In vivo study to assess dosage of allogeneic pig retinal progenitor cells: Long-term survival, engraftment, differentiation and safety.

Despite notable efforts and significant therapeutical advances, age-related macular degeneration remains the single most common reason for vision loss. Retinal progenitor cells (RPCs) are considered promising candidates for cellular treatments that repair and restore vision. In this allogenic study, the phenotypic profile of pig and human RPCs derived using similar manufacturing processes is compared. The long-term (12-week) survival of green fluorescent protein-pig retinal progenitor cells GFP-pRPC after subretinal transplantation into normal miniature pig (mini-pig) retina is investigated. Human eyes are both anatomically and physiologically mimicked by pig eyes, so the pig is an ideal model to show an equivalent way of delivering cells, immunological response and dosage. The phenotypic equivalency of porcine and clinically intended human RPCs was established. Thirty-nine mini-pigs are used in this study, and vehicle-injected eyes and non-injected eyes serve as controls. Six groups are given different dosages of pRPCs, and the cells are found to survive well in all groups. At 12 weeks, strong evidence of integration is indicated by the location of the grafted cells within the neuro-retina, extension of processes to the plexiform layers and expression of key retinal markers such as recoverin, rhodopsin and synaptophysin. No immunosuppression is used, and no immune response is found in any of the groups. No pRPC-related histopathology findings are reported in the major organs investigated. An initial dose of 250 k cells in 100 µl of buffer is established as an appropriate initial dose for future human clinical trials.

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema.

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus.

BACKGROUND: To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). METHODS: In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection. RESULTS: Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. CONCLUSION: A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules / Avaliação das alterações retinais no coelho após injeção intravítrea de sunitinib encapsulado em nanoparticulas lípidas sólidas e nanocapsulas polímeros

ABSTRACT Purpose: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. Methods: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. Results: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. Conclusions: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

RESUMO Objetivos: O presente estudo teve por objetivo avaliar a segurança da injeção intravítrea de 0,1 ml de sunitinibe em duas concentrações (1 mg/ml e 10 mg/ml), 0,1 ml de dispersão contendo nanopartículas lipídicas sólidas sem droga e 0,1 ml de dispersão contendo nanocápsulas poliméricas livre de drogas analisando os possíveis efeitos tóxicos à retina de coelhos albinos detectados pela eletrofisiologia e histologia por microscopia óptica. Métodos: Um estudo controlado experimental foi rea­lizado com 20 olhos de coelhos albinos. Foram realizadas injeções intravítrea de duas concentrações diferentes de suniti­nibe, uma dispersão contendo nanopartículas lipídicas sólidas e uma dispersão contendo nanocápsulas. O olho contralateral não recebeu tratamento e foi utilizado como controle. Resultados: Não foram observadas alterações eletrorretinográficas nos grupos do sunitinibe (1 mg/ml e 10 mg/ml) e no grupo das nanopartículas lipídicas sólidas. No grupo das nanocápsulas, houve alterações significativas tanto na morfologia, quanto na amplitude e tempo das ondas do eletrorretinograma. Ao estudo histológico, somente o grupo das nanocápsulas apresentou al­terações degenerativas (núcleos tumefeitos) com acentuado edema e formação de vacúolos citoplasmáticos, sugerindo toxidade retiniana. Conclusões: As injeções intravítreas de sunitinibe e nanopartículas lipídicas sólidas não foram tóxicas para a retina. No entanto, nanocápsulas mostraram ser tóxicas para a retina. Sendo assim, a possibilidade de poder combinar o potencial de uma droga que possui a capacidade de inibir duas importantes vias da angiogênese, às vantagens de liberação controlada das nanopartículas lipídicas sólidas, pode ser um importante recurso terapêutico para doenças vasoproliferativas oculares.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules.

PURPOSE: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. METHODS: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. RESULTS: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. CONCLUSIONS: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants.

PURPOSE: The development of photoreceptor replacement therapy for retinal degenerative disorders requires the identification of the optimal cell source and immunosuppressive regimen in a large animal model. Allotransplants are not acutely rejected in swine subretinal space, although it is not known if survival can be improved with immunosuppression. Here we investigated the survival and integration of expanded pig retinal progenitor cells (pRPCs) in normal recipients with and without transient anti-inflammatory suppression. METHODS: pRPCs were derived from the neural retina of E60 GFP transgenic pigs, expanded for six passages, characterized, and transplanted into the subretinal space of 12 pigs. Six recipients received a single intravitreal injection of rapamycin and dexamethasone. RESULTS: pRPCs expressed the photoreceptor development genes Sox2, Pax6, Lhx2, Crx, Nrl, and Recoverin in vitro. Transplanted cells were identified in 9 out of 12 recipients 4 weeks after the injection. pRPCs integrated primarily into the photoreceptor inner segment layer and outer nuclear layer with single cells present in the inner nuclear layer. Donor cells remained recoverin-positive and acquired rhodopsin. We did not observe any signs of graft proliferation. The immunosuppression did not affect the survival or distribution of grafts. No macrophage infiltration or loss of retinal structure was observed in either group. CONCLUSIONS: Local immunosuppression with rapamycin and dexamethasone does not improve the outcome of pRPC allotransplantation into the subretinal space. TRANSLATIONAL RELEVANCE: Survival and integration of pRPC together with the lack of graft proliferation suggests that allogeneic RPC transplantation without transient immunosuppression is a favorable approach for photoreceptor cell replacement.

Stem cell therapy for retinal diseases.

In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt's dystrophy, and patients with geographic atrophy, providing good outcomes. This study's intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients' vision, and, finally, approaching future directions and challenges for the treatment of several conditions.

Comparing intravitreal triamcinolone acetonide and bevacizumab injections for the treatment of diabetic macular oedema: a randomized double-blind study.

PURPOSE: To compare the effect of a single intravitreal injection of triamcinolone acetonide and bevacizumab in reducing macular thickness, which was measured by optical coherence tomography (OCT) in patients with diabetic macular oedema (DMO). METHODS: The patients received a single intravitreal injection of 1.25 mg bevacizumab in one randomly selected eye and 4.0 mg triamcinolone acetonide in the contralateral eye. Central foveal thickness measurement (CFT) with OCT was taken at the initial visit and at the 4-week, 12-week and 24-week visits. RESULTS: Eleven patients (22 eyes) were enrolled and statistically analysed. CFT reduced in the eyes treated with triamcinolone and those treated with bevacizumab in weeks 4 and 12 (p < 0.05). At the 24-week follow-up, no significant difference was noted, relative to the initial visit. Comparing the two groups treated with different drugs, a statistically significant difference in CFT in weeks 4 and 12 was noted, with a more significant reduction in triamcinolone-treated eyes (p < 0.05). Regarding visual acuity (VA), patients treated with triamcinolone had improvement in VA at 4-week (p = 0.02) and 12-week follow-up (p = 0.01), while the group treated with bevacizumab had VA improvement at 4 -week follow-up (p = 0.02). Among the eyes treated with triamcinolone, intraocular pressure (IOP) measurement of more than 21 mmHg was found in three eyes (27.3%). CONCLUSIONS: Intravitreal triamcinolone proved to be more efficient in reducing DMO, providing longer lasting visual improvement, relative to bevacizumab. Eyes treated with triamcinolone had the highest percentage increase in IOP. Further studies are needed to corroborate these findings.

[Retinal manifestations in patients with sickle cell disease referred to a University Eye Hospital]. / Alterações retinianas apresentadas em pacientes portadores de hemoglobinopatia falciforme atendidos em um Serviço Universitário de Oftalmologia.

PURPOSE: To identify retinal manifestations in patients with sickle cell disease referred to a reference eye hospital in Goiânia (GO). METHODS: Ophthalmic evaluation was made in 50 patients (100 eyes) with sickle cell disease to evaluate the most common manifestations of this group. RESULTS: Hemoglobinopathy SS was the most commonly found, followed by hemoglobin SC, AS and Stahl. Twenty-two percent of the patients had retinal changes, of these 73% were male. Retinal changes observed were: "sea fan", "black sunburst", vitreous hemorrhage, and retinal detachment. In the classification of retinopathy, 73% had proliferative form, seen in the types AS and SC and 27% had non-proliferative retinopathy, seen in patients with SS type. CONCLUSIONS: We observed a large numbers of patients with retinal changes, most of them with hemoglobinopathy SC, followed by AS and SS groups. The proliferative changes were the most commonly observed. Vitreous hemorrhage and retinal detachment were the most prevalent manifestations in proliferative retinopathy and showed to be more common in patients with SC hemoglobinopathy in the studied population.

[A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes]. / Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos.

PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.

Alterações retinianas apresentadas em pacientes portadores de hemoglobinopatia falciforme atendidos em um Serviço Universitário de Oftalmologia / Retinal manifestations in patients with sickle cell disease referred to a University Eye Hospital

OBJETIVOS: Identificar os principais achados fundoscópicos em pacientes portadores de anemia falciforme encaminhados a um Serviço Oftalmológico de Referência em Goiânia (GO). MÉTODOS: Foram realizados exames oftalmológicos em 50 pacientes (100 olhos) portadores de hemoglobinopatia falciforme para observar quais as alterações retinianas mais comuns nesse grupo. RESULTADOS: O tipo de hemoglobinopatia mais encontrado foi o SS, seguido pelas hemoglobinopatias SC, AS e Sthal. Dentro da amostra estudada, 22 por cento apresentaram alterações retinianas. Destes 73 por cento eram do sexo masculino. A alteração retinianas encontradas foram: "sea fan", "black sunburst", hemorragia vítrea e descolamento de retina. Em relação à classificação da retinopatia, 73 por cento apresentaram a forma proliferativa, sendo vista nos tipos AS e SC e 27 por cento apresentaram a forma não-proliferativa da retinopatia, sendo vista nos portadores do tipo SS. CONCLUSÃO: Foi observado elevado número de pacientes com alterações retinianas na amostra estudada, sendo o maior número em portadores da hemoglobinopatia SC, seguido dos grupos AS e SS. As alterações proliferativas foram as mais observadas. Hemorragia vítrea e descolamento de retina foram as manifestações proliferativas de maior prevalência e mostraram ser mais frequente em portadores da hemoglobinopatia SC na população estudada.

PURPOSE: To identify retinal manifestations in patients with sickle cell disease referred to a reference eye hospital in Goiânia (GO). METHODS: Ophthalmic evaluation was made in 50 patients (100 eyes) with sickle cell disease to evaluate the most common manifestations of this group. RESULTS: Hemoglobinopathy SS was the most commonly found, followed by hemoglobin SC, AS and Stahl. Twenty-two percent of the patients had retinal changes, of these 73 percent were male. Retinal changes observed were: "sea fan", "black sunburst", vitreous hemorrhage, and retinal detachment. In the classification of retinopathy, 73 percent had proliferative form, seen in the types AS and SC and 27 percent had non-proliferative retinopathy, seen in patients with SS type. CONCLUSIONS: We observed a large numbers of patients with retinal changes, most of them with hemoglobinopathy SC, followed by AS and SS groups. The proliferative changes were the most commonly observed. Vitreous hemorrhage and retinal detachment were the most prevalent manifestations in proliferative retinopathy and showed to be more common in patients with SC hemoglobinopathy in the studied population.

Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos / A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes

OBJETIVO: Determinar os níveis de toxicidade de duas e três aplicações intravítreas de infliximabe na retina de coelhos albinos, por meio de exames clínicos oftalmológicos, eletrorretinográficos e histológicos. MÉTODOS: Foram utilizados doze coelhos albinos divididos em dois grupos. No primeiro grupo de 10 coelhos, cada olho recebeu duas (n=10 olhos) ou três injeções (n=10 olhos) intravítreas de 2 mg de infliximabe dissolvidos em 0,06 ml de solução salina, em intervalos mensais. Um segundo grupo de dois coelhos, que serviu como grupo controle (n=4 olhos), foram submetidos a duas e três aplicações intravítreas de BSS. Noventa dias após, os coelhos foram novamente submetidos a exame oftalmológico (biomicroscopia, oftalmoscopia e tonometria), eletrorretinográfico e, após enucleados, a exame histológico. RESULTADOS: O exame biomicroscópico e oftalmoscópico não revelou anormalidades retinianas nos olhos injetados com infliximabe e no grupo controle. Alteração histológica notada foi a presença de raros linfócitos e eosinófilos no vítreo posterior em quatro e em seis olhos submetidos a duas e três aplicações de infliximabe sem significado clínico. A única alteração clinicamente significante foi uma reação inflamatória severa com presença de exsudatos vítreos na interface vítreo retiniana e discreto edema de células ganglionares nos dois olhos de um único coelho, sem alterações no vítreo posterior. Os exames eletrorretinográficos mostraram amplitudes em média 12-13 por cento menores daquelas obtidas antes do tratamento, contudo não houve nenhuma diferença estatisticamente significante quando comparamos as amplitudes e a latencia entre os achados electrorretinográficos pré e pós-tratamento. CONCLUSÃO: Duas e três aplicações intravítreas de infliximabe em olhos de coelhos em intervalos mensais, na dosagem de 2 mg, não provocam alterações significantes após um seguimento de noventa dias, quer no exame histológico, na eletrorretinografia e na avaliação clínica oftalmológica. Conclui-se que doses seriadas de infliximabe por via intravítrea é um procedimento seguro. Estudos clínicos em humanos devem ser realizados para melhor avaliação da segurança do seu uso no tratamento de determinadas doenças que acometem a retina e a coroide.

PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13 percent smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.

[Comparison of the analgesic effect between 90 mg etoricoxib and dipyrone after exeresis of primary pterygium with conjunctival autograft]. / Comparação do efeito analgésico entre etoricoxib 90 mg e dipirona sódica na exérese de pterígio primário com transplante autólogo de conjuntiva.

PURPOSE: To compare the analgesic effect between dipyrone, 90 mg etoricoxib, and placebo after excision of primary pterygium with conjunctival autograft. METHODS: Prospective, randomized, double-masked clinical trial. Three groups of 26 patients (one eye per patient) were submitted to surgery and received the study drugs for five days after surgery. A scale of pain was used, graduated from zero to ten, for patient evaluation in the first, third and fifth postoperative days. The pain was classified as absent (zero), mild (1 to 3), moderate (4 to 7) and severe (8 to 10). Statistical analysis was performed with the SPSS, version 11.5. RESULTS: A statistically significant difference was found between etoricoxib and dipyrone in the first and third postoperative days (p=0.001 and p=0.01; respectively). Etoricoxib was superior to placebo only in the first postoperative day (p=0.04). There was no significance in the comparison between dipyrone and placebo. CONCLUSIONS: Analgesia of etoricoxib was superior to placebo in the first postoperative day and to dipyrone in the third and fifth days after excision of primary pterygium with conjunctival autograft. There was no significant difference between dipyrone and placebo in all time points.

Comparação do efeito analgésico entre etoricoxib 90 mg e dipirona sódica na exérese de pterígio primário com transplante autólogo de conjuntiva / Comparison of the analgesic effect between 90 mg etoricoxib and dipyrone after exeresis of primary pterygium with conjunctival autograft

OBJETIVO: Comparar o efeito analgésico entre dipirona sódica e etoricoxib 90 mg após exérese de pterígio primário com transplante autólogo de conjuntiva. MÉTODOS: Trata-se de um ensaio clínico prospectivo, randomizado, duplo-mascarado. Três grupos de 26 pacientes (1 olho por paciente) foram operados e receberam as medicações em estudo durante os cinco dias seguintes à cirurgia. Foi utilizada uma escala de dor, numerada de zero a dez, para avaliação pelo paciente no 1É, 3É e 5É dias pós-operatórios. A dor foi classificada em ausente (zero), leve (1 a 3), moderada (4 a 7) e intensa (8 a 10). A análise estatística foi realizada com o software SPSS, versão 11.5. RESULTADOS: Foi observada diferença estatisticamente significativa entre etoricoxib e dipirona no 1É e 3É dia pós-operatório (PO) (p=0,001 e p=0,01; respectivamente). O etoricoxib foi superior ao placebo apenas no 1É PO (p=0,04). Não houve diferença de resultados entre dipirona e placebo. CONCLUSÕES: A analgesia do etoricoxib foi superior à do placebo no PO1 e à da dipirona no PO1 e PO3, na exérese de pterígio primário com transplante autólogo de conjuntiva. Não houve diferença significativa da analgesia pós-operatória entre dipirona e placebo no mesmo procedimento.

Purpose: To compare the analgesic effect between dipyrone, 90 mg etoricoxib, and placebo after excision of primary pterygium with conjunctival autograft. METHODS: Prospective, randomized, double-masked clinical trial. Three groups of 26 patients (one eye per patient) were submitted to surgery and received the study drugs for five days after surgery. A scale of pain was used, graduated from zero to ten, for patient evaluation in the first, third and fifth postoperative days. The pain was classified as absent (zero), mild (1 to 3), moderate (4 to 7) and severe (8 to 10). Statistical analysis was performed with the SPSS, version 11.5. RESULTS: A statistically significant difference was found between etoricoxib and dipyrone in the first and third postoperative days (p=0.001 and p=0.01; respectively). Etoricoxib was superior to placebo only in the first postoperative day (p=0.04). There was no significance in the comparison between dipyrone and placebo. CONCLUSIONS: Analgesia of etoricoxib was superior to placebo in the first postoperative day and to dipyrone in the third and fifth days after excision of primary pterygium with conjunctival autograft. There was no significant difference between dipyrone and placebo in all time points.

Perfil sorológico para doença de Chagas dos doadores de sangue do Hemocentro Regional de Uberaba / Serological profile concerning Chagas' disease of blood donors at Uberaba Blood Center

Atualmente, um dos maiores problemas na triagem sorológica de doadores de sangue para doença de Chagas é a alta freqüência de reações indeterminadas, o que faz com que muitos indivíduos sadios sejam rotulados como portadores de uma doença grave. O presente trabalho tem o objetivo de analisar o comportamento sorológico para doença de Chagas dos doadores do Hemocentro Regional de Uberaba, MG e propor mecanismos para reduzir o índice de inaptidão sorológica para essa doença. Através de estudo retrospectivo, foi analisado o resultado sorológico de 79.729 amostras obtidas de doações de sangue realizadas neste Serviço entre janeiro de 2000 e dezembro de 2004. Os resultados foram analisados quanto às variáveis: tipo de doador (novo e de retorno), gênero e idade (inferior ou igual a 30 anos e superior a 30 anos). Para a análise estatística foram realizados os testes do Qui-Quadrado e de comparação de proporções (Z). A ocorrência de doações com sorologia não negativa para doença de Chagas entre doadores novos foi significativamente superior aos de retorno, com p< 0,0001. Quanto à idade, a proporção de positivos no grupo maior de 30 anos foi significativamente superior à do grupo com idade igual ou inferior a 30 anos (p< 0,0001). O elevado número de reações indeterminadas nesse Serviço está de acordo com estudos recentes, reforçando a necessidade da implementação de testes sorológicos 100 por cento específicos ou de exames confirmatórios práticos e rápidos, passíveis de serem introduzidos nas rotinas dos serviços de hemoterapia, reduzindo o descarte desnecessário de bolsas de sangue.

Currently one of the major problems in the serological selection of blood donors in respect to Chagas' disease is the high incidence of indeterminate reactions, making a large number of healthy individuals incorrectly diagnosed as seriously ill. This paper aims at evaluating the serological pattern of Chagas' disease of donors of the Uberaba Blood Center and also to propose mechanisms to reduce the rate of serological ineligibility due to suspicion of this disease. A retrospective study of the serological results of 79,729 samples of blood was carried out between January 2000 and December 2004. The results were analyzed according to the following variables: type of donor (first-time and multiple), gender and age (less than or equal to 30 or more than 30 years old). The statistical analysis was made using the chi-square test and a comparison of proportions (Z). Indeterminate results in respect to Chagas' disease among first-time donors were significantly higher than those of multiple donations with p < 0.0001. As for age, the proportion of positivity in the over 30-year-old group was significantly higher to that of the under or equal to 30-year-old group (p < 0.0001). The high number of indeterminate reactions at this center is in accordance with recent studies, highlighting the need of implementing serological tests with 100 percent specificity or the use of practical and fast confirmation tests to be routinely introduced in hemotherapy services, reducing the unnecessary rejection of blood bags.