bluuebunny/crossref_metadata_2025 huggingface dataset:
Greek Brief Pain Inventory: Validation and Utility in Cancer Pain
Authors: Mystakidou Kyriaki , Mendoza Tito , Tsilika Eleni , Befon Sofia , Parpa Efi , Bellos George , Vlahos Lambros , Cleeland Charles
Published: April 2003

Objective: The Brief Pain Inventory (BPI) is a pain assessment tool. It has been translated into and validated in several languages. The purpose of this study was the translation into and validation of the BPI in Greek. Moreover, we wanted to detect cultural and social differences, if any, of pain interference in patients’ lives. Methods: The translation and validation of the inventory took place at the Areteion Hospital. The final validation sample consisted of 220 cancer patients (123 males, 97 females, age range 21–87 years, mean age 61.3). Primary cancer locations were lung 25.6%, gastrointestinal tract 25.6%, breast 11.5%, prostate 7.07%, gynecological cancers 9.6% and others 20.57%. The patients themselves completed the majority of the Greek BPI (G-BPI) papers. The pain management index (PMI) was also calculated in order to assess the adequacy of pain treatment. Assessing the reliability and the validity made the actual validation of the G-BPI. Results: Pain severity and pain management: 147 patients reported severe pain, 48 patients moderate, and 25 patients mild pain (mean average pain 6.22). From these patients only 21 were found on strong and 33 on weak opioid treatment, while 166 patients were found on no opioid analgesic treatment. In agreement with these data is the PMI which was positive only for 9 patients, while 44 patients had PMI = 0 and all the others had negative PMI scores. Reliability and Validity of the G-BPI: Coefficient alphas were 0.849 for the interference items and 0.887 for the severity items. Additionally, the factor analysis of the G-BPI items results in a two-factor solution, that satisfies the criteria of reproducibility, interpretability and confirmatory setting. Conclusion: This study shows the efficacy of the G-BPI for the assessment of pain severity as well as the pain management in Greece, and therefore its utility in improving the analgesic treatment outcome in Greek patients.
Combined Treatment with High-Dose Methotrexate, Vincristine and Procarbazine, without Intrathecal Chemotherapy, Followed by Consolidation Radiotherapy for Primary Central Nervous System Lymphoma in Immunocompetent Patients
Authors: Ferreri Andrés J.M. , Reni Michele , Dell’Oro Stefania , Ciceri Fabio , Bernardi Massimo , Camba Lionello , Ponzoni Maurilio , Terreni Maria Rosa , Tomirotti Maurizio , Spina Michele , Villa Eugenio
Published: April 2003

Objectives: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. Methods: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age ≤70, ECOG performance status ≤3, HIV-negative and no prior treatment. Thirteen patients (1996–1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1–14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. Results: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. Conclusions: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.
Ultrasound Biomicroscopy in the Assessment of Penetrating or Blunt Anterior-Chamber Trauma
Authors: Genovesi-Ebert F. , Rizzo S. , Chiellini S. , Romani A. , Gabbriellini G. , Sartini M.S. , Nardi M.
Published: April 2003

Ultrasound biomicroscopy (UBM) was employed in the assessment of the anterior chamber in patients affected by penetrating and blunt traumas. UBM detected correctly the extent and the localization of penetrating injuries and the presence of foreign bodies, IOL dislocation, and angular structures or ciliary body damages.
Congenital Retinoblastoma: Appearance of Calcifications during Short-Term Follow-Up
Authors: Gallenga P.E. , Mancini A. , Di Bastiano W. , Colangelo L. , Carpineto P. , Lobefalo L.
Published: April 2003

An echographic follow-up of a case of congenital retinoblastoma was performed by monitoring variations in the tumoral echostructure concomitant with the appearance of microcalcifications. A previously unreported echographic aspect regarding the first phase of observation is described. The calcifications in the tumour were evidenced on the 41st day of the patient’s life.
Echographic Follow-Up in Patients Who Have Undergone Sclero-Uveotumorectomy
Authors: Sabetti Lelio , Specchia Giuseppe , Toscano Andrea , Balestrazzi Emilio
Published: April 2003

A-B scan echography provides accurate information on the location, the nature, the extension of a neoplasm and the involvement of neighbouring tissues as well as on the postsurgical evolution. In this study, we intend to give accurate and useful indications to the surgeon concerning conservative surgery and the follow-up after sclero-uveotumorectomy in cases of uveal neoformations. Between January 1988 and June 1996, we examined 46 patients by means of echography before and after sclero-uveotumorectomy.
Dynamic Magnetic Resonance Imaging of the Levator palpebrae superioris Muscle
Authors: Ettl Armin , Daxer Albert , Priglinger Siegfried , Kramer Josef , Koornneef Leo
Published: April 2003

The relationship between upper lid elevation (h) and shortening (s) of the levator palpebrae superioris muscle (LPS) has an influence on the dose-response relationship in ptosis surgery. In order to investigate the relationship between upper lid elevation and shortening of the LPS, parasagittal T1-weighted MR images of the orbit were obtained in healthy subjects with the eye in down- and upgaze. The position of the upper lid margin and the length of the LPS were measured in the images in down- and upgaze and the amount of h and s was determined. For a mean (± SD) vertical upper lid elevation of 15 ± 1 mm, the mean (± SD) shortening of the LPS muscle was 21 ± 3 mm (n = 4). The mean ratio of h:s was calculated to be 1:1.4, which means that the levator muscle must contract by 1.4 cm in order to achieve a lid elevation of 1 cm. Therefore, the force of the LPS which is necessary to lift the upper eyelid can be smaller than the lid-closing force. This strongly suggests a physiological mechanism which reduces the muscle force necessary for lifting the upper eyelid.
Does Light Stimulus at Eye Opening of the Developing Rat Influence Retinal Expression of GTP-Binding Protein (Go)?
Authors: Oguni Masami , Shinohara Haruo , Asano Tomiko , Kato Kanefusa , Setogawa Tomoichi
Published: April 2003

We previously hypothesized that light stimulus at eye opening of rats on postnatal days (P) 13 or 14 has an effect on the expression of GTP-binding proteins (Go in the retina) because the concentration of Goα increased rapidly between P10 and P15. This hypothesis was also supported by the findings that the distribution of Goα in the retina was almost the same as that of adult rats between P10 and P15. In this study, pregnant rats were kept in a dark room after vaginal plugs were identified; they gave birth to their pups in the dark, and their pups were reared by their mothers in the dark. The postnatal rats were sacrificed at P10, P15, P18, P22, P24, P27, and P30. Their retinas were investigated immunochemically and immunohistochemically, using Goα antibody, and these results were compared with those of the rat pups reared normally. Only Goα immunoreactivity in the inner nuclear layer of rats reared in the dark room was weaker than in the controls; the distribution of Goα in the retina did not change, as compared with pups reared in normal conditions. In addition, in pups reared in the dark, Goα increased rapidly from P10 to P15. However, the concentration of Goα in the retina of rat pups reared in the dark was significantly low at P22 (p < 0.01) and P30 (p < 0.05), as compared with pups reared in normal conditions. Although the function of Go in the retina may have something to do with the light stimulus after eye opening, it appeared that the expression of Go was not influenced by light stimulus at eye opening.
Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress
Authors: Andersson Madeleine , Sjöstrand Johan , Petersen Anne , Karlsson Jan-Olof
Published: April 2003

The purpose of this study was to examine changes in calcium-dependent proteolytic activity in the lens epithelium from whole rabbit lenses exposed to long-term oxidative stress at near physiological levels. Rabbit lenses, incubated in 50 µM H2O2 for 1 or 24 h, were checked for clarity and morphological changes in the epithelium. Proteolytic activity was measured in the epithelium using a fluorogenic synthetic substrate; N-succinyl-Leu-Tyr-7-amino-4-methylcoumarin, both in the presence and the absence of calcium (1 mM Ca2+ and 5 mM EDTA respectively). The effect on transparency and morphology of the epithelium following a 1-hour incubation in 100 µM H2O2 was also studied. Lenses incubated in 50 µM H2O2 were clear even after 24 h. After a 1-hour incubation in 50 µM H2O2 the epithelium of the exposed lens appeared normal. However, after 24 h the epithelium cells appeared swollen and microscopical examination showed extensive intracellular and subepithelial vacuolization. Incubation in 100 µM H2O2 for 1 h caused loss of transparency; vacuole formation, globulization of the superficial lens fibers and death of the epithelial cells. There was a 55% increase in calcium-dependent proteolytic activity after 1 h in 50 µM H2O2, implying a role for the calcium-activated protease calpain in oxidatively induced cataract.
Secretion of Cytokines by Human Choroidal Melanoma Cells and Skin Melanoma Cell Lines in vitro
Authors: Enzmann Volker , Faude Frank , Kohen Leon , Wiedemann Peter
Published: April 2003

The selective secretion of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), basic fibroblast growth factor (b-FGF) and transforming growth factor beta 1 (TGFβ-1) in tissue culture of choroidal melanomas and two established skin melanoma cell lines was investigated with ELISA analysis. Values of choroidal melanoma cells were compared with the melanoma cell lines and human fibroblasts as a physiological control. High secretion of IL-6 was detectable in choroidal melanoma cultures but not in the cell lines. IL-8 secretion was found in all melanoma cultures. However, IL-10 was only secreted by one skin melanoma cell line and in choroidal melanoma cell cultures. B-FGF secretion by choroidal melanomas was higher than by cell lines. No differences were seen in the amounts of TGFβ-1 produced by melanoma cells. Human fibroblasts produce higher amounts of IL-6 and IL-8 but lower of b-FGF in vitro in contrast to the melanoma cells. The secretion of cytokines by choroidal melanoma cells suggests an important role of these soluble factors in the interaction of tumour and healthy tissue.
Ultrastructural Study of the Conjunctival Epithelium in the Mongolian Gerbil (Meriones unguiculatus)
Authors: Micali Antonio , Puzzolo Domenico , Pisani Antonina , Arco Alba M. , Bruschetta Daniele , Santoro Giuseppe , Aragona Pasquale
Published: April 2003

The conjunctival epithelium of the Mongolian gerbil (Meriones unguiculatus) was studied using the transmission and scanning electron microscopy. The superficial cells of the conjunctival epithelium were isoprismatic in shape and were covered, on their luminal surface, with microplicae. They were connected with the adjacent cells by junctional complexes and desmosomes. Some of the superficial cells were partially or completely detached from the underlying intermediate cells: this morphological pattern was interpreted as an expression of cellular renewal of the conjunctival surface. Goblet cells were either isolated or gathered in clusters: in any case, they were firmly connected with the adjacent epithelial cells. The apical part of the goblet cells was covered with a great number of long microvilli: they showed a variety of morphological aspects, which were interpreted as occurring in a sequential pattern during the secretory process. The Mongolian gerbil can be considered among the laboratory animals used for ophthalmic research.
Regulatory Effects of Soluble Growth Factors on Choriocapillaris Endothelial Growth and Survival
Authors: Liu Xipu , Ye Xiaodan , Yanoff Myron , Li Weiye
Published: April 2003

The effects of soluble growth factors on regulating the survival and growth of choriocapillaris endothelial (CCE) cells were investigated in vitro. CCE cells were cultured in a serum-free medium in the presence or absence of various soluble growth factors. Cell growth and cell viability were assessed by counting viable cells. Results showed that acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) significantly stimulated CCE growth in a dose-dependent manner. Platelet-derived growth factor BB (PDGF, 0.4–10 ng/ml), insulin-like growth factor (IGF, 0.4–10 ng/ml) or insulin (0.4–10 µg/ml) alone did not affect the growth of CCE cells. In the presence of insulin (10 µg/ml), however, PDGF stimulated CCE growth in a dose-dependent manner. By contrast, transforming growth factor β1 (TGF-β1) induced CCE death in the absence of other growth factors and inhibited the CCE growth induced by aFGF, bFGF or VEGF. When CCE cells had been cultured in media containing aFGF, bFGF, VEGF or the combination of PDGF and insulin for 48 h, withdrawal of aFGF, bFGF or VEGF, but not PDGF, from the media resulted in CCE death. The CCE death induced by either an introduction of TGF-β1 or withdrawal of aFGF, bFGF or VEGF was defined as apoptosis based on morphologic characteristics (condensation and fragmentation of nuclei, shrinkage of cells in size) and DNA fragmentation in multiples of approximately 180 base pairs. Phorbol 12-myristate 13-acetate (PMA, 2 or 5 nM) protected CCE cells against apoptosis induced by the introduction of TGF-β1 and withdrawal of aFGF, bFGF or VEGF, while H7 (50 µM), but not HA1004 (50 µM), abrogated the protective effect of PMA on CCE apoptosis. However, cycloheximide (0.1 µM), a protein synthesis inhibitor, was only effective to protect CCE cells from apoptosis induced by aFGF, bFGF or VEGF withdrawal, but not that induced by the introduction of TGF-β1. Moreover, cycloheximide and a low concentration of PMA (2 nM) showed an additive effect on protecting CCE cells from apoptosis as the result of a growth factor withdrawal. These data may suggest that some growth factors, such as aFGF, bFGF, VEGF and TGF-β1, play a more critical role than the others, such as PDGF and IGF, in the regulation of CCE growth and survival. CCE apoptosis as a result of withdrawal of a survival factor or of receiving a death factor such as TGF-β1 may involve different mechanisms, which merits further study.
Upregulation of Retinal Vascular Endothelial Growth Factor mRNAs in Spontaneously Diabetic Rats without Ophthalmoscopic Retinopathy
Authors: Segawa Yasunori , Shirao Yutaka , Yamagishi Sho-ichi , Higashide Tomomi , Kobayashi Miho , Katsuno Kenji , Iyobe Akira , Harada Hiromu , Sato Fumiyasu , Miyata Hiroshi , Asai Hiroshi , Nishimura Akira , Takahira Masayuki , Souno Tsutomu , Segawa Youji , Maeda Kazuhiko , Shima Kenji , Mizuno Akira , Yamamoto Hiroshi , Kawasaki Kazuo
Published: April 2003

Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.
The Glutathione Content of Retinal Müller (Glial) Cells: The Effects of Aging and of Application of Free-Radical Scavengers
Authors: Paasche Gerrit , Huster Dominik , Reichenbach Andreas
Published: April 2003

The dependence of intracellular glutathione (GSH), an important radical scavenger, on aging with or without externally applied Ginkgo biloba extract EGb 761, another established radical scavenger, was studied in guinea pig Müller (retinal glial) cells by using the fluorescent dye monochlorobimane. The GSH content of freshly dissociated cells from untreated aged animals was significantly lower than that of young controls; most of this reduction was prevented by application of EGb 761. Culturing the cells in amino-acid-free Ringer’s solution for 7 h caused a loss of up to 50% of the initial GSH content. When the culture medium contained 100 µM glutamate and 100 µM cystine, ongoing GSH synthesis counteracted the loss of GSH. The rates of net GSH synthesis were equal for the two groups of aged animals but significantly higher for cells from young controls. It is concluded that externally applied radical scavengers may enhance the protective glutathione ‘reserve’ of Müller cells in cases of neuronal degeneration.
Laminin Heterogeneity around Schlemm’s Canal in Normal Humans and Glaucoma Patients
Authors: Dietlein T.S. , Jacobi P.C. , Paulsson M. , Smyth N. , Krieglstein G.K.
Published: April 2003

Background: The laminins play an important role in cell attachment to the extracellular matrix. This study was undertaken in order to investigate and to compare the presence of several laminin chains and isoforms in normal and glaucomatous trabecular meshwork. Methods: Fresh-frozen trabeculectomy specimens from glaucoma patients and trabecular meshwork from human donor eyes were included for immunohistochemistry. We used antibodies against laminin 1 (EHS-laminin/α1β1γ1), laminin 2 (merosin/α2β1γ1), the subunits α2 (M laminin), β1 (B1 laminin), γ1 (B2 laminin), β2 (s laminin) and γ2 and the laminin-associated glycoprotein nidogen. Results: For laminin 1, laminin 2, the subunits α2, β1, β2, γ1 and nidogen, the immunoreactivity of the juxtacanalicular zone underneath the inner wall of Schlemm’s canal was always stronger than of the uveal and corneoscleral trabecular meshwork. Staining for laminin chain γ2 could not be demonstrated in the outflow structures. Pattern and intensity of labelling for the laminins were not different between normal and glaucomatous eyes. Discussion: Heterogeneity of the laminins suggests structural complexity of the juxtacanalicular region. However, the presence of laminin around Schlemm’s canal seems to be unaffected by glaucoma and by age. This might indicate maintenance of basement membrane stability in the trabecular meshwork for life.
Immunohistochemical Markers in Full-Thickness Embryonic Rabbit Retinal Transplants
Authors: Ghosh Fredrik , Bruun Anitha , Ehinger Berndt
Published: April 2003

Purpose: To examine immunohistochemical markers in straight, well-laminated retinal transplants with special attention paid to the interphotoreceptor matrix, the Müller cells and the ganglion cells as these three retinal components have been abnormal in transplants produced by previous methods. Methods: Nine rabbits underwent subretinal transplantation of a complete full-thickness embryonic neuroretina. After 31 or 49 days, the transplants were stained for light microscopy and processed for immunohistochemistry. Results: Six of 9 eyes contained transplants with straight, well-laminated regions with all light-microscopic characteristics of a normal retina. In the outer segment region, the expression of peanut agglutinin showed segmental labeling of cone domains in the interphotoreceptor matrix, and interphotoreceptor retinoid binding protein immunoreactivity was found. Glial fibrillary acidic protein and vimentin immunoreactivity revealed normal Müller cell morphology. In 3 transplants the AB5-antibody-labeled ganglion cells in the ganglion cell layer and all transplants contained nerve fibers in the nerve fiber layer labeled by an antibody against neurofilament of 160 kD. The latter also labeled fibers connecting the transplant with the host. Conclusions: Full-thickness embryonic retinal transplants develop the normal retinal appearance and display several of the retinal components necessary for normal function which are not found in transplants produced by previous methods.
Interleukin 10 Treatment Does Not Prolong Experimental Corneal Allograft Survival
Authors: Torres Paulo F. , de Vos Alex F. , Martins Berta , Kijlstra Aize
Published: April 2003

In view of the known anti-inflammatory activities of interleukin (IL) 10, we investigated whether the administration of recombinant murine IL-10 prolonged corneal graft survival. A major histocompatibility complex mismatched rat model with AO rats as recipients of PVG donor corneas was used. A total of 39 corneal allografts was included in this study and divided into 7 groups for different treatments. Group I (n = 6), II (n = 8), III (n = 6) and IV (n = 7) were injected subconjunctivally with saline (control), 0.5 ng, 5 ng or 50 ng of IL-10, respectively, on the day of transplantation and then on postoperative days (POD) 2, 4, 6, 8 and 10. Group V (n = 4) and group VI (n = 4) were injected intraperitoneally with saline (control) or 1 µg of IL-10, respectively, on the day before surgery, the day of grafting and then on POD 2, 4 and 6. Finally, group VII (n = 4) was injected with both subconjuctival 5 ng of IL-10 and intraperitoneal 1 µg of IL-10 on the same days as the previous groups. The median days for corneal rejection in the various groups were: group I, 11.3 ± 0.9; group II, 11.5 ± 0.9; group III, 11.6 ± 0.8, and group IV, 10 ± 1.0. Statistical analysis revealed a trend towards rejection (p = 0.08) in group IV (compared to group I). In groups V and VI, corneal rejection was evident on day 12 and in group VII the median time for rejection was 10.5 ± 0.8 days. These results indicate that IL-10 treatment does not prolong corneal allograft survival and may even accelerate rejection.
The Ocular Pharmacokinetics of Topical Diclofenac Is Affected by Ocular Inflammation
Authors: Palmero M. , Bellot J.L. , Alcoriza N. , García-Cabanes C. , Orts A.
Published: April 2003

The ocular pharmacokinetics of topical diclofenac sodium was studied in two experimental models of ocular inflammation and compared to physiological conditions. Keratitis or uveitis were induced by intrastromal injection of clove oil or by intravitreal lipopolysaccharide in rabbits. The control eyes were not inflamed. Simultaneously to the induction of inflammation, 30 µl of 0.1% diclofenac were applied topically in the right eye. Diclofenac levels were measured by HPLC in the cornea, aqueous humor (AH), iris/ciliary body (ICB) and plasma 30 min, 1, 3, 6 and 12 h after application. In physiological conditions, diclofenac reached a peak level in the cornea and ICB at 30 min slowly decreasing afterwards. Low levels of diclofenac were found in AH. In keratitic eyes, two peak levels which were significantly higher than in the controls were found in the cornea 30 min and 3 h after application. Diclofenac concentrations in keratitic AH and ICB were lower than in controls. In uveitic eyes, corneal and ICB levels peaked at 30 min, being significantly higher than in controls, and decreased quickly to very low levels at 1 h after application. In uveitic AH, diclofenac levels were lower than in controls. Plasma levels were very low (less than 0.1 µg/ml) in all experimental groups. It is concluded that the ocular pharmacokinetics of topical diclofenac is affected by inflammatory processes in the eye, reaching higher levels in the target tissues.
Superoxide Dismutase, Catalase, Glutathione Peroxidase and Xanthine Oxidase in Diabetic Rat Lenses
Authors: Çekiç Osman , Bardak Yavuz , Totan Yüksel , Akyol Ömer , Zilelioglu Güler
Published: April 2003

The activities of the protective enzymes, superoxide dismutase, catalase, glutathione peroxidase and of xanthine oxidase, an enzyme acting as a source of O–2, were measured in the lenses of alloxan-induced diabetic and control rats. Superoxide dismutase and glutathione peroxidase activities were found to be significantly decreased, while catalase and xanthine oxidase activities were increased. This means that the ratio of the oxidant/antioxidant enzymes increases in the diabetic rat lens, suggesting an increased oxidative stress. This imbalance is possibly an important contributing factor in the pathogenesis of diabetic cataract.
Immunolocalization of c-Fos and c-Jun in Rat Ocular Surface Epithelium
Authors: Saika Shizuya , Okada Yuka , Shirai Kumi , Kawashima Yoshiji , Yamanaka Osamu , Ohnishi Yoshitaka , Ooshima Akira
Published: April 2003

We immunohistochemically located c-Fos and c-Jun, the major components of transcription factor activator protein 1 (AP1), in normal epithelia of rat cornea and conjunctiva to determine the expression of these genes in the ocular surface epithelia. Immunoreactivity for c-Fos was detected in the nuclei of basal cells of the limbal and conjunctival epithelia, while that for c-Jun was detected in the cytoplasm of the cells of these epithelia. The corneal epithelium lacked immunoreactivity for either protein. AP1 may have an important role in the maintenance of homeostasis of limbal and conjunctival epithelia.
The Effects of Induced Acute Hyperglycemia in the Cat on the Retinal Capillary Blood Flow
Authors: Ben-nun Joshua , Alder Valerie A. , Constable Ian J.
Published: April 2003

Purpose: To study the effect of acute hyperglycemia on the erythrocyte flow in specific retinal capillary paths. Methods: A technique for fluorescent labeling of a known fraction of the erythrocyte moiety of systemic blood was combined with fluorescence viewing of the retinal capillary network in live cats. This technique was developed to enable visualization of the erythrocyte flow in the retinal capillary network and used to acquire video recording of the retinal capillary erythrocyte flow in normal feline eyes. The pattern of capillary erythrocyte flow under normal blood glucose levels and normal systemic blood pressure served as baseline. Acute hyperglycemia was induced by intravenous injection of glucose while monitoring the systemic blood pressure. Two subsets of functional capillary pathways previously defined as S (simple) and C (complex) were identified in the recorded data. The relationship between erythrocyte flux in random selections of these two pathways and the level of hyperglycemia and systemic blood pressure was determined. Results: Induction of acute hyperglycemia led to acute elevation of the systemic blood pressure that returned to baseline levels within few minutes, while blood glucose remained high. The capillary erythrocyte flux in S paths was significantly higher than in C paths at all values of systemic blood pressure. The capillary erythrocyte flux in the S paths was directly proportional to the systemic blood pressure whereas the flux in C paths was minimally affected by acute hyperglycemia for the systemic blood pressure range between 110 and 160 mm Hg. Conclusions: The erythrocyte flux in S paths is affected by the changes of the systemic blood pressure and these paths act as ‘shunt vessels’ when acute elevation of the systemic blood pressure occurs. C paths maintain stable perfusion under changing conditions, most probably in an effort to minimally alter the basic metabolic needs of the retinal tissue. Hyperglycemia per se was not responsible for changes of the cell flux in these capillary paths.
Concentrations of Serum Albumin and Nonesterified Fatty Acids in Bovine Aqueous Humor with Regard to the Fatty Acid Sensitivity of Bovine Lens Epithelial Cells
Authors: John Mike , Glaesser Dietmar
Published: April 2003

Concentrations of albumin and nonesterified fatty acids (FAs) have been determined in bovine serum and aqueous humor (AH) with regard to the FA-to-albumin molar ratio, which has been proved decisive for the FA cytotoxicity to bovine lens epithelial cells as described previously. In 6- to 7-month-old female calves the average albumin level was reduced 309-fold from 638 µmol/l in serum to 2.00 µmol/l in AH, in 72- to 84-month-old cows 405-fold from 632 to 1.56 µmol/l, and in 12- to 18-month-old bulls 395-fold from 553 to 1.40 µmol/l. In 64% of the animals the albumin concentration in AH differed significantly between both eyes. The serum albumin values resulted in a Gaussian curve, but the frequency distribution for AH albumin values skewed to the right. Using an enzymatic method the concentrations of nonesterified FAs were determined in serum as well as in concentrated AH samples. In all animals investigated the molar FA-to-albumin ratio was higher in AH than in serum. The results are discussed in view of the assumption that unsaturated nonesterified FAs might be cataractogenic risk factors.
Irradiation for Inhibition of Endothelial Cell Growth in vitro
Authors: Joussen A.M. , Kruse F.E. , Oetzel D. , Voelcker H.E.
Published: April 2003

The clinical effect of ionising radiation on ocular neovascularisations is controversial, not only because of the variety of treatment modalities. The aim of our study was to investigate an experimental model which allows to evaluate radiation parameters and to study the mechanism of the inhibitory effect on neoangiogenesis. In vitro experiments were performed using human umbilical vein endothelial cells and human corneal keratocytes. The cells were irradiated with different doses of photon beam radiation and counted daily after treatment. Cell cultures confirmed the efficiency of irradiation in inhibiting proliferation of vascular endothelial cells. Radiosensitivity was shown to be higher in vascular endothelial cells than in corneal stromal keratocytes. This might be helpful in investigating therapy parameters for treating ocular neovascularisations, as well as underlying mechanisms.
The Effect of Prinomastat (AG3340), a Synthetic Inhibitor of Matrix Metalloproteinases, on Posttraumatic Proliferative Vitreoretinopathy
Authors: Ozerdem Ugur , Mach-Hofacre Beata , Keefe Kelly , Pham Tony , Soules Kelly , Appelt Krzysztof , Freeman William R.
Published: April 2003

In a search for a pharmacologic adjuvant in the management of posttraumatic proliferative vitreoretinopathy (PVR), we investigated the effect of intravitreal injection of prinomastat (AG3340) on an experimental model. Posterior penetrating eye trauma was created in one eye each of 24 New Zealand white rabbits. One week after the surgery, all rabbits were randomized (1:1) to receive 0.5 mg prinomastat or the vehicle of the drug intravitreally every week for 6 weeks. The degree of PVR for each hemiretina was scored, and the two scores were summed to obtain a total eye score. The mean total eye score was 3.58 in the treatment group and 5.75 in the control group (p = 0.0307). The numbers of eyes with tractional retinal detachment in the prinomastat-treated (n = 12) and control (n = 12) groups were 3 and 9, respectively (p = 0.0391). These results suggest that intravitreally administered prinomastat has an inhibitory effect on posttraumatic PVR.
Antisense Basic Fibroblast Growth Factor Oligonucleotide Reduced Adhesion of Retinal Pigment Epithelial Cells to Extracellular Matrix Molecules and Their Proliferation
Authors: Heun Rho Sae , Seong Yoon Hee , Won Yoo Kyung , Chan Park Woo , Hee Jeong Jin , Hyun Yoo Young
Published: April 2003

We investigated the effect of extracellular matrix molecules on the adhesion of retinal pigment epithelial cells and their subsequent proliferation. Fibronectin, collagen type I and vitronectin enhanced their adhesion and proliferation. In addition, the effect of basic fibroblast growth factor (bFGF) on their adhesion and proliferation was studied. bFGF enhanced their adhesion and proliferation, whereas antisense bFGF reduced their adhesion to and their proliferation on extracellular matrix molecules.
Disruption of the Blood-Aqueous Barrier following Retinal Laser Photocoagulation and Cryopexy in Pigmented Rabbits
Authors: Inoue Masanori , Tsukahara Yasutomo , Shirabe Hisamitsu , Yamamoto Misao
Published: April 2003

Disruption of the blood-aqueous barrier (BAB) induced by retinal photocoagulation and cryopexy in pigmented rabbits was evaluated by laser flare photometry. A significant increase in flare values after retinal photocoagulation was measured from the 1st postoperative day, with values returning to baseline levels by day 7. Cryopexy induced consistently high flare values for 14 days. Intravitreal injection of interleukin (IL) 1, IL-6 and prostaglandin (PG) E2 induced a significant increase in flare values. Following these treatments, introduction of a PG synthetase inhibitor can partially ameliorate BAB disruption. IL-1, IL-6 and PGE2 may be involved in BAB disruption following retinal photocoagulation and cryopexy.
Three-Dimensional Confocal Microscopy of the Human Cornea in vivo
Authors: Masters Barry R. , Böhnke Matthias
Published: April 2003

This paper reviews the literature from 1990 to 2000 and evaluates the seminal investigations performed with the confocal microscope on the in vivo human cornea. Our pedagogical technique is to illustrate both the advantages and the problems associated with occular confocal microscopy by way of annotated examples. Confocal microscopy offers improved resolution and has resulted in new discoveries of corneal pathology at the cellular level. The ability to provide high-resolution, real-time images of the full thickness of the cornea gives the clinician and the researcher an important new tool for the investigation of the cornea.
Role of VEGF-A in Endothelial Phenotypic Shift in Human Diabetic Retinopathy and VEGF-A-Induced Retinopathy in Monkeys
Authors: Hofman P. , Blaauwgeers H.G.T. , Vrensen G.F.J.M. , Schlingemann R.O.
Published: April 2003

The endothelium-specific antigen PAL-E, associated with transport vesicles in non-barrier endothelium, is almost absent from barrier capillaries in the normal brain and retina. We have recently demonstrated that only leaking retinal capillaries in diabetic retinopathy (DR) in humans characteristically express PAL-E. Here we investigated the relation between the expression of the PAL-E antigen and vascular endothelial growth factor-A (VEGF) in human post-mortem eyes of individuals with diabetes mellitus (DM) and in experimental VEGF-induced retinopathy in cynomolgus monkeys. Cryosections were cut of eyes of 41 individuals with and 30 individuals without DM and eyes of 2 cynomolgus monkeys who received 4 injections of 0.5 µg VEGF in the vitreous of one eye and PBS in the other. The sections were stained with antibodies against VEGF, PAL-E and endogenous markers for microvascular leakage. Specific retinal vascular staining for VEGF was only observed in 10 out of the 41 cases with DM. These 10 cases also had marked uniform PAL-E staining and widespread vascular leakage. In contrast, diabetic patients without microvascular leakage and controls were negative for VEGF and PAL-E. Likewise, PAL-E was found only in the leaky retinal vessels of monkey eyes injected with VEGF. These results indicate that increased expression of the PAL-E antigen in retinal endothelium in conditions with microvascular leakage is related to VEGF and suggest that VEGF directly or indirectly induces PAL-E. PAL-E expression may reflect important endothelial changes involved in the disturbance of the blood-retina barrier in DR.
Effects of Check Size on Visual Cortex Activation Studied by Functional Magnetic Resonance Imaging
Authors: Miki Atsushi , Liu Grant T. , Goldsmith Zachariah G. , Zhou Lan , Siegfried John , Hulvershorn Justin , Raz Jonathan , Haselgrove John C.
Published: April 2003

We studied functional magnetic resonance imaging (fMRI) of visual cortex during checkerboard visual stimulation with three standard check sizes to examine whether activation in the visual cortex varied among these sizes. We acquired fMRI at 1.5 T in 8 normal subjects, each receiving the best refractive correction. Each subject underwent an experiment consisting of four conditions: black and white checkerboards with three check sizes (0.25-, 0.5-, and 1.0-degree) flickering at 8 Hz, and a black screen. SPM96 was used for a group data analysis with a random effects model after each of the subject’s data was motion-corrected and spatially normalized to a standard brain. The activation in the visual cortex showed the greatest signal changes with the 0.5-degree check among the three check sizes. When standard check sizes are used to stimulate visual cortex in fMRI experiments, our results suggest that 0.5-degree checks flickering at 8 Hz produce the most vigorous activation in visual cortex.
Protective Effect of Docosahexaenoic Acid against Retinal Ischemic Injury: An Electroretinographic Study
Authors: Miyauchi O. , Mizota A. , Adachi-Usami E. , Nishikawa M.
Published: April 2003

Purpose: To determine whether docosahexaenoic acid (DHA) can reduce the retinal damage induced by transient retinal ischemia. Methods: Retinal ischemia was induced by increasing intraocular pressure (IOP). Retinal circulation was restored by lowering IOP. An intraperitoneal injection of 1,000 mg/kg of DHA-ester (DHA-E) was given 5 h before the ischemia. Electroretinograms were recorded just before the ischemia and at 60-min intervals up to 4 h after circulation was restored. Results: The ratio of the amplitudes after the ischemia to that just before ischemia was significantly higher in eyes administered DHA-E than in controls at each time point (p < 0.01). Conclusion: DHA-E is effective in protecting the retina against transient retinal ischemia.
Photoreceptor Protection against Constant Light-Induced Damage by Isopropyl Unoprostone, a Prostaglandin F2α Metabolite-Related Compound
Authors: Hayami Kayoko , Unoki Kuzuhiko
Published: April 2003

Some of the antiglaucoma drugs have shown neuroprotective effects in ischemic retinal damage and optic nerve injury. We studied photoreceptor protection against constant light-induced damage using isopropyl unoprostone, a prostaglandin F2α metabolite-related compound. Albino Sprague-Dawley rats were administered isopropyl unoprostone solution intravitreally in one eye (the test eye) and vehicle alone in the contralateral eye (the control eye) and were exposed to constant light for 7 days. Histological examinations were performed to evaluate photoreceptor protection by quantifying the outer nuclear layer (ONL) thickness and scoring the rescue of ONL. Seven-day constant light affected photoreceptors and produced a marked disruption of photoreceptor outer segments and inner segments and a decrease in the thickness of the ONL. As compared with control eyes, pretreatment by intravitreal administration of isopropyl unoprostone 2 days prior to constant light exposure provided protection from the light insult, and the effects of rescue were dependent on the dose of the agent (0.6–6.0 µg), the maximum dose protecting about 70% of the photoreceptors. Topical application of the drug had little rescue effect. Aberrant macrophages in light-exposed eyes with unoprostone injection were more numerous than in normal eyes, but the extent did not differ significantly from that of degenerated eyes injected with vehicle only. Isopropyl unoprostone has shown protection of photoreceptors against constant light-induced damage, and it is thus suggested that the agent has neuroprotective activity in vivo.
Experimental Intravitreal Application of Trovafloxacin in Rabbits
Authors: Gürler Bülent , Ozkul Yasar , Bitiren Muharrem , Satici Ahmet , Oguz Halit , Karadede Sezin
Published: April 2003

This study was performed to examine the retinal toxicity of trovafloxacin, a broad-spectrum fourth-generation fluoroquinolone, in rabbit eyes after intravitreal injection. The left eyes of 20 albino rabbits were divided into four groups, and each was injected intravitreally with 0.1 ml of trovafloxacin in a 50-µg, 100-µg, 250-µg or 500-µg concentration. The right eyes of these rabbits served as control and received normal saline solution. Retinal function was assessed from the electroretinogram (ERG), and retinal structure was also examined by ophthalmoscopy and histologic study (light microscopy). The intravitreal injections of 50 µg, 100 µg, and 250 µg trovafloxacin did not significantly change the ERG a-wave, b-wave or the oscillatory potential throughout the follow-up period of 4 weeks. While no ERG changes were observed at 4 weeks after injection, in the 3 eyes that received trovaloxacin 500 µg/0.1 ml, the a-wave amplitudes showed a diminution of 56–49% and those of b-waves one of 53–44% of the preinjection amplitudes at 4 weeks after injection, but oscillatory potentials remained unchanged in the other 2 rabbits intravitreally injected with 500 µg trovafloxacin. However, in none of the injected eyes and the control eyes in all groups were ophthalmoscopically visible fundus changes and histologic abnormality observed. The results suggest that intravitreally injected trovafloxacin at a dose of up to 500 µg is nontoxic to the rabbit retina. If future studies in other species confirm our findings, intravitreal trovafloxacin may be a good alternative in the treatment and prevention of clinical bacterial endophthalmitis.
Role of Thyroid Hormone in Craniofacial and Eye Development Using a Rat Model
Authors: Gamborino M. José , Sevilla-Romero Enrique , Muñoz Alberto , Hernández-Yago José , Renau-Piqueras Jaime , Pinazo-Durán M. Dolores
Published: April 2003

Thyroid hormones (TH) are essential for somatic and neural development. Epidemiological studies have pointed to TH-dependent craniofacial features occurring during development. In an attempt to elucidate the precise role of TH in the developing eyes and adnexa (orbit, lids, nasolacrimal structures), we analysed the craniofacial and eyeball developmental characteristics in a rat model of congenital-neonatal hypothyroidism (HG), induced by combined chemical-surgical thyroidectomy. The heads and eyeballs from control and HG animals were obtained at key developmental stages and processed for scanning electron, light and transmission electron microscopy. On embryological day 13 (E13), significantly reduced values for head parameters (25% less), optic primordia area (0.053 ± 0.0085 vs. 0.111 ± 0.012 µm2; p < 0.05) and volume (3.96 ± 0.141 vs. 8.09 ± 0.123 µm3; p < 0.05) were found in the HG with respect to the controls. In addition, a delayed prenatal eye closure and postnatal eye opening took place in the treated rats. The photoreceptor and ganglion cell layer thickness displayed significantly lower values (p < 0.001) in HG, at each developmental time point. Postnatally, a delay in photoreceptor outer segment morphogenesis (in relation to retarded disc formation) and significantly lower values for ganglion cell nuclear volumes (p < 0.001) and nuclear pore density (p < 0.01) were observed in the TH-deficient animals. All data suggest that TH play a pivotal role in the development of the face and eye. Therefore, a series of defects due to a loss of TH actions involved in anterior-posterior development of the head and face and the loss of TH-dependent signals crucial for cell differentiation, migration, proliferation and establishment of definitive cell phenotypes in the eyes may appear. Gestational and neonatal screenings for thyroid functioning are suggested to paediatricians and ophthalmologists in order to prevent craniofacial malformations and visual abnormalities.
Apolipoprotein E Polymorphisms in Age-Related Macular Degeneration in an Italian Population
Authors: Simonelli Francesca , Margaglione Maurizio , Testa Francesco , Cappucci Giuseppe , Manitto Maria Pia , Brancato Rosario , Rinaldi Ernesto
Published: April 2003

Objective: Apolipoprotein E (apoE) is an important regulator of cholesterol and lipid transport during compensatory synaptogenesis. Our purpose was to investigate the role of apoE gene polymorphisms in Italian patients with age-related macular degeneration (AMD). Methods: We used the polymerase chain reaction technique to analyze apoE genotypes in 87 patients with AMD, in 47 age-matched controls and in 1,287 individuals from a general reference population. Results: The frequency of allele Ε4 carriers was significantly higher (p = 0.002) in the general population than in AMD patients, while the frequency of allele Ε2 was higher in the patients (p = 0.069) with an increased risk for AMD in the patients versus the population-based controls (odds ratio = 1.7; 95% confidence interval: 1.0–2.9). Allele Ε4 was associated with a decreased risk for AMD in the patients versus the population-based controls (odds ratio = 0.3; 95% confidence interval: 0.1–0.8). Clinical Relevance: These data suggest that apoE testing may represent a tool for the evaluation of the relative risk of AMD. Consequently, a preventive strategy can be initiated at an early stage of the disorder. Conclusion: The apoE gene polymorphism showed a significant association with the risk of AMD. The lower frequency of the Ε4 allele in AMD patients suggests that the apoE gene could play a protective role in the pathogenesis of the disease. In contrast, the Ε2 allele was found associated with a slightly increased risk of AMD, although we did not find a statistically significant effect.