes. Taken together, we suggest that AFP induces cell death and inflammatory response by influencing mitochondrial function in HCET cells. In addition, we recommend that stringent air quality regulations are needed for eye health. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Laser-induced damage in optical materials

    CERN Document Server

    Ristau, Detlev

    2014-01-01

    Dedicated to users and developers of high-powered systems, Laser-Induced Damage in Optical Materials focuses on the research field of laser-induced damage and explores the significant and steady growth of applications for high-power lasers in the academic, industrial, and military arenas. Written by renowned experts in the field, this book concentrates on the major topics of laser-induced damage in optical materials and most specifically addresses research in laser damage that occurs in the bulk and on the surface or the coating of optical components. It considers key issues in the field of hi

  8. Quantitative analysis of thermally-induced alterations of corneal stroma by second-harmonic generation imaging

    Science.gov (United States)

    Matteini, P.; Rossi, F.; Ratto, F.; Cicchi, R.; Kapsokalyvas, D.; Pavone, F. S.; Pini, R.

    2010-02-01

    Thermal modifications induced in the corneal stroma were investigated by means of second harmonic generation (SHG) imaging. Whole fresh cornea samples were heated in a water bath at temperatures in the 35-80 °C range for a 4-min time. SHG images of the structural modifications induced at each temperature were acquired from different areas of cross-sectioned corneal stroma by using an 880 nm linearly- and circularly-polarized excitation light emitted by a mode-locked Ti:Sapphire laser. The SHG images were then analyzed by means of both an empirical approach and a 2D-theoretical model. The proposed analyses provide a detailed description of the changes occurring in the structural architecture of the cornea during the thermal treatment. Our results allow us to depict a temperature-dependent biochemical model for the progressive destructuration occurring to collagen fibrils and nonfibrillar components of the stroma.

  9. Induced corneal astigmatism by palpebral spring for the treatment of lagophthalmos.

    Science.gov (United States)

    Avni-Zauberman, Noah; Rosen, Nachum; Ben Simon, Guy J

    2008-08-01

    To report a patient with decreased vision after insertion of an upper eyelid palpebral spring. Interventional case report. A 44-year-old man presented with decreased vision in his right eye. Several months before presentation, he underwent palpebral spring insertion in his upper eyelid for lagophthalmos. He had developed seventh cranial nerve palsy after removal of the right facial nerve neuroma. Decreased vision was related to induced astigmatism by upper eyelid pressure. Surgical replacement of the spring resulted in less astigmatism and improvement in visual acuity. Ocular rehabilitation surgery with insertion of a palpebral spring to the upper eyelid may induce corneal astigmatism and decrease vision in the normal eye. This may be reversible by replacing or repositioning the spring so that it will imply less corneal pressure.

  10. Capsaicin-induced corneal lesions in mice and the effects of chemical sympathectomy.

    Science.gov (United States)

    Shimizu, T; Izumi, K; Fujita, S; Koja, T; Sorimachi, M; Ohba, N; Fukuda, T

    1987-11-01

    Effects of chemical sympathectomy on corneal changes induced in mice by a s.c. injection of capsaicin were investigated. Pretreatment with a s.c. injection of 6-hydroxydopamine (6-OHDA) on the 1st and 2nd postnatal day or on the 14th and 15th postnatal day led to a marked suppression of the capsaicin-induced corneal lesions. This suppressive effect also was evident in case of administration after capsaicin treatment. Intraventricular injection of 6-OHDA had a slight, transient effect. DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], another potent substance used for sympathetic denervation, had a suppressive effect similar to that of 6-OHDA. The concentration of capsaicin in tissues of the head was unaltered with 6-OHDA. The content of substance P (SP) in the ocular anterior segments was decreased, dose-dependently, with capsaicin administration. Neonatal administration of 6-OHDA decreased the rate of capsaicin-induced reduction of SP. However, this effect of 6-OHDA was too slight to explain the suppression of the corneal lesions, as the intensity score of lesions with a large dose of capsaicin after 6-OHDA was lower than that with a small dose of capsaicin without 6-OHDA, whereas SP content in the former was still much lower than that in the latter. On the other hand, the content of norepinephrine in the ocular tissues was decreased in the presence of 6-OHDA but not capsaicin. These results suggest that the corneal changes induced by capsaicin are largely inhibited by a decreased activity in the peripheral sympathetic system.

  11. Assessment of corneal morphological changes induced by the use of daily disposable contact lenses.

    Science.gov (United States)

    Del Águila-Carrasco, Antonio J; Domínguez-Vicent, Alberto; Pérez-Vives, Cari; Ferrer-Blasco, Teresa; Montés-Micó, Robert

    2015-02-01

    To assess the effect of different disposable soft contact lenses upon corneal thickness, and upon anterior and posterior corneal curvatures using a dual-Scheimpflug imaging based device. Twenty-eight young, healthy subjects wore four different types of daily disposable soft contact lenses on four different days: Dailies Total1, Proclear 1 Day, Clariti 1-Day and 1-Day Acuvue Moist. The lenses had different material and water content. Pachymetry maps and keratometry values were obtained using the Galilei G4 twice a day: one before putting the lens on and one after an eight-hour period of contact-lens wear. Measurements were also recorded without any contact lenses being worn during a day. Clariti 1-Day lens caused the greatest thickening in the central (8.9±2.8 μm; p<0.01) and in the peripheral cornea (10.1±4.6 μm; p<0.01), whereas Dailies Total1 was the lens that had the most similar behaviour to the non-contact lens scenario. All the lenses caused a slight flattening in the anterior corneal curvature, except Clariti 1-Day, which induced a very slight steepening. The four lenses caused a steepening of different magnitude in the posterior corneal curvature. The magnitude of the changes introduced by the use of soft contact lenses over the eight-hour wearing period was rather small. Thus it is probable it will not influence the vision nor the comfort of the subject. Also, variations on corneal parameters seem to depend on the type of contact lens used. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  12. Biomechanical corneal changes induced by different flap thickness created by femtosecond laser

    Directory of Open Access Journals (Sweden)

    Fabricio W. Medeiros

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the impact of the creation of corneal flaps at different thicknesses on the biomechanical properties of swine corneas. METHOD: Twelve swine eyes were obtained to form two groups: 100 μm flap thickness and 300 μm flap thickness. Each eye was submitted to the following examinations: raster topography to investigate corneal curvature alterations, ocular response analyzer to investigate corneal hysteresis change, optical coherence tomography to measure central corneal and flap thickness and sonic wave propagation velocity as a measure of stiffness, before and immediately after flap creation. After flap amputation, surface wave velocity measurements were repeated. RESULTS: Measured flap thicknesses were statistically different for thin and thick flap groups, with an average of 108.5 + 6.9 and 307.8 + 11.5 μm respectively. Hysteresis and corneal resistance factor did not change significantly after flap creation in the thin flap group. With thicker flaps, both parameters decreased significantly from 8.0 +1.0 to 5.1 +1.5 mmHg and from 8.2 + 1.6 to 4.1 +2.5 mmHg respectively. Simulated keratometry values increased in the thick flap group (from 39.5 + 1 D to 45.9+1.2 D after flap creation but not in the thin flap group (from 40.6 + 0.6 D to 41.4+ 1.0 D. Regarding surface wave velocity analysis, the surgical procedures induced statistically lower results in some positions. CONCLUSION: In the experimental conditions established by this model, thicker flaps presented a greater biomechanical impact on the cornea.

  13. Corneal shrinkage induced by nonmechanical Q-switched erbium:YAG laser trephination for penetrating keratoplasty in porcine eyes.

    Science.gov (United States)

    Stojkovic, Milenko; Seitz, Berthold; Küchle, Michael; Langenbucher, Achim; Viestenz, Arne; Viestenz, Anja; Hofmann-Rummelt, Carmen; Naumann, Gottfried O H

    2003-08-01

    To assess the degree of corneal diameter shrinkage induced by Q-switched mid-infrared laser corneal trephination for penetrating keratoplasty in an experimental model. Corneal trephination was performed in 80 enucleated porcine eyes fixed in a holder centered on an automated globe rotation device, by Q-switched (2.94 microm) Er:YAG laser along open masks. Four types of masks were used to protect the underlying corneal tissue: metal masks (donor and recipient) and ceramic masks (donor and recipient). Two spot diameters (0.65 mm and 0.96 mm) were combined with two energy settings (40 mJ/pulse and 50 mJ/pulse) for each of the masks used. Repetition rate was fixed at 5 Hz. Diameters of donor buttons/recipient beds (horizontal and vertical) were measured immediately after the trephination and compared to the given mask size. Minimum corneal shrinkage was found in the recipient metal mask group (mean +/- SD=0.3+/-0.4%) with 50 mJ pulse energy and 0.65 mm spot diameter (in the horizontal diameter), while the maximum shrinkage (5.3+/-2.8%) was found in the donor metal mask group with 50 mJ pulse energy and 0.96 mm spot diameter. Corneal shrinkage was less pronounced in recipient beds than in donor buttons (P0.05). Mean induced corneal diameter discrepancies between the donor button and the recipient bed (with metal and ceramic masks) were 2.5% and 2.5% in vertical diameter and 3.4% and 2.4% in horizontal diameter. The Q-switched Er:YAG laser experimental corneal trephination for penetrating keratoplasty may induce minor degrees of corneal diameter shrinkage in donor buttons and recipient openings. Oversizing of donor masks by 0.25-0.35 mm (i.e. 3-4% of graft size) may be a valid option to avoid refractive consequences.

  14. Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients.

    Science.gov (United States)

    Caporossi, Aldo; Mazzotta, Cosimo; Baiocchi, Stefano; Caporossi, Tomaso; Denaro, Rosario; Balestrazzi, Angelo

    2012-03-01

    Evaluation of stability and functional response after riboflavin-UVA–induced cross-linking in a population of patients younger than 18 years with progressive keratoconus after 36 months of follow-up. Prospective nonrandomized phase II open trial conducted at the Department of Ophthalmology, Siena University, Italy. The "Siena CXL Pediatrics" trial involved 152 patients aged 18 years or younger (10–18 years) with clinical and instrumental evidence of keratoconus progression. The population was divided into 2 groups according to corneal thickness (>450 and 450 μm) and +0.14 and +0.15 Snellen lines, respectively, in the thinner group (corneal thickness <450 μm). Patients in the latter group already showed a better and faster functional recovery than the thicker group at 3-month follow-up. Topographic results showed statistically significant improvement in K readings and asymmetry index values. Coma reduction was also statistically significant. The study demonstrated significant and rapid functional improvement in pediatric patients younger than 18 years with progressive keratoconus, undergoing riboflavin-UVA–induced cross-linking. In pediatric age, a good functional response and keratoconus stability was obtained after corneal cross-linking in a 36-month follow-up.

  15. Simultaneous bilensectomy and endothelial keratoplasty for angle-supported phakic intraocular lens-induced corneal decompensation

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2011-01-01

    Full Text Available A 40-year-old lady presented with severe endothelial cell loss in both eyes 14 years after angle-supported phakic intraocular lens (AS PIOL implantation. The left eye had severe corneal edema with bullous keratopathy. The right eye had markedly reduced endothelial cell count (655 cells/mm 2 although the cornea was clear. She underwent simultaneous bilensectomy (AS PIOL explantation and phacoemulsification and Descemet′s stripping and endothelial keratoplasty (DSEK in the left eye. Explanted AS PIOL was identified as ZSAL-4 (Morcher, Stuttgart, Germany model. Corneal edema cleared completely in 2 months with a best corrected visual acuity (-2.25 D sph of 20/60. No intervention was done in the right eye. The present case illustrates that AS PIOL-induced endothelial decompensation can be effectively managed by simultaneous bilensectomy and endothelial keratoplasty.

  16. CoQ10-containing eye drops prevent UVB-induced cornea cell damage and increase cornea wound healing by preserving mitochondrial function.

    Science.gov (United States)

    Mencucci, Rita; Favuzza, Eleonora; Boccalini, Carlotta; Lapucci, Andrea; Felici, Roberta; Resta, Francesco; Chiarugi, Alberto; Cavone, Leonardo

    2014-10-09

    We evaluated the potential protective effects of Coenzyme Q10 (CoQ10) on human corneal cells and rabbit eyes after ultraviolet B (UVB) exposure and a model of wound healing in rabbit eyes after corneal epithelium removal. Human corneal epithelium cells (HCE) were exposed to a source of UVB radiation (312 nM) in the presence of different CoQ10 concentrations or vehicle. The mitochondrial function and cell survival were evaluated by means of 3-(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium (MTT) reduction and lactic dehydrogenase (LDH) release. Furthermore, quantitation of oxygen consumption and mitochondrial membrane potential were conducted. In vivo rabbit models were adopted to evaluate the effect of CoQ10 on UVB-induced conjunctival vessel hyperemia and corneal recovery after ethanol induced corneal lesion. In UVB-exposed HCE cells, CoQ10 addition led to an increased survival rate and mitochondrial function. Furthermore, oxygen consumption was maintained at control levels and adenosine triphosphate (ATP) decline was completely prevented in the CoQ10-treated cells. Interestingly, in an in vivo model, CoQ10 was able dose-dependently to reduce UVB-induced vessel hyperemia. Finally, in a model of corneal epithelium removal, 12 hours from surgery, animals treated with CoQ10 showed a reduction of damaged area in respect to vehicle controls, which lasted until 48 hours. We demonstrated that CoQ10 reduces corneal damages after UVB exposure in vivo and in vitro by preserving mitochondrial function. Also, for the first time to our knowledge we showed that the administration of CoQ10 after corneal epithelium removal promotes corneal wound healing. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  17. Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

    Directory of Open Access Journals (Sweden)

    Xiao-Dan Hao

    2016-02-01

    Full Text Available AIM: To uncover the mutations profile of transforming growth factor beta-induced (TGFBI gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS: Forty-two subjects (6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS: We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy (GCD (including 3 families and 8 sporadic patients and lattice corneal dystrophy (LCD (including 2 families and 9 sporadic patients. The next phenotypes were corneal dystrophy of Bowman layer (CDB (1 family and 1 sporadic patient and epithelial basement membrane dystrophy (EBMD (1 sporadic patient. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient. CONCLUSION: GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD. Our findings extend the mutational spectrum of TFGBI, and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.

  18. Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Ji-Min Wang

    2014-12-01

    Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.

  19. Muscle damage induced by electrical stimulation.

    Science.gov (United States)

    Nosaka, Kazunori; Aldayel, Abdulaziz; Jubeau, Marc; Chen, Trevor C

    2011-10-01

    Electrical stimulation (ES) induces muscle damage that is characterised by histological alterations of muscle fibres and connective tissue, increases in circulating creatine kinase (CK) activity, decreases in muscle strength and development of delayed onset muscle soreness (DOMS). Muscle damage is induced not only by eccentric contractions with ES but also by isometric contractions evoked by ES. Muscle damage profile following 40 isometric contractions of the knee extensors is similar between pulsed current (75 Hz, 400 μs) and alternating current (2.5 kHz delivered at 75 Hz, 400 μs) ES for similar force output. When comparing maximal voluntary and ES-evoked (75 Hz, 200 μs) 50 isometric contractions of the elbow flexors, ES results in greater decreases in maximal voluntary contraction strength, increases in plasma CK activity and DOMS. It appears that the magnitude of muscle damage induced by ES-evoked isometric contractions is comparable to that induced by maximal voluntary eccentric contractions, although the volume of affected muscles in ES is not as large as that of eccentric exercise-induced muscle damage. It seems likely that the muscle damage in ES is associated with high mechanical stress on the activated muscle fibres due to the specificity of motor unit recruitment (i.e., non-selective, synchronous and spatially fixed manner). The magnitude of muscle damage induced by ES is significantly reduced when the second ES bout is performed 2-4 weeks later. It is possible to attenuate the magnitude of muscle damage by "pre-conditioning" muscles, so that muscle damage should not limit the use of ES in training and rehabilitation.

  20. Bean grain hysteresis with induced mechanical damage

    Directory of Open Access Journals (Sweden)

    Renata C. Campos

    Full Text Available ABSTRACT This study aimed to evaluate the effect of mechanical damage on the hysteresis of beans with induced mechanical damage under different conditions of temperature and relative humidity. Beans (Phaseolus vulgaris L. harvested manually with 35% water content (w.b. were used. Part of this product was subjected to induced mechanical damage by Stein Breakage Tester and controlled drying (damaged and control sample, for sorption processes. The sorption isotherms of water were analyzed for different temperature conditions: 20, 30, 40 and 50 oC; and relative humidity: 0.3; 0.4; 0.5; 0.7 and 0.9 (decimal. Equilibrium moisture content data were correlated with six mathematical models, and the Modified Oswin model was the one that best fitted to the experimental data. According to the above mentioned isotherms, it was possible to observe the phenomenon of hysteresis of damaged and control samples, and this phenomenon was more pronounced in control ones.

  1. Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

  2. Surgically induced astigmatism after 3.0 mm temporal and nasal clear corneal incisions in bilateral cataract surgery

    Directory of Open Access Journals (Sweden)

    Je Hwan Yoon

    2013-01-01

    Full Text Available Aims: To compare the corneal refractive changes induced after 3.0 mm temporal and nasal corneal incisions in bilateral cataract surgery. Materials and Methods: This prospective study comprised a consecutive case series of 60 eyes from 30 patients with bilateral phacoemulsification that were implanted with a 6.0 mm foldable intraocular lens through a 3.0 mm horizontal clear corneal incision (temporal in the right eyes, nasal in the left eyes. The outcome measures were surgically induced astigmatism (SIA and uncorrected visual acuity (UCVA 1 and 3 months, post-operatively. Results: At 1 month, the mean SIA was 0.81 diopter (D for the temporal incisions and 0.92 D for nasal incisions (P = 0.139. At 3 months, the mean SIA were 0.53 D for temporal incisions and 0.62 D for nasal incisions (P = 0.309. The UCVA was similar in the 2 incision groups before surgery, and at 1 and 3 months post-operatively. Conclusion: After bilateral cataract surgery using 3.0 mm temporal and nasal horizontal corneal incisions, the induced corneal astigmatic change was similar in both incision groups. Especially in Asian eyes, both temporal and nasal incisions (3.0 mm or less would be favorable for astigmatism-neutral cataract surgery.

  3. Corneal haze induced by excimer laser photoablation in rabbits is reduced by preserved human amniotic membrane graft

    Science.gov (United States)

    Wang, Ming X.; Gray, Trevor; Prabhasawat, Pinnita; Ma, Xiong; Culbertson, William; Forster, Richard; Hanna, Khalil; Tseng, Scheffer C. G.

    1998-06-01

    We conducted a study to determine if preserved human amniotic membrane can reduce corneal haze induced by excimer laser photoablation. Excimer photoablation was performed bilaterally on 40 New Zealand white rabbits with a 6 mm ablation zone and 120 micrometer depth (PTK) using the VISX Star. One eye was randomly covered with a preserved human amniotic membrane and secured using four interrupted 10 - 0 nylon sutures; the other eye served as control. The amniotic membranes were removed at one week, and the corneal haze was graded with a slit-lamp biomicroscopy by three masked corneal specialists (WC, KH and RF) biweekly for the ensuing 12 weeks. Histology and in situ TUNEL staining (for fragmented DNA as an index for apoptosis) was performed at days 1, 3 and 7 and at 12 weeks. One week after excimer photoablation, the amniotic membrane-covered corneas showed more anterior stromal edema, which resolved at the second week. A consistent grading of organized reticular corneal haze was noted among the three masked observers. Such corneal haze peaked at the seventh week in both groups. The amniotic membrane-covered group showed statistically significant less corneal haze (0.50 plus or minus 0.15) than the control groups (1.25 plus or minus 0.35) (p less than 0.001). The amniotic membrane-covered corneas had less inflammatory response at days 1 and 3, showing nearly nil DNA fragmentation on keratocytes on the ablated anterior stromal and less stromal fibroblast activation. There is less altered epithelial cell morphology and less epithelial hyperplasia at 1 week in these amniotic membrane-treated eyes. We concluded from this study that amniotic membrane matrix is effective in reducing corneal haze induced by excimer photoablation in rabbits and may have clinical applications.

  4. Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals.

    Science.gov (United States)

    Higuchi, Akihiro; Inoue, Hiroyoshi; Kaneko, Yoshio; Oonishi, Erina; Tsubota, Kazuo

    2016-11-11

    The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.

  5. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung-Ho [Chonnam National University, Gwangju (Korea, Republic of)

    2006-07-01

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  6. Effect of basic fibroblast growth factor on corneal endothelial cell damage after cataract surgery%bFGF改善白内障手术引发角膜内皮损伤

    Institute of Scientific and Technical Information of China (English)

    孙丹宇; 包赫; 姜仕先

    2016-01-01

    目的:探究碱性成纤维细胞生长因子(bFGF)对白内障手术引发角膜内皮损伤修复的作用。方法采用超声乳化摘除30只兔子(60眼)的晶体,将其分为2组,随机分为bFGF治疗组和对照组。bFGF治疗组滴用bFGF眼用凝胶,对照组滴用相同体积的生理盐水,分别每天滴用3次。观察记录2组眼睛消肿的时间;在手术后不同时间,分别检测2组切口的愈合面积、角膜厚度、角膜内皮细胞密度,分别取各组前房水,检测各组前房水中NO、IL-1、IL-6和TNF-α的含量。结果 bFGF治疗组的眼睛消肿时间较对照组显著减少(P<0.05);bFGF治疗加速了切口愈合速率、角膜厚度和角膜内皮细胞密度的恢复及前房水内NO、IL-1、IL-6和TNF-α的减少。结论 bFGF可改善白内障手术引起的角膜内皮细胞损伤。%Objective To explore the effect of basic fibroblast growth factor (bFGF)on corneal endothelial cell damage after cataract surgery.Methods Thirty rabbits (60 eyes)whose lens extraction were done by phacoemulsification were divided into 2 groups,namely,bF-GF treatment group and control group.bFGF ophthalmic gel was used to treat the eyes 3 times daily in bFGF treatment group,and the saline of the same volume was used to treat the eyes in control group.The time of corneal edema subsidence was recorded;the healing area of inci-sion,corneal thickness,the density of corneal endothelial cells and the NO,IL-1 ,IL-6 and TNF-αcontents of the aqueous sample in anterior chamber were measured.Results The time of corneal edema subsidence of bFGF treatment group decreased significantly compared with con-trol group;bFGF treatment accelerated the healing rate of incision,the recovery of corneal thickness and the density of corneal endothelial cells and the decrease of the NO,IL-1 IL-6 and TNF-αcontents of the aqueous sample in anterior chamber.Conclusion bFGF treatment can accelerate the recovery of the corneal

  7. Corneal Laceration

    Medline Plus

    Full Text Available ... Laceration? Corneal Laceration Diagnosis Corneal Laceration Treatment What Is Corneal Laceration? Written By: Daniel Porter Reviewed By: ... A Harrison MD Sep. 01, 2016 The cornea is the clear front window of the eye . A ...

  8. Modelling of settlement induced building damage

    NARCIS (Netherlands)

    Giardina, G.

    2013-01-01

    This thesis focuses on the modelling of settlement induced damage to masonry buildings. In densely populated areas, the need for new space is nowadays producing a rapid increment of underground excavations. Due to the construction of new metro lines, tunnelling activity in urban areas is growing.

  9. Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

    Science.gov (United States)

    Tsai, Ching-Yao; Woung, Lin-Chung; Yen, Jiin-Cherng; Tseng, Po-Chen; Chiou, Shih-Hwa; Sung, Yen-Jen; Liu, Kuan-Ting; Cheng, Yung-Hsin

    2016-01-01

    Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.

  10. Molecular mechanisms of dust-induced toxicity in human corneal epithelial cells: Water and organic extract of office and house dust.

    Science.gov (United States)

    Xiang, Ping; Liu, Rong-Yan; Sun, Hong-Jie; Han, Yong-He; He, Rui-Wen; Cui, Xin-Yi; Ma, Lena Q

    2016-01-01

    Human corneal epithelial (HCE) cells are continually exposed to dust in the air, which may cause corneal epithelium damage. Both water and organic soluble contaminants in dust may contribute to cytotoxicity in HCE cells, however, the associated toxicity mechanisms are not fully elucidated. In this study, indoor dust from residential houses and commercial offices in Nanjing, China was collected and the effects of organic and water soluble fraction of dust on primary HCE cells were examined. The concentrations of heavy metals in the dust and dust extracts were determined by ICP-MS and PAHs by GC-MS, with office dust having greater concentrations of heavy metals and PAHs than house dust. Based on LC50, organic extract was more toxic than water extract, and office dust was more toxic than house dust. Accordingly, the organic extracts induced more ROS, malondialdehyde, and 8-Hydroxydeoxyguanosine and higher expression of inflammatory mediators (IL-1β, IL-6, and IL-8), and AhR inducible genes (CYP1A1, and CYP1B1) than water extracts (pdust presented greater suppression of superoxide dismutase and catalase activity than those of house dust. In addition, exposure to dust extracts activated NF-κB signal pathway except water extract of house dust. The results suggested that both water and organic soluble fractions of dust caused cytotoxicity, oxidative damage, inflammatory response, and activation of AhR inducible genes, with organic extracts having higher potential to induce adverse effects on primary HCE cells. The results based on primary HCE cells demonstrated the importance of reducing contaminants in indoor dust to reduce their adverse impacts on human eyes.

  11. Tissue culture and in vivo modelling of corneal opacification and ocular injuries induced by millimeter waves. Annual summary report, June 1981-May 1982

    Energy Technology Data Exchange (ETDEWEB)

    Trevithick, J.R.

    1982-06-01

    The eventual aims of these experiments are to use intact corneas incubated in vitro and corneas of rats in vivo to high-energy pulsed millimeter waves to study the development of corneal damage. Such experiments are expected to establish conditions for corneal damage and to elucidate the mechanisms by which the damage occurs. If intact corneal explants are cultured in tissue culture dishes in medium 35.5 C continuing outgrowth of the epithelial cells occurrs from the edge of the explants during a period of at least two weeks. Exposure for shorter periods of such cultured corneas to elevated temperatures and vitamin A followed by fixation for light microscopy (SEM) revealed progressive cellular damage as the temperature increased and some vitamin uptake which is being studied further, buy biochemical techniques.

  12. Chronic exposure to the ultraviolet radiation levels from arc welding does not result in obvious damage to the human corneal endothelium.

    Science.gov (United States)

    Oblak, Emil; Doughty, Michael J

    2002-11-01

    Occupational exposure of the cornea to ultraviolet radiation (UVR, e.g. in welding) is a well-known cause of 'arc eye' (photo-keratoconjunctivitis), but has also been considered to be a risk for the development of alterations in the size (polymegethism) and shape (pleomorphism) of the deeper-lying human corneal endothelial cells. Human data are however limited and so a further study was undertaken, with a control group. Non-contact specular micrographs of the central region of the corneal endothelium were obtained from 40 white males aged between 32 and 63 years; 20 were arc welders with an average of 25 +/- 7 years job experience, while the others were office workers (n = 20). All the welders reported occupational exposure to UVR (i.e. welders 'flashes') and up to 3 times per year. None of the subjects had a history of contact lens wear, major eye disease or surgery. The endothelial image was scanned, projected onto an overlay and cell border marking carried out in a masked fashion. The overlay was independently analysed, by a customised semi-automated method, providing cell-border-adjusted data on cell areas and cell shape (sides) on 124 to 260 cells per image. The endothelial cell density (ECD) values were also calculated from individual cell area values. All corneas appeared to be healthy, and showed no fluorescein staining indicating damage to the surface epithelium. Central corneal thickness values were normal at 0.531 +/- 0.031 (mean +/- SD) and 0.527 +/- 0.036 mm in the welders and non-welders respectively. All endothelia appeared healthy, with no evidence of cell oedema. The group-mean endothelial cell area was 393 +/- 35 and 392 +/- 21 microm2, ECD values were 2855 +/- 224 cells mm(-2) and 2852 +/- 210 cells mm(-2), while the percentages of 6-sided cells were 60 +/- 5.2 and 59 +/- 4.1% respectively. Cell area distributions were statistically identical (p > or = 0.8), and cell area-side relationships were marginally, but not statistically different. This

  13. Epidermal growth factor (EGF)-induced corneal epithelial wound healing through nuclear factor κB subtype-regulated CCCTC binding factor (CTCF) activation.

    Science.gov (United States)

    Wang, Ling; Wu, Xiaolin; Shi, Ting; Lu, Luo

    2013-08-23

    Epidermal growth factor (EGF) plays an important role in corneal epithelial migration and proliferation to improve the wound healing process. This study aimed to understand the role of NFκB in EGF-induced corneal epithelial wound healing through regulation of CTCF activity, which plays important roles in cell motility and migration to promote wound healing. The effect of NFκB p50 on corneal epithelial wound healing was investigated by comparing the eyes of wild-type and p50 knockout mice. We found that there was a significant retardation in corneal epithelial wound healing in the corneas of p50 knockout mice. Wound closure rates were measured in human corneal epithelial cells transfected with an NFκB activation-sensitive CTCF expression construct to demonstrate the effect of human CTCF expression under the control of EGF-induced NFκB activation on wound healing. EGF stimulation activated NFκB, which directly triggered the expression of the exogenous human CTCF in transfected cells and, subsequently, promoted human corneal epithelial cell motility, migration, and wound healing. Overexpression of CTCF in corneal epithelial cells and mouse corneas significantly enhanced the wound healing process. Furthermore, the effect of overexpressing NFκB p50 in corneal epithelial cells on the promotion of wound healing was abolished by knockdown of CTCF with CTCF-specific shRNA. Thus, a direct regulatory relationship between EGF-induced NFκB p50 and CTCF activation affecting corneal epithelial wound healing has been established, indicating that CTCF is, indeed, a NFκB p50-targeted and effective gene product in the core transcriptional network downstream from the growth factor-induced NFκB signaling pathway.

  14. Transforming growth factor-β2 induces morphological alteration of human corneal endothelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing; Wang; Ting-Jun; Fan; Xiu-Xia; Yang; Shi-Min; Chang

    2014-01-01

    AIM:To investigate the morphological altering effect of transforming growth factor-β2(TGF-β2) on untransfected human corneal endothelial cells(HCECs)in vitro.METHODS:After untransfected HCECs were treated with TGF-β2 at different concentrations, the morphology,cytoskeleton distribution, and type IV collagen expression of the cells were examined with inverted contrast light microscopy, fluorescence microscopy,immunofluorescence or Western Blot.RESULTS:TGF-β2 at the concentration of 3-15 μg/L had obviously alterative effects on HCECs morphology in dose and time-dependent manner, and 9 μg/L was the peak concentration. TGF-β2(9 μg/L) altered HCE cell morphology after treatment for 36 h, increased the mean optical density(P <0.01) and the length of F-actin,reduced the mean optical density(P <0.01) of the collagen type IV in extracellular matrix(ECM) and induced the rearrangement of F-actin, microtubule in cytoplasm and collagen type IV in ECM after treatment for 72 h.·CONCLUTION: TGF-β2 has obviously alterative effect on the morphology of HCECs from polygonal phenotype to enlarged spindle-shaped phenotype, in dose and time-dependence manner by inducing more, elongation and alignment of F-actin, rearrangement of microtubule and larger spread area of collagen type IV.

  15. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  16. Corneal Laceration

    Medline Plus

    Full Text Available ... your vision. Privacy Policy Related People with Advanced Keratoconus May Have A Future Alternative to Full Corneal ... 2016 Corneal Collagen Cross-linking Approved to Treat Keratoconus in U.S. Aug 01, 2016 Firework Blinds Teenager, ...

  17. Corneal Laceration

    Medline Plus

    Full Text Available ... lost sight from a corneal scar as a child. Now that I’m older, will a corneal transplant help me? May 15, 2015 Why Do My Eyes Burn After Inserting My Contacts? Feb 27, 2015 Dark ...

  18. Corneal Abrasions

    Science.gov (United States)

    ... and lead to a serious condition called a corneal ulcer . That's why it's important to see a doctor to get a corneal abrasion checked out. What Causes a Corneal ... and land on your cornea, tears help to wash the particles away. Sometimes, ...

  19. Inhibition by a selective IkappaB kinase-2 inhibitor of interleukin-1-induced collagen degradation by corneal fibroblasts in three-dimensional culture.

    Science.gov (United States)

    Kondo, Yukiko; Fukuda, Ken; Adachi, Tadafumi; Nishida, Teruo

    2008-11-01

    Corneal ulcer results from excessive collagen degradation in the corneal stroma. Interleukin (IL)-1 promotes this process by activating signaling molecules that include nuclear factor (NF)-kappaB and stimulating the synthesis of matrix metalloproteinases (MMPs) in corneal fibroblasts. NF-kappaB activation is mediated by phosphorylation of the inhibitor IkappaB by IkappaB kinase (IKK)-2 and consequent IkappaB degradation. The authors investigated the effects of the IKK-2 inhibitor [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1) on collagen degradation by corneal fibroblasts. Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels. Collagen degradation was evaluated by spectrophotometric quantitation of hydroxyproline in culture supernatants subjected to acid-heat hydrolysis. Expression of MMPs was evaluated by immunoblot analysis, gelatin zymography, and real-time reverse transcription polymerase chain reaction analysis. The phosphorylation and degradation of IkappaBalpha and the subcellular localization of NF-kappaB were examined by immunoblot and immunofluorescence analyses, respectively. IL-1beta-induced collagen degradation by corneal fibroblasts was inhibited by TPCA-1 in a concentration- and time-dependent manner. TPCA-1 inhibited the IL-1beta-induced expression of MMP-1, -3, and -9 in these cells at both the mRNA and protein levels and the IL-1beta-induced activation of pro-MMP-2. In contrast to dexamethasone, TPCA-1 inhibited the phosphorylation and degradation of IkappaBalpha and the nuclear translocation of NF-kappaB induced by IL-1beta. An IKK-2 inhibitor blocked IL-1beta-induced collagen degradation by corneal fibroblasts by inhibiting the activation of the NF-kappaB signaling pathway and the upregulation of MMPs. IKK-2 inhibitors are thus potential alternatives to dexamethasone for the treatment of corneal ulcer.

  20. Monitoring of cornea elastic properties changes during UV-A/riboflavin-induced corneal collagen cross-linking using supersonic shear wave imaging: a pilot study.

    Science.gov (United States)

    Nguyen, Thu-Mai; Aubry, Jean-François; Touboul, David; Fink, Mathias; Gennisson, Jean-Luc; Bercoff, Jeremy; Tanter, Mickael

    2012-08-31

    Keratoconus disease or post-LASIK corneal ectasia are increasingly treated using UV-A/riboflavin-induced corneal collagen cross-linking (CXL). However, this treatment suffers from a lack of techniques to provide an assessment in real-time of the CXL effects. Here, we investigated the potential interest of corneal elasticity as a biomarker of the efficacy of this treatment. For this purpose, supersonic shear wave imaging (SSI) was performed both ex vivo and in vivo on porcine eyes before and after CXL. Based on ultrasonic scanners providing ultrafast frame rates (~30 kHz), the SSI technique generates and tracks the propagation of shear waves in tissues. It provides two- and three-dimensional (2-D and 3-D) quantitative maps of the corneal elasticity. After CXL, quantitative maps of corneal stiffness clearly depicted the cross-linked area with a typical 200-μm lateral resolution. The CXL resulted in a 56% ± 15% increase of the shear wave speed for corneas treated in vivo (n = 4). The in vivo CXL experiments performed on pigs demonstrated that the quantitative estimation of local stiffness and the 2-D elastic maps of the corneal surface provide an efficient way to monitor the local efficacy of corneal cross-linking.

  1. Modeling of Corrosion-induced Concrete Damage

    DEFF Research Database (Denmark)

    Thybo, Anna Emilie A.; Michel, Alexander; Stang, Henrik

    2013-01-01

    In the present paper a finite element model is introduced to simulate corrosion-induced damage in concrete. The model takes into account the penetration of corrosion products into the concrete as well as non-uniform formation of corrosion products around the reinforcement. To ac-count for the non......-uniform formation of corrosion products at the concrete/reinforcement interface, a deterministic approach is used. The model gives good estimates of both deformations in the con-crete/reinforcement interface and crack width when compared to experimental data. Further, it is shown that non-uniform deposition...... of corrosion products affects both the time-to cover cracking and the crack width at the concrete surface....

  2. Ion irradiation induced direct damage to DNA

    CERN Document Server

    Wang, Wei; Su, Wenhui

    2008-01-01

    Ion beams have been widely applied in a few biological research fields such as radioactive breeding, health protection, and tumor therapy. Up to now many interesting and impressive achievements in biology and agriculture have been made. Over the past several decades, scientists in biology, physics, and chemistry have pursued investigations focused on understanding the mechanisms of these radiobiological effects of ion beams. From the chemical point of view, these effects are due to the ion irradiation induced biomolecular damage, direct or indirect. In this review, we will present a chemical overview of the direct effects of ion irradiation upon DNA and its components, based on a review of literature combined with recent experimental results. It is suggested that, under ion bombardment, a DNA molecule undergoes a variety of processes, including radical formation, atomic displacement, intramolecular bond-scissions, emission of fragments, fragment recombination and molecular crosslink, which may lead to genetic...

  3. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hong [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); Wu, Xinyi, E-mail: xywu8868@163.com [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-{beta}. Black-Right-Pointing-Pointer Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. Black-Right-Pointing-Pointer Hypoxia inhibits Acanthamoeba-induced the activation of NF-{kappa}B and ERK1/2 in HCECs. Black-Right-Pointing-Pointer Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. Black-Right-Pointing-Pointer LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cells has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-{beta} (IFN-{beta}) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-{beta}. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-{kappa}B and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response gene (88

  4. Progress of research on corneal collagen cross-linking for corneal melting

    Directory of Open Access Journals (Sweden)

    Ke-Ren Xiao

    2016-06-01

    Full Text Available Corneal collagen cross-linking(CXLcould increase the mechanical strength, biological stability and halt ectasia progression due to covalent bond formed by photochemical reaction between ultraviolet-A and emulsion of riboflavin between collagen fibers in corneal stroma. Corneal melting is an autoimmune related noninfectious corneal ulcer. The mechanism of corneal melting, major treatment, the basic fundamental of ultraviolet-A riboflavin induced CXL and the clinical researches status and experiment in CXL were summarized in the study.

  5. Involvement of P38MAPK in human corneal endothelial cell migration induced by TGF-β(2).

    Science.gov (United States)

    Joko, Takeshi; Shiraishi, Atsushi; Akune, Yoko; Tokumaru, Sho; Kobayashi, Takeshi; Miyata, Kazunori; Ohashi, Yuichi

    2013-03-01

    Because human corneal endothelial cells do not proliferate once the endothelial monolayer is formed, corneal wound healing is thought to be mediated by cell enlargement or migration rather than proliferation. However, the cellular mechanisms involved in corneal wound healing have not been fully determined. Because transforming growth factor-β(2) (TGF-β(2)) isoform is present in high concentrations in normal human aqueous humor, it may play a role in human corneal endothelial cell wound healing. The purpose of this study was to determine the effect of TGF-β(2) on the proliferation and migration of cultured human corneal endothelial cells (HCECs). To achieve this, we first examined the effect of TGF-β(2) on the wound closure rate in an in vitro HCEC wound healing model. However, unexpectedly TGF-β(2) had no effect on the wound closure rate in this model. Therefore, a real-time cell electronic sensing (RT-CES) system and the BrdU incorporation assay were used to determine the effect of TGF-β(2) (0.1-10 ng/ml) on cultured HCEC proliferation during in vitro wound healing. The specificity of this effect was confirmed by adding the TGF-β receptor I kinase inhibitor. TGF-β(2) inhibited the proliferation of HCECs in a dose dependent way and was blocked by TGF-β receptor I kinase inhibitor. Next, the Boyden chamber assay was used to determine how TGF-β(2) (10 ng/ml) affect HCEC migration. Exposure to TGF-β(2) increased cell migration, and a synergistic effect was observed when FGF-2 was added. To determine whether the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the migration of HCECs, western blot analysis and Bio-Plex™ suspension array were used to detect phosphorylation of Erk1/2, p38, and JNK in HCECs stimulated by TGF-β(2) and/or FGF-2. The effect of the p38 MAPK inhibitor, SB239063 (10 μM), on TGF-β(2) and/or FGF-2-induced cellular migration was determined by the Boyden chamber assay. Both TGF-β(2) and FGF-2-induced p38

  6. Corneal Topographic Changes After Eyelid Ptosis Surgery.

    Science.gov (United States)

    Savino, Gustavo; Battendieri, Remo; Riso, Monica; Traina, Salvatore; Poscia, Andrea; DʼAmico, Giovanni; Caporossi, Aldo

    2016-04-01

    To evaluate the corneal topography and the topographic changes after ptosis surgery on patients affected by congenital and acquired blepharoptosis. Twenty eyes of 17 patients affected by acquired and congenital ptosis underwent surgical correction through anterior levator complex tightening. Computerized tomography (Syrius Sistem; CSO) was used to analyze any change in corneal astigmatism (CYL), simulated keratometry, anterior corneal symmetry index front, apical keratometry front, and central corneal thickness. Visual acuity, margin reflex distance, and levator function were also measured. After surgical ptosis repair, corneal topography demonstrated a reduction in average keratometry of 0.15 ± 0.47 diopters (D) and in corneal astigmatism of 0.26 ± 1.12 D. Significant differences were found in apical keratometry front (-1.84 ± 1.76 D) and in best-corrected visual acuity (-0.18 ± 0.06 logMAR) in the postoperative examinations. Central corneal thickness did not show significant differences between preoperative and postoperative examinations. Postoperative topographic maps showed a reduction of symmetry index front (0.10 ± 0.64 D). Eyelid ptosis modifies anterior corneal surface inducing refractive errors and modifying corneal astigmatism in patients, thus affecting the quality of vision. The surgical correction of blepharoptosis induces anterior corneal surface modification, restoring corneal symmetry and regular corneal astigmatism. Postoperative corneal topography showed normal corneal contours.

  7. Reconstruction of Rabbit Corneal Layer Composed of Corneal Fibroblasts and Corneal Epithelium on the Lyophilized Amniotic Membrane

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Many researchers have employed the cryopreserved amniotic membrane(CAM) and corneal epithelial cells in the treatment of a severely damaged burned cornea, with corneal epithelial cells cultured on an amniotic membrane (AM). The lyophilized amniotic membrane (LAM) has a higher graft take and a longer shelf life; it is easier to store and safer because of gamma irradiation. Two Teflon rings(Ahn's supporter) were made for culturing the cells on the LAM, and were then used to support the LAM. To reconstruct a corneal layer composed of corneal fibroblasts and epithelium, the corneal fibroblasts were first cultivated on the stromal side of LAM for five days, followed by epithelial cells culture on the epithelial side, by using the air-liquid interface culture. The reconstructed corneal layer composed of corneal fibroblasts and corneal epithelial cells has a much healthier basal layer of corneal epithelium than the reconstructed corneal epithelium, which was got by using only corneal epithelial cells, and resembles the epithelium of normal corneas, without the horny layer. Thus, the reconstruction of the corneal layer by using a LAM is considered to be a good in vitro model, not only for its application in toxicological test kits, but also for transplantation in patients with a severely damaged cornea.

  8. Apoptosis of Corneal Epithelial Cells Caused by Ultraviolet B-induced Loss of K(+) is Inhibited by Ba(2.).

    Science.gov (United States)

    Glupker, Courtney D; Boersma, Peter M; Schotanus, Mark P; Haarsma, Loren D; Ubels, John L

    2016-07-01

    UVB exposure at ambient outdoor levels triggers rapid K(+) loss and apoptosis in human corneal limbal epithelial (HCLE) cells cultured in medium containing 5.5 mM K(+), but considerably less apoptosis occurs when the medium contains the high K(+) concentration that is present in tears (25 mM). Since Ba(2+) blocks several K(+) channels, we tested whether Ba(2+)-sensitive K(+) channels are responsible for some or all of the UVB-activated K(+) loss and subsequent activation of the caspase cascade and apoptosis. Corneal epithelial cells in culture were exposed to UVB at 80 or 150 mJ/cm(2). Patch-clamp recording was used to measure UVB-induced K(+) currents. Caspase-activity and TUNEL assays were performed on HCLE cells exposed to UVB followed by incubation in the presence or absence of Ba(2+). K(+) currents were activated in HCLE cells following UVB-exposure. These currents were reversibly blocked by 5 mM Ba(2+). When HCLE cells were incubated with 5 mM Ba(2+) after exposure to UVB, activation of caspases-9, -8, and -3 and DNA fragmentation were significantly decreased. The data confirm that UVB-induced K(+) current activation and loss of intracellular K(+) leads to activation of the caspase cascade and apoptosis. Extracellular Ba(2+) inhibits UVB-induced apoptosis by preventing loss of intracellular K(+) when K(+) channels are activated. Ba(2+) therefore has effects similar to elevated extracellular K(+) in protecting HCLE cells from UVB-induced apoptosis. This supports our overall hypothesis that elevated K(+) in tears contributes to protection of the corneal epithelium from adverse effects of ambient outdoor UVB.

  9. Corneal collagen crosslinking: a systematic review.

    Science.gov (United States)

    Sorkin, Nir; Varssano, David

    2014-01-01

    Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.

  10. The Effects of Triptolide on HLA Antigens Expression of Corneal Epithelial Cells Induced by Interferon-γin Vitro

    Institute of Scientific and Technical Information of China (English)

    Qi Zhao; Yiezi Liu; Quanfu Li

    2000-01-01

    Objective: To observe the effects of immunosuppressants triptolide (TL) and cyclosporine A (CSA) on HLA antigens expression induced by interferon-γ(INF -γ) in vitro.Method: By using an indirect immunofluorescent method and analysing with ACAS-570, the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ. After incubation with one of the immunosuppressants (CSA, TL) for 72 hrs, the amount of HLA-A BC and HLA-DR antigens was measured.Result: There was no significant difference ( P > 0.05) between the group with CSA and the positive control group without CSA. In contrast to CSA, TL dramatically inhibited INF-γ induced expression of HLA antigens of corneal epithelial cells (P<0.001), compared with the control group without TL.Conclusion: TL had direct inhibition on the expression of HLA-ABCand HLA-DR antigens induced by INF-γin vitro, while CSA had no obvious inhibition. Eye Science 2000; 16:34 ~ 37.

  11. Blood-induced joint damage: novel targets for therapy

    NARCIS (Netherlands)

    van Meegeren, M.E.R.

    2012-01-01

    -induced joint damage can occur due to a trauma but also during surgery when blood leaks into the joint cavity. Besides that, it is one of the major causes of morbidity amongst haemophilia patients. The aims of this thesis were to further unravel the pathogenesis of blood-induced joint damage and to

  12. Nanoscale topography-induced modulation of fundamental cell behaviors of rabbit corneal keratocytes, fibroblasts, and myofibroblasts.

    Science.gov (United States)

    Pot, Simon A; Liliensiek, Sara J; Myrna, Kathern E; Bentley, Ellison; Jester, James V; Nealey, Paul F; Murphy, Christopher J

    2010-03-01

    Keratocyte-to-myofibroblast differentiation is a key factor in corneal wound healing. The purpose of this study was to determine the influence of environmental nanoscale topography on keratocyte, fibroblast, and myofibroblast cell behavior. Primary rabbit corneal keratocytes, fibroblasts, and myofibroblasts were seeded onto planar polyurethane surfaces with six patterned areas, composed of anisotropically ordered grooves and ridges with a 400-, 800-, 1200-, 1600-, 2000-, and 4000-nm pitch (pitch = groove + ridge width). After 24 hours cells were fixed, stained, imaged, and analyzed for cell shape and orientation. For migration studies, cells on each patterned surface were imaged every 10 minutes for 12 hours, and individual cell trajectories and migration rates were calculated. Keratocytes, fibroblasts, and myofibroblasts aligned and elongated to pitch sizes larger than 1000 nm. A lower limit to the topographic feature sizes that the cells responded to was identified for all three phenotypes, with a transition zone around the 800- to 1200-nm pitch size. Fibroblasts and myofibroblasts migrated parallel to surface ridges larger than 1000 nm but lacked directional guidance on submicron and nanoscale topographic features and on planar surfaces. Keratocytes remained essentially immobile. Corneal stromal cells elongated, aligned, and migrated, differentially guided by substratum topographic features. All cell types failed to respond to topographic features approximating the dimensions of individual stromal fibers. These findings contribute to our understanding of corneal stromal cell biology in health and disease and their interaction with biomaterials and their native extracellular matrix.

  13. Acrylonitrile-induced oxidative DNA damage in rat astrocytes.

    Science.gov (United States)

    Pu, Xinzhu; Kamendulis, Lisa M; Klaunig, James E

    2006-10-01

    Chronic administration of acrylonitrile results in a dose-related increase in astrocytomas in rat brain, but the mechanism of acrylonitrile carcinogenicity is not fully understood. The potential of acrylonitrile or its metabolites to induce direct DNA damage as a mechanism for acrylonitrile carcinogenicity has been questioned, and recent studies indicate that the mechanism involves the induction of oxidative stress in rat brain. The present study examined the ability of acrylonitrile to induce DNA damage in the DI TNC1 rat astrocyte cell line using the alkaline Comet assay. Oxidized DNA damage also was evaluated using formamidopyrimidine DNA glycosylase treatment in the modified Comet assay. No increase in direct DNA damage was seen in astrocytes exposed to sublethal concentrations of acrylonitrile (0-1.0 mM) for 24 hr. However, acrylonitrile treatment resulted in a concentration-related increase in oxidative DNA damage after 24 hr. Antioxidant supplementation in the culture media (alpha-tocopherol, (-)-epigallocathechin-3 gallate, or trolox) reduced acrylonitrile-induced oxidative DNA damage. Depletion of glutathione using 0.1 mM DL-buthionine-[S,R]-sulfoximine increased acrylonitrile-induced oxidative DNA damage (22-46%), while cotreatment of acrylonitrile with 2.5 mM L-2-oxothiazolidine-4-carboxylic acid, a precursor for glutathione biosynthesis, significantly reduced acrylonitrile-induced oxidative DNA damage (7-47%). Cotreatment of acrylonitrile with 0.5 mM 1-aminobenzotriazole, a suicidal inhibitor of cytochrome P450, prevented the oxidative DNA damage produced by acrylonitrile. Cyanide (0.1-0.5 mM) increased oxidative DNA damage (44-160%) in astrocytes. These studies demonstrate that while acrylonitrile does not directly damage astrocyte DNA, it does increase oxidative DNA damage. The oxidative DNA damage following acrylonitrile exposure appears to arise mainly through the P450 metabolic pathway; moreover, glutathione depletion may contribute to the

  14. Corneal Laceration

    Science.gov (United States)

    ... drugs. These drugs thin the blood and may increase bleeding. After you have finished protecting the eye, see a physician immediately. Next Corneal Laceration Symptoms Related Ask an Ophthalmologist Answers I lost sight from a corneal scar as a child. Now that I’m older, ...

  15. Corneal Laceration

    Medline Plus

    Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration ... Laceration Treatment What Is Corneal Laceration? Leer en Español: ¿Qué Es una Laceración de la Córnea? Written ...

  16. Corneal Laceration

    Medline Plus

    Full Text Available ... Health Find an Ophthalmologist Academy Store Eye Health A-Z Symptoms Glasses & Contacts Tips & Prevention News Ask ... Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration Sections What Is Corneal Laceration? ...

  17. Corneal Laceration

    Medline Plus

    Full Text Available ... Health Find an Ophthalmologist Academy Store Eye Health A-Z Symptoms Glasses & Contacts Tips & Prevention News Ask ... Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration Sections What Is Corneal Laceration? ...

  18. Heat induced damage detection in composite materials by terahertz radiation

    Science.gov (United States)

    Radzieński, Maciej; Mieloszyk, Magdalena; Rahani, Ehsan Kabiri; Kundu, Tribikram; Ostachowicz, Wiesław

    2015-03-01

    In recent years electromagnetic Terahertz (THz) radiation or T-ray has been increasingly used for nondestructive evaluation of various materials such as polymer composites and porous foam tiles in which ultrasonic waves cannot penetrate but T-ray can. Most of these investigations have been limited to mechanical damage detection like inclusions, cracks, delaminations etc. So far only a few investigations have been reported on heat induced damage detection. Unlike mechanical damage the heat induced damage does not have a clear interface between the damaged part and the surrounding intact material from which electromagnetic waves can be reflected back. Difficulties associated with the heat induced damage detection in composite materials using T-ray are discussed in detail in this paper. T-ray measurements are compared for different levels of heat exposure of composite specimens.

  19. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  20. Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.

    Science.gov (United States)

    Kovács, Illés; Dienes, Lóránt; Perényi, Kristóf; Quirce, Susana; Luna, Carolina; Mizerska, Kamila; Acosta, M Carmen; Belmonte, Carlos; Gallar, Juana

    2016-09-15

    Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; Placosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (Placosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease.

  1. Chemically induced intestinal damage models in zebrafish larvae.

    Science.gov (United States)

    Oehlers, Stefan H; Flores, Maria Vega; Hall, Christopher J; Okuda, Kazuhide S; Sison, John Oliver; Crosier, Kathryn E; Crosier, Philip S

    2013-06-01

    Several intestinal damage models have been developed using zebrafish, with the aim of recapitulating aspects of human inflammatory bowel disease (IBD). These experimentally induced inflammation models have utilized immersion exposure to an array of colitogenic agents (including live bacteria, bacterial products, and chemicals) to induce varying severity of inflammation. This technical report describes methods used to generate two chemically induced intestinal damage models using either dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). Methods to monitor intestinal damage and inflammatory processes, and chemical-genetic methods to manipulate the host response to injury are also described.

  2. Laser-Induced Thermal Damage of Skin

    Science.gov (United States)

    1977-12-01

    As with the eye model, ther- mal damage is predicted using Henriques damage integral (11). This criterion involves integrating temperature- dependent...epide•: mal layers are much larger than the coefficients for the entire skin presented in Figure 5. This observation suggests there should be twd...EXPOI"’ES INVOLVJINS MUMtPLE PULSES OTOODYCIZO 010OTO OJO SI tNGLE PUL.$LSE 19(M."ft 7.13NP#R5 xxsLlimft p DO 3 ?V 36 Ep(MgiSNPRCL) *~To so 36

  3. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  4. A Plasticity Induced Anisotropic Damage Model for Sheet Forming Processes

    NARCIS (Netherlands)

    Niazi, M.S.; Meinders, V.T.; Wisselink, H.H.; Horn, ten C.H.L.J.; Klaseboer, G.; Boogaard, van den A.H.

    2013-01-01

    Plastic deformation induces damage in Advanced High Strength Steels (AHSS). Therefore damage development in these steels shall be studied and incorporated in the simulations for accurate failure predictions in forming processes and for determination of the product properties after forming. An effici

  5. Corneal Laceration

    Medline Plus

    Full Text Available ... from Laundry Packets On the Rise Jun 30, 2017 People with Advanced Keratoconus May Have A Future Alternative to Full Corneal Transplantation Nov 29, 2016 Combating Eye Injuries from Air Guns Aug 30, ...

  6. Corneal transplant

    Science.gov (United States)

    ... lenses to achieve the best vision. Laser vision correction may be an option if you have nearsightedness, ... Editorial team. Related MedlinePlus Health Topics Corneal Disorders Refractive Errors Browse the Encyclopedia A.D.A.M., Inc. ...

  7. Corneal Laceration

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    Full Text Available ... Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide ... What Is Corneal Laceration? Leer en Español: ¿Qué ...

  8. Corneal Laceration

    Medline Plus

    Full Text Available ... itself. A corneal laceration is a very serious injury and requires immediate medical attention to avoid severe ... Dangerous for Your Eyes Sep 20, 2017 Eye Injuries from Laundry Packets On the Rise Jun 30, ...

  9. Corneal Laceration

    Medline Plus

    Full Text Available ... itself. A corneal laceration is a very serious injury and requires immediate medical attention to avoid severe ... 27, 2015 Dark Spot in Vision After Blunt Trauma Dec 21, 2014 Pain a Year After Eyelid ...

  10. Corneal Laceration

    Medline Plus

    Full Text Available ... itself. A corneal laceration is a very serious injury and requires immediate medical attention to avoid severe ... and preserving your vision. Privacy Policy Related Eye Injuries from Laundry Packets On the Rise Jun 30, ...

  11. Corneal Laceration

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    Full Text Available ... 2017 People with Advanced Keratoconus May Have A Future Alternative to Full Corneal Transplantation Nov 29, 2016 Combating Eye Injuries from Air Guns Aug 30, ... Public & Patients: Contact Us About ...

  12. Corneal Laceration

    Medline Plus

    Full Text Available ... by something sharp flying into the eye. It can also be caused by something striking the eye ... If the corneal laceration is deep enough it can cause a full thickness laceration. This is when ...

  13. Corneal Laceration

    Medline Plus

    Full Text Available ... Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide ... What Is Corneal Laceration? Written By: Daniel Porter ...

  14. Corneal Laceration

    Medline Plus

    Full Text Available ... By: Devin A Harrison MD Sep. 01, 2017 The cornea is the clear front window of the eye . A corneal laceration is a cut on the cornea. It is usually caused by something sharp ...

  15. Corneal Laceration

    Medline Plus

    Full Text Available ... itself. A corneal laceration is a very serious injury and requires immediate medical attention to avoid severe ... 27, 2015 Dark Spot in Vision After Blunt Trauma Dec 21, 2014 Pain a Year After Eyelid ...

  16. Simulation study of radiation damage induced by energetic helium nuclei

    CERN Document Server

    Hoang Dac Luc; Hoang Dac Dat

    2003-01-01

    High energy alpha particles produced by neutron-induced nuclear reactions can damage severely reactor materials. Simulation of this process is described using theoretical calculation and ion irradiation experiments at different displacement doses and Helium doses.

  17. Micromechanics of diffusion-induced damage evolution in reinforced polymers

    DEFF Research Database (Denmark)

    Abhilash, A.S.; Joshi, Shailendra P.; Mukherjee, Abhijit

    2011-01-01

    -induced damage provides synergistic conditions for the rapid evolution of debonding under subsequent mechanical loading. The results indicate that microstructural heterogeneity strongly affects the moisture diffusion characteristics that in turn hurt the overall load carrying capacity of a composite due...

  18. Density of oxidation-induced stacking faults in damaged silicon

    NARCIS (Netherlands)

    Kuper, F.G.; Hosson, J.Th.M. De; Verwey, J.F.

    1986-01-01

    A model for the relation between density and length of oxidation-induced stacking faults on damaged silicon surfaces is proposed, based on interactions of stacking faults with dislocations and neighboring stacking faults. The model agrees with experiments.

  19. Hypochlorite-induced damage to nucleosides

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    2001-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated...

  20. A Case of Transforming Growth Factor-β-Induced Gene-Related Oculorenal Syndrome: Granular Corneal Dystrophy Type II with a Unique Nephropathy

    Science.gov (United States)

    Iwafuchi, Yoichi; Morioka, Tetsuo; Oyama, Yuko; Nozu, Kandai; Iijima, Kazumoto; Narita, Ichiei

    2016-01-01

    Many types of inherited renal diseases have ocular features that occasionally support a diagnosis. The following study describes an unusual example of a 40-year-old woman with granular corneal dystrophy type II complicated by renal involvement. These two conditions may coincidentally coexist; however, there are some reports that demonstrate an association between renal involvement and granular corneal dystrophy type II. Granular corneal dystrophy type II is caused by a mutation in the transforming growth factor-β-induced (TGFBI) gene. The patient was referred to us because of the presence of mild proteinuria without hematuria that was subsequently suggested to be granular corneal dystrophy type II. A kidney biopsy revealed various glomerular and tubular basement membrane changes and widening of the subendothelial space of the glomerular basement membrane by electron microscopy. However, next-generation sequencing revealed that she had no mutation in a gene that is known to be associated with monogenic kidney diseases. Conversely, real-time polymerase chain reaction, using a simple buccal swab, revealed TGFBI heteromutation (R124H). The TGFBI protein plays an important role in cell-collagen signaling interactions, including extracellular matrix proteins which compose the renal basement membrane. This mutation can present not only as corneal dystrophy but also as renal disease. TGFBI-related oculorenal syndrome may have been unrecognized. It is difficult to diagnose this condition without renal electron microscopic studies. To the best of our knowledge, this is the first detailed report of nephropathy associated with a TGFBI mutation.

  1. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  2. Simulations of explosion-induced damage to underground rock chambers

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    A numerical approach is presented to study the explosion-induced pressure load on an underground rock chamber wall and its resultant damage to the rock chamber.Numerical simulations are carried out by using a modified version of the commercial software AUTODYN.Three different criteria,i.e.a peak particle velocity (PPV) criterion,an effective strain (ES) criterion,and a damage criterion,are employed to examine the explosion-induced damaged zones of the underground rock chamber.The results show that the charg...

  3. A robust model for simultaneously inducing corneal neovascularization and retinal gliosis in the mouse eye

    OpenAIRE

    2011-01-01

    Purpose To develop an animal model for simultaneously eliciting corneal angiogenesis and retinal gliosis that will enable the assessment of inhibitor efficacy on these two pathological processes in separate anatomic sites of the ocular globe. Methods Four to six week-old mice in a C57BL/6J background were anesthetized and 0.15 N NaOH was applied to the cornea, followed by mechanical scraping of the epithelium from limbus and central cornea. After this injury, mice were treated with vehicle or...

  4. Laser-Induced Damage Initiation and Growth of Optical Materials

    Directory of Open Access Journals (Sweden)

    Jingxia Yu

    2014-01-01

    Full Text Available The lifetime of optical components is determined by the combination of laser-induced damage initiation probability and damage propagation rate during subsequent laser shots. This paper reviews both theoretical and experimental investigations on laser-induced damage initiation and growth at the surface of optics. The damage mechanism is generally considered as thermal absorption and electron avalanche, which play dominant roles for the different laser pulse durations. The typical damage morphology in the surface of components observed in experiments is also closely related to the damage mechanism. The damage crater in thermal absorption process, which can be estimated by thermal diffusion model, is typical distortion, melting, and ablation debris often with an elevated rim caused by melted material flow and resolidification. However, damage initiated by electron avalanche is often accompanied by generation of plasma, crush, and fracture, which can be explained by thermal explosion model. Damage growth at rear surface of components is extremely severe which can be explained by several models, such as fireball growth, impact crater, brittle fracture, and electric field enhancement. All the physical effects are not independent but mutually coupling. Developing theoretical models of multiphysics coupling are an important trend for future theoretical research. Meanwhile, more attention should be paid to integrated analysis both in theory and experiment.

  5. Polar Value Analysis of Corneal Astigmatism in Intrastromal Corneal Ring Segment Implantation

    OpenAIRE

    Chang Rae Rho; Min-Ji Kim; Choun-Ki Joo

    2016-01-01

    Purpose. To evaluate surgically induced astigmatism (SIA) and the average corneal power change in symmetric intrastromal corneal ring segment (ICRS) implantation. Methods. The study included 34 eyes of 34 keratoconus patients who underwent symmetric Intacs SK ICRS implantation. The corneal pocket incision meridian was the preoperative steep meridian. Corneal power data were obtained before and 3 months after Intacs SK ICRS implantation using scanning-slit topography. Polar value analysis was ...

  6. SURGICALLY INDUCED ASTIGMATISM AFTER 2.8 MM TEMPORAL AND NASAL CLEAR CORNEAL INCISIONS IN PHACOEMULSIFICATION CATARACT SURGERY OF SAME PATIENT

    Directory of Open Access Journals (Sweden)

    Preeti

    2015-04-01

    Full Text Available PURPOSE: To evaluate and compare the surgically induced astigmatism in phacoemulsification cataract surgery after 2.8 mm temporal and nasal clear corneal incision of same patient . MATERIAL AND METHOD : This prospective study comprised a consecutive case series of 60 eyes. Eyes from 30 patients with phacoemulsification those were implanted with a 6.00 mm foldable intraocular le ns through a 2.8 mm horizontal clear corneal incision (temporal in the right eye , nasal in the left eye. RESULTS : T he outcome measures were surgically induced astigmatism (SIA and uncorrected visual acuity (UCVA , at 1 and 3 months post - operatively. A 1 month the mean SIA was 0.81 D. for the temporal incision and 0.92 D for nasal incision (P = 0.139 at 3 months the mean SIA was 0.53 D for temporal incision and 0.62 D for nasal incision (P =0.309. The pre - operative parameters i.e. (UCVA , mean keratomet ry & keratometric cylinder between these groups were comparable. There was no statistically significant difference found between three groups pre - operatively . CONCLUSION : After cataract surgery using 2.8mm temporal and nasal horizontal corneal incision , t he induced corneal astigmatic changes was similar in both incision groups. Especially in Asian eyes , both temporal and nasal incisions (2.8 mm or less would be equally favourable for astigmatism neutral cataract surgery

  7. Bleomycin and radiation-induced lung damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H.; Down, J.D.; Pearson, A.E.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1983-01-01

    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

  8. Difference in volatiles of poplar induced by various damages

    Institute of Scientific and Technical Information of China (English)

    HUZeng-hui; YANGDi; SHENYing-bai

    2004-01-01

    Three treatments including mechanical damage, Lymantria dispar attacking and daubing oral secretions of the insects on mechanically damaged cut were conducted on Populus simoniixPopulus pyramibalis c.v. in order to find the genuine reason leading to effective resistance response of tree to insects attacking. The release situation of the induced volatiles of the plant was analyzed by TCT-GC/MS at 24 hours after damages. The results indicated that some of the volatiles such as (Z)-3-hexenyl acetate, decanal, 3-hexenyl isovalerate, nonanal, ocimene, and 2-cyanobutane can be induced by both insects attacking and mechanical damage, while 2,6-dimethyl-1,3,5,7-octatetraene, 2-methyl-6-methylene-1,7-octadien-3-one, caryophyllene,Isovaleronitrile, diethyl-methyl-benzamide, and dicapryl phthalate were only induced by insects attacking. Such difference in volatiles was attributed to that there existed active components in oral sections of the larvae of Lymantria dispar

  9. A pre-application drop containing carboxymethylcellulose can reduce multipurpose solution-induced corneal staining.

    Science.gov (United States)

    Paugh, Jerry R; Marsden, Harue J; Edrington, Timothy B; Deland, Paul N; Simmons, Peter A; Vehige, Joseph G

    2007-01-01

    Use of polyhexanide based multipurpose solutions (MPSs) for contact lens disinfection has been linked to low-grade corneal staining. In vitro data suggest that carboxymethylcellulose (CMC) may neutralize polyhexanides. The purpose of this investigation was to determine whether a pre-application drop of CMC reduces polyhexanide staining in vivo. Thirty adapted soft contact lens (SCL) wearers participated in this investigator-masked, randomized, two-way cross-over study. Subjects wore a new Group II lens (alphafilcon A, 66% water) daily for 4 weeks and disinfected lenses using a MPS containing 0.0001% polyaminopropyl biguanide. A lens lubricant containing either CMC or povidone as the primary viscolyzer was applied to the lens each day before lens wear. Biomicroscopic signs and symptomatology were assessed. The difference in scores, 0 to 4 weeks and the difference between lubricants were analyzed. The cumulative fluorescein staining scores for combined eyes demonstrated a significant increase over time (e.g., cumulative staining score; p=0.004 and ppolyhexanide MPS. This result is consistent with a proposed mechanism for CMC to neutralize cationic disinfectants and may offer clinicians another means to reduce this type of corneal staining.

  10. Tissue culture and in vivo modeling of corneal opacification and ocular injuries induced by pulsed millimeter waves. Annual report (Final), 1 October 1980-31 May 1984

    Energy Technology Data Exchange (ETDEWEB)

    Trevithick, J.R.

    1985-02-01

    The eventual aims of these experiments were to use intact corneas incubated in vitro and corneas of rats or rabbits exposed in vivo to high-energy pulsed millimeter waves to study the development of corneal damage. Such experiments were expected (1) to establish conditions for corneal damage and (2) to elucidate the mechanisms by which the damage occurs. In order to perform these tests, studies of damage top corneas exposed to elevated temperatures in vitro are required as controls to establish a baseline. Rabbit corneas were exposed for a period of 30 minutes to elevated temperatures. Epithelial-cell changes appeared to be more pronounced than endothelial cell changes at all temperatures. Epithelial cells changed from flat cells with elevated intercellular junctions and short cylindrical microvilli increased damage was seen, including cell curling to look like potato chips, increased stromal denudation and fibrous cell surfaces. Both these changes and endothelial changes were accentuated in vitamin E-containing medium. For endothelial cells also, progressive increases in damage were seen as temperature increased: potato chip cells, some cell swelling obscuring cell boundaries, clumps, and cell processes covering cell surfaces leading to rough fibrous-cell surfaces, with many holes. Stromal changes, leading to stromal disorganization and separation into many fine individual strands, also occurred with increasing temperature.

  11. Laser induced damage in optical materials: 1989

    Science.gov (United States)

    Bennett, H. E.; Chase, L. L.; Guenther, A. H.; Newnam, B. E.; Soileau, M. J.

    1990-10-01

    The 21st Annual Symposium on Optical Materials for High Power Lasers was divided into sessions concerning Materials and Measurements, Mirrors and Surfaces, Thin Films, and, finally, Fundamental Mechanisms. As in previous years, the emphasis of the papers presented was directed toward new frontiers and new developments. Particular emphasis was given to materials for high power apparatus. The wavelength range of the prime interest included surface characterization, thin film substrate boundaries, and advances in fundamental laser matter threshold interactions and mechanisms. The scalling of damage thresholds with pulse duration, focal area, and wavelength was discussed in detail.

  12. Human adenovirus type 19 infection of corneal cells induces p38 MAPK-dependent interleukin-8 expression

    Directory of Open Access Journals (Sweden)

    Chodosh James

    2008-01-01

    Full Text Available Abstract Background Human adenovirus type 19 (HAdV-19 is a major cause of epidemic keratoconjunctivitis, the only ocular adenoviral infection associated with prolonged corneal inflammation. In this study, we investigated the role of p38 mitogen-activated protein kinase (MAPK in HAdV-19 infection, with particular attention to the role of p38 MAPK in the transcriptional control of interleukin-8 (IL-8, a chemokine previously shown to be central to the initiation of adenovirus keratitis. Results We found that infection of corneal cells with HAdV-19 led to activation of p38 MAPK and its downstream targets, HSP-27 and ATF-2, within 15 to 30 minutes post-infection. Infection also induced phosphorylation of IκB and NFκB in a p38 MAPK-dependent fashion. Furthermore, HAdV-19 induced an interaction between p38 MAPK and NFκB-p65, followed by nuclear translocation of activated NFκB-p65 and its binding to the IL-8 promoter. The interaction between p38 MAPK and NFκB-p65 was inhibited in concentration-dependent fashion by SB203580, a chemical inhibitor of p38 MAPK, but not by SP600125, an inhibitor of JNK – another MAPK implicated in chemokine expression by HAdV-19 infected cells. IL-8 gene expression in HAdV-19 infection was significantly reduced in the presence of sequence-specific p38 MAPK siRNA but not control siRNA. Conclusion These results provide the first direct evidence for transcriptional regulation of IL-8 in HAdV-19 infected cells through the activation of the p38 MAPK signaling pathway. The p38 MAPK pathway may play a biologically important role in regulation of IL-8 gene expression in the adenovirus-infected cornea.

  13. Experimental Investigation of DNA Damage Induced by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    DNA is considered the critical target for radiobiological effects. It is highly important to study DNAdamage induced by ionizing radiation. Especially DNA double strand breaks have been identified as themost initial damage. In this experiment, DNA double strand breaks induced by heavy ions wereinvestigated with atomic force microscopy (AFM).

  14. Characterization of vitamin C-induced cell sheets formed from primary and immortalized human corneal stromal cells for tissue engineering applications.

    Science.gov (United States)

    Grobe, Gesa Maria; Reichl, Stephan

    2013-01-01

    The purpose of this study was to compare the ability of primary human corneal stromal cells (HuFib cells) and SV40-immortalized human corneal keratocytes (HCK cells) to synthesize their own extracellular matrix induced by vitamin C supplementation. Therefore, the amount of collagen secreted and resulting biomechanical properties based on the culture duration were assessed. Cells were cultivated for several weeks with or without vitamin C. The amount of collagen secreted by the cells was quantified based on the culture duration. Cell viability was simultaneously determined via the MTT assay. Collagen secretion was increased as a result of vitamin C supplementation. The effect was stronger in primary cells. In addition, vitamin C supplementation had a positive effect on HuFib cell viability. Vitamin C supplementation induced the formation of detachable cell sheets in both primary and immortalized cells. The biomechanical properties of the sheets were evaluated using a static material testing machine, and the ultrastructure of the cell sheets was examined using scanning electron microscopy. The cell sheets formed from HuFib cells had a higher percentage of light transmission between 400 and 800 nm and were superior in terms of E-modulus and ultimate strength testing. Indirect immunofluorescence and Western blot confirmed the presence of collagen type I in the HuFib and HCK cell cultures. Stimulating secretion of the extracellular matrix in corneal stromal cells is a promising approach for corneal stroma reconstruction for tissue engineering applications. Copyright © 2013 S. Karger AG, Basel.

  15. Hypochlorite-induced damage to proteins

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    1998-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl damages proteins by reaction with amino acid side-chains or backbone cleavage. Little information is available about the mechanisms and intermediates involved...... in these reactions. EPR spin trapping has been employed to identify radicals on proteins, peptides and amino acids after treatment with HOCl. Reaction with HOCl gives both high- and low-molecular-mass nitrogen-centred, protein-derived radicals; the yield of the latter increases with both higher HOCl:protein ratios...... and enzymic digestion. These radicals, which arise from lysine side-chain amino groups, react with ascorbate, glutathione and Trolox. Reaction of HOCl-treated proteins with excess methionine eliminates radical formation, which is consistent with lysine-derived chloramines (via homolysis of N-Cl bonds) being...

  16. Hyperosmotic Stress-induced ATF-2 Activation through Polo-like Kinase 3 in Human Corneal Epithelial Cells*

    Science.gov (United States)

    Wang, Ling; Payton, Reid; Dai, Wei; Lu, Luo

    2011-01-01

    Elevated extracellular solute concentration (hyperosmotic stress) perturbs cell function and stimulates cell responses by evoking MAPK cascades and activating AP-1 transcription complex resulting in alterations of gene expression, cell cycle arrest, and apoptosis. The results presented here demonstrate that hyperosmotic stress elicited increases in ATF-2 phosphorylation through a novel Polo-like kinase 3 (Plk3) pathway in human corneal epithelial (HCE) cells. We found in hyperosmotic stress-induced HCE cells that Plk3 transferred to the nuclear compartment and was colocalized with ATF-2 in nuclei. Kinase activity of Plk3 was significantly activated by hyperosmotic stimulation. Further downstream, active Plk3 phosphorylated ATF-2 at the Thr-71 site in vivo and in vitro. Overexpression of Plk3 and its mutants enhanced hyperosmotic stress-induced ATF-2 phosphorylation. In contrast, suppression of Plk3 by knocking down Plk3 mRNA effectively diminished the effect of hyperosmotic stress-induced ATF-2 phosphorylation. The effect of hyperosmotic stress-induced activation of Plk3 on ATF-2 transcription factor function was also examined in CRE reporter-overexpressed HCE cells. Our results for the first time reveal that hyperosmotic stress can activate the Plk3 signaling pathway that subsequently regulates the AP-1 complex by directly phosphorylating ATF-2 independent from the effects of JNK and p38 activation. PMID:21098032

  17. Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in human corneal epithelial cells.

    Science.gov (United States)

    Wang, Ling; Payton, Reid; Dai, Wei; Lu, Luo

    2011-01-21

    Elevated extracellular solute concentration (hyperosmotic stress) perturbs cell function and stimulates cell responses by evoking MAPK cascades and activating AP-1 transcription complex resulting in alterations of gene expression, cell cycle arrest, and apoptosis. The results presented here demonstrate that hyperosmotic stress elicited increases in ATF-2 phosphorylation through a novel Polo-like kinase 3 (Plk3) pathway in human corneal epithelial (HCE) cells. We found in hyperosmotic stress-induced HCE cells that Plk3 transferred to the nuclear compartment and was colocalized with ATF-2 in nuclei. Kinase activity of Plk3 was significantly activated by hyperosmotic stimulation. Further downstream, active Plk3 phosphorylated ATF-2 at the Thr-71 site in vivo and in vitro. Overexpression of Plk3 and its mutants enhanced hyperosmotic stress-induced ATF-2 phosphorylation. In contrast, suppression of Plk3 by knocking down Plk3 mRNA effectively diminished the effect of hyperosmotic stress-induced ATF-2 phosphorylation. The effect of hyperosmotic stress-induced activation of Plk3 on ATF-2 transcription factor function was also examined in CRE reporter-overexpressed HCE cells. Our results for the first time reveal that hyperosmotic stress can activate the Plk3 signaling pathway that subsequently regulates the AP-1 complex by directly phosphorylating ATF-2 independent from the effects of JNK and p38 activation.

  18. Oxidative stress and DNA damages induced by cadmium accumulation

    Institute of Scientific and Technical Information of China (English)

    LIN Ai-jun; ZHANG Xu-hong; CHEN Mei-mei; CAO Qing

    2007-01-01

    Experimental evidence shows that cadmium (Cd) could induce oxidative stress and then causes DNA damage in animal cells, however, whether such effect exists in plants is still unclear. In the present study, Vicia faba plants was exposed to 5 and 10 mg/L Cd for 4 d to investigate the distribution of Cd in plant, the metal effects on the cell lipids, antioxidative enzymes and DNA damages in leaves. Cd induced an increase in Cd concentrations in plants. An enhanced level of lipid peroxidation in leaves and an enhanced concentration of H2O2 in root tissues suggested that Cd caused oxidative stress in Vicia faba. Compared with control, Cd-induced enhancement in superoxide dismutase activity was significant at 5 mg/L than at 10 mg/kg in leaves, by contrast, catalase and peroxidaseactivities were significantly suppressed by Cd addition. DNA damage was detected by neutral/neutral, alkaline/neutral and alkaline/alkaline Comet assay. Increased levels of DNA damages induced by Cd occurred with reference to oxidative stress in leaves, therefore, oxidative stress induced by Cd accumulation in plants contributed to DNA damages and was possibly an important mechanism of Cd-phytotoxicity in Vicia faba plants.

  19. Inducible repair of oxidative DNA damage in Escherichia coli.

    Science.gov (United States)

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

  20. Quercitrin protects skin from UVB-induced oxidative damage.

    Science.gov (United States)

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin.

  1. Corneal Transplantation

    DEFF Research Database (Denmark)

    Hjortdal, Jesper Østergaard

    Corneal transplantation has been performed for more than 100 years. Until 15 years ago the state-of-the art type of transplantation was penetrating keratoplasty, but since the start of this millennium, newly designed surgical techniques have developed considerably. Today, the vast majority of ker...

  2. Corneal Laceration

    Medline Plus

    Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration ... After Eyelid Scratch Jul 28, 2014 Leer en Español: ¿Qué Es una Laceración de la Córnea? Find ...

  3. Corneal topography

    DEFF Research Database (Denmark)

    Andersen, J.; Koch-Jensen, P.; Østerby, Ole

    1993-01-01

    The central corneal zone is depicted on keratoscope photographs using a small target aperture and a large object distance. Information on the peripheral area is included by employing a hemispherical target with a dense circular and radial pattern. On a 16 mm (R = 8 mm) reference steel sphere...

  4. Corneal chromoblastomycosis.

    Science.gov (United States)

    Barton, K; Miller, D; Pflugfelder, S C

    1997-03-01

    We sought to illustrate the difficulty in managing uncommon, pigmented mold-related corneal ulceration and to highlight the role of itraconazole in treating these patients. We describe the management and clinical course of a patient with a recurring corneal infection caused by Fonsecaea pedrosoi and discuss this experience in the light of existing literature on management of cutaneous chromoblastomycosis. A corneal ulcer caused by this organism healed initially on treatment with topical and systemic antifungal medication, but infection recurred in the deep stroma 4 months after cessation of therapy. After failure to respond to a further period of medical therapy, a small therapeutic penetrating keratoplasty was performed. Culture of a fibrinous membrane from the anterior iris surface demonstrated intraocular fungal infection, and postoperatively, an episode of marked fibrinous uveitis developed, suggesting the presence of viable intraocular fungal elements. A large penetrating keratoplasty was therefore performed with excision of involved iris in combination with extracapsular cataract extraction. F. pedrosoi was again cultured from the fibrinous membrane adherent to the iris and from the anterior lens capsule. Postoperatively the patient received a 5-month course of systemic itraconazole, and no further recurrences have been encountered after a further 2 months. F. pedrosoi is the organism most commonly isolated from the chronic cutaneous mycosis, chromoblastomycosis, and is relatively resistant to medical therapy. As has been reported for cutaneous disease, surgery in combination with systemic itraconazole may provide the best chance of cure in corneal chromoblastomycosis.

  5. pH Induced Conformational Transitions in the Transforming Growth Factor β-Induced Protein (TGFβIp) Associated Corneal Dystrophy Mutants.

    Science.gov (United States)

    Murugan, Elavazhagan; Venkatraman, Anandalakshmi; Lei, Zhou; Mouvet, Victoria; Rui Yi Lim, Rayne; Muruganantham, Nandhakumar; Goh, Eunice; Swee Lim Peh, Gary; Beuerman, Roger W; Chaurasia, Shyam S; Rajamani, Lakshminarayanan; Mehta, Jodhbir S

    2016-03-31

    Most stromal corneal dystrophies are associated with aggregation and deposition of the mutated transforming growth factor-β induced protein (TGFβIp). The 4(th)_FAS1 domain of TGFβIp harbors ~80% of the mutations that forms amyloidogenic and non-amyloidogenic aggregates. To understand the mechanism of aggregation and the differences between the amyloidogenic and non-amyloidogenic phenotypes, we expressed the 4(th)_FAS1 domains of TGFβIp carrying the mutations R555W (non-amyloidogenic) and H572R (amyloidogenic) along with the wild-type (WT). R555W was more susceptible to acidic pH compared to H572R and displayed varying chemical stabilities with decreasing pH. Thermal denaturation studies at acidic pH showed that while WT did not undergo any conformational transition, the mutants exhibited a clear pH-dependent irreversible conversion from αβ conformation to β-sheet oligomers. The β-oligomers of both mutants were stable at physiological temperature and pH. Electron microscopy and dynamic light scattering studies showed that β-oligomers of H572R were larger compared to R555W. The β-oligomers of both mutants were cytotoxic to primary human corneal stromal fibroblast (pHCSF) cells. The β-oligomers of both mutants exhibit variations in their morphologies, sizes, thermal and chemical stabilities, aggregation patterns and cytotoxicities.

  6. Heat Induced Damage Detection by Terahertz (THz) Radiation

    Science.gov (United States)

    Rahani, Ehsan Kabiri; Kundu, Tribikram; Wu, Ziran; Xin, Hao

    2011-06-01

    Terahertz (THz) and sub-terahertz imaging and spectroscopy are becoming increasingly popular nondestructive evaluation techniques for damage detection and characterization of materials. THz radiation is being used for inspecting ceramic foam tiles used in TPS (Thermal Protection System), thick polymer composites and polymer tiles that are not good conductors of ultrasonic waves. Capability of THz electromagnetic waves in detecting heat induced damage in porous materials is investigated in this paper. Porous pumice stone blocks are subjected to long time heat exposures to produce heat induced damage in the block. The dielectric properties extracted from THz TDS (Time Domain Spectroscopy) measurements are compared for different levels of heat exposure. Experimental results show noticeable and consistent change in dielectric properties with increasing levels of heat exposure, well before its melting point.

  7. HSP25 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June; Lee, Yoon Jin; Kwon, Hee Choong; Lee, Su Jae; Bae, Sang Woo; Lee, Yun Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

    2005-07-01

    Irradiation (IR) is a central treatment modality administered for head and neck malignancies. A significant consequence of this IR treatment is irreversible damage to salivary gland in the IR field. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that heat shock protein 25 (HSP25) induced radioresistance in vitro. HSP25 interferes negatively with apoptosis through several pathways which involve its direct interaction with cytochrome c, protein kinase c delta or Akt. And localized gene transfer to salivary glands has great potential for the treatment of salivary gland. Herein, we investigated whether HSP25 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  8. Shock-induced damage in rocks: Application to impact cratering

    Science.gov (United States)

    Ai, Huirong

    Shock-induced damage beneath impact craters is studied in this work. Two representative terrestrial rocks, San Marcos granite and Bedford limestone, are chosen as test target. Impacts into the rock targets with different combinations of projectile material, size, impact angle, and impact velocity are carried out at cm scale in the laboratory. Shock-induced damage and fracturing would cause large-scale compressional wave velocity reduction in the recovered target beneath the impact crater. The shock-induced damage is measured by mapping the compressional wave velocity reduction in the recovered target. A cm scale nondestructive tomography technique is developed for this purpose. This technique is proved to be effective in mapping the damage in San Marcos granite, and the inverted velocity profile is in very good agreement with the result from dicing method and cut open directly. Both compressional velocity and attenuation are measured in three orthogonal directions on cubes prepared from one granite target impacted by a lead bullet at 1200 m/s. Anisotropy is observed from both results, but the attenuation seems to be a more useful parameter than acoustic velocity in studying orientation of cracks. Our experiments indicate that the shock-induced damage is a function of impact conditions including projectile type and size, impact velocity, and target properties. Combined with other crater phenomena such as crater diameter, depth, ejecta, etc., shock-induced damage would be used as an important yet not well recognized constraint for impact history. The shock-induced damage is also calculated numerically to be compared with the experiments for a few representative shots. The Johnson-Holmquist strength and failure model, initially developed for ceramics, is applied to geological materials. Strength is a complicated function of pressure, strain, strain rate, and damage. The JH model, coupled with a crack softening model, is used to describe both the inelastic response of

  9. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  10. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study.

    Science.gov (United States)

    Caporossi, Aldo; Baiocchi, Stefano; Mazzotta, Cosimo; Traversi, Claudio; Caporossi, Tomaso

    2006-05-01

    To assess the effectiveness of riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen in reducing progression of keratoconus and in improving visual acuity in patients with progressive keratoconus. Department of Ophthalmology, Siena University, Siena, Italy. This was a second-phase prospective nonrandomized open study. Starting in September 2004, 10 eyes of 10 patients (mean age 31.4 years) with bilateral keratoconus were treated by combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking. Radiant energy was 3 mW/cm2 or 5.4 joule/cm2 for a 30-minute exposure at 1 cm from the corneal apex. A complete ophthalmologic examination (uncorrected visual acuity [UCVA], sphere spectacles corrected visual acuity (SSCVA), best spectacle-corrected visual acuity [BSCVA]) was performed. Patients had corneal computerized topographic examination, linear scan optical tomography, endothelial cell count, ultrasound pachometry, intraocular pressure (IOP) evaluation, and HRT II system confocal microscopy at 1, 2, 3, and 6 months. After treatment, eyes were medicated and dressed with a soft contact lens. Comparative preoperative and postoperative results showed increases of 3.6 lines for UCVA (P = .0000112), 1.85 lines for SSCVA (P = .00065), and 1.66 lines for BSCVA (P = .00071). Topographic analysis showed a mean K reduction of 2.1 +/- 0.13 diopters (D) in the central 3.0 mm. Statistical analysis of IOP and endothelial cell count did not show significant differences. Topo-aberrometric analysis findings of corneal symmetry showed a trend toward increasing corneal symmetry with a major reduction in asymmetry between vertical hemimeridians. Refractive results showed a reduction of about 2.5 D in the mean spherical equivalent, topographically confirmed by the reduction in mean K. Results of surface aberrometric analysis showed improvement in morphologic symmetry with a significant reduction in comatic aberrations.

  11. Localization and Expression of Zonula Occludins-1 in the Rabbit Corneal Epithelium following Exposure to Benzalkonium Chloride

    Science.gov (United States)

    Zhang, Zhenhao; Chen, Lelei; Xie, Hui; Dong, Nuo; Chen, Yongxiong; Liu, Zuguo

    2012-01-01

    Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo. PMID:22815857

  12. Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride.

    Directory of Open Access Journals (Sweden)

    Wensheng Chen

    Full Text Available Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC, a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT, fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo.

  13. Fungus induces the release of IL- 8 in human corneal epithelial cells, via Dectin-1-mediated protein kinase C pathways

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong; Peng; Gui-Qiu; Zhao; Jing; Lin; Nan; Jiang; Qiang; Xu; Cheng-Cheng; Zhu; Jian-Qiu; Qu; Lin; Cong; Hui; Li

    2015-01-01

    AIM: To identify whether Aspergillus fumigatus(A.fumigatus) hyphae antigens induced the release of interleukin-8(IL-8) in anti-fungal innate immunity of cultured human corneal epithelial cells(HCECs) and determine the involvement of intracellular signalling pathways. METHODS: HCECs were treated with A. fumigatus hyphae antigens with different concentrations and time.The cytoplasmic calcium of HCECs were assessed by fluorescence imaging. Western blot was used to detect the expression of Ca2 +-dependent protein kinase C(PKC). The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay(ELISA) and reverse transcriptase polymerase chain reaction(RT-PCR). Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to A.fumigatus hyphae antigens. RESULTS: Cells exposed to A. fumigatus hyphae antigens showed higher level of IL-8 m RNA expression and protein production. We demonstrated here that stimulation of HCECs with A. fumigatus hyphae triggers an intracellular Ca2 +flux and results in the activation of Ca2 +-dependent PKC(α, βⅠ and βⅡ) which can be attenuated by pre-treatment of cells with laminarin,suggesting that Dectin-1 signals pathway induced cytoplasmic calcium and influence the activation of PKC in HCECs. Inhibitors of Ca2 +-dependent PKC(Ro-31-8220 and Go6976) significantly abolished hyphae-induced expression of IL-8.CONCLUSION: Our findings suggest that A. fumigatushyphae-induced IL-8 expression was regulated by the activation of Dectin-1-mediated Ca2 +-dependent PKC in HCECs.

  14. Protective effects of honokiol against methylglyoxal-induced osteoblast damage.

    Science.gov (United States)

    Suh, Kwang Sik; Chon, Suk; Choi, Eun Mi

    2016-01-25

    Honokiol is an active compound isolated from Magnolia officinalis that has been used without notable side effects in traditional medicine. We investigated the effects of honokiol against methylglyoxal (MG)-induced cytotoxicity in MC3T3-E1 osteoblast cells and the possible molecular mechanism(s) involved. The results showed that honokiol alleviated MG-induced cell death and the production of intracellular ROS, mitochondrial superoxide, cardiolipin peroxidation, and inflammatory cytokines. MG induction of the soluble receptor for advanced glycation end product (AGE) was reduced by pretreatment with honokiol. Furthermore, honokiol increased the levels of Nrf2 and increased the levels of glutathione and the activity of glyoxalase I. Pretreatment with honokiol prior to MG exposure reduced MG-induced mitochondrial dysfunction and alleviated MG-induced reduction of nitric oxide and PGC1α levels, suggesting that honokiol may induce mitochondrial biogenesis. It was concluded that honokiol could be useful in the attenuation of MG-induced cell damage.

  15. Surgical induced astigmatism correlated with corneal pachymetry and intraocular pressure: transconjunctival sutureless 23-gauge versus 20-gauge sutured vitrectomy in diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Yan; Shao; Li-Jie; Dong; Yan; Zhang; Hui; Liu; Bo-Jie; Hu; Ju-Ping; Liu; Xiao-Rong; Li

    2015-01-01

    AIM: To determine the difference of surgical induced astigmatism between conventional 20-gauge sutured vitrectomy and 23-gauge transconjunctival sutureless vitrectomy, and the influence of corneal pachymetry and intraocular pressure(IOP) on surgical induced astigmatism in diabetic patients.METHODS: This retrospective, consecutive case series consisted of 40 eyes of 38 diabetic subjects who underwent either 20-gauge or 23-gauge vitrectomy. The corneal curvature and thickness were measured with Scheimpflug imaging before surgery and 1wk; 1, 3mo after surgery. We compared the surgical induced astigmatism(SIA) on the true net power in 23-gauge group with that in 20-gauge group. We determined the correlation between corneal thickness change ratio, IOP and SIA measured by Pentacam. RESULTS: The mean SIAs were 1.082 ±0.085 D( mean ± SEM), 0.689 ±0.070 D and 0.459 ±0.063 D at postoperative 1wk; 1, 3mo respectively in diabetic subjects. The vitrectomy induced astigmatisms were declined significantly with time(F2,36=33.629, P =0.000)postoperatively. The 23-gauge surgery group induced significantly less astigmatism than 20-gauge surgery group(F1,37=11.046, P =0.020). Corneal thickness in diabetes elevated after surgery(F3,78=10.532, P =0.000).The linear regression analysis at postoperatively 1wk went as: SIA =-4.519 +4.931 change ratio(Port3) +0.026IOP(R2=0.46, P =0.000), whereas the rate of cornealthickness change and IOP showed no correlation with the change of astigmatism at postoperatively 1 and 3mo.CONCLUSION: There are significant serial changes in both 20-gauge and 23-gauge group in diabetic subjects.23-gauge induce less astigmatism than 20-gauge and become stable more rapidly than 20-gauge. The elevation of corneal thickness and IOP was associated with increased astigmatim at the early postoperative stage both in 23-gauge and 20-gauge surgery group.

  16. Zebrafish fin regeneration after cryoinjury-induced tissue damage

    Directory of Open Access Journals (Sweden)

    Bérénice Chassot

    2016-06-01

    Full Text Available Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump.

  17. Damage induced by femtosecond laser in optical dielectric films

    Institute of Scientific and Technical Information of China (English)

    Caihua Huang; Yiyu Xue; Zhilin Xia; Yuanan Zhao; Fangfang Yang; Peitao Guo

    2009-01-01

    Both the nature of avalanche ionization (AI) and the role of multi-photon ionization (MPI) in the studies of laser-induced damage have remained controversial up to now. According to the model proposed by Stuart et al., we study the role of MPI and AI in laser-induced damage in two dielectric films, fused silica (FS) and barium aluminum borosilicate (BBS), irradiated by 780-nm laser pulse with the pulse width range of 0.01 鈥? 5 ps. The effects of MPI and initial electron density on seed electron generation are numerically analyzed. For FS, laser-induced damage is dominated by AI for the entire pulse width regime due to the wider band-gap. While for BBS, MPI becomes the leading power in damage for the pulse width r less than about 0.03 ps. MPI may result in a sharp rise of threshold fluence Fth on 蟿, and AI may lead to a mild increase or even a constant value of Fth on 蟿. MPI serves the production of seed electrons for AI when the electron density for AI is approached or exceeded before the end of MPI. This also means that the effect of initial electron can be neglected when MPI dominates the seed electron generation. The threshold fluence Fth decreases with the increasing initial electron density when the latter exceeds a certain critical value.

  18. Obesity Exacerbates Sepsis-Induced Oxidative Damage in Organs.

    Science.gov (United States)

    Petronilho, Fabricia; Giustina, Amanda Della; Nascimento, Diego Zapelini; Zarbato, Graciela Freitas; Vieira, Andriele Aparecida; Florentino, Drielly; Danielski, Lucinéia Gainski; Goldim, Mariana Pereira; Rezin, Gislaine Tezza; Barichello, Tatiana

    2016-12-01

    Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.

  19. Inhibition of TGF-β signaling enables human corneal endothelial cell expansion in vitro for use in regenerative medicine.

    Directory of Open Access Journals (Sweden)

    Naoki Okumura

    Full Text Available Corneal endothelial dysfunctions occurring in patients with Fuchs' endothelial corneal dystrophy, pseudoexfoliation syndrome, corneal endotheliitis, and surgically induced corneal endothelial damage cause blindness due to the loss of endothelial function that maintains corneal transparency. Transplantation of cultivated corneal endothelial cells (CECs has been researched to repair endothelial dysfunction in animal models, though the in vitro expansion of human CECs (HCECs is a pivotal practical issue. In this study we established an optimum condition for the cultivation of HCECs. When exposed to culture conditions, both primate and human CECs showed two distinct phenotypes: contact-inhibited polygonal monolayer and fibroblastic phenotypes. The use of SB431542, a selective inhibitor of the transforming growth factor-beta (TGF-β receptor, counteracted the fibroblastic phenotypes to the normal contact-inhibited monolayer, and these polygonal cells maintained endothelial physiological functions. Expression of ZO-1 and Na(+/K(+-ATPase maintained their subcellular localization at the plasma membrane. Furthermore, expression of type I collagen and fibronectin was greatly reduced. This present study may prove to be the substantial protocol to provide the efficient in vitro expansion of HCECs with an inhibitor to the TGF-β receptor, and may ultimately provide clinicians with a new therapeutic modality in regenerative medicine for the treatment of corneal endothelial dysfunctions.

  20. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous.

  1. The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man.

    Science.gov (United States)

    de Tommaso, M; Libro, G; Guido, M; Sciruicchio, V; Puca, F

    2001-09-07

    Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

  2. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  3. Feline corneal disease.

    Science.gov (United States)

    Moore, Phillip Anthony

    2005-05-01

    The cornea is naturally transparent. Anything that interferes with the cornea's stromal architecture, contributes to blood vessel migration, increases corneal pigmentation, or predisposes to corneal edema, disrupts the corneas transparency and indicates corneal disease. The color, location, and shape and pattern of a corneal lesion can help in determining the underlying cause for the disease. Corneal disease is typically divided into congenital or acquired disorders. Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired corneal disease associated with nonulcerative or ulcerative keratitis is common. Primary ocular disease, such as tear film instability, adenexal disease (medial canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are associated with the majority of acquired corneal disease in cats. Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative disease in cats, such as chronic corneal epithelial defects and corneal sequestration are more common than progressive corneal ulcerations.

  4. Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

    Directory of Open Access Journals (Sweden)

    Maryam Ferdousi

    Full Text Available There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04 and warm sensation (P = 0.03 thresholds with a significantly reduced sural sensory (P<0.01 and peroneal motor (P<0.01 nerve conduction velocity, corneal nerve fibre density (CNFD, nerve branch density (CNBD and nerve fibre length (CNFL (P<0.0001. Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02, and CNFL (r = -0.8, P<0.0001 and CNBD (r = 0.63, P = 0.003 were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003. Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

  5. Factores pronósticos del astigmatismo corneal inducido en pacientes operados de catarata por la técnica tunelizada Prognostic factors of induced corneal astigmatism in patients operated on from cataract by the tunnel technique

    Directory of Open Access Journals (Sweden)

    Ricardo Montejo Valdes

    2008-12-01

    Full Text Available OBJETIVO: Evaluar factores anatómico corneales y del transoperatorio por la técnica tunelizada de catarata que den lugar al astigmatismo inducido. MÉTODOS: Estudio descriptivo, longitudinal y prospectivo. El universo estuvo conformado por 120 ojos de pacientes provenientes de la consulta de Oftalmología del Hospital Clínicoquirúrgico "Hermanos Ameijeiras" de diciembre de 2005 a octubre de 2006, operados de catarata senil con lente intraocular de cámara posterior, el cual fue calculado por la fórmula SRK-T para la emetropía. Se les realizó un examen oftalmológico preoperatorio y a los dos meses del posoperatorio. Se hace referencia al astigmatismo inducido, su relación con los factores anatómicos corneales y los transoperatorios. La evaluación del astigmatismo inducido, el defecto esférico posoperatorio y el astigmatismo preoperatorio queratométrico se evaluaron mediante indicadores cualitativos y cuantitativos. RESULTADOS: El astigmatismo inducido a los dos meses fue de 1,42 dioptrías (D, el cual aumenta en la incisión anterior y no autosellable. Este tipo de astigmatismo es mayor que 2 dioptrías si la profundidad del túnel es superficial o profunda con una probabilidad significativa. La media del astigmatismo preoperatorio es mayor, según aumenta el valor de la esfera posoperatoria. CONCLUSIONES: La incisión esclerocorneal anterior, superficial y no autosellable producen astigmatismo inducido. Las complicaciones también lo favorecen. El defecto esférico posoperatorio estuvo presente en la mayoría de los pacientes y sus valores más altos se corresponden con el astigmatismo preoperatorio mayor.OBJECTIVE: To evaluate the corneal anatomical factors and the transoperative factors by the tunnel technique of cataract surgery that gives rise to induced astigmatism. METHODS: A prospective longitudinal and descriptive research study. The universe of study was made up of 120 eyes from patients seen at the opthalmological service

  6. Laser induced damage studies in mercury cadmium telluride

    Science.gov (United States)

    Garg, Amit; Kapoor, Avinashi; Tripathi, K. N.; Bansal, S. K.

    2007-10-01

    We have investigated laser induced damage at 1.06 μm laser wavelength in diamond paste polished (mirror finish) and carborundum polished Hg0.8Cd0.2Te (MCT) samples with increasing fluence as well as number of pulses. Evolution of damage morphology in two types of samples is quite different. In case of diamond paste polished samples, evolution of damage morphological features is consistent with Hg evaporation with transport of Cd/Te globules towards the periphery of the molten region. Cd/Te globules get accumulated with successive laser pulses at the periphery indicating an accumulation effect. Real time reflectivity (RTR) measurement has been done to understand melt pool dynamics. RTR measurements along with the thermal profile of the melt pool are in good agreement with thermal melting model of laser irradiated MCT samples. In case of carborundum polished samples, laser damage threshold is significantly reduced. Damage morphological features are significantly influenced by surface microstructural condition. From comparison of the morphological features in the two cases, it can be inferred that laser processing of MCT for device applications depends significantly on surface preparation conditions.

  7. Statistical analysis of vibration-induced bone and joint damages.

    Science.gov (United States)

    Schenk, T

    1995-01-01

    Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

  8. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    OpenAIRE

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into ...

  9. Anchor-induced chondral damage in the hip

    OpenAIRE

    Matsuda, Dean K.; Bharam, Srino; White, Brian J.; Matsuda, Nicole A.; SAFRAN, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five ...

  10. Phosphine-induced oxidative damage in rats: attenuation by melatonin.

    Science.gov (United States)

    Hsu, C; Han, B; Liu, M; Yeh, C; Casida, J E

    2000-02-15

    Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).

  11. Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion.

    Science.gov (United States)

    Juvekar, Ashish; Hu, Hai; Yadegarynia, Sina; Lyssiotis, Costas A; Ullas, Soumya; Lien, Evan C; Bellinger, Gary; Son, Jaekyoung; Hok, Rosanna C; Seth, Pankaj; Daly, Michele B; Kim, Baek; Scully, Ralph; Asara, John M; Cantley, Lewis C; Wulf, Gerburg M

    2016-07-26

    We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative breast cancer (K14-Cre BRCA1(f/f)p53(f/f)), the PI3K inhibitor BKM120 led to a precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA synthesis in normal tissues was less affected. In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors.

  12. Stochastics of diffusion induced damage in intercalation materials

    Science.gov (United States)

    Barai, Pallab; Mukherjee, Partha P.

    2016-10-01

    Fundamental understanding of the underlying diffusion-mechanics interplay in the intercalation electrode materials is critical toward improved life and performance of lithium-ion batteries for electric vehicles. Especially, diffusion induced microcrack formation in brittle, intercalation active materials, with emphasis on the grain/grain-boundary (GB) level implications, has been fundamentally investigated based on a stochastic modeling approach. Quasistatic damage evolution has been analyzed under lithium concentration gradient induced stress. Scaling of total amount of microcrack formation shows a power law variation with respect to the system size. Difference between the global and local roughness exponent indicates the existence of anomalous scaling. The deterioration of stiffness with respect to microcrack density displays two distinct regions of damage propagation; namely, diffused damage evolution and stress concentration driven localized crack propagation. Polycrystalline material microstructures with different grain sizes have been considered to study the diffusion-induced fracture in grain and GB regions. Intergranular crack paths are observed within microstructures containing softer GB region, whereas, transgranular crack paths have been observed in microstructures with relatively strong GB region. Increased tortuosity of the spanning crack has been attributed as the reason behind attaining increased fracture strength in polycrystalline materials with smaller grain sizes.

  13. Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

    Science.gov (United States)

    Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

    2015-01-01

    Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

  14. PARP-1 modulates amyloid beta peptide-induced neuronal damage.

    Directory of Open Access Journals (Sweden)

    Sara Martire

    Full Text Available Amyloid beta peptide (Aβ causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose polymerase (PARP-1. To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25-35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.

  15. Equine corneal stromal abscesses

    DEFF Research Database (Denmark)

    Henriksen, M. D. L.; Andersen, P. H.; Plummer, C. E.

    2013-01-01

    The last 30 years have seen many changes in the understanding of the pathogenesis and treatment of equine corneal stromal abscesses (SAs). Stromal abscesses were previously considered an eye problem related to corneal bacterial infection, equine recurrent uveitis, corneal microtrauma and corneal...

  16. Phosphine-induced oxidative damage in rats: role of glutathione.

    Science.gov (United States)

    Hsu, Ching-Hung; Chi, Bei-Ching; Liu, Ming-Yie; Li, Jih-Heng; Chen, Chiou-Jong; Chen, Ruey-Yu

    2002-09-30

    Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH(3) induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-induced oxidative toxicity is controversial. GSH levels in various tested tissues were reduced in aluminium phosphide-poisoned rats and humans, while the levels remained unchanged in insects and mammalian cells. This study examines the effectiveness of endogenous GSH as a protective agent against PH(3)-induced oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30 min after treatment for PH(3) toxicity to organs. PH(3) significantly decreased GSH, GSH peroxidase and catalase, while significantly increased lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8-hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P., 30 min before PH(3)), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3)) significantly enhanced the effect of PH(3) on GSH loss and lipid peroxidation elevation in lung. These findings indicate that (1) endogenous GSH plays a crucial role as a protective factor in modulating PH(3)-induced oxidative damage, and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.

  17. Stromal demarcation line induced by corneal cross-linking in eyes with keratoconus and nonkeratoconic asymmetric topography.

    Science.gov (United States)

    Malta, João B N; Renesto, Adimara C; Moscovici, Bernardo K; Soong, H K; Campos, Mauro

    2015-02-01

    To evaluate stromal demarcation lines following corneal cross-linking (CXL) using anterior segment optical coherence tomography in patients with keratoconus and nonkeratoconic asymmetric topography. Fifth-nine eyes of 59 patients were enrolled in a retrospective comparative case series, of which 19 eyes had keratoconus and 40 eyes had asymmetric topography. Eyes with asymmetric topography were treated in preparation for photorefractive keratectomy. One month after CXL, a stromal demarcation line was evaluated at 5 standardized corneal points using anterior segment optical coherence tomography. Mean stromal demarcation line depths were measured at 5 points on the cornea, namely, centrally, 3.0 mm temporally, 1.5 mm temporally, 3.0 mm nasally, and 1.5 mm nasally. For the keratoconus group, the values were 178 ± 47, 123 ± 15, 152 ± 47, 125 ± 23, and 160 ± 43 μm, respectively. For the asymmetric corneal topography group (without keratoconus), they were 305 ± 64, 235 ± 57, 294 ± 50, 214 ± 54, and 285 ± 58 μm, respectively. There was no correlation between central corneal pachymetry and stromal demarcation line depth in all 5 measured corneal points in both groups. CXL treatment profiles are similar in keratoconic and nonkeratoconic eyes with asymmetric topography.

  18. Prevention of downhill walking-induced muscle damage by non-damaging downhill walking.

    Science.gov (United States)

    Maeo, Sumiaki; Yamamoto, Masayoshi; Kanehisa, Hiroaki; Nosaka, Kazunori

    2017-01-01

    Mountain trekking involves level, uphill, and downhill walking (DW). Prolonged DW induces damage to leg muscles, reducing force generating ability and muscle coordination. These increase risks for more serious injuries and accidents in mountain trekking, thus a strategy to minimize muscle damage is warranted. It has been shown that low-intensity eccentric contractions confer protective effect on muscle damage induced by high-intensity eccentric contractions. This study tested the hypothesis that 5-min non-damaging DW would attenuate muscle damage induced by 40-min DW, but 5-min level walking (LW) would not. Untrained young men were allocated (n = 12/group) to either a control or one of the two preconditioning groups (PRE-DW or PRE-LW). The PRE-DW and PRE-LW groups performed 5-min DW (-28%) and 5-min LW, respectively, at 5 km/h with a load of 10% body mass, 1 week before 40-min DW (-28%, 5 km/h, 10% load). The control group performed 40-min DW only. Maximal knee extension strength, plasma creatine kinase (CK) activity, and muscle soreness (0-100 mm visual analogue scale) were measured before and 24 h after 5-min DW and 5-min LW, and before and 24, 48, and 72 h after 40-min DW. No significant changes in any variables were evident after 5-min DW and 5-min LW. After 40-min DW, the control and PRE-LW groups showed significant (P<0.05) changes in the variables without significant differences between groups (control vs. PRE-LW; peak strength reduction: -19.2 ± 6.9% vs. -18.7 ± 11.0%, peak CK: 635.5 ± 306.0 vs. 639.6 ± 405.4 U/L, peak soreness: 81.4 ± 14.8 vs. 72.0 ± 29.2 mm). These changes were significantly (P<0.05) attenuated (47-64%) for the PRE-DW group (-9.9 ± 9.6%, 339.3 ± 148.4 U/L, 27.8 ± 16.8 mm). The results supported the hypothesis and suggest that performing small volume of downhill walking is crucial in preparation for trekking.

  19. Corneal neovascularization and contemporary antiangiogenic therapeutics.

    Science.gov (United States)

    Hsu, Chih-Chien; Chang, Hua-Ming; Lin, Tai-Chi; Hung, Kuo-Hsuan; Chien, Ke-Hung; Chen, Szu-Yu; Chen, San-Ni; Chen, Yan-Ting

    2015-06-01

    Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

  20. Retinal damage induced by commercial light emitting diodes (LEDs).

    Science.gov (United States)

    Jaadane, Imene; Boulenguez, Pierre; Chahory, Sabine; Carré, Samuel; Savoldelli, Michèle; Jonet, Laurent; Behar-Cohen, Francine; Martinsons, Christophe; Torriglia, Alicia

    2015-07-01

    Spectra of "white LEDs" are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Investigation of cutting-induced damage in CMC bend bars

    Directory of Open Access Journals (Sweden)

    Neubrand A.

    2015-01-01

    Full Text Available Ceramic matrix composites (“CMC” with a strong fibre-matrix interface can be made damage-tolerant by introducing a highly porous matrix. Such composites typically have only a low interlaminar shear strength, which can potentially promote damage when preparing specimens or components by cutting. In order to investigate the damage induced by different cutting methods, waterjet cutting with and without abrasives, laser-cutting, wire eroding and cutoff grinding were used to cut plates of two different CMCs with a matrix porosity up to 35 vol.-%. For each combination of cutting method and composite, the flexural and interlaminar shear strength of the resulting specimens was determined. Additionally, the integrity of the regions near the cut surfaces was investigated by high-resolution x-ray computer tomography. It could be shown that the geometrical quality of the cut is strongly affected by the cutting method employed. Laser cut and waterjet cut specimens showed damage and delaminations near the cut surface leading to a reduced interlaminar shear strength of short bend bars in extreme cases.

  2. Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin

    Institute of Scientific and Technical Information of China (English)

    Mohamed A Fahim; Hazem Kataya; Rkia El-Kharrag; Dena AM Amer; Basel al-Ramadi; Sherif M Karam

    2011-01-01

    AIM: To examine the influence of ghrelin on the regenerative potential of gastrointestinal (GI) epithelium.METHODS: Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin (10 and 6 mg/kg). Some of the doxorubicin-treated mice received a continuous subcutaneous infusion of ghrelin (1.25 μg/h) for 10 d via implanted mini-osmotic pumps. To label dividing stem cells in the S-phase of the cell cycle, all mice received a single intraperitoneal injection of 5'-bromo-2'-deoxyuridine (BrdU) one hour before sacrifice. The stomach along with the duodenum were then removed and processed for histological examination and immunohistochemistry using anti-BrdU antibody. RESULTS: The results showed dramatic damage to the GI epithelium 3 d after administration of chemotherapy which began to recover by day 10. In ghrelin-treated mice, attenuation of GI mucosal damage was evident in the tissues examined post-chemotherapy. Immunohistochemical analysis showed an increase in the number of BrdU-labeled cells and an alteration in their distribution along the epithelial lining in response to damage by doxorubicin. In mice treated with both doxorubicin and ghrelin, the number of BrdU-labeled cells was reduced when compared with mice treated with doxorubicin alone. CONCLUSION: The present study suggests that ghrelin enhances the regenerative potential of the GI epithelium in doxorubicin-treated mice, at least in part, by modulating cell proliferation.

  3. Natural polyphenols may ameliorate damage induced by copper overload.

    Science.gov (United States)

    Arnal, Nathalie; Tacconi de Alaniz, María J; Marra, Carlos Alberto

    2012-02-01

    The effect of the simultaneous exposure to transition metals and natural antioxidants frequently present in food is a question that needs further investigation. We aimed to explore the possible use of the natural polyphenols caffeic acid (CA), resveratrol (RES) and curcumin (CUR) to prevent damages induced by copper-overload on cellular molecules in HepG2 and A-549 human cells in culture. Exposure to 100μM/24h copper (Cu) caused extensive pro-oxidative damage evidenced by increased TBARS, protein carbonyls and nitrite productions in both cell types. Damage was aggravated by simultaneous incubation with 100μM of CA or RES, and it was also reflected in a decrease on cellular viability explored by trypan blue dye exclusion test and LDH leakage. Co-incubation with CUR produced opposite effects demonstrating a protective action which restored the level of biomarkers and cellular viability almost to control values. Thus, while CA and RES might aggravate the oxidative/nitrative damage of Cu, CUR should be considered as a putative protective agent. These results could stimulate further research on the possible use of natural polyphenols as neutralizing substances against the transition metal over-exposure in specific populations such as professional agrochemical sprayers and women using Cu-intrauterine devices.

  4. Leaf damage induces twining in a climbing plant.

    Science.gov (United States)

    Gianoli, Ernesto; Molina-Montenegro, Marco A

    2005-08-01

    Successful climbing by vines not only prevents shading by neighbouring vegetation, but also may place the vines beyond ground herbivores. Here we tested the hypothesis that herbivory might enhance climbing in a vine species, and that such induced climbing should be greater in the shade. We assessed field herbivory in climbing and prostrate ramets of the twining vine Convolvulus arvensis. We evaluated plant climbing after mechanical damage in a glasshouse under both sun and shade conditions, and determined whether control and damaged plants differed in growth rate or photosynthetic capacity. Plants experienced greater herbivory when growing prostrate than when climbing onto companion plants, in both an open habitat and a shaded understorey. Experimental plants increased their twining rate on a stake after suffering leaf damage, in both high- and low-light conditions, and this induced climbing was not coupled to an increase in growth rate. Increased photosynthesis was associated with enhanced twining rate only in the shade. Herbivory may be an ecological factor promoting the evolution of a climbing habit in plants.

  5. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  6. Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage

    Institute of Scientific and Technical Information of China (English)

    Lining Ke; Wei Guo; Jianwen Xu; Guodong Zhang; Wei Wang; Wenhua Huang

    2014-01-01

    The microglia-mediated inlfammatory reaction promotes neuronal damage under cerebral isch-emia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-αin a co-culture system containing activated N9 microglial cells. Ginse-noside Rb1 also signiifcantly decreased nitric oxide and superoxide production induced by N9 microglia. Our ifndings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neu-rons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-αexpression in hypoxia-activated microglia.

  7. The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.

    Science.gov (United States)

    Lee, Jong Soo; Kim, Young Hi; Park, Young Min

    2015-12-01

    This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

  8. Chlorambucil induced chromosome damage in juvenile chronic arthritis.

    Science.gov (United States)

    Palmer, R G; Varonos, S; Doré, C J; Denman, A M; Ansell, B M

    1985-01-01

    Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies. Images Fig. 1 PMID:4073932

  9. Effect of Contraction Velocity on Selected Muscle Damage Indices Following Acute Eccentric Exercise-Induced Muscle Damage: A Review

    Directory of Open Access Journals (Sweden)

    Farzaneh Movaseghi

    2016-12-01

    Full Text Available Background & Objective: Eccentric muscle action is mechanically more efficient but employs a unique activation strategy which predisposes the muscle to damage. Type II muscle fibers are more susceptible than type I fibers to muscle damage; hence, velocity probably interferes with mechanical stress and thus may modulate muscle damage. The purpose of this review study was to investigate the effect of contraction velocity on selected muscle damage indices following acute eccentric exercise-induced muscle damage. Material & Method: Looking up related articles published in valid scientific databases such as PubMed, Springer, Elsevier, Science Direct, and SID with standard keywords and according to the research criteria, 16 studies (1980 to 2015 were selected. Results: Ten studies showed that high velocity eccentric exercise induced greater muscle damage. Five studies showed no differences between velocities, and a single study indicated a greater magnitude of muscle damage following slow eccentric exercise. Conclusion: Thus, greater magnitude of damage is induced by contractions performed at a higher velocity. However, considering differences during tension in the majority of studies, focusing on elbow flexor muscles and muscle damage profile variety in various muscle groups, and more animal and human studies in other muscular groups are necessary to confirm how the velocity of acute eccentric exercise would affect the muscle damage.

  10. Fullerene derivatives protect endothelial cells against NO-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Lao Fang; Han Dong; Qu Ying; Liu Ying; Zhao Yuliang; Chen Chunying [CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190 (China); Li Wei [CAS Key Laboratory for Nuclear Analytical Techniques, Institute of High Energy Physics (IHEP), Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: chenchy@nanoctr.cn

    2009-06-03

    Functional fullerene derivatives have been demonstrated with potent antioxidation properties. Nitric oxide (NO) is a free radical that plays a part in leading to brain damage when it is accumulated to a high concentration. The possible scavenging activity of NO by the hydroxylated fullerene derivative C{sub 60}(OH){sub 22} and malonic acid derivative C{sub 60}(C(COOH){sub 2}){sub 2} was investigated using primary rat brain cerebral microvessel endothelial cells (CMECs). Results demonstrate that sodium nitroprusside (SNP), used as an NO donor, caused a marked decrease in cell viability and an increase in apoptosis. However, fullerene derivatives can remarkably protect against the apoptosis induced by NO assault. In addition, fullerene derivatives can also prevent NO-induced depolymerization of cytoskeleton and damage of the nucleus and accelerate endothelial cell repair. Further investigation shows that the sudden increase of the intercellular reactive oxygen species (ROS) induced by NO was significantly attenuated by post-treatment with fullerene derivatives. Our results suggest that functional fullerene derivatives are potential applications for NO-related disorders.

  11. Proton induced radiation damage in fast crystal scintillators

    Science.gov (United States)

    Yang, Fan; Zhang, Liyuan; Zhu, Ren-Yuan; Kapustinsky, Jon; Nelson, Ron; Wang, Zhehui

    2016-07-01

    This paper reports proton induced radiation damage in fast crystal scintillators. A 20 cm long LYSO crystal, a 15 cm long CeF3 crystal and four liquid scintillator based sealed quartz capillaries were irradiated by 800 MeV protons at Los Alamos up to 3.3 ×1014 p /cm2. Four 1.5 mm thick LYSO plates were irradiated by 24 GeV protons at CERN up to 6.9 ×1015 p /cm2. The results show an excellent radiation hardness of LYSO crystals against charged hadrons.

  12. Laser beam shaping for studying thermally induced damage

    CSIR Research Space (South Africa)

    Masina, BN

    2011-08-01

    Full Text Available for studying thermally induced damage Bathusile N. Masinaa, Richard Bodkinc, Bonex Mwakikungad and Andrew Forbesa,b?, aCSIR National Laser Centre, P. O. Box 395, Pretoria 0001, South Africa bSchool of Physics, University of KwaZulu-Natal, Private Bag X... from the blackbody at each wavelength, it is possible to determine the temperature of the blackbody or of the object by fitting the blackbody spectrum to the measured light. The advantage of using the blackbody emission is that there is no physical...

  13. Eye-Directed Overpressure Airwave-Induced Trauma Causes Lasting Damage to the Anterior and Posterior Globe: A Model for Testing Cell-Based Therapies.

    Science.gov (United States)

    Bricker-Anthony, Courtney; Hines-Beard, Jessica; Rex, Tonia S

    2016-06-01

    Characterization of the response of the Balb/c mouse to an eye-directed overpressure airwave, with the hypothesis that this mouse strain and model is useful for testing potential therapeutics for the treatment of traumatic eye injury. The left eyes of adult Balb/c mice were exposed to an eye-directed overpressure airwave. Intraocular pressure (IOP) was measured and eyes were inspected for gross pathology changes. Optical coherence tomography and histology were used to examine the structural integrity of the retina and optic nerve. Immunohistochemistry, in vivo molecular fluorophores, and a multiplex enzyme-linked immunosorbent assay were utilized to identify changes in cell death, neuroinflammation, and oxidative stress. This model induced a transient increase in IOP, corneal injuries, infrequent large retinal detachments, retinal pigment epithelium (RPE) vacuolization, glial reactivity, and retinal cell death. Both the corneal damage and RPE vacuolization persisted with time. Optic nerve degeneration occurred as early as 7 days postinjury and persisted out to 60 days. Retinal cell death, increased levels of reactive oxygen species, and neuroinflammation were detected at 7 days postinjury. The injury profile of the Balb/c mouse is consistent with commonly observed pathologies in blast-exposed patients. The damage is throughout the eye and persistent, making this mouse model useful for testing cell-based therapies.

  14. [Corneal manifestations in systemic diseases].

    Science.gov (United States)

    Zarranz Ventura, J; De Nova, E; Moreno-Montañés, J

    2008-01-01

    Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

  15. Bee products prevent agrichemical-induced oxidative damage in fish.

    Directory of Open Access Journals (Sweden)

    Daiane Ferreira

    Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

  16. Quercetin protection against ciprofloxacin induced liver damage in rats.

    Science.gov (United States)

    Taslidere, E; Dogan, Z; Elbe, H; Vardi, N; Cetin, A; Turkoz, Y

    2016-01-01

    Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

  17. Corneal ulcers in horses.

    Science.gov (United States)

    Williams, Lynn B; Pinard, Chantale L

    2013-01-01

    Corneal ulceration is commonly diagnosed by equine veterinarians. A complete ophthalmic examination as well as fluorescein staining, corneal cytology, and corneal bacterial (aerobic) and fungal culture and sensitivity testing are necessary for all infected corneal ulcers. Appropriate topical antibiotics, topical atropine, and systemic NSAIDs are indicated for all corneal ulcers. If keratomalacia (melting) is observed, anticollagenase/antiprotease therapy, such as autologous serum, is indicated. If fungal infection is suspected, antifungal therapy is a necessity. Subpalpebral lavage systems allow convenient, frequent, and potentially long-term therapy. Referral corneal surgeries provide additional therapeutic options when the globe's integrity is threatened or when improvement has not been detected after appropriate therapy.

  18. The AID-induced DNA damage response in chromatin

    DEFF Research Database (Denmark)

    Daniel, Jeremy A; Nussenzweig, André

    2013-01-01

    with somatic hypermutation and class switch recombination, chromatin must be made accessible for activation-induced cytidine deaminase (AID)-mediated deamination of cytosines in DNA. These lesions are recognized and removed by various DNA repair pathways but, if not handled properly, can lead to formation......Chemical modifications to the DNA and histone protein components of chromatin can modulate gene expression and genome stability. Understanding the physiological impact of changes in chromatin structure remains an important question in biology. As one example, in order to generate antibody diversity...... of oncogenic chromosomal translocations. In this review, we focus the discussion on how chromatin-modifying activities and -binding proteins contribute to the native chromatin environment in which AID-induced DNA damage is targeted and repaired. Outstanding questions remain regarding the direct roles...

  19. Anchor-induced chondral damage in the hip

    Science.gov (United States)

    Matsuda, Dean K.; Bharam, Srino; White, Brian J.; Matsuda, Nicole A.; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16–41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5–6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface. PMID:27011815

  20. Anchor-induced chondral damage in the hip.

    Science.gov (United States)

    Matsuda, Dean K; Bharam, Srino; White, Brian J; Matsuda, Nicole A; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16-41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5-6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface.

  1. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  2. Femtosecond laser's application in the corneal surgery

    Directory of Open Access Journals (Sweden)

    Shu-Liang Wang

    2015-10-01

    Full Text Available With the rapid development over the past two decades,femtosecond(10-15slasers(FShas become a new application in ophthalmic surgery. As laser power is defined as energy delivered per unit time, decreasing the pulse duration to femtosecond level(100fsnot only increases the power delivered but also decreases the fluence threshold for laser induced optical breakdown. In ablating tissue, FS has an edge over nanosecond lasers as there is minimal collateral damage from shock waves and heat conduction during surgical ablation. Thus, application of FS has been widely spread, from flap creation for laser-assisted in situ keratomileusis(LASIKsurgery, cutting of donor and recipient corneas in keratoplasty, creation of pockets for intracorneal ring implantation. FS applied in keratoplasty is mainly used in making graft and recipient bed, and can exactly cut different tissue of keratopathy. FS can also cut partial tissue of cornea, even if it is under the moderate corneal macula and corneal edema condition.

  3. Scaling Relations for Intercalation Induced Damage in Electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; Mukherjee, Partha P.

    2016-06-01

    Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. In this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based on a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. The reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.

  4. DAMAGE OF SILICONE RUBBER INDUCED BY PROTON IRRADIATION

    Institute of Scientific and Technical Information of China (English)

    Li-xin Zhang; Shi-qin Yang; Shi-yu He

    2003-01-01

    In this paper, the damage to methyl silicone rubber induced by irradiation with protons of 150 keV energy was studied. The surface morphology, tensile strength, Shore hardness, cross-linking density and glass transition temperature were examined. Positron annihilation lifetime spectrum analysis (PALS) was perfomed to reveal the damage mechanisms of the rubber. The results showed that tensile strength and Shore hardness of the rubber increased first and then decreased with increasing irradiation fluence. The PALS characteristics τ3 and I3, as well as the free volume Vf, decreased with increasing irradiation fluence up to 1015 cm-2, and then increased slowly. It indicates that proton irradiation causes a decrease of free volume in the methyl silicone rubber when the fluence is less than l015 cm-2, while the free volume increases when the fluence is greater than 1015 cm-2. The results on cross-linking density indicate that the cross-linking induced by proton irradiation is dominant at smaller proton fluences, increasing the tensile strength and Shore hardness of the rubber, while the degradation of rubber dominates at greater fluence, leading to a decrease of tensile strength and Shore hardness.

  5. Defense mechanisms against radiation induced teratogenic damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair.

  6. Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.

    Science.gov (United States)

    Franz, Alexander; Behringer, Michael; Harmsen, Jan-Frieder; Mayer, Constantin; Krauspe, Rüdiger; Zilkens, Christoph; Schumann, Moritz

    2017-08-22

    Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion-injury (I/R-Injury) during surgery. Due to similarities between the pathophysiological formation of I/R-injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca, an increased production of reactive oxygen species and increased pro-inflammatory signaling, the purpose of the present study was to investigate whether IPC performed prior to eccentric exercise may also protect against EIMD. Nineteen healthy men were matched to an eccentric only (ECC) (n=9) or eccentric proceeded by IPC group (IPC+ECC) (n=10). The exercise protocol consisted of bilateral biceps curls (3x10 repetitions at 80% of the concentric 1RM). In IPC+ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mmHg) immediately prior to the exercise (3x5 minutes of occlusion, separated by 5 minutes of reperfusion). Creatine Kinase (CK), arm circumference, subjective pain (VAS score) and radial displacement (Tensiomyography, Dm) were assessed before IPC, pre-exercise, post-exercise, 20 minutes-, 2 hours-, 24 hours-, 48 hours- and 72 hours post-exercise. CK differed from baseline only in ECC at 48h (pexercise. After 24h, 48h and 72h, CK was increased in ECC compared to IPC+ECC (between groups: 24h: p=0.004, 48h: pexercise, when compared to IPC+ECC (between groups: all pexercise days in ECC (all peccentric exercise of the elbow flexors blunts EIMD and exercise-induced pain, while maintaining the contractile properties of the muscle.

  7. TRPM2 channels mediate acetaminophen-induced liver damage.

    Science.gov (United States)

    Kheradpezhouh, Ehsan; Ma, Linlin; Morphett, Arthur; Barritt, Greg J; Rychkov, Grigori Y

    2014-02-25

    Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death.

  8. Corneal transplant - discharge

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000243.htm Corneal transplant - discharge To use the sharing features on this page, please enable JavaScript. You had a corneal transplant. Most of the tissue of your cornea (the ...

  9. Polar Value Analysis of Corneal Astigmatism in Intrastromal Corneal Ring Segment Implantation

    Science.gov (United States)

    Rho, Chang Rae; Kim, Min-Ji

    2016-01-01

    Purpose. To evaluate surgically induced astigmatism (SIA) and the average corneal power change in symmetric intrastromal corneal ring segment (ICRS) implantation. Methods. The study included 34 eyes of 34 keratoconus patients who underwent symmetric Intacs SK ICRS implantation. The corneal pocket incision meridian was the preoperative steep meridian. Corneal power data were obtained before and 3 months after Intacs SK ICRS implantation using scanning-slit topography. Polar value analysis was used to evaluate the SIA. Hotelling's trace test was used to compare intraindividual changes. Results. Three months postoperatively, the combined mean polar value for SIA changed significantly (Hotelling's T2 = 0.375; P = 0.006). The SIA was 1.54 D at 99° and the average corneal power decreased significantly by 3.8 D. Conclusion. Intacs SK ICRS placement decreased the average corneal power and corneal astigmatism compared to the preoperative corneal power and astigmatism when the corneal pocket incision was made at the preoperative steep meridian. PMID:27795856

  10. Polar Value Analysis of Corneal Astigmatism in Intrastromal Corneal Ring Segment Implantation

    Directory of Open Access Journals (Sweden)

    Chang Rae Rho

    2016-01-01

    Full Text Available Purpose. To evaluate surgically induced astigmatism (SIA and the average corneal power change in symmetric intrastromal corneal ring segment (ICRS implantation. Methods. The study included 34 eyes of 34 keratoconus patients who underwent symmetric Intacs SK ICRS implantation. The corneal pocket incision meridian was the preoperative steep meridian. Corneal power data were obtained before and 3 months after Intacs SK ICRS implantation using scanning-slit topography. Polar value analysis was used to evaluate the SIA. Hotelling’s trace test was used to compare intraindividual changes. Results. Three months postoperatively, the combined mean polar value for SIA changed significantly (Hotelling’s T2=0.375; P=0.006. The SIA was 1.54 D at 99° and the average corneal power decreased significantly by 3.8 D. Conclusion. Intacs SK ICRS placement decreased the average corneal power and corneal astigmatism compared to the preoperative corneal power and astigmatism when the corneal pocket incision was made at the preoperative steep meridian.

  11. Survival and integration of tissue-engineered corneal stroma in a model of corneal ulcer.

    Science.gov (United States)

    Zhang, Chao; Nie, Xin; Hu, Dan; Liu, Yuan; Deng, Zhihong; Dong, Rui; Zhang, Yongjie; Jin, Yan

    2007-08-01

    Tissue-engineered replacement of diseased or damaged tissue has become a reality for some types of tissue, such as skin and cartilage. Tissue-engineered corneal stroma represents a promising concept to overcome the limitations of cornea replacement with allograft. In this study, porcine cornea was decellularized by a series of extraction methods, and the in vivo biocompatibility of the scaffold was measured subcutaneously in rabbits (n = 8). These were not acutely rejected and no abscesses were observed by hematoxylin and eosin staining at the 8th week, indicating that the scaffolds had good biocompatibility. To investigate the potential value of clinical applications, rabbit stromal keratocytes were implanted onto decellularized scaffolds to fabricate tissue-engineered corneal stroma. Allograft, tissue-engineered corneal stroma, or scaffolds were implanted into a model of corneal ulcer. The survival and reconstruction of corneal transplantation were morphologically evaluated by light and electron microscopy until the 32nd week after implantation. Experiments involving transplantation indicated that the epithelial and stromal defect healed quickly, with improvement in corneal clarity. The integration of the graft was accompanied by neurite ingrowth from the host tissue. By 16 weeks after transplantation, the cornea had gradually regained an intact state similar to that of normal cornea. Our results demonstrate that the tissue-engineered corneal stroma with allogenetic cells is a promising therapeutic method for corneal injury.

  12. Earthquake-induced Landslidingand Ground Damage In New Zealand

    Science.gov (United States)

    Hancox, G. T.; Perrin, N. D.; Dellow, G. D.

    A study of landsliding caused by 22 historical earthquakes in New Zealand was completed at the end of 1997 (Hancox et al., 1997). The main aims of that study were to determine: (a) the nature and extent of landsliding and other ground damage (sand boils, subsidence and lateral spreading due to soil liquefaction) caused by historical earthquakes; (b) relationships between landsliding and earthquake magnitude, epicentre, faulting, geology and topography; (c) improved environmental criteria and ground classes for assigning MM intensities and seismic hazard assessments in N.Z. The data and results of the 1997 study have recently been summarised and expanded (Hancox et al., in press), and are described in this paper. Relationships developed from these studies indicate that the minimum magnitude for earthquake-induced landsliding (EIL) in N.Z. is about M 5, with significant landsliding occurring at M 6 or greater. The minimum MM intensity for landsliding is MM6, while the most common intensities for significant landsliding are MM7-8. The intensity threshold for soil liquefaction in New Zealand was found to be MM7 for sand boils, and MM8 for lateral spreading, although such effects may also occur at one intensity level lower in highly susceptible materials. The minimum magnitude for liquefaction phenomena in N.Z. is about M 6, compared to M 5 overseas where highly susceptible soils are probably more widespread. Revised environmental response criteria (landsliding, subsidence, liquefaction-induced sand boils and lateral spreading) have also been established for the New Zealand MM Intensity Scale, and provisional landslide susceptibility Ground Classes developed for assigning MM intensities in areas where there are few buildings. Other new data presented include a size/frequency distribution model for earthquake-induced landslides over the last 150 years and a preliminary EIL Opportunity model for N.Z. The application of EIL data and relationships for seismic hazard

  13. Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Long Shi

    Full Text Available Advanced Glycation End Products (AGEs has been implicated in the progression of diabetic keratopathy. However, details regarding their function are not well understood. In the present study, we investigated the effects of intracellular reactive oxygen species (ROS and JNK, p38 MAPK on AGE-modified bovine serum albumin (BSA induced Human telomerase-immortalized corneal epithelial cells (HUCLs apoptosis. We found that AGE-BSA induced HUCLs apoptosis and increased Bax protein expression, decreased Bcl-2 protein expression. AGE-BSA also induced the expression of receptor for advanced glycation end product (RAGE. AGE-BSA-RAGE interaction induced intracellular ROS generation through activated NADPH oxidase and increased the phosphorylation of p47phox. AGE-BSA induced HUCLs apoptosis was inhibited by pretreatment with NADPH oxidase inhibitors, ROS quencher N-acetylcysteine (NAC or neutralizing anti-RAGE antibodies. We also found that AGE-BSA induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked AGE-BSA-induced HUCLs apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.

  14. DNA damage and mutations induced by arachidonic acid peroxidation.

    Science.gov (United States)

    Lim, Punnajit; Sadre-Bazzaz, Kianoush; Shurter, Jesse; Sarasin, Alain; Termini, John

    2003-12-30

    Endogenous cellular oxidation of omega6-polyunsaturated fatty acids (PUFAs) has long been recognized as a contributing factor in the development of various cancers. The accrual of DNA damage as a result of reaction with free radical and electrophilic aldehyde products of lipid peroxidation is believed to be involved; however, the genotoxic and mutation-inducing potential of specific membrane PUFAs remains poorly defined. In the present study we have examined the ability of peroxidizing arachidonic acid (AA, 20:4omega6) to induce DNA strand breaks, base modifications, and mutations. The time-dependent induction of single-strand breaks and oxidative base modifications by AA in genomic DNA was quantified using denaturing glyoxal gel electrophoresis. Mutation spectra were determined in XP-G fibroblasts and a repair-proficient line corrected for this defect by c-DNA complementation (XP-G(+)). Mutation frequencies were elevated from approximately 5- to 30-fold over the background following reaction of DNA with AA for various times. The XPG gene product was found to be involved in the suppression of mutations after extended reaction of DNA with AA. Arachidonic acid-induced base substitutions were consistent with the presence of both oxidized and aldehyde base adducts in DNA. The frequency of multiple-base substitutions induced by AA was significantly reduced upon correction for the XPG defect (14% vs 2%, P = 0.0015). Evidence is also presented which suggests that the induced frequency of multiple mutations is lesion dependent. These results are compared to published data for mutations stimulated by alpha,beta-unsaturated aldehydes identified as products of lipid peroxidation.

  15. Knee proprioception after exercise-induced muscle damage.

    Science.gov (United States)

    Torres, R; Vasques, J; Duarte, J A; Cabri, J M H

    2010-06-01

    The purpose of the present study was to investigate whether exercise-induced quadriceps muscle damage affects knee proprioception such as joint position sense (JPS), force sense and the threshold to detect passive movement (TTDPM). Fourteen young men performed sets of eccentric quadriceps contractions at a target of 60% of the maximal concentric peak torque until exhaustion; the exercise was interrupted whenever the subject could not complete two sets. Muscle soreness, JPS, the TTDPM and force sense were examined before the exercise as well as one, 24, 48, 72 and 96 h after exercise. The results were compared using one-way repeated-measure ANOVA. Plasma CK activity, collected at the same times, was analyzed by the Friedman's test to discriminate differences between baseline values and each of the other assessment moments (pknee flexion and force sense were significantly decreased up to 48 h, whereas TTDPM decreased significantly at only one hour and 24 h after exercise, at 30 and 70 degrees of the knee flexion, respectively. The results allow the conclusion that eccentric exercise leading to muscle damage alters joint proprioception, suggesting that there might be impairment in the intrafusal fibres of spindle muscles and in the tendon organs.

  16. Protection of cadmium chloride induced DNA damage by Lamiaceae plants

    Institute of Scientific and Technical Information of China (English)

    Ramaraj Thirugnanasampandan; Rajarajeswaran Jayakumar

    2011-01-01

    Objective: To analyze the total phenolic content, DNA protecting and radical scavenging activity of ethanolic leaf extracts of three Lamiaceae plants, i.e. Anisomelos malabarica (A. malabarica), Leucas aspera (L. aspera) and Ocimum basilicum (O. basilicum). Methods: The total polyphenols and flavonoids were analyzed in the ethanolic leaf extracts of the lamiaceae plants. To determine the DNA protecting activity, various concentrations of the plant extracts were prepared and treated on cultured HepG2 human lung cancer cells. The pretreated cells were exposed to H2O2 to induce DNA damage through oxidative stress. Comet assay was done and the tail length of individual comets was measured. Nitric oxide and superoxide anion scavenging activities of lamiaceae plants were analyzed. Results: Among the three plant extracts, the highest amount of total phenolic content was found in O. basilicum (189.33 mg/g), whereas A. malabarica showed high levels of flavonoids (10.66 mg/g). O. basilicum also showed high levels of DNA protecting (85%) and radical scavenging activity. Conclusions: The results of this study shows that bioactive phenols present in lamiaceae plants may prevent carcinogenesis through scavenging free radicals and inhibiting DNA damage.

  17. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  18. X-Ray induced DNA damage – why use plants?

    Directory of Open Access Journals (Sweden)

    John William Einset

    2015-06-01

    Full Text Available The comet assay was used to monitor DNA repair after X-ray exposures caused by 0.2-15 Gy. A clear distinction in the time course of DNA repair after 2 Gy was observed with an early ‘rapid phase’, lasting 20-40 minutes, being followed by a ‘slow phase’ which actually consists of a period of negligible repair and then rapid repair during 140-160 minutes. The fact that homozygous mutants for both ATM and BRCA1 fail to repair DNA completely during 3 hours after 2 Gy exposures indicates that repair processes occurring during the ‘slow phase’ involve ds breaks in DNA. Both BRCA1 and Rad51 expression are strongly upregulated by X-rays in Arabidopsis. Rye grass, Norway spruce and Sawara cypress also have ‘slow phase’ repair similar to Arabidopsis, suggesting that the requisite enzymes have to be induced in these plants as well. To look at the effect of genome size in relation to sensitivity to DNA damage, we exposed isolated nuclei from Norway spruce (19.2 Gbp genome, celery (14.1 Gbp, spinach (12.6 Gbp Sawara cypress (8.9 Gbp, lettuce (2.6 Gbp and Arabidopsis (0.135 Gbp to X-rays. After a 1 Gy exposure, a linear relationship was seen between % tails and genome size, confirming the idea that larger genomes are more sensitive to X-ray damage.

  19. Limits for Beam-Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  20. Limits for Beam Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  1. Sonic-boom-induced building structure responses including damage.

    Science.gov (United States)

    Clarkson, B. L.; Mayes, W. H.

    1972-01-01

    Concepts of sonic-boom pressure loading of building structures and the associated responses are reviewed, and results of pertinent theoretical and experimental research programs are summarized. The significance of sonic-boom load time histories, including waveshape effects, are illustrated with the aid of simple structural elements such as beams and plates. Also included are discussions of the significance of such other phenomena as three-dimensional loading effects, air cavity coupling, multimodal responses, and structural nonlinearities. Measured deflection, acceleration, and strain data from laboratory models and full-scale building tests are summarized, and these data are compared, where possible, with predicted values. Damage complaint and claim experience due both to controlled and uncontrolled supersonic flights over communities are summarized with particular reference to residential, commercial, and historic buildings. Sonic-boom-induced building responses are compared with those from other impulsive loadings due to natural and cultural events and from laboratory simulation tests.

  2. Ecabet sodium alleviates neomycin-induced hair cell damage.

    Science.gov (United States)

    Rah, Yoon Chan; Choi, June; Yoo, Myung Hoon; Yum, Gunhwee; Park, Saemi; Oh, Kyoung Ho; Lee, Seung Hoon; Kwon, Soon Young; Cho, Seung Hyun; Kim, Suhyun; Park, Hae-Chul

    2015-12-01

    Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 μg/mL for 1 h, followed by 125 μM neomycin for 1h. The positive control group was established by 125 μM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 μM/ml ES treatment (12.98 ± 2.59 cells) comparing to that of the negative control group (14.15 ± 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 ± 0.91 cells, p neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 μM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation.

  3. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  4. Pyrosequencing: applicability for studying DNA damage-induced mutagenesis.

    Science.gov (United States)

    Minko, Irina G; Earley, Lauriel F; Larlee, Kimberly E; Lin, Ying-Chih; Lloyd, R Stephen

    2014-10-01

    Site-specifically modified DNAs are routinely used in the study of DNA damage-induced mutagenesis. These analyses involve the creation of DNA vectors containing a lesion at a pre-determined position, DNA replication, and detection of mutations at the target site. The final step has previously required the isolation of individual DNA clones, hybridization with radioactively labeled probes, and verification of mutations by Sanger sequencing. In the search for an alternative procedure that would allow direct quantification of sequence variants in a mixed population of DNA molecules, we evaluated the applicability of pyrosequencing to site-specific mutagenesis assays. The progeny DNAs were analyzed that originated from replication of N(6) -(deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG)-containing vectors in primate cells, with the lesion being positioned in the 5'-GCNGG-3' sequence context. Pyrosequencing detected ∼8% G to T transversions and ∼3.5% G to A transitions, a result that was in excellent agreement with frequencies previously measured by the standard procedure (Earley LF et al. [2013]: Chem Res Toxicol 26:1108-1114). However, ∼3.5% G to C transversions and ∼2.0% deletions could not be detected by pyrosequencing. Consistent with these observations, the sensitivity of pyrosequencing for measuring the single deoxynucleotide variants differed depending on the deoxynucleotide identity, and in the given sequence contexts, was determined to be ∼1-2% for A and T and ∼5% for C. Pyrosequencing of other DNA isolates that were obtained following replication of MeFapy-dG-containing vectors in primate cells or Escherichia coli, identified several additional limitations. Collectively, our data demonstrated that pyrosequencing can be used for studying DNA damage-induced mutagenesis as an effective complementary experimental approach to current protocols.

  5. Shortwave UV-induced damage as part of the solar damage spectrum is not a major contributor to mitochondrial dysfunction.

    Science.gov (United States)

    Gebhard, Daniel; Matt, Katja; Burger, Katharina; Bergemann, Jörg

    2014-06-01

    Because of the absence of a nucleotide excision repair in mitochondria, ultraviolet (UV)-induced bulky mitochondrial DNA (mtDNA) lesions persist for several days before they would eventually be removed by mitophagy. Long persistence of this damage might disturb mitochondrial functions, thereby contributing to skin ageing. In this study, we examined the influence of shortwave UV-induced damage on mitochondrial parameters in normal human skin fibroblasts. We irradiated cells with either sun-simulating light (SSL) or with ultraviolet C to generate bulky DNA lesions. At equivalent antiproliferative doses, both irradiation regimes induced gene expression of mitochondrial transcription factor A (TFAM) and matrix metallopeptidase 1 (MMP-1). Only irradiation with SSL, however, caused significant changes in mtDNA copy number and a decrease in mitochondrial respiration. Our results indicate that shortwave UV-induced damage as part of the solar spectrum is not a major contributor to mitochondrial dysfunction.

  6. Influence of Ambient Temperature on Nanosecond and Picosecond Laser-Induced Bulk Damage of Fused Silica

    Directory of Open Access Journals (Sweden)

    L. Yang

    2014-01-01

    Full Text Available The nanosecond (ns and picosecond (ps pulsed laser-induced damage behaviors of fused silica under cryogenic and room temperature have been investigated. The laser-induced damage threshold (LIDT and damage probability are used to understand the damage behavior at different ambient temperatures. The results show that the LIDTs for both ns and ps slightly increased at cryogenic temperature compared to that at room temperature. Meanwhile, the damage probability has an inverse trend; that is, the damage probability at low temperature is smaller than that at room temperature. A theoretical model based on heated crystal lattice is well consistent with the experimental results.

  7. Progress in corneal wound healing.

    Science.gov (United States)

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  8. Progress in corneal wound healing

    Science.gov (United States)

    Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

    2015-01-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and

  9. Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis

    Science.gov (United States)

    Matteini, P.; Rossi, F.; Ratto, F.; Bruno, I.; Nesi, P.; Pini, R.

    2008-02-01

    Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.

  10. Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.

    Directory of Open Access Journals (Sweden)

    Xurui Zhang

    Full Text Available Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.

  11. Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

    Science.gov (United States)

    Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

    2017-01-01

    The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

  12. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  13. Myostatin induces DNA damage in skeletal muscle of streptozotocin-induced type 1 diabetic mice.

    Science.gov (United States)

    Sriram, Sandhya; Subramanian, Subha; Juvvuna, Prasanna Kumar; McFarlane, Craig; Salerno, Monica Senna; Kambadur, Ravi; Sharma, Mridula

    2014-02-28

    One of the features of uncontrolled type 1 diabetes is oxidative stress that induces DNA damage and cell death. Skeletal muscle atrophy is also considerable in type 1 diabetes, however, the signaling mechanisms that induce oxidative stress culminating in muscle atrophy are not fully known. Here, we show that in Streptozotocin-induced diabetic wild type mice, hypo-phosphorylation of Akt, resulted in activation of Foxa2 transcription factor in the muscle. Foxa2 transcriptionally up-regulated Myostatin, contributing to exaggerated oxidative stress leading to DNA damage via p63/REDD1 pathway in skeletal muscle of Streptozotocin-treated wild type mice. In Myostatin(-/-) mice however, Streptozotocin treatment did not reduce Akt phosphorylation despite reduced IRS-1 signaling. Moreover, Foxa2 levels remained unaltered in Myostatin(-/-) mice, while levels of p63/REDD1 were higher compared with wild type mice. Consistent with these results, relatively less DNA damage and muscle atrophy was observed in Myostatin(-/-) muscle in response to Streptozotocin treatment. Taken together, our results for the first time show the role of Foxa2 in Myostatin regulation in skeletal muscle in diabetic mice. Altogether, these results demonstrate the mechanism by which Myostatin contributes to DNA damage in skeletal muscle of the diabetic mice that would lead to myofiber degeneration.

  14. Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications

    Institute of Scientific and Technical Information of China (English)

    Xing Liu; Fen-Fen Yu; Yi-Min Zhong; Xin-Xing Guo; Zhen Mao

    2015-01-01

    Background:Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity.Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance.This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment.Methods:Fifty-eight patients (101 eyes),who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria,were included in the analysis.All patients were maintained the original topical anti-glaucoma treatment.In the SH-treated group (56 eyes),unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days.In the control group (55 eyes),phosphate-buffered saline were administered with 3 times daily for 90 days.Ocular Surface Disease Index (OSDI) questionnaire,break-up time (BUT) test,corneal fluorescein staining,corneal and conjunctival rose Bengal staining,Schirmer test,and conjunctiva impression cytology were performed sequentially on days 0 and 91.Results:Compared with the control group,SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test:H =38.668,P < 0.001),fluorescein and rose Bengal scores (Wilcoxon signed-ranks test:z =-3.843,P< 0.001,and z =-3.508,P < 0.001,respectively),increase in tear film BUT (t-test:t =-10.994,P < 0.001) and aqueous tear production (t-test:t =-10.328,P < 0.001) on day 91.The goblet cell density was increased (t-test:t =-9.981,P < 0.001),and the morphology of the conjunctival epithelium were also improved after SH treatment.Conclusions:SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment.SH could be proposed as a new attempt to reduce ocular surface toxicity,and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.

  15. Positional accommodative intraocular lens power error induced by the estimation of the corneal power and the effective lens position

    Directory of Open Access Journals (Sweden)

    David P Piñero

    2015-01-01

    Full Text Available Purpose: To evaluate the predictability of the refractive correction achieved with a positional accommodating intraocular lenses (IOL and to develop a potential optimization of it by minimizing the error associated with the keratometric estimation of the corneal power and by developing a predictive formula for the effective lens position (ELP. Materials and Methods: Clinical data from 25 eyes of 14 patients (age range, 52-77 years and undergoing cataract surgery with implantation of the accommodating IOL Crystalens HD (Bausch and Lomb were retrospectively reviewed. In all cases, the calculation of an adjusted IOL power (P IOLadj based on Gaussian optics considering the residual refractive error was done using a variable keratometric index value (n kadj for corneal power estimation with and without using an estimation algorithm for ELP obtained by multiple regression analysis (ELP adj . P IOLadj was compared to the real IOL power implanted (P IOLReal , calculated with the SRK-T formula and also to the values estimated by the Haigis, HofferQ, and Holladay I formulas. Results: No statistically significant differences were found between P IOLReal and P IOLadj when ELP adj was used (P = 0.10, with a range of agreement between calculations of 1.23 D. In contrast, P IOLReal was significantly higher when compared to P IOLadj without using ELP adj and also compared to the values estimated by the other formulas. Conclusions: Predictable refractive outcomes can be obtained with the accommodating IOL Crystalens HD using a variable keratometric index for corneal power estimation and by estimating ELP with an algorithm dependent on anatomical factors and age.

  16. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  17. Corneal surface reconstruction - a short review

    Directory of Open Access Journals (Sweden)

    Madhavan H N

    2009-01-01

    patients with persistent epithelial defects, pterygium, symblepharon, and for ocular surface reconstruction. The role of AMT in ocular disorders has been recently re-evaluated by Schwab and coworkers.11 They carefully examined the protocols used in the manufacture of the bio-engineered construct to assess the risks and reviewed 20 published reports of human trials conducted between 1996 and 2005 in a report suggesting that the currently used transplant procedures carry potential health risks not only to individuals but also to "the wider community" because they "rely on the use of materials from animal and human donors". Their review revealed that most protocols used animal-derived products including fetal calf serum (FCS with a potential for transmissible spongiform encephalopathy (TSE infection (of the brain or allergic reactions and further state that the use of commercially available fibrin tissue "adds to the risk of microbial or prion contamination". Since no investigations have been done, the use of AMT can potentially induce "disease transmission through contamination with bacteria, viruses, or other infectious agents", they also stated that with 3T3 cells being commonly used (that come from mice possibilities of "xenozoonosis", or animal-to-human disease transmission are a concern.Several studies have been undertaken using oral mucosal epithelial cells cultivated on amniotic membrane for useful tissue engineering of damaged corneal surface. Higa and Shimazaki have carried out a study of transplantation in cultivated oral mucosal epithelial which has been useful in achieving a stable ocular surface. However, in addition to using epithelial sheets with AM, they developed a technique for generating carrier-free sheets using fibrin sealants. These sheets seem to contain more differentiated epithelium than those obtained with AM while retaining similar levels of colony-forming progenitor cells. In terms of isolation and cultivation of corneal epithelial stem

  18. Robustness of various metals against high THz field induced damage

    DEFF Research Database (Denmark)

    Zhu, Jianfei; Iwaszczuk, Krzysztof; Tarekegne, Abebe Tilahun;

    2016-01-01

    We investigate various metals for their robustness against damage caused by strong THz field. Even though the damage process is not of a thermal nature we observe a correlation between robustness and the melting temperature. Influence of the substrate material on the damage pattern is also studied....

  19. Radiation damage of insulating crystals induced by electronic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Noriaki

    1988-05-01

    A review is given on radiation damage of insulating crystals arising from energy imparted to solids into electronic excitation. Emphasis is placed in describing the mechanism. The role of the exciton-phonon interaction in the production of radiation damage is described and the radiation damage processes in a few typical insulators such as alkali halides, alkali earth fluorides and silicon dioxide are described.

  20. Fatigue-induced damage of high-strength steels

    Science.gov (United States)

    Shetulov, D. I.; Myl'nikov, V. V.

    2014-03-01

    The issues on the estimation of the surface damage of the products produced from high-strength alloys are considered. Mathematical relationships for a numerical calculation of the surface damage are given. The peculiarities of the evaluation of the surface damage are investigated, as applied to high-strength alloys.

  1. The effects of pre-exercise vibration stimulation on the exercise-induced muscle damage

    Science.gov (United States)

    Kim, Ji-Yun; Kang, Da-Haeng; Lee, Joon-Hee; O, Se-Min; Jeon, Jae-Keun

    2017-01-01

    [Purpose] To investigate the effects of pre-induced muscle damage vibration stimulation on the pressure-pain threshold and muscle-fatigue-related metabolites of exercise-induced muscle damage. [Subjects and Methods] Thirty healthy, adult male subjects were randomly assigned to the pre-induced muscle damage vibration stimulation group, post-induced muscle damage vibration stimulation group, or control group (n=10 per group). To investigate the effects of pre-induced muscle damage vibration stimulation, changes in the pressure-pain threshold (lb), creatine kinase level (U/L), and lactate dehydrogenase level (U/L) were measured and analyzed at baseline and at 24 hours, 48 hours, and 72 hours after exercise. [Results] The pressure-pain thresholds and concentrations of creatine kinase and lactate dehydrogenase varied significantly in each group and during each measurement period. There were interactions between the measurement periods and groups, and results of the post-hoc test showed that the pre-induced muscle damage vibration stimulation group had the highest efficacy among the groups. [Conclusion] Pre-induced muscle damage vibration stimulation is more effective than post-induced muscle damage vibration stimulation for preventing muscle damage. PMID:28210056

  2. Hevin plays a pivotal role in corneal wound healing.

    Directory of Open Access Journals (Sweden)

    Shyam S Chaurasia

    Full Text Available BACKGROUND: Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK in hevin-null (hevin(-/- mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin to rescue the stromal cellular components damaged by the excimer laser. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and hevin (-/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM, transmission electron microscopy (TEM, immunohistochemistry (IHC and western blotting (WB. IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin (-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts, inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. CONCLUSIONS/SIGNIFICANCE: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin (-/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued

  3. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    Science.gov (United States)

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  4. A mouse model of ocular blast injury that induces closed globe anterior and posterior pole damage

    Science.gov (United States)

    Hines-Beard, Jessica; Marchetta, Jeffrey; Gordon, Sarah; Chaum, Edward; Geisert, Eldon E.; Rex, Tonia S.

    2012-01-01

    We developed and characterized a mouse model of primary ocular blast injury. The device consists of: a pressurized air tank attached to a regulated paintball gun with a machined barrel; a chamber that protects the mouse from direct injury and recoil, while exposing the eye; and a secure platform that enables fine, controlled movement of the chamber in relation to the barrel. Expected pressures were calculated and the optimal pressure transducer, based on the predicted pressures, was positioned to measure output pressures at the location where the mouse eye would be placed. Mice were exposed to one of three blast pressures (23.6, 26.4, or 30.4psi). Gross pathology, intraocular pressure, optical coherence tomography, and visual acuity were assessed 0, 3, 7, 14, and 28 days after exposure. Contralateral eyes and non-blast exposed mice were used as controls. We detected increased damage with increased pressures and a shift in the damage profile over time. Gross pathology included corneal edema, corneal abrasions, and optic nerve avulsion. Retinal damage was detected by optical coherence tomography and a deficit in visual acuity was detected by optokinetics. Our findings are comparable to those identified in Veterans of the recent wars with closed eye injuries as a result of blast exposure. In summary, this is a relatively simple system that creates injuries with features similar to those seen in patients with ocular blast trauma. This is an important new model for testing the short-term and long-term spectrum of closed globe blast injuries and potential therapeutic interventions. PMID:22504073

  5. SHI induced damage in electrical properties of silicon NPN BJTs

    Science.gov (United States)

    Kumar, M. Vinay; Kumar, Santhosh; Yashoda, T.; Krishnaveni, S.

    2016-05-01

    The investigation of radiation damage in Si microelectronic circuitry and devices are being carried out by various research groups globally. In particular the Si Bipolar junction transistors are very sensitive to high energetic radiation. In the present study, radiation response of NPN Bipolar junction transistor (2N3773) has been examined for 60 MeV B4+ ion. Key electrical properties like Gummel, dc current gain and capacitance - voltage (C-V) characteristics of 60 MeV B4+ ion irradiated transistor were studied before and after irradiation. Ion irradiation and subsequent electrical characterizations were performed at room temperature. Current voltage (I-V) measurements showed the increase in collector current for VBE ≤ 0.4 V as a function of fluence, which is due to B4+ ion induced surface leakage currents. Base current is observed to be more sensitive than collector current and gain appears to be degraded with ion fluence. Also, C-V measurements shows that both built in potential and doping concentration increased significantly after irradiation.

  6. Time evolution of damage in thermally induced creep rupture

    KAUST Repository

    Yoshioka, N.

    2012-01-01

    We investigate the time evolution of a bundle of fibers subject to a constant external load. Breaking events are initiated by thermally induced stress fluctuations followed by load redistribution which subsequently leads to an avalanche of breakings. We compare analytic results obtained in the mean-field limit to the computer simulations of localized load redistribution to reveal the effect of the range of interaction on the time evolution. Focusing on the waiting times between consecutive bursts we show that the time evolution has two distinct forms: at high load values the breaking process continuously accelerates towards macroscopic failure, however, for low loads and high enough temperatures the acceleration is preceded by a slow-down. Analyzing the structural entropy and the location of consecutive bursts we show that in the presence of stress concentration the early acceleration is the consequence of damage localization. The distribution of waiting times has a power law form with an exponent switching between 1 and 2 as the load and temperature are varied.

  7. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  8. Novel DNA damage checkpoint in mitosis: Mitotic DNA damage induces re-replication without cell division in various cancer cells.

    Science.gov (United States)

    Hyun, Sun-Yi; Rosen, Eliot M; Jang, Young-Joo

    2012-07-06

    DNA damage induces multiple checkpoint pathways to arrest cell cycle progression until damage is repaired. In our previous reports, when DNA damage occurred in prometaphase, cells were accumulated in 4 N-DNA G1 phase, and mitosis-specific kinases were inactivated in dependent on ATM/Chk1 after a short incubation for repair. We investigated whether or not mitotic DNA damage causes cells to skip-over late mitotic periods under prolonged incubation in a time-lapse study. 4 N-DNA-damaged cells re-replicated without cell division and accumulated in 8 N-DNA content, and the activities of apoptotic factors were increased. The inhibition of DNA replication reduced the 8 N-DNA cell population dramatically. Induction of replication without cell division was not observed upon depletion of Chk1 or ATM. Finally, mitotic DNA damage induces mitotic slippage and that cells enter G1 phase with 4 N-DNA content and then DNA replication is occurred to 8 N-DNA content before completion of mitosis in the ATM/Chk1-dependent manner, followed by caspase-dependent apoptosis during long-term repair. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Laser-Induced Damage Growth on Larger-Aperture Fused Silica Optical Components at 351 nm

    Institute of Scientific and Technical Information of China (English)

    HUANG Wan-Qing; ZHANG Xiao-Min; HAN Wei; WANG Fang; XIANG Yong; LI Fu-Quan; FENG Bin; JING Feng; WEI Xiao-Feng; ZHENG Wan-Guo

    2009-01-01

    Laser-induced damage is a key lifetime limiter for optics in high-power laser facility. Damage initiation and growth under 351 nm high-fluence laser irradiation are observed on larger-aperture fused silica optics. The input surface of one fused silica component is damaged most severely and an explanation is presented. Obscurations and the area of a scratch on it are found to grow exponentially with the shot number. The area of damage site grows linearly. Micrographs of damage sites support the micro-explosion damage model which could be used to qualitatively explain the phenomena.

  10. Thermal Model of Laser-Induced Eye Damage

    Science.gov (United States)

    1974-10-08

    Eq. A-13 yields ’ cp’R! Cp + 1 = RI1 (A-14) Taking logarithms of both sides of Eq. A-14 yieldsI ’ log( cpRI - cp + 1) = ck’log R1 (A-15) Finally...LA 1 F A ND0 ST r)R I ,J T N ICI S A T W H ICH T F PPFRA T UR F" ~ RF P R IN T E1 103. ID2=IU2+TPE 1014. 1F (1n1 *LT * PA ) ID1IPA 108. 15 FUPMAT(1H0...1IM)ICM~ RF (Z+)Z~3 -Vo Io SAMPLE DATA FOR CORNEAL MODEL -- - --------------------------------- ------- ........... 06-IA CARD 1 ........... " .0’•5

  11. Effect of Vacuum on the Laser-Induced Damage of Anti-Reflection Coatings

    Institute of Scientific and Technical Information of China (English)

    LING Xiu-Lan; ZHAO Yuan-An; LI Da-Wei; ZHOU Ming; SHAO Jian-Da; FAN Zheng-Xiu

    2009-01-01

    In the comparison of damage modifications, absorption measurement and energy dispersive x-ray analysis, the effect of vacuum on the laser-induced damage of anti-reflection coatings is analyzed. It is found that vacuum decreases the laser-induced damage threshold of the films. The low laser-induced damage threshold in vacuum environments as opposed to air environments is attributed to water absorption and the formation of the O/Si,O/Zr sub-stoichiometry in the course of laser irradiation.

  12. Corneal mucus plaques.

    Science.gov (United States)

    Fraunfelder, F T; Wright, P; Tripathi, R C

    1977-02-01

    Corneal mucus plaques adhered to the anterior corneal surface in 17 of 67 advanced cases of keratoconjunctivitis sicca. The plaques were translucent to opaque and varied in size and shape, from multiple isolated islands to bizarre patterns involving more than half the corneal surface. Ultrastructurally, they consisted of mucus mixed with desquamated degenerating epithelial cells and proteinaceous and lipoidal material. The condition may be symptomatic but can be controlled and prevented in most cases by topical ocular application of 10% acetylcysteine.

  13. Laser-induced damage tests based on a marker-based watershed algorithm with gray control

    Institute of Scientific and Technical Information of China (English)

    Yajing; Guo; Shunxing; Tang; Xiuqing; Jiang; Yujie; Peng; Baoqiang; Zhu; Zunqi; Lin

    2014-01-01

    An effective damage test method based on a marker-based watershed algorithm with gray control(MWGC) is proposed to study the properties of damage induced by near-field laser irradiation for large-aperture laser facilities.Damage tests were performed on fused silica samples and information on the size of damage sites was obtained by this new algorithm,which can effectively suppress the issue of over-segmentation of images resulting from non-uniform illumination in darkfield imaging.Experimental analysis and results show that the lateral damage growth on the exit surface is exponential,and the number of damage sites decreases sharply with damage site size in the damage site distribution statistics.The average damage growth coefficients fitted according to the experimental results for Corning-7980 and Heraeus-Suprasil312 samples at 351 nm are 1.10 ± 0.31 and 0.60 ± 0.09,respectively.

  14. Inhibition of Ultraviolet B-Induced Expression of the Proinflammatory Cytokines TNF-α and VEGF in the Cornea by Fucoxanthin Treatment in a Rat Model

    Directory of Open Access Journals (Sweden)

    Shiu-Jau Chen

    2016-01-01

    Full Text Available Ultraviolet B (UVB irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α and vascular endothelial growth factor (VEGF, significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration.

  15. Blast-Induced Damage on Millisecond Blasting Model Test with Multicircle Vertical Blastholes

    Directory of Open Access Journals (Sweden)

    Qin-yong Ma

    2015-01-01

    Full Text Available To investigate the blast-induced damage effect on surrounding rock in vertical shaft excavation, 4 kinds of millisecond blasting model tests with three-circle blastholes were designed and carried out with excavation blasting in vertical shaft as the background. The longitudinal wave velocity on the side of concrete model was also measured before and after blasting. Then blast damage factor was then calculated by measuring longitudinal wave velocity before and after blasting. The test results show that the blast-induced damage factor attenuated gradually with the centre of three-circle blastholes as centre. With the threshold value of 0.19 for blast-induced damage factor, blast-induced damage zones for 4 kinds of model tests are described and there is an inverted cone blast-induced damage zone in concrete model. And analyses of cutting effect and blast-induced damage zone indicate that in order to minimize the blast-induced damage effect and ensure the cutting effect the reasonable blasting scheme for three-circle blastholes is the inner two-circle blastholes initiated simultaneously and the outer third circle blastholes initiated in a 25 ms delay.

  16. Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

    Science.gov (United States)

    Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

    2014-05-29

    Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist

  17. Sunlight-induced DNA damage in human mononuclear cells

    DEFF Research Database (Denmark)

    Møller, Peter; Wallin, Hakan; Holst, Erik

    2002-01-01

    of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individual's background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could......In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single-cell gel electrophoresis. The level of DNA damage was influenced by the average daily influx of sunlight ... to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect...

  18. Clinical correlates of common corneal neovascular diseases: a literature review

    Institute of Scientific and Technical Information of China (English)

    Nizar; Saleh; Abdelfattah; Mohamed; Amgad; Amira; A; Zayed; Hamdy; Salem; Ahmed; E; Elkhanany; Heba; Hussein; Nawal; Abd; El-Baky

    2015-01-01

    A large subset of corneal pathologies involves the formation of new vessels(neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization(CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis,contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatment available so far.

  19. Characterization of Corneal Indentation Hysteresis.

    Science.gov (United States)

    Ko, Match W L; Dongming Wei; Leung, Christopher K S

    2015-01-01

    Corneal indentation is adapted for the design and development of a characterization method for corneal hysteresis behavior - Corneal Indentation Hysteresis (CIH). Fourteen porcine eyes were tested using the corneal indentation method. The CIH measured in enucleated porcine eyes showed indentation rate and intraocular pressure (IOP) dependences. The CIH increased with indentation rate at lower IOP ( 25 mmHg). The CIH was linear proportional to the IOP within an individual eye. The CIH was positively correlated with the IOP, corneal in-plane tensile stress and corneal tangent modulus (E). A new method based on corneal indentation for the measurement of Corneal Indentation Hysteresis in vivo is developed. To our knowledge, this is the first study to introduce the corneal indentation hysteresis and correlate the corneal indentation hysteresis and corneal tangent modulus.

  20. Helium vs. Proton Induced Displacement Damage in Electronic Materials

    Science.gov (United States)

    Ringo, Sawnese; Barghouty, A. F.

    2010-01-01

    In this project, the specific effects of displacement damage due to the passage of protons and helium nuclei on some typical electronic materials will be evaluated and contrasted. As the electronic material absorbs the energetic proton and helium momentum, degradation of performance occurs, eventually leading to overall failure. Helium nuclei traveling at the same speed as protons are expected to impart more to the material displacement damage; due to the larger mass, and thus momentum, of helium nuclei compared to protons. Damage due to displacement of atoms in their crystalline structure can change the physical properties and hence performance of the electronic materials.

  1. Chromatin remodeling in the UV-induced DNA damage response

    NARCIS (Netherlands)

    Ö.Z. Aydin (Özge)

    2014-01-01

    markdownabstract__Abstract__ DNA damage interferes with transcription and replication, causing cell death, chromosomal aberrations or mutations, eventually leading to aging and tumorigenesis (Hoeijmakers, 2009). The integrity of DNA is protected by a network of DNA repair and associated signalling

  2. Damage induced by paracetamol compared with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    Abdullah Kisaoglu

    2014-09-01

    Conclusion: Thiamine pyrophosphate and N-acetylcysteine had a similar positive effect on oxidative damage caused by paracetamol hepatotoxicity. These findings show that TPP may be beneficial in paracetamol hepatotoxicity.

  3. Continuous cytokine exposure of colonic epithelial cells induces DNA damage

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole Haagen

    2005-01-01

    Chronic inflammatory diseases of the intestinal tract are associated with an increased risk of colorectal cancer. As an example ulcerative colitis (UC) is associated with a production of reactive oxygen species (ROS), including nitrogen monoxide (NO), which is produced in high amounts by inducibl...... nitrogen oxide synthase (iNOS). NO as well as other ROS are potential DNA damaging agents. The aim was to determine the effect of long-term cytokine exposure on NO formation and DNA damage in epithelial cells....

  4. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Science.gov (United States)

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages. PMID:26625350

  5. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Directory of Open Access Journals (Sweden)

    Alejandro Flores-Palacios

    Full Text Available Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  6. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Science.gov (United States)

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  7. Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy

    Institute of Scientific and Technical Information of China (English)

    Uchechukwu; L.Osuagwu; Saud; A.Alanazi

    2015-01-01

    AIM: To assess the effects of eye rubbing on corneal thickness(CT) and intraocular pressure(IOP)measurements obtained 0-30 min after habitual eye rubbing in symptomatic patients.METHODS: Measurements of IOP and CT were obtained at five locations(central, temporal, superior,nasal and inferior) before, and every 5min for 30 min interval after 30 s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing(for IOP), and for each corneal location(for CT)]and comparison were then made between groups(allergic versus control) for differences in any observed effects.RESULTS: Within groups, baseline mean IOPs in the allergic patient-group(14.2 ±3.0 mm Hg) and in the control group(13.1±1.9 mm Hg) were similar at all times,after eye rubbing(P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups(allergic versus control), the changes in IOP remained under 1 mm Hg at all times(P =0.2) after 30 min of eye rubbing. Between 0and 30 min of CT measurements after eye rubbing, the mean central CT(CCT), inferior CT(ICT), superior CT(SCT), temporal CT(TCT) and nasal CT(NCT) did not vary significantly from baseline values in the control and allergic-subject groups(P >0.05, for both). Between both groups, changes in CT were similar at all locations(P >0.05)except for the TC which was minimally thinner by about4.4 μm(P =0.001) in the allergic subjects than in the control subjects, 30 min following 30 s of eye rubbing.CONCLUSION: IOP measured in allergic subjects after30 s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and30 min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it

  8. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

    Science.gov (United States)

    Baumert, Philipp; Lake, Mark J; Stewart, Claire E; Drust, Barry; Erskine, Robert M

    2016-09-01

    Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage.

  9. Neurotoxin-induced DNA damage is persistentin SH-SY5Y cells and LC neurons

    Science.gov (United States)

    Wang, Yan; Musich, Phillip R.; Cui, Kui; Zou, Yue; Zhu, Meng-Yang

    2015-01-01

    Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathologic characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxincamptothecin (CPT)to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured LC and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficientin DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathologic characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insultsin vivo. PMID:25724887

  10. Processo de reparação de lesões da córnea e a membrana amniótica na oftalmologia Repair process of corneal damage and the amniotic membrane in ophthalmology

    Directory of Open Access Journals (Sweden)

    Kelly Cristine de Sousa Pontes

    2011-12-01

    Full Text Available Os eventos que fazem parte do processo de reparação de lesões da córnea ocorrem simultaneamente e envolvem proliferação, migração, diferenciação e apoptose celular, além da comunicação intercelular. Vários fatores solúveis, além de proteínas da matriz mesenquimal, proteoglicanos, enzimas proteolíticas e alguns tipos celulares são abordados nesta revisão, na qual explicam-se os processos de reparação de lesões superficiais ou penetrantes da córnea. A membrana amniótica, muito utilizada na cirurgia oftálmica, foi estudada por apresentar funções que colaboram com o processo de reparação. Entretanto, tais funções poderão ser perdidas quando tal tecido for submetido à conservação. Assim, torna-se importante conhecer o processo de reparação de lesões que envolvem, ou não, a córnea em toda a sua espessura e escolher a melhor forma de utilização da membrana amniótica quando ela for indicada na terapia para estas lesões.The events included in the process of repair of corneal damage occur simultaneously and involve proliferation, migration, differentiation, cell apoptosis and intercellular communication. Several soluble factors, mesenchymal matrix proteins, proteoglycans, proteolytic enzymes and some cell types are covered in this review, which explains the processes of repair of corneal wounds, either superficial or penetrating. The amniotic membrane, used in ophthalmic surgery, was studied because of the contribution of its functions to the repair process. However, these functions may be lost when the amniotic membrane is subjected to conservation. Therefore, it is important to understand the repair process of lesions involving or not the entire thickness of the cornea, and choose the best use of the amniotic membrane, when it is indicated for the treatment of these lesions.

  11. Theoretical analysis for temperature dependence of laser- induced damage threshold of optical thin films

    Science.gov (United States)

    Mikami, K.; Motokoshi, S.; Somekawa, T.; Jitsuno, T.; Fujita, M.; Tanaka, KA; Azechi, H.

    2016-03-01

    The temperature dependence of the laser-induced damage threshold on optical coatings was studied in detail for laser pulses from 123 K to 473 K at different temperatures. The laser-induced damage threshold increased with decreasing temperatures when we tested long pulses (200 ps and 4 ns). The temperature dependence, however, was reversed for pulses shorter than a few picoseconds (100 fs testing). We propose a scaling model with a flowchart that includes three separate processes: free-electron generation, electron multiplication, and electron heating. Furthermore, we calculated the temperature dependence of laser-induced damage thresholds at different temperatures. Our calculation results agreed well with the experimental results.

  12. Exercise-induced muscle damage and the potential protective role of estrogen.

    Science.gov (United States)

    Kendall, Becky; Eston, Roger

    2002-01-01

    Exercise-induced muscle damage is a well documented phenomenon that often follows unaccustomed and sustained metabolically demanding activities. This is a well researched, but poorly understood area, including the actual mechanisms involved in the muscle damage and repair cycle. An integrated model of muscle damage has been proposed by Armstrong and is generally accepted. A more recent aspect of exercise-induced muscle damage to be investigated is the potential of estrogen to have a protective effect against skeletal muscle damage. Estrogen has been demonstrated to have a potent antioxidant capacity that plays a protective role in cardiac muscle, but whether this antioxidant capacity has the ability to protect skeletal muscle is not fully understood. In both human and rat studies, females have been shown to have lower creatine kinase (CK) activity following both eccentric and sustained exercise compared with males. As CK is often used as an indirect marker of muscle damage, it has been suggested that female muscle may sustain less damage. However, these findings may be more indicative of the membrane stabilising effect of estrogen as some studies have shown no histological differences in male and female muscle following a damaging protocol. More recently, investigations into the potential effect of estrogen on muscle damage have explored the possible role that estrogen may play in the inflammatory response following muscle damage. In light of these studies, it may be suggested that if estrogen inhibits the vital inflammatory response process associated with the muscle damage and repair cycle, it has a negative role in restoring normal muscle function after muscle damage has occurred. This review is presented in two sections: firstly, the processes involved in the muscle damage and repair cycle are reviewed; and secondly, the possible effects that estrogen has upon these processes and muscle damage in general is discussed. The muscle damage and repair cycle is

  13. Laser Induced Damage Studies in Borosilicate Glass Using nanosecond and sub nanosecond pulses

    CERN Document Server

    Rastogi, Vinay; Munda, D S

    2016-01-01

    The damage mechanism induced by laser pulse of different duration in borosilicate glass widely used for making confinement geometry targets which are important for laser driven shock multiplication and elongation of pressure pulse, is studied. We measured the front and rear surface damage threshold of borosilicate glass and their dependency on laser parameters. In this paper, we also study the thermal effects on the damage diameters, generated at the time of plasma formation. These induced damage width, geometries and microstructure changes are measured and analyzed with optical microscope, scanning electron microscope and Raman spectroscopy. The results show that at low energies symmetrical damages are found and these damage width increases nonlinearly with laser intensity. The emitted optical spectrum during the process of breakdown is also investigated and is used for the characterization of emitted plasma such as plasma temperature and free electron density. Optical emission lines from Si I at 500 nm, Si ...

  14. Residual force enhancement following eccentric induced muscle damage.

    Science.gov (United States)

    Power, Geoffrey A; Rice, Charles L; Vandervoort, Anthony A

    2012-06-26

    During lengthening of an activated skeletal muscle, the force maintained following the stretch is greater than the isometric force at the same muscle length. This is termed residual force enhancement (RFE), but it is unknown how muscle damage following repeated eccentric contractions affects RFE. Using the dorsiflexors, we hypothesised muscle damage will impair the force generating sarcomeric structures leading to a reduction in RFE. Following reference maximal voluntary isometric contractions (MVC) in 8 young men (26.5±2.8y) a stretch was performed at 30°/s over a 30° ankle excursion ending at the same muscle length as the reference MVCs (30° plantar flexion). Surface electromyography (EMG) of the tibialis anterior and soleus muscles was recorded during all tasks. The damage protocol involved 4 sets of 25 isokinetic (30°/s) lengthening contractions. The same measures were collected at baseline and immediately post lengthening contractions, and for up to 10min recovery. Following the lengthening contraction task, there was a 30.3±6.4% decrease in eccentric torque (Pmuscle damage (Pmuscle function compared to isometric actions succeeding damage. Thus, active force of cross-bridges is decreased because of impaired excitation-contraction coupling but force generated during stretch remains intact because force contribution from stretched sarcomeric structures is less impaired.

  15. Stress-induced DNA damage biomarkers: applications and limitations

    Science.gov (United States)

    Nikitaki, Zacharenia; Hellweg, Christine E.; Georgakilas, Alexandros G.; Ravanat, Jean-Luc

    2015-01-01

    A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data. PMID:26082923

  16. Current status of corneal xenotransplantation.

    Science.gov (United States)

    Kim, Mee Kum; Hara, Hidetaka

    2015-11-01

    Corneal allo-transplantation is a well-established technique to treat corneal blindness. However, the limited availability of human donors demands the exploration of alternative treatments such as corneal xenotransplantation (e.g., pigs as donors) and bioengineered corneas. Since the first attempt of corneal xenotransplantation using a donor pig cornea in 1844, great advances have been made in the development of genetically-engineered pigs, effective immunosuppressive protocols and the establishment of guidelines for the conduction of clinical trials. We highlight immunological and physio-anatomical barriers of corneal xenotransplantation, recent progress of corneal xenotransplantation in non-human-primates studies, and regulatory guidelines to conduct clinical trials for corneal xenotransplantation.

  17. Detection of DNA damage induced by heavy ion irradiation in the individual cells with comet assay

    Science.gov (United States)

    Wada, S.; Natsuhori, M.; Ito, N.; Funayama, T.; Kobayashi, Y.

    2003-05-01

    Investigating the biological effects of high-LET heavy ion irradiation at low fluence is important to evaluate the risk of charged particles. Especially it is important to detect radiation damage induced by the precise number of heavy ions in the individual cells. Thus we studied the relationship between the number of ions traversing the cell and DNA damage produced by the ion irradiation. We applied comet assay to measure the DNA damage in the individual cells. Cells attached on the ion track detector CR-39 were irradiated with ion beams at TIARA, JAERI-Takasaki. After irradiation, the cells were stained with ethidium bromide and the opposite side of the CR-39 was etched. We observed that the heavy ions with higher LET values induced the heavier DNA damage. The result indicated that the amount of DNA damage induced by one particle increased with the LET values of the heavy ions.

  18. Explosive-induced shock damage in copper and recompression of the damaged region

    Science.gov (United States)

    Turley, W. D.; Stevens, G. D.; Hixson, R. S.; Cerreta, E. K.; Daykin, E. P.; Graeve, O. A.; La Lone, B. M.; Novitskaya, E.; Perez, C.; Rigg, P. A.; Veeser, L. R.

    2016-08-01

    We have studied the dynamic spall process for copper samples in contact with detonating low-performance explosives. When a triangular shaped shock wave from detonation moves through a sample and reflects from the free surface, tension develops immediately, one or more damaged layers can form, and a spall scab can separate from the sample and move ahead of the remaining target material. For dynamic experiments, we used time-resolved velocimetry and x-ray radiography. Soft-recovered samples were analyzed using optical imaging and microscopy. Computer simulations were used to guide experiment design. We observe that for some target thicknesses the spall scab continues to run ahead of the rest of the sample, but for thinner samples, the detonation product gases accelerate the sample enough for it to impact the spall scab several microseconds or more after the initial damage formation. Our data also show signatures in the form of a late-time reshock in the time-resolved data, which support this computational prediction. A primary goal of this research was to study the wave interactions and damage processes for explosives-loaded copper and to look for evidence of this postulated recompression event. We found both experimentally and computationally that we could tailor the magnitude of the initial and recompression shocks by varying the explosive drive and the copper sample thickness; thin samples had a large recompression after spall, whereas thick samples did not recompress at all. Samples that did not recompress had spall scabs that completely separated from the sample, whereas samples with recompression remained intact. This suggests that the hypothesized recompression process closes voids in the damage layer or otherwise halts the spall formation process. This is a somewhat surprising and, in some ways controversial, result, and the one that warrants further research in the shock compression community.

  19. Hybrid molecular dynamics simulation for plasma induced damage analysis

    Science.gov (United States)

    Matsukuma, Masaaki

    2016-09-01

    In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam

  20. Laser-induced damage of DKDP crystal under different wavelengths

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Mingxia; Wang, Zhengping; Cheng, Xiufeng; Sun, Shaotao; Liu, Baoan; Gao, Hui; Xu, Xinguang [State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100 (China); Ji, Lailin [Shanghai Institute of Laser and Plasmas, CAEP, P. O. Box 800-229, Shanghai, 201800 (China); Zhao, Yuanan [Shanghai Institute of Optics and Fine Mechanics, Jiading, 201800 (China); Sun, Xun

    2010-07-15

    In this paper, DKDP crystals were grown from 80% deuterated solution by traditional temperature-reduction method. The crystal samples were selected to test laser damage threshold (LDT) and laser conditioning of 1{omega}, 2{omega} and 3{omega}. We found that the laser conditioning of 3{omega} has much more effect on improving the LDT. The damage site was observed by microscope and its effects on micro-structure and optical properties were also studied. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  1. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC) Damages.

    Science.gov (United States)

    Zhang, Yumei; Pan, Yu; Bian, Zhixiang; Chen, Peihua; Zhu, Shijian; Gu, Huiyi; Guo, Liping; Hu, Chun

    2016-01-01

    Here, we studied the underlying mechanism of aldosterone (Aldo)-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L) inhibited human umbilical vein endothelial cells (HUVEC) survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18) production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P), an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS) inhibitor PDMP or the ceramide (C6) potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR) antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1) is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

  2. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

    Directory of Open Access Journals (Sweden)

    Yumei Zhang

    Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

  3. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  4. The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.

    Science.gov (United States)

    Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

    2001-01-01

    Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

  5. A sport-physiological perspective on bird migration : Evidence for flight-induced muscle damage

    NARCIS (Netherlands)

    Guglielmo, C; Piersma, T; Williams, TD; Williams, Tony D.

    2001-01-01

    Exercise-induced muscle damage is a well-described consequence of strenuous exercise, but its potential importance in the evolution of animal activity patterns is unknown. We used plasma creatine kinase (CK) activity as an indicator of muscle damage to investigate whether the high intensity, long-du

  6. A sport-physiological perspective on bird migration : Evidence for flight-induced muscle damage

    NARCIS (Netherlands)

    Guglielmo, C; Piersma, T; Williams, TD; Williams, Tony D.

    Exercise-induced muscle damage is a well-described consequence of strenuous exercise, but its potential importance in the evolution of animal activity patterns is unknown. We used plasma creatine kinase (CK) activity as an indicator of muscle damage to investigate whether the high intensity,

  7. The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore.

    Science.gov (United States)

    Jacobs, G P; Samuni, A; Czapski, G

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  8. Contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P. (Hebrew Univ., Jerusalem (Israel). School of Pharmacy); Samuni, A. (Hebrew Univ., Jerusalem (Israel). School of Medicine); Czapski, G. (Hebrew Univ., Jerusalem (Israel). Dept. of Physical Chemistry)

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  9. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations,

  10. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocat

  11. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  12. DNA-damage response during mitosis induces whole-chromosome missegregation.

    Science.gov (United States)

    Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

    2014-11-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

  13. Effect of native defects and laser-induced defects on multi-shot laser-induced damage in multilayer mirrors

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Yuanan Zhao; Tanda Shao; Zhengxiu Fan

    2011-01-01

    The roles of laser-induced defects and native defects in multilayer mirrors under multi-shot irradiation condition are investigated. The HfO2/SiO2 dielectric mirrors are deposited by electron beam evaporation (EBE). Laser damage testing is carried out on both the 1-on-l and S-on-1 regimes using 355-nm pulsed laser at a duration of 8 ns. It is found that the single-shot laser-induced damage threshold (LIDT) is much higher than the multi-shot LIDT. In the multi-shot mode, the main factor influencing LIDT is the accumulation of irreversible laser-induced defects and native defects. The surface morphologies of the samples are observed by optical microscopy. Moreover, the number of laser-induced defects affects the damage probability of the samples. A correlative model based on critical conduction band (CB) electron density (ED) is presented to simulate the multi-shot damage behavior.%@@ The roles of laser-induced defects and native defects in multilayer mirrors under multi-shot irradiation condition are investigated.The Hf02/SiO2 dielectric mirrors are deposited by electron beam evaporation (EBE).Laser damage testing is carried out on both the 1-on-1 and S-on-1 regimes using 355-nn pulsed laser at a duration of 8 us.It is found that the single-shot laser-induced damage threshold(LIDT)is much higher than the multi-shot LIDT.In the multi-shot mode,the main factor influencing LIDT is the accumulation of irreversible laser-induced defects and native defects.The surface morphologies of the samples are observed by optical microscopy.Moreover,the number of laser-induced defects affects the damage probability of the samples.A correlative model based on critical conduction band(CB)electron density(ED)is presented to simulate the multi-shot damage behavior.

  14. Catastrophic nanosecond laser induced damage in the bulk of potassium titanyl phosphate crystals

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Frank R., E-mail: frank.wagner@fresnel.fr; Natoli, Jean-Yves; Akhouayri, Hassan; Commandré, Mireille [Institut Fresnel, CNRS, Aix-Marseille Université, Ecole Centrale Marseille, Campus de St Jérôme, 13013 Marseille (France); Duchateau, Guillaume [CELIA, UMR 5107 Université Bordeaux 1-CNRS-CEA, 351 Cours de la Libération, 33405 Talence Cedex (France)

    2014-06-28

    Due to its high effective nonlinearity and the possibility to produce periodically poled crystals, potassium titanyl phosphate (KTiOPO{sub 4}, KTP) is still one of the economically important nonlinear optical materials. In this overview article, we present a large study on catastrophic nanosecond laser induced damage in this material and the very similar RbTiOPO{sub 4} (RTP). Several different systematic studies are included: multiple pulse laser damage, multi-wavelength laser damage in KTP, damage resistance anisotropy, and variations of the laser damage thresholds for RTP crystals of different qualities. All measurements were carried out in comparable experimental conditions using a 1064 nm Q-switched laser and some were repeated at 532 nm. After summarizing the experimental results, we detail the proposed model for laser damage in this material and discuss the experimental results in this context. According to the model, nanosecond laser damage is caused by light-induced generation of transient laser-damage precursors which subsequently provide free electrons that are heated by the same nanosecond pulse. We also present a stimulated Raman scattering measurement and confront slightly different models to the experimental data. Finally, the physical nature of the transient damage precursors is discussed and similarities and differences to laser damage in other crystals are pointed out.

  15. Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

    Science.gov (United States)

    Hao, Zhao-Qin; Song, Jin-Xin; Pan, Shi-Yin; Zhang, Lin; Cheng, Yan; Liu, Xian-Ning; Wu, Jie; Xiao, Xiang-Hua; Gao, Wei; Zhu, Hai-Feng

    2016-01-01

    AIM To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each). The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM) at 4wk. RESULTS A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (Pulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease. PMID:27990355

  16. Sirt1 Protects against High-Fat Diet-Induced Metabolic Damage

    National Research Council Canada - National Science Library

    Paul T. Pfluger; Daniel Herranz; Susana Velasco-Miguel; Manuel Serrano; Matthias H. Tschöp

    2008-01-01

    .... Mammalian Sirt1 is a protein deacetylase that has been involved in resveratrol-mediated protection from high-fat diet-induced metabolic damage, but direct proof for the implication of Sirt1 has remained elusive...

  17. Investigation of Friction-induced Damage to the Pig Cornea

    NARCIS (Netherlands)

    da Cruz Barros, Raquel; Van Kooten, Theo G.; Veeregowda, Deepak Halenahally

    2015-01-01

    Mechanical friction causes damage to the cornea. A friction measurement device with minimal intervention with the pig cornea tear film revealed a low friction coefficient of 0.011 in glycerine solution. Glycerine molecules presumably bind to water, mucins, and epithelial cells and therewith improve

  18. Early mechanisms in radiation-induced biological damage

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical. (ACR)

  19. Investigation of Friction-induced Damage to the Pig Cornea

    NARCIS (Netherlands)

    da Cruz Barros, Raquel; Van Kooten, Theo G.; Veeregowda, Deepak Halenahally

    2015-01-01

    Mechanical friction causes damage to the cornea. A friction measurement device with minimal intervention with the pig cornea tear film revealed a low friction coefficient of 0.011 in glycerine solution. Glycerine molecules presumably bind to water, mucins, and epithelial cells and therewith improve

  20. Mitochondrial DNA damage induces apoptosis in senescent cells

    NARCIS (Netherlands)

    Laberge, R-M; Adler, D; DeMaria, M; Mechtouf, N; Teachenor, R; Cardin, G B; Desprez, P-Y; Campisi, J; Rodier, F

    2013-01-01

    Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associate

  1. Corneal blindness and xenotransplantation.

    Science.gov (United States)

    Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder; Cooper, David K C

    2014-01-01

    Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world's blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies between parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty, and endothelial keratoplasty (EK). Indications for corneal transplantation vary between countries, with Fuchs' dystrophy being the leading indication in the USA and keratoconus in Australia. With the exception of the USA, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, for example stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future.

  2. BHT blocks NF-kappaB activation and ethanol-induced brain damage.

    Science.gov (United States)

    Crews, Fulton; Nixon, Kimberly; Kim, Daniel; Joseph, James; Shukitt-Hale, Barbara; Qin, Liya; Zou, Jian

    2006-11-01

    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol-induced degeneration is unknown, but is not simple glutamate-N-methyl-D-aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol-induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration. Adult Sprague-Dawley rats were treated with intragastric ethanol 3 times per day (8-12 g/kg/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor kappa B (NF-kappaB)-DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription-polymerase chain reaction (RT-PCR) of cyclooxygenase 2 (COX2). Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge-induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF-kappaB-DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge-induced NF-kappaB-DNA binding and COX2 expression. Binge-induced brain damage and activation of NF-kappaB-DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol-induced brain damage.

  3. Corneal collagen crosslinking for keratoconus. A review

    Directory of Open Access Journals (Sweden)

    M. M. Bikbov

    2014-10-01

    Full Text Available Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns. Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity increase by 328.9 % (on average, temperature tolerance increase by 5

  4. Corneal collagen crosslinking for keratoconus. A review

    Directory of Open Access Journals (Sweden)

    M. M. Bikbov

    2014-01-01

    Full Text Available Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns. Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity increase by 328.9 % (on average, temperature tolerance increase by 5

  5. Transplantation of reconstructed corneal layer composed of corneal epithelium and fibroblasts on a lyophilized amniotic membrane to severely alkali-burned cornea.

    Science.gov (United States)

    Jang, In-Keun; Ahn, Jae-Il; Shin, Jun-Seop; Kwon, Young-Sam; Ryu, Yang-Hwan; Lee, Jeong-Kyu; Park, Jung-Keug; Song, Kye-Yong; Yang, Eun-Kyung; Kim, Jae-Chan

    2006-06-01

    The purpose of this article was to evaluate the graft efficacy of reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on a lyophilized amniotic membrane (LAM), in a severely alkali-burned corneal model. After biopsy specimens were obtained from the left eyes of 24 rabbits, the corneal epithelial cells and fibroblasts were expanded in vitro and the corneal layer was reconstructed on LAM. Thirty-six eyes of rabbits underwent alkali burn (1 N NaOH, 30 s) to create a limbal deficiency and a deeply damaged corneal stroma. Four weeks later, group 1 underwent a graft of the reconstructed corneal layer composed of autologous corneal epithelium and fibroblasts on LAM. Group 2 was transplanted with a graft of the reconstructed autologous corneal epithelium, and group 3 served as a control without surgery. Wound healing and stabilization of the ocular surfaces occurred much faster in group 1 than in groups 2 and 3. The eyes in group 3 revealed typical limbal deficiencies with conjuctivalization and persistent corneal epithelial defects. However, the corneas in group 1 developed only mild peripheral neovascularization. Immunohistochemical staining in group 1 demonstrated that p63, cytokeratin 3, E-cadherin, transforming growth factor (TGF)-beta1, and collagen IV were expressed strongly in the corneal epithelium and basement membrane. On the basis of these results, transplantation of the reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on LAM, partially accelerated the recovery of the alkali-injured rabbit ocular surface, and might be useful therapeutically for the treatment of patients with severely damaged cornea.

  6. X-ray induced damage observations in ZERODUR mirrors

    Energy Technology Data Exchange (ETDEWEB)

    Takacs, P.Z.; Furenlid, K.; Furenlid, L.

    1997-07-01

    Catastrophic damage has been observed in some ZERODUR mirrors used as first mirrors in two beam lines at the National Synchrotron Light Source (NSLS). Despite the high reflectivity of the coatings used on these mirrors, a significant flux of high energy photons penetrates below the coating and is absorbed in the substrate. Although model calculations indicate that the local temperature does not increase significantly, the authors suspect that over long time periods the absorbed flux produces structural changes in the material, leading to a build-up of surface stress, gross figure changes, and growth of fractures. These changes are probably related to the nature of the two-phase glass-ceramic composition of the ZERODUR material. Metal mirrors and single-phase materials do not exhibit such catastrophic damage under similar exposure conditions.

  7. Damage mechanisms for ultrasound-induced cavitation in tissue

    Science.gov (United States)

    Warnez, M.; Vlaisavljevich, E.; Xu, Z.; Johnsen, E.

    2017-03-01

    In a variety of biomedical applications, cavitation occurs in soft tissue. Although significant amounts of research have been performed on cavitation in water, bubble dynamics, and related bioeffects remain poorly understood. We use numerical simulations of spherical bubble dynamics in soft tissue to assess the extent to which viscoelasticity affects "known" and introduces "new" damage mechanisms. We find that deviatoric stresses - although not an important damage mechanism in water - are significantly enhanced and could be an important bioeffect mechanism in tissue. Both the viscoelastic properties and the nonlinear, large-collapse radius contribute to stress amplification in the surroundings. In addition, temperatures in the surrounding medium increase more in the Zener tissue than in water, due to viscous heating.

  8. DNA damage-induced cell death: lessons from the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Helena Lobo Borges; Rafael Linden; Jean YJ Wang

    2008-01-01

    DNA damage can, but does not always, induce cell death. While several pathways linking DNA damage signals to mitochondria-dependent and -independent death machineries have been elucidated, the connectivity of these pathways is subject to regulation by multiple other factors that are not well understood. We have proposed two conceptual models to explain the delayed and variable cell death response to DNA damage: integrative surveillance versus autonomous pathways. In this review, we discuss how these two models may explain the in vivo regulation of cell death induced by ionizing radiation (IR) in the developing central nervous system, where the death response is regulated by radiation dose, cell cycle status and neuronal development.

  9. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  10. Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Seidensticker, Max, E-mail: max.seidensticker@med.ovgu.de [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany); Burak, Miroslaw [Pomeranian Medical University, Department of Diagnostic Imaging and Interventional Radiology (Poland); Kalinski, Thomas [Universitätsklinik Magdeburg, Institut für Pathologie (Germany); Garlipp, Benjamin [Universitätsklinik Magdeburg, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie (Germany); Koelble, Konrad [Philipps Universität Marburg, Fachbereich Medizin der, Abteilung für Neuropathologie (Germany); Wust, Peter [Charité Universitätsmedizin Berlin, Klinik für Radioonkologie und Strahlentherapie (Germany); Antweiler, Kai [Universitätsklinik Magdeburg, Institut für Biometrie und Medizinische Informatik (Germany); Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany)

    2015-02-15

    PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

  11. Metformin (dimethyl-biguanide induced DNA damage in mammalian cells

    Directory of Open Access Journals (Sweden)

    Rubem R. Amador

    2012-01-01

    Full Text Available Metformin (dimethyl-biguanide is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays and in mice (micronucleus assays. Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

  12. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    Science.gov (United States)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  13. A statistical mechanics model to predict electromigration induced damage and void growth in solder interconnects

    Science.gov (United States)

    Wang, Yuexing; Yao, Yao; Keer, Leon M.

    2017-02-01

    Electromigration is an irreversible mass diffusion process with damage accumulation in microelectronic materials and components under high current density. Based on experimental observations, cotton type voids dominate the electromigration damage accumulation prior to cracking in the solder interconnect. To clarify the damage evolution process corresponding to cotton type void growth, a statistical model is proposed to predict the stochastic characteristic of void growth under high current density. An analytical solution of the cotton type void volume growth over time is obtained. The synchronous electromigration induced damage accumulation is predicted by combining the statistical void growth and the entropy increment. The electromigration induced damage evolution in solder joints is developed and applied to verify the tensile strength deterioration of solder joints due to electromigration. The predictions agree well with the experimental results.

  14. DNA-Damage-Induced Type I Interferon Promotes Senescence and Inhibits Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Qiujing Yu

    2015-05-01

    Full Text Available Expression of type I interferons (IFNs can be induced by DNA-damaging agents, but the mechanisms and significance of this regulation are not completely understood. We found that the transcription factor IRF3, activated in an ATM-IKKα/β-dependent manner, stimulates cell-autonomous IFN-β expression in response to double-stranded DNA breaks. Cells and tissues with accumulating DNA damage produce endogenous IFN-β and stimulate IFN signaling in vitro and in vivo. In turn, IFN acts to amplify DNA-damage responses, activate the p53 pathway, promote senescence, and inhibit stem cell function in response to telomere shortening. Inactivation of the IFN pathway abrogates the development of diverse progeric phenotypes and extends the lifespan of Terc knockout mice. These data identify DNA-damage-response-induced IFN signaling as a critical mechanism that links accumulating DNA damage with senescence and premature aging.

  15. Single-molecule visualization of ROS-induced DNA damage in large DNA molecules.

    Science.gov (United States)

    Lee, Jinyong; Kim, Yongkyun; Lim, Sangyong; Jo, Kyubong

    2016-02-07

    We present a single molecule visualization approach for the quantitative analysis of reactive oxygen species (ROS) induced DNA damage, such as base oxidation and single stranded breaks in large DNA molecules. We utilized the Fenton reaction to generate DNA damage with subsequent enzymatic treatment using a mixture of three types of glycosylases to remove oxidized bases, and then fluorescent labeling on damaged lesions via nick translation. This single molecule analytical platform provided the capability to count one or two damaged sites per λ DNA molecule (48.5 kb), which were reliably dependent on the concentrations of hydrogen peroxide and ferrous ion at the micromolar level. More importantly, the labeled damaged sites that were visualized under a microscope provided positional information, which offered the capability of comparing DNA damaged sites with the in silico genomic map to reveal sequence specificity that GTGR is more sensitive to oxidative damage. Consequently, single DNA molecule analysis provides a sensitive analytical platform for ROS-induced DNA damage and suggests an interesting biochemical insight that the genome primarily active during the lysogenic cycle may have less probability for oxidative DNA damage.

  16. Refractive corneal surgery - discharge

    Science.gov (United States)

    Nearsightedness surgery - discharge; Refractive surgery - discharge; LASIK - discharge; PRK - discharge ... You had refractive corneal surgery to help improve your vision. This surgery uses a laser to reshape your cornea. It corrects mild-to-moderate nearsightedness, ...

  17. Equine corneal surgery and transplantation.

    Science.gov (United States)

    Denis, Heidi M

    2004-08-01

    Corneal disease is common in equine ophthalmology and requires vigilant monitoring and appropriate therapy to optimize the outcome. Many equine corneal diseases, particularly those that progress rapidly, may benefit from surgical intervention. These include descemetoceles, deep corneal lacerations and ulcers, corneal perforation/iris prolapse, ulcerative keratitis, corneal stromal abscesses, and corneoscleral neoplasia. Indications for corneal transplantation include optical, tectonic, therapeutic, and cosmetic purposes. Corneal transplantation is most often implemented in equine patients for tectonic and therapeutic reasons when a cornea is compromised by corneal stromal abscess, iris prolapse, or neoplasia. This article provides an outline of when to consider surgical intervention for corneal disease, the procedures available and expected outcomes, and how appropriate early surgical intervention can dramatically improve the end result.

  18. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  19. Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis.

    Science.gov (United States)

    Zhang, Minjie; Mani, Sriniwasan B; He, Yao; Hall, Amber M; Xu, Lin; Li, Yefu; Zurakowski, David; Jay, Gregory D; Warman, Matthew L

    2016-08-01

    Joints that have degenerated as a result of aging or injury contain dead chondrocytes and damaged cartilage. Some studies have suggested that chondrocyte death precedes cartilage damage, but how the loss of chondrocytes affects cartilage integrity is not clear. In this study, we examined whether chondrocyte death undermines cartilage integrity in aging and injury using a rapid 3D confocal cartilage imaging technique coupled with standard histology. We induced autonomous expression of diphtheria toxin to kill articular surface chondrocytes in mice and determined that chondrocyte death did not lead to cartilage damage. Moreover, cartilage damage after surgical destabilization of the medial meniscus of the knee was increased in mice with intact chondrocytes compared with animals whose chondrocytes had been killed, suggesting that chondrocyte death does not drive cartilage damage in response to injury. These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage following injury. Therefore, therapies targeted at reducing the catabolic phenotype may protect against degenerative joint disease.

  20. Central corneal abscess.

    Science.gov (United States)

    van Bijsterveld, O P

    1976-05-01

    Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.

  1. The mechanism of heat-induced damage of endothelial cells and its effect on vital organs

    Directory of Open Access Journals (Sweden)

    Lei SU

    2017-06-01

    Full Text Available As an important organ of the human body, vascular endothelial cells (VECs play a vital role in heat stress-induced tissue damage. Its integrity not only serves as a barrier for maintaining vascular permeability but also has major impact on cellular structure and function during acute phase response to heat stress. In heat stroke, a series of acute and complicated pathophysiological changes, including microcirculation change, damage VECs and thereby induce or aggravate multiple organ dysfunction syndrome (MODS. Meanwhile, studies have shown that, during heat stroke, VECs are the major responding cells and one of the most common cells that experience morphological and functional changes. Therefore, VECs damage might be an important mechanism involved in heat stroke. This article reviews the mechanism of heat-induced damage of VECs and its effect on vital organs. DOI: 10.11855/j.issn.0577-7402.2017.04.01

  2. Effects of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell counts.

    Science.gov (United States)

    Gao, Feng; Lin, Tao; Pan, Yingzhe

    2016-09-01

    Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: 10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.

  3. Stretch-activated channels in stretch-induced muscle damage: role in muscular dystrophy.

    Science.gov (United States)

    Yeung, Ella W; Allen, David G

    2004-08-01

    1. Stretch-induced muscle injury results in the damage that causes reduced force and increased membrane permeability. This muscle damage is caused, in part, by ionic entry through stretch-activated channels and blocking these channels with Gd3+ or streptomycin reduces the force deficit associated with damage. 2. Dystrophin-deficient muscles are more susceptible to stretch-induced muscle injury and the recovery from injury can be incomplete. We have found that Na+ entry associated with stretch-induced injury is enhanced in dystrophin-deficient muscles and that blockers of stretch-activated channels are capable of preventing ionic entry and reducing muscle damage. 3. A model is presented that proposes links between stretch-induced injury, opening of stretch-activated channels, increased levels of intracellular ions and various forms of muscle damage. Although changes in Na+ accompany stretch-induced muscle injury, we believe that changes in Ca2+ probably have a more central role in the damage process.

  4. The CXXC finger 5 protein is required for DNA damage-induced p53 activation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The tumor suppressor p53 is a critical component of the DNA damage response pathway that induces a set of genes responsible for cell cycle arrest,senescence,apoptosis,and DNA repair.The ataxia te-langiectasia mutated protein kinase(ATM) responds to DNA-damage stimuli and signals p53 stabiliza-tion and activation,thereby facilitating transactivation of p53 inducible genes and maintainence of genome integrity.In this study,we identified a CXXC zinc finger domain containing protein termed CF5 as a critical component in the DNA damage signaling pathway.CF5 induces p53 transcriptional activity and apoptosis in cells expressing wild type p53 but not in p53-deficient cells.Knockdown of CF5 in-hibits DNA damage-induced p53 activation as well as cell cycle arrest.Furthermore,CF5 physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin.These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage.

  5. Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo.

    Science.gov (United States)

    Dolan, Eimear B; Tallon, David; Cheung, Wing-Yee; Schaffler, Mitchell B; Kennedy, Oran D; McNamara, Laoise M

    2016-06-01

    Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures in vivo is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague-Dawley rat tibia were exposed to clinically relevant temperatures (47°C or 60°C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes (Rankl, Opg and M-csf), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production (Cox2), vascularization (Vegf) and inflammatory (Il1a) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the in vivo effect of thermally induced osteocyte damage on the gene expression profile.

  6. Effect of creatine supplementation on muscle damage and repair following eccentrically-induced damage to the elbow flexor muscles.

    Science.gov (United States)

    McKinnon, Neal B; Graham, Mitchell T; Tiidus, Peter M

    2012-01-01

    We investigated effects of creatine (Cr) supplementation (CrS) on exercise-induced muscle damage. Untrained males and females (N = 27) ages 18-25, with no CrS history in the past 4 months, were randomly assigned to CrS (creatine and carbohydrate) (n = 9), placebo (P) (carbohydrate only) (n = 9), or control (C) (no supplements) groups (n = 9). Participants followed a 5-day Cr loading protocol of 40 g·day(-1), divided for 5 days prior to exercise, reduced to 10 g g·day(-1) for 5 days following exercise. Testing consisted of 5 maximal isometric contractions at 90 arm flexion with the preferred arm on a CYBEX NORM dynamometer, assessed prior to, immediately following, and 24, 48, 72, and 96 hours post muscle-damaging procedures. Damage was induced to the elbow flexor muscles using 6 sets of 10 eccentric contractions at 75 °/sec, 90 °/sec and 120 °/sec. Participants were asked to rate their muscle soreness on a scale of 1-10. Data was analyzed using repeated-measures ANOVA, with an alpha of 0.05. No significant differences were found between muscle force loss and rate of recovery or muscle soreness between groups over the 96 hr recovery period (p > 0.05). Across all 3 experimental groups an initial decrease in force was observed, followed by a gradual recovery. Significant differences were found between baseline and all others times (p = 0.031,0 .022, 0.012, 0.001 respectively), and between the 48 hour and 96 hour time periods (p = 0.034). A weak negative correlation between subjectively rated muscle soreness and mean peak isometric force loss (R(2) = 0.0374 at 96 hours), suggested that muscle soreness and muscle force loss may not be directly related. In conclusion, 5 days of Cr loading, followed by a Cr maintenance protocol did not reduce indices of muscle damage or speed recovery of upper body muscles following eccentrically induced muscle damage.

  7. EFFECT OF CREATINE SUPPLEMENTATION ON MUSCLE DAMAGE AND REPAIR FOLLOWING ECCENTRICALLY-INDUCED DAMAGE TO THE ELBOW FLEXOR MUSCLES

    Directory of Open Access Journals (Sweden)

    Neal B. McKinnon

    2012-12-01

    Full Text Available We investigated effects of creatine (Cr supplementation (CrS on exercise-induced muscle damage. Untrained males and females (N = 27 ages 18-25, with no CrS history in the past 4 months, were randomly assigned to CrS (creatine and carbohydrate (n = 9, placebo (P (carbohydrate only (n = 9, or control (C (no supplements groups (n = 9. Participants followed a 5-day Cr loading protocol of 40 g·day-1, divided for 5 days prior to exercise, reduced to 10 g g·day-1 for 5 days following exercise. Testing consisted of 5 maximal isometric contractions at 90 arm flexion with the preferred arm on a CYBEX NORM dynamometer, assessed prior to, immediately following, and 24, 48, 72, and 96 hours post muscle-damaging procedures. Damage was induced to the elbow flexor muscles using 6 sets of 10 eccentric contractions at 75 °/sec, 90 °/sec and 120 °/sec. Participants were asked to rate their muscle soreness on a scale of 1-10. Data was analyzed using repeated-measures ANOVA, with an alpha of 0.05. No significant differences were found between muscle force loss and rate of recovery or muscle soreness between groups over the 96 hr recovery period (p > 0.05. Across all 3 experimental groups an initial decrease in force was observed, followed by a gradual recovery. Significant differences were found between baseline and all others times (p = 0.031,0 .022, 0.012, 0.001 respectively, and between the 48 hour and 96 hour time periods (p = 0.034. A weak negative correlation between subjectively rated muscle soreness and mean peak isometric force loss (R2 = 0.0374 at 96 hours, suggested that muscle soreness and muscle force loss may not be directly related. In conclusion, 5 days of Cr loading, followed by a Cr maintenance protocol did not reduce indices of muscle damage or speed recovery of upper body muscles following eccentrically induced muscle damage

  8. Quantitative proteomic analysis of mice corneal tissues reveals angiogenesis-related proteins involved in corneal neovascularization.

    Science.gov (United States)

    Shen, Minqian; Tao, Yimin; Feng, Yifan; Liu, Xing; Yuan, Fei; Zhou, Hu

    2016-07-01

    Corneal neovascularization (CNV) was induced in Balb/c mice by alkali burns in the central area of the cornea with a diameter of 2.5mm. After fourteen days, the cornea from one eye was collected for histological staining for CNV examination, while the cornea from the other eye of the same mouse was harvested for proteomic analysis. The label-free quantitative proteomic approach was applied to analyze five normal corneal tissues (normal group mice n=5) and five corresponding neovascularized corneal tissues (model group mice n=5). A total of 2124 proteins were identified, and 1682 proteins were quantified from these corneal tissues. Among these quantified proteins, 290 proteins were significantly changed between normal and alkali burned corneal tissues. Of these significantly changed proteins, 35 were reported or predicted as angiogenesis-related proteins. Then, these 35 proteins were analyzed using Ingenuity Pathway Analysis Software, resulting in 26 proteins enriched and connected to each other in the protein-protein interaction network, such as Lcn-2, αB-crystallin and Serpinf1 (PEDF). These three significantly changed proteins were selected for further Western blotting validation. Consistent with the quantitative proteomic results, Western blotting showed that Lcn-2 and αB-crystallin were significantly up-regulated in CNV model, while PEDF was down-regulated. This study provided increased understanding of angiogenesis-related proteins involved in corneal vascular development, which will be useful in the ophthalmic clinic of specifically target angiogenesis.

  9. Electron-induced damage to NPN transistors under different fluxes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Radiation damage of NPN transistors under different fluxes with electron energy of 1.5 MeV was investigated in this article. It has been shown that when NPN transistors were irradiated to a given fluence at different electron fluxes, the shift of base current was dependent on flux. With electron flux decreasing, the shift of base current becomes larger, while collector current almost keeps constant. Thus, more degradation of NPN transistors could be caused by low-electron-flux irradiation, similar to enhanced low-dose-rate sensitivity (ELDRS) of transistors under 60Co γ-irradiation. Finally, the underlying mechanisms were discussed here.

  10. Multiscale physics of ion-induced radiation damage.

    Science.gov (United States)

    Surdutovich, Eugene; Solov'yov, A V

    2014-01-01

    This is a review of a multiscale approach to the physics of ion-beam cancer therapy, an approach suggested in order to understand the interplay of a large number of phenomena involved in the radiation damage scenario occurring on a range of temporal, spatial, and energy scales. We describe different effects that take place on different scales and play major roles in the scenario of interaction of ions with tissue. The understanding of these effects allows an assessment of relative biological effectiveness that relates the physical quantities, such as dose, to the biological values, such as the probability of cell survival.

  11. p38γ regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage.

    Science.gov (United States)

    Wu, Chia-Cheng; Wu, Xiaohua; Han, Jiahuai; Sun, Peiqing

    2010-06-01

    In eukaryotic cells, DNA damage triggers activation of checkpoint signaling pathways that coordinate cell cycle arrest and repair of damaged DNA. These DNA damage responses serve to maintain genome stability and prevent accumulation of genetic mutations and development of cancer. The p38 MAPK was previously implicated in cellular responses to several types of DNA damage. However, the role of each of the four p38 isoforms and the mechanism for their involvement in DNA damage responses remained poorly understood. In this study, we demonstrate that p38γ, but not the other p38 isoforms, contributes to the survival of UV-treated cells. Deletion of p38γ sensitizes cells to UV exposure, accompanied by prolonged S phase cell cycle arrest and increased rate of apoptosis. Further investigation reveal that p38γ is essential for the optimal activation of the checkpoint signaling caused by UV, and for the efficient repair of UV-induced DNA damage. These findings have established a novel role of p38γ in UV-induced DNA damage responses, and suggested that p38γ contributes to the ability of cells to cope with UV exposure by regulating the checkpoint signaling pathways and the repair of damaged DNA.

  12. Endotoxin-induced liver damage in rats is minimized by β2- adrenoceptor stimulation

    NARCIS (Netherlands)

    Izeboud, C.A.; Hoebe, K.H.N.; Grootendorst, A.F.; Nijmeijer, S.M.; Miert, A.S. van; Witkamp, R.F.; Rodenburg, R.J.T.

    2004-01-01

    Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The

  13. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  14. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  15. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    Science.gov (United States)

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  16. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  17. A corneal mold to restore normal corneal dimensions.

    Science.gov (United States)

    Swinger, C A; Kornmehl, E W; York, S; Forman, J S

    1986-01-01

    A corneal mold is described that provides an MK corneal button of normal thickness and curvature from an edematous, post-mortem button. The uniform, processed tissue can then be used for experimental refractive surgery.

  18. Compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones

    Institute of Scientific and Technical Information of China (English)

    Ting ZHANG; Jun-ling LI; Jian XIN; Xiao-chao MA; Zeng-hong TU

    2004-01-01

    AIM: To compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones (FQ). METHODS: Lomefloxacin (LFLX), sparfloxacin (SPFX), ciprofloxacin (CPFX), and levofloxacin (LELX)were tested by comet assay and photodynamic DNA strand breaking activity under the different conditions of UVA irradiation. RESULTS: In comet assay, photogenotoxicity was evident at SPFX 1 mg/L, LFLX 5 mg/L, and CPFX 5 mg/L, and LELX 10 mg/L. In photodynamic DNA srand-breaking activity, SPFX and LFLX induced the conversion of the supercoiled form into the nicked relaxed form at 10-50 μmol/L, while CPFX at 25 μmol/L and LELX at 50 μmol/L. CONCLUSION: There were good correlations between the two methods to detect DNA damage induced by phototoxicity of fluoroquinolones. Photodynamic DNA strand breaking activity was a good method to detect DNA damage induced by photogenotoxicity of fluoroquinolones as well as comet assay.

  19. Effects of genipin corneal crosslinking in rabbit corneas.

    Science.gov (United States)

    Avila, Marcel Y; Narvaez, Mauricio; Castañeda, Juan P

    2016-07-01

    To evaluate the effect of genipin, a natural crosslinking agent, in rabbit eyes. Department of Ophthalmology, Universidad Nacional de Colombia Centro de Tecnologia Oftalmica, Bogotá, Colombia. Experimental study. Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin 1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam). In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas were crosslinked with genipin as described. Corneal curvature, corneal pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp examinations were performed 0, 7, 30, and 60 days after treatment. In the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit corneas with an increase in corneal density and a dose-dependent relationship. Corneal flattening was observed in treated eyes (mean 4.4 diopters ± 0.5 [SD]) compared with the control eyes. Pachymetry and IOP were stable in all evaluations. No eye showed toxicity in the anterior chamber or in the lens. Corneal crosslinking induced by genipin produced significant flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could be useful in the treatment of corneal ectasia and in the modification of corneal curvature. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  20. SHORT AND LONGER-TERM EFFECTS OF CREATINE SUPPLEMENTATION ON EXERCISE INDUCED MUSCLE DAMAGE

    Directory of Open Access Journals (Sweden)

    John Rosene

    2009-03-01

    Full Text Available The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo supplementation (20 g.d-1 for 7 d followed by 6g.d-1 for 23 d = 30 d. Prior to the supplementation period, measurements were obtained for maximal dynamic strength, maximal isometric force, knee range of motion, muscle soreness, and serum levels of creatine kinase (CK and lactate dehydrogenase (LDH. Following 7 days of creatine supplementation, on day 8, subjects began consuming 6 g.d-1 of creatine for 23 days. Additionally on days 8 and 31, subjects performed an eccentric exercise protocol using the knee extensors to induce muscle damage. Indirect markers of muscle damage, including maximal isometric force, knee range of motion, muscle soreness, and serum levels of CK and LDH, were collected at 12, 24, and 48 hours following each exercise bout. The results indicated that acute bouts of creatine have no effect on indirect markers of muscle damage for the acute (7 days bout. However, maximal isometric force was greater for the creatine group versus placebo for the chronic (30 days bout. This suggests that the ergogenic effect of creatine following 30 days of supplementation may have a positive impact on exercise induced muscle damage

  1. Quercetin prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced testicular damage in rats.

    Science.gov (United States)

    Ciftci, O; Aydin, M; Ozdemir, I; Vardi, N

    2012-06-01

    The protective effect of quercetin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular damage in rats was investigated. Twenty-two rats were equally divided into four groups; first group was kept as control and given corn oil as carrier. In second group, TCDD was orally administered at the dose of 2 μ (kg week)(-1) for 60 days. In third group, quercetin was orally administered at the dose of 20 mg (kg day)(-1) by gavages, and in fourth group TCDD and quercetin were given together at the same doses. Although TCDD increased the formation of thiobarbituric acid reactive substances (TBARS) significantly, it caused a significant decline in the levels of glutathione (GSH), catalase (CAT), GSH-Px and CuZn-Superoxide Dismutase (CuZn-SOD) in rats. In contrast, quercetin significantly increased the GSH, CAT, GSH-Px and CuZn-SOD levels but decreased the formation of TBARS. In addition, sperm motility, sperm concentration and serum testosterone levels were significantly decreased but abnormal sperm rate and testicular damage were increased with TCDD treatment. However, these effects of TCDD on sperm parameters, histological changes and hormone levels were eliminated by quercetin treatment. Our results show that administration of TCDD induces testicular damage (oxidative stress, testes tissue damage, serum hormone level and sperm parameters), and quercetin prevents TCDD-induced testicular damage in rats. Thus, quercetin may be useful for the prevention and treatment of TCDD-induced testicular damage.

  2. A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage.

    Science.gov (United States)

    Brand, Rhonda M; Epperly, Michael W; Stottlemyer, J Mark; Skoda, Erin M; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E; Greenberger, Joel S; Falo, Louis D

    2017-03-01

    Skin is the largest human organ, and it provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation-induced skin damage ranges from photoaging and cutaneous carcinogenesis caused by UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation-induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species. Mitochondria are particularly susceptible to oxidative stress, and mitochondrial-dependent apoptosis plays a major role in radiation-induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent reactive oxygen species accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrially targeted antioxidant prevents and mitigates radiation-induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin's antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Beam-Induced Damage Mechanisms and their Calculation

    CERN Document Server

    Bertarelli, A

    2016-01-01

    The rapid interaction of highly energetic particle beams with matter induces dynamic responses in the impacted component. If the beam pulse is sufficiently intense, extreme conditions can be reached, such as very high pressures, changes of material density, phase transitions, intense stress waves, material fragmentation and explosions. Even at lower intensities and longer time-scales, significant effects may be induced, such as vibrations, large oscillations, and permanent deformation of the impacted components. These lectures provide an introduction to the mechanisms that govern the thermomechanical phenomena induced by the interaction between particle beams and solids and to the analytical and numerical methods that are available for assessing the response of impacted components. An overview of the design principles of such devices is also provided, along with descriptions of material selection guidelines and the experimental tests that are required to validate materials and components exposed to interactio...

  4. Corneal Topography Analysis of Stromal Corneal Dystrophies

    OpenAIRE

    Kocluk, Yusuf; Yalniz-Akkaya, Zuleyha; Burcu, Ayse; Ornek, Firdevs

    2015-01-01

    Objective: The aim was to compare the corneal topography and tomography parameters of macular corneal dystrophy (MCD), granular corneal dystrophy (GCD) and lattice corneal dystrophy (LCD) patients obtained by Scheimpflug imaging system. Methods: The charts, photographs and topography images of patients were reviewed retrospectively. This study included 73 eyes of 73 patients (28 MCD, 20 GCG and 25 LCD patients). Topography images were obtained by Pentacam (Oculus Optikgerate, Wetzlar, Germany...

  5. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

    Directory of Open Access Journals (Sweden)

    Yijun Zheng

    2016-01-01

    Full Text Available Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc., survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

  6. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  7. Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats.

    Science.gov (United States)

    Nagai, Noriaki; Ogata, Fumihiko; Kawasaki, Naohito; Ito, Yoshimasa; Funakami, Yoshinori; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    Hypercalcemia is often observed in postmenopausal women as well as in patients with primary hyperparathyroidism or malignant tumors. In this study, we investigated the relationship between calcium ion (Ca(2+)) levels in lacrimal fluid and the rate of corneal wound healing in hypercalcemia using ovariectomized (OVX) rat debrided corneal epithelium. We also determined the effects of Ca(2+) levels on cell adhesion, proliferation and viability in a human cornea epithelial cell line (HCE-T). The calcium content in bones of OVX rats decreased after ovariectomy. Moreover, the Ca(2+) content in the blood of OVX rats was increased 1 month after ovariectomy, and decreased. The Ca(2+) content in the lacrimal fluid of OVX rats was also increased after ovariectomy, and then decreased similarly as in blood. Corneal wound healing in OVX rats was delayed in comparison with Sham rats (control rats), and a close relationship was observed between the Ca(2+) levels in lacrimal fluid and the rate of corneal wound healing in Sham and OVX rats (y=-0.7863x+8.785, R=0.78, n=25). In addition, an enhancement in Ca(2+) levels caused a decrease in the viability in HCE-T cells. It is possible that enhanced Ca(2+) levels in lacrimal fluid may cause a decrease in the viability of corneal epithelial cells, resulting in a delay in corneal wound healing. These findings provide significant information that can be used to design further studies aimed at reducing corneal damage of patients with hypercalcemia.

  8. Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

    Science.gov (United States)

    Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

    2016-03-01

    Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

  9. Autophagy in granular corneal dystrophy type 2.

    Science.gov (United States)

    Choi, Seung-Il; Kim, Eung Kweon

    2016-03-01

    Autophagy is a lysosomal degradative process that is essential for cellular homeostasis and metabolic stress adaptation. Defective autophagy is involved in the pathogenesis of many diseases including granular corneal dystrophy type 2 (GCD2). GCD2 is an autosomal dominant disorder caused by substitution of histidine for arginine at codon 124 (R124H) in the transforming growth factor β-induced gene (TGFBI) on chromosome 5q31. Transforming growth factor β-induced protein (TGFBIp) is degraded by autophagy, but mutant-TGFBIp accumulates in autophagosomes and/or lysosomes, despite significant activation of basal autophagy, in GCD2 corneal fibroblasts. Furthermore, inhibition of autophagy induces cell death of GCD2 corneal fibroblasts through active caspase-3. As there is currently no pharmacological treatment for GCD2, development of novel therapies is required. A potential strategy for preventing cytoplasmic accumulation of mutant-TGFBIp in GCD2 corneal fibroblasts is to enhance mutant-TGFBIp degradation. This could be achieved by activation of the autophagic pathway. Here, we will consider the role and the potential therapeutic benefits of autophagy in GCD2, with focus on TGFBIp degradation, in light of the recently established role of autophagy in protein degradation.

  10. 3,4-Methylenedioxymethamphetamine (MDMA) Abuse Markedly Inhibits Acetylcholinesterase Activity and Induces Severe Oxidative Damage and Liperoxidative Damage

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P<0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P<0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453. Conclusion The findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.

  11. Role of oxidative stress in impaired insulin signaling associated with exercise-induced muscle damage.

    Science.gov (United States)

    Aoi, Wataru; Naito, Yuji; Yoshikawa, Toshikazu

    2013-12-01

    Skeletal muscle is a major tissue that utilizes blood glucose. A single bout of exercise improves glucose uptake in skeletal muscle through insulin-dependent and insulin-independent signal transduction mechanisms. However, glucose utilization is decreased in muscle damage induced by acute, unaccustomed, or eccentric exercise. The decrease in glucose utilization is caused by decreased insulin-stimulated glucose uptake in damaged muscles with inhibition of the membrane translocation of glucose transporter 4 through phosphatidyl 3-kinase/Akt signaling. In addition to inflammatory cytokines, reactive oxygen species including 4-hydroxy-2-nonenal and peroxynitrate can induce degradation or inactivation of signaling proteins through posttranslational modification, thereby resulting in a disturbance in insulin signal transduction. In contrast, treatment with factors that attenuate oxidative stress in damaged muscle suppresses the impairment of insulin sensitivity. Muscle-damaging exercise may thus lead to decreased endurance capacity and muscle fatigue in exercise, and it may decrease the efficiency of exercise therapy for metabolic improvement.

  12. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Science.gov (United States)

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  13. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  14. Plastic Strain Induced Damage Evolution and Martensitic Transformation in Ductile Materials at Cryogenic Temperatures

    CERN Document Server

    Garion, C

    2002-01-01

    The Fe-Cr-Ni stainless steels are well known for their ductile behaviour at cryogenic temperatures. This implies development and evolution of plastic strain fields in the stainless steel components subjected to thermo-mechanical loads at low temperatures. The evolution of plastic strain fields is usually associated with two phenomena: ductile damage and strain induced martensitic transformation. Ductile damage is described by the kinetic law of damage evolution. Here, the assumption of isotropic distribution of damage (microcracks and microvoids) in the Representative Volume Element (RVE) is made. Formation of the plastic strain induced martensite (irreversible process) leads to the presence of quasi-rigid inclusions of martensite in the austenitic matrix. The amount of martensite platelets in the RVE depends on the intensity of the plastic strain fields and on the temperature. The evolution of the volume fraction of martensite is governed by a kinetic law based on the accumulated plastic strain. Both of thes...

  15. The Cartography of UV-induced DNA Damage Formation and DNA Repair.

    Science.gov (United States)

    Hu, Jinchuan; Adar, Sheera

    2017-01-01

    DNA damage presents a barrier to DNA-templated biochemical processes, including gene expression and faithful DNA replication. Compromised DNA repair leads to mutations, enhancing the risk for genetic diseases and cancer development. Conventional experimental approaches to study DNA damage required a researcher to choose between measuring bulk damage over the entire genome, with little or no resolution regarding a specific location, and obtaining data specific to a locus of interest, without a global perspective. Recent advances in high-throughput genomic tools overcame these limitations and provide high-resolution measurements simultaneously across the genome. In this review, we discuss the available methods for measuring DNA damage and their repair, focusing on genomewide assays for pyrimidine photodimers, the major types of damage induced by ultraviolet irradiation. These new genomic assays will be a powerful tool in identifying key components of genome stability and carcinogenesis. © 2016 The American Society of Photobiology.

  16. Laser-induced damage of 1064-nm narrow-band interference filters under different laser modes

    Institute of Scientific and Technical Information of China (English)

    Weidong Gao(高卫东); Hongbo He(贺洪波); Jianda Shao(邵建达); Zhengxiu Fan(范正修)

    2004-01-01

    The laser-induced damage behavior of narrow-band interference filters was investigated with a Nd:YAG laser at 1064 nm under single-pulse mode and free-running laser mode.The absorption measurement of such coatings has been performed by surface thermal lensing(STL)technique.The relationship between damage morphology and absorption under the two different laser modes was studied in detail.The explanation was given by the standing-wave distribution theory.

  17. Effects of polymorphisms in XRCC1 and APE1 on vinyl chloride-induced chromosome damage

    Institute of Scientific and Technical Information of China (English)

    王金伟

    2014-01-01

    Objective To evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride(VC)-induced chromosomal damage in peripheral lymphocytes.Methods In this study,317 workers occupationally exposed to VC were recruited from a factory in Shandong Province,China.The micronucleus(MN)frequency in peripheral lymphocytes was used as an indicator of chromosomal damage.Polymerase chain reaction-restriction fragment length polymorphism and created restriction site

  18. Protection of melatonin against damage of sperm mito-chondrial function induced by reactive oxygen species

    Institute of Scientific and Technical Information of China (English)

    Xue-JunShang; Yu-FengHuang; Zhang-QunYe; XiaoYu; Wan-JiaGu

    2004-01-01

    Aim: To study the mitochondrial function damage of sperm in-duced by reactive oxygen species (ROS) and the protection of melatonin (MLT) against the damage. Methods: Normal function spermatozoa were selected from semen samples by Percoll gradi-ent centrifugation technique. The ROS generated by the hypoxan-thine xanthine oxidase system was incubated with the normal sper-matozoa in the presence or absence of MLT (6 retool/L) for 30 and 60 minutes.

  19. Using ultra-sensitive next generation sequencing to dissect DNA damage-induced mutagenesis

    OpenAIRE

    Kaile Wang; Xiaolu Ma; Xue Zhang; Dafei Wu; Chenyi Sun; Yazhou Sun; Xuemei Lu; Chung-I Wu; Caixia Guo; Jue Ruan

    2016-01-01

    Next generation sequencing (NGS) technologies have dramatically improved studies in biology and biomedical science. However, no optimal NGS approach is available to conveniently analyze low frequency mutations caused by DNA damage treatments. Here, by developing an exquisite ultra-sensitive NGS (USNGS) platform “EasyMF” and incorporating it with a widely used supF shuttle vector-based mutagenesis system, we can conveniently dissect roles of lesion bypass polymerases in damage-induced mutagene...

  20. Triggering of toll-like receptors 2 and 4 by Aspergillus fumigatus conidia in immortalized human corneal epithelial cells to induce inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jie; WU Xin-yi

    2008-01-01

    Background Cornea epithelial cells play early and crucial roles in the initiation of ocular surface responses to pathogens.Participation of toll-like receptor(TLR)2 and TLR4,which are major forms of fungi receptors,may be involved in Aspergillus fumigatus induced immune responses.The obiective of the present study was to examine whether inactive Aspergillus fumigatus conidia induce NF-κB activation and production of proinflammaory cytokines,and whether the expression of TLR2 and TLR4 were amplified by conidia in cultured immortalized human corneal epithelial cells (THCEs).This may contribute to our knowledge of the mechanism by which the host cornea can successfully defend against invasive fungi.Methods Aspergillus fumigatus conidia were used to challenge THCE cells.THCE cells were harvested after 0.5,1,2or 4 hours incubation.Real-time quantitative PCR was performed to determine the expression of TLR2,TLR4,TNF-α and IL-8.Western blotting was performed to determine the expression of NF-κB.Enzyme-linked immunosorbent assay (EUSA)was performed to determine the expression of TNF-α and IL-8.And the release of TNF-α and IL-8 in the cell supematant were also assessed by ELISA with or without pretreatment with TLR2 and TLR4 neutralizing antibodies.Results Aspergillus fumigatus conidia elicited the expression of TLR2,TLR4,TNF-α and IL-8 mRNA in THCEs.Exposure of THCE cells to Aspergillus fumigatus conidia resulted in NF-κB activation,which increased at 30 minutes (increased from 11.35±2.74 in the controls to 19.12±3.48,P<0.05)and thereafter increased steadily up to 4 hours after challenge(P<0.01).Concomitant with NF-κB acfivation,secretion of TNF-α and IL-8 in conidia-challenged cells was increased in a time-dependent manner.Incubation of THCE cells with TLR2 antibody or TLR4 antibody before conidia challenge resulted in jnhibifion of conidia-induced TNF-α and IL-8 secretion(P<0.05),TLR2 antibody and TLR4 antibody together significantly increased

  1. Temozolomide-induced liver damage. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Becker, F.; Hecht, M.; Schmidtner, J.; Semrau, S.; Fietkau, R. [University of Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany)

    2014-04-15

    Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists. We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme. Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature. When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately. (orig.)

  2. [Corneal sensibility following epikeratophakia].

    Science.gov (United States)

    Biermann, H; Grabner, G; Baumgartner, I; Reim, M

    1992-07-01

    The postoperative rate of reinnervation following corneal surgery is widely considered to be a useful indicator of the healing process. This study reports the corneal sensitivity of 14 patients following epikeratophakia for different indications (myopia, aphakia and keratoconus) after time periods ranging from 7 to 104 weeks. All transplants were clear at the time of measurement. A newly developed aesthesiometer (using a low electric current for stimulation) was employed. Nine positions on the operated eye were chosen for the measurements, five locations of the non-operated fellow eye served as controls. On the operated eye the corneal sensitivity peripheral to the trephination were significantly reduced at the 9 and 12 o'clock positions as compared to the other eye. The 3 and 6 o'clock locations showed no significant difference. On the epikeratophakia lenticule the sensitivity was significantly reduced at all points, the center showing the largest difference (p less than 0.001). No correlation with age, sex or the indication for the procedure was observed. Although there was a trend of a positive correlation between the postoperative time period and the central corneal sensitivity, the follow-up was too short to reach significant levels. The nearly complete lack of corneal sensitivity, particularly in the center of the transplant is therefore well compatible with its long-time survival, even when the lenticule has been prepared with the cryolathe and lyophilized for transportation.

  3. Modeling of laser-induced damage and optic usage at the National Ignition Facility

    Science.gov (United States)

    Liao, Zhi M.; Nostrand, Mike; Carr, Wren; Bude, Jeff; Suratwala, Tayyab I.

    2016-07-01

    Modeling of laser-induced optics damage has been introduced to benchmark existing optic usage at the National Ignition Facility (NIF) which includes the number of optics exchanged for damage repair. NIF has pioneered an optics recycle strategy to allow it to run the laser at capacity since fully commissioned in 2009 while keeping the cost of optics usage manageable. We will show how the damage model is being used to evaluate strategies to streamline our optics loop efficiency, as we strive to increase the laser shot rate without increasing operating costs.

  4. Initiation, Growth and Mitigation of UV Laser Induced Damage in Fused Silica

    Energy Technology Data Exchange (ETDEWEB)

    Rubenchik, A M; Feit, M D

    2001-12-21

    Laser damage of large fused silica optics initiates at imperfections. Possible initiation mechanisms are considered. We demonstrate that a model based on nanoparticle explosions is consistent with the observed initiation craters. Possible mechanisms for growth upon subsequent laser irradiation, including material modification and laser intensification, are discussed. Large aperture experiments indicate an exponential increase in damage size with number of laser shots. Physical processes associated with this growth and a qualitative explanation of self-accelerated growth is presented. Rapid growth necessitates damage growth mitigation techniques. Several possible mitigation techniques are mentioned, with special emphasis on CO{sub 2} processing. Analysis of material evaporation, crack healing, and thermally induced stress are presented.

  5. Initiation, Growth and Mitigation of UV Laser Induced Damage in Fused Silica

    Energy Technology Data Exchange (ETDEWEB)

    Rubenchik, A M; Feit, M D

    2003-06-10

    Laser damage of large fused silica optics initiates at imperfections. Possible initiation mechanisms are considered. We demonstrate that a model based on nanoparticle explosions is consistent with the observed initiation craters. Possible mechanisms for growth upon subsequent laser irradiation, including material modification and laser intensification, are discussed. Large aperture experiments indicate an exponential increase in damage size with number of laser shots. Physical processes associated with this growth and a qualitative explanation of self-accelerated growth is presented. Rapid growth necessitates damage growth mitigation techniques. Several possible mitigation techniques are mentioned, with special emphasis on CO{sub 2} processing. Analysis of material evaporation, crack healing, and thermally induced stress are presented.

  6. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

    2006-03-15

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after {gamma}-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  7. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Science.gov (United States)

    Pandey, B. N.; Lathika, K. M.; Mishra, K. P.

    2006-03-01

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after γ-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  8. Modeling electrical power absorption and thermally-induced biological tissue damage.

    Science.gov (United States)

    Zohdi, T I

    2014-01-01

    This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

  9. Preliminary Results of Earthquake-Induced Building Damage Detection with Object-Based Image Classification

    Science.gov (United States)

    Sabuncu, A.; Uca Avci, Z. D.; Sunar, F.

    2016-06-01

    Earthquakes are the most destructive natural disasters, which result in massive loss of life, infrastructure damages and financial losses. Earthquake-induced building damage detection is a very important step after earthquakes since earthquake-induced building damage is one of the most critical threats to cities and countries in terms of the area of damage, rate of collapsed buildings, the damage grade near the epicenters and also building damage types for all constructions. Van-Ercis (Turkey) earthquake (Mw= 7.1) was occurred on October 23th, 2011; at 10:41 UTC (13:41 local time) centered at 38.75 N 43.36 E that places the epicenter about 30 kilometers northern part of the city of Van. It is recorded that, 604 people died and approximately 4000 buildings collapsed or seriously damaged by the earthquake. In this study, high-resolution satellite images of Van-Ercis, acquired by Quickbird-2 (Digital Globe Inc.) after the earthquake, were used to detect the debris areas using an object-based image classification. Two different land surfaces, having homogeneous and heterogeneous land covers, were selected as case study areas. As a first step of the object-based image processing, segmentation was applied with a convenient scale parameter and homogeneity criterion parameters. As a next step, condition based classification was used. In the final step of this preliminary study, outputs were compared with streetview/ortophotos for the verification and evaluation of the classification accuracy.

  10. Muscle damage induced by black cohosh (Cimicifuga racemosa).

    Science.gov (United States)

    Minciullo, P L; Saija, A; Patafi, M; Marotta, G; Ferlazzo, B; Gangemi, S

    2006-01-01

    Extracts of black cohosh (Cimicifuga racemosa) are commonly used for the treatment of symptoms associated with menopause. Adverse events with black cohosh are rare, mild and reversible. A few number of serious adverse events, including hepatic and circulatory conditions, have been also reported, but without a clear causality relationship. We report the case of a woman with severe asthenia and very high blood levels of creatine phosphokinase and lactate dehydrogenase. The patient referred to take a dietary supplement derived from black cohosh for ameliorating menopause vasomotor symptoms. To exclude a possible involvement of this product, the patient was suggested to discontinue this therapy. After suspicion the patient showed a progressive normalization of biochemical parameters and improvement of clinical symptoms. We can hypothesise a causative role for black cohosh in the muscle damage observed in this patient. Factors suggesting an association between black cohosh and the observed myopathy included the temporal relationship between use of herbal product and asthenia and the absence of other identified causative factors. Rechallenge with the suspected agent was inadvisable for ethic reasons because of the risk of a serious relapse. This is the first time that asthenia associated with high muscle enzymes serum levels by black cohosh has been reported. In our opinion, this report is of interest because of the widespread diffusion of use of black cohosh as an alternative medicine for relief from menopausal symptoms.

  11. The DNA damage response in viral-induced cellular transformation.

    Science.gov (United States)

    Nikitin, P A; Luftig, M A

    2012-01-31

    The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation.

  12. Derinat Protects Skin against Ultraviolet-B (UVB-Induced Cellular Damage

    Directory of Open Access Journals (Sweden)

    Wen-Li Hsu

    2015-11-01

    Full Text Available Ultraviolet-B (UVB is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca2+ and reactive oxygen species (ROS. Derinat (sodium deoxyribonucleate has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2 expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC channels (TRPCs, as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging.

  13. The effect of laser pulse width on laser-induced damage at K9 and UBK7 components surface

    Science.gov (United States)

    Zhou, Xinda; Ba, Rongsheng; Zheng, Yinbo; Yuan, Jing; Li, Wenhong; Chen, Bo

    2015-07-01

    In this paper, we investigated the effects of laser pulse width on laser-induced damage. We measured the damage threshold of K9 glass and UBK7 glass optical components at different pulse width, then analysis pulse-width dependence of damage threshold. It is shown that damage threshold at different pulse width conforms to thermal restriction mechanism, Because of cm size laser beam, defect on the optical component surface leads to laser-induced threshold decreased.

  14. Inductively Coupled Plasma-Induced Etch Damage of GaN p-n Junctions

    Energy Technology Data Exchange (ETDEWEB)

    SHUL,RANDY J.; ZHANG,LEI; BACA,ALBERT G.; WILLISON,CHRISTI LEE; HAN,JUNG; PEARTON,S.J.; REN,F.

    1999-11-03

    Plasma-induced etch damage can degrade the electrical and optical performance of III-V nitride electronic and photonic devices. We have investigated the etch-induced damage of an Inductively Coupled Plasma (ICP) etch system on the electrical performance of mesa-isolated GaN pn-junction diodes. GaN p-i-n mesa diodes were formed by Cl{sub 2}/BCl{sub 3}/Ar ICP etching under different plasma conditions. The reverse leakage current in the mesa diodes showed a strong relationship to chamber pressure, ion energy, and plasma flux. Plasma induced damage was minimized at moderate flux conditions ({le} 500 W), pressures {ge}2 mTorr, and at ion energies below approximately -275 V.

  15. Investigation of Laser-Induced Damage on Multi-Layer Dielectric Gratings

    Institute of Scientific and Technical Information of China (English)

    KONG Wei-Jin; SHEN Zi-Cai; SHEN Jian; SHAO Jian-Da; FAN Zheng-Xiu

    2005-01-01

    @@ We investigate mechanisms of laser induced damage thresholds (LIDTs) of multi-layer dielectric gratings (MDGs).It is found that the laser damage thresholds of MDGs and unstructured dielectric multi-layer coatings (the substrate of MDG) are 3.15J/cm2 and 9.32J/cm2, respectively, at 1064nm (12ns) with the Littrow angle 51.2°and the TEM00 mode. The laser-induced damage mechanism of multi-layer dielectric is presented with the analysis of the following factors: The dominant factor is the pollution on the corrugated surface, which is induced by the complex manufacture process of multi-layer dielectric gratings; another is the electric field distribution along the corrugated surface. The third reason is due to the reduction in stoichiometry of oxide films, resulting from the manufacture process of etching.

  16. DNA damage and oxidative stress induced by acetylsalicylic acid in Daphnia magna.

    Science.gov (United States)

    Gómez-Oliván, Leobardo Manuel; Galar-Martínez, Marcela; Islas-Flores, Hariz; García-Medina, Sandra; SanJuan-Reyes, Nely

    2014-08-01

    Acetylsalicylic acid is a nonsteroidal anti-inflammatory widely used due to its low cost and high effectiveness. This compound has been found in water bodies worldwide and is toxic to aquatic organisms; nevertheless its capacity to induce oxidative stress in bioindicators like Daphnia magna remains unknown. This study aimed to evaluate toxicity in D. magna induced by acetylsalicylic acid in water, using oxidative stress and DNA damage biomarkers. An acute toxicity test was conducted in order to determine the median lethal concentration (48-h LC50) and the concentrations to be used in the subsequent subacute toxicity test in which the following biomarkers were evaluated: lipid peroxidation, oxidized protein content, activity of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, and level of DNA damage. Lipid peroxidation level and oxidized protein content were significantly increased (pacetylsalicylic acid induces oxidative stress and DNA damage in D. magna.

  17. LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

    DEFF Research Database (Denmark)

    Poulsen, Ebbe Toftgaard; Nielsen, Nadia Sukusu; Jensen, Morten Mørk;

    2016-01-01

    at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo...... laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC......-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after...

  18. Serotonergic signaling inhibits hyperalgesia induced by spinal cord damage.

    Science.gov (United States)

    Horiuchi, Hideki; Ogata, Tadanori; Morino, Tadao; Takeba, Jun; Yamamoto, Haruyasu

    2003-02-14

    Although dysesthesia is one of the most serious problems in patients with spinal cord injury, most of them being unresponsive to conventional treatments. In this study, we established a rat thoracic spinal cord mild-compression model that revealed thermal hyperalgesia in the hind limb. The thoracic spinal cord was compressed gently, using a 20 g weight for 20 min. The withdrawal latency of the thermal stimulation of the bilateral hind-limb was monitored using Hargreaves' Plantar test apparatus. In this model, thermal-hyperalgesia was observed for 1 week after the injury. The spinal cord injury-induced thermal-hyperalgesia was mimicked by the intrathecal application of metergoline, a non-selective 5-HT antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]-piperazine hydrobromide (NAN190), a selective 5-HT1 antagonist, and 3-tropanyl-3,5-dichlorobenzoate (MDL72222), a selective 5-HT3 antagonist. Intraperitoneal application of fluvoxamine maleate, a selective serotonin reuptake inhibitor, reduced the intensity of hyperalgesia induced by spinal cord injury. The inhibitory effect of fluvoxamine maleate on thermal hyperalgesia was prevented by the application of the aforementioned nonselective or selective 5-HT receptor antagonists. Intrathecal application of fluvoxamine maleate and selective 5-HT receptor agonists, i.e., 8-hydroxy-2-(di-n-proplyamino)-tetralin hydrobromide (8-OH-DPAT: 5HT-1 selective) and 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT: 5HT-3 selective), inhibited the spinal cord injury-induced hyperalgesia. These results suggest that the change in the descending serotonergic signal plays an important role in hyperalgesia after the spinal cord injury, and that the application of selective serotonin reuptake inhibitors will be one of the candidates for new therapeutic methods against post-spinal cord injury dysesthesia.

  19. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, J.L.; Beck, P.L.; Morris, G.P. (Queen' s Univ., Kingston, Ontario (Canada))

    1988-01-01

    The role of leukotriene (LT) C{sub 4} as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC{sub 4} synthesis. LTC{sub 4} synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT{sub 4} synthesis paralleled the changes in LTC{sub 4} synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC{sub 4} synthesis does not confer protection to the mucosa, suggesting that LTC{sub 4} does not play an important role in the etiology of ethanol-induced gastric damage.

  20. Displacement damage induced in iron by gammas and neutrons under irradiation in the IFMIF test cell

    Science.gov (United States)

    Simakov, S. P.; Fischer, U.

    2011-10-01

    This work presents a complete comparative analysis of the radiation damage induced in iron-based materials in IFMIF by photons and neutrons. The gamma induced damage takes into account, for the first time, both photonuclear and photoatomic reaction mechanisms. The relevant cross sections were taken from available data evaluations. The gamma and neutron radiation fields were calculated by the McDeLicious Monte Carlo code using a 3-D geometry model. Finally the gamma and neutron induced damages in the iron have been assessed inside the IFMIF test cell and the surrounding concrete walls. It was found that the photoatomic mechanism dominates the photonuclear with at least one hundred times higher damage rates. The ratio of the gamma and the neutron induced displacement damage was found to be 10 -3 inside the concrete wall and 10 -5 in the components close to d-Li source. This fraction may increase a few times due to the uncertainty of the evaluated γ-dpa cross sections and the different surviving probabilities for defects produced by gammas and neutrons, nevertheless unlikely exceed 1%.

  1. Platinum nanoparticles induce damage to DNA and inhibit DNA replication

    Science.gov (United States)

    Nejdl, Lukas; Kudr, Jiri; Moulick, Amitava; Hegerova, Dagmar; Ruttkay-Nedecky, Branislav; Gumulec, Jaromir; Cihalova, Kristyna; Smerkova, Kristyna; Dostalova, Simona; Krizkova, Sona; Novotna, Marie; Kopel, Pavel

    2017-01-01

    Sparsely tested group of platinum nanoparticles (PtNPs) may have a comparable effect as complex platinum compounds. The aim of this study was to observe the effect of PtNPs in in vitro amplification of DNA fragment of phage λ, on the bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts and erythrocytes. In vitro synthesized PtNPs were characterized by dynamic light scattering (PtNPs size range 4.8–11.7 nm), zeta potential measurements (-15 mV at pH 7.4), X-ray fluorescence, UV/vis spectrophotometry and atomic absorption spectrometry. The PtNPs inhibited the DNA replication and affected the secondary structure of DNA at higher concentrations, which was confirmed by polymerase chain reaction, DNA sequencing and DNA denaturation experiments. Further, cisplatin (CisPt), as traditional chemotherapy agent, was used in all parallel experiments. Moreover, the encapsulation of PtNPs in liposomes (LipoPtNPs) caused an approximately 2.4x higher of DNA damage in comparison with CisPt, LipoCisPt and PtNPs. The encapsulation of PtNPs in liposomes also increased their antibacterial, cytostatic and cytotoxic effect, which was determined by the method of growth curves on S. aureus and HFF cells. In addition, both the bare and encapsulated PtNPs caused lower oxidative stress (determined by GSH/GSSG ratio) in the human erythrocytes compared to the bare and encapsulated CisPt. CisPt was used in all parallel experiments as traditional chemotherapy agent. PMID:28704436

  2. Strain-dependent Damage Evolution and Velocity Reduction in Fault Zones Induced by Earthquake Rupture

    Science.gov (United States)

    Zhong, J.; Duan, B.

    2009-12-01

    Low-velocity fault zones (LVFZs) with reduced seismic velocities relative to the surrounding wall rocks are widely observed around active faults. The presence of such a zone will affect rupture propagation, near-field ground motion, and off-fault damage in subsequent earth-quakes. In this study, we quantify the reduction of seismic velocities caused by dynamic rup-ture on a 2D planar fault surrounded by a low-velocity fault zone. First, we implement the damage rheology (Lyakhovsky et al. 1997) in EQdyna (Duan and Oglesby 2006), an explicit dynamic finite element code. We further extend this damage rheology model to include the dependence of strains on crack density. Then, we quantify off-fault continuum damage distribution and velocity reduction induced by earthquake rupture with the presence of a preexisting LVFZ. We find that the presence of a LVFZ affects the tempo-spatial distribu-tions of off-fault damage. Because lack of constraint in some damage parameters, we further investigate the relationship between velocity reduction and these damage prameters by a large suite of numerical simulations. Slip velocity, slip, and near-field ground motions computed from damage rheology are also compared with those from off-fault elastic or elastoplastic responses. We find that the reduction in elastic moduli during dynamic rupture has profound impact on these quantities.

  3. Simplified qPCR method for detecting excessive mtDNA damage induced by exogenous factors.

    Science.gov (United States)

    Gureev, Artem P; Shaforostova, Ekaterina A; Starkov, Anatoly A; Popov, Vasily N

    2017-05-01

    Damage to mitochondrial DNA (mtDNA) is a meaningful biomarker for evaluating genotoxicity of drugs and environmental toxins. Existing PCR methods utilize long mtDNA fragments (∼8-10kb), which complicates detecting exact sites of mtDNA damage. To identify the mtDNA regions most susceptible to damage, we have developed and validated a set of primers to amplify ∼2kb long fragments, while covering over 95% of mouse mtDNA. We have modified the detection method by greatly increasing the enrichment of mtDNA, which allows us solving the problem of non-specific primer annealing to nuclear DNA. To validate our approach, we have determined the most damage-susceptible mtDNA regions in mice treated in vivo and in vitro with rotenone and H2O2. The GTGR-sequence-enriched mtDNA segments located in the D-loop region were found to be especially susceptible to damage. Further, we demonstrate that H2O2-induced mtDNA damage facilitates the relaxation of mtDNA supercoiled conformation, making the sequences with minimal damage more accessible to DNA polymerase, which, in turn, results in a decrease in threshold cycle value. Overall, our modified PCR method is simpler and more selective to the specific sites of damage in mtDNA. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis.

    Science.gov (United States)

    Halliday, Gary M

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  5. Decrease of FIB-induced lateral damage for diamond tool used in nano cutting

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wei [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Xu, Zongwei, E-mail: zongweixu@163.com [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Fang, Fengzhou, E-mail: fzfang@gmail.com [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Liu, Bing; Xiao, Yinjing; Chen, Jinping [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Wang, Xibin [School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081 (China); Liu, Hongzhong [State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710049 (China)

    2014-07-01

    Highlights: • We mainly aim to characterize and decrease the FIB-induced damage on diamond tool. • Raman and XPS methods were used to characterize the nanoscale FIB-induced damage. • Lower energy FIB can effectively lessen the FIB-induced damage on diamond tool. • The diamond tools’ performance was greatly improved after FIB process optimization. • 6 nm chip thickness of copper was achieved by diamond tool with 22 nm edge radius. - Abstract: Diamond cutting tools with nanometric edge radius used in ultra-precision machining can be fabricated by focused ion beam (FIB) technology. However, due to the nanoscale effects, the diamond tools performance and the cutting edge lifetime in nano cutting would be degraded because of the FIB-induced nanoscale lateral damage. In this study, the methods of how to effectively characterize and decrease the FIB-induced lateral damage for diamond tool are intensively studied. Based on the performance optimization diamond machining tools, the controllable chip thickness of less than 10 nm was achieved on a single-crystal copper in nano cutting. In addition, the ratio of minimum thickness of chip (MTC) to tool edge radius of around 0.3–0.4 in nano cutting is achieved. Methods for decreasing the FIB-induced damage on diamond tools and adding coolant during the nano cutting are very beneficial in improving the research of nano cutting and MTC. The nano cutting experiments based on the sharp and high performance of diamond tools would validate the nano cutting mechanisms that many molecular dynamic simulation studies have put forward and provide new findings for nano cutting.

  6. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  7. The Influence of Soft Contact Lens Wear and Two Weeks Cessation of Lens Wear on Corneal Curvature

    OpenAIRE

    Lloyd McKernan, Aoife; O'Dwyer, Veronica; Simo Mannion, Luisa

    2014-01-01

    Abstract Introduction Accurate corneal measurements are crucial in corneal refractive surgery (CRS) to ensure successful outcomes. Soft contact lens (SCL) wear may result in changes to corneal curvature and structure. United States Food and Drug Administration (FDA) pre-operative guidelines recommend that prior to CRS, SCL wearers cease SCL wear for “at least two weeks before examination and treatment”[1]. Corneal curvature changes induced by SCL wear may take longer than two weeks to reso...

  8. Sestrin2 protects the myocardium against radiation-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong [Shengjing Hospital of China Medical University, Department of Medical Oncology, Cancer Center, Shenyang (China); Zeng, Jing [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Wang, Hong-Mei [Nanfang Hospital of Southern Medical University, Department of Radiation Oncology, Guangzhou (China)

    2016-05-15

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  9. Nanosecond multi-pulse laser-induced damage mechanisms in pure and mixed oxide thin films

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Frank R., E-mail: frank.wagner@fresnel.fr; Gouldieff, Céline, E-mail: celine.gouldieff@univ-rennes1.fr; Natoli, Jean-Yves, E-mail: jean-yves.natoli@fresnel.fr; Commandré, Mireille, E-mail: mireille.commandre@fresnel.fr

    2015-10-01

    We report on nanosecond laser-induced damage of pure and mixed oxide thin films deposited by ion beam sputtering. Silica, hafnia and alumina as well as their binary mixtures have been tested in S-on-1 mode at 355 nm and 266 nm using a multiscale approach. The results were analyzed qualitatively to discuss the different fatigue behaviors observed. The absence of a multi-photon absorption step in the 1-on-1 damage thresholds as a function of the band gap indicates defect-mediated damage mechanisms. During the multi-pulse experiments we observed laser-induced defects that cause fatigue effects and preexisting low-density defects, which are insensitive to multiple pulse irradiation. Depending on material and beam size both types of defects (preexisting and light-induced) may contribute equally to the observed damage probability. Comparing the fatigue behavior of the mixtures to their constituting pure oxides, we found that, in general, the fatigue behavior of binary mixtures cannot be interpolated from the behaviors of the pure oxides. - Highlights: • Multi-pulse laser damage can be analyzed plotting damaging shot number vs. fluence. • A fatigue effect was only observed for small laser beams, avoiding worse precursors. • The fatigue behavior of a mixture cannot be interpolated from the pure oxides. • SiO{sub 2} and Al{sub 2}O{sub 3} damage at 266 nm is due to deterministic material modifications. • Hafnia multi-pulse laser damage with small beams is stochastic even at 266 nm.

  10. Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was studied,and the mechanisms were discussed.The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 μmol/L) could induce apoptosis in immature cultures of cerebellar granule cells.Flow cytometry and HPLC analyses revealed that after treatment with SNAP,the mitochondrial transmembrane potential and the cellular ATP content decreased significantly.Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis.The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

  11. MCPIP is induced by cholesterol and participated in cholesterol-caused DNA damage in HUVEC.

    Science.gov (United States)

    Da, Jingjing; Zhuo, Ming; Qian, Minzhang

    2015-01-01

    Hypercholesterolemia is an important risk factor for atherosclerosis and cholesterol treatment would cause multiple damages, including DNA damage, on endothelial cells. In this work, we have used human umbilical vein endothelial cell line (HUVEC) to explore the mechanism of cholesterol induced damage. We have found that cholesterol treatment on HUVEC could induce the expression of MCPIP1. When given 12.5 mg/L cholesterol on HUVEC, the expression of MCPIP1 starts to increase since 4 hr after treatment and at 24 hr after treatment it could reach to 10 fold of base line level. We hypothesis this induction of MCPIP1 may contribute to the damaging process and we have used siRNA of MCPIP1 in further research. This MCPIP1 siRNA (siMCPIP) could down regulate MCPIP1 by 73.4% and when using this siRNA on HUVECs, we could see the cholesterol induced DNA damage have been reduced. We have detected DNA damage by γH2AX foci formation in nuclear, γH2AX protein level and COMET assay. Compare to cholesterol alone group, siMCPIP group shows much less γH2AX foci formation in nuclear after cholesterol treatment, less γH2AX protein level in cell and also less tail moment detected in COMET assay. We have also seen that using siMCPIP1 could result in less reactive oxygen species (ROS) in cell after cholesterol treatment. We have also seen that using siMCPIP could reduce the protein level of Nox4 and p47(phox), two major regulators in ROS production. These results suggest that MCPIP1 may play an important role in cholesterol induced damage.

  12. Investigation of focused ion beam induced damage in single crystal diamond tools

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Zhen [Centre for Precision Manufacturing, Department of Design, Manufacture & Engineering Management, University of Strathclyde, Glasgow G1 1XQ (United Kingdom); Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001 (China); Luo, Xichun, E-mail: Xichun.Luo@strath.ac.uk [Centre for Precision Manufacturing, Department of Design, Manufacture & Engineering Management, University of Strathclyde, Glasgow G1 1XQ (United Kingdom)

    2015-08-30

    Highlights: • The FIB-induced damage layer should be paid enough attention when shaping the cutting edges of nanoscale diamond tools. • During FIB processing cutting tools made of natural single crystal diamond, the Ga{sup +} collision will create a damage layer around tool tips. • The thicknesses of damaged layer and the level for amorphization of diamond significantly increase with beam energy. • The FIB-induced doping and defects during tool fabrication are responsible for the early detection of tool wear of nanoscale diamond tools. - Abstract: In this work, transmission electron microscope (TEM) measurements and molecular dynamics (MD) simulations were carried out to characterise the focused ion beam (FIB) induced damage layer in a single crystal diamond tool under different FIB processing voltages. The results obtained from the experiments and the simulations are in good agreement. The results indicate that during FIB processing cutting tools made of natural single crystal diamond, the energetic Ga{sup +} collision will create an impulse-dependent damage layer at the irradiated surface. For the tested beam voltages in a typical FIB system (from 8 kV to 30 kV), the thicknesses of the damaged layers formed on a diamond tool surface increased from 11.5 nm to 27.6 nm. The dynamic damage process of FIB irradiation and ion–solid interactions physics leading to processing defects in FIB milling were emulated by MD simulations. The research findings from this study provide the in-depth understanding of the wear of nanoscale multi-tip diamond tools considering the FIB irradiation induced doping and defects during the tool fabrication process.

  13. Malaria-induced renal damage: facts and myths.

    Science.gov (United States)

    Ehrich, Jochen H H; Eke, Felicia U

    2007-05-01

    Malaria infections repeatedly have been reported to induce nephrotic syndrome and acute renal failure. Questions have been raised whether the association of a nephrotic syndrome with quartan malaria was only coincidental, and whether the acute renal failure was a specific or unspecific consequence of Plasmodium falciparum infection. This review attempts to answer questions about "chronic quartan malaria nephropathy" and "acute falciparum malaria nephropathy". The literature review was performed on all publications on kidney involvement in human and experimental malarial infections accessible in PubMed or available at the library of the London School of Hygiene and Tropical Medicine. The association of a nephrotic syndrome with quartan malaria was mostly described before 1975 in children and rarely in adult patients living in areas endemic for Plasmodium malariae. The pooled data on malaria-induced acute renal failure included children and adults acquiring falciparum malaria in endemic areas either as natives or as travellers from non-tropical countries. Non-immunes (not living in endemic areas) had a higher risk of developing acute renal failure than semi-immunes (living in endemic areas). Children with cerebral malaria had a higher rate and more severe course of acute renal failure than children with mild malaria. Today, there is no evidence of a dominant role of steroid-resistant and chronic "malarial glomerulopathies" in children with a nephrotic syndrome in Africa. Acute renal failure was a frequent and serious complication of falciparum malaria in non-immune adults. However, recently it has been reported more often in semi-immune African children with associated morbidity and mortality.

  14. Corneal collagen cross-linking to stop corneal ectasia exacerbated by radial keratotomy.

    Science.gov (United States)

    Mazzotta, Cosimo; Baiocchi, Stefano; Denaro, Rosario; Tosi, Gian Marco; Caporossi, Tomaso

    2011-02-01

    To assess the efficacy of riboflavin ultraviolet A (UV-A) corneal collagen cross-linking in the management of keratoconic corneal ectasia exacerbated by radial keratotomy (RK). A patient with progressive corneal ectasia and hyperopic shift, occurring 10 years after RK performed in the left eye, was treated with riboflavin UV-A corneal collagen cross-linking according to the Siena protocol: Pilocarpin 0.1% drop (1 hour before), lidocaine 4% drops 15 minutes before, mechanical scraping of epithelium (9-mm-diameter area), preirradiation stromal soaking for 10 minutes in riboflavin 0.1%-dextrane 20% (Ricrolin; Sooft Italy) applied every 2 minutes, and 30 minutes of total exposure (6 steps of 5 minutes) to solid-state UV-A illuminator (Caporossi, Baiocchi, Mazzotta Vega X linker; CSO Opthalmics, Florence, Italy), energy delivered 3 mW/cm, and irradiated area 9 mm in diameter. After the operation, uncorrected visual acuity and best spectacle-corrected visual acuity improved from 0.2 to 0.6 and from 0.3 to 0.8 Snellen lines, respectively, in a 12-month follow-up. Improved topographical K readings and corneal symmetry index were also recorded starting from the first postoperative month and continuing thereafter. No adverse effects were recorded after treatment. Riboflavin UV-A-induced corneal cross-linking seems to be a promising surgical option in the management of unstable corneal ectasia exacerbated by RK, particularly in eyes with preexisting keratoconus. A large cohort and longer follow-up are needed to determine its long-term efficacy in this clinical setting.

  15. Manifestaciones corneales en las enfermedades sistémicas Corneal manifestations in systemic diseases

    Directory of Open Access Journals (Sweden)

    J. Zarranz-Ventura

    2008-01-01

    Full Text Available Un gran número de enfermedades sistémicas presentan manifestaciones corneales dentro de su espectro de enfermedad. El estudio detallado de todos los cuadros que asocian patología corneal resulta inabarcable, por ello se presentan las enfermedades más prevalentes o características. Este estudio contempla las enfermedades pulmonares y conectivopatías (colagenosis, enfermedades reumatológicas y enfermedades inflamatorias idiopáticas, las enfermedades dermatológicas, cardiovasculares, hematológicas y la patología digestiva y hepatopancreática. Se contemplan también, por ocasionar alteraciones corneales, las enfermedades endocrinas y metabólicas con algunas situaciones de malnutrición y estados carenciales, las infecciones sistémicas y las enfermedades renales. Otro área que produce afectación corneal es la patología otorrinolaringológica y las enfermedades genéticas. Se repasa brevemente la toxicidad y las alteraciones corneales provocadas por fármacos.Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases, dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

  16. Identification of pathways controlling DNA damage induced mutation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Lis, Ewa T; O'Neill, Bryan M; Gil-Lamaignere, Cristina; Chin, Jodie K; Romesberg, Floyd E

    2008-05-01

    Mutation in response to most types of DNA damage is thought to be mediated by the error-prone sub-branch of post-replication repair and the associated translesion synthesis polymerases. To further understand the mutagenic response to DNA damage, we screened a collection of 4848 haploid gene deletion strains of Saccharomyces cerevisiae for decreased damage-induced mutation of the CAN1 gene. Through extensive quantitative validation of the strains identified by the screen, we identified ten genes, which included error-prone post-replication repair genes known to be involved in induced mutation, as well as two additional genes, FYV6 and RNR4. We demonstrate that FYV6 and RNR4 are epistatic with respect to induced mutation, and that they function, at least partially, independently of post-replication repair. This pathway of induced mutation appears to be mediated by an increase in dNTP levels that facilitates lesion bypass by the replicative polymerase Pol delta, and it is as important as error-prone post-replication repair in the case of UV- and MMS-induced mutation, but solely responsible for EMS-induced mutation. We show that Rnr4/Pol delta-induced mutation is efficiently inhibited by hydroxyurea, a small molecule inhibitor of ribonucleotide reductase, suggesting that if similar pathways exist in human cells, intervention in some forms of mutation may be possible.

  17. Mitochondrial dysfunction and oxidative stress in corneal disease.

    Science.gov (United States)

    Vallabh, Neeru A; Romano, Vito; Willoughby, Colin E

    2017-05-23

    The cornea is the anterior transparent surface and the main refracting structure of the eye. Mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of inherited (e.g. Kearns Sayre Syndrome) and acquired corneal diseases (e.g. keratoconus and Fuchs endothelial corneal dystrophy). Both antioxidants and reactive oxygen species are found in the healthy cornea. There is increasing evidence of imbalance in the oxidative balance and mitochondrial function in the cornea in disease states. The cornea is vulnerable to mitochondrial dysfunction and oxidative stress due to its highly exposed position to ultraviolet radiation and high oxygen tension. The corneal endothelium is vulnerable to accumulating mitochondrial DNA (mtDNA) damage due to the post- mitotic nature of endothelial cells, yet their mitochondrial genome is continually replicating and mtDNA mutations can develop and accumulate with age. The unique physiology of the cornea predisposes this structure to oxidative damage, and there is interplay between inherited and acquired mitochondrial dysfunction, oxidative damage and a number of corneal diseases. By targeting mitochondrial dysfunction in corneal disease, emerging treatments may prevent or reduce visual loss. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  18. The improvement of laser induced damage resistance of optical workpiece surface by hydrodynamic effect polishing

    Science.gov (United States)

    Peng, Wenqiang; Guan, Chaoliang; Li, Shengyi; Wang, Zhuo

    2016-10-01

    Surface and subsurface damage in optical element will greatly decrease the laser induced damage threshold (LIDT) in the intense laser optical system. Processing damage on the workpiece surface can be inevitably caused when the material is removed in brittle or plastic mode. As a non-contact polishing technology, hydrodynamic effect polishing (HEP) shows very good performance on generating an ultra-smooth surface without damage. The material is removed by chemisorption between nanoparticle and workpiece surface in the elastic mode in HEP. The subsurface damage and surface scratches can be effectively removed after the polishing process. Meanwhile ultra-smooth surface with atomic level surface roughness can be achieved. To investigate the improvement of LIDT of optical workpiece, polishing experiment was conducted on a magnetorheological finishing (MRF) silica glass sample. AFM measurement results show that all the MRF directional plastic marks have been removed clearly and the root-mean-square (rms) surface roughness has decreased from 0.673nm to 0.177nm after HEP process. Laser induced damage experiment was conducted with laser pulse of 1064nm wavelength and 10ns time width. Compared with the original state, the LEDT of the silica glass sample polished by HEP has increased from 29.78J/cm2 to 45.47J/cm2. It demonstrates that LIDT of optical element treated by HEP can be greatly improved for ultra low surface roughness and nearly defect-free surface/subsurface.

  19. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Directory of Open Access Journals (Sweden)

    Joshua W Modell

    2014-10-01

    Full Text Available Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  20. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Science.gov (United States)

    Modell, Joshua W; Kambara, Tracy K; Perchuk, Barrett S; Laub, Michael T

    2014-10-01

    Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  1. A DNA Damage-Induced, SOS-Independent Checkpoint Regulates Cell Division in Caulobacter crescentus

    Science.gov (United States)

    Modell, Joshua W.; Kambara, Tracy K.; Perchuk, Barrett S.; Laub, Michael T.

    2014-01-01

    Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage. PMID:25350732

  2. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Directory of Open Access Journals (Sweden)

    Jennifer A Calvo

    2013-04-01

    Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  3. 5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

    Institute of Scientific and Technical Information of China (English)

    Yongquan Pan; Peng Zhang; Junqing Yang; Qiang Su

    2010-01-01

    A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum.In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-lipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage andspatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

  4. Resveratrol protects mouse oocytes from methylglyoxal-induced oxidative damage.

    Science.gov (United States)

    Liu, Yu; He, Xiao-Qin; Huang, Xin; Ding, Lu; Xu, Lin; Shen, Yu-Ting; Zhang, Fei; Zhu, Mao-Bi; Xu, Bai-Hui; Qi, Zhong-Quan; Wang, Hai-Long

    2013-01-01

    Methylglyoxal, a reactive dicarbonyl compound, is mainly formed from glycolysis. Methylglyoxal can lead to the dysfunction of mitochondria, the depletion of cellular anti-oxidation enzymes and the formation of advanced glycation ends. Previous studies showed that the accumulation of methylglyoxal and advanced glycation ends can impair the oocyte maturation and reduce the oocyte quality in aged and diabetic females. In this study, we showed that resveratrol, a kind of phytoalexin found in the skin of grapes, red wine and other botanical extracts, can alleviate the adverse effects caused by methylglyoxal, such as inhibition of oocyte maturation and disruption of spindle assembly. Besides, methylglyoxal-treated oocytes displayed more DNA double strands breaks and this can also be decreased by treatment of resveratrol. Further investigation of these processes revealed that methylglyoxal may affect the oocyte quality by resulting in excessive reactive oxygen species production, aberrant mitochondrial distribution and high level lipid peroxidation, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can protect the oocytes from methylglyoxal-induced cytotoxicity and this was mainly through the correction of the abnormity of cellular reactive oxygen species metabolism.

  5. Acetaminophen protects against iron-induced cardiac damage in gerbils.

    Science.gov (United States)

    Walker, Ernest M; Epling, Christopher P; Parris, Cordel; Cansino, Silvestre; Ghosh, Protip; Desai, Devashish H; Morrison, Ryan G; Wright, Gary L; Wehner, Paulette; Mangiarua, Elsa I; Walker, Sandra M; Blough, Eric R

    2007-01-01

    There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.

  6. Testosterone production and spermatogenic damage induced by organophosphorate pesticides.

    Science.gov (United States)

    Contreras, H R; Paredes, V; Urquieta, B; Del Valle, L; Bustos-Obregón, E

    2006-12-01

    Parathion is an organophosphorate pesticide amply used in agriculture. Many alterations induced by organophosphorate pesticides have been described, such as: cytogenetic alterations in germinal cells, oligozoospermia and teratozoospermia in the mouse. The effect of Parathion, both pure (PP) and commercial (PC), on mouse interstitial cell testosterone production was evaluated in vivo and in vitro. Male mice were intraperitoneally injected with a single dose of 1/3 LD50 of Parathion, both PP and PC. The animals were sacrificed at 1, 8 and 40 days post injection to evaluate the impact of disrupting testosterone production on spermatogonia, spermatocytes and elongated spermatids. The plasma testosterone was assayed by standard radioimmunoanalysis. The same method was used to assay testosterone in the culture medium of interstitial cells obtained from the control and Parathion treated animals at the same time intervals. Sperm count, sperm teratozoospermia and tubular blockage were analyzed for an appraisal of spermatogenesis. Increase in the teratozoospermia and tubular blockage was detected in the PP and PC group at 8 and 40 days post injection. Plasma testosterone levels drop significantly at 8 days and recovered slowly at 40 days only in PP animals as detected in vivo, implying interference of testicular steroidogenesis due to the toxicant. Recuperation of normality occurs at long time intervals. In conclusion, Parathion disturbs the synthesis of testosterone in mice affecting qualitatively the spermatogenesis

  7. Urea-induced oxidative damage in Elodea densa leaves.

    Science.gov (United States)

    Maleva, Maria; Borisova, Galina; Chukina, Nadezda; Prasad, M N V

    2015-09-01

    Urea being a fertilizer is expected to be less toxic to plants. However, it was found that urea at 100 mg L(-1) caused the oxidative stress in Elodea leaves due to the formation of reactive oxygen species (ROS) and lipid peroxidation that are known to stimulate antioxidant pathway. Urea at a concentration of 500 and 1000 mg L(-1) decreased low-molecular-weight antioxidants. In this case, the antioxidant status of plants was supported by the activity of antioxidant enzymes such as superoxide dismutase and guaiacol peroxidase. A significant increase in the soluble proteins and -SH groups was observed with high concentrations of urea (30-60 % of control). Thus, the increased activity of antioxidant enzymes, low-molecular-weight antioxidants, and induced soluble protein thiols are implicated in plant resistance to oxidative stress imposed by urea. We found that guaiacol peroxidase plays an important role in the removal of the peroxide in Elodea leaves exposed to 1000 mg L(-1)of urea.

  8. Induced DNA damage by dental resin monomers in somatic cells.

    Science.gov (United States)

    Arossi, Guilherme Anziliero; Lehmann, Mauricio; Dihl, Rafael Rodrigues; Reguly, Maria Luiza; de Andrade, Heloisa Helena Rodrigues

    2010-02-01

    The present in vivo study investigated the genotoxicity of four dental resin monomers: triethyleneglycoldimethacrylate (TEGDMA), hydroxyethylmethacrylate (HEMA), urethanedimethacrylate (UDMA) and bisphenol A-glycidylmethacrylate (BisGMA). The Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster was applied to analyse their genotoxicity expressed as homologous mitotic recombination, point and chromosomal mutation. SMART detects the loss of heterozygosity of marker genes expressed phenotypically on the fly's wings. This fruit fly has an extensive genetic homology to mammalians, which makes it a suitable model organism for genotoxic investigations. The present findings provide evidence that the mechanistic basis underlying the genotoxicity of UDMA and TEGDMA is related to homologous recombination and gene/chromosomal mutation. A genotoxic pattern can correspondingly be discerned for both UDMA and TEGDMA: their genotoxicity is attributed respectively to 49% and 44% of mitotic recombination, as well as 51% and 56% of mutational events, including point and chromosomal alterations. The monomer UDMA is 1.6 times more active than TEGDMA to induce mutant clones per treatment unit. BisGMA and HEMA had no statistically significant effect on total spot frequencies - suggesting no genotoxic action in the SMART assay. The clinical significance of these observations has to be interpreted for data obtained in other bioassays.

  9. Using corneal topography design personalized cataract surgery programs

    Directory of Open Access Journals (Sweden)

    Jin-Ou Huang

    2014-08-01

    Full Text Available AIM:To investigate how to design personalized cataract surgery programs to achieve surgical correction of preoperative corneal astigmatism with surgical astigmatism under the guidance of corneal topography, improve postoperative visual quality and reduce the cost of treatment. METHODS: Totally 202 cases(226 eyescataract patients were divided into randomized treatment group and individualized treatment group. According to the method and location of the incision, randomized treatment group were divided into 8 groups. Surgical astigmatism after different incision were calculated with the use of preoperative and postoperative corneal astigmatism through vector analysis method. Individualized treatment groups were designed personably for surgical method with reference of every surgically induced astigmatism, the surgical method chooses the type of surgical incision based on close link between preoperative corneal astigmatism and surgically induced astigmatism, and the incision was located in the steep meridian. The postoperative corneal astigmatism of individualized treatment group was observed. RESULTS: Postoperative corneal astigmatism of individualized treatment group were lower than that of 3.0mm clear corneal tunnel incision in the randomized treatment group, there were statistically significance difference, while with 3.0mm sclera tunnel incision group there were no statistically significance difference. After 55.8% of patients with the use of individualized surgical plan could undergo the operation of extracapsular cataract extraction with relatively low cost and rigid intraocular lens implantation, the per capita cost of treatment could be reduced. CONCLUSION: Personalized cataract surgery programs are designed to achieve surgical correction of preoperative corneal astigmatism under the use of corneal topography, improve postoperative visual quality and reduce the cost of treatment.

  10. Zinc acexamate reduces gastric damage induced by platelet-activating factor.

    Science.gov (United States)

    Escolar, G; Navarro, C; Galmés, J L; Casanovas, L I; Bulbena, O

    1989-10-01

    We have tested the ability of zinc acexamate (ZAC) to prevent platelet-activating-factor (Paf) induced gastric damage in rats. Lesions were characterized by a vascular congestion affecting the entire mucosa, oedema, haemorrhage and frequent necrosis of the more superficial areas. The gastric damage appearing after Paf was accompanied by degranulation of gastric mast cells. Leukocytes were often seen at the submucosal level. Oral pretreatment with ZAC reduced in a dose-dependent manner both gastric damage and mast cell degranulation observed after Paf. ZAC administered orally at a dose of 100 mg kg-1 statistically inhibited (p less than 0.01) gastric damage and mast cell degranulation. ZAC did not affect the hypotension induced by Paf confirming that gastric damage and hypotension appearing in rats after Paf administration are two independent phenomena. The present findings indicate that the inhibitory effect of ZAC upon gastric lesions induced by Paf may be related to the different protective actions exhibited by this zinc compound in a wide variety of experimental models of gastric ulcer.

  11. Attenuation of eccentric exercise-induced muscle damage conferred by maximal isometric contractions: a mini review

    Directory of Open Access Journals (Sweden)

    Leonardo Coelho Rabello Lima

    2015-10-01

    Full Text Available Although beneficial in determined contexts, eccentric exercise-induced muscle damage (EIMD might be unwanted during training regimens, competitions and daily activities. There are a vast number of studies investigating strategies to attenuate EIMD response after damaging exercise bouts. Many of them consist of performing exercises that induce EIMD, consuming supplements or using equipment that are not accessible for most people. It appears that performing maximal isometric contractions (ISOs 2-4 days prior to damaging bouts promotes significant attenuation of EIMD symptoms that are not related to muscle function. It has been shown that the volume of ISOs, muscle length in which they are performed, and interval between them and the damaging bout influence the magnitude of this protection. Additionally, it appears that this protection is not long-lived, lasting no longer than 4 days. Although no particular mechanisms for these adaptations were identified, professionals should consider applying this non-damaging stimulus before submitting their patients to unaccustomed exercised. However, it seems not to be the best option for athletes or relatively trained individuals. Future studies should focus on establishing if ISOs protect other populations (i.e., trained individuals or muscle groups (i.e., knee extensors against EIMD, as well as investigate different mechanisms for ISO-induced protection.

  12. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2015-06-01

    Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  13. Effects of a Strength Training Session After an Exercise Inducing Muscle Damage on Recovery Kinetics.

    Science.gov (United States)

    Abaïdia, Abd-Elbasset; Delecroix, Barthélémy; Leduc, Cédric; Lamblin, Julien; McCall, Alan; Baquet, Georges; Dupont, Grégory

    2017-01-01

    Abaïdia, A-E, Delecroix, B, Leduc, C, Lamblin, J, McCall, A, Baquet, G, and Dupont, G. Effects of a strength training session after an exercise inducing muscle damage on recovery kinetics. J Strength Cond Res 31(1): 115-125, 2017-The purpose of this study was to investigate the effects of an upper-limb strength training session the day after an exercise inducing muscle damage on recovery of performance. In a randomized crossover design, subjects performed the day after the exercise, on 2 separate occasions (passive vs. active recovery conditions) a single-leg exercise (dominant in one condition and nondominant in the other condition) consisting of 5 sets of 15 eccentric contractions of the knee flexors. Active recovery consisted of performing an upper-body strength training session the day after the exercise. Creatine kinase, hamstring strength, and muscle soreness were assessed immediately and 20, 24, and 48 hours after exercise-induced muscle damage. The upper-body strength session, after muscle-damaging exercise accelerated the recovery of slow concentric force (effect size = 0.65; 90% confidence interval = -0.06 to 1.32), but did not affect the recovery kinetics for the other outcomes. The addition of an upper-body strength training session the day after muscle-damaging activity does not negatively affect the recovery kinetics. Upper-body strength training may be programmed the day after a competition.

  14. Evaluation of service-induced damage and restoration of cast turbine blades

    Science.gov (United States)

    Persson, C.; Persson, P.-O.

    1993-08-01

    Conventionally cast turbine blades of Inconel 713C, from a military gas turbine aircraft engine, have been investigated with regard to service-induced microstructural damage and residual creep life time. For cast turbine blades, service life is defined by statistical values. The statistical methods can prove to be uneconomical, because safe limits must be stated with regard to the statistical probability that some blades will have higher damage than normal. An alternative approach is to determine the service-induced microstructural damage on each blade, or a representative number of blades, to better optimize blade us-age. Ways to use service-induced γ rafting and void formation as quantified microstructural damage pa-rameters in a service lifetime prediction model are suggested. The damage parameters were quantified, in blades with different service exposure levels, and correlated to remaining creep life evaluated from creep test specimens taken from different positions of serviced blades. Results from tests with different rejuvenation treatments, including hot isostatic pressing andJor heat treatment, are discussed briefly.

  15. Evaluation of service-induced damage and restoration of cast turbine blades

    Energy Technology Data Exchange (ETDEWEB)

    Persson, C.; Persson, P.O. (Celsius Materialteknik, Linkoeping (Sweden))

    1993-08-01

    Conventionally cast turbine blades of Inconel 713C, from a military gas turbine aircraft engine, have been investigated with regard to service-induced microstructural damage and residual creep life time. For cast turbine blades, service life is defined by statistical values. The statistical methods can prove to be uneconomical, because safe limits must be stated with regard to the statistical probability that some blades will have higher damage than normal. An alternative approach is to determine the service-induced microstructural damage on each blade, or a representative number of blades, to better optimize blade usage. Ways to use service-induced [gamma][prime] rafting and void formation as quantified microstructural damage parameters in a service lifetime prediction model are suggested. The damage parameters were quantified, in blades with different service exposure levels, and correlated to remaining creep life evaluated from creep test specimens taken from different positions of serviced blades. Results from tests with different rejuvenation treatments, including hot isostatic pressing and/or heat treatment, are discussed briefly.

  16. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

    Science.gov (United States)

    Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D.

    2015-01-01

    Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

  17. Correlation between helium atmospheric pressure plasma jet (APPJ) variables and plasma induced DNA damage

    Science.gov (United States)

    Adhikari, Ek R.; Ptasinska, Sylwia

    2016-09-01

    A helium atmospheric pressure plasma jet (APPJ) source with a dielectric capillary and two tubular electrodes was used to induce damage in aqueous plasmid DNA. The fraction of different types of DNA damage (i.e., intact or undamaged, double strand breaks (DSBs), and single strand breaks (SSBs)) that occurred as the result of plasma irradiation was quantified through analysis of agarose gel electrophoresis images. The total DNA damage increased with an increase in both flow rate and duration of irradiation, but decreased with an increase in distance between the APPJ and sample. The average power of the plasma was calculated and the length of APPJ was measured for various flow rates and voltages applied. The possible effects of plasma power and reactive species on DNA damage are discussed.

  18. Statistical evaluation of characteristic SDDLV-induced stress resultants to discriminate between undamaged and damaged elements

    Science.gov (United States)

    Hansen, L. M.; Johansen, R. J.; Ulriksen, M. D.; Tcherniak, D.; Damkilde, L.

    2015-07-01

    The stochastic dynamic damage location vector (SDDLV) method utilizes the vectors from the kernel of a damaged-induced transfer function matrix change to localize damages in a structure. The kernel vectors associated with the lowest singular values are converted into static pseudo-loads and applied alternately to an undamaged reference model with known stiffness matrix, hereby, theoretically, yielding characteristic stress resultants approaching zero in the damaged elements. At present, the discrimination between potentially damaged elements and undamaged ones is typically conducted on the basis of modified characteristic stress resultants, which are compared to a pre-defined tolerance value, without any thorough statistical evaluation. In the present paper, it is tested whether three widely-used statistical pattern-recognition-based damage-detection methods can provide an effective statistical evaluation of the characteristic stress resultants, hence facilitating general discrimination between damaged and undamaged elements. The three detection methods in question enable outlier analysis on the basis of, respectively, Euclidian distance, Hotelling's T2 statistics, and Mahalanobis distance. The study of the applicability of these methods is based on experimentally obtained accelerations of a cantilevered residential-sized wind turbine blade subjected to an unmeasured multi-impulse load. The characteristic stress resultants are derived by applying the static pseudo-loads to a representative finite element (FE) model of the actual blade.

  19. Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage

    Institute of Scientific and Technical Information of China (English)

    Yin LU; Wan-zhou ZHAO; Zai CHANG; Wen-xing CHEN; Lin LI

    2004-01-01

    AIM: To evaluate the inhibitory effects of Vitis vinifera procyanidins (PAs) on carcinogen-induced oxidative stress.METHODS: The single cell gel electrophoresis technique (comet assay) was employed to detect DNA damage induced by the carcinogen phorbol-12-myristate-13-acetate (PMA). The release of hydrogen peroxidase from polymorphonuclear leukocytes (PMNs) was assayed by the horseradish peroxidase-mediated oxidation of phenol red. The microplate assay was used to detect the presence of oxidative products by means of 2',7'-dichlorofiuorescindiacetate (DCFH-DA). The superoxide dismutase (SOD) activity of liver mitochondria was assayed, based on the ability of SOD to inhibit the generation of superoxidate anions by the xanthine-xanthine oxidase system. The malondialdehyde (MDA) level was determined by the thiobarbimric acid (TBA) assay. RESULTS: DNA of NIH3T3 cells was significantly damaged after addition of PMA. The length of the comet tail was observed ,while in normal cells the comet tail could not be observed. PAs showed significant protective effects on carcinogen PMA-induced DNA damage. Through assessment of DCFH-DA oxidation, PAs were shown to inhibit the PMA-induced release of hydrogen peroxide by PMNs, and to inhibit respiratory burst activity in NIH3T3 mouse fibroblasts. Ex vivo study showed that serum from rats administered with PAs displayed similar effects in a dose-dependent manner. In addition, PAs suppressed liver mitochondrial lipid peroxidation induced by PMA. PAs protected the activity of SOD and decreased the level of MDA in liver mitochondria damaged by PMA. CONCLUSION: Dietary PAs from grape seeds protect against carcinogen-induced oxidative cellular and genotoxic damage.

  20. TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition.

    Science.gov (United States)

    Zhao, Jing; Liang, Yuan; Song, Fan; Xu, Shouzhu; Nian, Lun; Zhou, Xuanxuan; Wang, Siwang

    2016-01-01

    Lysophosphatidylcholine (LPC) induces inflammation in endothelial cells (ECs) but the mechanism is not fully understood. The Notch signaling pathway is involved in chronic EC inflammation, but its functions in LPC-induced endothelial inflammatory damage and 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside's (TSG) protective effect during LPC-induced inflammatory damage in human umbilical vein endothelial cells (HUVECs) is largely unknown. We report that Notch signaling activation contributed to LPC-induced injury in HUVECs, and that TSG protected HUVECs from LPC-induced injury by antagonizing Notch signaling activation by LPC. γ-secretase inhibitor (DAPT), a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to inhibit Notch activity. HUVECs were exposed to LPC in the presence or absence of TSG, DAPT, and Notch1 siRNA. LPC treatment of HUVECs resulted in reduced cell viability, and Notch1 and Hes1 upregulation. Either silencing of Notch1 by siRNA or pharmacological inhibition of Notch signaling by DAPT prevented the loss of cell viability, and induction of apoptosis, and enhanced expression Notch1, Hes1 and MCP-1 by LPC in HUVECs. Similarly, TSG reduced LPC stimulation of Notch1, Hes1, and MCP-1 expression, prevented the release of IL-6 and CRP and rescued HUVECs from LPC-induced cell damage. Our data indicate that the Notch signaling pathway is a crucial mediator of endothelial inflammatory damage and that TSG protects against endothelial inflammatory damage by inhibiting the Notch signaling pathway. Our findings suggest that targeting Notch signaling by natural products such as TSG is a promising strategy for the prevention and treatment of chronic inflammation associated diseases, including atherosclerosis. © 2015 IUBMB Life, 68(1):37-50, 2016.

  1. The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats

    OpenAIRE

    Li, Xiaohuan; Yang, Shu; Lv,Xiangyang; Sun, Haimei; Weng, Jing; Liang, Yuanjing; Zhou, Deshan

    2013-01-01

    Objective Cisplatin is a widely used chemotherapeutic agent in the treatment of cancers in clinic; but it often induces adverse effects on ovarian functions such as reduced fertility and premature menopause. Mesna could attenuate the cisplatin-induced ovarian damages; however, the underlying mechanism is still unknown. This study aimed to figure out the underlying mechanism of the protection of mesna for ovaries against cisplatin therapy in cancers. Methods We performed female adult Sprague-D...

  2. Laser induced surface emission of neutral species and its relationship to optical surface damage processes

    Science.gov (United States)

    Chase, L. L.; Smith, L. K.

    1988-03-01

    The laser-induced emission of neutral constituents and impurities from surfaces of several optical materials is shown to be correlated with optical surface damage thresholds. The characteristics of the emission can be utilized to investigate physical processes involved in the absorption of laser energy at the surface. Examples are given of neutral emission correlated with catastrophic surface heating, changes in surface stoichiometry, and thermally-induced cracking.

  3. Investigation of DNA Damage Induced by 7Li and 12C Ions

    Institute of Scientific and Technical Information of China (English)

    SUILi; ZHAOKui; NIMei-nan; GUOJi-yu; LUOHong-bing; MEIJun-ping; KONGFu-quan; LUXiu-qin; ZHOUPing

    2003-01-01

    Deoxyribonucleic acid(DNA) is an important biomacromolecule. It is a carrier of genetic information and a critical target for radiobiological effects. Numerous lesions have been identified in irradiated DNA.DNA double strand breaks (DSBs) are considered as the most important initial damage of all biological effects induced by ionizing radiation. The goal of this experiment is to investigate DNA DSBs induced by heavy ions with atomic force microscopy (AFM).

  4. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

    OpenAIRE

    Dilek Pandir; Betul Unal; Hatice Bas

    2016-01-01

    Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ)-induced diabetic rat kidney. At the end of the experimental period (28 days), we found that lycopene markedly decreased the malondialdehide (MDA) levels in the kidney, urea, uric aci...

  5. NUMERICAL PREDICTION OF FATIGUE DAMAGE IN STEEL CATENARY RISER DUE TO VORTEX-INDUCED VIBRATION

    Institute of Scientific and Technical Information of China (English)

    GAO Yun; ZONG Zhi; SUN Lei

    2011-01-01

    For studying the characteristics of Steel Catenary Riser (SCR), a simplified pinned-pinned cable model of vibration is established. The natural frequencies, the normalized mode shapes and mode curvatures of the SCR are calculated. The fatigue damage of the SCR can be obtained by applying the modal superposition method combined with the parameters of S - N curve.For analyzing the relation between the current velocity and the SCR's fatigue damage induced by the vortex-induced vibration, ten different current states are evaluated. Then, some useful conclusions are drawn, especially an important phenomenon is revealed that the maximum fatigue damage in the riser usually occurs near the area of the boundary ends.

  6. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity

    DEFF Research Database (Denmark)

    Köpper, Frederik; Bierwirth, Cathrin; Schön, Margarete

    2013-01-01

    DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (γH2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed...... replication impaired by gemcitabine or by Chk1 inhibition. This rescue strictly depended on translesion DNA polymerases. In conclusion, instead of being an unavoidable consequence of DNA damage, alterations of replication speed and origin firing depend on MK2-mediated signaling....... knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation...

  7. Antioxidant Protective Effect of Honey in Cigarette Smoke-Induced Testicular Damage in Rats

    Directory of Open Access Journals (Sweden)

    Kuttulebbai Nainamohamed Salam Sirajudeen

    2011-08-01

    Full Text Available Cigarette smoke (CS can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily and honey supplementation (1.2 g/kg daily were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS and glutathione peroxidase (GPx activity, as well as reduced total antioxidant status (TAS and activities of superoxide dismutase (SOD and catalase (CAT. However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

  8. Damage of vascular endothelial barrier induced by explosive blast and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Wang; Jing Chen

    2016-01-01

    In recent years,injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities.Tear.bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage.Vascular endothelial barrier is the main defense of tissues and organs' integrity.This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier,blood-air barrier,and intestinal vascular barrier impairments.In addition,the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

  9. Radiation-damage-induced phasing: a case study using UV irradiation with light-emitting diodes.

    Science.gov (United States)

    de Sanctis, Daniele; Zubieta, Chloe; Felisaz, Franck; Caserotto, Hugo; Nanao, Max H

    2016-03-01

    Exposure to X-rays, high-intensity visible light or ultraviolet radiation results in alterations to protein structure such as the breakage of disulfide bonds, the loss of electron density at electron-rich centres and the movement of side chains. These specific changes can be exploited in order to obtain phase information. Here, a case study using insulin to illustrate each step of the radiation-damage-induced phasing (RIP) method is presented. Unlike a traditional X-ray-induced damage step, specific damage is introduced via ultraviolet light-emitting diodes (UV-LEDs). In contrast to UV lasers, UV-LEDs have the advantages of small size, low cost and relative ease of use.

  10. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1989-08-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

  11. Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

    Science.gov (United States)

    Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

    2015-05-01

    The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

  12. Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

    Directory of Open Access Journals (Sweden)

    José A. Hernández

    2016-01-01

    Full Text Available The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

  13. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan)], E-mail: s-oikawa@doc.medic.mie-u.ac.jp; Kobayashi, Hatasu; Tada-Oikawa, Saeko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); JSPS Research Fellow (Japan); Isono, Yoshiaki [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Kawanishi, Shosuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

    2009-02-10

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H{sub 2}O{sub 2})-resistant clone HP100 cells, suggesting the involvement of H{sub 2}O{sub 2}. In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using {sup 32}P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H{sub 2}O{sub 2} with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis.

  14. Ultrasonic Assessment of Impact-Induced Damage and Microcracking in Polymer Matrix Composites

    Science.gov (United States)

    Gyekanyesi, John (Technical Monitor); Liaw, Benjamin; Villars, Esther; Delmont, Frantz

    2003-01-01

    The main objective of this NASA Faculty Awards for Research (FAR) project is to conduct ultrasonic assessment of impact-induced damage and microcracking in fiber-metal laminated (FML) composites at various temperatures. It is believed that the proposed study of impact damage assessment on FML composites will benefit several NASA's missions and current interests, such as ballistic impact testing of composite fan containment and high strain rate deformation modeling of polymer matrix composites. Impact-induced damage mechanisms in GLARE and ARALL fiber-metal laminates subject to instrumented drop-weight impacts at various temperatures were studied. GLARE and ARALL are hybrid composites made of alternating layers of aluminum and glass- (for GLARE) and aramid- (for ARALL) fiber reinforced epoxy. Damage in pure aluminum panels impacted by foreign objects was mainly characterized by large plastic deformation surrounding a deep penetration dent. On the other hand, plastic deformation in fiber-metal laminates was often not as severe although the penetration dent was still produced. The more stiff fiber-reinforced epoxy layers provided better bending rigidity; thus, enhancing impact damage tolerance. Severe cracking, however, occurred due to the use of these more brittle fiber-reinforced epoxy layers. Fracture patterns, e.g., crack length and delamination size, were greatly affected by the lay-up configuration rather than by the number of layers, which implies that thickness effect was not significant for the panels tested in this study. Immersion ultrasound techniques were then used to assess damages generated by instrumented drop-weight impacts onto these fiber-metal laminate panels as well as 2024-T3 aluminum/cast acrylic sandwich plates adhered by epoxy. Depending on several parameters, such as impact velocity, mass, temperature, laminate configuration, sandwich construction, etc., various types of impact damage were observed, including plastic deformation, radiating

  15. Oxidative stress induces persistent telomeric DNA damage responsible for nuclear morphology change in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Elisa Coluzzi

    Full Text Available One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5 in vitro with hydrogen peroxide (100 and 200 µM for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs, we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.

  16. Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood-Brain Barrier Damage.

    Science.gov (United States)

    Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

    2017-01-01

    Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood-brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption.

  17. Induction of corneal collagen cross-linking in experimental corneal alkali burns in rabbits

    Directory of Open Access Journals (Sweden)

    Marcello Colombo-Barboza

    2014-10-01

    Full Text Available Objective: To evaluate the effect of riboflavin-ultraviolet-A-induced cross-linking (CXL following corneal alkali burns in rabbits. Methods: The right corneas and limbi of ten rabbits were burned using a 1N solution of NaOH and the animals were then divided into two groups: a control group submitted to clinical treatment alone and an experimental group that was treated 1 h after injury with CXL, followed by the same clinical treatment as administered to the controls. Clinical parameters were evaluated post-injury at 1, 7, 15, and 30 days by two independent observers. Following this evaluation, the corneas were excised and examined histologically. Results: There were no statistically significant differences in clinical parameters, such as hyperemia, corneal edema, ciliary injection, limbal ischemia, secretion, corneal neovascularization, symblepharon, or blepharospasm, at any of the time-points evaluated. However, the size of the epithelial defect was significantly smaller in the CXL group (p<0.05 (day 15: p=0.008 and day 30: p=0.008 and the extent of the corneal injury (opacity lesion was also smaller (day 30: p=0.021. Histopathology showed the presence of collagen bridges linking the collagen fibers in only the CXL group. Conclusions: These results suggest that the use of CXL may improve the prognosis of acute corneal alkali burns.

  18. Photodynamic DNA damage induced by phycocyanin and its repair in Saccharomyces cerevisiae

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    M. Pádula

    1999-09-01

    Full Text Available In the present study, we analyzed DNA damage induced by phycocyanin (PHY in the presence of visible light (VL using a set of repair endonucleases purified from Escherichia coli. We demonstrated that the profile of DNA damage induced by PHY is clearly different from that induced by molecules that exert deleterious effects on DNA involving solely singlet oxygen as reactive species. Most of PHY-induced lesions are single strand breaks and, to a lesser extent, base oxidized sites, which are recognized by Nth, Nfo and Fpg enzymes. High pressure liquid chromatography coupled to electrochemical detection revealed that PHY photosensitization did not induce 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo at detectable levels. DNA repair after PHY photosensitization was also investigated. Plasmid DNA damaged by PHY photosensitization was used to transform a series of Saccharomyces cerevisiae DNA repair mutants. The results revealed that plasmid survival was greatly reduced in rad14 mutants, while the ogg1 mutation did not modify the plasmid survival when compared to that in the wild type. Furthermore, plasmid survival in the ogg1 rad14 double mutant was not different from that in the rad14 single mutant. The results reported here indicate that lethal lesions induced by PHY plus VL are repaired differently by prokaryotic and eukaryotic cells. Morever, nucleotide excision repair seems to play a major role in the recognition and repair of these lesions in Saccharomyces cerevisiae.

  19. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    DEFF Research Database (Denmark)

    Kavanagh, J. N.; Currell, F. J.; Timson, D. J.;

    2010-01-01

    Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offe...

  20. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

    NARCIS (Netherlands)

    Jiang, Hong; Schiffer, Eric; Song, Zhangfa; Wang, Jianwei; Zürbig, Petra; Thedieck, Kathrin; Moes, Suzette; Bantel, Heike; Saal, Nadja; Jantos, Justyna; Brecht, Meiken; Jenö, Paul; Hall, Michael N; Hager, Klaus; Manns, Michael P; Hecker, Hartmut; Ganser, Arnold; Döhner, Konstanze; Bartke, Andrzej; Meissner, Christoph; Mischak, Harald; Ju, Zhenyu; Rudolph, K Lenhard

    2008-01-01

    Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase

  1. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation

    NARCIS (Netherlands)

    de Vries, M.; Heijink, Hilde; Gras, R.; den Boef, L. E.; Reinders-Luinge, M.; Pouwels, S. D.; Hylkema, Machteld; van der Toorn, Marco; Brouwer, U.; van Oosterhout, A. J. M.; Nawijn, M. C.

    2014-01-01

    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial

  2. Modeling of combined physical-mechanical moisture induced damage in asphaltic mixes

    NARCIS (Netherlands)

    Kringos, N.

    2007-01-01

    Moisture induced damage in asphaltic mixes is recognized as a major issue, resulting to the need for frequent maintenance operations. This does not only imply high maintenance costs, but also temporary closure of traffic and hence increased road congestion. Given the high costs for the road authorit

  3. Mitochondrial decay is involved in BaP-induced cervical damage.

    Science.gov (United States)

    Gao, Meili; Long, Jiangang; Li, Yongfei; Shah, Walayat; Fu, Ling; Liu, Jiankang; Wang, Yili

    2010-12-01

    Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon and a potent inducer of carcinogenesis. Many studies have reported that the carcinogenic effects of BaP might be due to its intermediate metabolites and to reactive oxygen species (ROS) that cause oxidative damage to the cells. However, the mechanisms of BaP-induced oxidative damage in cervical tissue are still not clear. We studied these mechanisms in female ICR mice treated with BaP either orally or intraperitoneally by measuring (1) several general biomarkers of oxidative stress in serum, (2) mitochondrial function in the cervix, and (3) the morphology of mitochondria in cervical tissue. BaP treatment (1) significantly lowered levels of vitamins A, C, and E and of glutathione; (2) reduced activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferases; and (3) significantly increased lipid peroxidation levels. In addition, significant increases in the levels of superoxide anion, hydrogen peroxide, and hydroxyl radical were observed. These results were confirmed by morphological changes in mitochondria and by decreases in membrane potential levels and in succinate dehydrogenase and malate dehydrogenase activities. The changes in these biomarkers and mitochondrial damage were BaP-dose-dependent and eventually induced both cell apoptosis and necrosis in cervical tissue. As mitochondria are the major sites of ROS generation, these findings show that mitochondrial decay greatly contributes to BaP-induced cervical damage.

  4. Anti- and pro-oxidant effects of (+)-catechin on hemoglobin-induced protein oxidative damage.

    Science.gov (United States)

    Lu, Naihao; Chen, Puqing; Yang, Qin; Peng, Yi-Yuan

    2011-06-01

    Evidence to support the role of heme proteins as major inducers of oxidative damage is increasingly present. Flavonoids have been widely used to ameliorate oxidative damage in vivo and in vitro, where the mechanism of this therapeutic action was usually dependent on their anti-oxidant effects. In this study, we investigated the influence of (+)-catechin, a polyphenol identified in tea, cocoa, and red wine, on hemoglobin-induced protein oxidative damage. It was found that (+)-catechin had the capacities to act as a free radical scavenger and reducing agent to remove cytotoxic ferryl hemoglobin, demonstrating apparent anti-oxidant activities. However, the presence of (+)-catechin surprisingly promoted hemoglobin-induced protein oxidation, which was probably due to the ability of this anti-oxidant to rapidly trigger the oxidative degradation of normal hemoglobin. In addition, hemoglobin-H2O2-induced protein carbonyl formation was significantly enhanced by (+)-catechin at lower concentrations, while it was efficiently inhibited when higher concentrations were used. These novel results showed that the dietary intake and therapeutic use of catechins might possess pro-oxidant activity through aggravating hemoglobin-related oxidative damage. The dual effects on hemoglobin redox reactions may provide new insights into the physiological implications of tea extract and wine (catechins) with cellular heme proteins.

  5. ORGANIC AND INORGANIC ARSENICALS SENSITIZE HUMAN BRONCHIAL EPITHELIAL CELLS TO HYDROGEN PEROXIDE-INDUCED DNA DAMAGE

    Science.gov (United States)

    The lungs are a target organ for arsenic carcinogenesis, however, its mechanism of action remains unclear. Furthermore, it has been suggested that inorganic arsenic (iAs) can potentiate DNA damage induced by other agents. Once inside the human body iAs generally undergoes two ...

  6. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  7. A new CT-based method to quantify radiation-induced lung damage in patients.

    Science.gov (United States)

    Ghobadi, Ghazaleh; Wiegman, Erwin M; Langendijk, Johannes A; Widder, Joachim; Coppes, Robert P; van Luijk, Peter

    2015-10-01

    A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT.

  8. The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Chauché, Caroline; Brown, David M;

    2015-01-01

    as one of the main contributors to nanomaterial (NM) induced adverse effects. One of the most important and widely investigated of these effects is genotoxicity. In general, systems that defend an organism against oxidative damage to DNA are very complex and include prevention of reactive oxygen species...

  9. The Effect of Mangiferin Against Brain Damage Caused by Oxidative Stress and Inflammation Induced by Doxorubicin

    Directory of Open Access Journals (Sweden)

    Soni Siswanto

    2016-04-01

    Full Text Available Doxorubicin (DOX is an anthracycline antibiotic used for anticancer therapy. However, this agent can cause various systemic side effects including cognitive impairments in chronic use. Brain damage due to DOX is caused by an increase of tumor necrosis factor-alpha (TNF-α level in the brain. Increased TNF-α can further lead to chronic inflammation which can lead to neuronal deaths or neurodegenerative diseases. Mangiferin (MAG, a compound extracted from Mangifera indica, has been found neuroprotective activities, but its effect on DOX-induced brain damage is unknown. This study aims to determine the effect of MAG on brain damage induced by DOX. Male Sprague-Dawley rats were induced by DOX intraperitoneally. MAG was given orally at the doses of 30 and 60 mg/kg bw for 7 consecutive weeks. The parameters measured were inflammatory and oxidative stress markers in brain tissue. Coadministration of MAG with DOX reduced inflammation which was marked by the reduction of TNF-α mRNA expression, decreased TNF-α level and reduction of oxidative stress marked by increase of superoxide dismutase level and decrease of malondialdehyde level. In conclusion, MAG was shown to have a neuroprotective effect on brain damage induced by DOX, partly due to inhibition of inflammation and oxidative stress.

  10. DNA Damage and Genomic Instability Induced by Inappropriate DNA Re-replication

    Science.gov (United States)

    2007-04-01

    Li, 2005). Task 2: Establish whether pre-RC reformation , re-initiation or re-elongation induces the DNA damage response. In task 2 of the...300 l of 0.5-mm glass beads (Biospec Products, Bartlesville, OK) and 300 l of SDS-PAGE loading buffer [8% glycerol (vol/vol), 100 mM Tris-HCl, pH

  11. Evaluation of circulating microRNA-92a for endothelial damage induced by percuatenous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    王虹

    2013-01-01

    Objective To explore the role of microRNA-92a(miR-92a) in evaluating endothelium damage induced by percutaneous coronary intervention(PCI). Methods A case control study was prospectively conducted. Fifty-eight patients with ST-segment elevation acute myocardial

  12. Mfd is required for rapid recovery of transcription following UV-induced DNA damage but not oxidative DNA damage in Escherichia coli.

    Science.gov (United States)

    Schalow, Brandy J; Courcelle, Charmain T; Courcelle, Justin

    2012-05-01

    Transcription-coupled repair (TCR) is a cellular process by which some forms of DNA damage are repaired more rapidly from transcribed strands of active genes than from nontranscribed strands or the overall genome. In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions. However, its contribution to the restoration of transcription and to global repair of oxidative damage has not been examined. Here, we report the first direct study of transcriptional recovery following UV-induced and oxidative DNA damage in E. coli. We observed that mutations in mfd or uvrA reduced the rate that transcription recovered following UV-induced damage. In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage. mfd mutants were also fully resistant to hydrogen peroxide (H(2)O(2)) and removed oxidative lesions from the genome at rates comparable to wild-type cells. The results demonstrate that Mfd promotes the rapid recovery of gene expression following UV-induced damage in E. coli. In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.

  13. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  14. Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage.

    Science.gov (United States)

    Dao, Vinh; Pandeswara, Srilakshmi; Liu, Yang; Hurez, Vincent; Dodds, Sherry; Callaway, Danielle; Liu, Aijie; Hasty, Paul; Sharp, Zelton D; Curiel, Tyler J

    2015-05-01

    Cancer prevention is a cost-effective alternative to treatment. In mice, the mTOR inhibitor rapamycin prevents distinct spontaneous, noninflammatory cancers, making it a candidate broad-spectrum cancer prevention agent. We now show that oral microencapsulated rapamycin (eRapa) prevents skin cancer in dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) carcinogen-induced, inflammation-driven carcinogenesis. eRapa given before DMBA/TPA exposure significantly increased tumor latency, reduced papilloma prevalence and numbers, and completely inhibited malignant degeneration into squamous cell carcinoma. Rapamycin is primarily an mTORC1-specific inhibitor, but eRapa did not reduce mTORC1 signaling in skin or papillomas, and did not reduce important proinflammatory factors in this model, including p-Stat3, IL17A, IL23, IL12, IL1β, IL6, or TNFα. In support of lack of mTORC1 inhibition, eRapa did not reduce numbers or proliferation of CD45(-)CD34(+)CD49f(mid) skin cancer initiating stem cells in vivo and marginally reduced epidermal hyperplasia. Interestingly, eRapa reduced DMBA/TPA-induced skin DNA damage and the hras codon 61 mutation that specifically drives carcinogenesis in this model, suggesting reduction of DNA damage as a cancer prevention mechanism. In support, cancer prevention and DNA damage reduction effects were lost when eRapa was given after DMBA-induced DNA damage in vivo. eRapa afforded picomolar concentrations of rapamycin in skin of DMBA/TPA-exposed mice, concentrations that also reduced DMBA-induced DNA damage in mouse and human fibroblasts in vitro. Thus, we have identified DNA damage reduction as a novel mechanism by which rapamycin can prevent cancer, which could lay the foundation for its use as a cancer prevention agent in selected human populations.

  15. Mutant human myocilin induces strain specific differences in ocular hypertension and optic nerve damage in mice.

    Science.gov (United States)

    McDowell, Colleen M; Luan, Tomi; Zhang, Zhang; Putliwala, Tasneem; Wordinger, Robert J; Millar, J Cameron; John, Simon W M; Pang, Iok-Hou; Clark, Abbot F

    2012-07-01

    Elevated intraocular pressure (IOP) is a causative risk factor for the development and progression of glaucoma. Glaucomatous mutations in myocilin (MYOC) damage the trabecular meshwork and elevate IOP in humans and in mice. Animal models of glaucoma are important to discover and better understand molecular pathogenic pathways and to test new glaucoma therapeutics. Although a number of different animal models of glaucoma have been developed and characterized, there are no true models of human primary open angle glaucoma (POAG). The overall goal of this work is to develop the first inducible mouse model of POAG using a human POAG relevant transgene (i.e. mutant MYOC) expression in mouse eyes to elevate IOP and cause pressure-induced damage to the optic nerve. Four mouse strains (A/J, BALB/cJ, C57BL/6J, and C3H/HeJ) were used in this study. Ad5.MYOC.Y437H (5 × 10(7) pfu) was injected intravitreally into one eye, with the uninjected contralateral eye serving as the control eye. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Optic nerve damage was determined by scoring PPD stained optic nerve cross sections. Retinal ganglion cell and superior colliculus damage was assessed by Nissl stain cell counts. Intravitreal administration of viral vector Ad5.MYOC.Y437H caused a prolonged, reproducible, and statistically significant IOP elevation in BALB/cJ, A/J, and C57BL/6J mice. IOPs increased to approximately 25 mm Hg for 8 weeks (p death or superior colliculus damage at the 8-week time point in any of the strains tested. These results demonstrate strain dependent responses to Ad5.MYOC.Y437H-induced ocular hypertension and pressure-induced optic nerve damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Effect of Mitomycin-C augmented trabeculectomy on corneal endothelial cells

    Directory of Open Access Journals (Sweden)

    Reza Zarei

    2015-01-01

    Conclusion: MMC application in trabeculectomy seems to cause a small but significant corneal endothelial loss. Most of the damage occurs intraoperatively, or in the early postoperative period, however progressive endothelial cell loss is not a major concern.

  17. Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

    Directory of Open Access Journals (Sweden)

    Zhao-Qin Hao

    2016-11-01

    Full Text Available AIM: To observe the therapeutic effect of corneal collagen cross-linking (CXL in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS: New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each. The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM at 4wk. RESULTS: A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P<0.05. The corneal epithelium defect areas of the combined group was smaller than that of the CXL group (P<0.05 on 7 and 14d, but there were no statistical differences on 3, 21 and 28d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28d. The diameters of the corneal collagen fiber bundles (42.960±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group were thicker than that of the control group (24.900±1.868 nm, but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION: CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.

  18. Molecular mechanism of the inhibition effect of Lipoxin A4 on corneal dissolving pathology process

    Directory of Open Access Journals (Sweden)

    Hong-Yan Zhou

    2013-02-01

    Full Text Available AIM: Excessive dissolve of corneal tissue induced by MMPs which were activated by cytokins and chemokines will lead to corneal ulcer. The molecular mechanism of Lipoxin A4 (LXA4 on corneal collagen degradation in three dimensions was investigated.METHODS:Rabbit corneal fibroblasts were harvested and suspended in serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal fibroblast suspension were mixed on ice. The resultant mixture solidified in an incubator, after which test reagents and plasminogen was overlaid and the cultures were returned to the incubator. The supernatants from collagen gel incubations were collected and the amount of hydroxyproline in the hydrolysate was measured. Immunoblot analysis of MMP-1, -3 and TMMP-1,-2 was performed. MMP-2,-9 was detected by the method of Gelatin zymography. Cytotoxicity assay was measured.RESULTS:LXA4 inhibited corneal collagen degradation in a dose and time manner. LXA4 inhibited the IL-1β induced increases in the pro-MMP-1, -2, -3, -9 and active MMP-1, -2, -3, -9 in a concentration dependent manner. LXA4 could also inhibit the IL-1β induced increases in TIMP-1, -2.CONCLUSION: As a potent anti-inflammation reagent, LXA4 can inhibit corneal collagen degradation induced by IL-1β in corneal fibroblasts thus inhibiting corneal dissolving pathology process.

  19. Few-cycle pulse laser induced damage threshold determination of ultra-broadband optics.

    Science.gov (United States)

    Kafka, Kyle R P; Talisa, Noah; Tempea, Gabriel; Austin, Drake R; Neacsu, Catalin; Chowdhury, Enam A

    2016-12-12

    A systematic study of few-cycle pulse laser induced damage threshold (LIDT) determination was performed for commercially-available ultra-broadband optics, (i.e. chirped mirrors, silver mirrors, beamsplitters, etc.) in vacuum and in air, for single and multi-pulse regime (S-on-1). Multi-pulse damage morphology at fluences below the single-pulse LIDT was studied in order to investigate the mechanisms leading to the onset of damage. Stark morphological contrast was observed between multi-pulse damage sites formed in air versus those in vacuum. One effect of vacuum testing compared to air included suppression of laser-induced periodic surface structures (LIPSS) formation, possibly influenced by a reduced presence of damage debris. Another effect of vacuum was occasional lowering of LIDT, which appears to be due to the stress-strain performance of the coating design during laser irradiation and under the external stress of vacuum ambience. A fused silica substrate is also examined, and a non-LIPSS nanostructuring is observed on the surface. Possible mechanisms are discussed.

  20. Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells.

    Science.gov (United States)

    Zhang, Zhuhong; Chen, Si; Mei, Hu; Xuan, Jiekun; Guo, Xiaoqing; Couch, Letha; Dobrovolsky, Vasily N; Guo, Lei; Mei, Nan

    2015-09-30

    Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.

  1. Using ultra-sensitive next generation sequencing to dissect DNA damage-induced mutagenesis

    Science.gov (United States)

    Wang, Kaile; Ma, Xiaolu; Zhang, Xue; Wu, Dafei; Sun, Chenyi; Sun, Yazhou; Lu, Xuemei; Wu, Chung-I; Guo, Caixia; Ruan, Jue

    2016-01-01

    Next generation sequencing (NGS) technologies have dramatically improved studies in biology and biomedical science. However, no optimal NGS approach is available to conveniently analyze low frequency mutations caused by DNA damage treatments. Here, by developing an exquisite ultra-sensitive NGS (USNGS) platform “EasyMF” and incorporating it with a widely used supF shuttle vector-based mutagenesis system, we can conveniently dissect roles of lesion bypass polymerases in damage-induced mutagenesis. In this improved mutagenesis analysis pipeline, the initial steps are the same as in the supF mutation assay, involving damaging the pSP189 plasmid followed by its transfection into human 293T cells to allow replication to occur. Then “EasyMF” is employed to replace downstream MBM7070 bacterial transformation and other steps for analyzing damage-induced mutation frequencies and spectra. This pipeline was validated by using UV damaged plasmid after its replication in lesion bypass polymerase-deficient 293T cells. The increased throughput and reduced cost of this system will allow us to conveniently screen regulators of translesion DNA synthesis pathway and monitor environmental genotoxic substances, which can ultimately provide insight into the mechanisms of genome stability and mutagenesis. PMID:27122023

  2. Investigation on the effect of developed product and new food for radiation-induced skin damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop [Chonnam National University, Gwangju (Korea, Republic of)

    2007-07-15

    In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

  3. Effectiveness of Disaster-prevention Technologies against Quake-induced Damage of MR Scanners during the Great East Japan Earthquake.

    Science.gov (United States)

    Yamaguchi-Sekino, Sachiko; Machida, Yoshio; Tsuchihashi, Toshio; Isoda, Haruo; Noguchi, Takashi; Nakai, Toshiharu

    2016-01-01

    In the present study, we have performed a statistical analysis to investigate damages in magnetic resonance (MR) scanners caused by the Great East Japan Earthquake (GEJE, magnitude 9.0) and evaluated whether these disaster-prevention technologies contributed to the reduction of damages in the GEJE or not. It was confirmed that the extent of damage was significantly different between seismic scale (SS) 5 and SS over 6. Our survey study demonstrated that anchoring of MR facilities reduced damages due to quakes and demonstrated that anchoring is an efficient method for quake-induced damage prevention. The odds ratio revealed that base isolation was very useful to prevent damages in MR scanners.

  4. Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Johansson, Sofie L.; Tan, Qihua; Holst, René;

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  5. Corneal tissue welding with infrared laser irradiation after clear corneal incision.

    Science.gov (United States)

    Rasier, Rfat; Ozeren, Mediha; Artunay, Ozgür; Bahçecioğlu, Halil; Seçkin, Ismail; Kalaycoğlu, Hamit; Kurt, Adnan; Sennaroğlu, Alphan; Gülsoy, Murat

    2010-09-01

    The aim of this study was to investigate the potential of infrared lasers for corneal welding to seal corneal cuts done in an experimental animal model. Full-thickness corneal cuts on freshly enucleated bovine eyes were irradiated with infrared (809-nm diode, 980-nm diode, 1070-nm YLF, and 1980-nm Tm:YAP) lasers to get immediate laser welding. An 809-nm laser was used with the topical application of indocyanine green to enhance the photothermal interaction at the weld site. In total, 60 bovine eyes were used in this study; 40 eyes were used in the first part of the study for the determination of optimal welding parameters (15 eyes were excluded because of macroscopic carbonization, opacification, or corneal shrinkage; 2 eyes were used for control), and 20 eyes were used for further investigation of more promising lasers (YLF and Tm:YAP). Laser wavelength, irradiating power, exposure time, and spot size were the dose parameters, and optimal dose for immediate closure with minimal thermal damage was estimated through histological examination of welded samples. In the first part of the study, results showed that none of the applications was satisfactory. Full-thickness success rates were 28% (2 of 7) for 809-nm and for 980-nm diode lasers and 67% (2 of 3) for 1070-nm YLF and (4 of 6) for 1980-nm Tm:YAP lasers. In the second part of the study, YLF and Tm:YAP lasers were investigated with bigger sample size. Results were not conclusive but promising again. Five corneal incisions were full-thickness welded out of 10 corneas with 1070-nm laser, and 4 corneal incisions were partially welded out of 10 corneas with 1980-nm laser in the second part of the study. Results showed that noteworthy corneal welding could be obtained with 1070-nm YLF laser and 1980-nm Tm:YAP laser wavelengths. Furthermore, in vitro and in vivo studies will shed light on the potential usage of corneal laser welding technique.

  6. Hepatoprotective activity of Amomum subulatum Roxb against ethanol-induced liver damage

    Directory of Open Access Journals (Sweden)

    Parmar Mihir

    2009-01-01

    Full Text Available The hepatoprotective activity of methanolic extract of Amomum subulatum Roxb (Zingiberaceae seeds was studied against 20 % ethanol (3.76 g/kg/days, p.o for 18 days induced liver damage in rats. Ethanol produced significant changes in various liver parameters such as functional (thiopentone-induced sleeping time and physical (increased liver weight and volume. It also increased the biochemical parameters such as serum glutamate oxaloacetic transaminase and glutamate pyruvic transaminase, alkaline phosphatase, total and direct bilirubin, total cholesterol, triglyceride and decreased total protein along with changes in histological parameters (damage to hepatocytes. Treatment with methanolic extract of A. subulatum (100 and 300 mg/kg/day, p.o. for 18 days and silymarin significantly prevented the functional, physical, biochemical and histological changes induced by ethanol, indicating the recovery of hepatic cells. These results demonstrate that methanolic extract of A. subulatum seeds possessed the hepatoprotective activity.

  7. Gold nanoparticles' blocking effect on UV-induced damage to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Calzolai, Luigi, E-mail: luigi.calzolai@jrc.ec.europa.eu; Laera, Stefania; Ceccone, Giacomo; Gilliland, Douglas [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy); Hussain, Rohanah; Siligardi, Giuliano [Diamond Light Source (United Kingdom); Rossi, Francois [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy)

    2013-01-15

    Ultraviolet radiation can cause the unfolding and destabilization of proteins. By using high energy photons from a synchrotron radiation source, we show that the UV-induced destabilization of human serum albumin (HSA) can be detected and monitored by measuring the circular dichroism spectrum of the protein. The high flux radiation source damages the HSA protein by causing a partial unfolding of the protein and a significant reduction in the amount of its secondary structure. Gold nanoparticles can effectively stop this UV-induced unfolding of HSA caused by synchrotron radiation. These phenomena could offer interesting applications to protect HSA protein from UV-induced damage and provide an alternative method to measure the relative stability of HSA.

  8. Photoelectrochemical Sensors for the Rapid Detection of DNA Damage Induced by Some Nanoparticles

    Directory of Open Access Journals (Sweden)

    M. Jamaluddin Ahmed

    2010-06-01

    Full Text Available Photoelectrochemcal sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DNA damage is detected by monitoring the change of photocurrent of the indicator. In one sensor configuration, a DNA intercalator, Ru(bpy2 (dppz2+ [bpy=2, 2′ -bipyridine, dppz=dipyrido( 3, 2-a: 2′ 3′-c phenazine], was employed as the photoelectrochemical indicator. The damaged DNA on the sensor bound lesser Ru(bpy2 (dppz2+ than the intact DNA, resulting in a drop in photocurrent. In another configuration, ruthenium tris(bipyridine was used as the indicator and was immobilized on the electrode underneath the DNA layer. After oxidative damage, the DNA bases became more accessible to photoelectrochemical oxidation than the intact DNA, producing a rise in photocurrent. Both sensors displayed substantial photocurrent change after incubation in titanium dioxide / polystyrene solution in a time – dependent manner. According to the data, damage of the DNA film was completed in 1h in titanium dioxide / polystyrene solution. In addition, the titanium dioxide induced much more sever damage than polysterene. The results were verified independently by gel electrophoresis and UV-Vis absorbance experiments. The photoelectrochemical reaction can be employed as a new and inexpensive screening tool for the rapid assessment of the genotoxicity of existing and new chemicals.

  9. The DNA damage response induced by infection with human cytomegalovirus and other viruses.

    Science.gov (United States)

    Xiaofei, E; Kowalik, Timothy F

    2014-05-23

    Viruses use different strategies to overcome the host defense system. Recent studies have shown that viruses can induce DNA damage response (DDR). Many of these viruses use DDR signaling to benefit their replication, while other viruses block or inactivate DDR signaling. This review focuses on the effects of DDR and DNA repair on human cytomegalovirus (HCMV) replication. Here, we review the DDR induced by HCMV infection and its similarities and differences to DDR induced by other viruses. As DDR signaling pathways are critical for the replication of many viruses, blocking these pathways may represent novel therapeutic opportunities for the treatment of certain infectious diseases. Lastly, future perspectives in the field are discussed.

  10. Heavy Metal-Induced Oxidative DNA Damage in Earthworms: A Review

    Directory of Open Access Journals (Sweden)

    Takeshi Hirano

    2010-01-01

    Full Text Available Earthworms can be used as a bio-indicator of metal contamination in soil, Earlier reports claimed the bioaccumulation of heavy metals in earthworm tissues, while the metal-induced mutagenicity reared in contaminated soils for long duration. But we examined the metal-induced mutagenicity in earthworms reared in metal containing culture beddings. In this experiment we observed the generation of 8-oxoguanine (8-oxo-Gua in earthworms exposed to cadmium and nickel in soil. 8-oxo-Gua is a major premutagenic form of oxidative DNA damage that induces GC-to-TA point mutations, leading to carcinogenesis.

  11. Ampelopsin protects endothelial cells from hyperglycemia-induced oxidative damage by inducing autophagy via the AMPK signaling pathway.

    Science.gov (United States)

    Liang, Xinyu; Zhang, Ting; Shi, Linying; Kang, Chao; Wan, Jing; Zhou, Yong; Zhu, Jundong; Mi, Mantian

    2015-01-01

    Diabetic angiopathy is a major diabetes-specific complication that often begins with endothelial dysfunction induced by hyperglycemia; however, the pathological mechanisms of this progression remain unclear. Ampelopsin is a natural flavonol that has strong antioxidant activity, but little information is available regarding its antidiabetic effect. This study focused on the effect of ampelopsin on hyperglycemia-induced oxidative damage and the underlying mechanism of this effect in human umbilical vein endothelial cells (HUVECs). We found that hyperglycemia impaired autophagy in HUVECs through the inhibition of AMP-activated protein kinase (AMPK), which directly led to endothelial cell damage. Ampelopsin significantly attenuated the detrimental effect of hyperglycemia-induced cell dysfunction in a concentration-dependent manner in HUVECs. Ampelopsin significantly upregulated LC3-II, Beclin1, and Atg5 protein levels but downregulated p62 protein levels in HUVECs. Transmission electron microscopy and confocal microscopy indicated that ampelopsin notably induced autophagosomes and LC3-II dots, respectively. Additionally, the autophagy-specific inhibitor 3-MA, as well as Atg5 and Beclin1 siRNA pretreatment, markedly attenuated ampelopsin-induced autophagy, which subsequently abolished the protective effect of ampelopsin against hyperglycemia in HUVECs. Moreover, ampelopsin also increased AMPK activity and inhibited mTOR (mammalian target of rapamycin) complex activation. Ampelopsin-induced autophagy was attenuated by the AMPK antagonist compound C but strengthened by the AMPK agonist AICAR (5-minoimidazole-4-carboxamide ribonucleotide). Furthermore, AMPK siRNA transfection eliminated ampelopsin's alleviation of cell injury induced by hyperglycemia. The protective effect of ampelopsin against hyperglycemia-induced cell damage, which functions by targeting autophagy via AMPK activation, makes it a promising pharmacological treatment for type-2 diabetes.

  12. Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

    Science.gov (United States)

    Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

    2015-01-01

    Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients.

  13. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  14. Delayed repair of radiation induced clustered DNA damage: Friend or foe?

    Energy Technology Data Exchange (ETDEWEB)

    Eccles, Laura J., E-mail: laura.eccles@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); O' Neill, Peter, E-mail: peter.oneill@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Lomax, Martine E., E-mail: martine.lomax@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2011-06-03

    A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a 'friend', leading to cell killing in tumour cells or as a 'foe', resulting in the formation of mutations and genetic instability in normal tissue.

  15. Photorefractive keratectomy combined with corneal wavefront-guided and hyperaspheric ablation profiles to correct myopia.

    Science.gov (United States)

    Lee, Hun; Park, Si Yoon; Yong Kang, David Sung; Ha, Byoung Jin; Choi, Jin Young; Kim, Eung Kweon; Seo, Kyoung Yul; Kim, Tae-Im

    2016-06-01

    To evaluate the effects of photorefractive keratectomy (PRK) combined with corneal wavefront-guided ablation profiles and hyperaspheric ablation profiles on changes in higher-order aberrations (HOAs). Yonsei University College of Medicine and Eyereum Clinic, Seoul, South Korea. Comparative observational case series. Medical records of patients who had corneal wavefront-guided hyperaspheric PRK, corneal wavefront-guided mild-aspheric PRK, or non-corneal wavefront-guided mild-aspheric PRK were analyzed. The logMAR uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), and changes in corneal aberrations (root-mean-square [RMS] HOAs, spherical aberration, coma) were evaluated 1, 3, and 6 months postoperatively. The records of 61 patients (96 eyes) were reviewed. There was no statistically significant difference in logMAR UDVA or MRSE between the 3 groups at any timepoint. Corneal RMS HOAs were significantly smaller in the corneal wavefront-guided hyperaspheric group and the corneal wavefront-guided mild-aspheric group than in the noncorneal wavefront-guided mild-aspheric group at each timepoint. Corneal spherical aberration was significantly smaller for corneal wavefront-guided hyperaspheric PRK than for noncorneal wavefront-guided mild-aspheric PRK 6 months postoperatively. Changes in corneal spherical aberration (preoperatively and 6 months postoperatively) in corneal wavefront-guided hyperaspheric PRK were significantly smaller than in corneal wavefront-guided mild-aspheric PRK (P = .046). Corneal coma was significantly smaller with corneal wavefront-guided hyperaspheric PRK and corneal wavefront-guided mild-aspheric PRK than with noncorneal wavefront-guided mild-aspheric PRK 3 months and 6 months postoperatively. Corneal wavefront-guided hyperaspheric PRK induced less corneal spherical aberration 6 months postoperatively than corneal wavefront-guided mild-aspheric PRK and noncorneal wavefront-guided mild-aspheric PRK

  16. Comparison of radiation damage in silicon induced by proton and neutron irradiation

    CERN Document Server

    Ruzin, A; Glaser, M; Zanet, A; Lemeilleur, F; Watts, S

    1999-01-01

    The subject of radiation damage to Si detectors induced by 24-GeV/c protons and nuclear reactor neutrons has been studied. Detectors fabricated on single-crystal silicon enriched with various impurities have been tested. Significant differences in electrically active defects have been found between the various types of material. The results of the study suggest for the first time that the widely used nonionizing energy loss (NIEL) factors are insufficient for normalization of the electrically active damage in case of oxygen- and carbon-enriched silicon detectors. It has been found that a deliberate introduction of impurities into the semiconductor can affect the radiation hardness of silicon detectors. (16 refs).

  17. Deformation-induced damage and recovery in model hydrogels - A molecular dynamics simulation

    Science.gov (United States)

    Zidek, Jan; Milchev, Andrey; Jancar, Josef; Vilgis, Thomas A.

    2016-09-01

    Using molecular dynamics simulation of a model hybrid cross-link hydrogel, we investigate the network damage evolution and the related structure transformations. We model the hydrogel structure as a network-connected assembly of crosslinked clusters whereby deformation-induced damage is considered along with network recovery. The two principal mechanisms involved in hydrogel recovery from deformation include segment hops of the building structure units (segments) between clusters and cluster shape modification. These mechanisms act either instantaneously, or with a certain time delay after the onset of deformation. By elucidating the conditions under which one of the mechanisms prevails, one may design hydrogel materials with a desired response to deformation.

  18. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kong, Wei-Yuan; Tong, Li-Quan; Zhang, Hai-Jun; Cao, Yong-Gang; Wang, Gong-Chen; Zhu, Jin-Zhi; Zhang, Feng; Sun, Xue-Ying; Zhang, Tie-Hui; Zhang, Lin-Lin

    2016-01-01

    Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

  19. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Wei-Yuan Kong

    2016-01-01

    Full Text Available Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg−1 in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg−1 , NPS-2390 (an antagonist of CaSR, 0.20 g kg−1 , or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA, lower superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK, p38, and extracellular signaling-regulated kinase (ERK 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

  20. Increased sensitivity to light-induced damage in a mouse model of autosomal dominant retinal disease.

    Science.gov (United States)

    White, D Alan; Fritz, Jason J; Hauswirth, William W; Kaushal, Shalesh; Lewin, Alfred S

    2007-05-01

    To describe a sensitivity to light-induced damage associated with expression of a T17M mutant human rhodopsin (hT17M) transgene in mice, with the goal of minimizing retinal injury during the subretinal delivery of rAAV-mediated gene therapy. Mice were bred to express the hT17M rhodopsin transgene in a line that was hemizygous null for wild-type mouse rhodopsin (mrho(+/-)), and the eyes of transgenic mice and nontransgenic littermates were exposed for 2.5 minutes to unilateral illumination with fiber-optic light ranging from 5,000 to 10,000 lux. Funduscopic images were made with a handheld camera (Genesis; Kowa Company, Ltd., Tokyo, Japan). Full-field scotopic electroretinographic analysis (ERG) was performed to measure loss of retinal function. Morphometry in the light microscope was used to measure loss of rod photoreceptors. TUNEL staining and a nucleosome release assay were used to measure levels of apoptosis in retinal specimens. mrho(+/-);hT17M mice exhibited a sensitivity to light-induced damage that caused severe loss of a- and b-wave ERG responses. hT17M transgenic mice on the mrho(+/+) background were equally sensitive to light-induced damage. Histologic analysis showed a concomitant loss of photoreceptors and TUNEL labeling of fragmented DNA in rod photoreceptor cells, demonstrating that the damage occurred via an apoptotic pathway. Nontransgenic littermate mice were not affected by this exposure to light. Mice expressing an hP23H mutant human rhodopsin transgene were minimally sensitive to light-induced damage at these intensities, in comparison to hT17M mice. Treating the hT17M mice with an equivalent regimen of exposure to red light was less damaging to the retina, as measured by ERG and histology. Expression of a human hT17M mutant rhodopsin transgene in mice is associated with photoreceptor apoptosis in response to moderate exposure to light. This phenotype was not observed in nontransgenic littermates or in mice expressing an hP23H mutant human

  1. Substratum topography modulates corneal fibroblast to myofibroblast transformation.

    Science.gov (United States)

    Myrna, Kathern E; Mendonsa, Rima; Russell, Paul; Pot, Simon A; Liliensiek, Sara J; Jester, James V; Nealey, Paul F; Brown, Donald; Murphy, Christopher J

    2012-02-01

    The transition of corneal fibroblasts to the myofibroblast phenotype is known to be important in wound healing.