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Sample records for corneal edema induced

  1. Corneal edema induced by cold in trigeminal nerve palsy

    SciTech Connect

    Thorgaard, G.L.; Holland, E.J.; Krachmer, J.H.

    1987-05-15

    We examined a 34-year-old man who complained of decreased visual acuity in the right eye when exposed to cold environmental temperatures. Although examination at room temperature was unremarkable, he developed prominent unilateral corneal edema of the right eye when placed in a cold room at 4 C. Corneal thickness increased from 525 to 789 microns in the affected eye. Further examination disclosed a right-sided trigeminal nerve palsy. He was eventually found to have a 3 X 2-cm tentorial ridge meningioma on the right.

  2. Silicone elastomer lens wear induces less overnight corneal edema than sleep without lens wear.

    PubMed

    Sweeney, D F; Holden, B A

    1987-12-01

    Corneal thickness was measured on awakening in both eyes of ten subjects who slept with a silicone elastomer lens in one eye only. The mean corneal edema level with the silicone lens after eight hours of sleep was 2.0 +/- 2.0% and was significantly lower (p less than 0.01) than the level in the eye that did not wear a lens (3.6 +/- 2.1%). This indicates that the oxygen level supplied to the anterior cornea during sleep with silicone elastomer lenses is higher than without a lens. We hypothesize that the lower overnight swelling with the silicone lenses is a result of reduced resistance to oxygen flow from the eyelid capillaries to the corneal epithelial cells possibly due to decreased tear film thickness. Other possible explanations include insulating the cornea from the hypo-osmotic shift that occurs with sleep.

  3. Oxygen-deficient metabolism and corneal edema.

    PubMed

    Leung, B K; Bonanno, J A; Radke, C J

    2011-11-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem-Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema.

  4. Oxygen-deficient metabolism and corneal edema

    PubMed Central

    Leung, B.K.; Bonanno, J.A.; Radke, C.J.

    2014-01-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

  5. Corona sign: manifestation of peripheral corneal epithelial edema as a possible marker of the progression of corneal endothelial dysfunction.

    PubMed

    Inoue, Tomoyuki; Hara, Yuko; Kobayashi, Takeshi; Zheng, Xiaodong; Suzuki, Takashi; Shiraishi, Atsushi; Ohashi, Yuichi

    2016-09-01

    To describe a characteristic form of the corona sign and its clinical relevance to the degree of corneal endothelial decompensation and investigate the underlying mechanism using a rabbit model. These observational cases include 31 patients undergoing penetrating keratoplasty (PKP) and 15 patients undergoing Descemet stripping automated endothelial keratoplasty (DSAEK) with special attention to the circumferentially developed corneal epithelial edema. We also conducted a laboratory observation of horizontal water flow in the rabbit cornea. We consistently observed the corona sign at the superior periphery during the initial stage of corneal endothelial decompensation after PKP. With progressive corneal endothelial cellular loss, the epithelial edema gradually expanded circumferentially in the periphery. The endothelial cellular density associated with the corona sign significantly (P < 0.01) decreased compared with that without the sign. The endothelial cellular density decreased significantly (P < 0.05) in cases with a circumferential corona sign compared with a superior corona sign. After DSAEK, however, the corneal epithelial edema subsided from the center but persisted peripherally as a corona sign in all cases. By 3 months postoperatively, the epithelial edema was confined to the superior periphery along with uneventful corneal endothelial healing. Rabbit experiments showed that total corneal endothelial decompensation decreased the horizontal intracorneal water migration (Inoue-Ohashi phenomenon) in the corneal periphery and induced peripheral corneal edema. The slit-lamp microscopic findings of the corona-like epithelial edema in the peripheral cornea are associated with the stage of corneal endothelial function. To support this, the developmental mechanism of the corona sign was demonstrated experimentally.

  6. Methylene blue-related corneal edema and iris discoloration.

    PubMed

    Timucin, Ozgur Bulent; Karadag, Mehmet Fatih; Aslanci, Mehmet Emin; Baykara, Mehmet

    2016-04-01

    We report the case of a 70-year-old female patient who developed corneal edema and iris discoloration following the inadvertent use of 1% methylene blue instead of 0.025% trypan blue to stain the anterior capsule during cataract phacoemulsification surgery. Copious irrigation was performed upon realization of incorrect dye use. Corneal edema and iris discoloration developed during the early postoperative period and persisted at 24-months follow-up. However, keratoplasty was not required. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Copious irrigation for at least 30 min using an anterior chamber maintainer may improve outcomes.

  7. UUnilateral corneal edema caused by a hidden foreign body.

    PubMed

    Galvis, V; Tello, A; Frederick, G A; Laiton, A N

    2017-09-01

    A middle-aged adult male was referred to our institution due to unilateral corneal edema for a possible corneal transplant. At first, the patient denied a history of trauma. A small foreign body, which had been overlooked by the primary ophthalmologist, was detected by gonioscopy, embedded in the anterior chamber angle. It was successfully surgically removed and visual results were good. In any patient with unilateral unexplained corneal edema, it is necessary to rule out the presence of a foreign body in the anterior chamber. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency.

    PubMed

    Hos, Deniz; Bukowiecki, Anne; Horstmann, Jens; Bock, Felix; Bucher, Franziska; Heindl, Ludwig M; Siebelmann, Sebastian; Steven, Philipp; Dana, Reza; Eming, Sabine A; Cursiefen, Claus

    2017-08-03

    Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema. Pharmacological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thickness due to delayed drainage of corneal edema and a trend towards prolonged corneal opacification. Notably, lymphatics are also detectable in the cornea of a patient with acute edema due to spontaneous Descemet´s (basement) membrane rupture in keratoconus, mimicking this animal model and highlighting the clinical relevance of lymphangiogenesis in corneal fluid homeostasis. Together, our findings provide evidence that lymphangiogenesis plays an unexpectedly beneficial role in the regulation of corneal edema and transparency. This might open new treatment options in blinding diseases associated with corneal edema and transparency loss. Furthermore, we demonstrate for the first time that physiological lymphangiogenesis also occurs in primarily avascular sites.

  9. Vessel Cauterization as a Therapeutic Adjunct in Persistent Disciform Corneal Stromal Edema

    PubMed Central

    Muideen, Lasisi Akinola; Shiela, Ezeronye Ugochi

    2014-01-01

    This is a case report of a symptomatic non-clearing, vascularized, disciform, corneal stromal edema with a feeder vessel that has remained refractory to medical therapy of antiviral, steroid, and antibiotics, for a period of three weeks, but showed a rapid improvement in visual acuity of 0.1 Log mar within five days of feeder vessel cauterization, together with improvement of two psychometric scales in corneal cloudiness on a scale range of 0 to 3, clinical evidence of resolution of corneal edema, and subjective resolution of the patient's symptoms. Cauterization was done under magnification with a ball cautery point warmed in a spirit lamp following topical anesthesia. This intervention may become handy in difficult non-clearing corneal edema and prevent blinding consequences, in a low-resource facility, in selected applicable cases. PMID:25191102

  10. Corneal toxicity induced by vesicating agents and effective treatment options

    PubMed Central

    Goswami, Dinesh G.; Tewari-Singh, Neera; Agarwal, Rajesh

    2016-01-01

    The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

  11. A Surprising Cause for Corneal Edema after Cataract Surgery: A Missed Posterior Chamber Intraocular Lens Haptic Remnant.

    PubMed

    Elyashiv, Sivan; Barequet, Irina

    2015-01-01

    We present a case of retained intraocular lens (IOL) haptic segment in the anterior chamber, diagnosed seven months following a reportedly uneventful cataract surgery due to manifestation of inferior corneal edema. Specular microscopy revealed low endothelial counts of 513/mm(2). Upon diagnosis, prompt surgical removal of the IOL haptic segment resulted in rapid resolution of the corneal edema within a week. Despite the clearing of the cornea, no improvement in the visual acuity occurred and cystoid macular edema was diagnosed and treated with topical anti-inflammatory agents and two intra-vitreal anti-VEGF injections, followed by complete resolution of ocular findings and improvement of the visual acuity.

  12. Corneal Biomechanical Findings in Contact Lens Induced Corneal Warpage

    PubMed Central

    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

  13. Pulmonary edema induced by intravenous ethchlorvynol.

    PubMed

    Conces, D J; Kreipke, D L; Tarver, R D

    1986-11-01

    The intravenous injection of ethchlorvynol is an uncommon cause of noncardiac pulmonary edema. Two cases of intravenous ethchlorvynol-induced pulmonary edema are presented. The patients fell asleep after injecting the liquid contents of Placydil capsules (ethchlorvynol) and awoke several hours later with severe dyspnea. Arterial blood gases demonstrated marked hypoxia. Chest radiographs revealed bilateral diffuse alveolar densities. The patients' symptoms and radiographic findings resolved after several days of supportive care. Changes in the lung caused by ethchlorvynol may be the result of direct effect of the drug on the lung.

  14. Comparison of the effects of bevacizumab and ranibizumab injection on corneal angiogenesis in an alkali burn induced model

    PubMed Central

    Dursun, Ayhan; Arici, Mustafa Kemal; Dursun, Feyza; Ozec, Ayse Vural; Toker, Mustafa Ilker; Erdogan, Haydar; Topalkara, Aysen

    2012-01-01

    AIM To investigate the effects of bevacizumab and ranibizumab on corneal neovascularization in an alkali burn-induced model of corneal angiogenesis. METHODS Fifteen Wistar albino rats were divided randomly into 3 groups after chemical cauterization of the cornea. The first group received a single dose of 0.1mL saline solution as a control group whereas second and third groups received a single dose of 2.5mg bevacizumab or 1mg ranibizumab by subconjunctival injection, respectively. After three weeks, the rat corneas were evaluated by biomicroscopy and corneal photographs were taken. The percentage of neovascularization area, length of the longest new vessel, corneal edema and corneal opacity scores were assessed. RESULTS The analysis of digital photographs showed that the percentage of neovascularization area to the total corneal area, the length of the longest new vessel, corneal edema and opacity scores were significantly lower in both study groups compared to the control group (P<0.05). Additionally, the percentage of corneal neovascularization area, the length of the longest new vessel and corneal opacity score were less with bevacizumab than ranibizumab. CONCLUSION Subconjunctival bevacizumab and ranibizumab treatments may be effective methods in reducing corneal neovascularization. Furthermore, bevacizumab is more effective than ranibizumab in the inhibition of corneal neovascularization. PMID:22937503

  15. Corneal edema after overnight lid closure of rabbits wearing silicone rubber contact lenses.

    PubMed

    Koch, J M; Refojo, M F; Leong, F L

    1991-03-01

    Elastofilcon A silcone rubber contact lenses induce less corneal swelling than no lens wear during sleep, and increasing the central thickness and volume of the lens does not influence its overnight performance. We sought to elucidate whether a silicone rubber lens can promote the distribution of atmospheric O2 on the cornea through a small interpalpebral opening under closed-eye conditions. Three groups of rabbit eyes comprised 12 eyes wearing Silflex (Dk 79.8 barrer) lenses, 12 with elastofilcon A (Dk 340 barrer) lenses, and 12 without lenses. All eyes were surgically closed overnight; six eyes in each group had a complete lid closure and six eyes had a partial tarsorrhaphy that left a small, central gap approximately 3 mm in length. When the lids were opened the next morning, the partially closed elastofilcon A eyes showed less corneal swelling (6.2 +/- 1.4%) than the partially closed no-lens eyes did (9.6 +/- 1.3%) (p less than 0.01), whereas the partially closed Silflex eyes were significantly more swollen (12.8 +/- 2.1%) (p = 0.01) than the other two partially closed groups were. The completely closed eyes showed no significant difference in corneal swelling among the groups. These results indicate that small lid gaps during sleep may lead to less corneal swelling when elastofilcon A lenses are used than with no lenses.

  16. Edema

    MedlinePlus

    Edema means swelling caused by fluid in your body's tissues. It usually occurs in the feet, ankles ... it can involve your entire body. Causes of edema include Eating too much salt Sunburn Heart failure ...

  17. Chlorpromazine-induced corneal endothelial phototoxicity

    SciTech Connect

    Hull, D.S.; Csukas, S.; Green, K.

    1982-04-01

    Chlorpromazine, which has been used extensively for the treatment of psychiatric disorders, is known to accumulate in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Specular microscopic perfusion of corneal endothelial cells in darkness with 0.5 mM chlorpromazine HCl resulted in a swelling rate of 18 +/- 2 micrometer/hr, whereas corneas exposed to long-wavelength ultraviolet light for 3 min in the presence of 0.5 mM chlorpromazine swelled at 37 +/- 9 micrometer/hr (p less than 0.01). Preirradiation of 0.5 mM chlorpromazine solution with ultraviolet light for 30 min and subsequent corneal perfusion with the solution resulted in a corneal swelling rate of 45 +/- 19 micrometer/hr. Cornea endothelial cells perfused with 0.5 mM chlorpromazine that was preirradiated with ultraviolet light showed marked swelling on scanning electron microscopic examination, whereas those perfused with nonirradiated chlorpromazine were flat and showed a normal mosaic pattern. Combining either 500 U/ml catalase or 290 U/ml superoxide dismutase with chlorpromazine did not alter photoinduction of corneal swelling. The data suggest that corneal endothelial chlorpromazine phototoxicity is secondary to cytotoxic products resulting from the photodynamically induced decomposition of chlorpromazine and is not caused by hydrogen peroxide or superoxide anion generated during the phototoxic reaction.

  18. Sudden corneal edema due to retained lens nuclear fragment presenting 8.5 years after cataract surgery.

    PubMed

    Pandit, Rahul T; Coburn, Amy G

    2011-06-01

    A 79-year-old woman presented with a 1-week history of sudden onset of decreased vision, pain, and redness in the right eye. Ocular history included uneventful cataract surgery in both eyes more than 8 years prior to presentation. Slitlamp examination revealed significant corneal edema and mild iritis. Gonioscopy revealed a retained lens nuclear fragment in the inferior angle. Surgical removal of the fragment improved the patient's condition. The retained nuclear fragment presumably lodged behind the iris at the time of the initial surgery and spontaneously moved forward more than 8 years later. To our knowledge, this is the longest reported delay between phacoemulsification and presentation of a retained nuclear fragment. Before this case, retained nuclear fragments had been associated with complications within a year of surgery only. We recommend gonioscopy in cases of sudden-onset corneal edema extending to the inferior limbus in patients with a history of phacoemulsification.

  19. Edema

    MedlinePlus

    ... and symptoms Pregnancy Edema can be a side effect of some medications, including: High blood pressure medications Nonsteroidal anti-inflammatory drugs Steroid drugs Estrogens Certain diabetes medications called ...

  20. Drug-induced pulmonary edema and acute respiratory distress syndrome.

    PubMed

    Lee-Chiong, Teofilo; Matthay, Richard A

    2004-03-01

    Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

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

    PubMed Central

    Mittal, Vikas; Mittal, Ruchi; Singh, Daljit

    2011-01-01

    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/mm2) 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. PMID:21666321

  2. Corneal endothelial cytotoxicity of the Calotropis procera (ushaar) plant.

    PubMed

    Al-Mezaine, Hani S; Al-Amry, Mohammed A; Al-Assiri, Abdullah; Fadel, Talal S; Tabbara, Khalid F; Al-Rajhi, Ali A

    2008-05-01

    To report 6 eyes of 5 patients with transient corneal edema after exposure to the milky latex of Calotropis procera (ushaar). Interventional case series. Intracorneal penetration of ushaar latex can lead to permanent endothelial cell loss with morphologic alteration. Corneal edema resolved completely in approximately 2 weeks in all cases, despite reduced endothelial cell count and abnormal morphology. Corneal endothelial toxicity of ushaar latex is caused by its ability to penetrate the corneal stroma and induce permanent loss of endothelial cells. Corneal edema resolves if sufficient endothelial cell viability is still present after resolution of ushaar keratitis.

  3. Corneal bee sting-induced endothelial changes.

    PubMed

    Gürlü, Vuslat Pelitli; Erda, Nazan

    2006-09-01

    To report the acute management and clinical findings of a case of corneal bee sting and to report the outcome of corneal endothelial cell analysis 1 year after trauma. Clinical findings, anterior segment photographs, corneal endothelial images, and medical treatment of a case of right corneal bee sting are presented. Right and left central corneal endothelial cell analysis was performed by noncontact specular microscopy. The stinger was removed from the cornea. Systemic, subconjunctival, and topical steroids and systemic and topical antibiotics were given. One year later, a corneal scar and anterior capsular opacity of the lens in the right eye were shown by slit-lamp examination. Endothelial cell analysis determined that the endothelial cell density of the right eye was substantially decreased compared with the left eye. Corneal infiltration gradually decreased, presumably because of the systemic, topical, and subconjunctival steroids. Late complications observed in this case included a substantial decrease in cornea endothelial cell density, a corneal scar, and anterior capsular opacity.

  4. Exercise-Induced Pulmonary Edema in a Triathlon

    PubMed Central

    Yamanashi, Hirotomo; Koyamatsu, Jun; Nobuyoshi, Masaharu; Murase, Kunihiko; Maeda, Takahiro

    2015-01-01

    Introduction. Family physicians have more opportunities to attend athletic competitions as medical staff at first-aid centers because of the increasing popularity of endurance sports. Case. A 38-year-old man who participated in a triathlon race experienced difficulty in breathing after swimming and was moved to a first-aid center. His initial oxygen saturation was 82% and a thoracic computed tomography scan showed bilateral ground glass opacity in the peripheral lungs. His diagnosis was noncardiogenic pulmonary edema associated with exercise or swimming: exercise-induced pulmonary edema (EIPE) or swimming-induced pulmonary edema (SIPE). Treatment with furosemide and corticosteroid relieved his symptoms of pulmonary edema. Discussion. Noncardiogenic pulmonary edema associated with endurance sports is not common, but knowledge about EIPE/SIPE or neurogenic pulmonary edema associated with hyponatremia, which is called Ayus-Arieff syndrome, is crucial. Knowledge and caution for possible risk factors, such as exposure to cold water or overhydration, are essential for both medical staff and endurance athletes. Conclusion. To determine the presence of pulmonary edema associated with strenuous exercise, oxygen saturation should be used as a screening tool at a first-aid center. To avoid risks for EIPE/SIPE, knowledge about these diseases is essential for medical staff and for athletes who perform extreme exercise. PMID:26229538

  5. Effects of metformin treatment on glioma-induced brain edema

    PubMed Central

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

  6. Effects of metformin treatment on glioma-induced brain edema.

    PubMed

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

  7. Noncardiac Pulmonary Edema induced by Sitagliptin Treatment

    PubMed Central

    Belice, Tahir; Yuce, Suleyman; Kizilkaya, Bayram; Kurt, Aysel; Cure, Erkan

    2014-01-01

    A 74-year-old male patient with type 2 diabetes mellitus admitted to the emergency department with the complaints of progressive breathlessness, dry cough, and swollen lower extremities. Our patient had type 2 diabetes mellitus and hypertension for 3 years. His HbA1c was not within the target range so sitagliptin was added to on-going therapy. After 1 week of starting sitagliptin therapy, even though the patient had not heart failure he applied to the emergency department with a complaint of dyspnea. The cardiovascular safety and efficacy of many anti-hyperglycemic agents such as sitagliptin, saxagliptin are unclear. Our case has shown that dipeptidyl peptidase 4 inhibitors may cause pulmonary edema. Hence, it should be used with cautious, especially in patients with heart failure. PMID:25657966

  8. Noncardiac Pulmonary Edema induced by Sitagliptin Treatment.

    PubMed

    Belice, Tahir; Yuce, Suleyman; Kizilkaya, Bayram; Kurt, Aysel; Cure, Erkan

    2014-01-01

    A 74-year-old male patient with type 2 diabetes mellitus admitted to the emergency department with the complaints of progressive breathlessness, dry cough, and swollen lower extremities. Our patient had type 2 diabetes mellitus and hypertension for 3 years. His HbA1c was not within the target range so sitagliptin was added to on-going therapy. After 1 week of starting sitagliptin therapy, even though the patient had not heart failure he applied to the emergency department with a complaint of dyspnea. The cardiovascular safety and efficacy of many anti-hyperglycemic agents such as sitagliptin, saxagliptin are unclear. Our case has shown that dipeptidyl peptidase 4 inhibitors may cause pulmonary edema. Hence, it should be used with cautious, especially in patients with heart failure.

  9. Staphylococcus aureus Blepharitis Associated with Multiple Corneal Stromal Microabscess, Stromal Edema, and Uveitis.

    PubMed

    Boto-de-los-Bueis, Ana; del Hierro Zarzuelo, Almudena; García Perea, Adela; de Pablos, Manuela; Pastora, Natalia; Noval, Susana

    2015-04-01

    We report a case of an immunocompetent woman with atypical marginal keratitis. She presented with recurrent episodes of multiples microabscess distributed in a triangular pattern associated with stromal oedema and anterior chamber uveitis, affecting both eyes, but not simultaneously. The episodes responded to steroid drops, corneal inflammation was coincidental with a worsening of her blepharitis in the affected eye and S. aureus was isolated from the lids.

  10. Corneal honeybee sting.

    PubMed

    Al-Towerki, Abdul-Elah

    2003-10-01

    To report a rare case of corneal honeybee sting. The corneal honeybee stinger was removed under slit-lamp guidance using a 27-gauge needle. Corneal edema resolved by 90% the next day after removal of the honeybee stinger without using topical steroids. The patient's condition improved significantly after removal of the corneal honeybee stinger, and corneal edema disappeared. The patient was evaluated in 1 week and then 3 months with permanent mild central corneal opacity.

  11. Lipopolysaccharide induced acute red eye and corneal ulcers.

    PubMed

    Schultz, C L; Morck, D W; McKay, S G; Olson, M E; Buret, A

    1997-01-01

    Using a new animal model, the aims of this study were to assess the role played by purified lipopolysaccharide (LPS) and neutrophils in the pathogenesis of acute red-eye reactions (ARE) and corneal ulcers. In addition, IL-1 alpha was assessed for its implications in the formation of corneal ulcers. Following corneal abrasion, eyes of rabbits underwent single or double exposures to various doses of LPS from Pseudomonas aeruginosa or Serratia marcescens. This protocol induced ARE symptoms, and their severity depended on the dosage, number of LPS exposures, and type of LPS used (LPS from S. marcescens showing highest virulence). Corneal ulcers were induced by delivering a high dose of Serratia LPS (100 micrograms) followed by a low dose (10 micrograms). Histopathological examination revealed that both ARE and corneal ulceration were associated with prominent neutrophil infiltration. In addition, many lymphocytes and other monocytic cells infiltrated ulcerated ocular tissue. Tear fluids obtained from ulcerated eyes contained high concentrations of a protein recognized by anti-rabbit IL-1 alpha antibodies as demonstrated by immunoblotting studies. The results indicate that LPS can induce ARE and corneal ulceration in the absence of any live bacteria. Moreover, the findings implicate the accumulation of neutrophils and IL-1 alpha-related proteins in the pathogenesis of ARE and corneal ulcers.

  12. Corneal changes in neurosurgically induced neurotrophic keratitis.

    PubMed

    Lambiase, Alessandro; Sacchetti, Marta; Mastropasqua, Alessandra; Bonini, Stefano

    2013-12-01

    Neurotrophic keratitis (NK) represents a sight-threatening complication after trigeminal impairment. To our knowledge, the duration for which trigeminal injury may affect corneal structures and function has not been investigated previously. To describe the long-term clinical, morphological, and functional outcomes of NK after neurosurgical trigeminal damage. Observational case series performed at a corneal and ocular surface diseases referral center in 2010. Eight consecutive patients with monolateral NK from 1 to 19 years after neurosurgery and 20 age- and sex-matched healthy participants were included. Complete eye examination, tear film function tests, corneal staining, and Cochet-Bonnet esthesiometry were performed. The number and density of corneal nerves, number of hyperreflective keratocytes, and corneal epithelial, endothelial, and keratocyte cell densities were evaluated by in vivo slit scanning confocal microscopy. Clinical and morphological data were compared with the contralateral unaffected eyes and with the eyes of healthy control participants. All patients showed superficial punctate keratitis and dry eye in the NK eye and a healthy contralateral eye. Decreased corneal sensitivity was observed in all affected eyes (mean [SD], 2.0 [1.9] mm in the affected eyes vs 5.8 [0.3] mm in the contralateral unaffected eyes; P = .01) and was related to decreased subbasal nerve length (P = .04; R = 0.895). Corneal epithelial and endothelial cell densities were significantly decreased and the number of hyperreflective keratocytes was significantly increased in NK eyes compared with contralateral unaffected eyes and with the eyes of healthy participants. A longer duration of NK was associated with lower endothelial cell density (P = .046; R = -0.715). Corneal morphology and function were impaired even years after neurosurgical trigeminal damage, suggesting that assessment of tear film and corneal sensitivity as well as in vivo confocal microscopy examination should

  13. Pulmonary edema induced by calcium-channel blockade for tocolysis.

    PubMed

    Bal, Laurence; Thierry, Stéphane; Brocas, Elsa; Adam, Marie; Van de Louw, Andry; Tenaillon, Alain

    2004-09-01

    Nicardipine is used in the treatment of premature labor. There are no previous reports in the anesthesia literature of serious side effects associated with this drug. We report a case of pulmonary edema induced by nicardipine therapy for tocolysis in a pregnant 27-yr-old patient admitted to our hospital for preterm labor with intact membranes at 27 wk of gestation.

  14. Corneal hydrops induced by diabetic ketoacidosis: A case report

    PubMed Central

    Feng, Meiyan; Wang, Chao

    2016-01-01

    To the best of our knowledge, there have been no reports of corneal hydrops associated with diabetic ketoacidosis. The present study first reports a case of a 20-year-old male patient with diabetic ketoacidosis-induced corneal hydrops. The patient exhibited mild hydrops in their left eyelid, which was accompanied by mixed hyperemia, and hazy turbid in a white color was observed in the cornea. To alleviate the corneal hydrops, 5% glucose was administered dropwise to the left eye for 2 h to alleviate the inflammation. Finally, the patient was discharged from the hospital with a satisfactory outcome. PMID:27602094

  15. Chlorpromazine-induced skin pigmentation with corneal and lens opacities.

    PubMed

    Huff, Laura S; Prado, Renata; Pederson, Jon F; Dunnick, Cory A; Lucas, Lisa M

    2014-05-01

    Chlorpromazine is known to cause abnormal oculocutaneous pigmentation in sun-exposed areas. We present the case of a psychiatric patient who developed blue-gray pigmentation of the skin as well as corneal and lens opacities following 7 years of chlorpromazine treatment. Ten months after discontinuation of chlorpromazine, the skin discoloration and anterior lens deposits showed partial improvement, but the corneal deposits remained unchanged. A review of the literature on the reversibility of chlorpromazine-induced abnormal oculocutaneous pigmentation also is provided.

  16. Effect of Corneal Nerve Ablation on Immune Tolerance Induced by Corneal Allografts, Oral Immunization, or Anterior Chamber Injection of Antigens

    PubMed Central

    Mo, Juan; Neelam, Sudha; Mellon, Jessamee; Brown, Joseph R.; Niederkorn, Jerry Y.

    2017-01-01

    Purpose Severing corneal nerves during corneal transplantation does not affect first corneal transplants, but abolishes immune privilege of subsequent corneal allografts. This abrogation of immune privilege is attributable to the disabling of T regulatory cells (T regs) induced by corneal transplantation. The goal of this study was to determine if severing corneal nerves induces the development of contrasuppressor (CS) cells, which disable T regs that impair other forms of immune tolerance. Methods Effect of corneal nerve ablation on immune tolerance was assessed in four forms of immune tolerance: anterior chamber–associated immune deviation (ACAID); oral tolerance; corneal transplantation, and intravenously (IV) induced immune tolerance. T regulatory cell activity was assessed by adoptive transfer and by local adoptive transfer (LAT) of suppression assays. Results Corneal nerve ablation prevented ACAID and oral tolerance, but did not affect IV-induced immune tolerance. Contrasuppressor cells blocked the action of T regs that were generated by anterior chamber injection, oral tolerance, or orthotopic corneal transplantation. The neuropeptide substance P (SP) was crucial for contrasuppressor activity as CS cells could not be induced in SP−/− mice and the SP receptor inhibitor, Spantide II, prevented the expression of CS cell activity in vivo. Contrasuppressor cells expressed CD11c surface marker that identifies dendritic cells (DC). Conclusions The loss of immune privilege produced by corneal nerve ablation following corneal transplantation extends beyond the eye and also affects immune tolerance induced through mucosal surfaces and appears to be mediated by a novel cell population of CD11c+ CS cells that disables T regs. PMID:28114571

  17. Escin attenuates cerebral edema induced by acute omethoate poisoning.

    PubMed

    Wang, Tian; Jiang, Na; Han, Bing; Liu, Wenbo; Liu, Tongshen; Fu, Fenghua; Zhao, Delu

    2011-06-01

    Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60 mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood-brain barrier.

  18. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    PubMed Central

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

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

    NASA Astrophysics Data System (ADS)

    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.

  20. 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.

    PubMed

    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.

  1. Ceramide-induced apoptosis in rabbit corneal fibroblasts.

    PubMed

    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.

  2. The effect and safety of intravitreal injection of ranibizumab and bevacizumab on the corneal endothelium in the treatment of diabetic macular edema.

    PubMed

    Guzel, Huseyin; Bakbak, Berker; Koylu, Mehmet Talay; Gonul, Saban; Ozturk, Banu; Gedik, Sansal

    2017-03-01

    To investigate the effect and safety of intravitreal injection (IVI) of bevacizumab and ranibizumab on corneal endothelial cell count and morphology in patients with diabetic macular edema. A total of 60 eyes from 60 consecutive patients who received 0.5 mg/0.05 ml IVIs of bevacizumab (n = 30, IVB group) or 1.25 mg/0.05 ml ranibizumab (n = 30, IVR group) for three consecutive months were investigated prospectively. Specular microscopy was performed to evaluate endothelial cell count, the percentage of hexagonal cells (pleomorphism), and the coefficient of variation of the cell size (polymegathism); optical biometry was performed to evaluate central corneal thickness. Results before injection and 1 month after the first and third injections were compared. The groups were matched for age (p = 0.11) and gender (p = 0.32). There was no significant difference in endothelial cell count (IVB group, p = 0.66; IVR group, p = 0.74), pleomorphism (IVB group, p = 0.44; IVR group, p = 0.88) and polymegathism (IVB group, p = 0.21; IVR group, p = 0.24) before injection or 1 month after the first and third injections. There was also no difference in central corneal thickness (IVB group, p = 0.15; IVR group, p = 0.58) before injection or 1 month after the first and third injections. Monthly 1.25 mg/0.05 ml IVIs of bevacizumab or 0.5 mg/0.05 ml of ranibizumab for three consecutive months in the treatment of diabetic macular edema does not affect corneal morphology and has no harmful effects on the endothelium.

  3. Ultraviolet Irradiation-Induced Volume Alteration of Corneal Epithelial Cells

    PubMed Central

    Wang, Ling; Lu, Luo

    2016-01-01

    Purpose The purpose of the study is to understand how extracellular stresses, such as ultraviolet (UV) irradiation, affect corneal epithelial cells. Cell volume changes, damage to corneal epithelial integrity, and cellular responses were assessed after exposure to UVC stresses. Methods Primary human and rabbit corneal epithelial cells were exposed to UVC light in culture conditions. Ultraviolet C irradiation–induced changes in cell size and volume were measured by real-time microscopy and self-quenching of the fluorescent dye calcein, respectively. The effects of UVC irradiation on Src and focal adhesion kinase (FAK) phosphorylation and FAK-dependent integrin signaling were detected by ELISA, immunoblotting, and immunostaining. Results Ultraviolet C irradiation induced both size and volume shifts in human and rabbit corneal epithelial cells. Ultraviolet C irradiation-induced decrease of cell volume elicited activation of Src and FAK, characterized by increased phosphorylations of SrcY416, FAKY397, and FAKY925. In addition, immunostaining studies showed UVC irradiation–induced increases in phosphorylation of FAK and formation of integrin β5 clustering. Application of Kv channel blockers, including 4-aminopyridine (4-AP), α-DTX, and depressing substance-1 (BDS-1), effectively suppressed UVC irradiation–induced cell volume changes, and subsequently inhibited UVC irradiation–induced phosphorylation of Src/FAK, and formation of integrin β5 clustering, suggesting UVC irradiation–induced volume changes and Src/FAK activation. Hyperosmotic pressure–induced volume decreases were measured in comparison with effects of UVC irradiation on volume and Src/FAK activation. However, Kv channel blocker, 4-AP, had no effect on hyperosmotic pressure–induced responses. Conclusions The present study demonstrates that UVC irradiation–induced decreases in cell volume lead to Src/FAK activation due to a rapid loss of K ions through membrane Kv channels. PMID:27978555

  4. Topical Tetrodotoxin Attenuates Photophobia Induced by Corneal Injury in the Rat.

    PubMed

    Green, Paul G; Alvarez, Pedro; Levine, Jon D

    2015-09-01

    Corneal injury can produce photophobia, an aversive sensitivity to light. Using topical application of lidocaine, a local anesthetic, and tetrodotoxin (TTX), a selective voltage-sensitive sodium channel blocker, we assessed whether enhanced aversiveness to light induced by corneal injury in rats was caused by enhanced activity in corneal afferents. Eye closure induced by 30 seconds of exposure to bright light (460-485 nm) was increased 24 hours after corneal injury induced by de-epithelialization. Although the topical application of lidocaine did not affect the baseline eye closure response to bright light in control rats, it eliminated the enhancement of the response to the light stimulus after corneal injury (photophobia). Similarly, topical application of TTX had no effect on the eye closure response to bright light in rats with intact corneas, but it markedly attenuated photophobia in rats with corneal injury. Given the well-established corneal toxicity of local anesthetics, we suggest TTX as a therapeutic option to treat photophobia and possibly other symptoms that occur in clinical diseases that involve corneal nociceptor sensitization. Perspective: We show that lidocaine and TTX attenuate photophobia induced by corneal injury. Although corneal toxicity limits use of local anesthetics, TTX may be a safer therapeutic option to reduce the symptom of photophobia associated with corneal injury. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Systemic adalimumab induces peripheral corneal infiltrates: a case report.

    PubMed

    Matet, Alexandre; Daruich, Alejandra; Beydoun, Talal; Cosnes, Jacques; Bourges, Jean-Louis

    2015-06-06

    Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.

  6. Multipurpose Care Solution–Induced Corneal Surface Disruption and Pseudomonas aeruginosa Internalization in the Rabbit Corneal Epithelium

    PubMed Central

    Posch, Leila C.; Zhu, Meifang; Robertson, Danielle M.

    2014-01-01

    Purpose. To evaluate the effects of a chemically preserved multipurpose contact lens care solution (MPS) on the corneal epithelial surface and Pseudomonas aeruginosa (PA) internalization in the rabbit corneal epithelium. Methods. Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A) soaked overnight in a borate-buffered MPS (BioTrue). The contralateral eye was fit with a lens removed directly from the blister pack containing borate-buffered saline (control). Lenses were worn for 2 hours. Upon lens removal, corneas were challenged ex vivo with invasive PA strain 6487 and assessed for PA internalization. Ultrastructural changes were assessed using scanning electron (SEM) and transmission electron microscopy (TEM). Results. Scanning electron microscopy showed frank loss of surface epithelium in MPS-exposed eyes, while control eyes exhibited occasional loss of surface membranes but retention of intact junctional borders. Transmission electron microscopy data supported and extended SEM findings, demonstrating the presence of epithelial edema in MPS-treated eyes. There was a 12-fold increase in PA uptake into the corneal epithelium following wear of the MPS-treated lens compared to control (P = 0.008). Conclusions. These data demonstrate that corneal exposure to MPS during lens wear damages the surface epithelium and are consistent with our previous clinical data showing an increase in bacterial binding to exfoliated epithelial cells following MPS use with resultant increased risk for lens-mediated infection. These findings also demonstrate that the PA invasion assay may provide a highly sensitive quantitative metric for assessing the physiological impact of lens-solution biocompatibility on the corneal epithelium. PMID:24876286

  7. Vitamin D Induces Global Gene Transcription in Human Corneal Epithelial Cells: Implications for Corneal Inflammation.

    PubMed

    Reins, Rose Y; Mesmar, Fahmi; Williams, Cecilia; McDermott, Alison M

    2016-05-01

    Our previous studies show that human corneal epithelial cells (HCEC) have a functional vitamin D receptor (VDR) and respond to vitamin D by dampening TLR-induced inflammation. Here, we further examined the timing of the cytokine response to combined vitamin D-TLR treatment and used genome-wide microarray analysis to examine the effect of vitamin D on corneal gene expression. Telomerase-immortalized HCEC (hTCEpi) were stimulated with polyinosinic-polycytidylic acid (poly[I:C]) and 1,25-dihydroxyvitamin D3 (1,25D3) for 2 to 24 hours and interleukin (IL)-8 expression was examined by quantitative (q)PCR and ELISA. Telomerase-immortalized HCEC and SV40-HCEC were treated with 1,25D3 and used in genome-wide microarray analysis. Expression of target genes was validated using qPCR in both cell lines and primary HCEC. For confirmation of IκBα protein, hTCEpi were treated with 1,25D3 for 24 hours and cell lysates used in an ELISA. Treatment with 1,25D3 increased poly(I:C)-induced IL-8 mRNA and protein expression after 2 to 6 hours. However, when cells were pretreated with 1,25D3 for 24 hours, 1,25D3 decreased cytokine expression. For microarray analysis, 308 genes were differentially expressed by 1,25D3 treatment in hTCEpi, and 69 genes in SV40s. Quantitative (q)PCR confirmed the vitamin D-mediated upregulation of target genes, including nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α (IκBα). In addition to increased transcript levels, IκBα protein was increased by 28% following 24 hours of vitamin D treatment. Microarray analysis demonstrates that vitamin D regulates numerous genes in HCEC and influences TLR signaling through upregulation of IκBα. These findings are important in dissecting the role of vitamin D at the ocular surface and highlight the need for further research into the functions of vitamin D and its influence on corneal gene expression.

  8. Dependence of EGF-Induced Increases in Corneal Epithelial Proliferation and Migration on GSK-3 Inactivation

    DTIC Science & Technology

    2009-10-01

    phosphoryla- tion, but did not increase proliferation. We have identified in rabbit corneal epithelial cells (RCEC) similar interaction in response to...Inhibitory effect of PGE2 on EGF-induced MAP kinase activity and rabbit corneal epithelial proliferation. Invest Ophthalmol Vis Sci. 2000;41:2164–2169. 4...Dependence of EGF-Induced Increases in Corneal Epithelial Proliferation and Migration on GSK-3 Inactivation Zheng Wang,1 Hua Yang,1 Fan Zhang,1 Zan

  9. Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.

    PubMed

    Murataeva, Natalia; Li, Shimin; Oehler, Olivia; Miller, Sally; Dhopeshwarkar, Amey; Hu, Sherry Shu-Jung; Bonanno, Joseph A; Bradshaw, Heather; Mackie, Ken; McHugh, Douglas; Straiker, Alex

    2015-05-01

    Cannabinoid CB1 receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail. We determined the role of CB1 receptors in corneal healing. We examined the consequences of their activation on migration and proliferation in bovine CECs (bCECs). We additionally examined the mRNA profile of cannabinoid-related genes and CB1 protein expression as well as CB1 signaling in bovine CECs. We now report that activation of CB1 with physiologically relevant concentrations of the synthetic agonist WIN55212-2 (WIN) induces bCEC migration via chemotaxis, an effect fully blocked by the CB1 receptor antagonist SR141716. The endogenous agonist 2-arachidonoylglycerol (2-AG) also enhances migration. Separately, mRNA for most cannabinoid-related proteins are present in bovine corneal epithelium and cultured bCECs. Notably absent are CB2 receptors and the 2-AG synthesizing enzyme diglycerol lipase-α (DAGLα). The signaling profile of CB1 activation is complex, with inactivation of mitogen-activated protein kinase (MAPK). Lastly, CB1 activation does not induce bCEC proliferation, but may instead antagonize EGF-induced proliferation. In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis.

  10. Cannabinoid-Induced Chemotaxis in Bovine Corneal Epithelial Cells

    PubMed Central

    Murataeva, Natalia; Li, Shimin; Oehler, Olivia; Miller, Sally; Dhopeshwarkar, Amey; Hu, Sherry Shu-Jung; Bonanno, Joseph A.; Bradshaw, Heather; Mackie, Ken; McHugh, Douglas; Straiker, Alex

    2015-01-01

    Purpose. Cannabinoid CB1 receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail. Methods. We determined the role of CB1 receptors in corneal healing. We examined the consequences of their activation on migration and proliferation in bovine CECs (bCECs). We additionally examined the mRNA profile of cannabinoid-related genes and CB1 protein expression as well as CB1 signaling in bovine CECs. Results. We now report that activation of CB1 with physiologically relevant concentrations of the synthetic agonist WIN55212-2 (WIN) induces bCEC migration via chemotaxis, an effect fully blocked by the CB1 receptor antagonist SR141716. The endogenous agonist 2-arachidonoylglycerol (2-AG) also enhances migration. Separately, mRNA for most cannabinoid-related proteins are present in bovine corneal epithelium and cultured bCECs. Notably absent are CB2 receptors and the 2-AG synthesizing enzyme diglycerol lipase-α (DAGLα). The signaling profile of CB1 activation is complex, with inactivation of mitogen-activated protein kinase (MAPK). Lastly, CB1 activation does not induce bCEC proliferation, but may instead antagonize EGF-induced proliferation. Conclusions. In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis. PMID:26024113

  11. In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury

    NASA Astrophysics Data System (ADS)

    Xu, Zhun; Zhu, Quing; Wang, Lihong V.

    2011-06-01

    For the first time, we have implemented photoacoustic tomography (PAT) to image the water content of an edema in vivo. We produced and imaged a cold-induced cerebral edema transcranially, then obtained blood vessel and water accumulation images at 610 and 975 nm, respectively. We tracked the changes at 12, 24, and 36 h after the cold injury. The blood volume decreased after the cold injury, and the maximum area of edema was observed 24 h after the cold injury. We validated PAT of the water content of the edema through magnetic Resonance Imaging and the water spectrum from the spectrophotometric measurement.

  12. Feline corneal disease.

    PubMed

    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.

  13. Thermoelectrically controlled device for studies of temperature-induced corneal shrinkage

    NASA Astrophysics Data System (ADS)

    Borja, David; Manns, Fabrice; Fernandez, Viviana; Lamar, Peggy; Soederberg, Per G.; Parel, Jean-Marie A.

    2002-06-01

    The purpose of this study was to design and calibrate a device to measure the dynamics of thermal shrinkage in corneal and scleral strips. The apparatus consists of a thermoelectric cell controlled by a temperature controller designed to generate temperatures up to 90 degree(s)C in rectangular corneal strips; a copper cuvette filled with Dextran solution that holds the corneal strip and a displacement sensor that measures the change in length of the tissue during heat-induced shrinkage. The device was tested on corneal tissue from Florida Eye-Bank eyes that were cut into 2x4mm rectangular strips. Preliminary results indicate that our system can reproducibly create and accurately measure thermally induced corneal shrinkage. Shrinkage experiments will be used to optimize laser parameters for corneal shrinkage during laser thermokeratoplasty and laser scleral buckling.

  14. Exposure Stress Induces Reversible Corneal Graft Opacity in Recipients With Herpes Simplex Virus-1 Infections

    PubMed Central

    Rowe, Alexander M.; Yun, Hongmin; Hendricks, Robert L.

    2017-01-01

    Purpose Most of the inflammation in murine herpes simplex virus type 1 (HSV-1)-induced stromal keratitis (HSK) is due to exposure stress resulting from loss of corneal nerves and blink reflex. Corneal grafts often fail when placed on corneal beds with a history of HSK. We asked if corneal exposure contributes to the severe pathology of corneal grafts on HSV-1–infected corneal beds. Methods Herpes simplex virus type 1–infected corneas were tested for blink reflex. Opacity and vascularization were monitored in allogeneic and syngeneic corneal grafts that were transplanted to corneal beds with no blink reflex or to those that retained blink reflex in at least one quadrant following infection. Results Retention of any level of blink reflex significantly reduced inflammation in HSV-1–infected corneas. Corneal allografts placed on HSV-1–infected beds lacking corneal blink reflex developed opacity faster and more frequently than those placed on infected beds that partially or completely retained blink reflex. Corneal grafts placed on infected corneal beds with no blink reflex rapidly became opaque to a level that would be considered rejection. However, protecting these grafts from exposure by tarsorrhaphy prevented or reversed the opacity in both syngeneic and allogenic grafts. Conclusions Exposure due to HSV-1–engendered hypoesthesia causes rapid, severe, persistent, but reversible opacification of both allogeneic and syngeneic corneal grafts. This opacity should not be interpreted as immunologic rejection. Exposure stress may contribute to the high rate of corneal graft pathology in patients with recurrent HSK. PMID:28055100

  15. Involvement of COX2-Thromboxane Pathway in TCDD-Induced Precardiac Edema in Developing Zebrafish

    PubMed Central

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E.; Stegeman, John J.; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2015-01-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was cancelled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

  16. PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

    PubMed Central

    Kim, Dae Won; Lee, Sung Ho; Shin, Min Jea; Kim, Kibom; Ku, Sae Kwang; Youn, Jong Kyu; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Son, Ora; Sohn, Eun Jeong; Cho, Sung-Woo; Park, Jong Hoon; Kim, Hyun Ah; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-01-01

    FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623] PMID:25817214

  17. Efficacy of moclobemide in a rat model of neurotoxicant-induced edema.

    PubMed

    Girard, Philippe; Verniers, Danielle; Pansart, Yannick; Gillardin, Jean-Marie

    2007-05-01

    The potent antidepressant effect of moclobemide, a selective and reversible type A monoamine oxidase (MAO) inhibitor, is clinically established. In view of the ongoing debate on the neuroprotective properties of MAO inhibitors, the present study was undertaken to further define the protective effect of moclobemide in a rat model of neurotoxicant-induced edema. In this model, daily oral triethyltin (TET) administration for 5 consecutive days strongly perturbed the rat behaviour and induced a cerebral edema at the 5th day. Oral coadministration of moclobemide (2 x 100 mg.kg-1.day-1) with TET blocked the development of brain edema and the increase in the cerebral chloride content induced by TET. Moreover, moclobemide reduced the increase in the cerebral sodium content and attenuated the neurological deficit. In conclusion, moclobemide possesses potent protective properties in this rat model of cerebral edema, suggesting potential clinical utility as a neuroprotectant.

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

    PubMed

    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.

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

    PubMed Central

    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

  20. Activity of some Mexican medicinal plant extracts on carrageenan-induced rat paw edema.

    PubMed

    Meckes, M; David-Rivera, A D; Nava-Aguilar, V; Jimenez, A

    2004-07-01

    The extracts obtained from 14 plants of the Mexican medicinal flora were assessed for anti-inflammatory activity by carrageenan-induced rat paw edema model. The i.p. administration of the extracts at a dose of 400 mg/kg produced a high reduction of edema with 70% of the plant extracts. Oenothera rosea methanol extract, Sphaeralcea angustifolia chloroform extract, Acaciafarnesiana, Larrea tridentata and Rubus coriifolius methanol extracts as well as the aqueous extract of Chamaedora tepejilote were demonstrated to be particularly active against the induced hind-paw edema. Moderate inhibition of edema formation was also demonstrated with the methanol extracts of Astianthus viminalis, Brickellia paniculata, C. tepejilote and Justicia spicigera.

  1. Aripiprazole induced non-cardiogenic pulmonary edema: a case report.

    PubMed

    Cetin, Mustafa; Celik, Mustafa; Cakıcı, Musa; Polat, Mustafa; Suner, Arif

    2014-01-01

    Aripiprazole is a second-generation antipsychotic drug with partial dopamine agonistic activity. Although the adverse cardiovascular effects of both typical and atypical antipsychotics are well known, similar data on aripiprazole, which was recently introduced, are scarce. Herein we report a 35-year-old female that presented to our emergency department with non-cardiogenic pulmonary edema. Chest X-ray and thoracic CT showed pulmonary edema and bilateral pleural effusion. Anamnesis showed that she had been taking sertraline 200 mg d-1 for obsessive-compulsive disorder for a long time and that aripiprazole10 mg d-1 was added for augmentation 2 months prior to presentation. We think that the CYP 2D6 inhibitor sertraline might have played a role in increasing the plasma concentration and toxicity of aripiprazole in the presented patient.

  2. Complement component C5 deficiency reduces edema formation in murine ligation-induced acute pancreatitis.

    PubMed

    Merriam, L T; Webster, C; Joehl, R J

    1997-01-01

    The complement cascade is activated in humans and animals with acute pancreatitis. Activation of complement component C5 liberates C5a, C5a-desarg, and terminal complement complexes (TCCs) that increase capillary permeability, edema, and leukocyte chemotaxis at injured sites. Complement activation plays a major role in pathogenesis of capillary leak and edema formation in severe acute pancreatitis; however, the contribution of C5 (C5a/C5a-desarg, TCCs) has not been defined. Using He gene mutant mice lacking circulating C5, the role of C5 in ligation-induced acute pancreatitis was evaluated. We performed the following experiments: C5-sufficient (Hc1/Hc1) and C5-deficient (Hc0/Hc0) mice had bile and pancreatic ducts ligated. Sham-operated mice had ducts dissected but not ligated. Mice were killed at 4, 8, and 24 hr after bilepancreatic duct ligation. Serologic and morphologic evidences of acute pancreatitis were evaluated. Pancreatic edema was assessed using analysis of pancreatic water content, histologic edema score, and determination of wet weight ratio. After 4, 8, and 24 hr of bile-pancreatic duct ligation, hyperamylasemia and histologic changes of acute pancreatitis were observed in both C5-deficient and C5-sufficient mice. Edema developed in all mice with acute pancreatitis. However, when compared to C5-sufficient mice, mice deficient in C5 developed significantly less pancreatic edema at both 8 and 24 hr of bile-pancreatic duct ligation. This difference was not observed 4 hr after induction of acute pancreatitis. We conclude that C5 contributes to edema formation in murine ligation-induced acute pancreatitis. The presence of an early C5-independent phase, in conjunction with the observation of significant edema in mice deficient in C5, suggests there are other mediators of edema formation in this acute pancreatitis model.

  3. Select noxious stimuli induce changes on corneal nerve morphology.

    PubMed

    Hegarty, Deborah M; Hermes, Sam M; Yang, Katherine; Aicher, Sue A

    2017-06-01

    The surface of the cornea contains the highest density of nociceptive nerves of any tissue in the body. These nerves are responsive to a variety of modalities of noxious stimuli and can signal pain even when activated by low threshold stimulation. Injury of corneal nerves can lead to altered nerve morphology, including neuropathic changes which can be associated with chronic pain. Emerging technologies that allow imaging of corneal nerves in vivo are spawning questions regarding the relationship between corneal nerve density, morphology, and function. We tested whether noxious stimulation of the corneal surface can alter nerve morphology and neurochemistry. We used concentrations of menthol, capsaicin, and hypertonic saline that evoked comparable levels of nocifensive eye wipe behaviors when applied to the ocular surface of an awake rat. Animals were sacrificed and corneal nerves were examined using immunocytochemistry and three-dimensional volumetric analyses. We found that menthol and capsaicin both caused a significant reduction in corneal nerve density as detected with β-tubulin immunoreactivity 2 hr after stimulation. Hypertonic saline did not reduce nerve density, but did cause qualitative changes in nerves including enlarged varicosities that were also seen following capsaicin and menthol stimulation. All three types of noxious stimuli caused a depletion of CGRP from corneal nerves, indicating that all modalities of noxious stimuli evoked peptide release. Our findings suggest that studies aimed at understanding the relationship between corneal nerve morphology and chronic disease may also need to consider the effects of acute stimulation on corneal nerve morphology.

  4. [Clinical aspects of corneal burns].

    PubMed

    Borderie, V

    2004-12-01

    Clinical aspects and prognosis of corneal burns mainly depend on the agent responsible for the trauma. The most severe burns are caustic burns, which should be classified as burns caused by basic agents, associated with deep and prolonged injuries, and burns caused by acidic agents, associated with more superficial injuries. At the acute stage, caustic burns induce epithelial defects, corneal edema, and ischemic necrosis of the limbus, conjunctiva, iris and ciliary body. At the early stage, reepithelialization occurs and is often associated with corneal vascularization and stromal infiltrates, followed by corneal scar formation. At the chronic stage, the following complications are possible: corneal scars, limbal stem cell insufficiency, lachrymal insufficiency, irregular astigmatism, ocular surface fibrosis, cataract, glaucoma, decreased intraocular pressure, and ocular atrophy. The Ropper-Hall classification is based on the extent of limbal ischemia. Thermal burns induce epithelial defects at the acute stage, with the more severe forms giving the same complications as caustic burns. Radiation-related burns can be caused by ultraviolet radiations (acute epithelial keratitis, pterygium, droplet-like keratitis), microwaves, infrared radiations, ionizing radiations or, laser radiations. Electrical burns are often a result of torture and give corneal stroma opacification.

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

    PubMed

    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 (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit 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.

  6. Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye

    PubMed Central

    Paunicka, Kathryn J.; Mellon, Jessamee; Robertson, Danielle; Petroll, Matthew; Brown, Joseph R.; Niederkorn, Jerry Y.

    2015-01-01

    Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a three-fold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft. PMID:25872977

  7. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome

    PubMed Central

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-01-01

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES. PMID:27455237

  8. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome.

    PubMed

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-07-21

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES.

  9. The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema.

    PubMed

    Qin, Xu-Jun; Li, Ying-Na; Liang, Xin; Wang, Peng; Hai, Chun-Xu

    2008-02-29

    Phosgene is a toxic gas that is widely used in modern industry, and its inhalation can cause severe pulmonary edema. There is no effective clinical treatment because the mechanism of phosgene-induced pulmonary edema still remains unclear. Many studies have demonstrated that the Na(+)/K(+)-ATPase plays a critical role in clearing pulmonary edema and the inhibition of Na(+)/K(+)-ATPase protein expression has been found in many other pulmonary edema models. In the present study, after the mice were exposed to phosgene, there was serious pulmonary edema, indicating the dysfunction of the ATPases in mice. However, in vitro enzyme study showed that there were increases in the activities of the Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Further investigation showed that the ATP content and mitochondrial respiratory control ratio (RCR) in the lungs decreased significantly. The oxidative stress product, malondialdehyde (MDA), increased while the antioxidants (GSH, SOD, and TAC) decreased significantly. These results indicate that mitochondrial respiration is the target of phosgene. The dysfunction of ATPases due to impaired mitochondrial respiration may be a new mechanism of phosgene-induced pulmonary edema.

  10. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice

    PubMed Central

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-01-01

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy. PMID:27405815

  11. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-07-11

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.

  12. Ibuprofen prevents synthetic smoke-induced pulmonary edema

    SciTech Connect

    Shinozawa, Y.; Hales, C.; Jung, W.; Burke, J.

    1986-12-01

    Multiple potentially injurious agents are present in smoke but the importance of each of these agents in producing lung injury as well as the mechanisms by which the lung injury is produced are unknown. In order to study smoke inhalation injury, we developed a synthetic smoke composed of a carrier of hot carbon particles of known size to which a single known common toxic agent in smoke, in this case HCI, could be added. We then exposed rats to the smoke, assayed their blood for the metabolites of thromboxane and prostacyclin, and intervened shortly after smoke with the cyclooxygenase inhibitors indomethacin or ibuprofen to see if the resulting lung injury could be prevented. Smoke exposure produced mild pulmonary edema after 6 h with a wet-to-dry weight ratio of 5.6 +/- 0.2 SEM (n = 11) compared with the non-smoke-exposed control animals with a wet-to-dry weight ratio of 4.3 +/- 0.2 (n = 12), p less than 0.001. Thromboxane B, and 6-keto-prostaglandin F1 alpha rose to 1660 +/- 250 pg/ml (p less than 0.01) and to 600 +/- 100 pg/ml (p greater than 0.1), respectively, in the smoke-injured animals compared with 770 +/- 150 pg/ml and 400 +/- 100 pg/ml in the non-smoke-exposed control animals. Indomethacin (n = 11) blocked the increase in both thromboxane and prostacyclin metabolites but failed to prevent lung edema.

  13. Swimming-induced immersion pulmonary edema while snorkeling can be rapidly life-threatening: case reports.

    PubMed

    Cochard, G; Henckes, A; Deslandes, S; Noël-Savina, E; Bedossa, M; Gladu, G; Ozier, Y

    2013-01-01

    It is well known that immersion pulmonary edema can be life-threatening for divers using a self-contained underwater breathing apparatus (scuba). Swimming-induced pulmonary edema in otherwise healthy individuals is not an object of dispute but its real severity is not well known and is probably underestimated. We report two cases of life-threatening acute respiratory distress while swimming and snorkeling, one of which is well documented for swimming-induced pulmonary edema. The interest of these case reports lies in the suddenness of these life-threatening events. Such accidents can mimic a loss of consciousness due to cardiac dysrhythmia and lead to drowning. In the case of swimming-induced pulmonary edema, the prognosis is far better than for a cardiac disorder, but it is also dependent on the efficiency of the supervision. Swimmers, divers, race organizers and supervising physicians should be given knowledge of this pathology and its potentially acute occurrence. Adequate organizational dispositions are mandatory to prevent swimming-induced pulmonary edema-related deaths.

  14. New Developments in the Pathogenesis of Smoke Inhalation-Induced Pulmonary Edema

    PubMed Central

    Witten, Mark L.; Quan, Stuart F.; Sobonya, Richard E.; Lemen, Richard J.

    1988-01-01

    Smoke inhalation causes most of the deaths in fire-related injuries, with pulmonary edema as a major determinant in the outcome of smoke-inhalation injury. The pathophysiology of pulmonary edema is thought to be related to the products of incomplete combustion. Damage to the integrity of the alveolar epithelium is one of the determinants of the development of smoke-induced pulmonary edema. In recent studies using lung clearance of aerosolized pentetic acid (DTPA [diethylenetriaminepentaacetic acid]) labeled with technetium Tc 99m to assess the permeability of the alveolar epithelium, several factors were identified that may increase a person's susceptibility to smoke-induced acute lung injury. These are increased initial alveolar permeability and alterations in the number and activity of alveolar macrophages. Clinical measurement of 99mTcDTPA clearance may provide a sensitive and convenient method for the early detection and serial assessment of smoke-induced alveolar epithelial permeability changes. Images PMID:3277334

  15. Involvement of mast cells and histamine in edema induced in mice by Scolopendra viridicornis centipede venom.

    PubMed

    Távora, Bianca C L F; Kimura, Louise F; Antoniazzi, Marta M; Chiariello, Thiago M; Faquim-Mauro, Eliana L; Barbaro, Katia C

    2016-10-01

    Bites caused by Scolopendra viridicornis centipede are mainly characterized by burning pain, paresthesia and edema. On this regard, the aim of this work was to study the involvement of mast cells and histamine in edema induced by Scolopendra viridicornis (Sv) centipede venom. The edema was analyzed on mice paws. The mice were pretreated with cromolyn (mast cell degranulation inhibitor) and antagonists of histamine receptors, such as promethazine (H1R), cimetidine (H2R) and thioperamide (H3/H4R). The analyses were carried out at different times after the injection of Sv venom (15 μg) or PBS in the footpad of mice. Our results showed a significant inhibition of the edema induced by Sv venom injection in mice previously treated: cromolyn (38-91%), promethazine (50-59%) and thioperamide (around 30%). The treatment with cimetidine did not alter the edema induced by Sv venom. Histopathological analysis showed that Sv venom injection (15 μg) induced edema, leukocyte recruitment and mast cells degranulation, when compared with the PBS-injected mice. Direct effects of the Sv venom on mast cells were studied in PT-18 line (mouse mast cell) and RBL-2H3 cells (rat mast cells). The data showed that higher doses (3.8 and 7.5 μg) of Sv venom were cytotoxic for both cell lineages and induced morphological changes. However, lower doses of the venom induced degranulation of both mast cell lines, as well as the secretion of MCP-1, IL-6 and IL-1β. The production of PGD2 was only observed in the RBL-2H3 line incubated with Sv venom. Taking our results together, we demonstrated that upon Sv venom exposure, mast cells and histamine are crucial for the establishment of the local inflammatory reaction.

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

    PubMed

    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.

  17. Pheochromocytoma-induced acute pulmonary edema and reversible catecholamine cardiomyopathy mimicking acute myocardial infarction.

    PubMed

    Pineda Pompa, Luis Ramón; Barrera-Ramírez, Carlos Felipe; Martínez-Valdez, Jesús; Rodríguez, Pedro Domínguez; Guzmán, Carlos E

    2004-04-01

    Acute noncardiogenic pulmonary edema and catecholamine-induced cardiomyopathy as the first presentations of pheochromocytoma are uncommon events, but usually rapidly fatal. A 36-year-old man presented acute pulmonary edema in a setting of hypertensive emergency after arthroscopy, later developing catecholamine-induced cardiotoxicity mimicking an acute myocardial infarction, with elevation of cardiac damage markers, normal coronary arteries, and with full recovery from electrical abnormalities. Magnetic resonance imaging revealed a right adrenal mass. Elevated levels of catecholamines and metanephrines, and a positive 131I-metaiodobenzylguanidine scan confirmed a pheochromocytoma. Once the patient had been hemodynamically stabilized, he was successfully operated.

  18. Ethanol-induced hyponatremia augments brain edema after traumatic brain injury.

    PubMed

    Katada, Ryuichi; Watanabe, Satoshi; Ishizaka, Atsushi; Mizuo, Keisuke; Okazaki, Shunichiro; Matsumoto, Hiroshi

    2012-04-01

    Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.

  19. Galectin-1-mediated suppression of Pseudomonas aeruginosa-induced corneal immunopathology.

    PubMed

    Suryawanshi, Amol; Cao, Zhiyi; Thitiprasert, Thananya; Zaidi, Tanveer S; Panjwani, Noorjahan

    2013-06-15

    Corneal infection with Pseudomonas aeruginosa leads to a severe immunoinflammatory lesion, often causing vision impairment and blindness. Although past studies have indicated a critical role for CD4(+) T cells, particularly Th1 cells, in corneal immunopathology, the relative contribution of recently discovered Th17 and regulatory T cells is undefined. In this study, we demonstrate that after corneal P. aeruginosa infection, both Th1 and Th17 cells infiltrate the cornea with increased representation of Th17 cells. In addition to Th1 and Th17 cells, regulatory T cells also migrate into the cornea during early as well as late stages of corneal pathology. Moreover, using galectin-1 (Gal-1), an immunomodulatory carbohydrate-binding molecule, we investigated whether shifting the balance among various CD4(+) T cell subsets can modulate P. aeruginosa-induced corneal immunopathology. We demonstrate in this study that local recombinant Gal-1 (rGal-1) treatment by subconjunctival injections significantly diminishes P. aeruginosa-mediated corneal inflammation through multiple mechanisms. Specifically, in our study, rGal-1 treatment significantly diminished corneal infiltration of total CD45(+) T cells, neutrophils, and CD4(+) T cells. Furthermore, rGal-1 treatment significantly reduced proinflammatory Th17 cell response in the cornea as well as local draining lymph nodes. Also, rGal-1 therapy promoted anti-inflammatory Th2 and IL-10 response in secondary lymphoid organs. Collectively, our results indicate that corneal P. aeruginosa infection induces a strong Th17-mediated corneal pathology, and treatment with endogenously derived protein such as Gal-1 may be of therapeutic value for the management of bacterial keratitis, a prevalent cause of vision loss and blindness in humans worldwide.

  20. Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression

    PubMed Central

    2012-01-01

    Introduction Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action. Methods Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance. Results Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro. Conclusions Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes. PMID:23036239

  1. Ability of eugenol to reduce tongue edema induced by Dieffenbachia picta Schott in mice.

    PubMed

    Dip, Etyene Castro; Pereira, Nuno Alvarez; Fernandes, Patricia Dias

    2004-05-01

    Dieffenbachia picta Schott (Araceae), known in Brazil as "comigo-ninguém-pode" is an ornamental plant with toxic properties. Its juice, when chewed, causes a painful edema of the oral mucous membranes, buccal ulcerations and tongue hypertrophy. This acute inflammation sometimes becomes severe enough to produce glottis obstruction, respiratory compromise and death. Eugenol (4-alil-2-metoxiphenol), the essential oil extracted from Caryophyllus aromaticus (Myrtaceae) is widely used in odontology. In this study, our objective was to standardize, in mice, a measurable methodology for the tongue edema induced by the topical application of the D. picta stem juice; evaluate the effects of eugenol in this model and compare the results with emergency treatment used in hospitals. Our results show that in spite of a small increase in edema a few minutes after administration, emergency treatment reduced by 70% the overall edema. When compared with the combination of the above drugs, eugenol, even at the smallest dose of 5 microg/kg, regardless of the chosen administration route, or the moment the treatment began, presents better results in the reduction and inhibition of the tongue edema induced by the D. picta juice.

  2. Correlation of Vascular Endothelial Growth Factor Production with Photochemical Reaction-induced Retinal Edema

    PubMed Central

    Shan, Liang; Zheng, Mi; Zhang, Yuan; Qu, Yuan; Niu, Tian; Gu, Qing; Liu, Kun; Xia, Xin

    2016-01-01

    Background: Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model. Methods: A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1. Results: Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05). Conclusions: This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema

  3. Effects of chalazia on corneal astigmatism : Large-sized chalazia in middle upper eyelids compress the cornea and induce the corneal astigmatism.

    PubMed

    Jin, Ki Won; Shin, Young Joo; Hyon, Joon Young

    2017-03-31

    A chalazion is a common eyelid disease that causes eye morbidity due to inflammation and cosmetic disfigurement. Corneal topographic changes are important factors in corneal refractive surgery, intraocular lens power calculations for cataract surgery, and visual acuity assessments. However, the effects of chalazia on corneal astigmatism have not been thoroughly investigated. The changes in corneal astigmatism according to chalazion size and location is necessary for better outcome of ocular surgery. The aim of this study is to evaluate changes in corneal astigmatism according to chalazion size and location. In this cross-sectional study, a total of 44 eyes from 33 patients were included in the chalazion group and 70 eyes from 46 patients comprised the control group. Chalazia were classified according to location and size. An autokeratorefractometer (KR8100, Topcon; Japan) and a Galilei™ dual-Scheimpflug analyzer (Ziemer Group; Port, Switzerland) were utilized to evaluate corneal changes. Oblique astigmatism was greater in the chalazion group compared with the control group (p < 0.05). Astigmatism by simulated keratometry (simK), steep K by simK, total root mean square, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the upper eyelid group (p < 0.05). Astigmatism by simK, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the large-sized chalazion group (p < 0.05). Corneal wavefront aberration was the greatest in the upper eyelid chalazion group, whole area group, and large-sized chalazion group (p < 0.05). Large-sized chalazia in the whole upper eyelid should be treated in the early phase because they induced the greatest change in corneal topography. Chalazion should be treated before corneal topography is performed preoperatively and before the diagnosis of corneal diseases.

  4. Development of a program for toric intraocular lens calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position.

    PubMed

    Eom, Youngsub; Ryu, Dongok; Kim, Dae Wook; Yang, Seul Ki; Song, Jong Suk; Kim, Sug-Whan; Kim, Hyo Myung

    2016-10-01

    To evaluate the toric intraocular lens (IOL) calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position (ELP). Two thousand samples of corneal parameters with keratometric astigmatism ≥ 1.0 D were obtained using bootstrap methods. The probability distributions for incision-induced keratometric and posterior corneal astigmatisms, as well as ELP were estimated from the literature review. The predicted residual astigmatism error using method D with an IOL add power calculator (IAPC) was compared with those derived using methods A, B, and C through Monte-Carlo simulation. Method A considered the keratometric astigmatism and incision-induced keratometric astigmatism, method B considered posterior corneal astigmatism in addition to the A method, method C considered incision-induced posterior corneal astigmatism in addition to the B method, and method D considered ELP in addition to the C method. To verify the IAPC used in this study, the predicted toric IOL cylinder power and its axis using the IAPC were compared with ray-tracing simulation results. The median magnitude of the predicted residual astigmatism error using method D (0.25 diopters [D]) was smaller than that derived using methods A (0.42 D), B (0.38 D), and C (0.28 D) respectively. Linear regression analysis indicated that the predicted toric IOL cylinder power and its axis had excellent goodness-of-fit between the IAPC and ray-tracing simulation. The IAPC is a simple but accurate method for predicting the toric IOL cylinder power and its axis considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and ELP.

  5. Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.

    PubMed

    Horita, Shoko; Nakamura, Motonobu; Satoh, Nobuhiko; Suzuki, Masashi; Seki, George

    2015-01-01

    Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.

  6. Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats.

    PubMed

    Hoffmeister, Carin; Trevisan, Gabriela; Rossato, Mateus Fortes; de Oliveira, Sara Marchesan; Gomez, Marcus Vinícius; Ferreira, Juliano

    2011-08-01

    Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (ED(50) [ie, the necessary dose of MSU to elicit 50% of the response relative to the control value]=0.04 [95% confidence interval 0.01-0.11]mg/paw) and edema (ED(50)=0.08 [95% confidence interval 0.04-0.16]mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor (also known as capsaicin receptor and vanilloid receptor-1) antagonists SB366791 or AMG9810 largely prevented nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as pretreatment with the tachykinin NK(1) receptor antagonist RP 67580 also significantly prevented MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeated treatment with the compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively prevented nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin, and tryptase in the injected tissue, confirming mast cell degranulation. Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception of MSU. Finally, the prevention of the tryptase activity was capable of largely reducing both MSU-induced nociception and edema. Collectively, the present findings demonstrate that MSU produces nociceptive and edematogenic responses mediated by TRPV1 receptor activation and mast cell degranulation. Copyright © 2011 International Association for the Study of

  7. Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression.

    PubMed

    Chen, Hong-li; Bai, Hua; Xi, Miao-miao; Liu, Riu; Qin, Xu-jun; Liang, Xin; Zhang, Wei; Zhang, Xiao-di; Li, Wen-li; Hai, Chun-xu

    2013-01-01

    Phosgene is a poorly water-soluble gas penetrating the lower respiratory tract which can induce acute lung injury characterized by a latent phase of fatal pulmonary edema. Pulmonary edema caused by phosgene is believed to be a consequence of oxidative stress and inflammatory responses. Ethyl pyruvate (EP) has been demonstrated to have anti-inflammatory and anti-oxidative properties in vivo and in vitro. The potential therapeutic role of EP in phosgene-induced pulmonary edema has not been addressed so far. In the present study, we aim to investigate the protective effects of EP on phosgene-induced pulmonary edema and the underlying mechanisms. Rats were administered with EP (40 mg kg(-1)) and RAW264.7 cells were also incubated with it (0, 2, 5 or 10 µm) immediately after phosgene (400 ppm, 1 min) or air exposure. Wet-to-dry lung weight ratio (W:D ratio), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, cyclooxygenase2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, and mitogen-activated protein kinases activities (MAPKs) were measured. Our results showed that EP treatment attenuated phosgene-induced pulmonary edema and decreased the level of NO and PGE(2) dose-dependently. Furthermore, EP significantly reduced COX-2 expression, iNOS expression and MAPK activation induced by phosgene. Moreover, specific inhibitors of MAPKs reduced COX-2 and iNOS expression induced by phosgene. These findings suggested that EP has a protective role against phosgene-induced pulmonary edema, which is mediated in part by inhibiting MAPK activation and subsequently down-regulating COX-2 and iNOS expression as well as decreasing the production of NO and PGE(2). Copyright © 2011 John Wiley & Sons, Ltd.

  8. Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.

    PubMed

    Jiang, Lei; Wang, Yixin; Su, Chenglei; Sun, Hao; Zhang, Huazhong; Zhu, Baoli; Zhang, Hengdong; Xiao, Hang; Wang, Jun; Zhang, Jinsong

    2015-01-01

    Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.

  9. The role of corneal innervation in LASIK-induced neuropathic dry eye.

    PubMed

    Chao, Cecilia; Golebiowski, Blanka; Stapleton, Fiona

    2014-01-01

    Almost half the patients who undergo laser in situ keratomileusis (LASIK) experience dry eye following the procedure. However, the etiology of LASIK-induced dry eye is unclear. The purpose of this review is to examine and summarize the current evidence for the etiology of LASIK-induced dry eye, with a focus on ocular surface sensitivity and corneal innervation. Evidence suggests that the alteration of corneal nerves after LASIK is the most likely cause of the subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and the clinical indicators of dry eye return to apparently normal values within a year due to the partial recovery of the corneal nerve plexus. The hypothesis is explored that dry eye symptoms following LASIK may result from abnormal sensation due to LASIK-induced corneal neuropathy. Other factors, such as alterations in conjunctival goblet cell density, might also contribute to the symptoms and signs of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear neuropeptide levels and dry eye require further investigation. A better understanding of this phenomenon may result in improved management of post-LASIK dry eye.

  10. Edema and Nociception Induced by Philodryas patagoniensis Venom in Mice: A Pharmacological Evaluation with Implications for the Accident Treatment.

    PubMed

    Lopes, Priscila Hess; Rocha, Marisa M T; Kuniyoshi, Alexandre Kazuo; Portaro, Fernanda Calheta Vieira; Gonçalves, Luís Roberto C

    2017-06-01

    We have investigated the mechanisms involved in the genesis of edema and nociception induced by Philodryas patagoniensis venom (PpV) injected into the footpad of mice. PpV induced dose-related edema and nociceptive effects. Pretreatment of mice with cyclooxygenase inhibitor (indomethacin), but not with cyclooxygenase 2 inhibitor (celecoxib) markedly inhibited both effects. Pretreatments with H1 receptor antagonist (promethazine) or with dual histamine-serotonin inhibitor (cyproheptadine) failed in inhibiting both effects. In groups pretreated with captopril (angiotensin-converting enzyme inhibitor) the edema was unaltered, but nociception was clearly increased, suggesting the participation of kinins in the pathophysiology of the nociception but not of the edema-forming effect of PpV. When PpV was treated with EDTA, the nociception was similar to the one induced by untreated venom, but edema was markedly reduced. We concluded that PpV-induced edema and nociception have cyclooxygenase eicosanoids as the main mediators and no participation of vasoactive amines. Kinins seem to participate in nociception but not in edema induced by PpV. The results also suggest that metalloproteinases are the main compounds responsible for the edema, but not for the nociception induced by this venom. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Vorinostat: A Potent Agent to Prevent and Treat Laser-induced Corneal Haze

    PubMed Central

    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.

    2015-01-01

    PURPOSE 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. METHODS 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. RESULTS Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit 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. CONCLUSIONS 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. PMID:22386369

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

    PubMed

    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.

  13. Serine protease inhibitor attenuates intracerebral hemorrhage-induced brain injury and edema formation in rat.

    PubMed

    Nakamura, Takehiro; Kuroda, Yasuhiro; Hosomi, Naohisa; Okabe, Naohiko; Kawai, Nobuyuki; Tamiya, Takashi; Xi, Guohua; Keep, Richard F; Itano, Toshifumi

    2010-01-01

    Our previous studies have demonstrated that thrombin plays an important role in intracerebral hemorrhage (ICH)-induced brain injury and edema formation. We, therefore, examined whether nafamostat mesilate (FUT), a serine protease inhibitor, can reduce ICH-induced brain injury. Anesthetized male Sprague-Dawley rats received an infusion of autologous whole blood (100 microL), thrombin (5U/50 microL) or type VII collagenase (0.4 U/2 microL) into the right basal ganglia, the three ICH models used in the present study. FUT (10 mg/kg) or vehicle was administered intraperitoneally 6 h after ICH (or immediately after thrombin infusion) and then at 12-h intervals (six treatments in total, n = 5 in each group). All rats were sacrificed 72 h later. We also examined whether FUT promotes rebleeding in a model in which ICH was induced by intracerebral injection of collagenase. Systemic administration of FUT starting 6 h after ICH reduced brain water content in the ipsilateral basal ganglia 72 h after ICH compared with vehicle. FUT attenuated ICH-induced changes in 8-OHdG and thrombin-reduced brain edema. FUT did not increase collagenase-induced hematoma volume. FUT attenuates ICH-induced brain edema and DNA injury suggesting that serine protease inhibitor may be potential therapeutic agent for ICH.

  14. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

    PubMed

    Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

    2014-03-01

    Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

  15. Contact Lens Induced Corneal Ulcer Management in a Tertiary Eye Unit in Oman - A descriptive study.

    PubMed

    Shah, Rikin; Shah, Manali; Khandekar, Rajiv; Al-Raisi, Abdulatif

    2008-11-01

    The corneal disease is a priority problem in Oman. We present patients with contact lens (CL) induced severe keratitis, admitted in the corneal unit of Al Nahdha Hospital in Oman. The study was conducted in 2005-2006. Ophthalmologists examined the eyes using slit lamp bio-microscope. Visual acuity was noted using Snellen's distance vision chart. Specimens of corneal scraping and CLs were sent for culture and sensitivity tests. Patients with severe keratitis were admitted and treated with medicines. Corneal and visual statuses were noted at the time of discharge from hospital and after six weeks. Numbers, percentages and their 95% confidence intervals were calculated. Pre- and post-treatment vision were compared using a scattergram. The 52 eyes of 15 males and 37 female patients with corneal ulcers were examined. Thirty-two patients were between 20 to 30 years of age. Only 13 (25%) patients had visited an ophthalmologist within 24 hours of developing severe keratitis. Seventeen (33%) had central ulcers and six (11.5%) had ulcer ≥5 mm in size. Pseudomonas was found in 29 (55.8%) of CL and corneal material scraped from the eyes of 15 (28.8%) patients. Vision was <6/60 (legally blind) in 12 (23.1%) eyes before and in five (9.6%) eyes after treatment. Twenty-six (50%) patients were lost to follow up. CL related severe keratitis causes visual disabilities. Prevention and proper records are essential. Treatment improves vision and hence facilities for management should be strengthened.

  16. Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

    PubMed Central

    Li, Zhanrong; Yao, Lin; Li, Jingguo; Zhang, Wenxin; Wu, Xianghua; Liu, Yi; Lin, Miaoli; Su, Wenru; Li, Yongping; Liang, Dan

    2012-01-01

    Purpose Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism. Methods To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea. Results The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm2 to 2.29 ± 0.61 mm2, respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced

  17. Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells

    PubMed Central

    Cieślar-Pobuda, Artur; Rafat, Mehrdad; Knoflach, Viktoria; Skonieczna, Magdalena; Hudecki, Andrzej; Małecki, Andrzej; Urasińska, Elżbieta; Ghavami, Seaid; Łos, Marek J.

    2016-01-01

    The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches. PMID:27275539

  18. Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema.

    PubMed

    Lim, Hyun-Kyung; Kim, Kyoung Mee; Jeong, Seong-Yun; Choi, Eun Kyung; Jung, Joohee

    2016-05-05

    Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non-small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.

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

    PubMed

    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.

  20. Polytetrafluoroethylene fume-induced pulmonary edema: a case report and review of the literature.

    PubMed

    Hamaya, Rikuta; Ono, Yuko; Chida, Yasuyuki; Inokuchi, Ryota; Kikuchi, Ken; Tameda, Tadanobu; Tase, Choichiro; Shinohara, Kazuaki

    2015-05-14

    Polytetrafluoroethylene is ubiquitous in materials commonly used in cooking and industrial applications. Overheated polytetrafluoroethylene can generate toxic fumes, inducing acute pulmonary edema in some cases. However, neither the etiology nor the radiological features of this condition have been determined. For clarification, we report an illustrative case, together with the first comprehensive literature review. A previously healthy 35-year-old Japanese man who developed severe dyspnea presented to our hospital. He had left a polytetrafluoroethylene-coated pan on a gas-burning stove for 10 hours while unconscious. Upon admission, he was in severe respiratory distress. A chest computed tomographic scan showed massive bilateral patchy consolidations with ground-glass opacities and peripheral area sparing. A diagnosis of polytetrafluoroethylene fume-induced pulmonary edema was made. He was treated with non-invasive positive pressure ventilation and a neutrophil elastase inhibitor, which dramatically alleviated his symptoms and improved his oxygenation. He was discharged without sequelae on hospital day 11. A literature review was performed to survey all reported cases of polytetrafluoroethylene fume-induced pulmonary edema. We searched the PubMed, Embase, Web of Science and OvidSP databases for reports posted between the inception of the databases and 30 September 2014, as well as several Japanese databases (Ichushi Web, J-STAGE, Medical Online, and CiNii). Two radiologists independently interpreted all chest computed tomographic images. Eighteen relevant cases (including the presently reported case) were found. Our search revealed that (1) systemic inflammatory response syndrome was frequently accompanied by pulmonary edema, and (2) common computed tomography findings were bilateral ground-glass opacities, patchy consolidation and peripheral area sparing. Pathophysiological and radiological features were consistent with the exudative phase of acute respiratory

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

    PubMed

    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 < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-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. Bi-directional corneal accommodation in alert chicks with experimentally-induced astigmatism.

    PubMed

    Chu, Chin-Hung Geoffrey; Zhou, Yongjin; Zheng, Yongping; Kee, Chea-Su

    2014-05-01

    This study aimed to characterize corneal accommodation in alert chicks with and without experimentally-induced astigmatism. Refraction and corneal biometry were measured in 16 chicks with experimentally-induced astigmatism (>1.00 D) and 6 age-matched control chicks (astigmatism ⩽ 1.00 D). Corneal accommodation was detected using a Placido-ring based videokeratography system, by measuring changes in corneal curvature from a series of consecutive images acquired from alert chicks. The correlation between the magnitudes of corneal accommodation and astigmatism was analyzed by including data from all 22 chicks. Data from all eyes showed obvious bi-directional changes in corneal accommodation. There was no significant difference in corneal accommodative changes between the fellow eyes of the treated birds, and the right and left eyes of control birds. However, positive accommodation (PA) and maximum magnitude of PA (MPA) were significantly higher in the astigmatic vs. the fellow eyes of treated chicks (mean ± SE: PA=+2.24 ± 0.44 D vs. +1.26 ± 0.20 D; MPA=+7.53 ± 0.81 D vs. +4.38 ± 0.53 D, both p<0.05). This was not the case for negative accommodation (NA) or maximum magnitude of NA (MNA) (NA=-0.46 ± 0.15 D vs. -0.33 ± 0.04 D; MNA=-0.92 ± 0.23 D vs. -0.73 ± 0.12D, respectively, p>0.05). Furthermore, higher PA and MPA were found to be correlated with higher refractive astigmatism (both r=0.34, p<0.05). These results suggest that the presence of astigmatism may interfere with accommodative function in chicks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    PubMed

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Involvement of NADPH oxidases in alkali burn-induced corneal injury.

    PubMed

    Gu, Xue-Jun; Liu, Xian; Chen, Ying-Ying; Zhao, Yao; Xu, Man; Han, Xiao-Jian; Liu, Qiu-Ping; Yi, Jing-Lin; Li, Jing-Ming

    2016-07-01

    Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double‑immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn‑induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury.

  5. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    SciTech Connect

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

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

    PubMed

    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

  7. On the Need to Compensate for Edema-Induced Dose Reductions in Preplanned {sup 131}Cs Prostate Brachytherapy

    SciTech Connect

    Chen, Z. Jay Deng Jun; Roberts, Kenneth; Nath, Ravinder

    2008-01-01

    Purpose: Surgical trauma-induced edema and its protracted resolution can lead to significant dose reductions in preplanned {sup 131}Cs prostate brachytherapy. The purpose of this work was to examine whether these dose reductions should be actively compensated for and to estimate the magnitude of the additional irradiation needed for dose compensation. Methods and Materials: The quantitative edema resolution characteristics observed by Waterman et al. were used to examine the physical and radiobiologic effects of prostate edema in preplanned {sup 131}Cs implants. The need for dose compensation was assessed using the dose responses observed in {sup 125}I and {sup 103}Pd prostate implants. The biologically effective dose, calculated with full consideration of edema evolution, was used to estimate the additional irradiation needed for dose compensation. Results: We found that the edema-induced dose reduction in preplanned {sup 131}Cs implants could easily exceed 10% of the prescription dose for implants with moderate or large edema. These dose reductions could lead to a >10% reduction in the biochemical recurrence-free survival for individual patients if the effect of edema was ignored. For a prescribed dose of 120 Gy, the number of 2-Gy external beam fractions needed to compensate for a 5%, 10%, 15%, 20%, and 25% edema-induced dose reduction would be one, four, six, seven, and nine, respectively, for prostate cancer with a median potential doubling time of 42 days. The required additional irradiation increased for fast-growing tumors and/or those less efficient in sublethal damage repair. Conclusion: Compensation of edema-induced dose reductions in preplanned {sup 131}Cs prostate brachytherapy should be actively considered for those implants with moderate or large edema.

  8. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.

    PubMed

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F; Hoyle, Gary W

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury.

  9. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    PubMed Central

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

    2013-01-01

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. PMID:23800689

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

    PubMed

    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) at the time of enrollment. The riboflavin-UVA–induced corneal cross-linking was performed in all patients according to the standard epi-off protocol. Parameters recorded preoperatively and postoperatively were as follows: uncorrected visual acuity, best spectacle–corrected visual acuity, corneal topography and surface aberrometry (CSO Eye Top topographer; Florence, Italy), optical pachometry (Visante OCT; Zeiss Meditec, Jena, Germany), and HRT II confocal microscopy (Rostock Cornea Module, Heidelberg, Germany). Functional data at 36 months showed an increase of +0.18 and +0.16 Snellen lines for uncorrected visual acuity and best spectacle-corrected visual acuity, respectively, in the thicker group (corneal thickness >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

  11. Purification of Pseudomonas aeruginosa proteases and microscopic characterization of pseudomonal protease-induced rabbit corneal damage.

    PubMed Central

    Kreger, A S; Gray, L D

    1978-01-01

    Extracellular proteases of three cornea-virulent strains of Pseudomonas aeruginosa were isolated by sequential ammonium sulfate precipitation, Ultrogel AcA 54 gel filtration, and flat-bed isoelectric focusing. The purity of the preparations was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis , thin-layer isoelectric focusing in polyacrylamide gel, immunodiffusion and immunoelectrophoretic procedures, and tests for the presence of other known pseudomonal products. Light and electron microscopic examination of rabbit corneal lesions observed 4 to 6 h after the intracorneal injection of submicrogram amounts of the proteases revealed: (i) degeneration and necrosis of epithelium, endothelium, and keratocytes, (ii) infiltration, degeneration, and necrosis of polymorphonuclear leukocytes, (iii) loss of the characteristic weblike pattern, colloidal iron staining, and ruthenium red staining of the stromal proteoglycan ground substance, (iv) dispersal of strucutrally normal appearing collagen fibrils, ground substance, (iv) dispersal of structurally normal appearing collagen fibrils, and (v) accumulation of plasma proteins and fibrin in the necrotic corneas. These structural alterations are very similar to those observed previously during experimental P. aeruginosa keratitis, and this similarity supports the idea that pseudomonal proteases are responsible, at least in part, for the rapid and extensive liquefaction necrosis characteristic of pseudomonal-induced keratitis. In addition, the results support the idea that pseudomonal proteases elicit severe corneal damage by causing the loss of the corneal proteoglycan ground substance, thus resulting in dispersal of undamaged collagen fibrils, weakening of the corneal stroma, and subsequent descemetocele formation and corneal perforation by the anterior chamber pressure. Images PMID:415981

  12. The Effects of Portulaca oleracea on Hypoxia-Induced Pulmonary Edema in Mice

    PubMed Central

    Yue, Tan; Xiaosa, Wen; Ruirui, Qi; Wencai, Shi; Hailiang, Xin

    2015-01-01

    Abstract Tan Yue, Wen Xiaosa, Qi Ruirui, Shi Wencai, Xin Hailiang, and Li Min. The effects of Portulaca oleracea on hypoxia-induced pulmonary edema in mice. High Alt Med Biol 16:43–51, 2015—Portulaca oleracea L. (PO) is known as “a vegetable for long life” due to its antioxidant, anti-inflammatory, and other pharmacological activities. However, the protective activity of the ethanol extract of PO (EEPO) against hypoxia-induced pulmonary edema has not been fully investigated. In this study, we exposed mice to a simulated altitude of 7000 meters for 0, 3, 6, 9, and 12 h to observe changes in the water content and transvascular leakage of the mouse lung. It was found that transvascular leakage increased to the maximum in the mouse lung after 6 h exposure to hypobaric hypoxia. Prophylactic administration of EEPO before hypoxic exposure markedly reduced the transvascular leakage and oxidative stress, and inhibited the upregulation of NF-kB in the mouse lung, as compared with the control group. In addition, EEPO significantly reduced the levels of proinflammatory cytokines and cell adhesion molecules in the lungs of mice, as compared with the hypoxia group. Our results show that EEPO can reduce initial transvascular leakage and pulmonary edema under hypobaric hypoxia conditions. PMID:25761168

  13. TGF-{beta}2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

    SciTech Connect

    Lu Jiawei; Lu Zhenyu; Reinach, Peter

    2006-11-01

    The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-{beta}2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-{beta}2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-{beta}2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-{beta}2 and FGF-2 oppositely affect BCE cell proliferation and TGF-{beta}2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-{beta}2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-{beta}2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-{beta}2-induced suppression of the PI3-kinase/AKT signaling pathway.

  14. Corneal topographic changes and surgically induced astigmatism following combined phacoemulsification and 25-gauge vitrectomy

    PubMed Central

    Sayed, Khulood Mohammed; Farouk, Mahmoud M.; Katome, Takashi; Nagasawa, Toshihiko; Naito, Takeshi; Mitamura, Yoshinori

    2017-01-01

    AIM To evaluate corneal topographic changes and surgically induced astigmatism (SIA) after combined phacoemulsification and 25-gauge transconjunctival sutureless vitrectomy (25-G TSV). METHODS A retrospective study on 96 eyes of 87 patients who underwent combined phacoemulsification and 25-G TSV. The different topographic parameters and SIA were analyzed pre- and postoperatively. RESULTS There was no significant changes in corneal topographic parameters at different follow up periods. Only surface regularity index changed significantly in the 2nd postoperative week and then returned to baseline values thereafter. Mean SIA gradually decreased to reach 0.12 D by the 6th postoperative month. CONCLUSION Corneal surface and astigmatic changes are insignificant in either early or late postoperative periods following combined phacoemulsification and 25-G TSV. The SIA was the minimum among previous reports on sutureless vitrectomy alone or combined with phacoemulsification. Improvement of SIA did not stop at the 3rd postoperative month but it continued till the 6th month postoperatively. PMID:28149780

  15. A case of recurrent swimming-induced pulmonary edema in a triathlete: the need for awareness.

    PubMed

    Smith, R; Brooke, D; Kipps, C; Skaria, B; Subramaniam, V

    2016-08-03

    This report discusses a rare case of a 55-year-old female triathlete who developed recurrent episodes of swimming-induced pulmonary edema (SIPE). She had two hospital admissions with pulmonary edema after developing breathlessness while swimming, including a near-drowning experience in an open water swim. With increasing popularity of triathlon and open water sports, this case highlights the importance of a greater awareness of SIPE among health professionals, event organizers, and athletes. This report explores the previous reported cases in triathletes and those who have suffered recurrent episodes. It is paramount that an accurate diagnosis is made as these individuals may be at an increased risk of future life-threatening episodes.

  16. PROLIFERATIVE CAPACITY OF CORNEAL ENDOTHELIAL CELLS

    PubMed Central

    Joyce, Nancy C.

    2011-01-01

    The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic “pump” functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the in vivo induction of transient corneal endothelial cell division or the in vitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new

  17. Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

    PubMed

    Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

    2015-07-28

    Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

  18. Transient corneal opacification induced by cold in Raynaud's disease.

    PubMed

    McWhae, J A; Andrews, D M

    1991-05-01

    A 48-year-old man presented with longstanding complaints of transient blurring of vision on exposure to cold temperatures. A review of family history was noteworthy in that two of the patient's four sons and the patient's brother had similar complaints. All affected individuals had Raynaud's disease. Results of ophthalmic evaluation showed transient corneal opacities. Slit-lamp video photography under cold stress demonstrated conjunctival vascular changes consistent with Raynaud's phenomenon. An extensive work-up for systemic disease was otherwise negative. To the best of the authors' knowledge, anterior segment changes have not been described previously in idiopathic Raynaud's disease.

  19. Therapeutic and inducing effect of corneal crosslinking on infectious keratitis

    PubMed Central

    Jiang, Liang-Zhu; Qiu, Shi-Yan; Li, Zhi-Wei; Zhang, Xiao; Tao, Xiang-Chen; Mu, Guo-Ying

    2016-01-01

    The corneal crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) is a new therapy method to successfully treat infectious keratitis in clinical practice. However, there are rare reports on the complications of CXL such as the secondary keratitis. The diverse clinical outcomes on keratitis have highlighted the necessity to further evaluate the efficacy and complications of CXL. We reviewed the positive and negative reports on UVA/riboflavin related with keratitis and provided our opinion on the therapeutic and side effect of UVA/riboflavin crosslinking on keratitis. PMID:28003986

  20. Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity: comparison of acute corneal barrier dysfunction induced by travoprost Z and travoprost.

    PubMed

    Uematsu, Masafumi; Kumagami, Takeshi; Shimoda, Kenichiro; Kusano, Mao; Teshima, Mugen; To, Hideto; Kitahara, Takashi; Kitaoka, Takashi; Sasaki, Hitoshi

    2011-10-01

    To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives. Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay. Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC. Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.

  1. [Transplantation of corneal endothelial cells].

    PubMed

    Amano, Shiro

    2002-12-01

    endothelial cells. Cultured rabbit corneal endothelial cells that endocytosed iron were injected into the anterior chamber of rabbits whose corneal endothelium was cryo-injured, and were pulled to Descemet's membrane by putting a magnet on the eyelid. In these rabbits, corneal edema decreased more quickly than in the control group and no intraocular pressure rise was observed during 8 weeks after the operation, suggesting that the direct delivery of cultured HCECs into the anterior chamber can be an alternative method of choice. The following obstacles should be addressed to make the transplantation of cultured corneal endothelial cells clinically applicable. 1. To reconstruct a cornea that is the same as or superior to the normal cornea, more innovation is necessary in the method of culturing and seeding HCECs. We should consider utilizing HCECs obtained from fetuses after clearing ethical issues. Moreover, we need to develop a method to enhance the cell density and the cell functions. 2. Porcine corneal stroma is promising as a carrier of HCECs instead of human corneal stroma, which is in very limited supply. The usefulness of porcine corneal stroma acellularized to prevent retrovirus infection should be evaluated. 3. To make the self immature cells applicable to corneal transplantation, we should elucidate the corneal endothelial cell specific markers and the factors that are necessary to induce self immature cells to become corneal endothelial cells. 4. The direct delivery of cultured HCECs into the anterior chamber can be an alternative method of choice when its long-term safety is confirmed.

  2. Modulation of corneal and stromal matrix metalloproteinase by the mannose-induced Acanthamoeba cytolytic protein

    PubMed Central

    Alizadeh, Hassan; Li, Haochuan; Neelam, Sudha; Niederkorn, Jerry Y.

    2008-01-01

    The involvement of the mannose-induced Acanthamoeba cytopathic protein (MIP-133) in tissue injury and activation of metalloproteinase of corneal and stromal cells was examined in vitro. Activation of MMP-1, MMP-2, MMP-3, and MMP-9 induced by MIP-133 on human corneal epithelial and stromal cell cultures was examined by reverse transcriptase polymerase chain reaction (RT-PCR), and ELISA. MMP-1, MMP-2, MMP-3, and MMP-9 mRNA were expressed in both cultured human corneal epithelial and stromal cells. When the epithelial cells were exposed to MIP-133 protein, the mRNA expression for MMP-1 and MMP-9 was unchanged. However, the transcript for MMP-2 and MMP-3 was decreased by two fold. By contrast, the expression of MMP-2 and MMP-3 was significantly up-regulated (2–4 fold) in the corneal stromal cells 1, 4, and 8 hours after MIP-133 stimulation. At the protein level, there was no significant difference in the level of MMPs between the corneal epithelial cells before and after stimulation with MIP-133. By contrast, the levels of MMP-2 and MMP-3 were significantly higher in the corneal stromal cells stimulated with MIP-133. The supernatants from corneal stromal cells stimulated with MIP-133 were incubated with PMSF and MIP-133 antibody and the level of MMP-2 was measured by ELISA. Activation of MMP-2 by MIP-133 was inhibited in the supernatants pretreated with the serine protease inhibitor, PMSF, and anti-MIP-133. Supernatants pretreated with the cysteine protease inhibitor E6 or control antibody produced the same amount of MMP-2 as the untreated supernatants. To verify the possible of homology between MMPs and A. castellanii proteases, the mRNA from A. castellanii was prepared and analyzed for the expression of MMP genes by PT-PCR. The results showed that A. castellanii did not express mRNA for MMP-1, MMP-2, MMP-3, or MMP-9. Thus, A. castellanii mRNA does not cross react with human MMPs. Furthermore, ELISA was used to determine the cross reactivity of MMP antibodies with

  3. Basiliximab induced non-cardiogenic pulmonary edema in two pediatric renal transplant recipients.

    PubMed

    Dolan, Niamh; Waldron, Mary; O'Connell, Marie; Eustace, Nick; Carson, Kevin; Awan, Atif

    2009-11-01

    We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

  4. Acute ethanol-induced changes in edema and metabolite concentrations in rat brain.

    PubMed

    Liu, Huimin; Zheng, Wenbin; Yan, Gen; Liu, Baoguo; Kong, Lingmei; Ding, Yan; Shen, Zhiwei; Tan, Hui; Zhang, Guishan

    2014-01-01

    The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy ((1)H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

  5. Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

    PubMed Central

    Lefebvre, Nicolas; Forestier, Emmanuel; Farhi, David; Mahsa, Mohseni Zadeh; Remy, Véronique; Lesens, Olivier; Christmann, Daniel; Hansmann, Yves

    2007-01-01

    Background Hypersentivity Syndrome (HS) may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature. Case presentation A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months. Conclusion Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome. PMID:17511865

  6. Alkali burn versus suture-induced corneal neovascularization in C57BL/6 mice: an overview of two common animal models of corneal neovascularization.

    PubMed

    Giacomini, Chiara; Ferrari, Giulio; Bignami, Fabio; Rama, Paolo

    2014-04-01

    The purpose of the present study was to quantify and compare corneal hem- and lymphangiogenesis between alkali burn and suture-induced corneal neovascularization (CNV) in two commonly used mouse strains. A retrospective analysis was performed on C57BL/6 and FVB neovascularized corneas. CNV was induced by surface caustication with NaOH or intrastromal placement of three 10.0 nylon sutures. Hemangiogenesis and lymphangiogenesis extent was calculated on whole mounted corneas by CD31 and LYVE1 immunofluorescence analysis. Blood vessel growth was similar between alkali burn and suture-induced CNV in C57BL/6 mice, and between C57BL/6 and FVB sutured strains. On the contrary, corneal lymphangiogenesis was more pronounced in the C57BL/6 sutured mice versus the alkali burn group, and in the FVB strain versus both C57BL/6 models. These results indicate that significant differences occur in lymphangiogenesis, but not hemangiogenesis, in the alkali burn and suture-induced models in C57BL/6 mice. Furthermore, lymphangiogenesis is more pronounced in the albino (FVB) strain after suture placement. We suggest that the suture model has a number of advantages and may be preferentially used to study corneal lymphangiogenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Acute ozone-induced lung injury in rats: Structural-functional relationships of developing alveolar edema

    SciTech Connect

    Paterson, J.F.; Hammond, M.D.; Montgomery, M.R.; Sharp, J.T.; Farrier, S.E.; Balis, J.U. )

    1992-11-01

    As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH[sub 2]O/kg) from a control value of 0.84 [plus minus] 0.02 (SEM) to 0.72 [plus minus] 0.04 and 0.57 [plus minus] 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO[sub 2] to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H[sub 2]O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.

  8. Preliminary study of the association between corneal histocytological changes and surgically induced astigmatism after phacoemulsification.

    PubMed

    Du, Xing; Zhao, Guiqiu; Wang, Qing; Yang, Xian; Gao, Ang; Lin, Jing; Wang, Qian; Xu, Qiang

    2014-11-20

    Surgically induced astigmatism (SIA) was one of the factors that influences the desirable refractive outcome, and it was related to the length, type, location, structure of the incision and to the suture closure technique, etc. The aim was to evaluate the association of corneal histocytological changes with SIA after phacoemulsification. The study enrolled 68 cases of cataract patient (68 eyes). Corneal histocytological parameters at corneal incision, central cornea and contralateral incision obtained by confocal microscope through focusing (CMTF) were compared preoperatively and 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively. These biometric parameters included the endothelial cell density, keratocyte density of posterior stromal layer, and the morphological changes. SIA was calculated by Jaffe's vector analysis. 1 From preoperatively to 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively, the endothelail cell density was decreased significantly (p < 0.05). Keratocyte density of posterior stroma layer was increased significantly only at 1 week, 2 weeks, 1 month, 3 months postoperatively (p <0.05), but not statistically significant (p = 0.173) at 6 months postoperatively compared to preoperative values. 2 The histocytological observations indicated that the morphology changed significantly postoperatively at the corneal incision, including the cell absent area, wave-like area, dot-like and mass-like hyperreflection, stripe-like absent area, in the endothelial layer, and the keratocyte activation, microfolds, irregular hyporeflective or hyperreflective belt, and a little dot-like hyperreflection in the posterior stroma layer. 3 The reduction of the endothelial cell density at the corneal incision at 1 week, 2 weeks, 1 month postoperatively, were positively correlated with SIA (P1 week = 0.003, P2 weeks = 0.003, P1 month = 0.032), while others were not associated with SIA statistically. The reduction of endothelail cell density and the

  9. Wound stability and surgically induced corneal astigmatism after transconjunctival single-plane sclerocorneal incision cataract surgery.

    PubMed

    Hayashi, Ken; Ogawa, Soichiro; Yoshida, Motoaki; Yoshimura, Koichi

    2017-01-01

    To compare intraocular pressure (IOP) immediately after cataract surgery, and surgically induced corneal astigmatism (SIA) and corneal shape changes between eyes with transconjunctival single-plane sclerocorneal incisions (TSSIs) and eyes with clear corneal incisions (CCIs). Bilateral eyes of 64 patients undergoing phacoemulsification were randomized to undergo 2.4-mm temporal TSSI or CCI. IOP was measured preoperatively, and in the immediate postoperative periods. SIA was determined using vector analysis, and corneal shape changes and irregular astigmatism were evaluated using a videokeratography preoperatively, and in the early postoperative periods. Wound hydration was performed in 23 eyes (35.9 %) of the TSSI group and in 60 (93.8 %) of the CCI group (P < 0.0001). Mean IOP was significantly higher in the TSSI group than in the CCI group at 30, 60, and 120 min postoperatively (P ≤ 0.0179). SIA tended to be smaller in the TSSI group than the CCI group, but the difference was not significant. The higher order irregular astigmatism was smaller in the TSSI group than in the CCI group at 2 days (P = 0.0312). The videokeratography revealed a wound-related flattening postoperatively in both groups; this change disappeared within 4 weeks in the TSSI group, whereas it persisted until 12 weeks in the CCI group. IOP was significantly higher immediately after TSSI than after CCI and required less wound hydration, suggesting better stability with TSSI. Higher order irregular astigmatism and wound-related corneal flattening were smaller after TSSI than after CCI in the early periods, suggesting that fewer corneal shape changes with TSSI.

  10. Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice.

    PubMed

    Koshal, Prashant; Kumar, Puneet

    2016-07-01

    GLP-1 play important role in neuroprotection and GLP-1 receptor deficit mice showed decreased seizure threshold and increased cognitive impairment. Therefore, study was premeditated to investigate the effect of liraglutide (GLP-1 analogue) on cornel kindling epilepsy induced co-morbidities in mice. Corneal kindling was induced by electrical stimulation (6 mA, 50 Hz, 3 s); twice daily for 13 days. Liraglutide (75 and 150 µg/kg) and phenytoin (20 mg/kg) were administered in corneal kindled groups. On day 14, elevated plus maze, passive shock avoidance paradigms were performed, and on day 15, retention was taken. On day 16 tail suspension test were performed. On 20th day challenge test was performed with same electrical stimulation and retention was observed on elevated plus maze and passive avoidance paradigm. Animal were sacrificed on 21st day for biochemical (LPO, GSH, and nitrite) and neurochemical (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Electrical stimulation by corneal electrode for 13 days developed generalized clonic seizures, increased cognitive impairment, oxidative stress and neurochemical alteration in mice brain. Co-treatment with liraglutide (75 and 150 μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative stress and restored the altered level of neurotransmitters observed in corneal kindled mouse.

  11. Edema induced by Bothrops asper (Squamata: Viperidae) snake venom and its inhibition by Costa Rican plant extracts.

    PubMed

    Badilla, Beatriz; Chaves, Fernando; Mora, Gerardo; Poveda, Luis J

    2006-06-01

    We tested the capacity of leaf (Urera baccifera, Loasa speciosa, Urtica leptuphylla, Chaptalia nutans, and Satureja viminea) and root (Uncaria tomentosa) extracts to inhibit edema induced by Bothrops asper snake venom. Edema-forming activity was studied plethysmographically in the rat hind paw model. Groups of rats were injected intraperitoneally with various doses of each extract and, one hour later, venom was injected subcutaneously in the right hind paw. Edema was assessed at various time intervals. The edematogenic activity was inhibited in those animals that received an injection U. tomentosa, C. nutans or L. speciosa extract. The extract of U. baccifera showed a slight inhibition of the venom effect. Extract from S. viminea and, to a lesser extent that of U. leptuphylla, induced a pro-inflammatory effect, increasing the edema at doses of 250 mg/kg at one and two hours.

  12. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    PubMed

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats.

  13. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization

    PubMed Central

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo

    2016-01-01

    Abstract The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats. PMID:26348484

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

    PubMed

    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.

  15. Lovastatin Inhibits the Thrombin-Induced Loss of Barrier Integrity in Bovine Corneal Endothelium

    PubMed Central

    2010-01-01

    Purpose: Increased actomyosin contraction of the dense band of actin cytoskeleton at the apical junctional complex (perijunctional actomyosin ring, PAMR) breaks down the barrier integrity of corneal endothelium. This study has investigated the efficacy of statins, which inhibit activation of RhoA, in opposing the thrombin-induced loss of barrier integrity of monolayers of cultured bovine corneal endothelium. Methods: Myosin light chain (MLC) phosphorylation, a biochemical measure of actomyosin contraction, was assayed by urea–glycerol gel electrophoresis, followed by western blot analysis. The locus of MLC phosphorylation and changes in the organization of the PAMR were visualized by immunostaining. Phosphorylation of MYPT1, a regulatory subunit of myosin light-chain phosphatase (MLCP), was assessed by Western blot analysis to determine down-regulation of RhoA. The barrier integrity was assessed in terms of trans-endothelial electrical resistance (TER), and further confirmed by determining permeability to FITC dextran (10 kDa) and distribution of ZO-1, a marker of tight junctional assembly. Results: Lovastatin, a prototype of lipophilic statins, induced MLC dephosphorylation under basal conditions. It opposed increase in phosphorylation of MLC and MYPT1 in response to thrombin and nocodazole, agents known to activate RhoA in the endothelium. Pretreatment with the statin opposed the thrombin- and nocodazole-induced disruption of the PAMR and the thrombin-induced decline in TER. Lovastatin also opposed the thrombin- and nocodazole-induced increase in permeability to FITC dextran and redistribution of ZO-1. However, upon supplementation with GGPP (geranylgeranyl pyrophosphate), lovastatin failed to oppose the effects of thrombin and nocodazole on the PAMR, ppMLC, and ZO-1 distribution. Conclusions: Lovastatin attenuates RhoA activation in the corneal endothelium presumably by reducing its isoprenylation. This underlies the suppression of the thrombin-induced loss in

  16. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure.

    PubMed

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; Hahn, Rita A; Po, Iris P; Zhou, Peihong; Lacey, C Jeffrey; Pillai, Abhilash; C Young, Sherri; Flowers, Robert A; Gallo, Michael A; Laskin, Jeffrey D; Gerecke, Donald R; Svoboda, Kathy K H; Heindel, Ned D; Gordon, Marion K

    2016-04-01

    Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial-stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial-stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3-100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Nitrogen mustard-induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial-stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial-stromal attachment. Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial-stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial-stromal separation.

  17. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure

    PubMed Central

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; A. Hahn, Rita; P. Po, Iris; Zhou, Peihong; Lacey, C. Jeffrey; Pillai, Abhilash; C. Young, Sherri; A. Flowers II, Robert; A. Gallo, Michael; D. Laskin, Jeffrey; R. Gerecke, Donald; K. H. Svoboda, Kathy; D. Heindel, Ned; Gordon, Marion K.

    2016-01-01

    Purpose Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial–stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial–stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Methods Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3–100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Results Nitrogen mustard–induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial–stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial–stromal attachment. Conclusions Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial–stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial–stromal separation. PMID:27058125

  18. Acoustic radiation force for noninvasive evaluation of corneal biomechanical changes induced by cross-linking therapy.

    PubMed

    Urs, Raksha; Lloyd, Harriet O; Silverman, Ronald H

    2014-08-01

    To noninvasively measure changes in corneal biomechanical properties induced by ultraviolet-activated riboflavin cross-linking therapy using acoustic radiation force (ARF). Cross-linking was performed on the right eyes of 6 rabbits, with the left eyes serving as controls. Acoustic radiation force was used to assess corneal stiffness before treatment and weekly for 4 weeks after treatment. Acoustic power levels were within US Food and Drug Administration guidelines for ophthalmic safety. Strain, determined from ARF-induced displacement of the front and back surfaces of the cornea, was fit to the Kelvin-Voigt model to determine the elastic modulus (E) and coefficient of viscosity (η). The stiffness factor, the ratio of E after treatment to E before treatment, was calculated for treated and control eyes. At the end of 4 weeks, ex vivo thermal shrinkage temperature analysis was performed for comparison with in vivo stiffness measurements. One-way analysis of variance and Student t tests were performed to test for differences in E, η, the stiffness factor, and corneal thickness. Biomechanical stiffening was immediately evident in cross-linking-treated corneas. At 4 weeks after treatment, treated corneas were 1.3 times stiffer and showed significant changes in E (P= .006) and η (P= .007), with no significant effect in controls. Corneal thickness increased immediately after treatment but did not differ significantly from the pretreatment value at 4 weeks. Our findings demonstrate a statistically significant increase in stiffness in cross-linking-treated rabbit corneas based on in vivo axial stress/strain measurements obtained using ARF. The capacity to noninvasively monitor corneal stiffness offers the potential for clinical monitoring of cross-linking therapy. © 2014 by the American Institute of Ultrasound in Medicine.

  19. Acoustic Radiation Force for Noninvasive Evaluation of Corneal Biomechanical Changes Induced by Cross-linking Therapy

    PubMed Central

    Urs, Raksha; Lloyd, Harriet O.; Silverman, Ronald H.

    2015-01-01

    Objectives To noninvasively measure changes in corneal biomechanical properties induced by ultraviolet-activated riboflavin cross-linking therapy using acoustic radiation force (ARF). Methods Cross-linking was performed on the right eyes of 6 rabbits, with the left eyes serving as controls. Acoustic radiation force was used to assess corneal stiffness before treatment and weekly for 4 weeks after treatment. Acoustic power levels were within US Food and Drug Administration guidelines for ophthalmic safety. Strain, determined from ARF-induced displacement of the front and back surfaces of the cornea, was fit to the Kelvin-Voigt model to determine the elastic modulus (E) and coefficient of viscosity (η). The stiffness factor, the ratio of E after treatment to E before treatment, was calculated for treated and control eyes. At the end of 4 weeks, ex vivo thermal shrinkage temperature analysis was performed for comparison with in vivo stiffness measurements. One-way analysis of variance and Student t tests were performed to test for differences in E, η, the stiffness factor, and corneal thickness. Results Biomechanical stiffening was immediately evident in cross-linking–treated corneas. At 4 weeks after treatment, treated corneas were 1.3 times stiffer and showed significant changes in E(P= .006) and η (P= .007), with no significant effect in controls. Corneal thickness increased immediately after treatment but did not differ significantly from the pretreatment value at 4 weeks. Conclusions Our findings demonstrate a statistically significant increase in stiffness in cross-linking–treated rabbit corneas based on in vivo axial stress/strain measurements obtained using ARF. The capacity to noninvasively monitor corneal stiffness offers the potential for clinical monitoring of cross-linking therapy. PMID:25063407

  20. Complementary treatment of contact lens-induced corneal ulcer using honey: a case report.

    PubMed

    Majtanova, Nora; Vodrazkova, Erika; Kurilova, Veronika; Horniackova, Miroslava; Cernak, Martin; Cernak, Andrej; Majtan, Juraj

    2015-02-01

    The aim of this study was to report the complementary use of honey for treatment of a contact lens-induced corneal ulcer. A 23-year-old contact lens user presented with a corneal ulcer in her left eye. She had visual acuity reduced to hand movement. There was a history of wearing contact lenses while swimming in a lake seven days before presentation. The cultures from corneal scrapings and contact lenses were positive for Klebsiella oxytoca, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Pseudomonas spp. The treatment with topical levofloxacin and 25% (w/v) γ-irradiated honeydew honey solution was effective and the patient achieved final best corrected visual acuity of affected eye. In addition to positive clinical outcome, honeydew honey was shown to be highly effective in vitro against ocular isolates, in particular S. maltophilia. The minimal inhibitory concentrations for honeydew honey ranged from 5% to 10%. These results demonstrate that honey is a promising antibacterial agent in management of corneal ulcers. Moreover, honey exhibits anti-biofilm and anti-inflammatory properties, and thus becomes an interesting ophthalmologic agent.

  1. Therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary edema.

    PubMed

    Wang, Shih-Min; Lei, Huan-Yao; Huang, Mei-Chih; Wu, Jing-Min; Chen, Chun-Ta; Wang, Jieh-Neng; Wang, Jen-Ren; Liu, Ching-Chuan

    2005-03-01

    Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998-June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P=0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 +/- 17/min vs. 206 +/- 26/min, P=0.004). A marked decrease in IL-13 (77 +/- 9 pg/ml vs. 162 +/- 88 pg/ml, P=0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 +/- 4,537/mm3 vs. 19,475 +/- 7,798/mm3, P=0.009) and platelet (257 +/- 45 x 10(3)/mm3 vs. 400 +/- 87 x 10(3)/mm3, P=0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder.

  2. A Novel Zebrafish Model to Provide Mechanistic Insights into the Inflammatory Events in Carrageenan-Induced Abdominal Edema

    PubMed Central

    Huang, Shi-Ying; Feng, Chien-Wei; Hung, Han-Chun; Chakraborty, Chiranjib; Chen, Chun-Hong; Chen, Wu-Fu; Jean, Yen-Hsuan; Wang, Hui-Min David; Sung, Chun-Sung; Sun, Yu-Min; Wu, Chang-Yi; Liu, Wangta; Hsiao, Chung-Der; Wen, Zhi-Hong

    2014-01-01

    A suitable small animal model may help in the screening and evaluation of new drugs, especially those from natural products, which can be administered at lower dosages, fulfilling an urgent worldwide need. In this study, we explore whether zebrafish could be a model organism for carrageenan-induced abdominal edema. The research results showed that intraperitoneal (i.p.) administration of 1.5% λ-carrageenan in a volume of 20 µL significantly increased abdominal edema in adult zebrafish. Levels of the proinflammatory proteins tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were increased in carrageenan-injected adult zebrafish during the development of abdominal edema. An associated enhancement was also observed in the leukocyte marker, myeloperoxidase (MPO). To support these results, we further observed that i.p. methylprednisolone (MP; 1 µg), a positive control, significantly inhibited carrageenan-induced inflammation 24 h after carrageenan administration. Furthermore, i.p. pretreatment with either an anti-TNF-α antibody (1∶5 dilution in a volume of 20 µL) or the iNOS-selective inhibitor aminoguanidine (AG; 1 µg) inhibited carrageenan-induced abdominal edema in adult zebrafish. This new animal model is uncomplicated, easy to develop, and involves a straightforward inducement of inflammatory edema for the evaluation of small volumes of drugs or test compounds. PMID:25141004

  3. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats

    PubMed Central

    Akella, Aparna; Tiwari, Anil K.; Rai, Om P.; Deshpande, Shripad B.

    2016-01-01

    Objective: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Materials and Methods: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. Results: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema. PMID:26997727

  4. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats.

    PubMed

    Akella, Aparna; Tiwari, Anil K; Rai, Om P; Deshpande, Shripad B

    2016-01-01

    Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans

    PubMed Central

    Taylor, Bryan J.; Carlson, Alex R.; Miller, Andrew D.; Johnson, Bruce D.

    2014-01-01

    We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 yr) and 10 old (OLD; 69±5 yr) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (−10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9 ml/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23 ml, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (−7±4%) and 2 of the 10 OLD subjects (−10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema. PMID:24200644

  8. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    PubMed

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  9. Topical treatment of corneal alkali burns with Gly-thymosin β4 solutions and in situ hydrogels via inhibiting corneal neovascularization and improving corneal epidermal recovery in experimental rabbits.

    PubMed

    Zhang, Weili; Nie, Liya; Du, Lina; Chen, Wenyang; Wu, Zhihong; Jin, Yiguang

    2017-06-09

    Corneal alkali burns are a severe disease and commonly encountered in the emergent clinic. A rapid medical treatment for the burn is very important. Gly-thymosin β4 (Gly-Tβ4) is a biomimic derivative of natural thymosin β4. The aim of this study is to evaluate the corneal recovery effects of Gly-Tβ4 topical therapy on alkali burns in rabbit corneas. Rabbit alkali burns were induced with NaOH-contained filter paper. Phosphate-buffered solutions at pH 7.0, Gly-Tβ4 solutions, blank in situ hydrogels, and Gly-Tβ4in situ hydrogels were dropped on the burned corneas. The treatments were continued for 14 days. Conjunctiva hyperemia, corneal edema, intraeye extravasation, hemorrhaging, corneal neovascularization (CNV), and corneal opacity were observed. Corneal immunohistochemistry and histopathology were performed. Gly-Tβ4 solutions led to a lower corneal burn index than the other regimens. Hydrogels may stimulate the burned corneas due to the direct contact of them, and prevent the rapid release of Gly-Tβ4. Gly-Tβ4 significantly inhibited CNV according to the images of the corneas, CNV areas, and CD31 expression. Furthermore, Gly-Tβ4 improved corneal epidermal recovery according to the histopathological result. Gly-Tβ4 solutions are a promising formulation for topical treatment of corneal alkali burns. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  10. Hypoxia-inducible factor-1α contributes to brain edema after stroke by regulating aquaporins and glycerol distribution in brain.

    PubMed

    Higashida, Tetsuhiro; Peng, Changya; Li, Jie; Dornbos, David; Teng, Kailing; Li, Xiaohua; Kinni, Harish; Guthikonda, Murali; Ding, Yuchuan

    2011-02-01

    Brain edema following stroke is a critical clinical problem due to its association with increased morbidity and mortality. Despite its significance, present treatment for brain edema simply provides symptomatic relief due to the fact that molecular mechanisms underlying brain edema remain poorly understood. The present study investigated the role of hypoxia-inducible factor-1α (HIF-1α) and aquaporins (AQP-4 and -9) in regulating cerebral glycerol accumulation and inducing brain edema in a rodent model of stroke. Two-hours of middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in male Sprague-Dawley rats (250-280 g). Anti-AQP-4 antibody, anti-AQP-9 antibody, or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) was given at the time of MCAO. The rats were sacrificed at 1 and 24 hours after reperfusion and their brains were examined. Extracellular and intracellular glycerol concentration of brain tissue was calculated with an enzymatic glycerol assay. The protein expressions of HIF-1α, AQP-4 and AQP-9 were determined by Western blotting. Brain edema was measured by brain water content. Compared to control, edema (p < 0.01), increased glycerol (p < 0.05), and enhanced expressions of HIF-1α, AQP-4, and AQP-9 (p < 0.05) were observed after stroke. With inhibition of AQP-4, AQP-9 or HIF-1α, edema and extracellular glycerol were significantly (p < 0.01) decreased while intracellular glycerol was increased (p < 0.01) 1 hour after stroke. Inhibition of HIF-1α with 2ME2 suppressed (p < 0.01) the expression of AQP-4 and AQP-9. These findings suggest that HIF-1α serves as an upstream regulator of cerebral glycerol concentrations and brain edema via a molecular pathway involving AQP-4 and AQP-9. Pharmacological blockade of this pathway in stroke patients may provide novel therapeutic strategies.

  11. Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.

    PubMed

    Li, Yi-Han; Wen, Qian; Fan, Ting-Jun; Ge, Yuan; Yu, Miao-Miao; Sun, Ling-Xiao; Zhao, Yu

    2015-01-01

    Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed that PPF at concentrations ranging from 0.0625 to 1.0 g/l had poignant cytotoxicity to HCE cells, and the extent of its cytotoxicity was dose- and time-dependent. Further characterization indicated that PPF induced plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. In conclusion, PPF above 0.0625 g/l has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic.

  12. Edematogenic activity of scorpion venoms from the Buthidae family and the role of platelet-activating factor and nitric oxide in paw edema induced by Tityus venoms.

    PubMed

    Severino, D N; Pereira, R L; Knysak, I; Cândido, D M; Kwasniewski, F H

    2009-02-01

    We compared the edematogenic activity of venoms of scorpions from the Buthidae family, Tityus bahiensis (Tbv), Tityus serrulatus (Tsv) and Rhopalurus rochai (Rrv). Three doses (20, 40 and 80 microg/kg sc) of each venom were administrated in hind paw of mice and edema was measured from 5 min to 24 h. Tbv and Tsv both induced edema of rapid onset (135% of increase at 15 min); Rrv induced only a mild edema (40% of increase). We then investigated the involvement of platelet-activating factor (PAF) and endogenous nitric oxide (NO) in Tbv and Tsv-induced paw edema. Pretreatment of mice with a PAF antagonist (WEB-2170) inhibited Tsv but not Tbv-induced edema. Pretreatment with a non selective inhibitor of NO-synthases (L: -NAME) inhibited or increased the edema depending on the dose and the time the edema was measured. In conclusion, the venoms from Tityus are stronger inducers of edema than the venom from the Rhopalurus scorpion. The venoms of Tityus species are similar in potency and time-course edema development. PAF is involved in the edema induced only by Tsv.

  13. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery

    PubMed Central

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  14. Evaluation of acute corneal barrier change induced by topically applied preservatives using corneal transepithelial electric resistance in vivo.

    PubMed

    Kusano, Mao; Uematsu, Masafumi; Kumagami, Takeshi; Sasaki, Hitoshi; Kitaoka, Takashi

    2010-01-01

    We evaluated acute changes in corneal barrier function after instillation with preservatives using corneal transepithelial electric resistance (TER) in vivo and cytotoxicity tests in vitro. The corneal TER of live rabbits was measured using a volt-ohm meter and silver/silver chloride electrodes. The cornea was exposed to the preservatives benzalkonium chloride (BAC; 0.001%, 0.002%, 0.005%, 0.01%, and 0.02%), 0.04% paraben, 0.5% chlorobutanol, 0.005% chlorhexidine digluconate, 2% boric acid, and 0.01% ethylenediaminetetraacetic acid, and then changes in the TER were monitored for 60 seconds. Cultured normal rabbit corneal epithelial cells were exposed to the same preservatives for 60 seconds in vitro, and cell viability was evaluated using the WST-1 assay. The TER instantly decreased and became significantly lower than the control within 10 seconds after instillation with 0.01% and 0.02% BAC (P < 0.01) and within 60 seconds after that with 0.005% BAC (P < 0.01). The TER decreased concomitantly with increasing BAC concentration. Cell viability after instillation with 0.005%, 0.01%, and 0.02% BAC for 60 seconds was significantly lower than that of the control (P < 0.0001). None of the other preservatives significantly altered the TER or cell viability. Decreases in the TER correlated with cell viability (r = 0.94, P < 0.0001). Instillation with BAC immediately disrupted the corneal epithelium. Corneal epithelial cell death is supposed to be associated with a decline in barrier function; thus, corneal TER measurement in vivo can assess the acute toxicity of preservatives added to ophthalmic drugs.

  15. Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer

    PubMed Central

    Batawi, Hatim; Kothari, Nikisha; Camp, Andrew; Bernhard, Luis; Karp, Carol L.; Galor, Anat

    2016-01-01

    Purpose We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method This is an observational case report study. Results A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion Corneal hydrops can occur in the setting of corneal infections. PMID:26889160

  16. [The research advance of small molecules inducing embryonic stem cells to differentiate into corneal epithelial-like cells].

    PubMed

    Qin, L M; Chen, H; Huang, Y F

    2017-03-11

    Stem cells are becoming a hot topic of basic medicine and clinical research because of their wide self-renewal and differentiation potential in recent years. A number of small molecules that can be used to control stem cell self-renewal, lineage differentiation, reprogramming and regeneration could regulate stem cell fate quickly and reversibly. If small molecules could induce human embryonic stem cells to differentiate into corneal epithelial-like cells in vivo, corneal cell transplantation therapy will have unlimited source of corneal epithelium. More patients will obtain effective and timely treatment. (Chin J Ophthalmol, 2017, 53: 230-235).

  17. MYELIN IN THE CENTRAL NERVOUS SYSTEM AS OBSERVED IN EXPERIMENTALLY INDUCED EDEMA IN THE RAT

    PubMed Central

    Hirano, Asao; Zimmerman, H. M.; Levine, Seymour

    1966-01-01

    The compact arrangement of cells in the normal white matter of the brain makes an analysis of cellular architecture difficult. To overcome this difficulty, cerebral edema was induced in rats by means of the unilateral intracerebral implantation of silver nitrate. Within 48 hr, the brains were fixed by perfusion with glutaraldehyde followed by immersion in Dalton's chrome-osmium. Sections of the callosal radiations were studied in the electron microscope. The untreated hemisphere appeared entirely unaltered, whereas in the edematous hemisphere the edema fluid separated individual cell processes and small groups of them. The myelin sheaths and their relationships to the axons appeared essentially unaltered. In this material, analysis of cellular architecture was relatively easy, and the widely held theory of spiral wrapping could be confirmed. In addition, several other aspects of the myelin and myelin-forming cell relationships became apparent in the edematous tissue. Most of these were later confirmed by extensive and careful study of the nonedematous tissue. These included the presence of occasional isolated cytoplasmic areas in myelin and the presence of two complete sheaths around a single axon. Other observations, such as the appearance of mitochondria and dense bodies within the outer loop and the separation of myelin lamellae, are apparently limited to the edematous tissue. PMID:5971641

  18. Myelin in the central nervous system as observed in experimentally induced edema in the rat.

    PubMed

    Hirano, A; Zimmerman, H M; Levine, S

    1966-12-01

    The compact arrangement of cells in the normal white matter of the brain makes an analysis of cellular architecture difficult. To overcome this difficulty, cerebral edema was induced in rats by means of the unilateral intracerebral implantation of silver nitrate. Within 48 hr, the brains were fixed by perfusion with glutaraldehyde followed by immersion in Dalton's chrome-osmium. Sections of the callosal radiations were studied in the electron microscope. The untreated hemisphere appeared entirely unaltered, whereas in the edematous hemisphere the edema fluid separated individual cell processes and small groups of them. The myelin sheaths and their relationships to the axons appeared essentially unaltered. In this material, analysis of cellular architecture was relatively easy, and the widely held theory of spiral wrapping could be confirmed. In addition, several other aspects of the myelin and myelin-forming cell relationships became apparent in the edematous tissue. Most of these were later confirmed by extensive and careful study of the nonedematous tissue. These included the presence of occasional isolated cytoplasmic areas in myelin and the presence of two complete sheaths around a single axon. Other observations, such as the appearance of mitochondria and dense bodies within the outer loop and the separation of myelin lamellae, are apparently limited to the edematous tissue.

  19. Radiation induced endothelial cell retraction in vitro: correlation with acute pulmonary edema.

    PubMed

    Onoda, J M; Kantak, S S; Diglio, C A

    1999-01-01

    We determined the effects of low dose radiation (<200 cGy) on the cell-cell integrity of confluent monolayers of pulmonary microvascular endothelial cells (PMEC). We observed dose- and time-dependent reversible radiation induced injuries to PMEC monolayers characterized by retraction (loss of cell-cell contact) mediated by cytoskeletal F-actin reorganization. Radiation induced reorganization of F-actin microfilament stress fibers was observed > or =30 minutes post irradiation and correlated positively with loss of cell-cell integrity. Cells of irradiated monolayers recovered to form contact inhibited monolayers > or =24 hours post irradiation; concomitantly, the depolymerized microfilaments organized to their pre-irradiated state as microfilament stress fibers arrayed parallel to the boundaries of adjacent contact-inhibited cells. Previous studies by other investigators have measured slight but significant increases in mouse lung wet weight >1 day post thoracic or whole body radiation (> or =500 cGy). Little or no data is available concerning time intervals <1 day post irradiation, possibly because of the presumption that edema is mediated, at least in part, by endothelial cell death or irreversible loss of barrier permeability functions which may only arise 1 day post irradiation. However, our in vitro data suggest that loss of endothelial barrier function may occur rapidly and at low dose levels (< or =200 cGy). Therefore, we determined radiation effects on lung wet weight and observed significant increases in wet weight (standardized per dry weight or per mouse weight) in < or =5 hours post thoracic exposure to 50 200 cGy x-radiation. We suggest that a single fraction of radiation even at low dose levels used in radiotherapy, may induce pulmonary edema by a reversible loss of endothelial cell-cell integrity and permeability barrier function.

  20. Nitrogen mustard-induced corneal injury involves DNA damage and pathways related to inflammation, epithelial-stromal separation and neovascularization

    PubMed Central

    Goswami, Dinesh G; Tewari-Singh, Neera; Dhar, Deepanshi; Kumar, Dileep; Agarwal, Chapla; Ammar, David A; Kant, Rama; Enzenauer, Robert W; Petrash, J Mark; Agarwal, Rajesh

    2015-01-01

    Purpose To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to vesicating agent, nitrogen mustard (NM), a bi-functional alkylating analog of chemical warfare agent sulfur mustard (SM). Methods Toxic effects and associated mechanisms were examined in maximal affected corneal tissue employing corneal cultures and human corneal epithelial (HCE) cells exposed to nitrogen mustard (NM). Results Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation and levels of VEGF, COX-2 and MMP-9. In HCE cells, NM exposure resulted in a dose-dependent decrease in cell viability and proliferation, which was associated with DNA damage in terms of an increase in p53 ser15, total p53 and H2A.X ser139 levels. NM exposure also induced caspase-3 and PARP cleavage, suggesting their involvement in NM-induced apoptotic death in rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in COX-2, MMP-9 and VEGF levels in HCE cells, indicating a role of these molecules and related pathways in NM-induced corneal inflammation, epithelial-stromal separation and neovascularization. NM exposure also induced activation of AP-1 transcription factor proteins and upstream signaling pathways including MAPKs and Akt, suggesting that these could be key factors involved in NM-induced corneal injury. Conclusion Results from this study provide insight into the molecular targets and pathways that could be involved in NM-induced corneal injuries laying the background for further investigation of these pathways in vesicant–induced ocular injuries, which could be helpful in the development of targeted therapies. PMID:26555588

  1. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    PubMed Central

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy. PMID:27127397

  2. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction.

    PubMed

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  3. Comparison of genome-wide gene expression in suture- and alkali burn-induced murine corneal neovascularization

    PubMed Central

    Jia, Changkai; Zhu, Wei; Ren, Shengwei; Xi, Haijie; Li, Siyuan

    2011-01-01

    Purpose Suture placement and alkali burn to the cornea are often used to induce inflammatory corneal neovascularization (CorNV) models in animals. This study compares the changes in genome-wide gene expression under these two CorNV conditions in mice. Methods CorNV were induced in Balb/c mice by three interrupted 10–0 sutures placed at sites about 1 mm from the corneal apex, or by alkali burns that were 2 mm in size in the central area of the cornea. At the points in time when neovascularization progressed most quickly, some eyeballs were subjected to histological staining to examine CorNV and inflammatory cells infiltration, and some corneas were harvested to extract mRNA for microarray assay. After normalization and filtering, the microarray data were subject to statistical analysis using Significance Analysis of Microarray software, and interested genes were annotated using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) program. The expression change of classical proangiogenic molecule like vascular endothelial growth factor (VEGF) and antiangiogenic molecule like pigment epithelium-derived factor (PEDF) was further verified using western blotting. Results Suture placement induced CorNV in the areas between the suture and limbus, but did not affect the transparency of the yet unvasuclarized areas of the corneas. In contrast, alkali burn caused edema and total loss of transparency of the whole cornea. Histology showed that sutures only caused localized epithelial loss and inflammatory infiltration between the suture and limbus, but chemical burn depleted the whole epithelial layer of the central cornea and caused heavy cellular infiltration of the whole cornea. At day 5 after suture placement, 1,055 differentially expressed probes were identified, out of which 586 probes were upregulated and 469 probes were downregulated. At a comparable time point, namely on day 6 after the alkali burn to the corneas, 472 probes were upregulated

  4. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab.

    PubMed

    Gauci, Marie-Léa; Baroudjian, Barouyr; Laly, Pauline; Madelaine, Isabelle; Da Meda, Laetitia; Vercellino, Laetitia; Bagot, Martine; Lioté, Frédéric; Pages, Cécile; Lebbé, Céleste

    2017-10-01

    A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab. A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks. At week 4, before the 3rd infusion, he presented with inflammatory arthralgia, synovitis of proximal interphalangeal, wrist and ankle joints, and edema of both hands and forearms. Laboratory tests showed inflammatory syndrome (CRP = 8.4mg/dL), negative rheumatoid factor, and anti-CCP antibodies. Radiographs did not show any joint erosion but joint ultrasound displayed intra-articular effusion and tenosynovitis. PET/CT performed 6 and 3 months before treatment for melanoma work-up showed an isolated hypermetabolism of the shoulder girdle. The diagnosis of RS3PE was retained. A systemic corticosteroid treatment (0.5mg/kg/d) was initiated; nivolumab was hold during 4 weeks leading to remission of clinical symptoms within 10 days, CRP level normalization and without relapse when nivolumab was resumed. Corticosteroids were progressively tapered and stopped after 9 months. After 5 months, anti-PD1 was definitively stopped because of disease progression. With this atypical case, clinicians should remain alert on a whole range of autoimmune diseases susceptible to be induced. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. High molecular weight hyaluronan decreases oxidative DNA damage induced by EDTA in human corneal epithelial cells

    PubMed Central

    Ye, J; Wu, H; Wu, Y; Wang, C; Zhang, H; Shi, X; Yang, J

    2012-01-01

    Purpose To investigate the toxic effects of ethylenediaminetetraacetic acid disodium salt (EDTA), a corneal penetration enhancer in topical ophthalmic formulations, on DNA in human corneal epithelial cells (HCEs), and to investigate whether the effect induced by EDTA can be inhibited by high molecular weight hyaluronan (HA). Methods Cells were exposed to EDTA in concentrations ranging from 0.00001 to 0.01% for 60 min, or 30 min high molecular weight HA pretreatment followed by EDTA treatment. The cell viability was measured by the MTT test. Cell apoptosis was determined with annexin V staining by flow cytometry. The DNA single- and double-strand breaks of HCEs were examined by alkaline comet assay and by immunofluorescence microscope detection of the phosphorylated form of histone variant H2AX (γH2AX) foci, respectively. Reactive oxygen species (ROS) production was assessed by the fluorescent probe, 2′, 7′-dichlorodihydrofluorescein diacetate. Results EDTA exhibited no adverse effect on cell viability and did not induce cell apoptosis in human corneal epithelial cells at concentrations lower than 0.01%. However, a significant increase of DNA single- and double-strand breaks was observed in a dose-dependent manner with all the concentrations of EDTA tested in HCEs. In addition, EDTA treatment led to elevated ROS generation. Moreover, 30 min preincubation with high molecular weight HA significantly decreased EDTA-induced ROS generation and DNA damage. Conclusions EDTA could induce DNA damage in HCEs, probably through oxidative stress. Furthermore, high molecular weight HA was an effective protective agent that had antioxidant properties and decreased DNA damage induced by EDTA. PMID:22595911

  6. Inhibitory Effects of PPARγ Ligands on TGF-β1–Induced Corneal Myofibroblast Transformation

    PubMed Central

    Jeon, Kye-Im; Kulkarni, Ajit; Woeller, Collynn F.; Phipps, Richard P.; Sime, Patricia J.; Hindman, Holly B.; Huxlin, Krystel R.

    2015-01-01

    Corneal scarring, whether caused by trauma, laser refractive surgery, or infection, remains a significant problem for humans. Certain ligands for peroxisome proliferator-activated receptor gamma (PPARγ) have shown promise as antiscarring agents in a variety of body tissues. In the cornea, their relative effectiveness and mechanisms of action are still poorly understood. Here, we contrasted the antifibrotic effects of three different PPARγ ligands (15-deoxy-Δ12,14-prostaglandin J2, troglitazone, and rosiglitazone) in cat corneal fibroblasts. Western blot analyses revealed that all three compounds reduced transforming growth factor (TGF)-β1–driven myofibroblast differentiation and up-regulation of α-smooth muscle actin, type I collagen, and fibronectin expression. Because these effects were independent of PPARγ, we ascertained whether they occurred by altering phosphorylation of Smads 2/3, p38 mitogen–activated protein kinase, stress-activated protein kinase, protein kinase B, extracellular signal-regulated kinase, and/or myosin light chain 2. Only p38 mitogen–activated protein kinase phosphorylation was significantly inhibited by all three PPARγ ligands. Finally, we tested the antifibrotic potential of troglitazone in a cat model of photorefractive keratectomy–induced corneal injury. Topical application of troglitazone significantly reduced α-smooth muscle actin expression and haze in the stromal ablation zone. Thus, the PPARγ ligands tested here showed great promise as antifibrotics, both in vitro and in vivo. Our results also provided new evidence for the signaling pathways that may underlie these antifibrotic actions in corneal fibroblasts. PMID:24650561

  7. Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

    PubMed

    Yu, Jinyan; Ma, Zhongsen; Shetty, Sreerama; Ma, Mengshi; Fu, Jian

    2016-07-01

    Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction.

  8. Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema.

    PubMed

    Protti, Alessandro; Maraffi, Tommaso; Milesi, Marta; Votta, Emiliano; Santini, Alessandro; Pugni, Paola; Andreis, Davide T; Nicosia, Francesco; Zannin, Emanuela; Gatti, Stefano; Vaira, Valentina; Ferrero, Stefano; Gattinoni, Luciano

    2016-09-01

    Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis. Laboratory investigation. Animal unit. Thirty healthy piglets. Two groups of animals were ventilated for 54 hours with matched lung strains (ratio between tidal volume and functional residual capacity) but different lung strain rates (ratio between strain and inspiratory time). Individual strains ranged between 0.6 and 3.5 in both groups. Piglets ventilated with low strain rates had an inspiratory-to-expiratory time ratio of 1:2-1:3. Those ventilated with high strain rates had much lower inspiratory-to-expiratory time ratios (down to 1:9). Respiratory rate was always 15 breaths/min. Lung viscoelastic behavior, with ventilator setting required per protocol, was "quantified" as dynamic respiratory system hysteresis (pressure-volume loop [in Joules]) and stress relaxation (airway pressure drop during an end-inspiratory pause [in cm H2O]). Primary outcome was the occurrence of pulmonary edema within 54 hours. On average, the two study groups were ventilated with well-matched strains (2.1 ± 0.9 vs 2.1 ± 0.9; p = 0.864) but different strain rates (1.8 ± 0.8 vs 4.6 ± 1.5 s; p < 0.001), dynamic respiratory system hysteresis (0.6 ± 0.3 vs 1.4 ± 0.8 J; p = 0.001), and stress relaxation (3.1 ± 0.9 vs 5.0 ± 2.3 cm H2O; p = 0.008). The prevalence of pulmonary edema was 20% among piglets ventilated with low strain rates and 73% among those ventilated with high strain rates (p = 0.010). High strain rate is a risk factor for ventilator-induced pulmonary edema, possibly because it amplifies lung viscoelastic behavior.

  9. Role of oxidative stress and NFkB in hypoxia-induced pulmonary edema.

    PubMed

    Sarada, Sagi; Himadri, Patir; Mishra, Chitaranjan; Geetali, Pradhan; Ram, Mastoori Sai; Ilavazhagan, Govindan

    2008-09-01

    Hypoxia is well known to increase the free radical generation in the body, leading to oxidative stress. In the present study, we have determined whether the increased oxidative stress further upregulates the nuclear transcription factor (NFkB) in the development of pulmonary edema. The rats were exposed to hypobaric hypoxia at 7620 m (280 mm Hg) for different durations, that is, 3 hrs, 6 hrs, 12 hrs, and 24 hrs at 25+/-1 degrees C. The results revealed that exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, with time up to 6 hrs (256.38+/-61 rfu/g) as compared with control (143.63+/-60.1 rfu/g). There was a significant increase in reactive oxygen species, lipid peroxidation, and superoxide dismutase levels, with a concurrent decrease in lung glutathione peroxidase activity. There was 13-fold increase in the expression of NFkB level in nuclear fraction of lung homogenates of hypoxic animals over control rats. The DNA binding activity of NFkB was found to be increased significantly (P<0.001) in the lungs of rats exposed to hypoxia as compared with control. Further, we observed a significant increase in proinflammatory cytokines such as IL-1, IL-6, and TNF-alpha with concomitant upregulation of cell adhesion molecules such as ICAM-I, VCAM-I, and P-selectin in the lung of rats exposed to hypoxia as compared with control. Interestingly, pretreatment of animals with curcumin (NFkB blocker) attenuated hypoxia-induced vascular leakage in lungs with concomitant reduction of NFkB levels. The present study therefore reveals the possible involvement of NFkB in the development of pulmonary edema.

  10. Swimming-induced pulmonary edema in a tropical climate: a case report.

    PubMed

    Kwek, Wmj; Seah, M; Chow, W

    2017-01-01

    Swimming-induced pulmonary edema (SIPE) occurs during strenuous physical exertion in cold water and has been reported in scuba divers, free-diving competitors, combat swimmers, and triathletes. We describe a case of SIPE in a combat swimmer in warm tropical waters. A 21-year old diver trainee developed dyspnea, chest discomfort and hemoptysis after performing a 2-km sea swim in water temperatures of around 30°C. Over a two-hour period, his oxygen saturations deteriorated. Chest X-ray showed pulmonary edema. He was admitted to the general ward for observation and was given supportive treatment. His symptoms resolved over two days. Repeat CXR was normal. He was reviewed and certified fit to continue with diver training. Much of the earlier literature on SIPE describes the development of symptoms after exposure to temperate waters as one main risk factor. This case highlights the risk of development of SIPE in warm tropical waters. With a low reported incidence of SIPE in warm waters, this condition is likely to be underdiagnosed. There is therefore a need to increase local awareness of SIPE in the medical community. A deliberate effort to collate data on SIPE in our local community will help us to better understand the pathophysiology of SIPE in the context of a tropical climate. Development of SIPE in tropical waters suggests that other risk factors may be predominant. There should be a high index of suspicion when any strenuous in-water activity is conducted so that timely treatment may be instituted.

  11. Comparative effects of two potentiating peptides (KPP and BPP9a) on kinin-induced rat paw edema.

    PubMed

    Fernandes, P D; Guimarães, J A; Assreuy, J

    1991-03-01

    We have previously shown that KPP, a kinin potentiating peptide generated by tryptic digestion of human plasma proteins potentiated kinin effects on isolated smooth muscle preparations like guinea-pig ileum with high potency and specificity. We also obtained evidence suggesting that, unlike other potentiating peptides, KPP exerts its effect by a mechanism different from the inhibition of kinin metabolism by angiotensin converting enzyme, neutral endopeptidase and kininase I. Here we show the potentiating effect of KPP and of BPP9a, a potentiator derived from snake venom, towards the rat paw edema induced by bradykinin (BK). Our results show that: a) KPP is 25-fold more active than BPP9a in potentiating rat paw edema elicited by BK: b) like BPP9a, KPP is specific in potentiating kinin-induced edema, being ineffective in potentiating edema induced by histamine or serotonin; and c) DesArg9-BK (DABK) elicits a small edematogenic response which can be potentiated by both KPP and BPP9a.

  12. TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse.

    PubMed

    Moilanen, Lauri J; Laavola, Mirka; Kukkonen, Meiju; Korhonen, Riku; Leppänen, Tiina; Högestätt, Edward D; Zygmunt, Peter M; Nieminen, Riina M; Moilanen, Eeva

    2012-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.

  13. [Unilateral cystoid macular edema induced by citalopram--a case report].

    PubMed

    Alexík, M

    2011-10-01

    Citamopram is an antidepressant drug with fatigue, sleep disorders, appetite changes and visual impairment being the most common side effects. We are not aware of any published cases of cystoid macular edema following medication of this drug. We present a case of 55 year old woman with medical history of depression placed on Citalopram medication who noticed deterioration of right eye vision. Best corrected visual acuity was 20/120, ophthalmic coherence tomography and fluorescein angiography revealed cystoid macular edema. Two months following drug withdrawal edema disappeared and best corrected visual acuity improved to 20/32. Due to lack of other probable causes of edema and quick disappearance following drug withdrawal it is plausible to think of Citalopram as causative factor of cystoid macular edema in this patient.

  14. Effect of cysteamine on oxidative stress-induced cell death of human corneal endothelial cells.

    PubMed

    Shin, Young Joo; Seo, Jong Mo; Chung, Tae Young; Hyon, Joon Young; Wee, Won Ryang

    2011-10-01

    The principal objective of this study was to evaluate the protective effect of cysteamine against the oxidative stress-induced cell death of human corneal endothelial cells. In this study, human corneal endothelial cells (HCECs) were cultured according to a previously published method. With treatment of 0 mM or 5 mM of tert-butyl hydroperoxide (tBHP) with various concentrations (0-50 mM) of cysteamine, reactive oxygen species (ROS) production was measured using an oxidation-sensitive fluorescent probe, and dichlorofluorescein diacetate (DCFH-DA) methods. Cell viability was assayed via the Cell Counting Kit-8 method. The levels of cellular glutathione were also assessed enzymatically with glutathione reductase using a commercial glutathione assay kit (Cayman Chemical, USA). This study showed that cysteamine reduced 2',7'-dihydrodichlorofluorescein oxidation and increased glutathione. Cysteamine significantly inhibited tBHP-induced ROS production. Cysteamine-treated cells evidenced higher viability relative to the controls at 5 mM tBHP, and cysteamine also effectively protected HCECs against ROS-induced cell death via an increase in intracellular glutathione. Our data indicate that cysteamine was not toxic at low concentrations and, at high concentrations, protects HCECs against oxidative injury-mediated cell death via the inhibition of ROS production, although cysteamine is toxic in cells at high concentrations without oxidative stress.

  15. Involvement of water channel Aquaporin 5 in H2S-induced pulmonary edema.

    PubMed

    Xu, Chunyang; Jiang, Lei; Zou, Yuxia; Xing, Jingjing; Sun, Hao; Zhu, Baoli; Zhang, Hengdong; Wang, Jun; Zhang, Jinsong

    2017-01-01

    Acute exposure to hydrogen sulfide (H2S) poses a significant threat to life, and the lung is one of the primary target organs of H2S. However, the mechanisms involved in H2S-induced acute pulmonary edema are poorly understood. This study aims to investigate the effects of H2S on the expression of water channel aquaporin 5 (AQP5) and to elucidate the signaling pathways involved in AQP5 regulation. In an in vivo study, C57BL6 mice were exposed to sub-lethal concentrations of inhaled H2S, and histological injury of the lungs and ultrastructure injury of the epithelial cells were evaluated. With real-time PCR and western blot assays, we found that H2S exposure contributed to a significant decrease in AQP5 expression both in murine lung tissue and the A549 cell line, and the ERK1/2 and p38 MAPK signaling pathways were demonstrated to be implicated in AQP5 regulation. Therefore, adjusting AQP5 protein levels could be considered a therapeutic strategy for the treatment of APE induced by H2S and other hazardous gases.

  16. Cytotoxicity of atropine to human corneal endothelial cells by inducing mitochondrion-dependent apoptosis

    PubMed Central

    Wen, Qian; Tian, Cheng-Lei

    2016-01-01

    Atropine, a widely used topical anticholinergic drug, might have adverse effects on human corneas in vivo. However, its cytotoxic effect on human corneal endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated the cytotoxicity of atropine and its underlying cellular and molecular mechanisms using an in vitro model of HCE cells and verified the cytotoxicity using cat corneal endothelium (CCE) in vivo. Our results showed that atropine at concentrations above 0.3125 g/L could induce abnormal morphology and viability decline in a dose- and time-dependent manner in vitro. The cytotoxicity of atropine was proven by the induced density decrease and abnormality of morphology and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce dose- and time-dependent elevation of plasma membrane permeability, G1 phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/-3/-9 activation, mitochondrial transmembrane potential disruption, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose- and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis via a death receptor-mediated mitochondrion-dependent signaling pathway. Our findings provide new insights into the cytotoxicity and apoptosis-inducing effect of atropine which should be used with great caution in eye clinic. PMID:27022135

  17. Cytotoxicity of atropine to human corneal endothelial cells by inducing mitochondrion-dependent apoptosis.

    PubMed

    Wen, Qian; Fan, Ting-Jun; Tian, Cheng-Lei

    2016-07-01

    Atropine, a widely used topical anticholinergic drug, might have adverse effects on human corneas in vivo. However, its cytotoxic effect on human corneal endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated the cytotoxicity of atropine and its underlying cellular and molecular mechanisms using an in vitro model of HCE cells and verified the cytotoxicity using cat corneal endothelium (CCE) in vivo. Our results showed that atropine at concentrations above 0.3125 g/L could induce abnormal morphology and viability decline in a dose- and time-dependent manner in vitro. The cytotoxicity of atropine was proven by the induced density decrease and abnormality of morphology and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce dose- and time-dependent elevation of plasma membrane permeability, G1 phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/-3/-9 activation, mitochondrial transmembrane potential disruption, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose- and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis via a death receptor-mediated mitochondrion-dependent signaling pathway. Our findings provide new insights into the cytotoxicity and apoptosis-inducing effect of atropine which should be used with great caution in eye clinic. © 2016 by the Society for Experimental Biology and Medicine.

  18. Intranasal delivery of nerve growth factor attenuates aquaporins-4-induced edema following traumatic brain injury in rats.

    PubMed

    Lv, Qiushi; Fan, Xinying; Xu, Gelin; Liu, Qian; Tian, Lili; Cai, Xiaoyi; Sun, Wenshan; Wang, Xiaomeng; Cai, Qiankun; Bao, Yuanfei; Zhou, Lulu; Zhang, Yao; Ge, Liang; Guo, Ruibing; Liu, Xinfeng

    2013-02-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. Nerve growth factor (NGF) appears to be a viable strategy to treat brain edema and TBI. Unfortunately, due to its poor blood-brain barrier (BBB) permeability, the clinical application of NGF has been greatly limited. We previously demonstrated that intranasal NGF could bypass the BBB and distribute throughout the brain. Here we further studied whether intranasal NGF could attenuate TBI-induced brain edema and its putative mechanisms. TBI was produced by a modified weight-drop model. We found that intranasal administration of NGF (5μg/d) attenuated the brain edema, as assayed by hemisphere water content, at 12h, 24h and 72h after TBI induction. This attenuation was associated with a prominent decrease of the content of aquaporin-4, which plays a pivotal role in the formation of brain edema. By the use of RT-PCR and ELISA, we showed that intranasal NGF markedly inhibited the transcription and expression of pro-inflammatory cytokines including IL-1β and TNF-α. An electrophoretic mobility shift assay (EMSA) displayed a significant activation of nuclear factor-κB following TBI, which was, however, much lowered in the NGF-treated rats. Furthermore, upon intranasal NGF supplementation, mitochondria-mediated apoptosis following TBI was minimized, as indicated by upregulation of Bcl-2 and downregulation of caspase-3. Collectively, our findings suggested that intranasal NGF may be a promising strategy to treat brain edema and TBI.

  19. Early resistance training-induced increases in muscle cross-sectional area are concomitant with edema-induced muscle swelling.

    PubMed

    Damas, Felipe; Phillips, Stuart M; Lixandrão, Manoel E; Vechin, Felipe C; Libardi, Cleiton A; Roschel, Hamilton; Tricoli, Valmor; Ugrinowitsch, Carlos

    2016-01-01

    It has been proposed that skeletal muscle shows signs of resistance training (RT)-induced muscle hypertrophy much earlier (i.e., ~3-4 weeks of RT) than previously thought. We determined if early increases in whole muscle cross-sectional area (CSA) during a period of RT were concomitant with edematous muscle swelling and thus not completely attributable to hypertrophy. We analyzed vastus lateralis muscle ultrasound CSA images and their respective echo intensities (CSA-USecho) at the beginning (T1), in the 3rd week of RT (T2) and at the end (T3) of a 10-week RT period in ten untrained young men. Functional parameters [training volume (TV = load × reps × sets) and maximal voluntary contraction (MVC)] and muscle damage markers (myoglobin and interleukin-6) were also assessed. Muscle CSA increased significantly at T2 (~2.7%) and T3 (~10.4%) versus T1. Similarly, CSA-USecho increased at T2 (~17.2%) and T3 (~13.7%). However, when CSA-USecho was normalized to the increase in muscle CSA, only T2 showed a significantly higher USecho versus T1. Additionally, TV increased at T2 and T3 versus T1, but MVC increased only at T3. Myoglobin and Interleukin-6 were elevated at T2 versus T1, and myoglobin was also higher at T2 versus T3. We propose that early RT-induced increases in muscle CSA in untrained young individuals are not purely hypertrophy, since there is concomitant edema-induced muscle swelling, probably due to muscle damage, which may account for a large proportion of the increase. Therefore, muscle CSA increases (particularly early in an RT program) should not be labeled as hypertrophy without some concomitant measure of muscle edema/damage.

  20. Vitamin D Activation and Function in Human Corneal Epithelial Cells During TLR-Induced Inflammation

    PubMed Central

    Reins, Rose Yvonne; Baidouri, Hasna; McDermott, Alison Marie

    2015-01-01

    Purpose Vitamin D is recognized to be an important modulator of the immune system. In the eye, studies have shown that deficiencies and genetic differences in vitamin D–related genes have a significant impact on the development of various ocular diseases. Our current study examines the ability of human corneal epithelial cells (HCEC) to activate vitamin D and the effect of vitamin D treatment on antimicrobial peptide production and cytokine modulation during inflammation, with the ultimate goal of using vitamin D therapeutically for corneal inflammation. Methods Human corneal epithelial cells were treated with 10−7M vitamin D3 (D3) or 25-hydroxyvitamin D3 (25D3) for 24 hours and 1,25-dihydroxyvitamin D3 (1,25D3) detected by immunoassay. Human cathelicidin (LL-37) expression was examined by RT-PCR, immunoblot, and immunostaining following 1,25D3 treatment and antimicrobial activity of 1,25D3-treated cells was determined. Cells were stimulated with TLR3 agonist polyinosinic-polycytidylic acid (Poly[I:C]) for 24 hours and cytokine levels measured by RT-PCR, ELISA, and Luminex. Immunostaining determined expression of vitamin D receptor (VDR) and retinoic acid inducible gene-1 receptor (RIG-1) as well as NF-κB nuclear translocation. Results When treated with inactive vitamin D metabolites, HCEC produced active 1,25D3, leading to enhanced expression of the antimicrobial peptide, LL-37, dependent on VDR. 1,25-D3 decreased the expression of proinflammatory cytokines (IL-1β, IL-6, TNFα, and CCL20) and MMP-9 induced by Poly(I:C) as well as pattern recognition receptor expression (TLR3, RIG-1, MDA5). However, early activation of NF-κB was not affected. Conclusions These studies demonstrate the protective ability of vitamin D to attenuate proinflammatory mediators while increasing antimicrobial peptides and antipseudomonas activity in corneal cells, and further our knowledge on the immunomodulatory functions of the hormone. PMID:26641549

  1. Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats.

    PubMed

    Li, Zhanrong; Li, Jingguo; Zhu, Lei; Zhang, Ying; Zhang, Junjie; Yao, Lin; Liang, Dan; Wang, Liya

    The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting. Activated macrophages were elicited through mineral oil lumbar injection, labeled with 1,19-dioctadecyl-3-3-39,39-tetramethylindocarbocyanine (DiI) and implanted into the corneal micro-pocket to induce CNV and to assess the antiangiogenic effect in rats. CNV was morphometrically analyzed using ImageJ software. Histopathological features were evaluated by immunofluorescence immunostaining for vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) on day 2 after surgery. In the present study, the results indicated that CNMs significantly inhibited the migration and invasion of HUVECs; remarkably attenuated the expression of VEGF, tumor necrosis factor-α, interleukin-1α, monocyte chemoattractant protein 1, cytokine-induced neutrophil chemoattractant 3, and MMP-9 protein; and downregulated ERK1/2, p38 MAPK, NF-κB activation, and HIF-1α expression in macrophages. The peritoneal cells elicited using mineral oil were highly purified macrophages, and the length and area of CNV were significantly decreased in the CNMs group compared with the control group. There was a significant reduction in the expression of VEGF and MMP-9 in

  2. Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats

    PubMed Central

    Li, Zhanrong; Li, Jingguo; Zhu, Lei; Zhang, Ying; Zhang, Junjie; Yao, Lin; Liang, Dan; Wang, Liya

    2016-01-01

    The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting. Activated macrophages were elicited through mineral oil lumbar injection, labeled with 1,19-dioctadecyl-3-3-39,39-tetramethylindocarbocyanine (DiI) and implanted into the corneal micro-pocket to induce CNV and to assess the antiangiogenic effect in rats. CNV was morphometrically analyzed using ImageJ software. Histopathological features were evaluated by immunofluorescence immunostaining for vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) on day 2 after surgery. In the present study, the results indicated that CNMs significantly inhibited the migration and invasion of HUVECs; remarkably attenuated the expression of VEGF, tumor necrosis factor-α, interleukin-1α, monocyte chemoattractant protein 1, cytokine-induced neutrophil chemoattractant 3, and MMP-9 protein; and downregulated ERK1/2, p38 MAPK, NF-κB activation, and HIF-1α expression in macrophages. The peritoneal cells elicited using mineral oil were highly purified macrophages, and the length and area of CNV were significantly decreased in the CNMs group compared with the control group. There was a significant reduction in the expression of VEGF and MMP-9 in

  3. Using laser induced breakdown spectroscopy and acoustic radiation force elasticity microscope to measure the spatial distribution of corneal elasticity

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Li, Xin; Fan, Zhongwei; Kurtz, Ron; Juhasz, Tibor

    2017-02-01

    Corneal biomechanics plays an important role in determining the eye's structural integrity, optical power and the overall quality of vision. It also plays an increasingly recognized role in corneal transplant and refractive surgery, affecting the predictability, quality and stability of final visual outcome [1]. A critical limitation to increasing our understanding of how corneal biomechanics controls corneal stability and refraction is the lack of non-invasive technologies that microscopically measure local biomechanical properties, such as corneal elasticity within the 3D space. Bubble based acoustic radiation force elastic microscopy (ARFEM) introduce the opportunity to measure the inhomogeneous elastic properties of the cornea by the movement of a micron size cavitation bubble generated by a low energy femtosecond laser pulse [2, 3]. Laser induced breakdown spectroscopy (LIBS) also known as laser induced plasma spectroscopy (LIPS) or laser spark spectrometry (LSS) is an atomic emission spectroscopy [4]. The LIBS principle of operation is quite simple, although the physical processes involved in the laser matter interaction are complex and still not completely understood. In one sentence for description, the laser pulses are focused down to a target so as to generate plasma that vaporizes a small amount of material which the emitted spectrum is measured to analysis the elements of the target.

  4. Sema3A maintains corneal avascularity during development by inhibiting Vegf induced angioblast migration

    PubMed Central

    McKenna, Chelsey C.; Ojeda, Ana F.; Spurlin, James; Kwiatkowski, Sam; Lwigale, Peter Y.

    2014-01-01

    Corneal avascularity is important for optical clarity and normal vision. However, the molecular mechanisms that prevent angioblast migration and vascularization of the developing cornea are not clear. Previously we showed that periocular angioblasts and forming ocular blood vessels avoid the presumptive cornea despite dynamic ingression of neural crest cells. In the current study, we investigate the role of Semaphorin3A (Sema3A), a cell guidance chemorepellent, on angioblast migration and corneal avascularity during development. We show that Sema3A, Vegf, and Nrp1 are expressed in the anterior eye during cornea development. Sema3A mRNA transcripts are expressed at significantly higher levels than Vegf in the lens that is positioned adjacent to the presumptive cornea. Blockade of Sema3A signaling via lens removal or injection of a synthetic Sema3A inhibitor causes ectopic migration of angioblasts into the cornea and results in its subsequent vascularization. In addition, using bead implantation, we demonstrate that exogenous Sema3A protein inhibits Vegf-induced vascularization of the cornea. In agreement with these findings, loss of Sema/Nrp1 signaling in Nrp1Sema- mutant mice results in ectopic angioblasts and vascularization of the embryonic mouse corneas. Altogether, our results reveal Sema3A signaling as an important cue during the establishment of corneal avascularity in both chick and mouse embryos. Our study introduces cornea development as a new model for studying the mechanisms involved in vascular patterning during embryogenesis and it also provides new insights into therapeutic potential for Sema3A in neovascular diseases. PMID:24809797

  5. Effect of Fenoterol on PAF-induced lung edema in isolated and perfused rabbit lungs.

    PubMed

    Pesce, L; Tristano, S; Friedman, E; Comellas, A; Marcano, H; Sanchez de León, R

    1998-11-01

    We have studied the effects of fenoterol on PAF-induced response in pulmonary circulation. We used 28 isolated and perfused rabbit lungs preparations: eight control preparations (CP), four vehicles preparations (VP), eight PAF preparations (PP) with two doses of PAF, one called low dose (LD = 0.5 microg/kg of weight) and the other high dose (HD = 1 microg/kg of weight) and eight Fenoterol preparations (FP) which we administered 0.05 mg of Fenoterol for 15 min, followed by a LD and HD of PAF. FP prevented elevation of pulmonary artery pressure (Ppa) as compared to PP, at LD of PAF: 12.615 (CI 95%: 8.57-20.885) versus 83.705 (CI 95%: 50.55-114.3) cm of water; and at HD of PAF: 19.38 (CI 95%: 11.235-28.94) versus 205.1 (CI 95%: 141.3-271) cm of water respectively. FP prevented the increase in fluid filtration rate (FFR) observed in PP at both doses of PAF LD: 0.765 (CI 95%: 0.07-3.385) versus 0.01 (CI 95%: -0.05-0.005) g/min; HD: 5.515 (CI 95%: 2.425-8.865) versus 0.03 (CI 95%: 0-0.33) g/min. Our results suggest that PAF has a vasoconstrictor effect that produces lung edema and this effect is inhibited by fenoterol.

  6. Corneal Disorders

    MedlinePlus

    ... Injuries Dystrophies - conditions in which parts of the cornea lose clarity due to a buildup of cloudy material Treatments of corneal disorders include medicines, corneal transplantation, and corneal laser surgery. NIH: National Eye Institute

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

    PubMed

    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 (P<0.01). The differences in shrinkage between the use of ceramic and metal masks were insignificant (P>0.05). 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.

  8. Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil

    PubMed Central

    Moon, Richard E.; Martina, Stefanie D.; Peacher, Dionne F.; Potter, Jennifer F.; Wester, Tracy E.; Cherry, Anne D.; Natoli, Michael J.; Otteni, Claire E.; Kernagis, Dawn N.; White, William D.; Freiberger, John J.

    2016-01-01

    Background Swimming-induced pulmonary edema (SIPE) occurs during swimming or scuba diving, often in young individuals with no predisposing conditions, and its pathophysiology is poorly understood. This study tested the hypothesis that pulmonary artery and pulmonary artery wedge pressures are higher in SIPE-susceptible individuals during submerged exercise compared to the general population and are reduced by sildenafil. Methods and Results Ten study subjects with a history of SIPE (mean age 41.6 years) and 20 control subjects (mean age 36.2 years) were instrumented with radial artery and pulmonary artery catheters and performed moderate cycle ergometer exercise for 6–7 minutes while submersed in 20°C water. SIPE-susceptible subjects repeated the exercise 150 minutes after oral administration of 50 mg sildenafil. Work rate and mean arterial pressure during exercise were similar in controls and SIPE-susceptibles. Average VO2 and cardiac output (CO) in SIPE-susceptibles and controls were: VO2 2.42 L.min−1 vs. 1.95 L.min−1, P=0.2; CO 17.9 L.min−1 vs. 13.8 L.min−1, P=0.01). Accounting for differences in CO between groups, mean pulmonary artery pressure (MPAP) at CO=13.8 L.min−1 was 22.5 mmHg in controls vs. 34.0 mmHg in SIPE-susceptibles (P=0.004) and the corresponding pulmonary artery wedge pressure (PAWP) 11.0 mmHg vs. 18.8 mmHg (P=0.028). After sildenafil, there were no statistically significant differences in MPAP or PAWP between SIPE-susceptibles and controls. Conclusions These observations confirm that SIPE is a form of hemodynamic pulmonary edema. The reduction in pulmonary vascular pressures after sildenafil with no adverse effect on exercise hemodynamics suggests that it may be useful in SIPE prevention. Clinical Trial Registration Information ClinicalTrials.gov. Identifier: NCT00815646. PMID:26882910

  9. Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.

    PubMed

    Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

    2015-05-22

    The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events.

  10. Aplastic anemia induced disc edema and visual loss in pregnancy: a case report

    PubMed Central

    Gupta, Shailesh K; Brar, Vikram S; Keshavamurthy, Ravi; Chalam, Kakarla V

    2008-01-01

    Introduction A case of aplastic anemia diagnosed during pregnancy, which developed bilateral disc edema and acute pre-retinal hemorrhage leading to vision loss. Case Presentation A 20 year old primagravid female developed acute vision loss in her right eye, during hospitalization for treatment of aplastic anemia diagnosed during her pregnancy. Her best-corrected visual acuity (BCVA) was hand motions and fundus evaluation revealed a large pre-macular hemorrhage in the right eye (OD) and bilateral disc edema. Neuro-imaging studies did not reveal any signs of intracranial mass lesion or edema. Conclusion There was resolution of the disc edema with improvement in the pre-macular hemorrhage resulting in 20/50 vision in the right eye, following supportive transfusions. Ophthalmic manifestations developing in a pregnant patient with aplastic anemia can be successfully managed with supportive care including red blood cell and platelet transfusions. PMID:19017378

  11. An aqueous extract of Ilex paraguariensis reduces carrageenan-induced edema and inhibits the expression of cyclooxygenase-2 and inducible nitric oxide synthase in animal models of inflammation.

    PubMed

    Schinella, Guillermo; Neyret, Elisa; Cónsole, Gloria; Tournier, Horacio; Prieto, José M; Ríos, José-Luis; Giner, Rosa María

    2014-08-01

    Mate (Ilex paraguariensis) is a highly popular herbal beverage in South America due to its high content of caffeine. Its hypolipidemic and antioxidant properties are of increasing interest in the treatment of cardiovascular disorders and for weight control. In the present study, we show for the first time both the local and systemic anti-inflammatory effects of an aqueous extract of mate in three classic in vivo models, namely acute and chronic 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema and acute carrageenan-induced mouse paw edema. Caffeine, rutin, chlorogenic acid, 3,5-dicafeoyl quinic acid, and 4,5-dicafeoyl quinic acid, accompanied by a complex mixture of other simple phenolic acids, were identified in the extract by HPLC-UV analyses. In the acute edema model, mate extract applied topically (1 mg/ear) halved the 12-O-tetradecanoylphorbol 13-acetate-induced acute edema (50 %) and almost suppressed neutrophil infiltration (93 %), while in the 12-O-tetradecanoylphorbol 13-acetate-induced subchronic inflammation, the edema was significantly reduced by 62 % (1 mg/ear/day × seven doses). The oral administration of the mate extract (250 mg/kg) significantly reduced the carrageenan-induced edema at all time points, an effect which was accompanied by a 43 % and 53 % reduction of the expression of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Histological analyses confirmed a reduction of epithelium thickness, dermis with mild inflammation, hair follicles with some secretory cells of sebaceous glands, and hypodermic adipocytes. In conclusion, mate is endowed with in vivo preventative or therapeutic anti-inflammatory effects in both local and systemic inflammatory processes. Georg Thieme Verlag KG Stuttgart · New York.

  12. Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

    PubMed

    Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

    2001-09-01

    Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

  13. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    PubMed

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  14. Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

    PubMed Central

    Chen, Shao-Jun; Yang, Jia-Fang; Kong, Fan-Ping; Ren, Ji-Long; Hao, Ke; Li, Min; Yuan, Yuan; Chen, Xin-Can; Yu, Ri-Sheng; Li, Jun-Fa; Leng, Gareth; Chen, Xue-Qun; Du, Ji-Zeng

    2014-01-01

    Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca2+, and PKCε; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1+ and AQP4+, we show that transfected CRFR1+ contributes to edema via transfected AQP4+. In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema. PMID:25146699

  15. Amelioration of Cold Injury-Induced Cortical Brain Edema Formation by Selective Endothelin ETB Receptor Antagonists in Mice

    PubMed Central

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults. PMID:25000290

  16. Hypoxia-induced downregulation of ΔNp63α in the corneal epithelium

    PubMed Central

    Robertson, Danielle M.; Zhu, Meifang; Wu, Yu-Chieh; Cavanagh, H. Dwight

    2012-01-01

    Purpose To establish a relationship between hypoxic stress and the expression of ΔNp63α in an established rabbit contact lens model and in cultured corneal epithelial cells. Methods New Zealand White rabbits were fit in one eye with either a non-oxygen transmissible or hyper oxygen permeable rigid contact lens for 24 hours of wear; the contralateral eye was used as a control. All rabbits underwent a bilateral nictitating membranectomy to facilitate lens retention. ΔNp63α expression was analyzed by immunofluorescence and western blot. Telomerase-immortalized human corneal epithelial cells (hTCEpi) were grown in serum-free media and treated with the hypoxia mimetic cobalt chloride to simulate hypoxia for 6 (short term) or 24 (prolonged) hours. Transcriptional activity and protein levels were assessed using luciferase reporter assays, RT-PCR, and western blot. Cell viability was assessed by live/dead assay. Results Compared to the non-lens wearing eye, 24 hours of non-oxygen transmissible lens wear in vivo decreased ΔNp63α protein levels in both the limbal and central corneal epithelium; this decrease was not found in the hyper oxygen transmissible lens group. In hTCEpi cells in vitro, hypoxia increased the activity of the ΔN promoter, but reduced levels of ΔNp63α mRNA after 24 hours of prolonged culture. Similarly, ΔNp63α expression levels were unaffected from short term exposure, but decreased after 24 hours. Live/dead assay confirmed the presence of viable cells following CoCl2 treatment at 6 and 24 hour time points. Cells treated for 24 hours were viable but were smaller and rounded with signs of membrane blebbing, consistent with early stages of apoptosis. Conclusions Hypoxic stress induced by either prolonged wear of a non-oxygen transmissible lens in vivo or hypoxic-mimic conditions by cobalt chloride in vitro down regulates ΔNp63α in the corneal epithelium. The loss of ΔNp63α in response to hypoxic stress may contribute to the disruption of

  17. A 45-Year-Old Man With Recurrent Dyspnea and Hemoptysis during Exercise: Exercise-Induced Pulmonary Hemorrhage/Edema

    PubMed Central

    Kim, Dae Sung; Lee, Minhyeok; Kwon, Oh Jung; Jeong, Inbeom; Son, Ji Woong; Na, Moon Jun

    2015-01-01

    A 45-year-old man presented with dyspnea and hemoptysis during exercise. A chest computed tomography (CT) revealed multifocal diffuse patchy ground glass opacity and interlobular septal thickening in both the lungs. Permeability pulmonary edema or pulmonary hemorrhage was suspected. Serologic studies for autoimmune disorders and vasculitis were negative. There was no laboratory evidence of coagulopathy, other hematopoietic disease or infectious disease. Considering correlation with exercise, we diagnosed exercise-induced pulmonary hemorrhage (EIPH) or exercise-induced pulmonary edema (EIPE). The patient was managed with antifibrinolytics, antibiotics, and antitussive agent. After a week, follow-up chest CT revealed completely resolved pulmonary hemorrhage. About 2 months after the first event, he visited again with dyspnea and hemoptysis during running. In the present study, we report a case of recurrent pulmonary hemorrhage after exercise. PMID:26508928

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

    PubMed

    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.

  19. Correction of irregular and induced regular corneal astigmatism with toric IOL after posterior segment surgery: a case series.

    PubMed

    Kolozsvári, Bence L; Losonczy, Gergely; Pásztor, Dorottya; Fodor, Mariann

    2017-01-13

    Toric intraocular lens (IOL) implantation can be an effective method for correcting corneal astigmatism in patients with vitreoretinal diseases and cataract. Our purpose is to report the outcome of toric IOL implantation in two cases - a patient with scleral-buckle-induced regular corneal astigmatism and a patient with keratoconus following pars plana vitrectomy. As far as we are aware, there are no reported cases of toric IOL implantation in a vitrectomized eye with keratoconus nor of toric IOL implantation in patients with scleral-buckle-induced regular corneal astigmatism. Two patients with myopia and high corneal astigmatism underwent cataract operation with toric IOL implantation after posterior segment surgery. Myopia and high astigmatism (>2.5 diopter) were caused by previous scleral buckling in one case and by keratoconus in the other case. Pre- and postoperative examinations during the follow-up of included uncorrected and spectacle corrected distance visual acuity (UCDVA/CDVA), automated kerato-refractometry (Topcon), Pentacam HR, IOL Master (Zeiss) axial length measurements and fundus optical coherence tomography (Zeiss). One year postoperatively, the UCDVA and CDVA were 20/25 and 20/20 in both cases, respectively. The absolute residual refractive astigmatism was 1.0 and 0.75 Diopters, respectively. The IOL rotation was within 3° in both eyes, therefore IOL repositioning was not necessary. Complications were not observed in our cases. These cases demonstrate that toric IOL implantation is a predictable and safe method for the correction of high corneal astigmatism in complicated cases with different origins. Irregular corneal astigmatism in keratoconus or scleral-buckle-induced regular astigmatisms can be equally well corrected with the use of toric IOL during cataract surgery. Previous scleral buckling or pars plana vitrectomy seem to have no impact on the success of the toric IOL implantation, even in keratoconus. IOL rotational stability and

  20. Serine protease HtrA1 accumulates in corneal transforming growth factor beta induced protein (TGFBIp) amyloid deposits

    PubMed Central

    Karring, Henrik; Poulsen, Ebbe Toftgaard; Runager, Kasper; Thøgersen, Ida B.; Klintworth, Gordon K.; Højrup, Peter

    2013-01-01

    Purpose Specific mutations in the transforming growth factor beta induced (TGFBI) gene are associated with lattice corneal dystrophy (LCD) type 1 and its variants. In this study, we performed an in-depth proteomic analysis of human corneal amyloid deposits associated with the heterozygous A546D mutation in TGFBI. Methods Corneal amyloid deposits and the surrounding corneal stroma were procured by laser capture microdissection from a patient with an A546D mutation in TGFBI. Proteins in the captured corneal samples and healthy corneal stroma were identified with liquid chromatography-tandem mass spectrometry and quantified by calculating exponentially modified Protein Abundance Index values. Mass spectrometry data were further compared for identifying enriched regions of transforming growth factor beta induced protein (TGFBIp/keratoepithelin/βig-h3) and detecting proteolytic cleavage sites in TGFBIp. Results A C-terminal fragment of TGFBIp containing residues Y571-R588 derived from the fourth fasciclin 1 domain (FAS1–4), serum amyloid P-component, apolipoprotein A-IV, clusterin, and serine protease HtrA1 were significantly enriched in the amyloid deposits compared to the healthy cornea. The proteolytic cleavage sites in TGFBIp from the diseased cornea are in accordance with the activity of serine protease HtrA1. We also identified small amounts of the serine protease kallikrein-14 in the amyloid deposits. Conclusions Corneal amyloid caused by the A546D mutation in TGFBI involves several proteins associated with other varieties of amyloidosis. The proteomic data suggest that the sequence 571-YHIGDEILVSGGIGALVR-588 contains the amyloid core of the FAS1–4 domain of TGFBIp and point at serine protease HtrA1 as the most likely candidate responsible for the proteolytic processing of amyloidogenic and aggregated TGFBIp, which explains the accumulation of HtrA1 in the amyloid deposits. With relevance to identifying serine proteases, we also found glia-derived nexin

  1. Adenosine opposes thrombin-induced inhibition of intercellular calcium wave in corneal endothelial cells.

    PubMed

    D'hondt, Catheleyne; Srinivas, Sangly P; Vereecke, Johan; Himpens, Bernard

    2007-04-01

    In corneal endothelial cells, intercellular Ca(2+) waves elicited by a mechanical stimulus involve paracrine intercellular communication, mediated by ATP release via connexin hemichannels, as well as gap junctional intercellular communication. Both mechanisms are inhibited by thrombin, which activates RhoA and hence results in myosin light chain phosphorylation. This study was conducted to examine the effects of adenosine, which is known to oppose thrombin-induced RhoA activation, thereby leading to myosin light chain dephosphorylation, on gap junctional intercellular communication and paracrine intercellular communication in cultured bovine corneal endothelial cells. An intercellular Ca(2+) wave was elicited by applying a mechanical stimulus to a single cell in a confluent monolayer. The area of Ca(2+) wave propagation was measured by [Ca(2+)](i) imaging using the fluorescent dye Fluo-4. Gap junctional intercellular communication was assessed by fluorescence recovery after photobleaching. Activity of hemichannels was determined by uptake of the hydrophilic dye Lucifer yellow in a Ca(2+)-free medium containing 2 mM EGTA. Adenosine triphosphate (ATP) release in response to mechanical stimulation was measured using the luciferin-luciferase technique. Gap26, a connexin mimetic peptide, was used to block hemichannels. Exposure to thrombin or TRAP-6 (a selective PAR-1 agonist) inhibited the Ca(2+) wave propagation by 70%. Pretreatment with adenosine prevented this inhibitory effect of thrombin. NECA (a potent A2B agonist) and forskolin, agents known to elevate cAMP in bovine corneal endothelial cells, also suppressed the effect of thrombin. The A1 receptor agonist CPA failed to inhibit the effect of thrombin. Similar to the effects on Ca(2+) wave propagation, adenosine prevented the thrombin-induced reduction in the fluorescence recovery during photobleaching experiments. Furthermore, pretreatment with adenosine prevented both thrombin and TRAP-6 from blocking the

  2. Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1

    PubMed Central

    Xie, Zhao-lian; Xiao, Ou; Yang, Xiao-ru; Heng, Boon Chin; Sato, Yasufumi

    2010-01-01

    Purpose To evaluate the activity of recombinant adenovirus encoding human vasohibin-1 (Ad-Vasohibin-1) on mouse corneal neovasularization induced by alkali burn. Methods For the treatment group, 50 mice each received subconjunctival injection (5 μl) of 109 plaque forming units of replication-defective Ad-Vasohibin-1. Control group mice received the same dosage of blank adenoviral vector (AdNull). Five days after injection, corneal neovascularization (CNV) was induced by placing 2.5 μl of 0.1 M NaOH on the right cornea for 30 s. Subsequently, CNV was observed and photographed every 3 days for a total duration of 9 days after the alkali burn. The percentage of neovascularized area was measured and compared with the AdNull control. The expression of human vasohibin-1 protein was detected by immunohistochemistry and western blotting at 5, 8, and 14 days after injection. The mRNA expression levels of murine vascular endothelial growth factor (Vegf), VEGF receptor 1 and 2 (Vegfr1, Vegfr2), and vasohibin-1 (Vash1) were analyzed and compared by real time quantitative reverse-transcription polymerase chain reaction. Results The percentage of neovascularized area within the cornea was significantly reduced in mice treated with Ad-Vasohibin-1 compared to mice treated with AdNull at every time point after alkali-induced injury (7.11%±3.91% and 15.48%±1.79% of corneal area in the treatment and control groups, respectively, on day 3; 31.64%±4.71% and 43.93%±6.15% on day 6, and 45.02%±9.98% and 66.24%±7.17% on day 9, all p<0.001). Human vasohibin-1 protein was detected at the injection sites on day 3 after corneal burn and was highly expressed in the central subepithelial stroma and co-localized with neovascularized vessels within the alkali-treated cornea on day 6. On day 9, the peripheral cornea exhibited a similar staining pattern as the central cornea, but a more intense vasohibin-1 immunostaining signal was detected in the deep stroma. Some of the vasohibin-1 stain

  3. Structural requirements for the edema-inducing and hemolytic activities of mastoparan B isolated from the hornet (Vespa basalis) venom.

    PubMed

    Ho, C L; Lin, Y L; Chen, W C; Hwang, L L; Yu, H M; Wang, K T

    1996-09-01

    Mastoparan B (MP-B) is a cationic tetradecapeptide isolated from the black-bellied hornet (Vespa basalis) venom. It has a primary structure (LKLKSIVSWAKKVL-CONH2) distinct from other vespine mastoparans. The peptide caused a dose-dependent swelling in rat hind paw and showed a potent hemolytic activity in guinea pig red blood cells. Studies on the structure activity relationship of the peptide showed that replacing lysine at position 2 (Lys2) by asparagine (Asn) in the MP-B sequence caused about 40% decrease in its edema-inducing activity at 50 micrograms/paw and 90% decrease in hemolytic activity at 30 microM of the peptide, while the same substitution at Lys4 did not cause a significant change in either activity. Replacing either Lys11 or Lys12 by leucine (Leu) caused little or no decrease in the edema-inducing and hemolytic activities. Decreases in both activities were observed when both Lys11 and Lys12 were replaced by Leu. On the other hand, replacing tryptophan at position 9 (Trp9) by tyrosine or phenylalanine in MP-B sequence almost abolished its hemolytic activity, while the edema-inducing activity was only partially inhibited. Circular dichroism spectra of the peptides measured in 20% trifluoro-ethanol revealed that substitution of Lys and Trp did not cause a significant change in the conformation of MP-B. it appears that Lys2 is crucial for both hemolytic and edema-inducing activities of MP-B, while Trp9 is of special importance to the hemolytic activity of MP-B. Lys11 and Lys12 in MP-B probably play a lesser role in both activities.

  4. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

    PubMed

    Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

    2017-03-16

    The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation.

  5. Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane

    PubMed Central

    Alharbi, Saad S.; Asiri, Mohammed S.

    2016-01-01

    A 58-year-old female presented with intracameral retained perfluoro-n-octane (PFO) following previous retinal reattachment surgery. After 4 years of follow-up without related sequelae, the patient complained of a gradual decrease in vision secondary to corneal edema with whitish corneal precipitate inferiorly corresponding to the area of retained PFO. Three weeks after anterior chamber washout, corneal edema resolved and the patient obtained 20/40 visual acuity. Even though PFO considered to have a relatively good safety profile, early anterior chamber washout may prevent corneal toxicity and avoid later persistent corneal decompensation. PMID:27555718

  6. Post-LASIK edema-induced keratopathy (PLEK), a new name based on pathophysiology of the condition

    PubMed Central

    Galvis, Virgilio; Tello, Alejandro; Revelo, Mario Leandro; Valarezo, Paul

    2012-01-01

    A 33-year-old man who underwent uneventful laser in situ keratomileusis (LASIK) developed pressure-induced stromal edema resulting in an interface haze in both eyes and a pocket of fluid under the flap of the right eye 10 days after surgery, while receiving topical fluorometholone. Intraocular pressure by applanation tonometry was 16 mm Hg in his right eye (erroneous result due to the fluid in the interface) and 34 mm Hg in his left eye. After discontinuation of steroids and addition of ocular hypotensive medication, interface fluid collection disappeared in his right eye. Visual acuity improved and haze diminished in both eyes. This case illustrates that in the same patient a post-LASIK edema induced syndrome may be present with or without fluid in the interface, suggesting that both clinical pictures could be manifestations of a broad spectrum of the same condition. We suggest a new name for this non-inflammatory disorder: post-LASIK edema-induced keratopathy (PLEK). PMID:23112265

  7. Post-LASIK edema-induced keratopathy (PLEK), a new name based on pathophysiology of the condition.

    PubMed

    Galvis, Virgilio; Tello, Alejandro; Revelo, Mario Leandro; Valarezo, Paul

    2012-10-30

    A 33-year-old man who underwent uneventful laser in situ keratomileusis (LASIK) developed pressure-induced stromal edema resulting in an interface haze in both eyes and a pocket of fluid under the flap of the right eye 10 days after surgery, while receiving topical fluorometholone. Intraocular pressure by applanation tonometry was 16 mm Hg in his right eye (erroneous result due to the fluid in the interface) and 34 mm Hg in his left eye. After discontinuation of steroids and addition of ocular hypotensive medication, interface fluid collection disappeared in his right eye. Visual acuity improved and haze diminished in both eyes. This case illustrates that in the same patient a post-LASIK edema induced syndrome may be present with or without fluid in the interface, suggesting that both clinical pictures could be manifestations of a broad spectrum of the same condition. We suggest a new name for this non-inflammatory disorder: post-LASIK edema-induced keratopathy (PLEK).

  8. Pattern of fluid accumulation in NO2-induced pulmonary edema in dogs. A morphometric study.

    PubMed Central

    Vassilyadi, M.; Michel, R. P.

    1988-01-01

    To ascertain whether the pattern of fluid accumulation could be altered by an agent introduced through the airways, the authors studied the physiology and morphology of 11 dogs exposed to 150-494 ppm.hr NO2 and compared them with 3 new and 5 previously reported control dogs. NO2 caused a partly reversible decrease in systemic arterial pressure and cardiac output, a fall in arterial PO2, and rapid shallow breathing, while pulmonary arterial and wedge pressures remained normal. Post mortem, lower (LL) and middle (ML) lobes were frozen, sections fixed for light microscopy by freeze-substitution, and wet weight/dry weight (W/D) ratios were measured. Alveolar edema was graded, and the distribution of interstitial edema around arteries and veins and within bronchovascular bundles was studied with morphometry: edema ratios (ER) were calculated as area of interstitium/area of vessel or airway. We found that NO2 produced an exposure-dependent increase in lung water (r = 0.73), and that both LL and ML had similar W/D ratios (7.77 and 8.39, respectively) and percent alveolar edema (30% and 34%). Morphometry of interstitial edema showed that the ER for vessels and airways of edematous LL were essentially similar to controls, while those of the ML were markedly increased. It is concluded that NO2 produces exposure-related lung edema and preferential alveolar flooding with probable secondary interstitial accumulation. The discrepancies in interstitial edema between middle and lower lobes may be due to differences in lung volume or in ventilation. Images Figure 6 Figure 9 PMID:3337206

  9. Quinidine, but Not Eicosanoid Antagonists or Dexamethasone, Protect the Gut from Platelet Activating Factor-Induced Vasoconstriction, Edema and Paralysis

    PubMed Central

    Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

    2015-01-01

    Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 μM). The COX and LOX inhibitors ASA and AA861 (500 μM, 10 μM) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 μM, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 μM) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 μM) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments

  10. Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute lung injury.

    PubMed

    Sciuto, A M; Strickland, P T; Kennedy, T P; Guo, Y L; Gurtner, G H

    1996-01-01

    Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-threatening latent noncardiogenic pulmonary edema. Mechanisms related to its toxicity appear to involve lipoxygenase mediators of arachidonic acid (AA) and can be inhibited by pretreatment with drugs that increase adenosine 3',5'-cyclic monophosphate (cAMP). In the present study, we used the isolated buffer-perfused rabbit lung model to investigate the mechanisms by which cAMP protects against phosgene-induced lung injury. Posttreatment with dibutyryl cAMP (DBcAMP) was given 60-85 min after exposure by an intravascular or intratracheal route. Lung weight gain (LWG) was measured continuously. AA metabolites leukotriene (LT) C4, LTD4, and LTE4 and 6-ketoprostaglandin F1 alpha were measured in the perfusate at 70, 90, 110, 130, and 150 min after exposure. Tissue malondialdehyde and reduced and oxidized glutathione were analyzed 150 min postexposure. Compared with measurements in the lungs of rabbits exposed to phosgene alone, posttreatment with DBcAMP significantly reduced LWG, pulmonary arterial pressure, and inhibited the release of LTC4, LTD4, and LTE4. Intratracheal administration of DBcAMP was more effective than intravascular administration in reducing LWG. Posttreatment also decreased MDA and protected against glutathione oxidation observed with phosgene exposure. We conclude that phosgene causes marked glutathione oxidation, lipid peroxidation, release of AA mediators, and increases LWG. Posttreatment with DBcAMP attenuates these effects, not only by previously described inhibition of pulmonary endothelial or epithelial cell contraction but also by inhibition of AA-mediator production and a novel antioxidant effect.

  11. Tissue Engineering of Corneal Endothelium

    PubMed Central

    Mimura, Tatsuya; Yokoo, Seiichi; Yamagami, Satoru

    2012-01-01

    Human corneal endothelial cells (HCECs) do not replicate after wounding. Therefore, corneal endothelial deficiency can result in irreversible corneal edema. Descemet stripping automated endothelial keratoplasty (DSAEK) allows selective replacement of the diseased corneal endothelium. However, DSAEK requires a donor cornea and the worldwide shortage of corneas limits its application. This review presents current knowledge on the tissue engineering of corneal endothelium using cultured HCECs. We also provide our recent work on tissue engineering for DSAEK grafts using cultured HCECs. We reconstructed DSAEK grafts by seeding cultured DiI-labelled HCECs on collagen sheets. Then HCEC sheets were transplanted onto the posterior stroma after descemetorhexis in the DSAEK group. Severe stromal edema was detected in the control group, but not in the DSAEK group throughout the observation period. Fluorescein microscopy one month after surgery showed numerous DiI-labelled cells on the posterior corneal surface in the DSAEK group. Frozen sections showed a monolayer of DiI-labelled cells on Descemet’s membrane. These findings indicate that cultured adult HCECs, transplanted with DSAEK surgery, maintain corneal transparency after transplantation and suggest the feasibility of performing DSAEK with HCECs to treat endothelial dysfunction. PMID:24955745

  12. Cocaine-induced myocardial infarction associated with severe reversible systolic dysfunction and pulmonary edema.

    PubMed

    Arzola-Castañer, Daniel; Johnson, Charles

    2004-12-01

    Myocardial infarction (MI) associated to cocaine use was originally reported in 1982 and cases are being encountered more frequently in our milieu. The literature regarding this diagnosis has included mostly cases of cocaine associated chest pain and MI without serious sequelae. A lesser number of reports however focus on the clinical presentation of severe myocardial dysfunction and severe pulmonary edema, with the mechanism for pulmonary edema still being debated. Although previously described individually, these manifestations are thought to be an uncommon complication of cocaine ingestion. In this article the subject is reviewed and we report our experience with two patients that presented to our care with severe pulmonary edema and concomitant severe left ventricular systolic dysfunction that resolved spontaneously with supportive therapy. It is felt that this clinical picture after cocaine use may be more common than expected. In this article we discuss the possible mechanisms associated to this presentation as well as review the literature regarding this subject.

  13. Immune Modulation of B. terrestris Worker (a Type of Bumblebee), Extract on CFA-induced Paw Edema in Rats

    PubMed Central

    Kim, Soon Ja; Han, Jea Woong; Yoon, Hyung Joo; Hwang, Jae Sam; Yun, Eun Young

    2014-01-01

    To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava an pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2, sPLA2, VEGF, and TNF-α, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin. PMID:25584147

  14. Nickel dental alloys can induce laryngeal edema attacks: a case report.

    PubMed

    Buyukozturk, Suna; Gelincik, Asli; Demirtürk, Mustafa; Erdoğdu, Derya; Pur, Leyla; Colakoğlu, Bahattin; Deniz, Gunnur; Erdem Kuruca, Serap

    2013-09-01

    Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration.

  15. The corneal endothelium in an endotoxin-induced uveitis model: correlation between in vivo confocal microscopy and immunohistochemistry

    PubMed Central

    Trinh, Liem; Brignole-Baudouin, Françoise; Labbé, Antoine; Raphaël, Mathilde; Bourges, Jean-Louis

    2008-01-01

    Purpose To analyze the involvement of the corneal endothelium in uveitis to better understand the formation mechanisms and the keratic precipitate composition. In vivo confocal microscopy images were correlated with ex vivo immunostaining of corneal endothelium from rat eyes with endotoxin-induced uveitis (EIU). Methods EIU was induced in Lewis rats by lipopolysaccharide (LPS) injection. Slit-lamp examination and in vivo confocal microscopy were performed 6, 24, 48, 72, and 96 h after the LPS injection. One group of rats was killed at 24 h and the other rats at 96 h. Immunohistochemistry on corneal endothelium using antibodies to intercellular adhesion molecule (ICAM-1), phalloidin, CD68 (anti-macrophage), MCA967 (anti-granulocyte), T cell receptor alpha/beta (TCR alpha/beta; anti-lymphocyte), zonula occludens-1 (ZO-1), and occludin was performed on flat-mount corneas and was analyzed using a three dimensional (3D) laser confocal microscope. Results In vivo confocal microscopy showed numerous hyperreflective round dots on the corneal endothelium, in the anterior chamber, and in the anterior stroma corresponding to inflammatory cells with a maximum at 24 h after the injection and detectable until the 96th hour. Upon immunostaining, corneal endothelial cells in rats with EIU overexpressed ICAM-1. ZO-1 and occludin had a lower endothelial expression and more heterogeneous distribution in EIU rats than in controls, showing disruption of endothelial cell junctions. Compared to controls, CD68, MCA967, and TCR alpha/beta expression was observed in corneas in rats with EIU. The two techniques showed a circular peripheral network of corneal vessels derived from a large circumferential vascular structure resembling the major arterial circle of iris where the inflammatory cells marginalized to infiltrate the anterior stroma. Conclusions The correlation between in vivo confocal microscopy and ex vivo immunostaining helped to better understand in vivo confocal microscopy images

  16. The corneal endothelium in an endotoxin-induced uveitis model: correlation between in vivo confocal microscopy and immunohistochemistry.

    PubMed

    Trinh, Liem; Brignole-Baudouin, Françoise; Labbé, Antoine; Raphaël, Mathilde; Bourges, Jean-Louis; Baudouin, Christophe

    2008-06-16

    To analyze the involvement of the corneal endothelium in uveitis to better understand the formation mechanisms and the keratic precipitate composition. In vivo confocal microscopy images were correlated with ex vivo immunostaining of corneal endothelium from rat eyes with endotoxin-induced uveitis (EIU). EIU was induced in Lewis rats by lipopolysaccharide (LPS) injection. Slit-lamp examination and in vivo confocal microscopy were performed 6, 24, 48, 72, and 96 h after the LPS injection. One group of rats was killed at 24 h and the other rats at 96 h. Immunohistochemistry on corneal endothelium using antibodies to intercellular adhesion molecule (ICAM-1), phalloidin, CD68 (anti-macrophage), MCA967 (anti-granulocyte), T cell receptor alpha/beta (TCR alpha/beta; anti-lymphocyte), zonula occludens-1 (ZO-1), and occludin was performed on flat-mount corneas and was analyzed using a three dimensional (3D) laser confocal microscope. In vivo confocal microscopy showed numerous hyperreflective round dots on the corneal endothelium, in the anterior chamber, and in the anterior stroma corresponding to inflammatory cells with a maximum at 24 h after the injection and detectable until the 96th hour. Upon immunostaining, corneal endothelial cells in rats with EIU overexpressed ICAM-1. ZO-1 and occludin had a lower endothelial expression and more heterogeneous distribution in EIU rats than in controls, showing disruption of endothelial cell junctions. Compared to controls, CD68, MCA967, and TCR alpha/beta expression was observed in corneas in rats with EIU. The two techniques showed a circular peripheral network of corneal vessels derived from a large circumferential vascular structure resembling the major arterial circle of iris where the inflammatory cells marginalized to infiltrate the anterior stroma. The correlation between in vivo confocal microscopy and ex vivo immunostaining helped to better understand in vivo confocal microscopy images. The two new techniques applied

  17. Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma

    PubMed Central

    Hayes, Sally; Boote, Craig; Kamma-Lorger, Christina S.; Rajan, Madhavan S.; Harris, Jonathan; Dooley, Erin; Hawksworth, Nicholas; Hiller, Jennifer; Terill, Nick J.; Hafezi, Farhad; Brahma, Arun K.; Quantock, Andrew J.; Meek, Keith M.

    2011-01-01

    Purpose To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas. Methods Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin). Results Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (p<0.001); an increase in fibril diameter was also seen in two out of four unswollen normal corneas and one unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a decrease in tissue hydration in the swollen normal corneas only. Although there was no consistent treatment-induced change in hydration in the unswollen normal samples, iso-osmolar cross-linking of these corneas did result in a compaction of collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not seen in the swollen normal corneas. Collagen D-periodicity was not affected by either treatment. Conclusion The observed structural changes following Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking. PMID:21850225

  18. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation.

    PubMed

    Bakunowicz-Łazarczyk, Alina; Urban, Beata

    2016-03-01

    This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy.

  19. Thermal load from a CO2 laser radiant energy source induces changes in corneal surface asphericity, roughness, and transverse contraction.

    PubMed

    McCafferty, Sean J; Schwiegerling, Jim T; Enikov, Eniko T

    2012-06-28

    We examined corneal surface response to an isolated thermal load. Cadaveric porcine eyes were pressurized and stabilized for processing and imaging. A carbon dioxide (CO2) laser (1.75 W) delivered a uniform disk of continuous wave thermal radiant energy to the exposed corneal stromal surface without ablation. Thermal load was determined by measuring corneal surface temperature during CO2 laser irradiation. Corneal profilometry was measured with broad-band optical interferometry before and after CO2 laser irradiation. Photomicrographs of the stromal surface were taken before and after irradiation, and the images were superimposed to examine changes in positional marks, examining mechanical alterations in the stromal surface. Thermal load from uniform laser irradiation without ablation produces central corneal steepening and paracentral flattening in the central 3-mm diameter. Q values, measuring asphericity in the central 2 mm of the cornea increased significantly and it was correlated with the temperature rise (R2=0.767). Surface roughness increased significantly and also was correlated with temperature rise (R2=0.851). The central stromal surface contracted and underwent characteristic morphologic changes with the applied thermal load, which correlated well with the temperature rise (R2=0.818). The thermal load created by CO2 laser irradiation creates a characteristic spectrum of morphologic changes on the porcine corneal stromal surface that correlates to the temperature rise and is not seen with inorganic, isotropic material. The surface changes demonstrated with the CO2 laser likely are indicative of temperature-induced transverse collagen fibril contraction and stress redistribution. Refractive procedures that produce significant thermal load should be cognizant of these morphologic changes.

  20. Imatinib-induced bone edema: case report and review of literature.

    PubMed

    dos Santos, Lucas Vieira; Lima, João Paulo; Abdalla, Kathia Cristina; Bragagnoli, Arinilda Campos; Santos, Florinda Almeida; dos Anjos Jácome, Alexandre; Porto, Fabiano Elias

    2013-10-01

    Imatinib mesylate represents a revolution in the management of patients with metastatic gastrointestinal stromal tumors (GISTs). More recently, postoperative imatinib has been shown to improve both disease-free and overall survivals in patients with a high risk of recurrence. This article presents a well-documented case of a patient with painful and reversible bone edema related to imatinib.

  1. Alkali-induced corneal stromal melting prevention by a novel platelet-activating factor receptor antagonist.

    PubMed

    He, Jiucheng; Bazan, Nicolas G; Bazan, Haydee E P

    2006-01-01

    To evaluate the effect of LAU0901 (2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester), a novel platelet-activating factor (PAF) receptor antagonist, on a rabbit model of severe corneal alkali injury. Adult New Zealand albino rabbits were anesthetized and the right eyes were injured with 2N sodium hydroxide for 60 seconds using a 12-mm plastic well, then rinsed. After the injury, 10 rabbits were treated topically with LAU0901 every 2 hours 4 times per day and received a subconjunctival injection of 200 microL of LAU0901 once per week and 10 rabbits were treated with vehicle the same way. Over the course of 4 weeks, the corneas were examined daily by slitlamp microscopy and corneal ulcers were graded with a clinical scoring system. Ten additional rabbits were treated as described but 1 rabbit from each group was killed at 1, 3, 7, 14, or 21 days after injury. The corneas were processed for histopathologic and immunofluorescence examination. Persistent epithelial defects were present in both groups from day 5 postinjury, but from day 9 through day 25, the average clinical scores of both epithelial defects and stromal ulcerations in the vehicle-treated eyes were significantly higher than those in the LAU0901-treated eyes (P<.01). By day 28, 90% of the eyes in the vehicle-treated group perforated, while only 20% of the eyes in the LAU0901-treated group developed deep ulceration and none were perforated. Histologic examination showed that the corneas treated with LAU0901 for 4 weeks were completely reepithelialized, with fewer inflammatory polymorphonuclear leukocytes and more repair fibroblasts (myofibroblasts) in the stroma as compared with those treated with vehicle. LAU0901 inhibits corneal ulceration and perforation in a severe alkali-burn model in the rabbit. In the cornea, PAF is a strong inflammatory mediator, a chemotactic to inflammatory polymorphonuclear leukocytes, and an inducer of several proteases that degrade the extracellular matrix

  2. Morphometric analysis of oleic acid-induced permeability pulmonary edema: correlation with gravimetric lung water.

    PubMed

    Darien, B J; Saban, M R; Hart, A P; MacWilliams, P S; Clayton, M K; Kruse-Elliott, K T

    1997-07-01

    The technique used most commonly to quantitate pulmonary edema in in vivo animal models is postmortem gravimetric analysis (wet:dry) ratio. To determine whether lung water can be quantitated morphometrically, as accurately as by the commonly used gravimetric analysis, perivascular edema (cuff) area to vessel area ratio was correlated to wet:dry ratio. Anesthetized pigs were given either oleic acid (20 mg/kg/h, intravenously) or physiologic saline. At 4 h, lungs were excised and cuff:vessel and wet:dry ratio analysis was performed. The intermediate lobe was clamped across its main stem bronchus to maintain peak inspiratory inflation, excised, frozen in liquid nitrogen, and stored at -70 degrees C until cryostat sectioning and quantification of perivascular interstitial edema (cuff) area. Gravimetric analysis (wet:dry ratio) was performed on the remaining lung. Mean cuff:vessel and wet:dry analyzes showed that lung water increased significantly (p < .01) in the oleic-acid treated group (4.9 +/- .22 and 6.78 +/- .47, respectively), compared with the saline group (.03 +/- .02 and 2.55 +/- .27, respectively). The correlation coefficient between mean cuff:vessel and wet:dry ratios was .86 (p = .0016). This study demonstrates that cuff:vessel ratio analysis can be used to identify the distribution of edema fluid versus vessel diameter, and seems to be as effective a technique as gravimetric analysis to quantitate lung water changes in acute lung injury models. Moreover cuff:vessel ratio analysis can differentiate modest changes in pulmonary edema by direct quantitation, an important end-point not provided by wet:dry analysis. Therefore, it may be a more sensitive technique when investigating therapeutic interventions in in vivo models of acute lung injury.

  3. Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Serduc, Raphaël; van de Looij, Yohan; Francony, Gilles; Verdonck, Olivier; van der Sanden, Boudewijn; Laissue, Jean; Farion, Régine; Bräuer-Krisch, Elke; Siegbahn, Erik Albert; Bravin, Alberto; Prezado, Yolanda; Segebarth, Christoph; Rémy, Chantal; Lahrech, Hana

    2008-03-01

    Cerebral edema is one of the main acute complications arising after irradiation of brain tumors. Microbeam radiation therapy (MRT), an innovative experimental radiotherapy technique using spatially fractionated synchrotron x-rays, has been shown to spare radiosensitive tissues such as mammal brains. The aim of this study was to determine if cerebral edema occurs after MRT using diffusion-weighted MRI and microgravimetry. Prone Swiss nude mice's heads were positioned horizontally in the synchrotron x-ray beam and the upper part of the left hemisphere was irradiated in the antero-posterior direction by an array of 18 planar microbeams (25 mm wide, on-center spacing 211 mm, height 4 mm, entrance dose 312 Gy or 1000 Gy). An apparent diffusion coefficient (ADC) was measured at 7 T 1, 7, 14, 21 and 28 days after irradiation. Eventually, the cerebral water content (CWC) was determined by microgravimetry. The ADC and CWC in the irradiated (312 Gy or 1000 Gy) and in the contralateral non-irradiated hemispheres were not significantly different at all measurement times, with two exceptions: (1) a 9% ADC decrease (p < 0.05) was observed in the irradiated cortex 1 day after exposure to 312 Gy, (2) a 0.7% increase (p < 0.05) in the CWC was measured in the irradiated hemispheres 1 day after exposure to 1000 Gy. The results demonstrate the presence of a minor and transient cellular edema (ADC decrease) at 1 day after a 312 Gy exposure, without a significant CWC increase. One day after a 1000 Gy exposure, the CWC increased, while the ADC remained unchanged and may reflect the simultaneous presence of cellular and vasogenic edema. Both types of edema disappear within a week after microbeam exposure which may confirm the normal tissue sparing effect of MRT. For more information on this article, see medicalphysicsweb.org

  4. Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury.

    PubMed

    Lu, Kwok-Tung; Huang, Tai-Chun; Tsai, Ya-Hsin; Yang, Yi-Ling

    2017-03-01

    Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the MAPK cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission, and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device. Adult male Wistar rats were randomly assigned into sham and experimental groups for time-course studies of TRPV4 expression after TBI. Hippocampal TRPV4, NKCC1, MAPK, and PI-3K cascades were analyzed by western blot, and brain edema was also evaluated among the different groups. Expression of hippocampal TRPV4 peaked at 8 h after TBI, and phosphorylation of the MAPK cascade and Akt was significantly elevated. Administration of either the TRPV4 antagonist, RN1734, or NKCC1 antagonist, bumetanide, significantly attenuated TBI-induced brain edema through decreasing the phosphorylation of MEK, ERK, and Akt proteins. Bumetanide injection inhibited TRPV4 expression, which suggests NKCC1 activation is critical to TRPV4 activation. Our results showed that hippocampal NKCC1 activation increased TRPV4 expression after TBI and then induced severe brain edema and neuronal damage through activation of the MAPK cascade and Akt-related signaling pathway.

  5. Serine protease inhibitor A3K protects rabbit corneal endothelium from barrier function disruption induced by TNF-α.

    PubMed

    Hu, Jiaoyue; Zhang, Zhenhao; Xie, Hui; Chen, Lelei; Zhou, Yueping; Chen, Wensheng; Liu, Zuguo

    2013-08-09

    To determine if a serine protease inhibitor A3K (SA3K) reduces TNF-α-induced declines in rabbit corneal endothelial junctional barrier integrity. New Zealand rabbit corneas were incubated ex vivo for 24 hours in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS with or without TNF-α, in the presence or absence of SA3K at different concentrations. Corneal endothelial barrier function permeability was determined based on measurements of FITC-dextran tissue accumulation. Apical junctional complex (AJC) integrity was evaluated of zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, and filamentous actin (F-actin) and associated microtubules, as well as myosin light chain (MLC) by immunofluorescent staining, Western blot analysis, and/or RT-PCR. TNF-α (20 ng/mL) increased corneal endothelial FITC-dextran permeability by 1.8-fold compared with the untreated control. SA3K (100-200 nM) dose dependently suppressed TNF-α-induced increases in permeability. SA3K nearly completely reversed TNF-α-induced disruptions of tight junctional ZO-1 and subjacent adherens junctions VE-cadherin integrity. Interestingly, SA3K reversed TNF-α-induced disruption of AJC linkage to the cytoskeletal F-actin array by restoring F-actin double-band structures. SA3K also attenuated TNF-α-induced microtubule disassembly. Furthermore, SA3K blocked increases in MLC phosphorylation status elicited by TNF-α. SA3K exposure markedly reduced TNF-α-induced disruption of barrier structure and function in the rabbit corneal endothelium by maintaining AJC integrity. These protective effects are due to suppression of MLC activation. SA3K may have, in vivo, a therapeutic potential to offset TNF-α-induced declines in endothelial barrier structural integrity and function.

  6. The effect of bumetanide on photodynamic therapy-induced peri-tumor edema of C6 glioma xenografts.

    PubMed

    Zhang, Xufeng; Cong, Damin; Shen, Dawei; Gao, Xin; Chen, Lei; Hu, Shaoshan

    2014-07-01

    The aim of this study was to investigate the effect of bumetanide on peri-tumor edema caused by photodynamic therapy (PDT) of intraparenchymal C6 glioma xenografts. Seven days after inoculation with C6 cells, rats with MRI-confirmed glioma received hematoporphyrin monomethyl ether (HMME)-mediated PDT, injection of bumetanide or a combination of the two treatments. After treatment, tumor volume, tumor weight, brain water content, microvessel density, expression of NKCC-1, Zonula occludens-1 (ZO-1), and animal survival time were examined. In the PDT group, tumor growth was significantly inhibited and survival prolonged. Bumetanide enhanced the efficacy of PDT and reduced PDT-induced peri-tumor edema in the combined PDT + bumetanide treatment group where NKCC-1 expression in response to PDT was significantly suppressed. ZO-1 expression was significantly suppressed in the PDT-only group. This suppression was not observed in the combined PDT + bumetanide treatment group. PDT, in combination with bumetanide was seen to significantly inhibit the growth of C6 glioma, relieve peri-tumor edema caused by PDT alone and prolong survival. These results suggest that PDT, in combination with bumetanide, may be a useful and promising strategy in the treatment of human glioma. © 2014 Wiley Periodicals, Inc.

  7. Pulmonary edema

    MedlinePlus

    ... Saunders; 2015:chap 23. Matthay MA, Martin TR, Murray JF. Pulmonary edema. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray & Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, ...

  8. PACAP induces neurite outgrowth in cultured trigeminal ganglion cells and recovery of corneal sensitivity after flap surgery in rabbits.

    PubMed

    Fukiage, Chiho; Nakajima, Takeshi; Takayama, Yoshiko; Minagawa, Yoko; Shearer, Thomas R; Azuma, Mitsuyoshi

    2007-02-01

    To evaluate the ability of pituitary adenylate cyclase-activating polypeptide (PACAP) to induce growth of neuronal processes in cultured trigeminal ganglion cells, and to accelerate neurite outgrowth and recovery of corneal sensitivity after creation of a corneal flap in a rabbit model of laser-assisted in situ keratomileusis (LASIK) surgery. Animal study. The cDNA of rabbit PACAP was sequenced, and the expression of PACAP receptors in the trigeminal ganglia from rabbits was quantified by quantitative real-time polymerase chain reaction. Trigeminal ganglion cells were isolated from rabbits and cultured for 48 hours with or without PACAP27 (bioactive N-terminal peptide from PACAP). Cells were stained with antibody against neurofilaments, and neurite outgrowth was quantified by cell counting. In the rabbit LASIK model, a corneal flap with a planned thickness of 130 microm and 8.5 mm diameter was created with a microkeratome. The rabbits then received eyedrops containing PACAP27 four times a day for eight weeks, and corneal sensitivity was measured. Neurite outgrowth was assessed by staining histologic sections of the flap area for cholinesterase. The deduced amino acid sequence of PACAP in rabbit was identical to that of human. PACAP receptor, PAC1, was highly expressed in trigeminal ganglia from newborn and adult rabbits. PACAP27 at 1 microM induced growth of neuronal processes in cultured primary trigeminal ganglion cells. In the LASIK model, extensions of neuronal processes from amputated nerve trunks in cornea were observed after administration of eyedrops containing 1 or 10 microM PACAP27. The 10 microM PACAP27 treatment also greatly accelerated recovery of corneal sensitivity. PACAP may be a candidate drug for ameliorating dry eye after LASIK surgery.

  9. Microbiologic, Pharmacokinetic, and Clinical Effects of Corneal Collagen Cross-Linking on Experimentally Induced Pseudomonas Keratitis in Rabbits.

    PubMed

    Cosar, C Banu; Kucuk, Mutlu; Celik, Ekrem; Gonen, Tansu; Akyar, Isin; Serteser, Mustafa; Tokat, Fatma; Ince, Umit

    2015-10-01

    To determine the effects of corneal collagen cross-linking (CXL) on the penetration of topical 0.5% moxifloxacin, on the number of colony-forming units (CFUs) in the cornea, and on the clinical course in a rabbit eye model of experimentally induced Pseudomonas aeruginosa keratitis. In this prospective animal study, experimental Pseudomonas corneal ulcers were induced in 56 corneas of 28 albino New Zealand rabbits. The corneas were randomly divided into the following 4 groups: the control group (14 eyes), the MOX group (moxifloxacin) (14 eyes), the MOX + CXL group (14 eyes), and the CXL group (14 eyes). On day 4 of the experiment, the eyes in the control group were enucleated and CFU counting was performed. On day 10 of the experiment, all eyes were enucleated and CFU counting was performed. In the MOX and MOX + CXL groups, the moxifloxacin level in the cornea, aqueous humor, iris, plasma, and serum was measured by reverse-phase high-performance liquid chromatography. The difference in the corneal CFU count between the MOX group and the MOX + CXL group was not significant (P = 0.317). Clinical improvement was greatest in the MOX + CXL group (P < 0.001). The mean corneal moxifloxacin level was 0.391 ± 0.09 μg·mg in the MOX group versus 0.291 ± 0.09 μg·mg in the MOX + CXL group; as such, CXL did not have a significant effect on antibiotic penetrance (P = 0.386). Clinical improvement was greatest in the MOX + CXL group. The synergistic effect of CXL on corneal ulcer treatment is not through antibiotic penetrance.

  10. Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

    SciTech Connect

    Seomun, Young; Joo, Choun-Ki

    2008-07-18

    Lumican is a major proteoglycans of the human cornea. Lumican knock-out mice have been shown to lose corneal transparency and to display delayed wound healing. The purpose of this study was to define the role of lumican in corneal epithelial cell migration. Over-expression of lumican in human corneal epithelial (HCE-T) cells increased both cell migration and proliferation, and increased levels of integrins {alpha}2 and {beta}1. ERK 1/2 was also activated in lumican over-expressed cells. When we treated HCE-T cells with the ERK-specific inhibitor U0126, cell migration and the expression of integrin {beta}1 were completely blocked. These data provide evidence that lumican stimulates cell migration in the corneal epithelium by activating ERK 1/2, and point to a novel signaling pathway implicated in corneal epithelial cell migration.

  11. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    PubMed Central

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  12. Acute corneal hydrops in keratoconus

    PubMed Central

    Maharana, Prafulla K; Sharma, Namrata; Vajpayee, Rasik B

    2013-01-01

    Acute corneal hydrops is a condition characterized by stromal edema due to leakage of aqueous through a tear in descemet membrane. The patient presents with sudden onset decrease in vision, photophobia, and pain. Corneal thinning and ectasias combined with trivial trauma to the eye mostly by eye rubbing is considered as the underlying cause. With conservative approach self-resolution takes around 2 to 3 months. Surgical intervention is required in cases of non-resolution of corneal edema to avoid complications and for early visual rehabilitation. Intracameral injection of air or gas such as perflouropropane is the most common surgical procedure done. Recent investigative modality such as anterior segment optical coherence tomography is an extremely useful tool for diagnosis, surgical planning, and postoperative follow up. Resolution of hydrops may improve the contact lens tolerance and visual acuity but most cases require keratoplasty for visual rehabilitation. PMID:23925338

  13. Anti-thymocyte globulin induced non-cardiogenic pulmonary edema during renal transplantation.

    PubMed

    Parikh, Beena K; Bhosale, Guruprasad P; Shah, Veena R

    2011-10-01

    Non-cardiogenic pulmonary edema (NCPE) is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, without evidence of left atrial hypertension/congestive heart failure/fluid overload. The diagnosis of drugrelated NCPE relies upon documented exclusion of other causes of NCPE like gastric aspiration, sepsis, trauma, negative pressure pulmonary edema. We describe a 28year-old, 50 kg male with ASA risk III posted for laparoscopic renal transplantation, who developed NCPE after 4 hours of administration of rabbit anti-human thymocyte immunoglobulin (ATG). He was successfully treated with mechanical ventilatory support and adjuvant therapy. This report emphasizes that this fatal complication may occur with use of ATG.

  14. In vivo architectural analysis of clear corneal incisions using anterior segment optical coherence tomography.

    PubMed

    Dupont-Monod, Sylvère; Labbé, Antoine; Fayol, Nicolas; Chassignol, Alexis; Bourges, Jean-Louis; Baudouin, Christophe

    2009-03-01

    To use anterior segment optical coherence tomography (AS-OCT) to analyze the in vivo architecture of clear corneal incisions after phacoemulsification using different techniques. Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital, Paris, France. This prospective observational study analyzed clear corneal incisions used in phacoemulsification. All wounds were evaluated 1 day and 8 days postoperatively by AS-OCT (Visante). Incision architecture and pachymetry at the wound level were analyzed. Thirty-five clear corneal incisions were analyzed. Six eyes had 2.75 mm coaxial phacoemulsification, 19 had 2.20 mm microincision coaxial phacoemulsification, and 10 had 1.30 mm bimanual microincision phacoemulsification. The 1.30 mm incision had a straight-line configuration. The 2.20 mm and 2.75 mm incisions had an arcuate configuration. The angles of incidence of 1.30 mm incisions were greater than those of 2.20 mm incisions (P<.001). All incisions had slight corneal edema limited to the incision area. The edema was slightly greater around 1.30 mm incisions (mean pachymetry 1143 microm +/- 140 [SD]) than around 2.20 mm incisions (mean 1012 +/- 101 microm) (P = .001). Bimanual procedures had satisfactory endothelial apposition in the enlarged areas, where stromal edema was less than that surrounding the unenlarged 1.30 mm incisions. The 3 phacoemulsification techniques induced gaping of the endothelial edge, minor inadequate endothelial apposition, and mild stromal edema in the area of the clear corneal incisions. Bimanual microincision sleeveless phacoemulsification may alter the wound slightly more than coaxial 2.75 mm and microcoaxial 2.20 mm sleeved-tip phacoemulsification.

  15. Aqueous and Methanolic Extracts of Caulerpa mexicana Suppress Cell Migration and Ear Edema Induced by Inflammatory Agents

    PubMed Central

    Bitencourt, Mariana Angelica Oliveira; Dantas, Gracielle Rodrigues; Lira, Daysianne Pereira; Barbosa-Filho, Jose Maria; de Miranda, George Emmanuel Cavalcanti; de Oliveira Santos, Barbara Viviana; Souto, Janeusa Trindade

    2011-01-01

    The regulation of the inflammatory response is essential to maintaining homeostasis. Several studies have investigated new drugs that may contribute to avoiding or minimizing excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexicana on models inflammation. In mice, the inflammatory peritonitis model is induced by zymosan. Previous treatment of mice with aqueous and methanolic extracts of C. mexicana was able to suppress the cell migration to the peritoneal cavity, in a time-dependent but not in a dose-dependent manner. The treatment of mice with C. mexicana extracts also decreased the xylene-induced ear edema, exerting strong inhibitory leukocyte migration elicited by zymosan into the air pouch. We concluded that administration of the extracts resulted in a reduction of cell migration to different sites as well as a decrease in edema formation induced by chemical irritants. This study demonstrates for the first time the anti-inflammatory effect of aqueous and methanolic extracts from the green marine algae Caulerpa mexicana. PMID:21892348

  16. Aqueous and methanolic extracts of Caulerpa mexicana suppress cell migration and ear edema induced by inflammatory agents.

    PubMed

    Bitencourt, Mariana Angelica Oliveira; Dantas, Gracielle Rodrigues; Lira, Daysianne Pereira; Barbosa-Filho, Jose Maria; de Miranda, George Emmanuel Cavalcanti; Santos, Barbara Viviana de Oliveira; Souto, Janeusa Trindade

    2011-01-01

    The regulation of the inflammatory response is essential to maintaining homeostasis. Several studies have investigated new drugs that may contribute to avoiding or minimizing excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexicana on models inflammation. In mice, the inflammatory peritonitis model is induced by zymosan. Previous treatment of mice with aqueous and methanolic extracts of C. mexicana was able to suppress the cell migration to the peritoneal cavity, in a time-dependent but not in a dose-dependent manner. The treatment of mice with C. mexicana extracts also decreased the xylene-induced ear edema, exerting strong inhibitory leukocyte migration elicited by zymosan into the air pouch. We concluded that administration of the extracts resulted in a reduction of cell migration to different sites as well as a decrease in edema formation induced by chemical irritants. This study demonstrates for the first time the anti-inflammatory effect of aqueous and methanolic extracts from the green marine algae Caulerpa mexicana.

  17. Edema-producing activity of group A streptococcal polysaccharide and its possible role in the pathogenesis of cell wall-induced polyarthritis

    PubMed Central

    1983-01-01

    Edematous responses were induced in the limbs of Sprague-Dawley rats by intravenous, intraperitoneal, or intra-articular injections of group- specific polysaccharide (PS) isolated from the cell walls of group A streptococci. After intravenous injection of the edema-producing PS, vascular permeability increase (measured by 125I-human serum albumin) was detected in the limbs, but not in the heart, lungs, spleen, liver, thymus, kidney, skin, skeletal muscle, submandibular lymph nodes, mesenteric lymph nodes, or ascending colon. This indicates a selective effect on vascular endothelium of the joints. Evidence to suggest that the edema-producing activity of the PS might play an important role in the pathogenesis of cell wall-induced polyarthritis included the following: (a) the presence of edema-producing activity in arthropathogenic cell wall preparations; (b) cell wall preparations without edema-producing activity were significantly less active in inducing arthritis than were those which contained edema-producing activity; and (c) the addition of edema-producing PS to cell wall preparations increased both the incidence and the severity of arthritis. PMID:6833951

  18. Calotropis procera -induced keratitis.

    PubMed

    Pandey, Nidhi; Chandrakar, A K; Garg, M L; Patel, Santosh Singh

    2009-01-01

    Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  19. Stratified corneal limbal epithelial cells are protected from UVB-induced apoptosis by elevated extracellular K⁺.

    PubMed

    Schotanus, Mark P; Koetje, Leah R; Van Dyken, Rachel E; Ubels, John L

    2011-11-01

    The goal of this study was to determine whether elevated [K(+)] protects stratified corneal epithelial cells from entering apoptosis following exposure to ambient levels of UVB radiation. Human corneal limbal epithelial (HCLE) cells were stratified to form multilayered constructs in culture. The cells were exposed to UVB doses of 100-250 mJ/cm(2) followed by incubation in medium with 5.5-100 mM K(+). The protective effect of K(+) was determined by measuring the caspase-3 and -8 activity and TUNEL staining of the stratified HCLE constructs. In response to UVB exposure, activation of apoptotic pathways peaked at 24 h. Caspase-8 in stratified cells was activated by exposure to UVB at 100-250 mJ/cm(2), and activity was significantly reduced in response to 50 or 100 mM K(+). Caspase-3 was activated in the stratified cells in response to 100-250 mJ/cm(2) UVB and showed a significant reduction in activity in response to 25, 50 or 100 mM K(+). DNA fragmentation, as indicated by TUNEL staining, was elevated after exposure to 200 mJ/cm(2) UVB, and decreased following incubation with 25-100 mM K(+). These results show that in a culture system that models the intact corneal epithelium, elevated extracellular K(+) can reduce UVB-induced apoptosis which is believed to be initiated by loss of K(+) from cells. This is the basis of damage to the corneal epithelium caused by UVB exposure. Based on these observations it is suggested that the relatively high K(+) concentration in tears (20-25 mM) may play a role in protecting the corneal epithelium from ambient UVB radiation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Microscopic characterization of collagen modifications induced by low-temperature diode-laser welding of corneal tissue.

    PubMed

    Matteini, Paolo; Rossi, Francesca; Menabuoni, Luca; Pini, Roberto

    2007-08-01

    Laser welding of corneal tissue that employs diode lasers (810 nm) at low power densities (12-20 W/cm(2)) in association with Indocyanine Green staining of the wound is a technique proposed as an alternative to conventional suturing procedures. The aim of this study is to evaluate, by means of light (LM) and transmission electron microscopy (TEM) analyses, the structural modifications induced in laser-welded corneal stroma. Experiments were carried out in 20 freshly enucleated pig eyes. A 3.5 mm in length full-thickness cut was produced in the cornea, and was then closed by laser welding. Birefringence modifications in samples stained with picrosirius red dye were analyzed by polarized LM to assess heat damage. TEM analysis was performed on ultra-thin slices, contrasted with uranyl acetate and lead citrate, in order to assess organization and size of type I collagen fibrils after laser welding. LM evidenced bridges of collagen bundles between the wound edges, with a loss of regular lamellar organization at the welded site. Polarized LM indicated that birefringence properties were mostly preserved after laser treatment. TEM examinations revealed the presence of quasi-ordered groups of fibrils across the wound edges preserving their interfibrillar spacing. These fibrils appeared morphologically comparable to those in the control tissue, indicating that type I collagen was not denatured during the diode laser corneal welding. The preservation of substantially intact, undenatured collagen fibrils in laser-welded corneal wounds supported the thermodynamic studies that we carried out recently, which indicated temperatures below 66 degrees C at the weld site under laser irradiation. This observation enabled us to hypothesize that the mechanism, proposed in the literature, of unwinding of collagen triple helixes followed by fibrils "interdigitation" is not likely to occur in the welding process that we set up for the corneal suturing.

  1. Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity.

    PubMed

    Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F; Rosenblatt, Mark I

    2015-12-01

    In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication ("dry response"), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. These results demonstrate that tear hyperosmolarity, considered to be a "core" mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients.

  2. Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation*

    PubMed Central

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M.; Su, Yunchao

    2014-01-01

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326–333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor NG-nitro-l-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. PMID:25315770

  3. Preemptive hemodynamic intervention restricting the administration of fluids attenuates lung edema progression in oleic acid-induced lung injury.

    PubMed

    Gil Cano, A; Gracia Romero, M; Monge García, M I; Guijo González, P; Ruiz Campos, J

    2017-04-01

    A study is made of the influence of preemptive hemodynamic intervention restricting fluid administration upon the development of oleic acid-induced lung injury. A randomized in vivo study in rabbits was carried out. University research laboratory. Sixteen anesthetized, mechanically ventilated rabbits. Hemodynamic measurements obtained by transesophageal Doppler signal. Respiratory mechanics computed by a least square fitting method. Lung edema assessed by the ratio of wet weight to dry weight of the right lung. Histological examination of the left lung. Animals were randomly assigned to either the early protective lung strategy (EPLS) (n=8) or the early protective hemodynamic strategy (EPHS) (n=8). In both groups, lung injury was induced by the intravenous infusion of oleic acid (OA) (0.133mlkg(-1)h(-1) for 2h). At the same time, the EPLS group received 15mlkg(-1)h(-1) of Ringer lactate solution, while the EPHS group received 30mlkg(-1)h(-1). Measurements were obtained at baseline and 1 and 2h after starting OA infusion. After 2h, the cardiac index decreased in the EPLS group (p<0.05), whereas in the EPHS group it remained unchanged. Lung compliance decreased significantly only in the EPHS group (p<0.05). Lung edema was greater in the EPHS group (p<0.05). Histological damage proved similar in both groups (p=0.4). In this experimental model of early lung injury, lung edema progression was attenuated by preemptively restricting the administration of fluids. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  4. Functional depletion of capsaicin-sensitive primary afferent fibers attenuates rat pain-related behaviors and paw edema induced by the venom of scorpion Buthus martensi Karch.

    PubMed

    Bai, Zhan-Tao; Liu, Tong; Pang, Xue-Yan; Jiang, Feng; Cheng, Ming; Ji, Yong-Hua

    2008-10-01

    The role of capsaicin-sensitive primary afferent fibers in rat pain-related behaviors and paw edema induced by scorpion Buthus martensi Karch (BmK) venom was investigated in this study. It was found that functional depletion of capsaicin-sensitive primary afferent fibers with a single systemic injection of resiniferatoxin (RTX) dramatically decreased spontaneous nociceptive behaviors, prevented the development of primary mechanical and thermal hyperalgesia as well as mirror-image mechanical hyperalgesia. RTX treatment significantly attenuated BmK venom-induced c-Fos expression in all laminaes of bilateral L4-L5 lumbar spinal cord, especially in superficial laminaes. Moreover, RTX treatment markedly reduced the early paw edema induced by BmK venom. Thus, the results indicate that capsaicin-sensitive primary afferent fibers play a critical role in various pain-related behaviors and paw edema induced by BmK venom in rats.

  5. Corneal dystrophies

    PubMed Central

    Klintworth, Gordon K

    2009-01-01

    The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses

  6. Grading of corneal transparency.

    PubMed

    O'Donnell, Clare; Wolffsohn, James S

    2004-12-01

    To examine the academic literature on the grading of corneal transparency and to assess the potential use of objective image analysis. Reference databases of academic literature were searched and relevant manuscripts reviewed. Annunziato, Efron (Millennium Edition) and Vistakon-Synoptik corneal oedema grading scale images were analysed objectively for relative intensity, edges detected, variation in intensity and maximum intensity. In addition, corneal oedema was induced in one subject using a low oxygen transmissibility (Dk/t) hydrogel contact lens worn for 3h under a light eye patch. Recovery from oedema was monitored over time using ultrasound pachymetry, high and low contrast visual acuity measures, bulbar hyperaemia grading and transparency image analysis of the test and control eyes. Several methods for assessing corneal transparency are described in the academic literature, but none have gained widespread use in clinical practice. The change in objective image analysis with printed scale grade was best described by quadratic parametric or sigmoid 3-parameter functions. 'Pupil image scales' (Annunziato and Vistakon-Synoptik) were best correlated to average intensity; however, the corneal section scale (Efron) was strongly correlated to variations in intensity. As expected, patching an eye wearing a low Dk/t hydrogel contact lens caused a significant (F = 119.2, p < 0.001) 14.3% increase in corneal thickness, which gradually recovered under open eye conditions. Corneal section image analysis was the most affected parameter and intensity variation across the slit width, in isolation, was the strongest correlate, accounting for 85.8% of the variance with time following patching, and 88.7% of the variance with corneal thickness. Corneal oedema is best determined objectively by the intensity variation across the width of a corneal section. This can be easily measured using a slit-lamp camera connected to a computer. Oedema due to soft contact lens wear is not

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

    PubMed

    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.

  8. Prior Corneal Scarification and Injection of Immune Serum are Not Required Before Ocular HSV-1 Infection for UV-B-Induced Virus Reactivation and Recurrent Herpetic Corneal Disease in Latently Infected Mice.

    PubMed

    BenMohamed, Lbachir; Osorio, Nelson; Khan, Arif A; Srivastava, Ruchi; Huang, Lei; Krochmal, John J; Garcia, Jairo M; Simpson, Jennifer L; Wechsler, Steven L

    2016-06-01

    Blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (HSV-1) from latency, rather than to primary acute infection. Mice latently infected with HSV-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. HSV-1 reactivation can be induced in latently infected mice by several in vivo procedures, with UV-B-induced reactivation being one commonly used method. In the UV-B model, corneas are scarified (lightly scratched) just prior to ocular infection to increase efficiency of the primary infection and immune serum containing HSV-1 neutralizing antibodies is injected intraperitoneally (i.p.) to increase survival and decrease acute corneal damage. Since scarification can significantly alter host gene transcription in the cornea and in the trigeminal ganglia (TG; the site of HSV-1 latency) and since injection of immune serum likely modulates innate and adaptive herpes immunity, we investigated eliminating both treatments. Mice were infected with HSV-1 with or without corneal scarification and immune serum. HSV-1 reactivation and recurrent disease were induced by UV-B irradiation. When corneal scarification and immune serum were both eliminated, UV-B irradiation still induced both HSV-1 reactivation, as measured by shedding of reactivated virus in tears and herpetic eye disease, albeit at reduced levels compared to the original procedure. Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model.

  9. Diabetic macular edema.

    PubMed

    Stefánsson, Einar

    2009-07-01

    A variety of treatment options are available for the treatment of diabetic macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal steroids, and vitrectomy with or without release of vitreoretinal traction. A full understanding of the physiological mechanisms of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and thereby decreases leakage of plasma proteins from capillaries into the tissue. In addition, vitrectomy allows faster clearance of cytokines, such as VEGF, from the retina into the vitreous cavity. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary permeability. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF-induced vascular permeability causes plasma protein to leak into the tissue interstitial space, thus decreasing the osmotic pressure gradient between vessel and tissue, resulting in water accumulation, i.e. edema. This is reversed by reducing VEGF production, which is achieved with laser treatment; or by removing VEGF with antibodies or vitrectomy; or by reducing the permeability effect with steroids. At the same time, Starling's law takes into account hemodynamic changes that affect the hydrostatic gradient. High arterial blood pressure and hypoxic vasodilatation increase the hydrostatic pressure in the microcirculation, which increases water flux from vessel to tissue and induce edema. Treatment of arterial hypertension or reversal of retinal hypoxia with laser reverses this pathophysiology and reduces edema. Newton's third law explains, that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient

  10. Therapeutic efficiency of tissue-engineered human corneal endothelium transplants on rabbit primary corneal endotheliopathy.

    PubMed

    Fan, Ting-jun; Zhao, Jun; Hu, Xiu-zhong; Ma, Xi-ya; Zhang, Wen-bo; Yang, Chao-zhong

    2011-06-01

    To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP), TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mcHCECs) and modified denuded amniotic membranes (mdAMs) were transplanted into PCEP models of New Zealand white rabbits using penetrating keratoplasty. The TE-HCEs were examined using diverse techniques including slit-lamp biomicroscopy observation and pachymeter and tonometer measurements in vivo, and fluorescent microscopy, alizarin red staining, paraffin sectioning, scanning and transmission electron microscopy observations in vitro. The corneas of transplanted eyes maintained transparency for as long as 200 d without obvious edema or immune rejection. The corneal thickness of transplanted eyes decreased gradually after transplanting, reaching almost the thickness of normal eyes after 156 d, while the TE-HCE non-transplanted eyes were turbid and showed obvious corneal edema. The polygonal corneal endothelial cells in the transplanted area originated from the TE-HCE transplant. An intact monolayer corneal endothelium had been reconstructed with the morphology, cell density and structure similar to those of normal rabbit corneal endothelium. In conclusion, the transplanted TE-HCE can reconstruct the integrality of corneal endothelium and restore corneal transparency and thickness in PCEP rabbits. The TE-HCE functions normally as an endothelial barrier and pump and promises to be an equivalent of HCE for clinical therapy of human PCEP.

  11. The ROCK inhibitor eye drop accelerates corneal endothelium wound healing.

    PubMed

    Okumura, Naoki; Koizumi, Noriko; Kay, Eunduck P; Ueno, Morio; Sakamoto, Yuji; Nakamura, Shinichiro; Hamuro, Junji; Kinoshita, Shigeru

    2013-04-03

    To evaluate the effect of Rho kinase (ROCK)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction. As a corneal-endothelial partially injured model, the corneal endothelium of seven cynomolgus monkeys was damaged by transcorneal freezing; 10 mm of rock inhibitor Y-27632 was then applied topically 6 times daily. The phenotype of the reconstructed corneal endothelium was evaluated by immunohistochemical analysis and noncontact specular microscopy. For clinical study, the effect of Y-27632 eye drops after transcorneal freezing was evaluated in eight corneal endothelial dysfunction patients: four central corneal edema patients and four diffuse corneal edema patients. Slit-lamp microscopy revealed that both Y-27632-treated and -nontreated corneas became hazy after transcorneal freezing, and then recovered their transparency within 4 weeks. ROCK inhibitor Y-27632 promoted recovery of corneal endothelial cell density and wound healing in terms of both morphology and function. The percentage of ZO-1 and Na(+)/K(+)-ATPase positive cells in the regenerated area in the Y-27632 group was significantly higher than in the controls. Noncontact specular microscopy revealed that corneal endothelial cell density was significantly higher in the Y-27632 group compared with the controls at 4 weeks; cell density reached approximately 3000 cells/mm(2), as opposed to 1500 cells/mm(2) in the control group. In addition to the animal study findings, the clinical study findings showed that Y-27632 eye drops effectively improved corneal edema of corneal endothelial dysfunction patients with central edema. These findings show that rock inhibitor Y-27632 eye drops promote corneal endothelial wound healing in a primate animal model and suggest the possibility of Y-27632 as a novel therapeutic modality for certain forms of corneal endothelial dysfunction. (http://www.umin.ac.jp/ctr/ number, UMIN000003625.).

  12. The fibril core of transforming growth factor beta-induced protein (TGFBIp) facilitates aggregation of corneal TGFBIp

    PubMed Central

    Sørensen, Charlotte S.; Runager, Kasper; Scavenius, Carsten; Jensen, Morten M.; Nielsen, Nadia S.; Christiansen, Gunna; Petersen, Steen V.; Karring, Henrik; Sanggaard, Kristian W.; Enghild, Jan J.

    2016-01-01

    Mutations in the transforming growth factor beta-induced (TGFBI) gene result in a group of hereditary diseases of the cornea that are collectively known as TGFBI corneal dystrophies. These mutations translate into amino acid substitutions mainly within the fourth fasciclin 1 domain (FAS1-4) of the transforming growth factor beta-induced protein (TGFBIp) and cause either amyloid or non-amyloid protein aggregates in the anterior and central parts of the cornea, depending on the mutation. The A546T substitution in TGFBIp causes lattice corneal dystrophy (LCD), which manifests as amyloid-type aggregates in the corneal stroma. We previously showed that the A546T substitution renders TGFBIp and the FAS1-4 domain thermodynamically less stable compared with the wild-type (WT) protein, and the mutant FAS1-4 is prone to amyloid formation in vitro. In the present study, we identified the core of A546T FAS1-4 amyloid fibrils. Significantly, we identified the Y571-R588 region of TGFBIp, which we previously found to be enriched in amyloid deposits in LCD patients. We further found that the Y571-R588 peptide seeded fibrillation of A546T FAS1-4 and, more importantly, we demonstrated that native TGFBIp aggregates in the presence of fibrils formed by the core peptide. Collectively, these data suggest an involvement of the Y571-R588 peptide in LCD pathophysiology. PMID:25910219

  13. Inhibition of surgically induced miosis and prevention of postoperative macular edema with nepafenac

    PubMed Central

    Cervantes-Coste, Guadalupe; Sánchez-Castro, Yuriana G; Orozco-Carroll, Mónica; Mendoza-Schuster, Erick; Velasco-Barona, Cecilio

    2009-01-01

    Objective: To evaluate the effectiveness of prophylactic administration of nepafenac 0.1% in maintaining mydriasis and in preventing postoperative macular edema following cataract surgery. Methods: This was a prospective, randomized, single-masked comparative study in 60 patients undergoing phacoemulsification cataract surgery. Patients were randomized to either the nepafenac or the control group. Nepafenac was administered 3 times daily 1 day before surgery and continued for 6 weeks. The control group received tobramycin-dexamethasone treatment only. Trans-operative mydriasis was measured before surgery, after nuclear emulsification, following cortex aspiration, and at the conclusion of surgery. Macular optical coherence tomography determined central foveal thickness (FT) and total macular volume (TMV) before surgery and at 2 and 6 weeks after surgery. All patients received tobramycin-dexamethasone for 2 weeks after surgery. Results: The difference in mean pupil size, at the end of surgery, between the control group (6.84 ± 0.93 mm) and the nepafenac group (7.91 ± 0.74 mm) was statistically significant (p < 0.001). There were no significant differences in FT values between the two groups at any time point; however, TMV at 2 and at 6 weeks was statistically significantly different (p < 0.001), with higher TMV in the control group. Conclusion: Prophylactic use of nepafenac was effective in reducing macular edema after cataract surgery and in maintaining trans-operative mydriasis. PMID:19668569

  14. Ocular surface injury induces inflammation in the brain: in vivo and ex vivo evidence of a corneal-trigeminal axis.

    PubMed

    Ferrari, Giulio; Bignami, Fabio; Giacomini, Chiara; Capitolo, Eleonora; Comi, Giancarlo; Chaabane, Linda; Rama, Paolo

    2014-08-21

    To test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG), a structure located in the brain. At 4 and 8 days after alkali burn induced in the right eyes of mice, in vivo magnetic resonance imaging (MRI) of the brain was done before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers. Interleukin-1β, TNF-α, and VEGF-A transcripts were quantified on days 1, 4, and 8, and 4 days after corneal topical anti-inflammatory treatment with 0.2% dexamethasone. The expression of Substance P and its receptor NK-1R was also measured in the TG on day 4. Corneal alkali burn induced leukocyte infiltration, including T cells, in the right TG at 4 and 8 days. In vivo MRI showed an increased contrast uptake in the right TG, which peaked at day 8. Prussian Blue(+) USPIO(+) macrophages were observed in the right TG and exhibited an M2 phenotype. The M2-macrophage infiltration was preponderant in the TG after damage. The proinflammatory cytokines Substance P and NK-1R were significantly increased in both the TGs. The expression of IL-1β and VEGF-A was significantly reduced in the right TG with dexamethasone treatment. We suggest, for the first time, inflammatory involvement of brain structures following ocular surface damage. Our findings support the hypothesis that the neuropeptide Substance P may be involved in the propagation of inflammation from the cornea to the TG through corneal nerves. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  15. Anterior chemodenervation of levator palpebrae superioris with botulinum toxin type-A (Botox) to induce temporary ptosis for corneal protection.

    PubMed

    Naik, M N; Gangopadhyay, N; Fernandes, M; Murthy, R; Honavar, S G

    2008-09-01

    To evaluate the effectiveness of anterior chemodenervation of levator palpebrae superioris with Botulinum toxin type A (Botox) to induce temporary ptosis for corneal protection, and assess the incidence of superior rectus underaction. Prospective interventional case series. Patients with ocular surface pathology requiring temporary tarsorrhaphy underwent transcutaneous anterior chemodenervation of levator palpebrae superioris with Botox. The onset and duration of ptosis, corneal healing, and superior rectus underaction was evaluated. Ten eyes of 10 patients underwent transcutaneous anterior chemodenervation of levator muscle. Five patients had Bells palsy with exposure keratopathy, four patients had persistent epithelial defect, and one had neurotrophic ulcer. The median age at presentation was 30 years. Median dose of Botulinum toxin injection was 12.5 U (range 10-15 U). The mean palpebral fissure height of 9 mm (SD+/-2.1 mm) before injection, reduced to 2.8 mm (SD+/-1.9 mm) at 1-week post-injection. More than 50% reduction in palpebral fissure height was seen in nine out of 10 eyes (90%, 95% CI 71.4-100%) at 1 week, seven of nine eyes (77.8%, 95% CI 50.6-100%) at 2 weeks, and two of nine eyes (22.2%, 95% CI 0-49.4%) at 4 weeks, and returned to pretreatment level after mean duration of 9.2 weeks (range 5-16 weeks). Superior rectus underaction was not noted in any of the patient (95% CI 0-30%). Corneal pathology improved in all cases. Anterior chemodenervation of levator palpebrae superioris with Botulinum toxin type A (Botox) induces significant temporary ptosis and aids in corneal healing. Anterior placement of the toxin injection may avoid superior rectus underaction.

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

    PubMed

    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.

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

    SciTech Connect

    Pan, Hong; Wu, Xinyi

    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

  18. Effect of PEEP on phosgene-induced lung edema: pilot study on dogs using protective ventilation strategies.

    PubMed

    Li, Wenli; Rosenbruch, Martin; Pauluhn, Jürgen

    2015-02-01

    Various therapeutic regimes have been proposed for treatment of phosgene-induced acute lung injury (P-ALI). Most of these treatments rely on late-stage supportive measures to maintain the oxygenation of the lung. This exploratory proof-of-concept study on Beagle dogs focused on protective positive end-expiratory pressure (PEEP) ventilation, initiated early at the yet asymptomatic stage after phosgene exposure. Conscious, spontaneously breathing dogs were head-only exposed to a potentially lethal inhalation dose of phosgene (870 ppm × min). Shortly after exposure, the dogs were anesthetized, intubated and then subjected to mechanical ventilation (PEEP; tidal volume (VT)=10-12 mL/kg body weight, 40 breaths/min) at 0, 4, or 12 cm H2O over a post-exposure period of 8h (one dog per setting). For reference, one additional dog received the same dose of phosgene without anesthesia and mechanical ventilation. Time-course changes of hematocrit, leukocytes, and thrombocytes were determined in peripheral blood. At necropsy, changes lung weights, bronchoalveolar lavage, and histology were used to assess the efficacy of treatment. The most salient outcome in the non-ventilated dog was a time-related hemoconcentration and leukocytosis and autopsy findings suggestive of pulmonary congestion and edema. The pulmonary epithelium of the major airways was generally intact; however, in their lumen inflammatory cells, cellular debris and mucus were present. Relative to the dog receiving no intervention, the lung edema was markedly alleviated by PEEP at both 4 and 12 cm H2O but not at 0 cm H2O PEEP. In summary, the time-dependent progression into a life-threatening pulmonary edema can effectively be suppressed by protective, low-pressure PEEP when implemented early enough after exposure to phosgene. However, due to the exploratory nature of this study, the findings may suggest an association between PEEP and protection from pulmonary edema. However, definite conclusions and

  19. Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina.

    PubMed

    Geiger, P; Barben, M; Grimm, C; Samardzija, M

    2015-11-19

    Little is known about the mechanisms underlying macular degenerations, mainly for the scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl(-/-) double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and a strong photopic function that generates useful vision. Here we exposed R91W;Nrl(-/-) and wild-type (wt) mice to toxic levels of blue light and analyzed their retinas at different time points post illumination (up to 10 days). While exposure of wt mice resulted in massive pyknosis in a focal region of the outer nuclear layer (ONL), the exposure of R91W;Nrl(-/-) mice led to additional cell death detected within the inner nuclear layer. Microglia/macrophage infiltration at the site of injury was more pronounced in the all-cone retina of R91W;Nrl(-/-) than in wt mice. Similarly, vascular leakage was abundant in the inner and outer retina in R91W;Nrl(-/-) mice, whereas it was mild and restricted to the subretinal space in wt mice. This was accompanied by retinal swelling and the appearance of cystoid spaces in both inner and ONLs of R91W;Nrl(-/-) mice indicating edema in affected areas. In addition, basal expression levels of tight junction protein-1 encoding ZO1 were lower in R91W;Nrl(-/-) than in wt retinas. Collectively, our data suggest that exposure of R91W;Nrl(-/-) mice to blue light not only induces cone cell death but also disrupts the inner blood-retinal barrier. Macular edema in humans is a result of diffuse capillary leakage and microaneurysms in the macular region. Blue light exposure of the R91W;Nrl(-/-) mouse could therefore be used to study molecular events preceding edema formation in a cone-rich environment, and thus potentially help to develop treatment strategies for edema-based complications in macular degenerations.

  20. Comparison of surgically induced astigmatism between femtosecond laser and manual clear corneal incisions for cataract surgery.

    PubMed

    Diakonis, Vasilios F; Yesilirmak, Nilufer; Cabot, Florence; Kankariya, Vardhaman P; Kounis, George A; Warren, Daniel; Sayed-Ahmed, Ibrahim O; Yoo, Sonia H; Donaldson, Kendall

    2015-10-01

    To assess the surgically induced corneal astigmatism (SIA) introduced by femtosecond laser-assisted clear corneal incisions (CCIs) for cataract extraction and to compare it with the SIA of manually created CCIs. Bascom Palmer Eye Institute, Miller School of Medicine, Miami, Florida, USA. Prospective nonrandomized comparative case series. Eyes received femtosecond laser-assisted CCIs (Group 1) or manual CCIs (Group 2). The surgical plan included 1 primary and 1 secondary port; the sites of the incisions were the same in both groups and were diametrically opposed between the right eye and left eye. The SIA was assessed using the preoperative and 1-month postoperative keratometric values obtained from corneal topography examinations. This study included 72 eyes of 68 patients with a mean age of 69.0 years ± 9.87 (SD) (range 36 to 90 years). Thirty-six eyes received femtosecond laser-assisted CCIs (Group 1) and 36 received manual CCIs (Group 2). The mean preoperative topographic corneal astigmatism was -1.19 ± 0.68 diopters (D) (range 0 to 2.50 D) and -0.92 ± 0.63 D (range 0.10 to 2.45 D) for Group 1 and Group 2, respectively, whereas, 1 month after cataract surgery, it was -1.16 ± 0.63 D (range 0.20 to 2.57 D) and -0.95 ± 0.64 D (range 0.21 to 2.37 D), respectively. Multivariate vector analysis revealed no statistically significant difference between the 2 groups for preoperative astigmatism, postoperative astigmatism, and SIA (P > .05 for all comparisons between Group 1 and Group 2). Femtosecond laser-assisted and manual corneal incisions for cataract surgery did not appear to significantly alter corneal astigmatism, whereas they showed comparable SIA. Drs. Yoo and Donaldson are speakers for and consultants to Alcon Surgical, Inc., and Abbott Medical Optics, Inc. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  1. [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced Hypertension].

    PubMed

    Aida, Junko; Okutani, Hiroai; Oda, Yutaka; Okutani, Ryu

    2015-08-01

    A 27-year-old woman with mental retardation was admitted to a nearby hospital for an abrupt onset of seizure. Physical examination revealed remarkable hypertension and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH) accompanied by eclampsia. She was orotracheally intubated because of refractory seizure and hypoxemia, and transferred to our hospital for further treatment. Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the left posterior cerebrum by brain MRI. No abnormal findings were detected in the fetus, with heart rate of 150 beats x min. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean section under general anesthesia was scheduled. A male newborn was delivered with Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of nicardipine for controlling hypertension. Chest X-P on completion of surgery revealed remarkably alleviated pulmonary edema. She received intensive treatment and continued positive pressure ventilation for four days after delivery. She recovered with no neurological deficits and her child was well without any complications.

  2. Improvement of cold injury-induced mouse brain edema by endothelin ETB antagonists is accompanied by decreases in matrixmetalloproteinase 9 and vascular endothelial growth factor-A.

    PubMed

    Michinaga, Shotaro; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Minami, Shizuho; Kimura, Akimasa; Hatanaka, Shunichi; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Koyama, Yutaka

    2015-09-01

    Brain edema is a potentially fatal pathological state that often occurs after brain injuries such as ischemia and trauma. However, therapeutic agents that fundamentally treat brain edema have not yet been established. We previously found that endothelin ETB receptor antagonists attenuate the formation and maintenance of vasogenic brain edema after cold injury in mice. In this study, the effects of ETB antagonists on matrixmetalloproteinase (MMP)9 and vascular endothelial growth factor (VEGF)-A expression were examined in the cold injury model. Cold injury was performed in the left brain of male ddY mice (5-6 weeks old) for the induction of vasogenic edema. Expression of MMP9 and VEGF-A mRNA in the mouse cerebrum was increased by cold injury. Immunohistochemical observations showed that the MMP9 and VEGF-A were mainly produced in reactive astrocytes in the damaged cerebrum. Intracerebroventricular administration of BQ788 (10 μg) or IRL-2500 (10 μg) (selective ETB antagonists) attenuated brain edema and disruption of the blood-brain barrier after cold injury. BQ788 and IRL-2500 reversed the cold injury-induced increases in MMP9 and VEGF-A expression. The induction of reactive astrocytes producing MMP9 and VEGF-A in the damaged cerebrum was attenuated by BQ788 and IRL-2500. These results suggest that attenuations of astrocytic MMP9 and VEGF-A expression by ETB antagonists may be involved in the amelioration of vasogenic brain edema.

  3. A comparative study of corneal incisions induced by diamond and steel knives and two ultraviolet radiations from an excimer laser.

    PubMed Central

    Marshall, J; Trokel, S; Rothery, S; Krueger, R R

    1986-01-01

    This paper reviews the potential role of excimer lasers in corneal surgery. The morphology of incisions induced by two wavelengths of excimer laser radiation, 193 nm and 248 nm, are compared with the morphology of incisions produced by diamond and steel knives. Analysis suggests that ablation induced by excimer laser results from highly localised photochemical reactions and that 193 nm is the optimal wavelength for surgery. The only significant complication of laser surgery is loss of endothelial cells when incisions are within 40 micron of Descemet's membrane. Images PMID:3013283

  4. Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity

    PubMed Central

    Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F.; Rosenblatt, Mark I.

    2015-01-01

    Purpose In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. Methods In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Results Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication (“dry response”), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. Conclusions These results demonstrate that tear hyperosmolarity, considered to be a “core” mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients. PMID:26720465

  5. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    PubMed Central

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  6. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  7. Bone marrow chimeras and c-fms conditional ablation (Mafia) mice reveal an essential role for resident myeloid cells in lipopolysaccharide/TLR4-induced corneal inflammation.

    PubMed

    Chinnery, Holly R; Carlson, Eric C; Sun, Yan; Lin, Michelle; Burnett, Sandra H; Perez, Victor L; McMenamin, Paul G; Pearlman, Eric

    2009-03-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4(-/-) mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)(+)/C57BL/6 or eGFP(+)/TLR4(-/-) mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4(-/-) mice reconstituted with C57BL/6, but not TLR4(-/-) bone marrow cells donor cells were found to cause infiltration of eGFP(+) cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP(+) cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1alpha production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation.

  8. Bone Marrow Chimeras and c-fms Conditional Ablation (Mafia) Mice Reveal an Essential Role for Resident Myeloid Cells in Lipopolysaccharide/TLR4-Induced Corneal Inflammation1

    PubMed Central

    Chinnery, Holly R.; Carlson, Eric C.; Sun, Yan; Lin, Michelle; Burnett, Sandra H.; Perez, Victor L.; McMenamin, Paul G.; Pearlman, Eric

    2012-01-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4−/− mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)+/C57BL/6 or eGFP+/TLR4−/− mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4−/− mice reconstituted with C57BL/6, but not TLR4−/− bone marrow cells donor cells were found to cause infiltration of eGFP+ cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP+ cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1α production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation. PMID:19234168

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

    PubMed

    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

  10. Benzo(a)pyrene-induced pulmonary inflammation, edema, surfactant dysfunction, and injuries in rats: alleviation by farnesol.

    PubMed

    Qamar, Wajhul; Khan, Abdul Quaiyoom; Khan, Rehan; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat

    2012-02-01

    Benzo(a)pyrene (B(a)P) is a well-known environmental contaminant and carcinogen. Its sources include tobacco smoke, automobile exhaust, forest fire, and other combustion processes. Farnesol, an active principle of Vachellia farnesiana and other aromatic plants, possesses preventive properties against various toxicities. Present study was designed to estimate chemopreventive effects of farnesol against B(a)P-induced pulmonary injuries. To determine the protective effects of farnesol, it was administered orally at 2 doses (100 and 200 mg/kg body weight [b.w.]) once daily for 14 days. Rats were exposed intratracheally to B(a)P, 5 mg/kg b.w. on days 12 and 14, thereafter assessed for pulmonary toxicities 24 hours post last dose of B(a)P. B(a)P-induced edema, inflammation, oxidative stress, and consequent damages in lungs were assessed in terms of total protein, total cell count, nitric oxide (NO), lactate dehydrogenase (LDH), alkaline phosphatase, and in bronchoalveolar lavage fluid (BALF). B(a)P also reduced the levels of phospholipids (lung surfactants) in BALF. However, pretreatment with farnesol at both the doses significantly reduced the lung injuries and inflammatory responses. Farnesol also protected the levels of phospholipids to normal when compared with control. It also modified the activities of B(a)P metabolizing enzymes NADPH-cytochrome P450 reductase, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) in lung tissue of rats. Present findings suggest a prominent role of farnesol against B(a)P-induced lung inflammation, edema, surfactant dysfunction, and epithelial damages in Wistar rats. In conclusion, farnesol shows lung protection against B(a)P toxicities in Wistar rats.

  11. Transforming Growth Factor-β Signaling Cascade Induced by Mechanical Stimulation of Fluid Shear Stress in Cultured Corneal Epithelial Cells.

    PubMed

    Utsunomiya, Tsugiaki; Ishibazawa, Akihiro; Nagaoka, Taiji; Hanada, Kazuomi; Yokota, Harumasa; Ishii, Nobuhito; Yoshida, Akitoshi

    2016-11-01

    Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). The HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) with the parallel-plate type of flow chamber. Wound healing, cellular proliferation, growth factor expression, TGF-β1 concentration in the culture supernatant, and phosphorylation of SMAD2 were investigated. Monolayers of HCECs exposed to shear stress had delayed wound healing and decreased proliferation compared with those of the static control (0 dyne/cm2). With increasing shear stress, TGF-β1 expression and phosphorylation of SMAD2 increased significantly, but the levels of total TGF-β1 in the culture supernatant decreased significantly. Delayed wound healing, decreased proliferation, and phosphorylation of the SMAD2 by shear stress were canceled out with a TGF-β receptor inhibitor. Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism of shear stress-induced activation of TGF-β.

  12. Calotropis procera-induced keratitis

    PubMed Central

    Pandey, Nidhi; Chandrakar, A K; Garg, M L; Patel, Santosh Singh

    2009-01-01

    Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera-induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops. PMID:19075415

  13. Corneal Topographic Changes After Eyelid Ptosis Surgery.

    PubMed

    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.

  14. Corneal bee sting misdiagnosed as viral keratitis.

    PubMed

    Jain, Vandana; Shome, Debraj; Natarajan, Sundaram

    2007-12-01

    To report a case of chronic keratouveitis caused by a missed bee sting injury. A 17-year-old boy was referred for management of unresponsive viral keratouveitis. Ocular examination revealed corneal edema and scarring, atrophic patches on the iris, and anterior polar cataracts. Surprisingly, examination also revealed a retained intracorneal bee stinger. A retrospective inquiry confirmed a bee sting injury 2 years ago. The patient was started on medical treatment and underwent operative removal of the bee stinger. Postsurgery, visual acuity improved, and the corneal edema regressed over a 1-month follow-up. In cases of chronic keratouveitis, a meticulous examination is mandatory to rule out unusual causes like a retained corneal bee stinger. A retained intracorneal bee stinger may result in long-term corneal inflammation, which may not be controlled adequately with topical steroids. It should be removed, irrespective of the duration since the injury.

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

    PubMed

    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.

  16. Intravenous administration of hyperoxygenated solution attenuates pulmonary edema formation in phosgene-induced acute lung injury in rabbits.

    PubMed

    Wang, Ling; Liu, Chunran; Zhang, Hui; Gao, Changjun; Chai, Wei; Xu, Ruifen; Wang, Hui-xia; Xu, Lixian

    2010-11-01

    GSH and BALF GSH-Px increased compared with both PH and LRS group, respectively. There was no difference on lung tissue GSH among the PH, LRS, and HOS groups (P > 0.05). Intravenous HOS infusion after phosgene exposure can clearly lessen phosgene-induced lung edema formation, lipid peroxidatic reaction, and ameliorate hypoxemia associated with phosgenismus; it is a safe, simple, and effective measure to protect animals from phosgene-induced lung injury. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Youn, Hyun-Yi; 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 with UV radiations at various energy levels with and without filter protections. Cell viability after exposure was determined using the metabolic dye alamarBlue and by evaluating for changes in the nuclei, mitochondria, membrane permeability, and cell membranes of the cells using the fluorescent dyes Hoechst 33342, rhodamine 123, calcein AM, ethidium homodimer-1, and annexin V. High-resolution images of the cells were taken with a Zeiss 510 confocal laser scanning microscope. Results The alamarBlue assay results of UV-exposed cells without filters showed energy level-dependent decreases in cellular viability. However, UV treated cells with 400 nm LP filter protection showed the equivalent viability to untreated control cells at all energy levels. Also, UV irradiated cells with 320 nm LP filter showed lower cell viability than the unexposed control cells, yet higher viability than UV-exposed cells without filters in an energy level-dependent manner. The confocal microscopy results also showed that UV radiation can cause significant dose-dependent degradations of nuclei and mitochondria in ocular cells. The annexin V staining also showed an increased number of apoptotic cells after UV irradiation. Conclusions The findings suggest that UV-induced HCEC, HLEC, and ARPE-19 cell damage can be evaluated by bioassays that measure changes in the cell nuclei, mitochondria, cell membranes, and cell metabolism, and these assay methods provide a valuable in vitro model for evaluating the

  18. Inhibition of secretory phospholipase A2 activity attenuates acute cardiogenic pulmonary edema induced by isoproterenol infusion in mice after myocardial infarction.

    PubMed

    Kawabata, Kenichi; Fujioka, Daisuke; Kobayashi, Tsuyoshi; Saito, Yukio; Obata, Jun-Ei; Nakamura, Takamitsu; Yano, Toshiaki; Watanabe, Kazuhiro; Watanabe, Yosuke; Mishina, Hideto; Kugiyama, Kiyotaka

    2010-10-01

    Several types of secretory phospholipase A2 (sPLA2) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA2 activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA2 activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA2, and lung content of thromboxane A2 and leukotriene B4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA2 activity, para-bromophenacyl bromide. In conclusion, inhibition of sPLA2 activity suppressed acute cardiogenic pulmonary edema.

  19. Anti-inflammatory and immunomodulating properties of grape melanin. Inhibitory effects on paw edema and adjuvant induced disease.

    PubMed

    Avramidis, N; Kourounakis, A; Hadjipetrou, L; Senchuk, V

    1998-07-01

    Natural or synthetic melanin (CAS 8049-97-6) is a high molecular weight heteropolymer, product of the enzyme tyrosinase, found to possess radical scavenging and antioxidant functions. It was of interest, therefore, to study in detail the possible anti-inflammatory and/or immunosuppressive properties of a melanin isolated from grapes. The inhibitory effect of melanin on carrageenin-induced edema, as well as on edemas produced by other phlogistics, was remarkable suggesting that melanin interferes with the prostaglandin as well as the leukotriene and/or complement system mediated inflammation. Grape melanin showed potent inhibitory effect on adjuvant induced disease (AID) in rat, suppressing significantly the primary inflammation and almost totally the secondary lesions of arthritis. Melanin under the present experimental conditions not only strongly inhibited the in vitro lipid peroxidation of rat liver microsomal membranes, but furthermore protected the in vivo hepatic peroxidation occurring in AID rats, demonstrating its antioxidant and cytoprotective properties. The serum proinflammatory cytokines IL-1, IL-6 and TNF-a and the serum globulin fraction were elevated in AID rats, parameters which were more or less normalised by melanin treatment in contrast to the reduced serum levels of IL-2 which were not affected. Similarly to other lipoxygenase inhibitors and hydroxyl radical scavenger NSAIDs, melanin treatment did not affect IL-1 neither increased the splenic mitogenic responses, unlike the classical cyclooxygenase inhibitory NSAIDs. The subpopulation Th1 (T4+ or T8+) of lymphocytes is mainly responsible for cellular immune responses and thus their possible inhibition by melanin could lead to suppression of the development of AID, a model for cell-mediated immunity. The effect of melanin on T-cells is exhibited by the reduced spleen mitogenic responses to a T-cell mitogen and the reduced serum levels of IL-2 of treated rats. In conclusion, grape melanin is an

  20. Corneal Emergencies.

    PubMed

    Belknap, Ellen B

    2015-09-01

    Corneal emergencies can be due to a number of different causes and may be vision threatening if left untreated. In an attempt to stabilize the cornea, it is of benefit to place an Elizabethan collar on the patient to prevent further corneal damage. This article discusses the diagnosis, prognosis, and management of corneal emergencies in dogs and cats. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Effect of diet induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice

    PubMed Central

    Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Holmes, Amey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

    2015-01-01

    We determined the impact diet induced obesity (DIO) and types 1 and 2 diabetes has on peripheral neuropathy with emphasis on corneal nerve structural changes in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response to thermal and mechanical stimuli and innervation of the skin and cornea. DIO mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and both types 1 and 2 diabetic mice developed motor and sensory nerve conduction deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in sub-epithelial corneal nerves, innervation of the corneal epithelium and corneal sensitivity. Type 1 diabetic mice did not present with any significant changes in corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2 diabetic mice developed corneal structural damage more rapidly than type 1 diabetic mice even though hemoglobin A1C values were significantly higher in type 1 diabetic mice. This suggests that DIO with or without hyperglycemia contributes to development and progression of peripheral neuropathy and nerve structural damage in the cornea. PMID:25858759

  2. Postoperative Corneal and Surgically Induced Astigmatism following Superior Approach Manual Small Incision Cataract Surgery in Patients with Preoperative Against-the-Rule Astigmatism

    PubMed Central

    Sadik, Ahmed Abdul; Mireku, Felix Agyemang; Asiedu, Frank Yeboah; Ablordeppey, Reynolds Kwame

    2016-01-01

    The aim of the study was to report postoperative corneal and surgically induced astigmatism (SIA) in patients with preoperative against-the-rule (ATR) astigmatism who underwent superior approach manual small incision cataract surgery (MSICS). 58 eyes of 58 cataract patients with preoperative ATR astigmatism were involved in this study. All patients had operable cataracts and underwent superior approach MSICS. Keratometric (K) readings were taken prior to surgery and at 12 weeks after surgery. Centroid values of SIA, preoperative astigmatism, and postoperative astigmatism were calculated using Cartesian coordinates based analysis. Wilcoxon signed rank test was used to compute statistical significance between mean preoperative and postoperative corneal astigmatism. Cohen's d was used as effect size measure. Centroid values of 1.42 D × 179, 2.48 D × 0, and 1.07 D × 1 were recorded, respectively, for preoperative astigmatism, postoperative astigmatism, and SIA. Wilcoxon signed rank test indicated that mean ± SD postoperative corneal astigmatism (2.80 ± 1.40 D) was statistically significantly greater than preoperative corneal astigmatism (1.49 ± 1.34 D), Z = −6.263, p < 0.0001. A high Cohen's d of 1.32 was found. Our results suggest statistical and clinically significant greater postoperative corneal astigmatism than preoperative corneal astigmatism for ATR astigmatism cataract patients who underwent superior approach MSICS. PMID:28116142

  3. Nanoscale Topography–Induced Modulation of Fundamental Cell Behaviors of Rabbit Corneal Keratocytes, Fibroblasts, and Myofibroblasts

    PubMed Central

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

    2010-01-01

    Purpose. 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 Methods. 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 Results. 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 Conclusions. 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. PMID:19875665

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

    PubMed

    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.

  5. In situ injury-induced release of basic-fibroblast growth factor from corneal epithelial cells.

    PubMed Central

    Adamis, A. P.; Meklir, B.; Joyce, N. C.

    1991-01-01

    Basic-fibroblast growth factor (b-FGF) binds to heparan sulfate proteoglycan in Bowman's layer of the cornea. The mechanism by which the molecule is deposited in Bowman's layer is the subject of controversy since b-FGF lacks a signal peptide sequence for extracellular secretion. Using immunofluorescence, the authors studied the presence and distribution of b-FGF in the bovine cornea and the conditions under which it could be released and bound to Bowman's layer. The results indicate that corneal epithelium contains b-FGF but that uninjured corneas do not contain detectable levels of b-FGF in Bowman's layer. Injury to the corneal epithelium results in the binding of b-FGF to Bowman's layer. Removal of the intact corneal epithelium without cell injury does not result in the binding of b-FGF to Bowman's layer. These findings suggest that one mechanism for the release of b-FGF from corneal epithelial cells is passive leakage after cell injury with secondary binding to Bowman's layer. Images Figure 1 Figure 2 Figure 3 PMID:1951634

  6. Clinical evaluation of surgery-induced astigmatism in cataract surgery using 2.2 mm or 1.8 mm clear corneal micro-incisions

    PubMed Central

    Yang, Jun; Wang, Xiu; Zhang, Hong; Pang, Yi; Wei, Rui-Hua

    2017-01-01

    AIM To evaluate corneal astigmatism after phacoemulsification using 2.2 mm or 1.8 mm clear corneal micro-incisions and its effects on visual function. METHODS Sixty cases (60 eyes) with cataract were randomly divided into groups A (n=30) and B (n=30) respectively underwent 2.2 mm and 1.8 mm clear corneal tunnel incision phacoemulsification combined with folding intraocular lens implantation from the time direction of 11:00. On day 1 and at 1, 4, and 6wk after operation, patients' vision was measured and both the corneal curvature and corneal thickness (CT) were recorded using Pentacam. RESULTS The measured surgery-induced astigmatism (SIA) in both groups A and B peaked on day 1 after operation, and then gradually decreased and eventually stabilized in week 4. No statistically significant difference was found in corneal astigmatism between two groups (P>0.05). The measured corneal astigmatism at 4wk and 6wk postoperatively were 0.28±0.09 D and 0.27±0.10 D for groups A and 0.27±0.09 D and 0.25±0.10 D for groups B without statistically significant difference (P>0.05). In addition, no significant differences in visual acuity and CT were found between groups A and B before or after operation. CONCLUSION Both 2.2 mm and 1.8 mm micro-incision cataract surgeries result in relatively small SIA with no difference in visual function and corneal astigmatism between two surgery approaches. Thus, the two types of surgical systems are safe and efficient for cataract treatment, by which satisfactory uncorrected visual acuity can be regained early postoperatively. PMID:28149779

  7. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    PubMed Central

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  8. Dynamic Regulation of Barrier Integrity of the Corneal Endothelium

    PubMed Central

    Srinivas, Sangly P.

    2010-01-01

    The corneal endothelium maintains stromal deturgescence, which is a prerequisite for corneal transparency. The principal challenge to stromal deturgescence is the swelling pressure associated with the hydrophilic glycosaminoglycans in the stroma. This negative pressure induces fluid leak into the stroma from the anterior chamber, but the rate of leak is restrained by the tight junctions (TJs) of the endothelium. This role of the endothelium represents its barrier function. In healthy cornea, the fluid leak is counterbalanced by an active fluid pump mechanism associated with the endothelium itself. Although this Pump-Leak hypothesis was postulated several decades ago, the mechanisms underlying regulation of the balance between the pump and leak functions remain largely unknown. In the last couple of decades, the ion transport systems that support the fluid pump activity have been discovered. In contrast, despite significant evidence for corneal edema secondary to endothelial barrier dysfunction, the molecular aspects underlying its regulation are relatively unknown. Recent findings in our laboratory, however, indicate that barrier integrity (i.e., structural and functional integrity of the TJs) of the endothelium is sensitive to remodeling of its peri-junctional actomyosin ring (PAMR), which is located at the apical junctional complex. This review provides a focused perspective on dynamic regulation of the barrier integrity of endothelium vis-à-vis plasticity of the PAMR and its association with cell signaling downstream of small GTPases of the Rho family. Based on findings to date, it appears that development of specific pharmacological strategies to treat corneal edema in response to inflammatory stress would be possible in the near future. PMID:20142793

  9. Edema disease as a model for systemic disease induced by Shiga toxin-producing E. coli.

    PubMed

    Cornick, N A; Matise, I; Samuel, J E; Bosworth, B T; Moon, H W

    1999-01-01

    Edema disease (ED) is a naturally occurring disease of weaned pigs caused by host adapted strains of E. coli that produce Shiga toxin (STEC). We determined the temporal and quantitative relationships between intestinal colonization by STEC, levels of Shiga toxin (Stx2e) in the gut, in the blood, and clinical manifestations of ED. Bacterial colonization (10(8) CFU/cm ileum) was highest 4 days post inoculation (pi) in animals that did not develop clinical disease and 6 days pi in animals with clinical signs of ED. The mean time for the development of clinical signs of ED was 6 days pi (range 4-10). Average peak titers of Stx2e in the ileum were 1:16,384 in asymptomatic animals and 1:32,768 in clinical animals. Titers of Stx2e in the feces reflected the toxin titers in the ileum but were lower. Intestinal titers of Stx2e and the density of bacterial colonization were predictive of clinical ED for a group of animals but not for individuals. Approximately 50% of the pigs that had Stx2e titers of > or = 1:4096 and a bacterial density of > or = 10(6) CFU/cm in their ileum, had clinical ED. Pigs that had intestinal Stx2e titers < 1:4096 were asymptomatic. Stx2e was detected in the red cell fraction of blood from some of the pigs with clinical ED and in some that were asymptomatic. Stx2e was not detected in the serum of any animals. ED may be a useful model for predicting the temporal and quantitative relationships between bacterial colonization, Stx levels in the gut and blood and systemic disease for STEC in other species.

  10. Over-vibration induced blood perfusion and vascular permeability changes may lead to vocal edema.

    PubMed

    Wang, Jiajia; Devine, Erin; Fang, Rui; Jiang, Jack J

    2017-01-01

    To observe blood perfusion and vascular permeability changes under varying vibration frequency exposures. Animal model. Blood perfusion was measured using laser Doppler flowmetry in eight rabbit auricular vessels (four rabbits) under nonvibration, and 62.5-Hz/1-mm, 125-Hz/1-mm, and 250-Hz/0.5-mm vibration frequency/amplitude exposures. Another 12 rabbits were randomly divided into vibration only and vibration with histamine groups. After 3 hours of continuous 125-Hz, 1-mm amplitude vibration of the auricle, vascular permeability was analyzed by absorbance of Evans blue-albumin complex. Significantly lower blood perfusion was observed in the vibration group, compared with no vibration exposure controls. Blood perfusion decreased 29 ± 16% as the vibration frequency was increased from 62.5 Hz to 125 Hz with the vibration amplitude constant at 1 mm. When the frequency was increased from 125 Hz to 250 Hz, while the amplitude was decreased from 1 mm to 0.5 mm, blood flow perfusion further decreased 29 ± 29%, and the decline tendency in blood perfusion showed no significant difference (P = .992). Meanwhile, in the vibration with histamine group, vascular permeability of the vibrated ears increased significantly compared to the nonvibrated ears (P = .005). Overvibration of the vocal folds due to voice overuse or abuse may significantly reduce blood perfusion, and increase vascular permeability in the vocal fold in inflammatory situations, which may lead to the formation of vocal edema. NA Laryngoscope, 127:148-152, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Cell Swelling Contributes to Thickening of Low-Dose N-methyl-D-Aspartate–Induced Retinal Edema

    PubMed Central

    Chen, Junjie; Chiang, Chia-Wen; Zhang, Huiying; Song, Sheng-Kwei

    2012-01-01

    Purpose. The contribution of cell swelling versus vascular leakage in retinal edema remains largely undefined. The objective of this study was to use in vivo magnetic resonance imaging (MRI) to assess retinal cell swelling in the edematous mouse retina. Methods. Inner retinal edema was induced by intravitreal injection of 2.5 nmol N-methyl-D-aspartate (NMDA). To assess retinal cell swelling, diffusion MRI was performed at baseline, 3-hours, 1 day, 3 days, and 7 days (n ≥ 5 at each time point) after NMDA injection. To detect retinal vascular leakage, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced MRI was performed at baseline, 3 hours and 1 day (n = 5 for each group) after NMDA injection. Upon the completion of MRI, mouse eyes were enucleated, cryosectioned, and stained for assessing retinal layer thickness and cell death. Results. Inner retinal cell swelling was hyperintense on diffusion-weighted images at 3 hours and 1 day after NMDA injection. The thickened inner retina was also seen in anatomic MRI and histology. Quantitatively, inner retinal apparent diffusion coefficient (ADC) decreased approximately 20% at 3 hours and 1 day after NMDA injection (P < 0.05 compared with baseline), suggesting cell swelling. Systematic injection of paramagnetic Gd-DTPA did not alter vitreous longitudinal relaxation time (T1) at baseline or at 3 hours after NMDA injection. In contrast, vitreous T1 in mice decreased 16 ± 6% (P < 0.05), reflecting retinal vascular leakage at 1 day after NMDA injection. Conclusions. Noninvasive diffusion MRI was performed to detect retinal cell swelling in vivo. Our results demonstrated that retinal cell swelling could directly lead to retinal thickening independent of vascular leakage. PMID:22467578

  12. Cytotoxicity of atropine to human corneal epithelial cells by inducing cell cycle arrest and mitochondrion-dependent apoptosis.

    PubMed

    Tian, Cheng-Lei; Wen, Qian; Fan, Ting-Jun

    2015-10-01

    Atropine is an anticholinergic drug for mydriasis in eye clinic, and its abuse might be cytotoxic to the cornea and result in blurred vision. However, the cytotoxicity of atropine to the cornea and its cellular and molecular mechanisms remain unknown. In this study, we investigated the cytotoxicity of atropine to corneal epithelium and its underlying mechanisms using an in vitro model of non-transfected human corneal epithelial (HCEP) cells. Our results showed that atropine, above the concentration of 0.3125 g/l (1/32 of its therapeutic dosage in eye clinic), had a dose- and time-dependent toxicity to HCEP cells by inducing morphological abnormality, cytopathic effect, viability decline, and proliferation retardation. Moreover, the proliferation-retarding effect of atropine on the cells was achieved by inducing G1/S phase arrest and downregulation of E-cadherin and β-catenin. Besides, atropine also had an apoptosis-inducing effect on the cells by inducing phosphatidylserine externalization, plasma membrane permeability elevation, DNA fragmentation and apoptotic body formation. Furthermore, atropine could also induce activations of caspase-2, -3 and -9, disruption of mitochondrial transmembrane potential, downregulation of Bcl-2 and Bcl-xL, upregulation of Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor, implying a death receptor-mediated mitochondrion-dependent pathway is most probably involved in the apoptosis of HCEP cells induced by atropine. Taken together, our results suggest that atropine has remarkable cytotoxicity to HCEP cells by inducing cell cycle arrest and death receptor-mediated mitochondrion-dependent apoptosis.

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

    PubMed Central

    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

  14. Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy

    PubMed Central

    Allen, Edwin H.A.; Courtney, David G.; Atkinson, Sarah D.; Moore, Johnny E.; Mairs, Laura; Poulsen, Ebbe Toftgaard; Schiroli, Davide; Maurizi, Eleonora; Cole, Christian; Hickerson, Robyn P.; James, John; Murgatroyd, Helen; Smith, Frances J.D.; MacEwen, Carrie; Enghild, Jan J.; Nesbit, M. Andrew; Leslie Pedrioli, Deena M.; McLean, W.H. Irwin; Moore, C.B. Tara

    2016-01-01

    Meesmann epithelial corneal dystrophy (MECD) is a rare autosomal dominant disorder caused by dominant-negative mutations within the KRT3 or KRT12 genes, which encode the cytoskeletal protein keratins K3 and K12, respectively. To investigate the pathomechanism of this disease, we generated and phenotypically characterized a novel knock-in humanized mouse model carrying the severe, MECD-associated, K12-Leu132Pro mutation. Although no overt changes in corneal opacity were detected by slit-lamp examination, the corneas of homozygous mutant mice exhibited histological and ultrastructural epithelial cell fragility phenotypes. An altered keratin expression profile was observed in the cornea of mutant mice, confirmed by western blot, RNA-seq and quantitative real-time polymerase chain reaction. Mass spectrometry (MS) and immunohistochemistry demonstrated a similarly altered keratin profile in corneal tissue from a K12-Leu132Pro MECD patient. The K12-Leu132Pro mutation results in cytoplasmic keratin aggregates. RNA-seq analysis revealed increased chaperone gene expression, and apoptotic unfolded protein response (UPR) markers, CHOP and Caspase 12, were also increased in the MECD mice. Corneal epithelial cell apoptosis was increased 17-fold in the mutant cornea, compared with the wild-type (P < 0.001). This elevation of UPR marker expression was also observed in the human MECD cornea. This is the first reporting of a mouse model for MECD that recapitulates the human disease and is a valuable resource in understanding the pathomechanism of the disease. Although the most severe phenotype is observed in the homozygous mice, this model will still provide a test-bed for therapies not only for corneal dystrophies but also for other keratinopathies caused by similar mutations. PMID:26758872

  15. Menthol activation of corneal cool cells induces TRPM8-mediated lacrimation but not nociceptive responses in rodents.

    PubMed

    Robbins, Ashlee; Kurose, Masayuki; Winterson, Barbara J; Meng, Ian D

    2012-10-09

    Stimulation to the cornea via noxious chemical and mechanical means evokes tearing, blinking, and pain. In contrast, mild cooling of the ocular surface has been reported to increase lacrimation via activation of corneal cool primary afferent neurons. The purpose of our study was to determine whether menthol induces corneal cool cell activity and lacrimation via the transient receptor potential melastatin-8 (TRPM8) channel without evoking nociceptive responses. Tear measurements were made using a cotton thread in TRPM8 wild type and knockout mice after application of menthol (0.05-50 mM) to the cornea. In additional studies, nocifensive responses (eye swiping and lid closure) were quantified following cornea menthol application. Trigeminal ganglion electrophysiologic single unit recordings were performed in rats to determine the effect of low and high concentrations of menthol on corneal cool cells. At low concentrations, menthol increased tear production in TRPM8 wild type and heterozygous animals, but had no effect in TRPM8 knockout mice, while nocifensive responses remained unaffected. At the highest concentration, menthol (50 mM) increased tearing and nocifensive responses in TRPM8 wild type and knockout animals. A low concentration of menthol (0.1 mM) increased cool cell activity, yet a high concentration of menthol (50 mM) had no effect. These studies indicated that low concentrations of menthol can increase lacrimation via TRPM8 channels without evoking nocifensive behaviors. At high concentrations, menthol can induce lacrimation and nocifensive behaviors in a TRPM8 independent mechanism. The increase in lacrimation is likely due to an increase in cool cell activity.

  16. Cytokine expression and barrier disruption in human corneal epithelial cells induced by alarmin released from necrotic cells.

    PubMed

    Fukuda, Ken; Ishida, Waka; Miura, Yusaku; Kishimoto, Tatsuma; Fukushima, Atsuki

    2017-07-19

    Dying cells release endogenous molecules known as alarmins that signal danger to surrounding tissue. We investigated the effects of necrotic cell-derived alarmins on cytokine expression and barrier function in human corneal epithelial cells. The release of interleukin (IL)-6 and IL-8 from immortalized human corneal epithelial (HCE) cells in culture was measured with enzyme-linked immunosorbent assays. The abundance of IL-6 and 8 mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analysis. Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular localization of the p65 subunit of the transcription factor NF-κB was determined by immunofluorescence analysis, and phosphorylation of the endogenous NF-κB inhibitor IκBα was examined by immunoblot analysis. A necrotic cell supernatant prepared from HCE cells induced the up-regulation of IL-6 and 8 expression at both mRNA and protein levels as well as reduced TER in intact HCE cells. Among alarmins tested, only IL-1α (not IL-33 or HMGB1) mimicked these effects of the necrotic cell supernatant. Furthermore, IL-1 receptor antagonist (IL-1RA) and neutralizing antibodies to IL-1α (but not those to IL-1β) each attenuated the effects of the necrotic cell supernatant. Exposure of HCE cells to the necrotic cell supernatant also induced the phosphorylation and degradation of IκBα as well as translocation of the p65 subunit of NF-κB to the nucleus. IL-1α released from necrotic corneal epithelial cells may trigger inflammatory responses at the ocular surface, including cytokine production and barrier disruption.

  17. Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

    SciTech Connect

    Testylier, Guy . E-mail: guytestylier@crssa.net; Lahrech, Hana; Montigon, Olivier; Foquin, Annie; Delacour, Claire; Bernabe, Denis; Segebarth, Christoph; Dorandeu, Frederic; Carpentier, Pierre

    2007-04-15

    Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.

  18. Corneal Hydration Control in Fuchs' Endothelial Corneal Dystrophy

    PubMed Central

    Wacker, Katrin; McLaren, Jay W.; Kane, Katrina M.; Baratz, Keith H.; Patel, Sanjay V.

    2016-01-01

    Purpose To assess corneal hydration control across a range of severity of Fuchs' endothelial corneal dystrophy (FECD) by measuring the percent recovery per hour (PRPH) of central corneal thickness after swelling the cornea and to determine its association with corneal morphologic parameters. Methods Twenty-three corneas of 23 phakic FECD patients and 8 corneas of 8 healthy control participants devoid of guttae were graded (modified Krachmer scale). Effective endothelial cell density (ECDe) was determined from the area of guttae and local cell density in confocal microscopy images. Steady-state corneal thickness (CTss) and standardized central corneal backscatter were derived from Scheimpflug images. Corneal swelling was induced by wearing a low-oxygen transmissible contact lens for 2 hours in the morning. De-swelling was measured over 5 hours after lens removal or until corneal thickness returned to CTss. Percent recovery per hour was 100 × (1 – e−k), where k was determined from CT(t) = (de−kt) + CTss, and where d was the initial change from CTss. Results After contact lens wear, corneas swelled by 9% (95% CI 9–10). Percent recovery per hour was 49%/h (95% CI 41–57) in controls and 37%/h in advanced FECD (95% CI 29–43, P = 0.028). Low PRPH was associated with disease severity, low ECDe, and increased anterior and posterior corneal backscatter. Anterior backscatter was associated with PRPH in a multivariable model (R2 = 0.44). Conclusions Corneal hydration control is impaired in advanced FECD and is inversely related to anterior corneal backscatter. Anterior corneal backscatter might serve as an indicator of impaired endothelium in FECD. PMID:27661858

  19. Prior Corneal Scarification and Injection of Immune Serum are Not Required Before Ocular HSV-1 Infection for UV-B-Induced Virus Reactivation and Recurrent Herpetic Corneal Disease in Latently Infected Mice

    PubMed Central

    BenMohamed, Lbachir; Osorio, Nelson; Khan, Arif A.; Srivastava, Ruchi; Huang, Lei; Krochmal, John J.; Garcia, Jairo M.; Simpson, Jennifer L.; Wechsler, Steven L.

    2017-01-01

    Purpose Blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (HSV-1) from latency, rather than to primary acute infection. Mice latently infected with HSV-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. HSV-1 reactivation can be induced in latently infected mice by several in vivo procedures, with UV-B-induced reactivation being one commonly used method. In the UV-B model, corneas are scarified (lightly scratched) just prior to ocular infection to increase efficiency of the primary infection and immune serum containing HSV-1 neutralizing antibodies is injected intraperitoneally (i.p.) to increase survival and decrease acute corneal damage. Since scarification can significantly alter host gene transcription in the cornea and in the trigeminal ganglia (TG; the site of HSV-1 latency) and since injection of immune serum likely modulates innate and adaptive herpes immunity, we investigated eliminating both treatments. Material and Methods Mice were infected with HSV-1 with or without corneal scarification and immune serum. HSV-1 reactivation and recurrent disease were induced by UV-B irradiation. Results When corneal scarification and immune serum were both eliminated, UV-B irradiation still induced both HSV-1 reactivation, as measured by shedding of reactivated virus in tears and herpetic eye disease, albeit at reduced levels compared to the original procedure. Conclusion Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model. PMID:26398722

  20. Synthetic stigmasterol derivatives inhibit capillary tube formation, herpetic corneal neovascularization and tumor induced angiogenesis: Antiangiogenic stigmasterol derivatives.

    PubMed

    Michelini, Flavia M; Lombardi, María Gabriela; Bueno, Carlos A; Berra, Alejandro; Sales, María Elena; Alché, Laura E

    2016-11-01

    Angiogenesis plays a critical role in initiating and promoting several diseases, such as cancer and herpetic stromal keratitis (HSK). Herein, we studied the inhibitory effect of two synthetic stigmasterol derivatives on capillary tube-like structures and on cell migration in human umbilical vein endothelial cells (HUVEC): (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2). We also studied their effect on VEGF expression in IL-6 stimulated macrophages and in LMM3 breast cancer cells. Furthermore, we investigated the antiangiogenic activity of the compounds on corneal neovascularization in the murine model of HSK and in an experimental model of tumor-induced angiogenesis in mice. Both compounds inhibited capillary tube-like formation, but only compound 1 restrained cell migration. Compound 1, unlike compound 2, was able to reduce VEGF expression. Only compound 1 not only reduced the incidence and severity of corneal neovascularization, when administered at the onset of HSK, but it also restrained the development of neovascular response induced by tumor cells in mice skin. Our results show that compound 1 inhibits angiogenesis in vitro and in vivo. Therefore, compound 1 would be a promising drug in the treatment of those diseases where angiogenesis represents one of the main pathogenic events.

  1. Reduced hippocampal manganese-enhanced MRI (MEMRI) signal during pilocarpine-induced status epilepticus: edema or apoptosis?

    PubMed

    Malheiros, Jackeline Moraes; Persike, Daniele Suzete; Castro, Leticia Urbano Cardoso de; Sanches, Talita Rojas Cunha; Andrade, Lúcia da Conceição; Tannús, Alberto; Covolan, Luciene

    2014-05-01

    Manganese-enhanced MRI (MEMRI) has been considered a surrogate marker of Ca(+2) influx into activated cells and tracer of neuronal active circuits. However, the induction of status epilepticus (SE) by kainic acid does not result in hippocampal MEMRI hypersignal, in spite of its high cell activity. Similarly, short durations of status (5 or 15min) induced by pilocarpine did not alter the hippocampal MEMRI, while 30 min of SE even reduced MEMRI signal Thus, this study was designed to investigate possible explanations for the absence or decrease of MEMRI signal after short periods of SE. We analyzed hippocampal caspase-3 activation (to evaluate apoptosis), T2 relaxometry (tissue water content) and aquaporin 4 expression (water-channel protein) of rats subjected to short periods of pilocarpine-induced SE. For the time periods studied here, apoptotic cell death did not contribute to the decrease of the hippocampal MEMRI signal. However, T2 relaxation was higher in the group of animals subjected to 30min of SE than in the other SE or control groups. This result is consistent with higher AQP-4 expression during the same time period. Based on apoptosis and tissue water content analysis, the low hippocampal MEMRI signal 30min after SE can potentially be attributed to local edema rather than to cell death.

  2. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    PubMed

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  3. Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema

    PubMed Central

    Sehm, Tina; Fan, Zheng; Ghoochani, Ali; Rauh, Manfred; Engelhorn, Tobias; Minakaki, Georgia; Dörfler, Arnd; Klucken, Jochen; Buchfelder, Michael

    2016-01-01

    The glutamate transporter xCT (SCL7a11, system Xc-, SXC) is an emerging key player in glutamate/cysteine/glutathione homeostasis in the brain and in cancer. xCT expression correlates with the grade of malignancy. Here, we report on the use of the U.S. Food and Drug Administration and EMA-approved xCT inhibitor, sulfasalazine (SAS) in gliomas. SAS does not affect cell viability in gliomas at concentrations below 200 μM. At higher concentrations SAS becomes gliomatoxic. Mechanistically SAS inhibits xCT and induces ferroptotic cell death in glioma cells. There is no evidence for impact on autophagic flux following SAS application. However, SAS can potentiate the efficacy of the standard chemotherapeutic and autophagy-inducing agent temozolomide (Temcat, Temodal or Temodar®). We also investigated SAS in non-transformed cellular constituents of the brain. Neurons and brain tissue are almost non-responding to SAS whereas isolated astrocytes are less sensitive towards SAS toxicity compared to gliomas. In vivo SAS treatment does not affect experimental tumor growth and treated animals revealed comparable tumor volume as untreated controls. However, SAS treatment resulted in reduced glioma-derived edema and, hence, total tumor volume burden as revealed by T2-weighted magnetic resonance imaging. Altogether, we show that SAS can be utilized for targeting the glutamate antiporter xCT activity as a tumor microenvironment-normalizing drug, while crucial cytotoxic effects in brain tumors are minor. PMID:27074570

  4. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice

    PubMed Central

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-01-01

    Background Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Material/Methods Mice were dosed with allyl nitrile (0–200 μmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Results Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Conclusions Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities. PMID:26932717

  5. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice.

    PubMed

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-02-29

    Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Mice were dosed with allyl nitrile (0-200 µmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities.

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

    PubMed

    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 p<0.001 for CMC and povidone, respectively, matched pairs t-test, two-tailed), suggesting that for both lubricants the staining worsened with wear. This effect was expected and likely driven by the MPS. However, the mean cumulative staining scores for CMC and povidone were 2.8 and 2.6 out of 20 possible at baseline, increasing to 4.9 and 7.1 at 4 weeks, respectively. The increases were significantly different (p=0.003, matched pairs t-test, two-tailed) suggesting a greater increase in corneal staining for the povidone lubricant. The symptom scores were not significantly different, 0 to 4 weeks by regimen or between preinstillation drops. These results suggest that a CMC-containing preapplication drop can reduce corneal staining resulting from disinfection with a polyhexanide MPS. This result is consistent with a proposed mechanism for CMC to neutralize cationic disinfectants and may offer clinicians another means to reduce

  7. Tissue-type transglutaminase and the effects of cystamine on intracerebral hemorrhage-induced brain edema and neurological deficits

    PubMed Central

    Okauchi, Masanobu; Xi, Guohua; Keep, Richard F.; Hua, Ya

    2009-01-01

    Introduction Neurodegeneration occurs after intracerebral hemorrhage (ICH) and tissue-type transglutaminase (tTG) has a role in neurodegenerative disorders. The present study investigated tTG expression after ICH and the effects of a tTG inhibitor, cystamine, on ICH-induced brain edema and neurological deficits. Methods This study had two parts. In the first, male Sprague-Dawley rats received an intracaudate injection of 100 µL autologous whole blood or a needle insertion (sham). Rats were killed 3 days later and the brains used for immunohistochemistry, Western blots and real-time quantitative polymerase chain reaction. In the second set, ICH rats were treated intraperitoneally with either a tTG inhibitor, cystamine, or vehicle. Rats underwent behavioral testing and were killed at day-3 for measurement of brain swelling. Results tTG positive cells were found in the ipsilateral basal ganglia after ICH and most of those cells were neuron-like. Western blot analysis showed a 3-fold increase in tTG in the ipsilateral basal ganglia (p<0.01 vs. sham) after ICH. tTG mRNA levels were also significantly higher (8.5-fold increase vs. sham). Cystamine treatment attenuated ICH-induced brain swelling (day 3: 14.4±3.2 vs. 21.4±4.0% in vehicle-treated rats, p<0.01), neuronal death and improved functional outcome (forelimb placing score: 47±23 vs. 17±16% in vehicle-treated rats, p<0.05). Conclusions ICH induces perihematomal tTG upregulation and cystamine, a tTG inhibitor, reduces ICH-induced brain swelling and neurological deficits. PMID:19007756

  8. Vortex or whorl formation of cultured human corneal epithelial cells induced by magnetic fields.

    PubMed

    Dua, H S; Singh, A; Gomes, J A; Laibson, P R; Donoso, L A; Tyagi, S

    1996-01-01

    The terms 'vortex keratopathy' and 'hurricane keratopathy' describe two similar conditions affecting the corneal surface. In the former, a vortex or whorl pattern is seen on the corneal surface and is due to the deposition of substances such as pigment, iron or drugs in the epithelial cells. In the latter, a similar pattern is presented by migrating epithelial cells but, unlike the former, the pattern is rendered more visible by fluorescein staining. Both represent the migratory pattern of normal epithelial cells which is otherwise not visible due to the slow rate of epithelial turnover and migration. The whorl pattern has a clockwise predisposition in the majority of cases and is hypothesised to be due to the influence of ocular electro-magnetic fields on the migrating epithelial cells. In this study we tested in vitro the effect of static magnetic fields on corneal epithelial cells. We were able to reproduce dramatic vortex or whorl patterns in response to magnetic fields, but without preferential migration towards the North or South Pole.

  9. Resolution of Intrathecal Hydromorphone or Morphine-induced Peripheral Edema by Opioid Rotation to Fentanyl: A Case Series.

    PubMed

    Veizi, Elias; Tornero-Bold, Melissa; Hayek, Salim M

    2016-07-01

    Intrathecal therapy [IT] has become an important modality for treatment of intractable cancer and noncancer pain although adverse events limit its effectiveness. The purpose of this case series was to report and discuss the lower limb edema from IT hydromorphone and morphine therapy and its resolution or nonrecurrence upon rotating the IT solution to fentanyl. Case series. Five patients, 4 women and 1 man, 55 to 67 years old implanted with IT delivery device systems [IDDS] were treated with continuous infusion of hydromorphone [4 subjects] at 95 ± 40 mcg/24 hours and morphine [1 subject] at 0.67 mg/24 hours. They developed peripheral edema of the lower extremities at an average of 4.2 months [mean, range 1 to 8 months] after implant. In 4 subjects, peripheral edema resolved by changing the IT agent to fentanyl. The mean time for complete resolution of edema was 50 ± 20 days while patients were treated with continuous infusion of fentanyl. It should be noted that all patients were receiving bupivacaine in addition to the IT opioid. In one subject, infusion of IT saline resulted in faster resolution of peripheral edema. Peripheral lower extremity edema may occur in patients treated with IT infusion of hydromorphone or morphine, even at low doses. This report presents, to the best of our knowledge, the first case series describing the benefit of IT opioid rotation to fentanyl in alleviating challenging lower extremity edema from IT hydromorphone and morphine. © 2016 World Institute of Pain.

  10. Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy type 2

    PubMed Central

    Choi, Seung-Il; Kim, Bong-Yoon; Dadakhujaev, Shorafidinkhuja; Oh, Jun-Young; Kim, Tae-Im; Kim, Joo Young; Kim, Eung Kweon

    2012-01-01

    Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease characterized by a progressive age-dependent extracellular accumulation of transforming growth factor β-induced protein (TGFBI). Corneal fibroblasts from GCD2 patients also have progressive degenerative features, but the mechanism underlying this degeneration remains unknown. Here we observed that TGFBI was degraded by autophagy, but not by the ubiquitin/proteasome-dependent pathway. We also found that GCD2 homozygous corneal fibroblasts displayed a greater number of fragmented mitochondria. Most notably, mutant TGFBI (mut-TGFBI) extensively colocalized with microtubule-associated protein 1 light chain 3β (MAP1LC3B, hereafter referred to as LC3)-enriched cytosolic vesicles and CTSD in primary cultured GCD2 corneal fibroblasts. Levels of LC3-II, a marker of autophagy activation, were significantly increased in GCD2 corneal fibroblasts. Nevertheless, levels of SQSTM1/p62 and of polyubiquitinated protein were also significantly increased in GCD2 corneal fibroblasts compared with wild-type (WT) cells. However, LC3-II levels did not differ significantly between WT and GCD2 cells, as assessed by the presence of bafilomycin A1, the fusion blocker of autophagosomes and lysosomes. Likewise, bafilomycin A1 caused a similar change in levels of SQSTM1. Thus, the increase in autophagosomes containing mut-TGFBI may be due to inefficient fusion between autophagosomes and lysosomes. Rapamycin, an autophagy activator, decreased mut-TGFBI, whereas inhibition of autophagy increased active caspase-3, poly (ADP-ribose) polymerase 1 (PARP1) and reduced the viability of GCD2 corneal fibroblasts compared with WT controls. These data suggest that defective autophagy may play a critical role in the pathogenesis of GCD2. PMID:22995918

  11. Observation on ultrastructure and histopathology of cornea following femtosecond laser-assisted deep lamellar keratoplasty for acute corneal alkaline burns.

    PubMed

    Li, Wen-Jing; Hu, Yu-Kun; Song, Hui; Gao, Xiao-Wei; Zhao, Xu-Dong; Dong, Jing; Guo, Yun-Lin; Cai, Yan

    2016-01-01

    To demonstrate the changes in ultrastructure and histopathology of the cornea in acute corneal alkaline burns after femtosecond laser-assisted deep lamellar keratoplasty. The New Zealand white rabbits treated with alkaline corneal burn were randomized into two groups, Group A (16 eyes) with femtosecond laser-assisted deep lamellar keratoplasty 24h after burn and Group B (16 eyes) without keratoplasty as controls. All eyes were evaluated with transmission electron microscopy (TEM) at 1, 2, 3, and 4wk follow-up, then all corneas were tested by hematoxylin and eosin staining histology. The corneal grafts in Group A were transparent, while those in Group B showed corneal stromal edema and loosely arranged collagen fibers. One week after treatment, TEM revealed the intercellular desmosomes in the epithelial layers and intact non-dissolving nuclei in Group A. At week 4, the center of the corneas in Group A was transparent with regularly arranged collagen fibers and fibroblasts in the stroma. In Group B, squamous cells were observed on the corneal surface and some epithelial cells were detached. Femtosecond laser-assisted deep lamellar keratoplasty can suppress inflammatory responses, prevent toxic substance-induced injury to the corneal endothelium and inner tissues with quicker recovery and better visual outcomes.

  12. Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes

    PubMed Central

    Mallet, Justin D.; Bastien, Nathalie; Gendron, Sébastien P.; Rochette, Patrick J.

    2016-01-01

    Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced. PMID:27611318

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

    PubMed

    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.

  14. Antioxidant and Anti-inflammatory Activities of a Commercial Noni Juice revealed by Carrageenan-induced Paw Edema.

    PubMed

    Yilmazer, N; Coskun, C; Gurel-Gurevin, E; Yaylim, I; Eraltan, E H; Ikitimur-Armutak, E I

    2016-09-01

    This study aimed to investigate antioxidant and anti-inflammatory activities of a commercial product of noni (Morinda citrifolia) juice. Carrageenan-induced rat paw edema was employed as inflammatory model. One control and three experimental groups were formed. Experimental groups were administered noni juice alone, noni juice+carrageenan, and carrageenan alone. Oxidant and antioxidant capacity were determined by d-ROMs test and BAP test, respectively. Plasma concentrations of endothelin-1 and leptin were measured by ELISA. Measurements were performed at zero time and 2nd hour of inflammation. Oxidant capacity decreased in noni-received groups at 2nd hour (p=0.019). Antioxidant capacity of the group which received noni alone was found to be higher at 2nd hour (p=0.036). Plasma concentrations of endothelin-1 and leptin were notably lower in noni-received groups (p=0.001 and p=0.021, respectively). The results show that the commercial noni juice investigated has pronounced antioxidant and anti-inflammatory activities.

  15. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  16. Corneal Abrasions

    MedlinePlus

    ... Causes a Corneal Abrasion? Your eye has other defenses besides the orbital bone: The eyelids and eyelashes ... The Nemours Foundation, iStock, Getty Images, Corbis, Veer, Science Photo Library, Science Source Images, Shutterstock, and Clipart. ...

  17. Corneal transplant

    MedlinePlus

    ... 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. ...

  18. Corneal Abrasions

    MedlinePlus

    ... fingernails short, too.Use care when putting in contact lenses. Make sure you clean them properly each day.Don’t sleep in your contact lenses.Trim low-hanging tree branches. Corneal abrasion treatment ...

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

    PubMed Central

    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. PMID:27781206

  20. Management of corneal bee sting.

    PubMed

    Razmjoo, Hassan; Abtahi, Mohammad-Ali; Roomizadeh, Peyman; Mohammadi, Zahra; Abtahi, Seyed-Hossein

    2011-01-01

    Corneal bee sting is an uncommon environmental eye injury that can result in various ocular complications with an etiology of penetrating, immunologic, and toxic effects of the stinger and its injected venom. In this study we present our experience in the management of a middle-aged male with a right-sided deep corneal bee sting. On arrival, the patient was complaining of severe pain, blurry vision with acuity of 160/200, and tearing, which he had experienced soon after the injury. Firstly, we administered conventional drugs for eye injuries, including topical antibiotic, corticosteroid, and cycloplegic agents. After 2 days, corneal stromal infiltration and edema developed around the site of the sting, and visual acuity decreased to 100/200. These conditions led us to remove the stinger surgically. Within 25 days of follow-up, the corneal infiltration decreased gradually, and visual acuity improved to 180/200. We suggest a two-stage management approach for cases of corneal sting. For the first stage, if the stinger is readily accessible or primary dramatic reactions, including infiltration, especially on the visual axis, exist, manual or surgical removal would be indicated. Otherwise, we recommend conventional treatments for eye injuries. Given this situation, patients should be closely monitored for detection of any worsening. If the condition does not resolve or even deteriorates, for the second stage, surgical removal of the stinger under local or generalized anesthesia is indicated.

  1. Recovery of Corneal Endothelial Cells from Periphery after Injury

    PubMed Central

    Choi, Sang Ouk; Jeon, Hyun Sun; Hyon, Joon Young; Oh, Yun-Jung; Wee, Won Ryang; Chung, Tae-young; Shin, Young Joo; Kim, Jeong Won

    2015-01-01

    Background Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury. Aim To investigate the recovery process of corneal endothelial cells (CECs) from corneal endothelial injury. Methods Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group). Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue. Results Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal. Conclusions CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium. PMID:26378928

  2. Serratia corneal ulcers: a retrospective clinical study.

    PubMed

    Mah-Sadorra, Jeane Haidee; Najjar, Dany M; Rapuano, Christopher J; Laibson, Peter R; Cohen, Elisabeth J

    2005-10-01

    To study the clinical and microbiological profile of Serratia corneal ulcers at the Cornea Service of the Wills Eye Hospital. This was a retrospective, observational case series. The clinical records of patients with Serratia marcescens corneal ulcers seen at the Cornea Service of the Wills Eye Hospital between January 1, 1998 and December 31, 2002 were reviewed. Twenty-four cases of Serratia keratitis were identified in 21 patients. Two patients (9.5%) had recurrent keratitis, 1 of which recurred twice. Both had corneal graft edema and were on topical steroids and antiglaucoma drops. The Serratia infection in 15 patients (71%) was associated with an abnormal corneal surface. Twelve of these patients (57%) had the ulcer in a corneal graft, 4 (19%) of which were associated with suture infiltrates. Fifteen patients (71%) were on topical medications-15 used corticosteroids and 13 used antiglaucoma drops. Six patients (29%) were contact lens wearers-1 had a concomitant suture infiltrate associated with a corneal graft, and 5 had otherwise healthy corneas. One isolate lacked in vitro susceptibility to ciprofloxacin and ofloxacin but was susceptible to gentamicin and tobramycin. Nineteen patients had a favorable response to medical therapy. Two patients with poor outcome had large corneal ulcers with severe necrosis and thinning associated with delay in treatment. Serratia marcescens keratitis is associated with the presence of an abnormal corneal surface, use of topical medications, and contact lens wear. Prompt medical therapy results in a good clinical response in the majority of cases.

  3. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice.

    PubMed

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histopathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model.

  4. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice

    PubMed Central

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model. PMID:26426535

  5. Sclareol exhibits anti-inflammatory activity in both lipopolysaccharide-stimulated macrophages and the λ-carrageenan-induced paw edema model.

    PubMed

    Huang, Guan-Jhong; Pan, Chun-Hsu; Wu, Chieh-Hsi

    2012-01-27

    Sclareol (1) is a natural fragrance compound used widely in the cosmetic and food industries. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the λ-carrageenan-induced edema mouse paw model were applied to examine the anti-inflammatory potential of 1 and its possible molecular mechanisms. The experimental results obtained demonstrated that this compound inhibited cell growth, nitric oxide (NO) production, and the expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in LPS-stimulated macrophages. Compound 1 also reduced paw edema, the tissue content of NO, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), iNOS and COX-2 protein expression, and neutrophil infiltration within the tissues after λ-carrageenan stimulation. The present study suggests that the anti-inflammatory mechanisms of 1 might be related to a decrease of inflammatory cytokines and an increase of antioxidant enzyme activity.

  6. Butorphanol decreases edema following carrageenan-induced paw inflammation in rats.

    PubMed

    Vachon, Pascal; Moreau, Jean-Pierre

    2002-11-01

    The objectives of this study were to evaluate the anti-inflammatory effects and possible drug interactions of butorphanol by using carrageenan-induced paw inflammation in rats. We injected the right hind footpads of 64 female Sprague-Dawley rats (approximate weight, 100 g) with 50 microL of a 0.5% solution of carrageenan. Indomethacin (0, 1, 2.5, or 5 mg/kg) was administered by gavage to each of four groups 1 h prior to carrageenan injections. Half of the animals in each group received butorphanol (2 mg/kg) subcutaneously 1 h prior to carrageenan injections. Butorphanol decreased paw inflammation following carrageenan injections with or without concurrent administration of indomethacin. No drug interaction with indomethacin was observed. In conclusion, when using butorphanol for its analgesic properties, investigators should be mindful of the drug's anti-inflammatory effects, which may interfere with the experimentation.

  7. Fluvoxamine inhibits some inflammatory genes expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rat

    PubMed Central

    Rafiee, Laleh; Hajhashemi, Valiollah; Javanmard, Shaghayegh Haghjooy

    2016-01-01

    Objective(s): Fluvoxamine is a well-known selective serotonin reuptake inhibitor (SSRI); Despite its anti-inflammatory effect, little is known about the precise mechanisms involved. In our previous work, we found that IP administration of fluvoxamine produced a noticeable anti-inflammatory effect in carrageenan-induced paw edema in rats. In this study, we aimed to evaluate the effect of fluvoxamine on the expression of some inflammatory genes like intercellular adhesion molecule (ICAM1), vascular cell adhesion molecule (VCAM1), cyclooxygenases2 (COX2), and inducible nitric oxide synthase (iNOS). Materials and Methods: An in vitro model of LPS stimulated human endothelial cells and U937 macrophages were used. Cells were pretreated with various concentrations of fluvoxamine, from 10-8 M to 10-6 M. For in vivo model, fluvoxamine was administered IP at doses of 25 and 50 mg/kg-1, before injection of carrageenan. At the end of experiment, the expression of mentioned genes were measured by quantitative real time (RT)-PCR in cells and in paw edema in rat. Results: The expression of ICAM1, VCAM1, COX2, and iNOS was significantly decreased by fluvoxamine in endothelial cells, macrophages, and in rat carrageenan-induced paw edema. Our finding also confirmed that IP injection of fluvoxamine inhibits carrageenan-induced inflammation in rat paw edema. Conclusion: The results of present study provide further evidence for the anti-inflammatory effect of fluvoxamine. This effect appears to be mediated by down regulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of immunomodulatory effect of fluvoxamine. PMID:27803785

  8. Suppression of alkali-induced oxidative injury in the cornea by mesenchymal stem cells growing on nanofiber scaffolds and transferred onto the damaged corneal surface.

    PubMed

    Cejkova, Jitka; Trosan, Peter; Cejka, Cestmir; Lencova, Anna; Zajicova, Alena; Javorkova, Eliska; Kubinova, Sarka; Sykova, Eva; Holan, Vladimir

    2013-11-01

    The purpose of this study was to investigate whether rabbit bone marrow-derived mesenchymal stem cells (MSCs) effectively decrease alkali-induced oxidative stress in the rabbit cornea. The alkali (0.15 N NaOH) was applied on the corneas of the right eyes and then rinsed with tap water. In the first group of rabbits the injured corneas remained untreated. In the second group MSCs were applied on the injured corneal surface immediately after the injury and eyelids sutured for two days. Then the sutures were removed. In the third group nanofiber scaffolds seeded with MSCs (and in the fourth group nanofibers alone) were transferred onto the corneas immediately after the injury and the eyelids sutured. Two days later the eyelid sutures were removed together with the nanofiber scaffolds. The rabbits were sacrificed on days four, ten or fifteen after the injury, and the corneas were examined immunohistochemically, morphologically, for the central corneal thickness (taken as an index of corneal hydration) using an ultrasonic pachymeter and by real-time PCR. Results show that in untreated injured corneas the expression of malondialdehyde (MDA) and nitrotyrosine (NT) (important markers of lipid peroxidation and oxidative stress) appeared in the epithelium. The antioxidant aldehyde dehydrogenase 3A1 (ALDH3A1) decreased in the corneal epithelium, particularly in superficial parts, where apoptotic cell death (detected by active caspase-3) was high. (In control corneal epithelium MDA and NT are absent and ALDH3A1 highly present in all layers of the epithelium. Cell apoptosis are sporadic). In injured untreated cornea further corneal disturbances developed: The expressions of matrix metalloproteinase 9 (MMP9) and proinflammatory cytokines, were high. At the end of experiment (on day 15) the injured untreated corneas were vascularized and numerous inflammatory cells were present in the corneal stroma. Vascular endothelial growth factor (VEGF) expression and number of macrophages

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

    PubMed Central

    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

  10. The effect of sulfur mustard and nitrogen mustard on corneal collagen degradation induced by the enzyme collagenase.

    PubMed

    Naderi, Mostafa; Jadidi, Khosro; Falahati, Farzaneh; Alavi, Saayyed Ali

    2010-12-01

    Sulfur mustard (SM) is an alkylating agent that can affect cornea and induce various complications. With regard to the role of the enzyme collagenase in dermatologic complications induced by sm and its role in other ocular disorders, we studied the effect of SM and nitrogen mustard (NM) on collagen degradation by collagenase. This study included 7 groups of samples: The negative control group contained collagen without collagenase and toxins, the control group contained collagen and collagenase without any toxin, the positive control groups of NM and SM contained collagen and NM or SM without collagenase, the experimental groups of NM and SM contained collagen that was affected by NM or SM and collagenase, and the control group of collagenase contained only collagenase without containing collagen or receiving toxins. After incubation for 3.5 hours, the amount of hydroxyproline and the protein content of the samples were measured. Data were analyzed by analysis of variance (ANOVA). The protein concentrations of the negative control group and the positive control groups of SM and NM were significantly lower than those for all other groups of the study. There was a significant difference in hydroxyproline concentration of control group and negative control group; however, there was no significant difference between experimental group of SM and the positive control group of SM. There was no significant difference between the negative control group and the positive control group of SM in the hydroxyproline concentration of sediment samples. According to the results of this study, SM can affect the corneal collagen in a way in which collagenase cannot degrade it. In addition, it can be hypothesized that ineffective activity of this enzyme can result in increasing concentration of collagenase, which can lead to the destruction of the normal collagen of the cornea. The main result of this study confirms the hypothesis that SM inhibits the effect of collagenase on corneal

  11. Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

    PubMed Central

    Chamorro-Marín, Virginia; García-Delgado, Manuel; Touma-Fernández, Angel; Aguilar-Alonso, Eduardo; Fernández-Mondejar, Enrique

    2008-01-01

    Intoduction Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. β-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether β-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). Methods This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. Results In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 ± 0.27 versus 4.9 ± 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when

  12. Therapeutic effects of gel ointments containing tranilast nanoparticles on paw edema in adjuvant-induced arthritis rats.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2014-01-01

    Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.

  13. Blockade of the intermediate-conductance Ca(2+)-activated K+ channel inhibits the angiogenesis induced by epidermal growth factor in the treatment of corneal alkali burn.

    PubMed

    Yang, Huike; Li, Xiaodong; Ma, Jing; Lv, Xiaohong; Zhao, Shu; Lang, Wen; Zhang, Yafang

    2013-05-01

    Epidermal growth factor (EGF) is used to treat alkali-burned corneas. However, EGF-induced corneal angiogenesis, which is currently untreatable, is a side effect of this therapy. We therefore explored the role of the intermediate-conductance Ca(2+)-activated K(+) channel (KCa3.1) in EGF-induced angiogenesis and tested whether KCa3.1 blockade can suppress EGF-induced corneal angiogenesis. The proliferation, migration and tube formation of HUVECs (human umbilical vein endothelial cells) in response to EGF, the MEK inhibitor PD98059 and the KCa3.1 inhibitor TRAM-34 were analyzed in vitro via MTT, cell counting, scratch and tube formation assays. The protein and mRNA levels of KCa3.1, phosphorylated-ERK (P-ERK), total-ERK (T-ERK), cyclin-dependent kinase 4 (CDK4), vimentin and MMP-2 were assessed via western blotting and RT-PCR. KCa3.1 and vimentin expression were also detected through immunofluorescence staining. Flow cytometry was performed to examine the cell cycle. Further, an in vivo murine alkali-burned cornea model was developed and treated with EGF and TRAM-34 eye drops to analyze the effect of these treatments on corneal healing and angiogenesis. The corneas were also analyzed by histological staining. The in vitro results showed that EGF induces the upregulation of KCa3.1 and P-ERK in HUVECs and that this upregulation is suppressed by PD98059. EGF stimulates proliferation, migration and tube formation in HUVECs, and this effect can be suppressed by TRAM-34. TRAM-34 also arrests HUVECs in the G1 phase of the cell cycle and downregulates CDK4, vimentin and MMP-2 in these cells. The in vivo results indicated that TRAM-34 suppresses EGF-induced corneal angiogenesis without affecting EGF-induced corneal wound healing. In summary, the upregulation of KCa3.1 may be crucial for EGF-induced angiogenesis through the MAPK/ERK signaling pathway. Thus, KCa3.1 may be a potential target for the treatment of EGF-induced corneal angiogenesis.

  14. Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production

    PubMed Central

    Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation. PMID:26895409

  15. 4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

    PubMed Central

    Liu, Zhongyang; Xi, Ronggang; Zhang, Zhiran; Li, Wangping; Liu, Yan; Jin, Faguang; Wang, Xiaobo

    2014-01-01

    4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. PMID:25050781

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

    PubMed

    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.

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

    PubMed

    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; P<0.05) and cold response (21.2±1.7 vs. 16.8±1.3imp/s; P<0.05) as well as reduced cold threshold (1.5±0.1 vs. 2.8±0.2 Δ°C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (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.

  18. Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

    PubMed Central

    Michinaga, Shotaro; Koyama, Yutaka

    2015-01-01

    Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

  19. The genetics of Fuchs′ corneal dystrophy

    PubMed Central

    Iliff, Benjamin W; Riazuddin, S Amer; Gottsch, John D

    2013-01-01

    Fuchs′ corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments. PMID:23585771

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

    PubMed

    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.

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

    PubMed Central

    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

  2. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    PubMed

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

  3. Corneal epithelial response of the primate eye to gas permeable corneal contact lenses: a preliminary report.

    PubMed

    Bergmanson, J P; Ruben, M; Chu, L W

    1984-01-01

    The comparative corneal epithelial effects of rigid gas permeable and soft contact lenses are reported in the present preliminary study using two bush baby monkeys (Galago senegalensis). Both types of lenses produced early cell death among the surface squamous cells while internally the epithelium and its nerve fibers remained normal. Sporadically small abnormal groups of cells involving two to three of the surface layers were observed in both the hard and soft lens wearing corneas. It was concluded that this represented superficial punctate keratitis (SPK). Small superficial intracellular epithelial cysts with membranous contents were infrequently noted in the gas permeable lens wearing cornea and it is suggested here that they were mild forms or precursors of those seen clinically in human corneas. Since the gas permeable lens met the corneal oxygen requirement it is postulated that the traumatic effect of the rigidity of the lens caused the cystic formation to occur. The relative hypoxia induced by the soft contact lens resulted in a mild superficial epithelial edema.

  4. The role of free radicals in paraquat-induced corneal lesions.

    PubMed

    Nordquist, R E; Nguyen, H; Poyer, J L; Carubelli, R

    1995-07-01

    Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following accidental splashing of paraquat solutions onto the eyes. These studies were designed to document the generation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after intrastromal injection of paraquat, showed the signal of the free radical of paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections (100 microliters) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. In rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement membrane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits to the effects of paraquat. No lesions were observed following intrastromal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the proximal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significant plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabbit and monkeys as well as possible biochemical differences may account for the species differences observed.

  5. Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE(2), TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats.

    PubMed

    Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

    2012-01-01

    Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) Indomethacin (10 mg/kg, p.o.) or Gelam honey at different doses (1 or 2 g/kg, p.o.). The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE(2), TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE(2), TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days) showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID), both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions.

  6. Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE2, TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats

    PubMed Central

    Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

    2012-01-01

    Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) Indomethacin (10 mg/kg, p.o.) or Gelam honey at different doses (1 or 2 g/kg, p.o.). The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE2, TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE2, TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days) showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID), both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions. PMID:22919407

  7. Effects of one minute and ten minutes of walking activity in rats with arthritis induced by complete Freund's adjuvant on pain and edema symptoms.

    PubMed

    Gomes, Raquel Pinheiro; Bressan, Elisângela; Silva, Tatiane Morgana da; Gevaerd, Monique da Silva; Tonussi, Carlos Rogério; Domenech, Susana Cristina

    2014-01-01

    This study evaluated the effects of two protocols of exercise on nociception, edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 μL) into the right knee joint (TF; n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or ankle joints was evaluated by the variation of the articular diameter (DA, cm) and by the paw volume variation (EP, mL), respectively. Both were measured during 10 consecutive days. Two protocols of exercise were performed: (a) in the constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n = 13) didn't perform the exercise. After 10 days, the animals were euthanized for total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The variable exercise protocol inhibited incapacitation and edema for both joints. However, cell migration decreased only in the TF.The constant exercise reduced edema in both joints, and cell migration was decreased in the TT. However, the incapacitation was not reduced. Variable exercise seemed to be more effective in reducing the inflammatory parameters than constant exercise.

  8. [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

    PubMed

    Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

  9. Essential contribution of CCL3 to alkali-induced corneal neovascularization by regulating vascular endothelial growth factor production by macrophages

    PubMed Central

    Lu, Peirong; Li, Longbiao; Wu, Yu; Mukaida, Naofumi

    2008-01-01

    Purpose To evaluate the roles of CCL3 and its specific chemokine receptors, CCR1 and CCR5, in alkali-induced corneal neovascularization (CNV). Methods Chemical denudation of corneal and limbal epithelium was performed on wild-type (WT) BALB/c mice and CCL3-, CCR1-, and CCR5-deficienct (knockout [KO]) counterparts. Two weeks after injury CNV was quantified by immunostaining with anti-CD31. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by reverse transcription polymerase chain reaction (RT–PCR) and immunohistochemical analysis, respectively. Results Alkali injury augmented the intraocular mRNA expression of CCL3 and its receptors, CCR1 and CCR5, together with a transient infiltration of F4/80 positive macrophages and Gr-1 positive neutrophils. Compared with WT mice, CCL3-KO and CCR5-KO mice but not CCR1-KO mice exhibited reduced CNV two weeks after injury both macroscopically and microscopically as evidenced by CD31 positive areas. Concomitantly, the infiltration of F4/80 positive macrophages but not Gr-1 positive neutrophils was significantly attenuated in CCL3-KO mice compared with WT mice. Intracorneal infiltration of CCR5 expressing cells was significantly impaired in CCL3-KO mice compared with WT mice. Alkali injury induced a massive increase in the intraocular mRNA expression of a potent angiogenic factor, vascular endothelial growth factor (VEGF), in WT mice whereas these increments were severely retarded in CCL3-KO mice. Moreover, CCL3 enhanced VEGF expression by murine peritoneal macrophages at both the mRNA and the protein level. Furthermore, topical CCL3 application restored CNV, which was macroscopically and microscopically reduced in CCL3-KO mice after two weeks to levels similar to those found in WT mice. Conclusions In alkali-induced CNV, CCL3 induced macrophages to infiltrate and produce VEGF by binding to CCR5 but not to CCR1 and eventually promoted angiogenesis. PMID:18776949

  10. Long-Term Treatment by Vitamin B1 and Reduction of Serum Proinflammatory Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis

    PubMed Central

    Zaringhalam, Jalal; Akbari, Akhtar; Zali, Alireza; Manaheji, Homa; Nazemian, Vida; Shadnoush, Mahdi; Ezzatpanah, Somayeh

    2016-01-01

    Introduction: Immune system is involved in the etiology and pathophysiology of inflammation and vitamins are important sources of substances inducing nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines in the inflammation and pain induction, this study aimed to assess the effects of long-term administration of vitamin B1 on the proinflammatory cytokines, edema, and hyperalgesia during the acute and chronic phases of adjuvant-induced arthritis. Methods: On the first day of study, inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of rats. Vitamin B1 at doses of 100, 150, and 200 mg/kg was administrated intraperitoneally during 21 days of the study. Antinociceptive and anti-inflammatory effects of vitamin B1 were also compared to indomethacin (5 mg/kg). Inflammatory symptoms such as thermal hyperalgesia and paw edema were measured by radiant heat and plethysmometer, respectively. Serum TNF-α and IL-1β levels were checked by rat standard enzyme-linked immune sorbent assay (ELISA) specific kits. Results: The results indicated that vitamin B1(150 and 200 mg/kg) attenuated the paw edema, thermal hyperalgesia, and serum levels of TNF-α and IL-1β during both phases of CFA-induced inflammation in a dose-dependent manner. Effective dose of vitamin B1(150 mg/kg) reduced inflammatory symptoms and serum levels of TNF-α and IL-1β compare to indomethacin during the chronic phase of inflammation. Conclusion: Anti-inflammatory and antihyperalgesic effects of vitamin B1 during CFA-induced arthritis, more specifically after chronic vitamin B1 administration, suggest its therapeutic property for inflammation. PMID:27872694

  11. Terahertz sensing of corneal hydration.

    PubMed

    Singh, Rahul S; Tewari, Priyamvada; Bourges, Jean Louis; Hubschman, Jean Pierre; Bennett, David B; Taylor, Zachary D; Lee, H; Brown, Elliott R; Grundfest, Warren S; Culjat, Martin O

    2010-01-01

    An indicator of ocular health is the hydrodyanmics of the cornea. Many corneal disorders deteriorate sight as they upset the normal hydrodynamics of the cornea. The mechanisms include the loss of endothelial pump function of corneal dystophies, swelling and immune response of corneal graft rejection, and inflammation and edema, which accompany trauma, burn, and irritation events. Due to high sensitivity to changes of water content in materials, a reflective terahertz (300 GHz and 3 THz) imaging system could be an ideal tool to measure the hydration level of the cornea. This paper presents the application of THz technology to visualize the hydration content across ex vivo porcine corneas. The corneas, with a thickness variation from 470 - 940 µm, were successfully imaged using a reflective pulsed THz imaging system, with a maximum SNR of 50 dB. To our knowledge, no prior studies have reported on the use of THz in measuring hydration in corneal tissues or other ocular tissues. These preliminary findings indicate that THz can be used to accurately sense hydration levels in the cornea using a pulsed, reflective THz imaging system.

  12. uPA Binding to PAI-1 Induces Corneal Myofibroblast Differentiation on Vitronectin

    PubMed Central

    Wang, Lingyan; Ly, Christine M.; Ko, Chun-Ying; Meyers, Erin E.; Lawrence, Daniel A.; Bernstein, Audrey M.

    2012-01-01

    Purpose. Vitronectin (VN) in provisional extracellular matrix (ECM) promotes cell migration. Fibrotic ECM also includes VN and, paradoxically, strongly adherent myofibroblasts (Mfs). Because fibrotic Mfs secrete elevated amounts of urokinase plasminogen activator (uPA), we tested whether increased extracellular uPA promotes the persistence of Mfs on VN. Methods. Primary human corneal fibroblasts (HCFs) were cultured in supplemented serum-free medium on VN or collagen (CL) with 1ng/mL transforming growth factor β1 (TGFβ1). Adherent cells were quantified using crystal violet. Protein expression was measured by Western blotting and flow cytometry. Transfection of short interfering RNAs was performed by nucleofection. Mfs were identified by α-smooth muscle actin (α-SMA) stress fibers. Plasminogen activator inhibitor (PAI-1) levels were quantified by ELISA. Results. TGFβ1-treated HCFs secreted PAI-1 (0.5uM) that bound to VN, competing with αvβ3/αvβ5 integrin/VN binding, thus promoting cell detachment from VN. However, addition of uPA to cells on VN increased Mf differentiation (9.7-fold), cell-adhesion (2.2-fold), and binding by the VN integrins αvβ3 and -β5 (2.2-fold). Plasmin activity was not involved in promoting these changes, as treatment with the plasmin inhibitor aprotinin had no effect. A dominant negative PAI-1 mutant (PAI-1R) that binds to VN but does not inhibit uPA prevented the increase in uPA-stimulated cell adhesion and reduced uPA-stimulated integrin αvβ3/αvβ5 binding to VN by 73%. Conclusions. uPA induction of TGFβ1-dependent Mf differentiation on VN supports the hypothesis that elevated secretion of uPA in fibrotic tissue may promote cell adhesion and the persistence of Mfs. By blocking uPA-stimulated cell adhesion, PAI-1R may be a useful agent in combating corneal scarring. PMID:22700714

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

    PubMed

    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.

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

    PubMed Central

    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.

    2016-01-01

    Most stromal corneal dystrophies are associated with aggregation and deposition of the mutated transforming growth factor-β induced protein (TGFβIp). The 4th_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 4th_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. PMID:27030015

  15. Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells.

    PubMed

    Bigagli, Elisabetta; Cinci, Lorenzo; D'Ambrosio, Mario; Luceri, Cristina

    2017-08-01

    Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in oxidative stress, inflammation and cell death. The aim of this study was to investigate the potential protective effects of a commercial eye drop (Dacriovis™) containing Matricaria chamomilla and Euphrasia officinalis extracts on human corneal epithelial cells (HCEC-12) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the eye drops was evaluated by measuring the ferric reducing antioxidant power and the total phenolic content by Folin-Ciocalteu reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye drops at various concentrations. Cell viability, wound healing assay, reactive oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL-1β, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were able to protect corneal epithelial cells from UVB-induced cell death and ameliorated the wound healing; the eye drops exhibited a strong antioxidant activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops also exerted anti-inflammatory activities by decreasing COX-2, IL-1β, iNOS expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1 expression to control levels. These findings suggest that an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects against UVB induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from UVB exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  17. Localization of angiotensin converting enzyme in rabbit cornea and its role in controlling corneal angiogenesis in vivo

    PubMed Central

    Sharma, Ajay; Bettis, Daniel I.; Cowden, John W.

    2010-01-01

    Purpose The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT1 and AT2) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo. Methods New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to detect the presence of ACE, AT1, and AT2 gene expression. A corneal micropocket assay to implant a vascular endothelial growth factor (VEGF) pellet in the rabbit cornea was used to induce corneal angiogenesis. Rabbits of the control group received sterile water, and the treated group received 3 mg/kg enalapril intramuscularly once daily for 14 days starting from day 1 of pellet implantation. The clinical eye examination was performed by slit-lamp biomicroscopy. We monitored the level of corneal angiogenesis in live animals by stereomicroscopy at days 4, 9, and 14 after VEGF pellet implantation. Collagen type IV and lectin immunohistochemistry and fluorescent microscopy were used to measure corneal angiogenesis in tissue sections of control and enalapril-treated corneas of the rabbits. Image J software was used to quantify corneal angiogenesis in the rabbit eye in situ. Results Our data demonstrated the presence of ACE, AT1, and AT2 expression in corneal fibroblasts. Cells of corneal epithelium expressed AT1 and AT2 but did not show ACE expression. Slit-lamp examination did not show any significant difference between the degree of edema or cellular infiltration between the corneas of control and enalapril-treated rabbits. VEGF pellet implantation caused corneal angiogenesis in the eyes of vehicle-treated control rabbits, and the

  18. Localization of angiotensin converting enzyme in rabbit cornea and its role in controlling corneal angiogenesis in vivo.

    PubMed

    Sharma, Ajay; Bettis, Daniel I; Cowden, John W; Mohan, Rajiv R

    2010-04-23

    The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT(1) and AT(2)) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo. New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to detect the presence of ACE, AT(1), and AT(2) gene expression. A corneal micropocket assay to implant a vascular endothelial growth factor (VEGF) pellet in the rabbit cornea was used to induce corneal angiogenesis. Rabbits of the control group received sterile water, and the treated group received 3 mg/kg enalapril intramuscularly once daily for 14 days starting from day 1 of pellet implantation. The clinical eye examination was performed by slit-lamp biomicroscopy. We monitored the level of corneal angiogenesis in live animals by stereomicroscopy at days 4, 9, and 14 after VEGF pellet implantation. Collagen type IV and lectin immunohistochemistry and fluorescent microscopy were used to measure corneal angiogenesis in tissue sections of control and enalapril-treated corneas of the rabbits. Image J software was used to quantify corneal angiogenesis in the rabbit eye in situ. Our data demonstrated the presence of ACE, AT(1), and AT(2) expression in corneal fibroblasts. Cells of corneal epithelium expressed AT(1) and AT(2) but did not show ACE expression. Slit-lamp examination did not show any significant difference between the degree of edema or cellular infiltration between the corneas of control and enalapril-treated rabbits. VEGF pellet implantation caused corneal angiogenesis in the eyes of vehicle-treated control rabbits, and the mean area

  19. Intracranial pressure-induced optic nerve sheath response as a predictive biomarker for optic disc edema in astronauts.

    PubMed

    Wostyn, Peter; De Deyn, Peter Paul

    2017-09-04

    A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities. Understanding this syndrome, called visual impairment and intracranial pressure (VIIP), has become a high priority for National Aeronautics and Space Administration, especially in view of future long-duration missions (e.g., Mars missions). Moreover, to ensure selection of astronaut candidates who will be able to complete long-duration missions with low risk of the VIIP syndrome, it is imperative to identify biomarkers for VIIP risk prediction. Here, we hypothesize that the optic nerve sheath response to alterations in intracranial pressure may be a potential predictive biomarker for optic disc edema in astronauts. If confirmed, this biomarker could be used for preflight identification of astronauts at risk for developing VIIP-associated optic disc edema.

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

    PubMed Central

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

    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 mRNA 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. fumigatus hyphae-induced IL-8 expression was regulated by the activation of Dectin-1-mediated Ca2+-dependent PKC in HCECs. PMID:26085988

  1. Imaging, Reconstruction, And Display Of Corneal Topography

    NASA Astrophysics Data System (ADS)

    Klyce, Stephen D.; Wilson, Steven E.

    1989-12-01

    The cornea is the major refractive element in the eye; even minor surface distortions can produce a significant reduction in visual acuity. Standard clinical methods used to evaluate corneal shape include keratometry, which assumes the cornea is ellipsoidal in shape, and photokeratoscopy, which images a series of concentric light rings on the corneal surface. These methods fail to document many of the corneal distortions that can degrade visual acuity. Algorithms have been developed to reconstruct the three dimensional shape of the cornea from keratoscope images, and to present these data in the clinically useful display of color-coded contour maps of corneal surface power. This approach has been implemented on a new generation video keratoscope system (Computed Anatomy, Inc.) with rapid automatic digitization of the image rings by a rule-based approach. The system has found clinical use in the early diagnosis of corneal shape anomalies such as keratoconus and contact lens-induced corneal warpage, in the evaluation of cataract and corneal transplant procedures, and in the assessment of corneal refractive surgical procedures. Currently, ray tracing techniques are being used to correlate corneal surface topography with potential visual acuity in an effort to more fully understand the tolerances of corneal shape consistent with good vision and to help determine the site of dysfunction in the visually impaired.

  2. [Corneal dystrophies].

    PubMed

    Bourges, J-L

    2017-09-01

    Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09 % of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. Practically, the ophthalmologist manages functional symptoms, such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Corneal dystrophies.

    PubMed

    Bourges, J-L

    2017-06-01

    Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09% of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. In practice, the ophthalmologist manages functional symptoms such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Anti-edema effects of brown seaweed (Undaria pinnatifida) extract on phorbol 12-myristate 13-acetate-induced mouse ear inflammation.

    PubMed

    Khan, Mohammed Nurul Absar; Yoon, Seung-Je; Choi, Jae-Suk; Park, Nam Gyu; Lee, Hyung-Ho; Cho, Ji-Young; Hong, Yong-Ki

    2009-01-01

    The brown seaweed Undaria pinnatifida (Harvey) Suringar is used in traditional medicine to treat fever, urination problems, lumps and swelling, and as a dietary supplement for post-childbirth women. We examined the anti-inflammatory activities of the seaweed. The methanol extract of the seaweed was active against mouse ear edema induced by phorbol myristate acetate (PMA), with an IC(50) of 10.3 mg/ml. The extract reduced the edema to a half-maximal level when applied at the concentration of 40 mg/ml within 3 hours before or 2 hours after application of PMA. Extract taken from the blade section of the seaweed demonstrated the highest activity. The Northern form of U. pinnatifida was more active than the Southern form. In the analgesic test, the methanol extract suppressed the acetic acid-induced writhing response, with an IC(50) of 0.48 g/kg body weight. The extract also demonstrated antipyretic activity in yeast-induced hyperthermic mice. Activity-related constituents were arachidonic, eicosapentaenoic, and stearidonic acids.

  5. Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema.

    PubMed

    Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

    2016-12-13

    BACKGROUND Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). MATERIAL AND METHODS TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. RESULTS We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). CONCLUSIONS Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA.

  6. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats

    PubMed Central

    Mansouri, Mohammad Taghi; Hemmati, Ali Asghar; Naghizadeh, Bahareh; Mard, Seyyed Ali; Rezaie, Anahita; Ghorbanzadeh, Behnam

    2015-01-01

    Objectives: Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA. Materials and Methods: Carrageenan-induced mouse paw edema model was used for induction of inflammation. Results: The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E2 (PGE2) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1–30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26–14.76) mg/kg. It decreased the serum concentration of NO, PGE2, aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin. Conclusions: Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE2 overproduction. PMID:26069367

  7. Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema

    PubMed Central

    Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

    2016-01-01

    Background Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). Material/Methods TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. Results We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). Conclusions Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA. PMID:27959885

  8. Acute neurogenic airway plasma exudation and edema induced by inhaled wood smoke in guinea pigs: role of tachykinins and hydroxyl radical.

    PubMed

    Lin, Y S; Kou, Y R

    2000-04-07

    We studied the mechanisms underlying the wood smoke-induced acute airway injury in 120 anaesthetized guinea pigs. Five minutes after airway exposure, various doses of wood smoke produced a dose-dependent increase in Evans blue dye contents at all airway levels measured. Additionally, inhaled wood smoke produced submucosal edema of the trachea and bronchus, and peribronchial edema. These acute airway responses were nearly abolished by pretreatment with CP-96,345 alone [a tachykinin NK(1) receptor antagonist; (2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyc lo( 2.2.2.)-octan-3-amine] or with a combination of CP-96,345 and dimethylthiourea (a hydroxyl radical scavenger), and were attenuated by pretreatment with dimethylthiourea alone, yet were not affected by pretreatment with SR-48,968 [a tachykinin NK(2) receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl)-butyl)benzamide], with a combination of CP-96,344 and SR-48,965 (inactive enantiomers), with MK-886 [a leukotriene biosynthesis inhibitor; L-663, 536(3-(1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)-2, 2-dimethylpropanoic acid], with indomethacin (a cyclooxygenase inhibitor), or with N(G)-nitro-L-arginine methyl ester (a nitric oxide (NO) synthase inhibitor). The activity of airway neutral endopeptidase (an enzyme for tachykinin degradation) was not influenced by wood smoke at 5-min post-exposure. We conclude that both endogenous tachykinins and hydroxyl radical play an important role in producing smoke-induced acute airway plasma exudation and airway edema in guinea pigs. The contribution of tachykinins to these neurogenic responses is mediated via the activation of tachykinin NK(1) receptors and partly via a hydroxyl radical mechanism, and is not associated with inactivation of neutral endopeptidase.

  9. Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization

    PubMed Central

    Han, Kyu-Yeon; Tran, Jennifer A.; Chang, Jin-Hong; Azar, Dimitri T.; Zieske, James D.

    2017-01-01

    Specific factors from the corneal epithelium underlying the stimulation of stromal fibrosis and myofibroblast formation in corneal wound healing have not been fully elucidated. Given that exosomes are known to transfer bioactive molecules among cells and play crucial roles in wound healing, angiogenesis, and cancer, we hypothesized that corneal epithelial cell-derived exosomes may gain access to the underlying stromal fibroblasts upon disruption of the epithelial basement membrane and that they induce signaling events essential for corneal wound healing. In the present study, exosome-like vesicles were observed between corneal epithelial cells and the stroma during wound healing after corneal epithelial debridement. These vesicles were also found in the stroma following anterior stromal keratectomy, in which surgical removal of the epithelium, basement membrane, and anterior stroma was performed. Exosomes secreted by mouse corneal epithelial cells were found to fuse to keratocytes in vitro and to induce myofibroblast transformation. In addition, epithelial cell-derived exosomes induced endothelial cell proliferation and ex vivo aortic ring sprouting. Our results indicate that epithelial cell-derived exosomes mediate communication between corneal epithelial cells and corneal keratocytes as well as vascular endothelial cells. These findings demonstrate that epithelial-derived exosomes may be involved in corneal wound healing and neovascularization, and thus, may serve as targets for potential therapeutic interventions. PMID:28165027

  10. Role of Nigella sativa seed oil on corneal injury induced by formaldehyde in adult male albino rats.

    PubMed

    Salem, N A; Mahmoud, O M; Al Badawi, M H; Gab-Alla, A A

    2016-01-01

    Formaldehyde is frequently used in occupational environments, its toxicity concerns to all who work closely with it such as anatomists. Nigella sativa is an amazing herb with a rich historical and religious background; its seeds are the source of its active ingredients. The purpose of the present study was to evaluate the role of Nigella sativa oil on corneal injury induced by formaldehyde in adult male albino rats. Forty adult male albino rats were divided randomly to four groups 10 rats each: I - Control group, II - Formaldehyde exposed group, III - Nigella sativa oil group (40 mg/kg/day) via intragastric tube daily for 2 weeks and IV - Formaldehyde and Nigella sativa group. Rats were sacrificed with ether, the corneas were extracted, one processed for haematoxylin and eosin stain and the other was used for transmission electron microscopic examination. Our results in group II revealed marked disorganisation, erosion, vacuolation and necrosis of epithelial cells with loss of parts of epithelial layer. Large congested invasion of blood vessels with separation and disorganisation of stromal fibrils. The corneas of group IV showed intact layers of epithelial cells with appearance close to control group. Star shaped cells (limbal stem cells) were obviously noticed in basal and intermediate layer with intact Bowman's membrane. Stroma showed regular parallel collagen, limbal stem cells were also noticed in group III. We concluded that Nigella sativa oil can ameliorate the toxic changes of formaldehyde on rat corneas. (.

  11. Two mutations in the transforming growth factor beta-induced gene associated with familial Lattice corneal dystrophy

    PubMed Central

    Cao, Wen-Ping; Yuan, Hai-Gang; Liu, Ping; Li, Xue; Hu, Qi

    2017-01-01

    AIM To report a phenotypic variant pedigree of lattice corneal dystrophy (LCD) associated with two mutations, R124C and A546D, in the transforming growth factor beta-induced gene (TGFBI). METHODS A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction (PCR) of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband. RESULTS Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma. CONCLUSION We observed a novel LCD family which carried two pathogenic mutations (R124C and A546D) in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease, some different modifier alleles may influence the phenotype.

  12. Tissue Culture and in Vivo Modeling of Corneal Opacification and Ocular Injuries Induced by Pulsed Millimeter Waves.

    DTIC Science & Technology

    1985-02-01

    A179 878 TISSUE CULTURE AND IN VIVO MODELING OF COREL OPACIFICATION AND OCULAR I (U) UNIVERSITY OF NESTERN ONTARIO LONDON DEPT OF BIOCHEMISTRY J R...NATIONAL AiURfAU IF ;’ANUAI ,f’ 1q% A ’ , %’- . II AD _ _ _ _ TISSUE CULTURE AND IN VIVO MODELLING OF CORNEAL OPACIFICATION AND OCULAR INJURIES...Tissue Culture and In Vivo Modeling of Corneal Annual and Final Report Opacification and Ocular Injuries by Pulsed Oct. 1980 - 31 May 1984 Millimeter

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

    PubMed

    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.

  14. Efficacy of Primary Collagen Cross-Linking with Photoactivated Chromophore (PACK-CXL) for the Treatment of Staphylococcus aureus-Induced Corneal Ulcers.

    PubMed

    Tal, Kfir; Gal-Or, Orly; Pillar, Shani; Zahavi, Alon; Rock, Oded; Bahar, Irit

    2015-10-01

    To evaluate the efficacy of corneal collagen cross-linking (CXL) with photoactivated riboflavin (PACK-CXL) as primary therapy for Staphylococcus aureus-induced corneal ulcers in a rabbit model. The right eye of 40 rabbits was inoculated with S. aureus to induce formation of central corneal ulcers (day 1). The ulcer was examined on day 5, and rabbits were randomly assigned to 4 groups-group A: no treatment (control); group B: topical antibiotic treatment (cefazolin 50 mg/mL, garamycin 14 mg/mL drops, chloramphenicol 5% ointment every 2 hours); group C: PACK-CXL; group D: PACK-CXL + topical antibiotics. Follow-up by biomicroscopy was performed on day 5 and then every week for 1 month. The main outcome measures included infiltrates or the scar diameter, time to healing, time to full epithelialization, and a change in corneal thickness. After 1 month of treatment, group C ulcers had the smallest mean scar diameter (8.8 mm), followed by groups D (11.2 mm), B (13.0 mm), and A (24.5 mm) (P = 0.011). Group C had the shortest mean healing time (15.5 days), followed by groups D (17.2 days), B (19.7 days), and A (21.8 days). Analysis of relative reduction in the infiltrate size from day 5 yielded better results for groups C (P = 0.039) and D (P = 0.034) than those of group B. We demonstrate a beneficial effect of PACK-CXL as primary treatment, either as stand-alone or as an adjuvant to antimicrobial therapy.

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

    PubMed

    Ferdousi, Maryam; Azmi, Shazli; Petropoulos, Ioannis Nikolaos; Fadavi, Hassan; Ponirakis, Georgios; Marshall, Andrew; Tavakoli, Mitra; Malik, Imaan; Mansoor, Wasat; Malik, Rayaz Ahmed

    2015-01-01

    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.

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

    PubMed Central

    Ferdousi, Maryam; Azmi, Shazli; Petropoulos, Ioannis Nikolaos; Fadavi, Hassan; Ponirakis, Georgios; Marshall, Andrew; Tavakoli, Mitra; Malik, Imaan; Mansoor, Wasat; Malik, Rayaz Ahmed

    2015-01-01

    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. PMID:26430773

  17. Penetrating keratoplasty restoring vision in an unusual case of corneal opacity following exposure to Euphorbia latex.

    PubMed

    Dutta, Jayanta; Choudhury, Somnath; Lahiri, Kapildeb; Savale, Smruti; Banerjee, Monideepa; Datta, Himadri

    2015-10-01

    The milky sap of the Euphorbia plant is highly toxic and causes inflammation to the skin and eyes. Damage to the eye ranges from superficial epithelial defects, keratoconjunctivitis, mild to moderate corneal edema, anterior uveitis, Descemet membrane folds, raised intraocular pressure and rarely corneal opacity in severe untreated cases. Here we report a case of visual restoration by optical penetrating keratoplasty in a patient with severe corneal opacity following exposure to Euphorbia latex.

  18. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    SciTech Connect

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  19. Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema

    PubMed Central

    2010-01-01

    Background Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. Methods The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. Results The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. Conclusions It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in

  20. Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema.

    PubMed

    Maruyama, Hiroe; Sakamoto, Takashi; Araki, Yoko; Hara, Hideaki

    2010-06-23

    Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some

  1. Endotoxin treatment protects rats against ozone-induced lung edema: with evidence for the role of manganese superoxide dismutase

    SciTech Connect

    Rahman, I.; Massaro, D. )

    1992-03-01

    Ozone is a strong oxidizing agent that can cause lung damage and edema. There is evidence that it does so by causing peroxidation of membrane lipids. However, the elevation in lung activity of copper, zinc superoxide dismutase (Cu, ZnSOD), and manganese superoxide dismutase (MnSOD) during exposure to ozone suggests that increased production of superoxide could contribute to lung edema caused by ozone. This latter observation, and preliminary evidence that treatment of rats with endotoxin elevates lung activity of MnSOD without elevation of the activity of Cu, ZnSOD, catalase (CAT), or glutathione peroxidase (GP), led to the present study. We treated rats with endotoxin, exposed them to different concentrations of ozone, measured lung wet weight to dry weight ratio, thiobarbituric acid-reactive material (TBAR), and assayed lung tissue for Cu, ZnSOD, MnSOD, CAT, and GP activity. Our major findings are, (1) a strongly edemogenic concentration of ozone-lowered MnSOD activity; (2) endotoxin treatment of air-breathing rats did not decrease lipid peroxidation as indicated by the lung concentration of TBAR; (3) induction of increased MnSOD activity in lung by treatment with endotoxin was associated with virtually complete protection against an otherwise edemogenic concentration of ozone, with less lipid peroxidation, and with less loss of weight; and (4) this protection occurred without elevated Cu, ZnSOD, CAT, or GP activity.

  2. Involvement of the extrinsic and intrinsic pathways in ultraviolet B-induced apoptosis of corneal epithelial cells.

    PubMed

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

    2016-04-01

    The goal of this study was to elucidate the pathway by which UVB initiates efflux of K(+) and subsequently apoptosis in human corneal limbal epithelial (HCLE) cells. The initial focus of the study was on the extrinsic pathway involving Fas. HCLE cells transfected with Fas siRNA were exposed to 80-150 mJ/cm(2) UVB and incubated in culture medium with 5.5 mM K(+). Knockdown of Fas resulted in limited reduction in UVB-induced caspase-8 and -3 activity. Patch-clamp recordings showed no difference in UVB-induced normalized K(+) currents between Fas transfected and control cells. Knockdown of caspase-8 had no effect on the activation of caspase-3 following UVB exposure, while a caspase-8 inhibitor completely eliminated UVB activation of caspase-3. This suggests that caspase-8 is a robust enzyme, able to activate caspase-3 via residual caspase-8 present after knockdown, and that caspase-8 is directly involved in the UVB activation of caspase-3. Inhibition of caspase-9 significantly decreased the activation of caspases-8 and -3 in response to UVB. Knockdown of Apaf-1, required for activation of caspase-9, resulted in a significant reduction in UVB-induced activation of caspases-9, -8, and -3. Knockdown of Apaf-1 also inhibited intrinsic and UVB-induced levels of apoptosis, as determined by DNA fragmentation measured by TUNEL assay. In UVB exposed cultures treated with caspase-3 inhibitor, the percentage of apoptotic cells was reduced to control levels, confirming the necessity of caspase-3 activation in DNA fragmentation. The lack of effect of Fas knockdown on K(+) channel activation, as well as the limited effect on activation of caspases-8 and -3, strongly suggest that Fas and the extrinsic pathway is not of primary importance in the initiation of apoptosis in response to UVB in HCLE cells. Inhibition of caspase-8 and -3 activation following inhibition of caspase-9, as well as reduction in activation of caspases-9, -8, and -3 and DNA fragmentation in response to Apaf

  3. Quantitative Shotgun Proteomics of HD Induced Corneal Injury and Angiogenesis (Briefing Charts)

    DTIC Science & Technology

    2010-03-10

    Thermo-Finnigan LTQ XL High Performance Linear Ion Trap - Collision Induced Dissociation (CID) for generating peptide fragmentation - Pulsed Q...Quantitation CID Sequence Analysis Ratio 114:117 1.05:1.00 Quantitative Proteomics with Pulsed Q Dissociation and Collision Induced Dissociation Clearance... Dissociation (PQD) for generating more fragments and extending the low mass range Separate Layers / Lyse cells Digest Proteins Label with iTRAQ and

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

    PubMed

    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.

  5. Effect of siRNA‑induced inhibition of IL‑6 expression in rat cerebral gliocytes on cerebral edema following traumatic brain injury.

    PubMed

    Xu, Bin; Yu, Dong-Ming; Liu, Fu-Sheng

    2014-10-01

    The present study aimed to investigate the effect of RNA interference (RNAi) on the inhibition of interleukin (IL)‑6 expression in rat cerebral gliocytes in vitro and rat cerebral traumatic tissues in vivo, as well as the effect of RNAi on cerebral edema. pSUPER vectors containing IL‑6 small hairpin RNA (pSUPER‑IL‑6 1‑5) were designed, constructed and transfected into C6 rat glioma cells using cationic liposomes. ELISA was used to select the plasmid with the strongest interference effect. A freefall method was used to generate a rat brain injury model and rats were randomly divided into treatment, empty plasmid and control groups (n=14/group). IL‑6 levels, water content and sodium content were determined in the brain tissues at 24 and 72 h post‑injury. pSUPER‑IL‑6 was effectively transfected into C6 cells and was found to inhibit the expression of IL‑6 rather than IL‑8. The pSUPER‑IL‑6 1 vector was most effective in inducing RNAi. In vivo, IL‑6 levels were observed to be lowest in the interference group and there were statistically significant differences in water and sodium content among the experimental groups (P<0.05). RNAi was found to inhibit IL‑6 expression in vivo and in vitro in rat cerebral gliocytes, and the reduction of the IL‑6 levels was found to reduce post‑traumatic cerebral edema.

  6. Excipients of preservative-free latanoprost induced inflammatory response and cytotoxicity in immortalized human HCE-2 corneal epithelial cells

    PubMed Central

    Smedowski, Adrian; Paterno, Jussi J.; Toropainen, Elisa; Sinha, Debasish; Wylegala, Edward; Kaarniranta, Kai

    2014-01-01

    Various preservative-free eye drop formulations for glaucoma treatment have been marketed intending to decrease ocular surface side effects and improve tolerability. However, preservative-free eye drops including different solubilizers to dissolve the antiglaucoma drugs may induce detrimental effects in the eye. In this study, we exposed human corneal epithelial cells (HCE-2) for 1, 6, 12, 24 and 48 hours to the first preservative-free (PF) tafluprost (Taflotan®), the recently-launched preservative-free (PF) latanoprost (Monoprost®), preservative benzalkonium chloride (BAK) and the excipient macrogolglycerol hydroxystearate 40 (MGHS40) using dilutions 0.1%, 0.3%, 1.0%, 3.0% and 10.0% of the original products. The cells also were exposed to undiluted PF tafluprost and PF latanoprost once a day for 9 days. Cellular morphology was examined by light microscopy and cell proliferation by Ki-67 fluorescent staining with cell viability being determined by erythrosine staining and the release of lactate dehydrogenase (LDH). Mitochondrial metabolic activity was evaluated with the colorimetric MTT assay. The secretion of interleukin 6 (IL-6) was measured with ELISA. HCE-2 cells displayed no significant morphological changes after PF tafluprost treatment, but PF latanoprost caused clear cell loss. Moreover, PF latanoprost, BAK and MGHS40 evoked cellular damage and inflammation with increasing concentrations and time. Furthermore, undiluted daily PF latanoprost application significantly increased LDH release and IL-6 secretion as compared to PF tafluprost. MGHS40 was observed to be associated with the toxicity of PF latanoprost. Excipients in ocular drops should receive more attention in the future, since they seem to trigger similar detrimental effects in cells as preservatives. PMID:25530926

  7. Comparison of Surgically Induced Astigmatisms after Clear Corneal Incisions of Different Sizes

    PubMed Central

    Mohamed, Tarek; Fine, I. Howard

    2007-01-01

    Purpose This study was performed to assess efficiency and stability of astigmatic change by incision size after cataract surgery. Methods This work was designed as a retrospective, comparative, nonrandomized interventional study. A total of 121 cases of cataract surgery were reviewed in 98 patients performed by one surgeon at the Oregon Eye Institute in Eugene, OR, USA with 3-year follow-ups. All procedures were performed with the temporal approach of self-sealing incisions. The serial change in surgically induced astigmatisms were examined in all cases of three groups: Group A, cartridge injection of a foldable IOL through a 2.5 mm self-sealing incision; Group B, cartridge injection of a foldable IOL through a 3.0 mm self-sealing incision; Group C, cartridge injection of a foldable IOL through a 3.5 mm self-sealing incision. Keratometric data were obtained reoperatively, and 3 weeks, 3 months, 6 months, 9 months, 12 months, 24 months and 36 months postoperatively. Polar value analysis was performed to calculate the surgically induced astigmatism. Results The astigmatic change decreased over time in Group B (P<0.05). The other groups tended to remain in induced astigmatism. All groups showed anticlockwise torque at 3 weeks following surgery. Group B showed a decrease in deviation, but the other groups showed increases in their torque value at postoperative 12 months (P<0.05). Conclusions The 3.0 mm incision size correlated with the least surgically induced astigmatism. PMID:17460424

  8. Novel insights into phosgene-induced acute lung injury in rats: role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis.

    PubMed

    Li, Wenli; Liu, Fangfang; Wang, Chen; Truebel, Hubert; Pauluhn, Juergen

    2013-02-01

    Phosgene gas is a lower respiratory tract irritant. As such, it stimulates nociceptive vagal C-fiber-related reflexes in a dose-rate and concentration × exposure duration (C × t)-dependent manner. In rats, this reflex is characterized by extended apnea time periods, bradycardia, and hypothermia. Although inhalation exposures at nonlethal C × t products show rapid reversibility of reflexively induced changes in respiratory patterns, lethal C × t products seem to cause prolonged stimulation after discontinued exposure to phosgene. This observation has been taken as indirect evidence that phosgene-induced lethal lung edema is likely to be associated with a dysfunctional neurogenic control of cardiopulmonary and microvascular physiology. In order to verify this hypothesis, data from respiratory function measurements during and after the inhalation exposure to phosgene gas were compared with time-course measurements of cardiac function over 20 h post-phosgene exposure. These data were complemented by time-course analyses of nitric oxide (NO(e)) and carbon dioxide in exhaled breath, including time-dependent changes of extravasated protein in bronchoalveolar lavage fluid and hemoglobin in blood. The nitric oxidase synthetase inhibitors L-NAME and L-NIL were used to further elucidate the role of NO(e) in this type of acute lung injury and whether its analysis can serve as an early biomarker of pulmonary injury. Collectively, the sequence and time course of pathological events in phosgene-induced lung edema appear to suggest that overstimulated, continued sensorimotor vagal reflexes affect cardiopulmonary hemodynamics. A continued parasympathetic tone appears to be involved in this etiopathology.

  9. Functional role of PPARδ in corneal epithelial wound healing.

    PubMed

    Nakamura, Yoshikuni; Nakamura, Takahiro; Tarui, Takeshi; Inoue, Jun; Kinoshita, Shigeru

    2012-02-01

    The peroxisome proliferator-activated receptor (PPAR) δ is involved in tissue repair. In this study, we investigated the functional role of PPARδ in corneal epithelial wound healing. In an in vivo corneal wound-healing model, the changes of PPARδ expression in corneal epithelia were examined by immunofluorescence microscopy, and the effect of topical administrations of a PPARδ agonist on corneal wound healing was also evaluated. The inhibitory effect of a PPARδ agonist on the cytokine-induced death of human corneal epithelial cells was evaluated using a DNA fragmentation assay kit. The changes of PPARδ expression and epithelial cell death were also investigated using human corneoscleral tissues ex vivo. Our findings showed that PPARδ expression was temporally up-regulated in corneal epithelial cells during experimental wound healing and that topical administration of a PPARδ agonist significantly promoted the healing of experimental corneal epithelial wounds. In human corneal epithelial cells, up-regulation of PPARδ and DNA fragmentation was demonstrated by stimulation with cytokines, and the DNA fragmentation was significantly inhibited by pretreatment with a PPARδ agonist. By using human corneoscleral tissues ex vivo, PPARδ was up-regulated in both healthy corneal epithelia (during re-epithelialization) and diseased corneal epithelia. Inflammatory stimulation-induced corneal epithelial cell death was inhibited by pretreatment with a PPARδ agonist. These results strongly suggest that PPARδ is involved in the corneal epithelial wound healing. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2/3-driven actin polymerization.

    PubMed

    Maddugoda, Madhavi P; Stefani, Caroline; Gonzalez-Rodriguez, David; Saarikangas, Juha; Torrino, Stéphanie; Janel, Sebastien; Munro, Patrick; Doye, Anne; Prodon, François; Aurrand-Lions, Michel; Goossens, Pierre L; Lafont, Frank; Bassereau, Patricia; Lappalainen, Pekka; Brochard, Françoise; Lemichez, Emmanuel

    2011-11-17

    RhoA-inhibitory bacterial toxins, such as Staphylococcus aureus EDIN toxin, induce large transendothelial cell macroaperture (TEM) tunnels that rupture the host endothelium barrier and promote bacterial dissemination. Host cells repair these tunnels by extending actin-rich membrane waves from the TEM edges. We reveal that cyclic-AMP signaling produced by Bacillus anthracis edema toxin (ET) also induces TEM formation, which correlates with increased vascular permeability. We show that ET-induced TEM formation resembles liquid dewetting, a physical process of nucleation and growth of holes within a thin liquid film. We also identify the cellular mechanisms of tunnel closure and reveal that the I-BAR domain protein Missing in Metastasis (MIM) senses de novo membrane curvature generated by the TEM, accumulates at the TEM edge, and triggers Arp2/3-dependent actin polymerization, which induces actin-rich membrane waves that close the TEM. Thus, the balance between ET-induced TEM formation and resealing likely determines the integrity of the host endothelium barrier.

  11. Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells

    PubMed Central

    Li, Yanwei; Liu, Haifeng; Zeng, Wei; Wei, Jing

    2017-01-01

    An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner. We also found that edaravone could improve mitochondrial function in HCEpiCs by increasing the levels of ATP and mitochondrial membrane potential. MTT and LDH assays indicated that edaravone could attenuate hyperosmolarity-induced cell death. It was found that edaravone prevented apoptosis by decreasing the level of cleaved caspase-3, and attenuating the release of cytochrome C. Mechanistically, we found that edaravone augmented the expression of Nrf2 and its target genes, such as HO-1, GPx-1, and GCLC. PMID:28346481

  12. Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema.

    PubMed

    Li, Yuan-Yuan; Huang, Shyh-Shyun; Lee, Min-Min; Deng, Jeng-Shyan; Huang, Guan-Jhong

    2015-04-01

    Cardamonin is a chalcone isolated from Alpinia katsumadai. This study is aimed to evaluate treatment of cardamonin decreased the paw edema at the 5th hour after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT) and superoxide dismutase (SOD) in the anti-inflammatory test. We also demonstrated that cardamonin significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th hour after Carr injection. Cardamonin decreased the nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels on the serum level at the 5th hour after Carr injection. Western blotting revealed that cardamonin decreased Carr-induced inducible nitric oxide synthase (iNOS), cycloxyclase (COX-2), nuclear factor-κB (NF-κB) and MAPK [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), p38] expressions and increased heme oxygenase-1 (HO-1) expressions at the 5th hour in the edema paw. The anti-inflammatory mechanisms of cardamonin might be related to the decrease in the level of MDA, iNOS, COX-2, NF-κB, and MAPK and induction of the HO-1 expression in the edema paw via increasing the activities of CAT and SOD in the edema paw through the suppression of NO, TNF-α, IL-1β, and IL-6. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Inhibiting the effect of 90Sr-90Y ophthalmic applicators on rat corneal neovascularization induced by sutures

    PubMed Central

    Zhou, Hong-Yan; Wang, Shuang; Zhang, Hong; Wang, Ling; Zhang, Wen-Song

    2016-01-01

    AIM To investigate a practical technique used to inhibit corneal angiogenesis with a 90Sr-90Y ophthalmic applicator. METHODS A 90Sr-90Y ophthalmic applicator was detected with a radioactive nuclide application treatment healthy protection standard. The applicator used was produced through medical dosimetry research; it had a concave applicator add measured the applicator temperature, serviceable humidity range, applicator appearance status, applicator radiation homogeneity, radioautography, and radiological safety of the original applicator surface. A vessel model was established using newborn rats, with sutures around the corneal limbus. Corneal neovascularization (CNV) were observed with a slit lamp. The new vessel length and response area were measured. RESULTS Low-dose radiation can inhibit CNV after corneal sutures. The absorbed dose of the applicator (0.046 Gy/s) was safe for the treatment of it. The lengths of new vessels and the areas of new vessels were lower than the new born vessel rat group (P<0.01). CONCLUSION The optimal radiation dose emitting from the applicator can be safe and potentially used in humans. PMID:27672586

  14. Corneal response to rigid and hydrogel lenses during eye closure.

    PubMed

    O'Neal, M R; Polse, K A; Sarver, M D

    1984-07-01

    Corneal changes were monitored in 14 subjects following 3 hr of eye closure while wearing selected oxygen permeable rigid and hydrogel lenses. The mean increase in corneal thickness ranged from 82.5 to 29.5 microns for rigid lenses with oxygen transmissibilities (Dk/L) between 0.2 X 10(-9) and 57.0 X 10(-9) (cm/sec) (ml O2/ml X mmHg), respectively, and ranged from 82.5 to 23.5 microns for hydrogel lenses with Dk/L between 2.5 X 10(-9) and 70.0 X 10(-9) (cm/sec) (ml O2/ml X mmHg), respectively. No differences in the amount of swelling between rigid and hydrogel lenses of the same oxygen transmissibility were observed (t-test, P greater than 0.20). Combining the swelling data for both types of lenses shows that a minimum lens oxygen transmissibility of approximately 75 X 10(-9) (cm/sec) (ml O2/ml X mmHg) is necessary during eye closure to prevent contact lens induced edema. The estimated oxygen tension under a lens with this Dk/L value is 40 mmHg. Recovery of the cornea to baseline thickness follows a nonlinear time course, with the rate of dehydration decreasing as the cornea thins. For initial swelling of 40-54 microns, 55-69 microns, and 70 microns and above, the time to reach baseline thickness was 1.5, 2.0, and 2.5 hr, respectively. Effects on vision, corneal curvature, distortion, and epithelial integrity were not clinically significant during this short period of eye closure.

  15. Intrastromal Corneal Ring Implants for Corneal Thinning Disorders

    PubMed Central

    2009-01-01

    refractive surgeons. It involves creating tunnels in the corneal stroma to secure the implants either by a diamond knife or laser calibrated to an approximate depth of 70% of the cornea. Variable approaches have been employed by surgeons in selecting ring segment size, number and position. Generally, two segments of equal thickness are placed superiorly and inferiorly to manage symmetrical patterns of corneal thinning whereas one segment may be placed to manage asymmetric thinning patterns. Following implantation, the major safety concerns are for potential adverse events including corneal perforation, infection, corneal infiltrates, corneal neovascularization, ring migration and extrusion and corneal thinning. Technical results can be unsatisfactory for several reasons. Treatment may result in an over or under-correction of refraction and may induce astigmatism or asymmetry of the cornea. Progression of the corneal cone with corneal opacities is also invariably an indication for progression to corneal transplant. Other reasons for treatment failure or patient dissatisfaction include foreign body sensation, unsatisfactory visual quality with symptoms such as double vision, fluctuating vision, poor night vision or visual side effects related to ring edge or induced or unresolved astigmatism. Evidence-Based Analysis Methods The literature search strategy employed keywords and subject headings to capture the concepts of 1) intrastromal corneal rings and 2) corneal diseases, with a focus on keratoconus, astigmatism, and corneal ectasia. The initial search was run on April 17, 2008, and a final search was run on March 6, 2009 in the following databases: Ovid MEDLINE (1996 to February Week 4 2009), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2009 Week 10), OVID Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. Parallel search strategies were developed for the remaining databases

  16. Side Effects: Edema

    Cancer.gov

    Edema, a condition in which fluid builds up in your body’s tissues, may be caused by chemotherapy, cancer, and conditions not related to cancer. Learn about signs of edema, including swelling in your feet, ankles, and legs. Learn how prevent swelling.

  17. [Corneal manifestations in systemic diseases].

    PubMed

    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.

  18. Corneal Protection for Burn Patients

    DTIC Science & Technology

    2013-10-01

    corneal collagen as a treatment for keratoconus (1) indicating that it is a safe photosensitizer. The maximum percent inhibition using RF and blue light...Seiler (2003) Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus . Am J Ophthalmol, 135, 620-7. 2. Fujisato, T

  19. Corneal Protection for Burn Patients

    DTIC Science & Technology

    2010-07-01

    blue light. RF-5P with UVA irradiation has recently been used to crosslink corneal collagen as a treatment for keratoconus (2). Thus, RF-5P appears...induced collagen crosslinking for the treatment of keratoconus . American journal of ophthalmology. 2003 May;135(5):620-7. 3. McCall AS, Kraft S

  20. Corneal injury by bee sting with retained stinger--a case report.

    PubMed

    Chinwattanakul, Siriwan; Prabhasawat, Pinnita; Kongsap, Pipat

    2006-10-01

    To report a rare case of corneal injury by bee sting with its complication and management. A 3-year-old boy, who was attacked by a swarm of bees, was referred for the right eye's corneal ulcer evaluation. Two stingers were found and completely removed with jeweler forceps. Corneal epithelial defect, corneal edema, secondary bacterial keratitis, heterochromia iridis, and internal ophthalmoplegia were identified The corneal edema markedly improved 3 days after removing the retained bee stingers and treatment by topical antibiotics and steroids. The patient was evaluated after 1 week and 1 month and was found with permanent central corneal scar particularly at the area corresponding to the retained stinger The patient had subsequently localized traumatic anterior subcapsular cataract corresponding to where the stinger had penetrated the lens. Corneal bee sting injury is an uncommon ocular trauma, but can result in severe sight threatening complication. Even though the response of corneal edema is well inclined to topical steroid, awareness in adjusting the clinical treatment for the particular case needs a scrutinized investigation of the infection.

  1. Lamellar interface fluid accumulation following traumatic corneal perforation and laser in situ keratomileusis.

    PubMed

    Bushley, D Matthew; Holzinger, Karl A; Winkle, R Kevin; Le, Lam H; Olkowski, John D

    2005-06-01

    A 41-year-old man with myopic astigmatism had laser in situ keratomileusis (LASIK) in each eye in April 2002. Ten months later, he sustained a central perforating corneal injury to the right eye. One day following repair of the corneal wound, he presented with diffuse corneal epithelial microcystic edema, lamellar interface fluid accumulation, and 20/400 visual acuity. Additional sutures were placed to close a presumed posterior wound gape with complete resolution of the corneal edema and lamellar interface fluid collection. One year later, his best corrected visual acuity measured 20/20+ in the right eye. This case is the first to document lamellar interface fluid accumulation following LASIK owing to traumatic disruption of the corneal endothelium.

  2. Corneal ulcers in horses.

    PubMed

    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.

  3. Influence of corneal hydration on optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Twa, Michael D.; Vantipalli, Srilatha; Singh, Manmohan; Li, Jiasong; Larin, Kirill V.

    2016-03-01

    Corneal biomechanical properties are influenced by several factors, including intraocular pressure, corneal thickness, and viscoelastic responses. Corneal thickness is directly proportional to tissue hydration and can influence corneal stiffness, but there is no consensus on the magnitude or direction of this effect. We evaluated the influence of corneal hydration on dynamic surface deformation responses using optical coherence elastography (OCE). Fresh rabbit eyes (n=10) were prepared by removing the corneal epithelium and dropping with 0.9% saline every 5 minutes for 1 hour, followed by 20% dextran solution every 5 minutes for one hour. Corneal thickness was determined from structural OCT imaging and OCE measurements were performed at baseline and every 20 minutes thereafter. Micron-scale deformations were induced at the apex of the corneal tissue using a spatially-focused (150μm) short-duration (<1ms) air-pulse delivery system. These dynamic tissue responses were measured non-invasively with a phase-stabilized swept source OCT system. The tissue surface deformation response (Relaxation Rate: RR) was quantified as the time constant, over which stimulated tissue recovered from the maximum deformation amplitude. Elastic wave group velocity (GV) was also quantified and correlated with change in corneal thickness due to hydration process. Corneal thickness rapidly increased and remained constant following epithelium removal and changed little thereafter. Likewise, corneal stiffness changed little over the first hour and then decreased sharply after Dextran application (thickness: -46% [-315/682 μm] RR: - 24% [-0.7/2.88 ms-1]; GV: -19% [-0.6/3.2 m/s]). Corneal thickness and corneal stiffness (RR) were well correlated (R2 = .66). Corneal biomechanical properties are highly correlated with tissue hydration over a wide range of corneal thickness and these changes in corneal stiffness are quantifiable using OCE.

  4. Bilateral Keratoconus and Corneal Hydrops Associated with Eye Rubbing in a 7-year-old Girl

    PubMed Central

    Panahi-Bazaz, Mahmoud-Reza; Sharifipour, Farideh; Moghaddasi, Alireza

    2014-01-01

    Purpose To report a young child with bilateral keratoconus in the context of vernal keratoconjunctivitis (VKC) who developed bilateral corneal hydrops associated with eye rubbing, and to discuss the pathogenesis and review the pertinent literature. Case Report A seven-year-old girl with VKC and asymmetric keratoconus developed corneal hydrops due to habitual eye rubbing. Corneal edema subsided within 16 weeks in her right eye and 9 weeks in the left eye with subsequent corneal scarring. Conclusion Continuous mechanical trauma, such as eye rubbing, plays a significant role in the pathogenesis of keratoconus and subsequent hydrops even in childhood. PMID:24982739

  5. Corneal temperature in schizophrenia patients.

    PubMed

    Shiloh, Roni; Munitz, Hanan; Portuguese, Shirley; Gross-Isseroff, Ruth; Sigler, Mayanit; Bodinger, Liron; Katz, Nachum; Stryjer, Rafael; Hermesh, Haggai; Weizman, Abraham

    2005-12-01

    Most data imply that dopaminergic transmission is essential for proper hypothalamic-mediated core temperature regulation. Altered central dopaminergic transmission is suggested to be involved in the pathophysiology of schizophrenia. Thus, hypothetically, schizophrenia patients might be at increased risk of developing thermoregulatory dysregulation manifested by alterations in core temperature, as well as in peripheral tissue, the temperature of which has been shown to correlate with core temperature (e.g. cornea). Previous small pilot studies of ours showed that schizophrenia patients may exhibit corneal temperature abnormalities. Hence, we assessed corneal temperature in a controlled sample of drug-free ( n =11) and medicated ( n =28) schizophrenia patients compared to healthy comparison subjects ( n =9), using a FLIR thermal imaging camera. Drug-free schizophrenia patients exhibited significantly higher corneal temperature compared to healthy subjects, typical antipsychotic drug (APD)-treated patients ( n =16) and atypical APD-treated patients ( n =12) (37.08+/-1.46 degrees C vs. 33.37+/-2.51 degrees C, 31.08+/-1.43 degrees C and 31.67+/-0.44 degrees C respectively, p <0.0001; p <0.001 vs. each group separately). The healthy comparison subjects and the atypical APD-treated patients exhibited comparable corneal temperatures and these two groups exhibited higher corneal temperatures compared to the typical APD-treated patients ( p <0.01 and p =0.051 respectively). In conclusion, this study indicates that drug-free schizophrenia patients exhibit substantially higher corneal temperature compared to healthy comparison subjects or medicated patients, and that APDs may decrease corneal temperature either to normal (atypical APD) or to subnormal (typical APD) values. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying drug-induced corneal temperature alterations, the possible role of temperature-lowering drugs

  6. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    NASA Astrophysics Data System (ADS)

    Yue, Ning; Chen, Zhe; Nath, Ravinder

    2002-04-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125I and 103Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T) = Vp (1 + M exp(-0.693T/Te)) where Vp is the prostate volume before implantation, M is the edema magnitude and Te is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. Λg(r) αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125I and 103Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for 125I and 103Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for

  7. Corneal infection of herpes simplex virus type 2--induced neuronal apoptosis in the brain stem of mice with expression of tumor suppressor gene (p53) and transcription factors.

    PubMed

    Watanabe, D; Honda, T; Nishio, K; Tomita, Y; Sugiura, Y; Nishiyama, Y

    2000-12-01

    To understand the mechanism of neuronal apoptosis induced by herpes simplex virus (HSV) infection in vivo, the distribution of viral antigen, the appearance of apoptotic bodies, and the expressions of the tumor suppressor gene p53 and several transcription factors such as c-fos, c-jun and NF-kappaB were examined immunohistochemically and histopathologically after corneal infection of mice with HSV type 2 strain 186. Five days after HSV infection, viral antigen was diffusely detected in the corneal epithelium, the trigeminal ganglion and the pars caudalis of the spinal trigeminal nucleus. Neuronal apoptosis was observed in the brain stem ipsilateral to the HSV-infected side with the immunoreactivities of c-fos, c-jun, NF-kappaB and p53. Dual-labeling immunohistochemical studies revealed that almost all of the viral antigen-positive neurons and glia in the brain stem also showed p53 immunoreactivity. On the other hand, no neuronal apoptosis but only with the expression of c-jun was found in the trigeminal ganglion. Our results suggest that the different expression of transcription factors between the brain stem and the trigeminal ganglion may influence the neuronal apoptosis induced by HSV infection.

  8. Reexpansion pulmonary edema.

    PubMed

    Tarver, R D; Broderick, L S; Conces, D J

    1996-01-01

    Reexpansion pulmonary edema is a rare complication attending the rapid reexpansion of a chronically collapsed lung, such as occurs after evacuation of a large amount of air or fluid from the pleural space. The condition usually appears unexpectedly and dramatically-immediately or within 1 h in 64% of patients and within 24 h in the remainder. The clinical manifestations are varied; they range from roentgenographic findings alone in asymptomatic patients to severe cardiorespiratory insufficiency. The radiographic evidence of reexpansion pulmonary edema is a unilateral alveolar filling pattern, seen within a few hours of reexpansion of the lung. The edema may progress for 24-48 h and persist for 4-5 days. Human data on the pathophysiology of reexpansion pulmonary edema derive from small series of patients, case reports, and reviews of the literature. On the other hand, a larger body of data exists on experimental reexpansion pulmonary edema in cats, monkeys, rabbits, sheep, and goats. This review examines the clinical and experimental evidence for reexpansion pulmonary edema. In addition, we detail the historical background, clinical setting, treatment, and outcome of reexpansion pulmonary edema.

  9. Corneal transplant - discharge

    MedlinePlus

    ... 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 ...

  10. Subconjunctival injection of in vitro transforming growth factor-β-induced regulatory T cells prolongs allogeneic corneal graft survival in mice

    PubMed Central

    Xu, Qing; Tan, Xiaobo; Zhang, Yingnan; Jie, Ying; Pan, Zhiqiang

    2015-01-01

    This study is to investigate the effect of subconjunctival injection of in vitro induced regulatory T cells (iTregs) on the survival of corneal allografts. iTregs were expanded by culturing CD4+T cells with TGF-β in vitro. Foxp3, LAP and GARP were analyzed and the suppression ability of iTregs was assayed by co-culturing with effective T cells. Allogeneic transplantations in mice were modeled and randomly classified into PBS control, iTregs and TA groups. The allografts were observed for 60 days. CD25, Foxp3, LAP and GARP in CD4+T cells were analyzed on day 21 after the surgery. Inflammatory cells infiltrated in allografts were detected by flow cytometry and histopathological examination. Expressions of Foxp3, GARP and LAP in iTregs were high. iTregs suppressed the proliferation of effective T cells in vitro. The corneal allograft survival time for PBS, iTregs and TA groups was (18 ± 1.73) days, (38.6 ± 1.14) days and (60 ± 0) days, respectively. The corneal allograft survival time in iTregs group was significantly prolonged compared with PBS group (P < 0.05), but shorter than that in TA group (P < 0.05). No significant difference was observed in expressions of CD25, Foxp3, LAP or GARP in CD4+T cells (P > 0.05). Finally, CD3+CD4+T cell infiltration and fewer inflammatory cells were reduced in allografts in iTregs and TA groups compared with PBS group. The survival time of allografts were prolonged in mice after subconjunctival injection of iTregs. Local immune modulation might be involved in the mechanism. PMID:26884940

  11. Glycogen synthase kinase 3 activation is important for anthrax edema toxin-induced dendritic cell maturation and anthrax toxin receptor 2 expression in macrophages.

    PubMed

    Larabee, Jason L; Maldonado-Arocho, Francisco J; Pacheco, Sergio; France, Bryan; DeGiusti, Kevin; Shakir, Salika M; Bradley, Kenneth A; Ballard, Jimmy D

    2011-08-01

    Anthrax edema toxin (ET) is one of two binary toxins produced by Bacillus anthracis that contributes to the virulence of this pathogen. ET is an adenylate cyclase that generates high levels of cyclic AMP (cAMP), causing alterations in multiple host cell signaling pathways. We previously demonstrated that ET increases cell surface expression of the anthrax toxin receptors (ANTXR) in monocyte-derived cells and promotes dendritic cell (DC) migration toward the lymph node-homing chemokine MIP-3β. In this work, we sought to determine if glycogen synthase kinase 3 (GSK-3) is important for ET-induced modulation of macrophage and DC function. We demonstrate that inhibition of GSK-3 dampens ET-induced maturation and migration processes of monocyte-derived dendritic cells (MDDCs). Additional studies reveal that the ET-induced expression of ANTXR in macrophages was decreased when GSK-3 activity was disrupted with chemical inhibitors or with small interfering RNA (siRNA) targeting GSK-3. Further examination of the ET induction of ANTXR revealed that a dominant negative form of CREB could block the ET induction of ANTXR, suggesting that CREB or a related family member was involved in the upregulation of ANTXR. Because CREB and GSK-3 activity appeared to be important for ET-induced ANTXR expression, the impact of GSK-3 on ET-induced CREB activity was examined in RAW 264.7 cells possessing a CRE-luciferase reporter. As with ANTXR expression, the ET induction of the CRE reporter was decreased by reducing GSK-3 activity. These studies not only provide insight into host pathways targeted by ET but also shed light on interactions between GSK-3 and CREB pathways in host immune cells.

  12. Anti-inflammatory activities of Dangyuja (Citrus grandis Osbeck) in concanavalin A stimulated murine splenocytes and 12-O-tetradecanoylphorbol-13-acetate-induced murine skin edema.

    PubMed

    Herath, Kalahe Hewage Iresha Nadeeka Madushani; Bing, So Jin; Cho, Jinhee; Kim, Areum; Shin, Sumin; Kim, Gi-Ok; Lee, Jong-Chul; Jee, Youngheun

    2016-10-01

    Dangyuja (Citrus grandis Osbeck), a citrus cultivated in southern Korea, has been used in traditional medicine for its anti-inflammatory effect. In this study, we investigated the anti-inflammatory potential of extract of Citrus grandis Osbeck (ECGO). In in vitro assays, ECGO treatment of concanavalin A (10μg/ml, for 24h) stimulated splenocytes showed significant reduction in CD44/CD62L(+) T cell population and a marked decrease in the production of inflammatory cytokines IL-2, IFN-γ and IL-4. Interestingly, in vivo assays of ECGO topical treatment (100μg/20μl/ear) significantly mitigated the TPA (4μg/20μl/ear) induced edema induction and Myeloperoxidase activity. Anti-inflammatory potential of ECGO were further evidenced through its potent decrease in expression of inducible nitric oxide, cyclooxygenase-2, IL-1β and TNF-α and suppressed homing of CD3(+) T cells and F4/80(+) macrophages to site of inflammation. This study emphasizes the possibility of developing ECGO as an alternative natural topical agent to combat inflammatory diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Plasma-induced graft copolymerization of HEMA onto silicone rubber and TPX film improving rabbit corneal epithelial cell attachment and growth.

    PubMed

    Hsiue, G H; Lee, S D; Wang, C C; Shiue, M H; Chang, P C

    1994-02-01

    A poly(2-hydroxyethyl methacrylate) (pHEMA)-grafted polymer film was prepared by plasma-induced graft copolymerization onto an elastic material, silicone rubber, and a plastic material, poly(4-methyl-1-pentene) (TPX). The control, Ar plasma-treated and pHEMA-grafted silicone rubber and TPX surfaces were characterized by ESCA, FTIR-ATR, SEM and contact angle techniques. ESCA verified the respective chemical shift of control and Ar plasma-treated films. The presence of the grafted pHEMA was also verified by ESCA. The introduction of pHEMA onto a hydrophobic support provided an adequate surface for rabbit corneal epithelium cell attachment and growth. Cell attachment and growth onto these surfaces were examined by light microscopy. Cell attachment onto the control and Ar plasma-treated surfaces was negligible, while improved attachment and growth of rabbit corneal epithelium cells was demonstrated on the pHEMA-grafted polymeric surface. At 72 h, the pHEMA-grafted silicone rubber surface attached and grew more cells as compared with those on a pHEMA-grafted TPX surface. The pHEMA-grafted silicone rubber surface demonstrated a confluent cell layer after 72 h.

  14. Progress in corneal wound healing

    PubMed Central

    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

  15. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10.

    PubMed

    Nickols, Jordan; Obiako, Boniface; Ramila, K C; Putinta, Kevin; Schilling, Sarah; Sayner, Sarah L

    2015-12-15

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. Copyright © 2015 the American Physiological Society.

  16. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10

    PubMed Central

    Nickols, Jordan; Obiako, Boniface; Ramila, K. C.; Putinta, Kevin; Schilling, Sarah

    2015-01-01

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. PMID:26475732

  17. PERSISTENT CORNEAL EPITHELIAL DEFECT AFTER PARS PLANA VITRECTOMY.

    PubMed

    Chen, Hsi-Fu; Yeung, Ling; Yang, Ko-Jen; Sun, Chi-Chin

    2016-01-01

    To investigate the incidence, risk factors, and clinical course of persistent corneal epithelial defects (PCED) after pars plana vitrectomy (PPV). The charts of 426 consecutive patients (511 eyes) who received PPV from January 2008 to December 2011 were reviewed. Corneal complications were defined as the presence of corneal epithelial defects, corneal edema, or superficial punctate keratopathy at least 1 week after vitrectomy. The PCED was defined as corneal epithelial defects lasting longer than 2 weeks after vitrectomy despite conventional treatment. The demographic, preoperative, intraoperative, and postoperative data were compared between PCED and non-PCED corneal complication groups to evaluate the risk factors and clinical outcomes. Postoperative corneal complications developed in 103 of 460 (22.4%) eyes. Diabetes was associated with postoperative corneal epithelial defects (P = 0.021) and superficial punctate keratopathy (P = 0.022) but not corneal edema (P = 0.925). Among 103 eyes with corneal complications, 21 eyes developed PCED. The eyes with PCED had poor final visual acuity, with 23.8% (5/21) of the eyes in the PCED group having visual acuity of 20/200 or better compared with 51.2% (42/82) of the eyes in the non-PCED group (P = 0.024). Logistic regression analysis demonstrated that diabetes mellitus (P = 0.025), use of perfluoropropane (P = 0.001), and assistance of a first-year resident (P = 0.029) were statistically significant risk factors for PCED after PPV. There was also a high incidence of geographic herpes simplex virus epithelial keratitis among recalcitrant PCEDs lasting longer than 4 weeks (36%, 4/11 eyes). The overall incidence of PCED after PPV was 4.8%. Diabetes mellitus, intravitreal tamponade with perfluoropropane, and assistance of a first-year resident were risk factors for PCED after PPV. Persistent corneal epithelial defects after PPV were correlated with poor postoperative visual outcomes. Early and aggressive management is

  18. Longitudinal evaluation of central corneal thickness in congenital glaucoma.

    PubMed

    Paletta Guedes, R A; Pena, A B; Paletta Guedes, V M; Chaoubah, A

    2016-10-01

    To assess the central corneal thickness in primary congenital glaucoma before and after surgical treatment and compare it with a normal population. We conducted a longitudinal analysis of primary congenital glaucoma patients, in whom we measured central corneal thickness before and after treatment (Group 1). We compared our results with a normal population (Group 2), who underwent ophthalmological examination under anesthesia for other reasons. Mean age (months) in Group 1 (N=23) and Group 2 (N=40) at the time of the first exam was 5.5 and 9.2 (P=0.004), respectively. Mean central corneal thickness (microns) in Group 1 was: 663 before treatment and 557 after treatment (P<0.001). In Group 2, mean central corneal thickness (microns) was 551. Comparisons show statistical difference between mean values before and after treatment (P<0.001), but not between post-treatment CCT mean values in Group 1 and mean CCT values in Group 2 (P=0.627). In primary congenital glaucoma, central corneal thickness values show unique peculiarities. They are higher than normal before treatment (thicker corneas), due to corneal edema caused by elevated intraocular pressure. After surgical treatment, central corneal thickness measurements decrease toward the mean values for the normal population. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Aspergillus terreus recovered from a corneal scraping.

    PubMed

    Campbell, Suzanne

    2014-01-01

    A 52 year old, healthy male presented to his optometrist complaining of redness and irritation in the right eye. A foreign body was removed from the eye. The patient was started on ophthalmic solutions of vigamox and systane. At 48 hours, the patient reported increased redness, limited vision, and yellow discharge from the eye. The patient was referred to an ophthalmologist for further evaluation. Physical assessment revealed a superlative central infiltrate (extreme, centrally located injury that had permeated the cornea), diffuse corneal haze, and edema with a 3- to 4+ conjunctival injection and a 1 millimeter hypopyon (an effusion of pus into the anterior chamber of the eye). Corneal scrapings were collected for aerobic and anaerobic bacterial and fungal cultures. The patient was then prescribed. vancomycin, tobramycin, and natamycin ophthalmic eyedrops. On day three, fungal culture results indicated possible fungal forms seen. On day 12, results from the fungal culture of the corneal scraping revealed the causative agent to be Aspergillus terreus. Voriconazole eyedrops were added to the treatment regimen and continued for 10 weeks. The physician order for a fungal culture as well as laboratory data providing the final identification of Aspergillus terreus and laboratory comments indicating an elevated minimum inhibitory concentration (MIC) (> 2 microg/mL) to amphotericin B is associated with treatment failure positively impacted the patient outcome. After completion of the treatment regimen, a photo-therapeutic keratectomy (PTK) was performed in an attempt to remove the dense corneal scarring caused by the fungal infection.

  20. Management of Corneal Bee Sting Injuries.

    PubMed

    Rai, Ruju R; Gonzalez-Gonzalez, Luis A; Papakostas, Thanos D; Siracuse-Lee, Donna; Dunphy, Robert; Fanciullo, Lisa; Cakiner-Egilmez, Tulay; Daly, Mary K

    2017-01-01

    To review the management of keratitis after corneal bee stings and to report a case of deep stromal corneal infiltrate secondary to a retained bee stinger managed conservatively in a patient who presented three days after unsanitary manipulation of the stinger apparatus. Case report and review of literature. A 57-year-old male beekeeper was evaluated for pain, blurry vision, and photosensitivity after a corneal bee sting. Of note, the venom sac had been removed with dirty tweezers three days prior to his visit. On exam, a focal infiltrate with diffuse edema was seen surrounding a retained bee stinger in the peripheral cornea. Trace cells in the anterior chamber were also noted. Based on a high suspicion for infectious keratitis, a conservative treatment strategy was elected. Administration of broad-spectrum topical antibiotics with concomitant abstention of corticosteroids led to rapid resolution of the symptoms. Over 16 months of follow-up, the stinger has remained in situ without migration and the patient has maintained 20/20 visual acuity without complications. There is debate on the preferred method for the management of corneal injury secondary to bee stings, especially when it is associated with a retained stinger. We herein present our findings in our appraisal of reported cases. In the aftermath of an ocular bee sting, close surveillance for inflammation and infection is essential. Individual manifestations of these injuries vary in timing, type, and severity; therefore, the accessibility of the stinger and the evolving clinical picture should guide therapeutic decisions.

  1. Intraneural edema following exposure to vibration.

    PubMed

    Lundborg, G; Dahlin, L B; Danielsen, N; Hansson, H A; Necking, L E; Pyykkö, I

    1987-08-01

    Peripheral neuropathy represents a well-known complication from long-term exposure to vibration. In the present study an experimental model is presented with the purpose of analyzing the formation of intraneural edema following vibration exposure. Vibration (82 Hz, peak-to-peak amplitude 0.21 mm) was induced in the hind limb of rats by the use of vibrating electric motors during 4 h/d for 5 d. Tracer techniques (with albumin Evans blue and horseradish peroxidase) were used to study the permeability of intraneural microvessels after the vibration exposure on day 5. It was found that the vibration trauma in this model induced epineurial edema in the sciatic nerve. It is hypothesized that the formation of intraneural edema may be an important pathophysiological factor in the occurrence of vibration-induced neuropathy.

  2. Proton nuclear magnetic resonance studies on brain edema

    SciTech Connect

    Naruse, S.; Horikawa, Y.; Tanaka, C.; Hirakawa, K.; Nishikawa, H.; Yoshizaki, K.

    1982-06-01

    The water in normal and edematous brain tissues of rats was studied by the pulse nuclear magnetic resonance (NMR) technique, measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). In the normal brain, T1 and T2 were single components, both shorter than in pure water. Prolongation and separation of T2 into two components, one fast and one slow, were the characteristic findings in brain edema induced by both cold injury and triethyl tin (TET), although some differences between the two types of edema existed in the content of the lesion and in the degree of changes in T1 and T2 values. Quantitative analysis of T1 and T2 values in their time course relating to water content demonstrated that prolongation of T1 referred to the volume of increased water in tissues examined, and that two phases of T2 reflected the distribution and the content of the edema fluid. From the analysis of the slow component of T2 versus water content during edema formation, it was demonstrated that the increase in edema fluid was steady, and its content was constant during formation of TET-induced edema. On the contrary, during the formation of cold-injury edema, water-rich edema fluid increased during the initial few hours, and protein-rich edema fluid increased thereafter. It was concluded that proton NMR relaxation time measurements may provide new understanding in the field of brain edema research.

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

    PubMed Central

    Piñero, David P; Camps, Vicente J; Ramón, María L; Mateo, Verónica; Pérez-Cambrodí, Rafael J

    2015-01-01

    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 (PIOLadj) based on Gaussian optics considering the residual refractive error was done using a variable keratometric index value (nkadj) for corneal power estimation with and without using an estimation algorithm for ELP obtained by multiple regression analysis (ELPadj). PIOLadj was compared to the real IOL power implanted (PIOLReal, 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 PIOLReal and PIOLadj when ELPadj was used (P = 0.10), with a range of agreement between calculations of 1.23 D. In contrast, PIOLReal was significantly higher when compared to PIOLadj without using ELPadj 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. PMID:26139807

  4. Acute vasogenic edema induced by thrombosis of a giant intracranial aneurysm: a cause of pseudostroke after therapeutic occlusion of the parent vessel.

    PubMed

    Hammoud, Dima; Gailloud, Philippe; Olivi, Alessandro; Murphy, Kieran J

    2003-01-01

    A 16-year-old male adolescent presenting with acute retro-orbital pain underwent emergent internal carotid occlusion for a giant cavernous aneurysm. Three weeks later, the patient complained of headache and right hemiparesis, which suggested an acute stroke. CT and MR imaging revealed vasogenic brain edema without infarct. The symptoms rapidly resolved with steroid therapy. Follow-up CT showed resolution of the edema. The imaging characteristics, clinical implications, and etiology of vasogenic edema occurring after thrombosis of a giant intracranial aneurysm are discussed.

  5. Biomechanics of Corneal Ring Implants

    PubMed Central

    2015-01-01

    Purpose: To evaluate the biomechanics of corneal ring implants by providing a related mathematical theory and biomechanical model for the treatment of myopia and keratoconus. Methods: The spherical dome model considers the inhomogeneity of the tunica of the eye, dimensions of the cornea, lamellar structure of the corneal stroma, and asphericity of the cornea. It is used in this study for calculating a strengthening factor sf for the characterization of different ring-shaped corneal implant designs. The strengthening factor is a measure of the amount of strengthening of the cornea induced by the implant. Results: For ring segments and incomplete rings, sf = 1.0, which indicates that these implants are not able to strengthen the cornea. The intracorneal continuous complete ring (MyoRing) has a strengthening factor of up to sf = 3.2. The MyoRing is, therefore, able to strengthen the cornea significantly. Conclusions: The result of the presented biomechanical analysis of different ring-shaped corneal implant designs can explain the different postoperative clinical results of different implant types in myopia and keratoconus. PMID:26312619

  6. Aronia melanocarpa Concentrate Ameliorates Pro-Inflammatory Responses in HaCaT Keratinocytes and 12-O-Tetradecanoylphorbol-13-Acetate-Induced Ear Edema in Mice.

    PubMed

    Goh, Ah Ra; Youn, Gi Soo; Yoo, Ki-Yeon; Won, Moo Ho; Han, Sang-Zin; Lim, Soon Sung; Lee, Keun Wook; Choi, Soo Young; Park, Jinseu

    2016-07-01

    Abnormal expression of pro-inflammatory mediators such as cell adhesion molecules and cytokines has been implicated in various inflammatory skin diseases, including atopic dermatitis. In this study, we investigated the anti-inflammatory activity of Aronia melanocarpa concentrate (AC) and its action mechanisms using in vivo and in vitro skin inflammation models. Topical application of AC on mouse ears significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema formation, as judged by measuring ear thickness and weight, and histological analysis. Topical administration of AC also reduced the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in TPA-stimulated mouse ears. Pretreatment with AC suppressed TNF-α-induced ICAM-I expression and subsequent monocyte adhesiveness in human keratinocyte cell line HaCaT. In addition, AC significantly decreased intracellular reactive oxygen species (ROS) generation as well as mitogen-activated protein kinase (MAPK) activation in TNF-α-stimulated HaCaT cells. AC and its constituent cyanidin 3-glucoside also attenuated TNF-α-induced IKK activation, IκB degradation, p65 phosphorylation/nuclear translocation, and p65 DNA binding activity in HaCaT cells. Overall, our results indicate that AC exerts anti-inflammatory activities by inhibiting expression of pro-inflammatory mediators in vitro and in vivo possibly through suppression of ROS-MAPK-NF-κB signaling pathways. Therefore, AC may be developed as a therapeutic agent to treat various inflammatory skin diseases.

  7. Corneal Equilibrium Flux as a Function of Corneal Surface Oxygen Tension.

    PubMed

    Compañ, Vicente; Aguilella-Arzo, Marcel; Weissman, Barry A

    2017-06-01

    Oxygen is essential for aerobic mammalian cell physiology. Oxygen tension (PO2) should reach a minimum at some position within the corneal stroma, and oxygen flux should be zero, by definition, at this point as well. We found the locations and magnitudes of this "corneal equilibrium flux" (xmin) and explored its physiological implications. We used an application of the Monod kinetic model to calculate xmin for normal human cornea as anterior surface PO2 changes from 155 to 20 mmHg. We find that xmin deepens, broadens, and advances from 1.25 μm above the endothelial-aqueous humor surface toward the epithelium (reaching a position 320 μm above the endothelial-aqueous humor surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg. Our model supports an anterior corneal oxygen flux of 9 μL O2 · cm · h and an epithelial oxygen consumption of approximately 4 μL O2 · cm · h. Only at the highest anterior corneal PO2 does our model predict that oxygen diffuses all the way through the cornea to perhaps reach the anterior chamber. Of most interest, corneal oxygen consumption should be supported down to a corneal surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the critical oxygen tension for hypoxia induced corneal swelling is more likely this range rather than a fixed value.

  8. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

    PubMed Central

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

    2014-01-01

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  9. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    PubMed

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. Copyright © 2014 the American Physiological Society.

  10. Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.

    PubMed

    Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

    2014-05-01

    Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.

  11. Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

    PubMed

    Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

    2014-07-15

    Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractio