Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

BACKGROUND: Melan-A and tyrosinase are new immunohistochemical markers that can be used in the diagnosis of melanocytic lesions. The aim of this study was to investigate the correlation between radiotherapy or clinicohistopathological parameters and the expression of melan-A and tyrosinase in uveal melanoma. METHODS: Thirty-six enucleated cases of uveal melanoma were studied. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against melan-A and tyrosinase. The samples were classified as either positive or negative. The chi-square or the Student-t tests were used to test for the correlation of the expression rates of melan-A and tyrosinase with clinico-pathological parameters. RESULTS: Melan-A and tyrosinase were positive in 33 (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant association between the expression of melan-A or tyrosinase and radiotherapy or any clinico-pathological parameter. All specimens were positive for at least one of the immunohistochemical markers. CONCLUSION: To the best of our knowledge this is the first study concluding that the expression of melanocytic markers such as melan-A and tyrosinase is not influenced by radiotherapy or any clinico-pathological parameter. Moreover, when tyrosinase and melan-A are used together, 100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested positive for one of those markers

Malignancy in the blind painful eye - report of two cases and literature review

Background: Few cases of malignant tumors arising in a blind painful eye have previously been described. We described two cases of a blind painful eye containing an unsuspected tumor, which were enucleated to relieve the pain.Case presentations: Case 1: A 57 year-old Caucasian man presented with recurrent orbital cellulitis and endophthalmitis in the left eye (OS). the OS was blind and painful and an enucleation was performed showing a uveal melanoma by histopathological exam. Case 2: A 54 year-old Caucasian man with previous history of a rhegmatogenous retinal detachment in his left eye presented a blind painful eye. Enucleation was performed revealing a well-differentiated B-cell lymphoma of uveal tract with extra ocular extension.Conclusion: in the management of a blind painful eye, it is extremely important to rule out an intraocular malignancy particularly in those patients who have not been followed by an ophthalmologist.Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilMcGill Univ, Dept Ophthalmol, Henry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2T5, CanadaPathol & Cytopathol Lab, LAC, Campo Grande, MS, BrazilUniv Desenvolvimento Estado & Regiao Pantanal, Campo Grande, MS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

<i>In vitro</i> antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

BackgroundCurrent approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity.MethodsSARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19.ResultsDaclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans.ConclusionsDaclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy

This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, SP, BrazilPontificia Univ Catolica Valparaiso, Fac Ciencias, Valparaiso, ChileUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, SP, BrazilWeb of Scienc

Malignancy in the blind painful eye – report of two cases and literature review

Abstract Background Few cases of malignant tumors arising in a blind painful eye have previously been described. We described two cases of a blind painful eye containing an unsuspected tumor, which were enucleated to relieve the pain. Case presentations Case 1: A 57 year-old Caucasian man presented with recurrent orbital cellulitis and endophthalmitis in the left eye (OS). The OS was blind and painful and an enucleation was performed showing a uveal melanoma by histopathological exam. Case 2: A 54 year-old Caucasian man with previous history of a rhegmatogenous retinal detachment in his left eye presented a blind painful eye. Enucleation was performed revealing a well-differentiated B-cell lymphoma of uveal tract with extra ocular extension. Conclusion In the management of a blind painful eye, it is extremely important to rule out an intraocular malignancy particularly in those patients who have not been followed by an ophthalmologist.</p

IFITM1 targets HIV-1 latently infected cells for antibody-dependent cytolysis.

HIV-1 persistence in latent reservoirs during antiretroviral therapy (ART) is the main obstacle to virus eradication. To date, there is no marker that adequately identifies latently infected CD4(+) T cells in vivo. Using a well-established ex vivo model, we generated latently infected CD4(+) T cells and identified interferon-induced transmembrane protein 1 (IFITM1), a transmembrane antiviral factor, as being overexpressed in latently infected cells. By targeting IFITM1, we showed the efficient and specific killing of a latently infected cell line and CD4(+) T cells from ART-suppressed patients through antibody-dependent cytolysis. We hypothesize that IFITM1 could mark natural reservoirs, identifying an immune target for killing of latently infected cells. These novel insights could be explored to develop clinical therapeutic approaches to effectively eradicate HIV-1