RESUMO
ABSTRACT Purpose: To estimate the prevalence and risk factors of dry eye disease symptoms and clinical diagnoses in Sao Paulo city, state of Sao Paulo, Brazil. Methods: A total of 582 participants over 18 years old, living in the east zone of Sao Paulo city responded to a short questionnaire. Dry eye disease was on that is defined by the presence of severe symptoms or previous clinical diagnosis of dry eye disease by an ophthalmologist. The association between dry eye disease and possible risk factors was assessed. Results: Overall dry eye disease severe symptoms and/or clinical diagnoses prevalence was calculated as 24.4% for both sexes. Women presented a higher frequency of severe symptoms of dry eye disease (16.07%) than men (8.48%; p=0.0244), as well as the composite of severe symptoms or diagnosed dry eye disease, presented by 26.86% of women and 18.18% of men (p=0.0366). In women, ages between 55 to 75 years old were associated with dry eye disease severe symptoms (OR=3.11; 95%CI 1.56-6.23, p=0.001) and diagnosed dry eye disease (OR=2.02; 95% CI 1.04-3.93, p=0.037). Hypertension was significantly associated with dry eye disease symptoms (OR=1.98; 95% CI 1.14-3.43, p=0.015) and diagnoses (OR=3.54; 95% CI 1.92-6.53, p=0.0001) in women. Eye drops use was associated with severe symptoms of dry eye disease and diagnosed dry eye disease in both women and men (p≤0.01). Conclusions: Dry eye disease prevalence in Sao Paulo city is higher in women than in men. Age and hypertension were stronger risk factors of dry eye disease for women, while eye drops use was a significant indicator of dry eye disease for both sexes.
RESUMO Objetivo Estimar a prevalência e os fatores de risco para os sintomas e o diagnóstico clínico da doença do olho seco na cidade de São Paulo, estado de São Paulo, Brasil. Métodos: Quinhentos e oitenta e dois participantes acima de 18 anos, residentes na zona leste da cidade de São Paulo responderam a um questionário de três perguntas sobre olho seco. A doença do olho seco foi definida pela presença de sintomas severos ou diagnóstico clínico prévio de doença do olho seco por um oftalmologista. A associação entre doença do olho seco e possíveis fatores de risco foi avaliada. Resultados: A prevalência de sintomas graves da doença do olho seco e/ou diagnóstico clínico foi calculada em 24,4% para ambos os sexos. O sexo feminino apresentou uma frequência maior de sintomas severos da doença do olho seco (16,07%) que o sexo masculino (8,48%; p=0,0244), assim como a associação de sintomas severos ou diagnóstico de doença do olho seco, foi de 26,86% no sexo feminino e 18,18% no sexo masculino (p=0,0366). No sexo feminino, a faixa etária entre 55 e 75 anos de idade foi associada com sintomas severos da DOS (odds ratios (OR) = 3,11; IC 95% 1,56-6,23; p=0,001) e com doença do olho seco diagnosticada (OR=2,02; IC 95% 1,04-3,93; p=0,037). Hipertensão foi associado com sintomas da doença do olho seco (OR=1,98; IC 95% 1,14-3,43; p=0,015) e diagnóstico da doença do olho seco (OR=3,54; IC 95% 1,92-6,53; p=0,001) no sexo feminino. Uso de colírios foi associado a sintomas severos e diagnóstico da doença do olho seco em ambos os sexos (p≤0,01). Conclusão: A prevalência da doença do olho seco na cidade de São Paulo é mais frequente no sexo feminino que no masculino. Idade e hipertensão foram fatores de risco maiores para doença do olho seco no sexo feminino, enquanto uso de colírios foi um indicador de doença do olho seco para ambos os sexos.
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Glioblastoma patients have a poor prognosis mainly due to temozolomide (TMZ) resistance. NRF2 is an important transcript factor involved in chemotherapy resistance due to its protective role in the transcription of genes involved in cellular detoxification and prevention of cell death processes, such as ferroptosis. However, the relation between NRF2 and iron-dependent cell death in glioma is still poorly understood. Therefore, in this study, we analyzed the role of NRF2 in ferroptosis modulation in glioblastoma cells. Two human glioblastoma cell lines (U251MG and T98G) were examined after treatment with TMZ, ferroptosis inducers (Erastin, RSL3), and ferroptosis inhibitor (Ferrostatin-1). Our results demonstrated that T98G was more resistant to chemotherapy compared to U251MG and showed elevated levels of NRF2 expression. Interestingly, T98G revealed higher sensitivity to ferroptosis, and significant GSH depletion upon system xc- blockage. NRF2 silencing in T98G cells (T98G-shNRF2) significantly reduced the viability upon TMZ treatment. On the other hand, T98G-shNRF2 was resistant to ferroptosis and reverted intracellular GSH levels, indicating that NRF2 plays a key role in ferroptosis induction through GSH modulation. Moreover, silencing of ABCC1, a well-known NRF2 target that diminishes GSH levels, has demonstrated a similar collateral sensitivity. T98G-siABCC1 cells were more sensitive to TMZ and resistant to Erastin. Furthermore, we found that NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. Altogether, our data indicate that high levels of NRF2 result in collateral sensitivity on glioblastoma via the expression of its pro-ferroptotic target ABCC1, which contributes to GSH depletion when the system xc- is blocked by Erastin. Thus, ferroptosis induction could be an important therapeutic strategy to reverse drug resistance in gliomas with high NRF2 and ABCC1 expression.
Assuntos
Ferroptose , Glioblastoma , Glioma , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Fator 2 Relacionado a NF-E2/genética , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Regulação para CimaRESUMO
PURPOSE: To estimate the prevalence and risk factors of dry eye disease symptoms and clinical diagnoses in Sao Paulo city, state of Sao Paulo, Brazil. METHODS: A total of 582 participants over 18 years old, living in the east zone of Sao Paulo city responded to a short questionnaire. Dry eye disease was on that is defined by the presence of severe symptoms or previous clinical diagnosis of dry eye disease by an ophthalmologist. The association between dry eye disease and possible risk factors was assessed. RESULTS: Overall dry eye disease severe symptoms and/or clinical diagnoses prevalence was calculated as 24.4% for both sexes. Women presented a higher frequency of severe symptoms of dry eye disease (16.07%) than men (8.48%; p=0.0244), as well as the composite of severe symptoms or diagnosed dry eye disease, presented by 26.86% of women and 18.18% of men (p=0.0366). In women, ages between 55 to 75 years old were associated with dry eye disease severe symptoms (OR=3.11; 95%CI 1.56-6.23, p=0.001) and diagnosed dry eye disease (OR=2.02; 95% CI 1.04-3.93, p=0.037). Hypertension was significantly associated with dry eye disease symptoms (OR=1.98; 95% CI 1.14-3.43, p=0.015) and diagnoses (OR=3.54; 95% CI 1.92-6.53, p=0.0001) in women. Eye drops use was associated with severe symptoms of dry eye disease and diagnosed dry eye disease in both women and men (p≤0.01). CONCLUSIONS: Dry eye disease prevalence in Sao Paulo city is higher in women than in men. Age and hypertension were stronger risk factors of dry eye disease for women, while eye drops use was a significant indicator of dry eye disease for both sexes.
Assuntos
Síndromes do Olho Seco , Hipertensão , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Adolescente , Brasil/epidemiologia , Prevalência , Fatores de Risco , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/diagnóstico , Soluções OftálmicasRESUMO
Glioblastoma patients have a poor prognosis mainly due to temozolomide (TMZ) resistance. NRF2 is an important transcript factor involved in chemotherapy resistance due to its protective role in the transcription of genes involved in cellular detoxification and prevention of cell death processes, such as ferroptosis. However, the relation between NRF2 and iron-dependent cell death in glioma is still poorly understood. Therefore, in this study, we analyzed the role of NRF2 in ferroptosis modulation in glioblastoma cells. Two human glioblastoma cell lines (U251MG and T98G) were examined after treatment with TMZ, ferroptosis inducers (Erastin, RSL3), and ferroptosis inhibitor (Ferrostatin-1). Our results demonstrated that T98G was more resistant to chemotherapy compared to U251MG and showed elevated levels of NRF2 expression. Interestingly, T98G revealed higher sensitivity to ferroptosis, and significant GSH depletion upon system xc− blockage. NRF2 silencing in T98G cells (T98G-shNRF2) significantly reduced the viability upon TMZ treatment. On the other hand, T98G-shNRF2 was resistant to ferroptosis and reverted intracellular GSH levels, indicating that NRF2 plays a key role in ferroptosis induction through GSH modulation. Moreover, silencing of ABCC1, a well-known NRF2 target that diminishes GSH levels, has demonstrated a similar collateral sensitivity. T98G-siABCC1 cells were more sensitive to TMZ and resistant to Erastin. Furthermore, we found that NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. Altogether, our data indicate that high levels of NRF2 result in collateral sensitivity on glioblastoma via the expression of its pro-ferroptotic target ABCC1, which contributes to GSH depletion when the system xc− is blocked by Erastin. Thus, ferroptosis induction could be an important therapeutic strategy to reverse drug resistance in gliomas with high NRF2 and ABCC1 expression.
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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and potentially fatal inflammatory vesiculobullous reactions that affect the skin and mucous membranes, and which are most often triggered by particular medications and infections. In Brazil, the drugs most frequently associated with TEN and SJS include cold medicine such as dipyrone and NSAIDs, followed by carbamazepine, phenobarbital, penicillin, and allopurinol. Genetic variations have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. The most closely associated genes found in Brazilian cold-medicine-related SJS/TEN patients with severe ocular complications are HLA-A*66:01 in those of mixed African and European ancestry and HLA-B*44:03 and HLA-C*12:03 in those of solely European ancestry. Our classification system for grading ocular surface complication severity in SJS/TEN patients revealed the most severe complications to be limbal stem cell deficiency and dry eye. Changes to the conjunctival flora have also been observed in SJS/TEN patients. Our group identified bacterial colonization in 95% of the eyes (55.5% of which were gram-positive cocci, 25.5% of which were gram-negative bacilli, and 19% of which were gram-positive bacilli). Several new treatment options in the acute and chronic ocular management of the SJS/TEN patients have been described. This article highlights some Brazilian institutions' contributions to ocular surface care in both the acute phase (including the use of amniotic membrane transplantation) and the chronic phase (such as eyelid margin and fornix reconstruction, minor salivary gland transplantation, amniotic membrane and limbal transplantation, scleral contact lenses, anti-angiogenic eyedrops for corneal neovascularization, ex-vivo cultivated limbal epithelium transplantation, conjunctival-limbal autografting, oral mucosa transplantation, and keratoprosthesis).
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A new species of Hyperaspidini, Tenuisvalvae quadripunctata sp. nov. is described and illustrated. The genus is now represented by 11 species, all native of South America, and the new taxon is integrated into the existing key to species of the genus. Ecological data for T. quadripunctata sp. nov. and a list with prey and host plants to the species of the genus Tenuisvalvae are provided.
Assuntos
Citrus , Besouros/classificação , Hemípteros , Animais , Brasil , Besouros/anatomia & histologia , Comportamento PredatórioRESUMO
MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.
Assuntos
Neoplasias da Mama/genética , Hemangiossarcoma/genética , Neoplasias Induzidas por Radiação/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Cutâneas/genética , Malformações Vasculares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Intervalo Livre de Doença , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/patologia , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-myc/biossíntese , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Malformações Vasculares/diagnóstico , Malformações Vasculares/patologiaRESUMO
Synthetic pesticide use has been the dominant form of pest control since the 1940s. However, biopesticides are emerging as sustainable pest control alternatives, with prevailing use in organic agricultural production systems. Foremost among botanical biopesticides is the limonoid azadirachtin, whose perceived environmental safety has come under debate and scrutiny in recent years. Coconut production, particularly organic coconut production, is one of the agricultural systems in which azadirachtin is used as a primary method of pest control for the management of the invasive coconut mite, Aceria guerreronis Keifer (Acari: Eriophyidae). The management of this mite species also greatly benefits from predation by Neoseiulus baraki (Athias-Henriot) (Acari: Phytoseiidae). Here, we assessed the potential behavioral impacts of azadirachtin on the coconut mite predator, N. baraki. We explored the effects of this biopesticide on overall predator activity, female searching time, and mating behavior and fecundity. Azadirachtin impairs the overall activity of the predator, reducing it to nearly half; however, female searching was not affected. In contrast, mating behavior was compromised by azadirachtin exposure particularly when male predators were exposed to the biopesticide. Consequently, predator fecundity was also compromised by azadirachtin, furthering doubts about its environmental safety and selectivity towards biological control agents.
Assuntos
Inseticidas/farmacologia , Controle Biológico de Vetores , Comportamento Predatório/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Brasil , Cocos/parasitologia , Feminino , Limoninas/farmacologia , Masculino , Ácaros/efeitos dos fármacos , Ácaros/fisiologia , Reprodução/efeitos dos fármacosRESUMO
Atypical vascular lesions (AVL) that occur in the field of prior radiation therapy for breast carcinoma are placed within the differential diagnosis with low grade angiosarcoma and other benign vascular lesions. Although considered a benign entity, the exact biological behavior of AVLs is not fully established because of the small number of cases reported in the literature. We aim to further characterize these lesions clinically and histopathologically, and to study their behavior. We report a series of 30 patients with AVL of the breast occurring after radiation exposure, diagnosed and treated at the European Institute of Oncology, Italy. Immunohistochemical study was performed in all cases, using CD31, D2-40, CD105, and Ki-67 antibodies. Twenty-seven patients were treated with standard doses of conventional adjuvant radiation therapy for the prior breast carcinoma. Three patients were treated with intraoperative radiotherapy with electrons. The post-radiation latency interval from breast carcinoma to AVL was 48.5 months (ranged from 1 to 146 months). Most of the lesions were classified as lymphatic type (78.6 %) based on D2-40 positivity. No extension into subcutaneous tissue or significant atypia was noted in all cases. Despite the fact that the AVL of our series have shown benign behavior in 93.3 %, one patient developed local recurrence of AVL, and two cases progressed to angiosarcoma at the previous AVL site. Further studies should be conducted to better understand the clinical behavior and to propose additional histopathologic diagnostic criteria to distinguish AVL from low grade angiosarcoma and those AVL with increased risk for malignant progression. Concerning current treatments of AVL, we recommend complete excision with free surgical margins and close follow up.
Assuntos
Neoplasias da Mama/patologia , Hemangiossarcoma/etiologia , Hemangiossarcoma/patologia , Adulto , Idoso , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/radioterapia , Feminino , Seguimentos , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/metabolismo , Hemangiossarcoma/cirurgia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação , Radioterapia/efeitos adversos , Resultado do TratamentoRESUMO
CBA macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. Employing a transcriptomic approach, we previously showed the up-regulation of the genes involved in the classical pathway of macrophage activation in resistant mice. However, microarray analyses do not evaluate changes in gene expression that occur after translation. To circumvent this analytical limitation, we employed a proteomics approach to increase our understanding of the modulations that occur during infection and identify novel targets for the control of Leishmania infection. To identify proteins whose expression changes in CBA macrophages infected with L. major or L. amazonensis, protein extracts were obtained and digested and the peptides were characterized using multi-dimensional liquid chromatography coupled with tandem mass spectrometry analyses. A total of 162 proteins were selected as potentially modulated. Using biological network analyses, these proteins were classified as primarily involved in cellular metabolism and grouped into cellular development biological networks. This study is the first to use a proteomics approach to describe the protein modulations involved in cellular metabolism during the initial events of Leishmania-macrophage interaction. Based on these findings, we hypothesize that these differentially expressed proteins likely play a pivotal role in determining the course of infection.