Descolamento ciliocoroidal e hipotonia causados por supressores do humor aquoso: síndrome da supersensibilidade aos supressores do humor aquoso

Os autores descrevem um caso de hipotonia e descolamento ciliocoroidal que ocorreu com administração de drogas supressoras do humor aquoso (timolol e acetazolamida) em paciente que havia sido submetido à trabeculectomia (3 meses antes). Por ser o 6° ou o 7° caso descrito na literatura, chamam atenção para esta rara síndrome que inclui a supersensibilidade do corpo ciliar aos supressores do HA, como causa de hipotonia e descolamento ciliocoroidal tardios em pacientes submetidos à cirurgia filtrante. Apresentam também um resumo dos casos encontrados na literatura.

Evaluation of IFA, MAT, ELISAs and immunoblotting for the detection of anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs

The study evaluated the efficiency of diagnostic laboratory methods to detect anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs. 18-mixed breed pigs were used during the experiment; these were divided into two groups, G1 (infected group, n = 10) and G2 (uninfected group, n = 8). Infection was performed with 4 × 10 4 VEG strain oocysts at day 0 by the oral route in G1 animals. All pigs were euthanized at day 60, when retina, aqueous humour, and blood samples were collected. Anti-T. gondii antibody levels were assessed in serum (s) and aqueous humour (ah) by indirect immunofluorescence assay (IFA), modified agglutination test (MAT), m-ELISA (using crude membranes from T. gondii tachyzoites as antigen) and r-ELISA (using rhoptries from T. gondii tachyzoites as antigen). Polymerase chain reactions (PCR) of samples from the retina were performed by using Tox4 and Tox5 primers. Antibody titers of G1 animals ranged from 128 to 1024 and from 16 to 256 in serum and aqueous humour, respectively. There were differences in the correlation coefficients between IFA(s) × IFA (ah) (r = 0.62, P = 0.05), MAT(s) × MAT (ah) (r = 0.97, P < 0.0001); however, there was no significant difference between r-ELISA(s) × r-ELISA (ah) (r = 0.14, P = 0.7). Antibodies present in serum and aqueous humour recognized similar antigens. Samples of retina were positive by PCR in 30% (3/10) of infected pigs. G2 animals remained without antibody levels and were PCR negative throughout the experiment. These results suggest that the use of a combination of tests and immunoblotting for paired aqueous humour and serum samples could improve the sensitivity and specificity for the diagnosis of ocular toxoplasmosis. © 2007 Elsevier Ltd. All rights reserved.

Pressão intra-ocular, condições endoteliais e prostaglandina E2 no humor aquoso de cães com catarata senil madura ou hipermatura

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alterações clínicas, protéicas do humor aquoso, sorológicas e histopatológicas em olhos de cães (Canis familiaris) (Linnaeus, 1758), infectados experimentalmente, por via conjuntival, com Leishmania (Leishmania) chagasi (Cunha & Chagas, 1937)

Pós-graduação em Cirurgia Veterinária - FCAV

Condições do humor aquoso, quanto à contaminação, na facoemulsificação com implante de lente intraocular em cães

Pós-graduação em Cirurgia Veterinária - FCAV

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.

Cochlin in the eye: Functional implications

Aqueous humor is actively produced in the ciliary epithelium of the anterior chamber and has important functions for the eye. Under normal physiological conditions, the inflow and outflow of the aqueous humor are tightly regulated, but in the pathologic state this balance is lost. Aqueous outflow involves structures of the anterior chamber and experiences most resistance at the level of the trabecular meshwork (TM) that acts as a filter. The modulation of the TM structure regulates the filter and its mechanism remains poorly understood. Proteomic analyses have identified cochlin, a protein of poorly understood function, in the glaucomatous TM but not in healthy control TM from human cadaver eyes. The presence of cochlin has subsequently been confirmed by Western and immunohistochemical analyses. Functionally, cochlin undergoes multimerization induced by shear stress and other changes in the microenvironment. Cochlin along with mucopolysaccharide deposits have been found in the TM of glaucoma patients and in the inner ear of subjects affected by the hearing disorder DNFA9, a late onset, progressive disease that also involves alterations in fluid shear regimes. In vitro, cochlin induces aggregation of primary TM cells suggesting a role in cell adhesion, possibly in mechanosensation, and in modulation of the TM filter.

Increase in microbial contamination risk with compression of the lid margin in eyes having cataract surgery

Purpose: To assess the bacterial contamination risk in cataract surgery associated with mechanical compression of the lid margin immediately after sterilization of the ocular surface.

Setting: Department of Cataract, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design: Prospective randomized controlled double-masked trial.

Methods: Patients with age-related cataract were randomly assigned to 1 of 2 groups. In Group A (153 eyes), the lid margin was compressed and scrubbed for 360 degrees 5 times with a dry sterile cotton-tipped applicator immediately after ocular sterilization and before povidone-iodine irrigation of the conjunctival sac. Group B (153 eyes) had identical sterilization but no lid scrubbing. Samples from the lid margin, liquid in the collecting bag, and aqueous humor were collected for bacterial culture. Primary outcome measures included the rate of positive bacterial culture for the above samples. The species of bacteria isolated were recorded.

Results: Group A and Group B each comprised 153 eyes. The positive rate of lid margin cultures was 54.24%. The positive rate of cultures for liquid in the collecting bag was significantly higher in Group A (23.53%) than in Group B (9.80%) (P=.001).The bacterial species cultured from the collecting bag in Group B were the same as those from the lid margin in Group A. The positive culture rate of aqueous humor in both groups was 0%.

Conclusion: Mechanical compression of the lid margin immediately before and during cataract surgery increased the risk for bacterial contamination of the surgical field, perhaps due to secretions from the lid margin glands.

Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

The hypotensive effect of exercise on IOP : an interaction of physical fitness and parasympathetic efficacy

RÉSUMÉ Suite à une centaine de publications sur la réduction de la PIO post-exercice, il est connu que parmi un grand nombre de programme d'exercices de différentes durées et intensités, les effets hypotenseurs de l'exercice sur la PIO sont atténués chez les sujets en bonne condition physique. Le mécanisme proposé est l'augmentation potentielle de l'efficacité du système parasympathique avec l'activité physique. Le principal objectif de cette thèse est d'identifier les facteurs contribuants à la réduction de la PIO post-exercice et d'élucider les différents mécanismes possibles. L'étude 1, une méta-analyse, a été menée afin de quantifier les contributions relatives de l'intensité et de la durée de l'effet de l'exercice sur la PIO et la mesure dans laquelle ces variables affectent les sujets sédentaires et normalement actifs. La tendance ressortant des résultats est que la diminution de la PIO suite à de l'exercice aérobie est plus élevée chez les sujets sédentaires que les sujets en bonne condition physique. (ES = -4.198 mm Hg et -2.340 mm Hg, respectivement). L'absence d'un contrôle des liquides ingérés avant l'activité physique est à souligné dans cette étude. L'hyperosmolarité (un effet secondaire de la déshydratation) est l'un des mécanismes proposés influant l'effet hypotenseur de l'exercice. L'étude 2 comparait la réduction de la PIO dans deux conditions, soit hypohydraté et hyperhydraté, avant, pendant et après un effort de 90 minutes sur un ergocycle. Après une diminution initiale pour les deux conditions, la PIO revient aux valeurs de départ pour la condition hypohydratée malgré une perte de poids significative et elle augmente pour la condition hyperhydratée (résultat du protocole d'hydratation). Étant donné le niveau élevé de participants en bonne condition physique dans l'étude 2, la troisième étude a été conçue afin de etude la relation entre la PIO et la condition physique. À l'aide d'analyses corrélationnelles il a été possible d'observer la relation entre le test de vo2max et la moyenne des mesures de PIO prises sur un intervalle de huit semaines. Une relation significative n'existait que pour les participants se situant dans la portion supérieure du continuum de la condition physique. Conclusion: Les résultats de la présente étude suggèrent que l'effet hypotenseur de l'exercice sur la PIO est probablement une réponse homéostatique à la dérégulation de l'humeur aqueuse causée par l'initiation de l'exercice et le protocole d'ingestion de fluides pré-exercice.

Uveítis pediática no infecciosa, una experiencia de una cohorte colombiana

Resumen: •Antecedentes: La uveítis pediátrica no infecciosa tiene el potencial de desencadenar severas complicaciones visuales y su manejo farmacológico convencional está asociado a importantes efectos secundarios. 1 Infliximab (INF) y Adalimumab (ADA), son dos medicamentos biológicos disponibles para el manejo de la uveítis pediátrica refractaria. Se unen específicamente al TNFα y previenen la unión del mismo con los receptores celulares; interacción directamente implicada en el proceso inflamatorio y el subsecuente daño tisular. 2,3 •Métodos: Se realizó estudio de tipo cohorte retrospectiva mediante revisión de historias clínicas de 35 pacientes pediátricos diagnosticados con uveítis durante los años 2009-2015. Se comparó control de la inflamación ocular, tiempo de respuesta y eventos adversos en pacientes tratados con ADA o INF con dosis bajas de Metotrexate vs. Metotrexate (MTX) como única terapia. •Resultados: El 45.7% de la población estudiada correspondía al sexo femenino, cuya edad promedio de inicio de síntomas y de diagnósticos fue de 9 años. El 80% de los casos fueron uveítis idiopáticas, seguido por Vogt-Koyanagi-Harada (8,5%) y AIJ (5,7%). El 91,4% presentó compromiso ocular bilateral y se documentaron 2 casos de ambliopía. El 12,9% de los pacientes que recibieron MTX como tratamiento de primera línea requirieron escalonamiento terapéutico por presentar eventos adversos (Elevación de enzimas hepáticas e intolerancia gastrointestinal (GI)). El tiempo promedio para alcanzar control de la inflamación con MTX fue 9 semanas, y para Adalimumab fue de 8,75 semanas (P: 0,90). Se comparó la capacidad de controlar la inflamación del MTX vs Anti-TNF, y no se observaron diferencias significativas (P: 0.88).

Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (M-w < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.

Thermal analysis of biodegradable microparticles containing ciprofloxacin hydrochloride obtained by spray drying technique

Thermal analysis has been extensively used to obtain information about drug-polymer interactions and to perform pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles of poly(D,L-lactide-co-glycolide) (PLGA) containing ciprofloxacin hydrochloride (CP) in various drug:polymer ratios were obtained by spray drying. The main purpose of this study was to investigate the effect of the spray drying process on the drug-polymer interactions and on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG) and infrared spectroscopy (IR). The results showed that the high levels of encapsulation efficiency were dependant on drug:polymer ratio. DSC and TG/DTG analyses showed that for physical mixtures of the microparticles components the thermal profiles were different from those signals obtained with the pure substances. Thermal analysis data disclosed that physical interaction between CP and PLGA in high temperatures had occurred. The DSC and TG profiles for drug-loaded microparticles were very similar to the physical mixtures of components and it was possible to characterize the thermal properties of microparticles according to drug content. These data indicated that the spray dryer technique does not affect the physicochemical properties of the microparticles. In addition, the results are in agreement with IR data analysis demonstrating that no significant chemical interaction occurs between CP and PLGA in both physical mixtures and microparticles. In conclusion, we have found that the spray drying procedure used in this work can be a secure methodology to produce CP-loaded microparticles. (C) 2007 Elsevier B.V. All rights reserved.

Effects of meloxicam administered by different routes to control experimental uveitis in dogs

Foram estudados os efeitos do meloxicam, aplicado por diferentes vias, em uveítes experimentais em cães. Realizou-se paracentese de câmara anterior em dois momentos (M0 e M1), com intervalo de cinco horas entre si. em M0 e M1, foram coletados 0,2mL de humor aquoso e determinou-se a concentração de proteína total e de prostaglandina E2 (PGE2). Constituíram-se quatro grupos (n=5), que receberam meloxicam ao final de M0 pelas vias subcutânea (GI), subconjuntival (GII) e tópica (GIII). Um quarto grupo não recebeu tratamento (Controle). Procedeu-se à avaliação histopatológica nos indivíduos do GII. Os resultados foram avaliados estatisticamente (p≤0,05). em todos os grupos, encontrou-se aumento significativo dos níveis protéicos e de PGE2 em M1. Não se observou diferença significativa, em M1, entre os grupos para nenhum dos parâmetros estudados. Exsudado inflamatório de caráter agudo e hemorragia discreta foram vistos à histopatologia após a aplicação do meloxicam. O meloxicam foi ineficaz em inibir a síntese de PGE2 e o influxo de proteínas para a câmara anterior, por qualquer uma das vias testadas.

Effects of carprofen administered by different routes to control experimental uveitis in dogs

Estudaram-se os efeitos do carprofeno, aplicado por diferentes vias, em uveítes experimentais em cães. Realizou-se paracentese de câmara anterior em dois momentos (M0 e M1), com intervalo de cinco horas entre si. em M0 e M1, colheram-se 0,2mL de humor aquoso e determinaram-se as concentrações de proteína total e de prostaglandina E2 (PGE2). Constituíram-se quatro grupos (n = 8), que receberam carprofeno ao final de M0 pelas vias subcutânea (GI), subconjuntival (GII) e tópica (GIII). Um quarto grupo não recebeu tratamento (controle). Procedeu-se à avaliação histopatológica nos indivíduos do GII. em todos os grupos, encontrou-se aumento significativo dos níveis proteicos e de PGE2 em M1. Não se observou diferença significativa, em M1, entre os grupos para nenhum dos parâmetros estudados. Exsudado inflamatório de caráter agudo e hemorragia discreta foram vistos à histopatologia após a aplicação do fármaco. O carprofeno foi ineficaz em inibir a síntese de PGE2 e o influxo de proteínas para a câmara anterior, por qualquer uma das vias testadas. Contudo, a redução de 44% nos níveis de proteínas (via tópica), sugere que por esta via ele pode ser utilizado como adjuvante no controle da uveíte em cães.