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Purpose: To assess the accuracy of the intraocular lens (IOL) power calculation based on three methods using artificial intelligence (AI) and one formula using no AI. Methods: During cataract surgery on 114 eyes, one type of IOL was implanted, calculated with the Hill-RBF 2.0 method. The theoretical postoperative refractions were calculated using the Kane and the Pearl-DGS methods and a vergence based formula (Barrett Universal II, BUII). The differences between the manifest and objective postoperative refractions and the predicted refractions were calculated. The percentage of eyes within ±0.5 D and ±1.0 D prediction error (PE), the mean, and the median absolute errors (MAE and MedAE) were also determined. Results: The mean age of the patients was 69.48 years; the axial length was between 21.19 and 25.39 mm. The number of eyes within ±0.5/±1.0 D PE was 96/108 (84.21%/94.73%) using the Hill-RBF 2.0 method, 92/107 (80.70%/93.85%) with the Kane method, 91/107 (79.82%/93.85%) with the Pearl-DGS method, and 91/106 (79.82%/92.98%) with the BUII formula, using subjective refraction. With objective refractometric data, PEs were within ±0.5 D in 88 (77.19%), 83 (72.80%), 82 (71.92%), and 80 (70.17%) cases (Hill-RBF, Kane, Pearl-DGS, BUII, respectively). MAE and MedAE were also best with the Hill-RBF 2.0 method (0.3 D; 0.18 D). Conclusion: Better accuracy of PE might be obtained by the Hill-RBF 2.0 method compared with BUII. The Kane and Pearl-DGS methods showed similar accuracy when compared with BUII.

Purpose: To evaluate detailed corneal parameters of inflammatory bowel disease (IBD) patients, including Crohn’s disease (CD) and ulcerative colitis (UC) patients, and to assess association...

Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc.Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant.Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values.Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc.

The 14C/12C ratio of living organisms is largely determined by the 14C/12C ratio of consumed diet as well as by the atmospheric 14C concentration together with the body’s metabolic processes. The measured 14C content of living matter compared to the atmospheric radiocarbon level can provide invaluable information about developmental processes. Our aim was to determine the 14C content of ten different tissues of the human eye using the 14C bomb-pulse dating signature. The 14C content of the atmosphere, so called 14C “bomb-pulse” has labeled humanity offering an opportunity to determine these special formation, turnover and substitution courses in biology. The results allowed us to construct a 14C map of the bomb-peak labeled human eye. According to the anatomical location of the tissues, an unexpected picture emerged as in moving from the outer parts towards the inner parts of the eye, the 14C content of each tissue decreased. The data presented here are compatible with the view that the oldest parts of the eye are the sclera, the limbus and the cornea, in this order, and moving further inside, the youngest tissue of the eye is the retina.

To investigate corneal microstructure of systemic sclerosis (SSc) patients using in vivo confocal microscopy (IVCM). 33 patients with SSc and 30 age-matched healthy subjects were recruited. All participants underwent comprehensive ophthalmic examination including IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering GmbH, Heidelberg, Germany) and ocular surface evaluation. Subbasal nerve plexus morphology was investigated using automated software analysis (ACCMetrics V3; University of Manchester, Manchester, UK). Keratocyte cell densities in the anterior stroma were significantly lower in patients with SSc compared to controls (P

Purpose: To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls.Methods: A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional, observational, case-control study. Corneal parameters were evaluated by Pentacam. Objective clinical tests of dry eye disease (DED) were also performed.Results: All pachymetric measurements and corneal volumes (CVs) proved to be significantly lower both in PM and DM patients. The values of DM patients were closer to control values than those of the PM patients. For tear break-up time and Schirmer-I test values significant differences were observed between patients and controls, with values decreased both in PM and DM patients.Conclusions: PM patients rather than DM patients tend to develop thinner and low-volume corneas as compared to controls. Additionally, a high prevalence of DED among both PM and DM patients was also detected.

Purpose: Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was ...

The human precorneal tear film is a special body fluid, since it is a complex mixture of proteins, lipids, small bioactive molecules, and their concentrations and relative distribution represent not only the metabolic state of the ocular surface but also the systemic and local homeostasis of the outer eye and the human body. This suggests that biochemical analysis of the precorneal tear film composition may provide a non-invasive tool for diagnosis and monitoring of disease progression or treatment efficacy in human medicine. However, collecting tears is demanding, and obtaining reproducible and unaltered samples is challenging because of the small sample volumes of tears. Several methods are available for tear collection as a preparatory step of precorneal tear film analysis, and the collection method used has to be assessed since it has a critical impact on the effectiveness of the assays and on the quality of the results. Each sampling method has advantages and disadvantages; therefore, it is not easy to choose the appropriate collecting method for tear collection. To overcome these limitations various methods have been recommended by different authors for special aspects of specific tests. The aim of our review was to evaluate tear sampling methods with regard to our ongoing biochemical analysis. *Contributed equally.

Our aim was to summarize key aspects of the pathomechanism and the ocular involvements of rheumatic and systemic autoimmune diseases.Apart from a paper in French (Morax V, Ann Oculist 109:368-370, 1893), all papers referred to in this article were published in English. All the materials were peer-reviewed full-text papers, letters, reviews, or book chapters obtained through a literature search of the PubMed database using the keywords ocular manifestations; pathogenesis; systemic inflammatory rheumatic diseases; rheumatoid arthritis; osteoarthritis; fibromyalgia; systemic lupus erythematosus; seronegative spondyloarthritis; ankylosing spondylitis; reactive arthritis; enteropathic arthritis; psoriatic arthritis; systemic sclerosis; polymyalgia rheumatica and covering all years available. Some statements articulated in this paper reflect the clinical experience of the authors in their tertiary-referral center.Ophthalmic disorders are categorized by anatomical subgroups in all rheumatic diseases. The most common ocular manifestations are diverse types of inflammations of different tissues and dry eye disease (DED).The eye could be a responsive marker for the onset or aggravation of an immune reactivation in many rheumatic diseases, furthermore, ocular findings can antedate the diagnosis of the underlying rheumatic disease. By recognizing ocular manifestations of systemic rheumatic diseases it might be possible to avoid or at least delay many long term sequelae.

Eyelid margin is one of the most challenging anatomic regions in the human body and eyelid margin tumors raise special difficulties in the field of periocular surgery based on anatomical, histological and aesthetic points of view.

Purpose To measure tear clearance values in patients with meibomian gland dysfunction (MGD) with a dynamic nuclear medicine method, namely, dacryoscintigraphy (DSCI). Methods Twenty-four MGD patients and 24 healthy volunteers were examined. During DSCI one drop of a solution with 100 MBq/mL99mTc sodium pertechnetate was instilled with a micropipette into the lacrimal lake of both eyes. Measurements were performed according to a dynamic data acquisition protocol, which resulted in summed DSCI images. Data were also evaluated separately in special regions of interest (ROI), and consecutive time activity curves were created. Tear clearance (T½) values were calculated based on the activity curves. In addition, tear osmolarity measurements, tear breakup time (tBUT), and Schirmer I (STI) tests were performed prior to DSCI examination. Results The T½ values were 29.91 ± 11.61 min in MGD patients and 6.26 ± 1.5 min in healthy controls. Tear osmolarity parameters were 308 ± 9.41 mOsm/L and 288.9 ± 6.4 mOsm/L, tBUT values were 5.54 ± 2.73 s and 11.4 ± 2.7 s, while the STI test values were 6.17 ± 2.78 mm and 13.58 ± 3.8 mm, respectively. The differences were significant (p Conclusions Although the MGD patients’ lacrimal drainage systems were patent their tear clearance values were significantly higher than those of healthy volunteers, which may be caused by decreased drainage of tears from the eyes towards the nasal cavity. The understanding of new features regarding the altered physico-chemical characteristics of MGD tears has been augmented by the results of this study.

Although phacoemulsification is routinely performed with the patient in a supine position, certain locomotor deformities and other severe ailments can lead to the inability of the patient to recline flat.The present article surveys publications and summarizes our own experience regarding positioning techniques during cataract surgery on patients unable to adopt a supine position.The successful and effective performance of cataract surgery by phacoemulsification depend on the comfortable positioning of both the patient and the surgeon. In order to achieve the highest possible success rate in phacoemulsification surgery, optimal positioning of the patient and the operating microscope are essential. There are other features of pivotal importance, including the construction of the operating table, the anesthesia technique, and the surgical approach.Surgeons often have to rely on their own imagination and experience in finding optimal positioning in order to perform effective and successful phacoemulsification surgery.

Stem cell line from human limbal area was established to study in vitro cell growth and response to the toxic effects of antibiotics used in ophthalmology in terms of cell migration rates and structure of interphase chromatin. Recovery from cellular damages caused by ophthalmologic antibiotics was mimicked by an in vitro scratch model and followed by time-lapse microscopy, scanning electronmicroscopy and chromatin image analysis. Experiments revealed that broad spectrum antibiotics, chloramphenicol (0.5–1.0 mg/ml) and rifampicin (0.1–0.2 mg/ml), corresponding to concentrations in common clinical practice, slowed down the regeneration process. Results show that nuclei of naturally occurring limbal cells contain the same intermediates of chromatin condensation as seen in mammalian tumor cells and follow the common pathway of chromosome condensation. These intermediates included decondensed veil-like chromatin, fibrillary chromatin, supercoiled ribbon, chromatin bodies, early linear forms and metaphase chromosomes. Upon chloramphenicol and rifampicin treatment characteristic distorsions took place in the intermediates of chromosome condensation. Damaging effects in limbal stem cells in the presence of chloramphenicol or rifampicin indicate that ophthalmologic treatment with antibiotics should be used cautiously.

The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology.

The aim of this study was to evaluate the association between clinical signs and symptoms of dry eye disease (DED) in patients with systemic sclerosis (SSc). This cross-sectional observational study included 19 SSc patients and 19 normal subjects with no ocular symptoms or ocular surface disorders. Clinical parameters included tear film break-up time (tBUT), Schirmer I, lissamine green (LG) dye, and tear film osmolarity tests, tear production, and tear secretion flow. For assessment of the dry eye symptoms, the Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. The following mean values were found in SSc patients: OSDI 33.6 ± 19.86; osmolarity of the tear fluid 310.8 mOsmol/l ± 14.47; tBUT time 5.158 ± 2.328 s; Schirmer I test 5.395 mm/5 min; LG grading score 2.026 ± 0.8893; collected tear fluid volume 6.397 ± 2.761 µl. The calculated average tear velocity was 4.654 ± 1.963 µl/min. A significant correlation was found between the OSDI as a subjective parameter and disease duration. Early recognition of dry eye symptoms, a possible extra-intestinal manifestation of SSc, should be included in the check up of the disease to reduce ocular complications. The objective tear functional tests were strongly influenced by individual factors like age and disease duration.

Eyelid margin tumors require special attention based on both anatomical and histological perspectives. Our aim in this study was to evaluate carbon dioxide (CO2) laser therapy for the treatment of eyelid margin tumors. Fifty-two patients with 55 eyelid margin tumors were included in this study. All tumors were removed with a CO2 laser, and histopathological evaluation was obtained in 52 cases. All patients were followed up for a mean period of 8.5 months (range 6 to 14 months). There were no bleedings in the intra- and postoperative period; the wounds were dry and reepithelized after 10–14 days and no recurrence occurred during follow-up period. Compared to the surrounding tissue, the treated area was hypopigmented and maximum five eyelashes (average 2.5) were wasted during the procedure. We achieved complete patient and surgeon satisfaction with cosmetic and therapeutic results. CO2 laser treatment of eyelid margin is a safe and effective procedure; its cosmetic result is beneficial as it does not cause malposition of the eyelid or damage to the lacrimal drainage system if the tumor is located in its proximity.

The efficacy of a crude hydro-alcoholic extract of Cassia fistula (golden shower tree) fruit to protect the kidney against bromobenzene-induced toxicity was studied. Negative control mice received normal saline; positive control mice were given 460 mg/kg of bromobenzene; Cassia fistula treated mice received 200, 400, 600 and 800 mg/kg of Cassia fistula fruit extract followed by 460 mg/kg bromobenzene (daily by oral gavage for 10 days). On the 11th day, the mice were sacrificed, blood samples were obtained to assess blood urea nitrogen (BUN) and creatinine levels, and kidneys were removed for histological examination. We found that bromobenzene induced significant nephrotoxicity reflected by an increase in levels of BUN and creatinine that was dose dependently prevented by the Cassia fistula fruit extract. The nephroprotective effect of the Cassia fistula fruit extract was confirmed by the histological examination of the kidneys. To the best of our knowledge, this is the first study to demonstrate the protective effect of Cassia fistula in nephrotoxicity.

Several recent studies have shown the protective effects of resveratrol in various experimental conditions and pathological animal models. Clinical studies also indicate the beneficial effects of resveratrol in different human diseases. Resveratrol produces a cascade against of events from the initial death-provoking signal, DNA fragmentation, and cell death. Researchers recognized the beneficial effect of resveratrol, as an important component, of the overall injury that occurs in various disorders such as oxidative stress, myocardial injury, anticancer activity, antidiabetic activity, and antihypercholesterolemic effects. Many mechanisms have been proposed for the initiation of protective effects of resveratrol in various pathological events, and considerable evidence exists to indicate that many mediators are involved in the resveratrol- induced protection. The present review focuses on the history, and the beneficial effects and mechanisms of resveratrol in oxidative stress, myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic activities, and discusses those therapeutic tools, which warrant becoming clinically important. s

The receptorial responsiveness method (RRM) was proposed to characterize changes in the concentration of degradable agonists in the microenvironment of their receptors. The characterization is done by providing concentrations of a stable agonist for the same receptor that is equieffective with the change in concentration to be characterized. RRM is based on the analysis of concentration–effect (E/c) curves reflecting the simultaneous action of the degradable and the stable agonist. In the present study, we investigated whether dissimilar affinity and (or) efficacy of the coacting agonists as well as the steepness of the E/c curves influence the reliability of RRM. E/c curves were simulated based on the operational model and then analyzed with RRM. We found that dissimilarity in affinity of the coacting agonists did not affect the accuracy of RRM estimates. In contrast, accuracy of the estimation depended on the magnitude of the concentration to be assessed, the operational slope factor, and the operational efficacy ratio of the coacting agonists. However, our results suggest that proper choice of a stable agonist for a degradable one can help to ensure reliable results, since information about the change in concentration of a degradable agonist is otherwise difficult to obtain.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This has been proven in different models of retinal degeneration. The in vivo protective effects of PACAP have been shown in retinal degeneration induced by kainic acid, optic nerve transection and ischemia. We have previously shown by morphological, morphometrical and immunohistochemical analyses that intravitreal PACAP administration protects against monosodium glutamate (MSG)-induced damage in neonatal rats. The question was raised whether these apparent morphological improvements by PACAP administration also lead to functional amelioration in MSG-induced retinal damage. The aim of the present study was to investigate the functional consequences of MSG treatment and the subsequent PACAP administration using electroretinographic measurements. The histological and morphometrical analyses supported the earlier findings that PACAP protected the retina in MSG-induced excitotoxicity. ERG recordings revealed a marked decrease in both the b- and a-wave values, reflecting the function of the inner retinal layers and the photoreceptors, respectively. In retinas receiving intravitreal PACAP treatment, these values were significantly increased. Thus, the functional outcome, although not parallel with the morphology, was significantly improved after PACAP treatment. The present observations are important from the clinical point of view showing, for the first time, that PACAP treatment is able to improve the functional properties of the retina in excitotoxic damage.

We investigated the activity of caspofungin against a Candida tropicalis clinical isolate showing paradoxical growth in vitro. BALB/c mice immunosuppressed by cyclophosphamide were infected intraperitoneally using 10(7) CFU/mouse. Caspofungin was administered intraperitoneally once daily for 5 days or as a single dose using the following doses: 0.12, 0.25, 1, 2, 3, 5, and 15 mg/kg. The single dose of caspofungin was effective only at 5 and 15 mg/kg concentrations (100% survival). Five-day caspofungin treatment led to 100% survival at doses of 1 mg/kg or higher. Caspofungin treatment significantly decreased the number of viable yeasts in the peritoneal lavage samples as well as in the infected abscesses at doses 1, 3, 5, and 15 mg/kg caspofungin as compared to the untreated control (P0.001 in all cases), and even to the group treated with 0.12 mg/kg caspofungin (P0.05 in all cases). At 2 mg/kg caspofungin dose, sterilization of the internal organs was reproducibly incomplete, suggesting that the role of paradoxical growth in the late clinical failure cannot be excluded.

Aim: Ischemic preconditioning has been well established in healthy human hearts, but limited information is available about its occurrence or its integrity in the brain. The aim of the present study was therefore to investigate whether a prior cerebral ischemic episode (stroke or transient ischemic attack [TIA]) is able to confer protection against ischemic stroke, reflected by in-hospital case fatality. Methods: A total of 2874 acute stroke patients included in the prospective, hospital-based Debrecen Stroke Database were studied, of whom 673 had previous stroke and 195 had prior TIA. Results: Following adjustment for active confounders, TIA but not stroke in the history was associated with decreased odds for in-hospital case fatality (odds ratio, 0.53; 95% confidence interval: 0.29–0.98; P = 0.041). The fitness of the final multiple regression model was good (Hosmer–Lemeshow goodness-of-fit χ2 statistic (P = 0.328). Conclusion: TIA may have an ischemic preconditioning effect in the human brain.

Although serious ocular manifestations of systemic sclerosis (SSc) have been described, tear analysis of patients with SSc has not been performed in previous studies. Our aim was to measure a wide panel of cytokines and chemokines in tears of patients with SSc and to assess the most significant molecules with a more sensitive and specific method. Unstimulated tear samples were collected from nine patients with SSc and 12 age- and gender-matched healthy controls. The relative levels of 102 different cytokines were determined by a cytokine array, and then absolute levels of four key cytokines were determined by a magnetic bead assay. Array results revealed shifted cytokine profile characterized by predominance of inflammatory mediators. Of the 102 analyzed molecules, nine were significantly increased in tears of patients with SSc. Based on the multiplex bead results, C-reactive protein, interferon-γ-inducible protein-10, and monocyte chemoattractant protein-1 levels were significantly higher in tears of patients with SSc. Our current data depict a group of inflammatory mediators, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc patients with ocular manifestations.

Background. Systemic sclerosis is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. Changes in levels of proangiogenic cytokines had already been determined largely in serum. Our aim was to assess the levels of VEGF in human tears of patients with SSC.Patients and methods. Forty-three patients (40 female and 3 men, mean (SD) age 61 (48–74) years) with SSc and 27 healthy controls were enrolled in this study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples.Results. The average collected tear fluid volume developed 10.4 μL (1.6–31.2) in patients and 15.63 μL (3.68–34.5) in control subjects. The average total protein level was 6.9 μg/μL (1.8–12.3) in tears of patients and control tears contained an average of 4.132 μg/μL (0.1–14.1) protein. In patients with SSc the average concentration of VEGF was 4.9 pg/μL (3.5–8.1) and 6.15 pg/μL (3.84–12.3) in healthy samples.Conclusions. Total protein production was increased because of the smaller tear volume. Decreased VEGF in tear of SSc patients can be explained also by the decreased tear secretion of patients.

Purpose: The examination of the effects of second generation lotrafilcon B silicone hydrogel (SiH) lenses on the cornea when worn for three years of daily wear. Material and Methods: 55 healthy patients were divided into two groups: current hydrogel contact lens wearers refitted with lotrafilcon B lenses (Group 1; 28 patients) and neophyte contact lens wearers (Group 2; 27 patients). Each patient's subjective eye comfort was measured with a self-administered questionnaire. The corneas were analyzed using contact specular microscope to measure corneal thickness and the endothelium before the SiH lenses were fitted after four weeks, one month, six months, one year, two years, and three years of lens wear. Results: Subjective complaints of patients in Group 1 were reduced; however patients in Group 2 experienced discomfort during the first two to four weeks of use. In Group 1, objective examinations identified a decrease in endothelial cell density. In Group 2, the endothelial cell density increased slightly in the first two years but decreased after three years. The results indicate that lotrafilcon B slows down the deleterious effects of contact lenses. The coefficient of variation significantly decreased after six months in Group 1 (0.47 vs 0.44; p = 0.049), whereas, in Group 2, the hexagonal cells improved significantly after one month (27.78 vs 28.25; p = 0.025). Conclusion: Based on the subjects involved and the period of time under examination, it can be concluded that high-Dk SiH lenses support the physiological metabolism and functions of the cornea by improving oxygen provision.

To evaluate the potential of silver and gold nanoparticles in the healing of cornea damages cell regeneration was tested. Corneal limbal cell regrowth and structural changes in chromatin structure were studied in the presence of silver (AgNPs, 10 nm) and gold nanoparticles (AuNPs, 100 nm). An in vitro cell scratch model served to follow limbal cell growth by long-term scanning micro-photography. AgNPs exerted only a moderate delay on cell regeneration. Low concentration (80 ppm) of AuNPs did not affect severely, 160 and 320 ppm extended the repopulation of limbal monolayer in a included: a) decondensed veil-like, b) fibrillary chromatin, c) supercoiled ribbon structures, d) visible chromosomes as chromatin bodies, e) early linear forms, and e) finally as metaphase chromosomes. Characteristic distortions in chromatin structures took place in nuclei in the presence of nanoparticles. Ag nanoparticles prevented the formation of linear and metaphase chromosomes. Gold particles (80 ppm) allowed the formation of chromatin bodies, but not more condensed chromosomal forms. Higher concentrations of AuNPs prevented the formation of ribboned chromatin and higher chromosomal structures. Results show that cell regeneration and chromatin toxicity are dose dependent. In spite of their lower size, Ag nanoparticles (10 nm) were less toxic than larger Au particles (100 nm).

Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) on blood glucose and function of the retina with electroretinography (ERG) in a diabetic setting with or without ischemia-reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove that the SCSE has a retinoprotective effect in diabetic rats: according to ERG measurements, SCSE treatment mitigated the retinal function-damaging effect of diabetes, and proved to be protective in the diabetic eye against ischemia-reperfusion injuries of the retina. Outcomes suggest that the protective effects of SCSE may occur through several pathways, including HO-1 dependent mechanisms. The observation that SCSE treatment decreases blood glucose is also novel. These findings offer the possibility for development of novel therapeutic strategies utilizing this emerging functional food, in particular in the prevention of conditions resulting from high blood glucose or I/R injury, such as deterioration of retinal microcirculation.

Epiphora, an abnormal overflow of tears, is commonly caused by tear drainage system anomalies including nasolacrimal duct obstruction. To assess morphologic abnormalities, dacryocystography by CT is used when CT contrast material is syringed into the lacrimal drainage system. To evaluate the function of the system, dacryoscintigraphy is the most readily available noninvasive method. In the case presented, a 43-year-old man was referred to our clinic with an 8 months' history of indefinite left side epiphora. After performing dacryoscintigraphy, we acquired SPECT/CT images during dacryocystography by CT to establish the surgical indication.

Acanthamoeba keratitis (AK) infection is a rather frequently occurring disease all over the world which can still cause serious or even total loss of vision despite improved diagnostic and therapeutic options. It may cause mostly keratitis, scleritis or chorioretinitis in people with competent immune systems. It mainly affects contact lens wearers with poor hygiene. Corneal trauma due to foreign body injury and exposure to contaminated water may also be associated with Acanthamoeba infection. Those with Acanthamoeba keratitis generally are immunocompetent. Nevertheless, these individuals do not develop protective immunity, and thus reinfection can occur. In the mid 1980s, an epidemic of Acanthamoeba keratitis occurred in the US which was attributed to increased contact lens use and poor lens hygiene. Conditions promoting the disease include not only poor contact lens hygiene but also the use of home-made saline solutions and corneal abrasions (Stehr-Green at al., 1989). In the United Kingdom, there was a marked rise in the number of cases in the first half of the 1990s, associated with the introduction and increasing popularity of disposable soft contact lenses shown to be due to irregular and/or chlorine based disinfection. After 1995 there was a decrease, perhaps resulting from an improvement in CL hygiene following the widespread dissemination of the results of a paper on Acanthamoeba keratitis as well as the gaining penetrance of new CL hygiene systems (Radford et al., 1995, 1998, 2002).

Resume Introduction La citrullination ainsi que les anticorps anti-peptide/proteine citrullines (ACPA) ont ete incrimines dans la pathogenie de la polyarthrite rhumatoide (PR). Alors que les ACPA sont des marqueurs specifiques et sensibles pour le diagnostic de PR, il n’existe pratiquement pas d’etudes sur les ACPA dans la spondylarthrite ankylosante (SA). Le role potentiel des anticorps antimycobacterie hsp65 dans la SA n’a pas encore ete evalue. Nous avons recherche la prevalence des anticorps antivimentine mutee citrullinee (anti-MCV) et des Ac anti-hsp65 dans la SA car il est important de mettre en evidence de nouveaux marqueurs biologiques dans la SA. Methodes Au total, 43 patients atteints de SA et 44 temoins sains ont ete inclus dans cette etude. Les anticorps (Ac) seriques anti-MCV et anti-hsp65 ont ete mesures respectivement par methodes Elisa commerciale et Elisa « maison ». Les taux d’auto-anticorps seriques ont ete correles aux parametres suivants : vitesse de sedimentation (VS), proteine C reactive (CRP), presence de l’HLA-B27, tabagisme, intensite douloureuse, bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI) et bath ankylosing spondylitis metric index (BASMI). Resultats Les patients atteints de SA avaient des taux seriques d’Ac anti-MCV significativement plus eleves (17,3 U/mL, extremes : 8,3–31,5 U/mL) que les temoins sains (8,9 U/mL, extremes : 5,4–13,3 U/mL) ( p 20 U/mL). La concentration moyenne serique en Ac anti-hsp65 chez les patients avec SA etait de 124,8 AU/mL (extremes : 27,2–1000 AU/mL), alors que les temoins avaient des taux significativement plus faibles d’anti-hsp65 (moyenne : 51,8 AU/mL ; extremes : 22,5–88,5 AU/mL) ( p r = 0,613 ; p = 0,012) et les taux seriques d’Ac anti-MCV en valeurs absolues ( r = 0,553 ; p = 0,021) etaient correles aux taux d’Ac anti-hsp65. La positivite des Ac anti-MCV etait egalement correlee a la VS ( r = 0,437 ; p = 0,03). Conclusions Les Ac anti-MCV et les anti-hsp65 sont de nouveaux biomarqueurs potentiels dans la SA.

Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS.Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices.Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3-31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4-13.3 U/mL) (p0.01). Sixteen of the 43 AS patients (37%) and none of the 44 healthy controls (0%) were anti-MCV positive using the cut-off value recommended by the manufacturer (20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2-1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5-88.5 AU/mL) (p0.001). Correlation analysis revealed that both anti-MCV positivity (r=0.613; p=0.012) and absolute serum anti-MCV levels (r=0.553; p=0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR (r=0.437; p=0.03).Anti-MCV and anti-hsp65 may be novel biomarkers in AS.

Relationship between hyperglycemia and stroke outcome is unclear, partly due to the small sample size in most studies, and partly due to lack of consensus concerning the cutoff level for hyperglycemia.In a cohort study, we investigated whether on-admission hyperglycemia is an independent predictor for 30-day case fatality by analyzing data of 2496 consecutive computed tomography (CT) verified acute ischemic stroke patients (2077 non-diabetic and 419 diabetic) included in the prospective, hospital-based Debrecen Stroke Database. Instead of using an arbitrary cutoff level for hyperglycemia, quartiles of on-admission glucose level were used for Kaplan-Meier survival curves and Cox proportional hazard modeling.The four quartiles of serum glucose level were in the range as follows:5.2 mmol/l, 5.201-6.1 mmol/l, 6.101-7.5 mmol/l, and7.501 mmol/l (n = 664, 618, 597, and 617, respectively). Among all 2496 participants, the adjusted hazard ratios for death increased with each quartile of admission glucose 1.96 [95% confidence interval (CI): 1.07-3.60; P = 0.03], 1.56 (95% CI: 0.83-2.94; P = 0.17), and 3.04 (95% CI: 1.70-5.44; P0.0001) for the second, third, and fourth quartiles, respectively). Upon stratification with respect to diabetes, we found similarly high risk for poor outcome among non-diabetic patients, while the risk was considerably lower among diabetic patients.These data suggest that even mild elevation of on-admission glucose levels is an independent predictor of 30-day case fatality. So, we propose that the ideal target blood glucose level is lower for non-diabetic than diabetic patients.

Heme oxygenase-1 (HO-1) transgenic mice (Tg) were created using a rat HO-1 genomic transgene. Transgene expression was detected by RT-PCR and Western blots in the left ventricle (LV), right ventricle (RV) and septum (S) in mouse hearts, and its function was demonstrated by the elevated HO enzyme activity. Tg and non-transgenic (NTg) mouse hearts were isolated and subjected to ischemia/reperfusion. Significant post-ischemic recovery in coronary flow (CF), aortic flow (AF), aortic pressure (AOP) and first derivative of AOP (AOPdp/dt) were detected in the HO-1 Tg group compared to the NTg values. In HO-1 Tg hearts treated with 50 μmol/kg of tin protoporphyrin IX (SnPPIX), an HO enzyme inhibitor, abolished the post-ischemic cardiac recovery. HO-1 related carbon monoxide (CO) production was detected in NTg, HO-1 Tg and HO-1 Tg + SnPPIX treated groups, and a substantial increase in CO production was observed in the HO-1 Tg hearts subjected to ischemia/reperfusion. Moreover, in ischemia/reperfusion-induced tissue Na+ and Ca2+ gains were reduced in HO-1 Tg group in comparison with the NTg and HO-1 Tg + SnPPIX treated groups; furthermore K+ loss was reduced in the HO-1 Tg group. The infarct size was markedly reduced from its NTg control value of 37 ± 4% to 20 ± 6% (P < 0.05) in the HO-1 Tg group, and was increased to 47 ± 5% (P < 0.05) in the HO-1 knockout (KO) hearts. Parallel to the infarct size reduction, the incidence of total and sustained ventricular fibrillation were also reduced from their NTg control values of 92% and 83% to 25% (P < 0.05) and 8% (P < 0.05) in the HO-1 Tg group, and were increased to 100% and 100% in HO-1 KO−/− hearts. Immunohistochemical staining of HO-1 was intensified in HO-1 Tg compared to the NTg myocardium. Thus, the HO-1 Tg mouse model suggests a valuable therapeutic approach in the treatment of ischemic myocardium.

The receptorial responsiveness method (RRM) was proposed to estimate changes in the concentration of an agonist in the microenvironment of its receptor. Usually, this is done by providing the equieffective concentration of another agonist for the same receptor or for a largely overlapping postreceptorial signaling (“test agonist”). The RRM is a special nonlinear regression algorithm to analyze a concentration–response (E/c) curve that represents the simultaneous actions of a single agonist concentration to be estimated and of increasing concentrations of the test agonist. The aim of this study was to explore whether asymmetry of the E/c curve to be analyzed influences the reliability of the RRM. For this purpose, computer simulation was performed by constructing symmetric and asymmetric E/c curves using the operational model of agonism, and then these curves were analyzed with the RRM. To perform the RRM, 2 types of equations were used: one involving the Hill equation, the simplest model of the E/c relationship, and one containing the Richards equation, an advanced model properly handling E/c curve asymmetry. Results of this study indicate that E/c curve asymmetry does not significantly influence the accuracy of the estimates provided by the RRM. Thus, when using the RRM, it is not necessary to replace the Hill equation with the Richards equation to obtain useful estimates. Furthermore, it was found that estimation of a high concentration of a high-efficacy agonist can fail when the RRM is performed with a low-efficacy test agonist in a system characterized by a small operational slope factor.

Asymmetric dimethylarginine (ADMA) has been associated with atherosclerosis, vascular diseases and, recently, also with arthritis including rheumatoid arthritis (RA) and ankylosing spondylitis (AS).Serum ADMA, arginine and symmetric dimethylarginine (SDMA) levels were assessed by liquid chromatography in 61 AS and 26 osteoarthritis (OA) patients with no known cardiovascular disease.Serum ADMA levels were significantly increased in AS compared to OA patients (0.95 ± 0.17 μM versus 0.70 ± 0.25 μM; p0.001). There were no differences in serum arginine and SDMA levels. Serum ADMA levels also positively correlated with age (R = 0.258; p = 0.043), body mass index (R = 0.368; p = 0.003), erythrocyte sedimentation rate (R = 0.329; p = 0.009) and ADMA levels negative correlated with chest expansion (R = -0.251; p = 0.04). No correlations were found between ADMA levels and disease duration, pain intensity, BASDAI, BASFI, BASMI, quality of life, CRP, HLA-B27 positivity, endothelial dysfunction or carotid atherosclerosis.ADMA may serve as a marker of systemic inflammation and may reflect functional immobility in AS. Further studies are needed to assess the possible role of ADMA in AS and AS-related vascular disease.

Candida dubliniensis is a recently described yeast that causes infections in mucosal surfaces as well as sterile body sites. Candida dubliniensis develops resistance to fluconazole (FLC) more rapidly than the closely related species C. albicans. The killing activity of amphotericin B (AMB), 5-fluorocytosine (5FC), FLC, voriconazole (VRC) and posaconazole (POS) was determined against six C. dubliniensis clinical isolates, identified using molecular biological methods and C. dubliniensis CD36 reference strain. Minimum inhibitory concentrations (MICs) were determined using the Clinical and Laboratory Standards Institute standard procedure. Time-kill assays were performed using RPMI-1640 as test media over a 48-h period. AMB proved to be fungicidal at >or=0.5 microg ml(-1) against all clinical isolates after 48 h. 5FC was only fungicidal at 32-64x MIC (4-8 microg ml(-1)) against all C. dubliniensis isolates. FLC, VRC and POS were fungistatic; decrease in colony number was observed only at the highest concentrations tested (8, 4 and 4 microg ml(-1), respectively). Triazoles invariably showed fungistatic effect at concentrations attainable in the serum. In clinical situations when a fungicidal antifungal is desirable, AMB may be used.

The aim of the present study was to test the hypothesis that inhibition of adenosine deaminase (ADA) enhances the efficiency of signal-transduction of myocardial A 1 adenosine receptors in hyperthyroidism. The inotropic response to N 6 -cyclopentyladenosine (CPA), a selective A 1 adenosine receptor agonist resistant to ADA, was investigated in the absence or presence of erythro -9-(2-hydroxy-3-nonyl)adenine (EHNA), an ADA and cGMP-stimulated 3′,5′-cyclic nucleotide phosphodiesterase (PDE2) inhibitor, or of pentostatin (2′-deoxycoformycin; DCF), an exclusive ADA inhibitor, in left atria isolated from eu- or hyperthyroid guinea pigs. Both ADA inhibitors enhanced the effect of CPA only in hyperthyroid atria. EHNA significantly increased the E max (mean ± S.E.M.) from 83.8 ± 1.2% to 93.4 ± 1.2%, while DCF significantly decreased the log EC 50 from −7.5 ± 0.07 to −7.83 ± 0.07 in hyperthyroid samples. Conversely, EHNA also diminished the log EC 50 (from −7.5 ± 0.07 to −7.65 ± 0.07) and DCF also raised the E max (from 83.8 ± 1.2% to 85.7 ± 2%) in hyperthyroidism, but these changes were not significant. In conclusion, ADA inhibition moderately but significantly enhanced the efficiency of A 1 adenosine receptor signaling pathway in the hyperthyroid guinea pig atrium. This suggests that elevated intracellular adenosine level caused by ADA inhibition may improve the suppressed responsiveness to A 1 adenosine receptor agonists associated with the hyperthyroid state. Alternatively or in addition, the role of decreased concentration of adenosine degradation products cannot be excluded. Furthermore, in the case of EHNA, inhibition of PDE2 also appears to contribute to the enhanced A 1 adenosine receptor signaling in the hyperthyroid guinea pig atrium.

We have previously described that hydrated pollen grains and their allergenic extracts possess intrinsic NAD(P)H oxidase activity, which catalyzes the production of reactive oxygen species (ROS) and induces oxidative stress in the lung or conjunctiva. This oxidative insult promotes the development of adaptive immune responses against innocuous pollen proteins and augments allergic airway inflammation induced by pollen antigens. In this study we investigated the ROS-producing activity of short ragweed (Ambrosia artemisiifolia) pollen extract (RWE) in detail. First, we found that in the presence of NADPH, RWE produces more ROS than after addition of NADH. An in situ nitroblue tetrazolium assay demonstrated that at least two distinct enzymes are responsible for ROS generation in RWE. The first one can use both NADPH and NADH as substrates, while the second one produces ROS only in the presence of NADPH. We observed that despite the fact that sera from non-allergic individuals have lower non-enzymatic antioxidant capacity, they exhibit higher efficacy in inhibition of ROS generation by RWE compared to sera from allergic patients. Western blot analysis revealed that antibodies against some pollen proteins associated with ROS production of RWE are present only in the sera of non-allergic subjects. Our novel findings raise the possibility that these antibodies may be able to block the ROS production by pollen enzymes hereby prevent the sensitization of non-allergic individuals.

The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.

We compared the efficacy of single six mg/kg and 2×3 mg/kg caspofungin doses to the traditional one mg/kg daily against C. albicans in a neutropenic murine model. in lethality experiments, all regimens improved survival (p