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Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO). Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations. Results: There was a marked decline in ophthalmology patient visits (80-95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited. Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.
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Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.
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Doenças do Recém-Nascido , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Betametasona/uso terapêutico , Recém-Nascido Prematuro , Estudos Retrospectivos , Retardo do Crescimento Fetal/tratamento farmacológico , Corticosteroides/uso terapêutico , Doenças do Recém-Nascido/tratamento farmacológico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológicoRESUMO
PURPOSE: To report the anatomical and functional response of combined photodynamic therapy and intravitreal injection of bevacizumab in a patient with symptomatic circumscribed choroidal hemangioma. METHODS: The patient received a single-session full-fluence photodynamic therapy immediately followed by an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). RESULTS: One week after combined therapy, an improvement of best-corrected visual acuity from count fingers to 20/60 and a significant decrease in subretinal fluid were noted. One month later, we observed decreased leakage on fluorescein angiography in all phases of the study. Three months after treatment, the best-corrected visual acuity improved to 20/25 and spectral domain optical coherence tomography scans showed return to normal foveal architecture with no subretinal fluid and completely flat tumor. These findings were maintained during 4 years of follow-up. CONCLUSION: Combination therapy was associated with a rapid and persistent resolution of subretinal fluid, improvement of best-corrected visual acuity, and visual stability at 4 years of follow-up.
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Bevacizumab/administração & dosagem , Neoplasias da Coroide/tratamento farmacológico , Hemangioma/tratamento farmacológico , Fotoquimioterapia/métodos , Verteporfina/uso terapêutico , Acuidade Visual , Adulto , Inibidores da Angiogênese/administração & dosagem , Neoplasias da Coroide/diagnóstico , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Hemangioma/diagnóstico , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Tempo , Tomografia de Coerência Óptica/métodosRESUMO
Diverse spiro dihydroquinoline-oxindoles (JS series) were prepared using the BF3â¢OEt2-catalyzed imino Diels-Alder reaction between ketimine-isatin derivatives and trans-isoeugenol. Ten spiro-oxiindole derivatives were selected and evaluated at different stages of the life cycle of Leishmania braziliensis parasites, responsible for cutaneous leishmaniasis in South America. Among them, the 8'-ethyl-4'-(4-hydroxy-3-methoxyphenyl)-3'-methyl-3',4'-dihydro-1'H-spiro[indoline-3,2'-quinolin]-2-one called JS87 was able to inhibit the growth of promastigotes without affecting the mammalian cells viability, and to decrease the number of intracellular amastigotes of L. braziliensis. This spiro compound was found to act through the alteration of parasite internal regulation by disrupting the regulatory volume decrease (RVD), and to affect the sterol biosynthetic pathway at level of squalene epoxidase (SE) enzyme. These results revealed that the spiro annulation between quinoline and oxindole scaffolds enhances the anti-leishmanial activity, and could assist in the development of potent quinoline-oxindole hybrids against Leishmania braziliensis, the main etiological agent of cutaneous leishmaniasis in South America.
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Antiprotozoários/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Oxindóis/farmacologia , Quinolinas/farmacologia , Compostos de Espiro/farmacologia , Animais , Antiprotozoários/química , Concentração Inibidora 50 , Leishmania braziliensis/crescimento & desenvolvimento , Leishmania braziliensis/metabolismo , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Oxindóis/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacologia , Quinolinas/química , Compostos de Espiro/químicaRESUMO
PURPOSE: To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT). METHODS: This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m2) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm. RESULTS: In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections. CONCLUSIONS: Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative.
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Coriorretinopatia Serosa Central/terapia , Terapia a Laser/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Verteporfina/administração & dosagem , Adulto , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/fisiopatologia , Coriorretinopatia Serosa Central/cirurgia , Doença Crônica , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Verde de Indocianina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
Leishmania donovani is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by L. donovani Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine and also affects the parasite mitochondrion, inhibiting the cytochrome c oxidase, it is to be expected that this potent drug also produces its effect through other targets. In this context, it has been reported that the disruption of the intracellular Ca2+ homeostasis represents an important object for the action of drugs in trypanosomatids. Recently, we have described a plasma membrane Ca2+ channel in Leishmania mexicana, which is similar to the L-type voltage-gated Ca2+ channel (VGCC) present in humans. Remarkably, the parasite Ca2+ channel is activated by sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the present work we demonstrated that, similarly to sphingosine, miltefosine is able to activate the plasma membrane Ca2+ channel from L. donovani Interestingly, nifedipine, the classical antagonist of the human channel, was not able to fully block the parasite plasma membrane Ca2+ channel, indicating that the mechanism of interaction is not identical to that of sphingosine. In this work we also show that miltefosine is able to strongly affect the acidocalcisomes from L. donovani, inducing the rapid alkalinization of these important organelles. In conclusion, we demonstrate two new mechanisms of action of miltefosine in L. donovani, both related to disruption of parasite Ca2+ homeostasis.
Assuntos
Antiprotozoários/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Leishmania donovani/efeitos dos fármacos , Organelas/efeitos dos fármacos , Organelas/metabolismo , Fosforilcolina/análogos & derivados , Animais , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Homeostase/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nifedipino/farmacologia , Fosforilcolina/farmacologia , Esfingosina/farmacologiaRESUMO
PURPOSE: To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. METHODS: Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. RESULTS: A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg (p < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months (p < 0.0001). CONCLUSIONS: An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration.
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With the aim to identify a potential drug candidate to treat cutaneous leishmaniasis, a series of 1-phthalazinyl hydrazones were synthesized and tested against Leishmania braziliensis parasite, one of the main responsible of this disease in the world. A structure-activity relationship permitted to identify two phthalazines containing nitroheterocyclic moiety 3l and 3m as promising new lead compounds. These compounds showed a significant antileishmanial activity against promastigote form of L. braziliensis, with EC50 values in sub-micromolar and nanomolar ranges. The phthalazine 3l also displayed a selective and excellent activity against the clinically relevant intracellular amastigotes form, with a EC50 value in sub-micromolar range (0.59 µM), without affecting the viability of the host cells. Oxidative stress was identified as the possible mode of action of the most active phthalazine. Considering their significant antileishmanial activity and ease synthesis, the phthalazine containing nitroheterocyclic represents a promising agent against Leishmania braziliensis for the rational design of new leads.
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Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Desenho de Fármacos , Hidrazonas/síntese química , Hidrazonas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Ftalazinas/química , Animais , Antiprotozoários/química , Antiprotozoários/toxicidade , Linhagem Celular , Hidrazonas/química , Hidrazonas/toxicidade , Leishmania braziliensis/enzimologia , Leishmania braziliensis/crescimento & desenvolvimento , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Conformação Proteica , Relação Estrutura-Atividade , Superóxido Dismutase/química , Superóxido Dismutase/metabolismoRESUMO
Los tratamientos de primera línea para la enfermedad de Chagas generan importantes efectos adversos que acentúan el deterioro de la salud en los pacientes. La necesidad de generar fármacos alternativos ha permitido desarrollar estudios donde se emplean parásitos capaces de expresar una proteína fluorescente, a fin de correlacionar fluorescencia con población de protozoarios. En este sentido, ideamos una metodología para el seguimiento de la proliferación de Trypanosoma cruzi-GFP (Green Fluorescent Protein) en modelos in vitro e in vivo, empleando el equipo iBox- UVP. Los ensayos in vitro se iniciaron con una curva de calibración usando concentraciones entre 5x105 y 5x107 parásitos/mL. Seguidamente, con una curva de proliferación evidenciamos a través de la fluorescencia la susceptibilidad de los parásitos frente a la droga comercial Benznidazol (IC50= 5,3±1,3 μM). En el ensayo in vivo se corroboró cualitativamente el efecto quimioterapéutico del Benznidazol (100 mg/kg/día) en ratones C57BL/6, partiendo de un inóculo de 2,5x105 parásitos, haciendo captura de imágenes de fluorescencia cada dos días a partir del día 1, e inicio del tratamiento por vía oral el sexto día. El coeficiente de correlación cercano a 1 obtenido en la curva de calibración habla de un método de cuantificación parasitario sencillo y robusto; también los ensayos en modelos in vitro e in vivo permitieron monitorear el efecto dosis-dependiente de Benznidazol sobre T. cruzi-GFP. En síntesis, elaboramos una metodología novedosa, rápida, no invasiva y que sigue en tiempo real la respuesta quimioterapéutica de drogas anti-T. cruzi.
The first-line treatments for Chagas disease generate significant adverse effects that accentuate the health deterioration in patients. The need to generate alternative drugs has led to the development of studies in which parasites will express a fluorescent protein, and correlate this expression with protozoan population. We devised a methodology for monitoring the proliferation of Trypanosoma cruzi- GFP (Green Fluorescent Protein) in models in vitro and in vivo, using the equipment iBox-UVP. In vitro assays were initiated with a calibration curve using concentrations between 5x105 and 5x107 parasites/mL. Subsequently, with a proliferation curve, through fluorescence we determined the susceptibility of the parasites against the commercial drug Benznidazol (IC50= 5,3±1,3 μM). In vivo assays corroborated qualitatively the chemotherapeutic effect of Benznidazol (100 mg/kg/day) in C57BL/6 mice, starting from an inoculum of 2.5x105 parasites, making capture of fluorescence imaging every two days from day 1, and starting oral treatment on the sixth day. The correlation coefficient close to 1 obtained in the calibration curve showed that this quantification method of parasites is simple and robust; assays in vitro and in vivo allowed monitoring dose-dependent effects of Benznidazol agains T. cruzi-GFP. We have produced an innovative, rapid, non-invasive method that monitors in real time the chemotherapeutic response of anti-T. cruzi drugs.
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Purpose: This study was designed to evaluate the visual and anatomical outcomes after cataract surgery in diabetic patients with different intraoperative therapeutic strategies. Methods: The research design comprised of a multicentric, retrospective, interventional study conducted at 6 centers in Argentina, Brazil, Costa Rica, Puerto Rico, Spain, and Venezuela. We included 138 diabetic patients with at least 6-month follow-up following phacoemulsification and intraocular lens implantation. Best-corrected visual acuity (BCVA) and central subfield thickness were collected at baseline and at 1-, 2-, 3-, and 6-month follow-up. Of these, 42 cases were not treated with any intraoperative coadjuvant medication (Group 1), 59 patients received intraoperative bevacizumab (Group 2) and 37 patients received intraoperative triamcinolone (4 mg/0.1 ml) (Group 3). Results: The mean logMAR [± standard deviation (SD)] BCVA improved from 0.82 (± 0.43) at baseline, to 0.14 (± 0.23) at 6-month follow-up (p<0.001) in Group 1; from 0.80 (± 0.48) to 0.54 (± 0.45) (p<0.001) in Group 2; and from 1.0 (± 0.40) to 0.46 (± 0.34) (p<0.001) in Group 3. The mean central subfield thickness increased from 263.57 µm (± 35.7) at baseline to 274.57 µm (± 48.7) at 6-month follow-up (p=0.088) in Group 1; from 316.02 µm (± 100.4) to 339.56 µm (± 145.3) (p=0.184) in Group 2; and from 259.18 µm (± 97.9) to 282.21 µm (± 87.24) (p=0.044) in Group 3. Conclusion: Diabetic patients may significantly benefit from cataract surgery. This study provides evidence to support the use of intravitreal triamcinolone or bevacizumab at the time of cataract surgery in cases with pre-existent diabetic macular edema or moderate-severe non-proliferative diabetic retinopathy. .
Objetivo: Avaliar os resultados visuais e anatômicos após a cirurgia de catarata em pacientes diabéticos com estratégias terapêuticas intraoperatórias diferentes. Métodos: Estudo multicêntrico, retrospectivo, de intervenção realizado em 6 centros da Argentina, Brasil, Costa Rica, Porto Rico, Espanha e Venezuela. Foram incluídos 138 pacientes diabéticos com pelo menos 6 meses de seguimento após facoemulsificação com implante de lente intraocular. Acuidade visual melhor corrigida (BCVA) e a espessura subcampo central (CST ) foram coletadas no início e em 1, 2, 3 e 6 meses de seguimento. Destes, 42 casos não foram tratadas com qualquer co-adjuvante de medicamentos intra-operatório (Grupo 1), 59 pacientes receberam bevacizumab intraoperatório (Grupo 2), e 37 pacientes receberam triancinolona intraoperatória (4 mg/0,1 ml) (Grupo 3). Resultados: A média logMAR (± desvio-padrão [DP]) BCVA melhorou de 0,82 (± 0,43) no início do estudo, para 0,14 (± 0,23) aos 6 meses de seguimento (p<0,001) no Grupo 1; de 0,80 (± 0,48) para 0,54 (± 0,45) (p<0,001) no Grupo 2; e de 1,0 (± 0,40) para 0,46 (± 0,34) (p<0,001) no Grupo 3. A CST média aumentou de 263,57 µm (± 35,7) na linha de base para 274,57±48,7 µm em 6 meses acompanhamento (p=0,088) no Grupo 1; de 316,02 µm (± 100,4), para 339,56 µm (± 145,3) (p=0,184) no Grupo 2; e de 259,18 µm (± 97,9), para 282,21 µm (±87,24) (p=0,044) no grupo 3. Conclusões: Pacientes diabéticos podem se beneficiar significativamente da cirurgia de catarata. Este estudo parece fornecer evidências para apoiar o uso de triancinolona intravítrea ou bevacizumab no momento da cirurgia de catarata em casos com edema macular diabético preexistente (DME) ou retinopatia diabética não-proliferativa moderada a grave. .