Impact of dorzolamide, benzalkonium-preserved dorzolamide and benzalkonium-preserved brinzolamide on selected biomarkers of oxidative stress in the tear film.

BACKGROUND: Long-term use of topical, especially benzalkonium chloride (BAC)-preserved, antiglaucoma medications can cause a negative impact on the ocular surface. The aim of the study was to assess the effect of topical carbonic anhydrase inhibitors (CAIs) on selected oxidative stress biomarkers in the tear film. METHODS: The patients were divided into four sex-matched groups: group C (n = 25) - control group - subjects who did not use topical antiglaucoma medications, group DL (n = 14) - patients using preservative-free dorzolamide, group DL + BAC (n = 16) - patients using topical BAC-preserved dorzolamide, group BL + BAC (n = 17) - patients using BAC-preserved brinzolamide. Subjects in all the study groups have been using the eye drops two times daily for 6-12 months. The oxidative stress biomarkers in the tear film samples were measured: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). RESULTS: The advanced oxidation protein products content, Total Oxidant Status as well as superoxide dismutase and catalase activities in the group DL + BAC and BL + BAC were higher in comparison with the group C. The total sulfhydryl groups content was lower in the group DL + BAC and BL + BAC when compared to group C. Oxidative Stress Index was higher in the groups DL + BAC and BL + BAC in comparison with the groups DL and C. CONCLUSIONS: Use of topical benzalkonium chloride-preserved carbonic anhydrase inhibitors increases oxidative stress in the tear film.

Influence of timolol, benzalkonium-preserved timolol, and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film.

PURPOSE: The objective of this study was to investigate the influence of topical preservative-free timolol, benzalkonium chloride(BAC)-preserved timolol, BAC-preserved timolol, and BAC-preserved brimonidine on total protein concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response, and Oxidative Stress Index (OSI) in the tear film. METHODS: The patients were divided into four groups: group C (n = 25)-control group-subjects who did not use topical antiglaucoma medications, group T (n = 17)-patients using topical preservative-free timolol, group T + BAC (n = 24)-patients using topical BAC-preserved timolol, and group BR + BAC (n = 19)-patients using topical BAC-preserved brimonidine. RESULTS: The SOD, CAT, and GPx activities as well as AOPP, TOS, and OSI were found to be higher in the tear film of patients treated with BAC-preserved topical timolol or brimonidine in comparison with patients treated with preservative-free timolol or patients who did not use antiglaucoma topical medications. CONCLUSIONS: This indicates that using BAC-preserved topical medications increases oxidative stress in the tear film and may, in the long-term, contribute to the clinical presentation of dry eye disease.

Effect of Topical Prostaglandin F2α Analogs on Selected Oxidative Stress Parameters in the Tear Film.

Background and Objectives: Topically administered antiglaucoma medications, especially those containing benzalkonium chloride (BAC), may cause local adverse effects and compromise ocular surface. The aim of the study was to assess the effect of topical prostaglandin F2α analogs (PGAs): preservative-free latanoprost, BAC-preserved latanoprost, preservative-free tafluprost, and BAC-preserved bimatoprost, on selected oxidative stress parameters in the tear film. Materials and Methods: The patients were divided into five groups: group C (n = 25) control group-subjects who did not use topical antiglaucoma medications, group L (n = 22)-patients using topical preservative-free latanoprost, group L+BAC (n = 25)-patients using topical BAC-preserved latanoprost, group T (n = 19)-patients using topical preservative-free tafluprost, and group B+BAC (n = 17)-patients using topical BAC-preserved bimatoprost. The oxidative stress markers in the tear film samples were evaluated: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). Results: The TP concentrations in the groups L, L+BAC, and B+BAC were statistically significantly higher in comparison with group C. The SOD and CAT activities in the groups L+BAC and B+BAC were statistically significantly higher when compared to group C. As compared to group C, AOPP and TOS were statistically significantly higher in all the study groups. OSI was found to be statistically significantly higher in the groups L+BAC, T, and B+BAC in comparison with group C. Conclusion: Use of topical PGAs by the patients with ocular hypertension or primary open-angle glaucoma is associated with increased oxidative stress in the tear film which is additionally exacerbated by the presence of BAC in the formulation.

Safety and outcome of allogeneic stem cell transplantation in myelofibrosis.

OBJECTIVES: We evaluated the safety and outcome of allo-HSCTs in myelofibrosis (MF). METHODS: A total of 27 patients with primary (n = 20) or secondary (n = 7) MF, aged 51 (21-63) yr, transplanted from HLA-matched related (59%) or unrelated (41%) donors were analyzed. Conditioning was reduced in 26 and myeloablative in one patient; and ATG was used in 25. Sources of stem cells were as follows: peripheral blood (21), bone marrow (4) or both (2). RESULTS: Prognostic factors that adversely affected overall survival (OS) in the multivariate analysis were as follows: recipient age >45 yr (HR = 10.55, P = 0.025) and unrelated donor (HR=3.73, P = 0.026). Post-transplant transfusion dependence adversely affected OS in the univariate analysis: dependence from either both RBCs and platelets (HR = 33.26, P = 0.001) or from either of them (HR = 10.53, P = 0.043). Of 16 JAK2V617F-positive patients evaluated post-transplant, it was eradicated in 69% and decreased in 25%. Acute GVHD III-IV developed in 19% and extensive chronic GVHD in 26% of patients; the relapse in four patients was treated with second allo-HSCT. Spleen decreased in all evaluated patients (n = 24). Fibrotic changes improved or disappeared in 80% of evaluated patients (n = 10). CONCLUSIONS: Allo-HSCT may prolong survival, provide disease regression and improve quality of life in MF, especially in patients ≤ 45 yr transplanted from matched related donors. Achieving transfusion independence post-transplant indicates the favorable outcome.

Thalidomide affects the skeletal system of young rats.

Thalidomide has indications for the treatment of several immune-related, neoplastic, and inflammatory diseases, in both adults and children. Despite numerous therapeutic indications for the application of thalidomide, the influence of that drug upon skeletal system has not been recognized. The aim of the present study was to investigate the effects of thalidomide on the osseous tissue in young rats. The experiments were carried out on 5-week-old male Wistar rats. The animals were administered thalidomide in the doses of 15, 30 or 60 mg/kg p.o. over the period of 1, 3 or 6 weeks. The body mass gain, bone mass in the tibia, femur and L-4 vertebra, histomorphometric parameters of the femur (width of trabeculae, width of epiphyseal cartilage, the transverse cross-sectional area of the bone marrow cavity and the cortical bone) and the tibia (width of osteoid, diaphysis transverse growth, the transverse cross-sectional area of the bone marrow cavity and the cortical bone) were studied. The investigations carried out provide, for the first time, information concerning the influence of thalidomide upon bone remodeling processes in young rats. The effects of thalidomide on the skeletal system of young rats depended on the dose and upon application time. After administration of doses 15, 30 and 60 mg/kg p.o. for 1 and 3 weeks, no influence of thalidomide was noted upon the examined macrometric parameters and histomorphometric parameters of femur, tibia and L-4 vertebra in young rats. Significant disturbances of bone remodeling in young rats have been observed after 6 weeks of thalidomide application, while the progression of those changes increased with the increase of the dose administered. After administering the dose of 15 mg/kg p.o. for the period of 6 weeks, no significant changes were found, as regards the macrometric and histomorphometric parameters of bones. Thalidomide, applied 6 weeks in the dose of 30 mg/kg p.o., and in particular in the dose of 60 mg/kg p.o., turned out to disturb bone remodeling processes. In animals administered thalidomide in the dose of 60 mg/kg p.o., reduction mass of tibia, femur, and L-4 vertebra has been observed. In compact bone, thalidomide reduced the diaphysis transverse growth of tibia, reduced the width of osteoid, as well as reduced the transverse cross-sectional area of cortical bone, increased the transverse cross-sectional area of marrow cavity, and increased the transverse cross-sectional area of the marrow cavity/transverse cross-sectional area of the diaphysis ratio of tibia and femur. In cancellous bone, thalidomide reduced the width of bone trabeculae, and increased the width of epiphyseal cartilage. On the basis of the results obtained, one can conclude that thalidomide applied for 6 weeks in the dose of 60 mg/kg p.o. inhibited the bone formation processes and increased the bone resorption in young rats.

Late-Onset Neuromyelitis Optica Spectrum Disorder Mimicking a Non-Arteritic Anterior Ischemic Optic Neuropathy-Case Report.

A 60-year-old white woman presented to the emergency department with painless decrease of visual acuity in the left eye (LE). The diagnosis of a non-arteritic anterior ischemic optic neuropathy in the LE was established based on the clinical picture and the results of static perimetry, fluorescein angiography, visual evoked potential, and magnetic resonance imaging (MRI) of the brain and orbit. Six months later, the patient reported visual impairment in the right eye (RE). Best corrected visual acuity (BCVA) in the RE was 5/10. Gadolinium-enhanced MRI showing inflammation of both optic nerves and the optic chiasm in correlation with positivity for immunglobulin G antibody against aquaporin-4 led to the diagnosis of late-onset neuromyelitis optica spectrum disorder. High-dose intravenous methylprednisolone therapy followed by oral tapering was administered and oral azathioprine was started to reduce the risk of further relapse. At discharge, BCVA was 5/5 in the RE. The patient remains under the care of neurology and ophthalmology clinics, with no recurrences for two years. The possibility of neuromyelitis optica spectrum disorder with optic neuritis in older patients is important in the differential diagnosis of ischemic optic neuropathy.

Choroidal neovascularization associated with butterfly-shaped pattern dystrophy - a case report.

The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.

Combined central retinal vein and cilioretinal artery occlusion in a 25-year-old woman.

We report a case of a 25-year-old woman with sudden and painless diminution in vision and central scotoma in her left eye (LE). She was a smoker and had been taking combined oral contraceptive (COC) pills for 1 year. On admission, the best-corrected visual acuity (BCVA) was 1,5/50 in the LE. Posterior segment examination revealed optic disc edema with flame-shaped retinal hemorrhages, mildly tortuous and dilated retinal veins. Moreover, retinal edema in the peripapillary and perimacular region, foci of hemorrhages and Roth's spots in the posterior pole, as well as pale superior papillomacular bundle were observed. Fundus fluorescein angiography (FFA) confirmed the delayed flow of contrast through the cilioretinal artery in the LE. The clinical picture suggested left central retinal vein (CRVO) with cilioretinal artery occlusion (CLRAO). All laboratory and imaging tests were normal except for homozygous methylenetetrahydrofolate reductase (MTHFR) gene mutation (A1298C genotypes). However, serum homocysteine (Hcy) level was normal. Low molecular weight heparin (LMWH) treatment was administered. Retinal lesions, as well as BCVA improved, but central scotoma remained. Abbreviations: aPTT = activated partial thromboplastin time, BCVA = best-corrected visual acuity, CBC = complete blood count, CLRAO = cilioretinal artery occlusion, COC = combined oral contraceptive, CRA = central retinal artery, CRP = serum C-reactive protein, CRVO = central retinal vein occlusion, CT = computed tomography, CTA = computed tomography angiography, ECG = electrocardiography, ESR = erythrocyte sedimentation rate, FERG = flash electroretinogram, FFA = fundus fluorescein angiography, GCA = ganglion cell analysis, GCL = ganglion cell layer, Hcy = homocysteine, ICGA = indocyanine green angiography, INR = international normalized ratio, IOP = intraocular pressure, IPL = inner plexiform layer, LE = left eye, LMWH = low molecular weight heparin, mfERG = multifocal electroretinogram, MTHFR = methylenetetrahydrofolate reductase, OCT = optical coherence tomography, RE = right eye, VF = visual field.

Choroidal neovascularization secondary to ocular syphilis.

Choroidal neovascularization (CNV) is a very rare but sight-threatening complication of ocular syphilis. We reported the case of a 51-year-old woman who presented with a 2-week history of visual loss in the right eye (RE). Fundus examination demonstrated vitritis and the optic disc margin blurring. Fundus fluorescein angiography (FFA) showed the presence of optic nerve edema, macular edema, and diffused impairment of the blood-retinal barrier with leakage areas, which led to the diagnosis of bilateral neuroretinitis. Optical coherence tomography (OCT) of the right macula evidenced irregularities of the retinal pigment epithelium (RPE), subretinal fluid and hyperreflective material. Besides, workup indicated positive serology for syphilis and the patient received combined treatment of ceftriaxone, systemic and topical steroids as well as cycloplegic medications. The woman did not consent to lumbar puncture or intravitreal anti-vascular epithelial growth factor (anti-VEGF) injection, therefore the prognosis for improvement of visual acuity is poor. Abbreviations: anti-VEGF = anti-vascular epithelial growth factor, AMD = age related macular degeneration, BCVA = best corrected visual acuity, CNS = central nervous system, CNV = choroidal neovascularization, CSF = cerebrospinal fluid, FFA = fundus fluorescein angiography, FTA-ABS = fluorescent treponemal antibody absorption, HIV = human immunodeficiency virus, iCNV = inflammatory CNV, IOP = intraocular pressure, LE = left eye, MRI = magnetic resonance imaging, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, RE = right eye, RPE = retinal pigment epithelium, RPR = rapid plasma regain, TP-PA = Treponema pallidum particle agglutination, VDRL = Venereal Disease Research Laboratory.

Effect of caffeine on biomarkers of oxidative stress in lenses of rats with streptozotocin-induced diabetes.

INTRODUCTION: One of the major causes of cataract in diabetes is oxidative stress induced by reactive oxygen species (ROS). Nowadays, new substances with antioxidative properties that may prevent cataract development are needed. One such substance is caffeine - an alkaloid with well-documented antioxidative activity. MATERIAL AND METHODS: The study was conducted on lenses obtained from female rats, divided into 3 groups: control rats; diabetic rats; diabetic rats treated with caffeine at a dose of 20 mg/kg p.o. Type 1 diabetes was induced by streptozotocin (60 mg/kg i.p.). After 4 weeks of caffeine administration, the rats were sacrificed, and the lenses were collected, weighed and homogenized in PBS. The homogenate was used for analysis of protein content, glutathione (GSH) concentration, advanced oxidation protein product (AOPP) concentration, malondialdehyde (MDA) concentration and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). RESULTS: The SOD, CAT and GPx activities were found to be higher in the lenses of diabetic rats. There were also increased MDA and AOPP concentrations as well as decreased GSH concentration. The administration of caffeine resulted in decreased activity of SOD, CAT and GPx. The treatment with caffeine also caused an increase of GSH concentration and a decrease of MDA and AOPP concentrations. CONCLUSIONS: The results of the present study may be of relevance in determining the effect of caffeine on the processes induced by ROS in vivo. Further, they can be an indication for clinical observations aiming at the assessment of both preventive and therapeutic effects of caffeine in cataract.

Effect of Resveratrol, a Dietary-Derived Polyphenol, on the Oxidative Stress and Polyol Pathway in the Lens of Rats with Streptozotocin-Induced Diabetes.

Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this substance may counteract the oxidative stress and polyol pathway in the lens of diabetic rats. The study was conducted on the rats with streptozotocin-induced type 1 diabetes. After the administration of resveratrol (10 and 20 mg/kg po for 4 weeks), the oxidative stress markers in the lens were evaluated: activity of superoxide dismutase, catalase and glutathione peroxidase, as well as levels of total and soluble protein, level of glutathione, vitamin C, calcium, sulfhydryl group, advanced oxidation protein products, malonyldialdehyde, Total Oxidant Status and Total Antioxidant Reactivity. The obtained results indicate that the administration of resveratrol to the diabetic rats shows antioxidative properties. It is not a result of antiglycaemic activity but resveratrol probably directly affects the antioxidative system. Resveratrol did not affect the polyol pathway in the lens of diabetic rats. Our results may indirectly indicate benefits of consumption of foods as well as dietary supplements containing resveratrol in diminishing oxidative stress in lenses of individuals suffering from diabetes mellitus.

Occurrence of secondary malignancies in chronic myeloid leukemia during therapy with imatinib mesylate-single institution experience.

INTRODUCTION: Imatinib mesylate (IM) remains the treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for long disease-free survival. Due to prolonged administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised. OBJECTIVE: To investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML. MATERIAL AND METHODS: The records of 221 CML patients treated with IM between 2003-2013 in a single institution were reviewed. The Poisson regression model was used to estimate the relative risks for SM and death in CML patients. RESULTS: Secondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31-72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. All CML patients were in hematologic and complete cytogenetic response (CCR) at the time of SM development. All of them also met the criteria for major molecular response (BCR-ABL(IS) ≤0.1%). They continued their IM while receiving treatment for SM. Among eight patients with SM, five patients are alive and remain in CCR on IM whereas three patients died due to SM. The risks for SM development as well as death due to SM in CML patients were not statistically increased if compared to age-adjusted population. CONCLUSIONS: The association between IM therapy for CML and SM development has not been found.

Effects of thalidomide on the development of bone damage caused by prednisolone in rats.

BACKGROUND: The methods used in treatment of osteoporosis induced by glucocorticosteroids are not effective enough. There is a need for new drugs which could be useful in counteracting the influence of glucocorticosteroids on osseous tissue. The aim of the present study was to investigate the effects of thalidomide on the development of osteoporosis induced by glucocorticoid (prednisolone) in rats. METHODS: The experiments were carried out on 3-month-old male Wistar rats. The animals were divided into 4 groups: I--control rats; II--prednisolone (10 mg/kg po); III--prednisolone (10 mg/kg po) + thalidomide (15 mg/kg po); IV--prednisolone (10 mg/kg po) + thalidomide (60 mg/kg po). The drugs were administered for 3 weeks. The body mass gain, bone mass in the tibia, femur and L-4 vertebra, histomorphometric parameters of the tibia (width of osteoid, diaphysis transverse growth, area of the transverse cross-sectional of the bone marrow cavity and the cortical bone) and the femur (width of trabeculae, width of epiphyseal cartilage, diaphysis transverse growth, area of the transverse cross-sectional of the bone marrow cavity and the cortical bone) were studied. RESULTS: Prednisolone induced osteoporotic skeletal changes in mature male rats (decreases in the bone mass, the width of the periosteal and endosteal osteoid, the transverse cross-sectional area of the cortical bone, the width of trabeculae, and the diaphysis transverse growth were observed). Thalidomide administered at a dose of 15 mg/kg po inhibited the development of changes in macrometric and histomorphometric parameters induced by prednisolone in the skeletal system of rats. CONCLUSION: The results may constitute indirect evidence for possible clinical trials conducted in order to define the possibility to apply thalidomide in treatment of bone diseases in humans.