RESUMO

ABSTRACT Purpose: To evaluate early changes after the first antivascular endothelial growth factor injection for macular edema secondary to diabetic retinopathy and retinal vein occlusion and the relationship between longterm outcomes. Methods: The study enrolled patients who received anti-vascular endothelial growth factor injections for treatment-naive macular edema due to retinal vein occlusion and diabetic retinopathy. The central macular thickness was measured at baseline, post-injection day 1, week 2, and month 1, and at the last visit using spectral-domain optical coherence tomography. A good response was defined as a central macular thickness reduction of ≥10% on post-injection day 1. Patients were reassessed at the last visit with regard to treatment response on post-injection day 1 based on the favorable anatomic outcome defined as a central macular thickness <350 µm. Results: In total, 26 (44.8%) patients had macular edema-retinal vein occlusion and 32 (55.2%) had macular edema-diabetic retinopathy. The mean follow-up time was 24.0 (SD 8.5) months. A statistically significant decrease in the central macular thickness was observed in both patients with macular edema-retinal vein occlusion and macular edema-diabetic retinopathy after antivascular endothelial growth factor injection therapy (p<0.001 for both). All patients with macular edema-retinal vein occlusion were good responders at post-injection day 1. All nongood responders at post-injection day 1 belong to the macular edema-diabetic retinopathy group (n=16.50%). The rate of hyperreflective spots was higher in nongood responders than in good responders of the macular edema-diabetic retinopathy group (p=0.03). Of 42 (2.4%) total good responders, one had a central macular thickness >350 µm, whereas 5 (31.2%) of 16 total nongood responders had a central macular thickness >350 µm at the last visit (p=0.003). Conclusion: The longterm anatomical outcomes of macular edema secondary to retinal vein occlusion and diabetic retinopathy may be predicted by treatment response 1 day after antivascular endothelial growth factor injection.

RESUMO Objetivo: Avaliar as alterações precoces após a primeira injeção de anticorpos antifator de crescimento endotelial vascular (anti-VEGF) em casos de edema macular secundário à retinopatia diabética e oclusão da veia da retina e a relação entre essas alterações e o resultado a longo prazo. Métodos: Foram incluídos no estudo pacientes que receberam uma injeção de antifator de crescimento endotelial vascular para edema macular, virgem de tratamento e devido à oclusão da veia retiniana ou a retinopatia diabética. A espessura macular central foi medida no início do tratamento e no 1º dia, 2ª semana e 1º mês após a injeção, bem como na última visita, através de tomografia de coerência óptica de domínio espectral. Definiu-se uma "boa resposta" como uma redução ≥10% na espessura macular central no 1º dia após a injeção. Os pacientes foram reavaliados na última visita com relação à resposta ao tratamento no 1º dia após a injeção, com base em um resultado anatômico favorável, definido como uma espessura macular central <350 µm. Resultado: Foram registrados 26 (44,8%) pacientes com edema macular e oclusão da veia da retina e 32 (55,2%) com edema macular e retinopatia diabética. O tempo médio de acompanhamento foi de 24,0 meses (desvio-padrão de 8,5 meses). Foi observada uma diminuição estatisticamente significativa da espessura macular central após o tratamento antifator de crescimento endotelial vascular tanto em pacientes com edema macular e oclusão da veia retiniana quanto naqueles com edema macular e retinopatia diabética (p<0,001 para ambos). Todos os pacientes com edema macular e oclusão da veia retiniana responderam bem no 1º dia pós-injeção. Todos os que responderam mal no 1º dia pós-injeção pertenciam ao grupo com edema macular e retinopatia diabética (n=16,50%). A presença de manchas hiperrefletivas foi maior nos pacientes que responderam mal do que naqueles que tiveram boa resposta no grupo com edema macular e retinopatia diabética (p=0,03). Um dos 42 (2,4%) pacientes com boa resposta total teve espessura macular central >350 um, enquanto 5 (31,2%) do total de 16 pacientes com resposta ruim apresentaram espessura macular central >350 µm na última visita (p=0,003). Conclusão: O resultado anatômico de longo prazo do edema macular secundário à oclusão da veia retiniana e à retinopatia diabética pode ser previsto pela resposta ao tratamento no 1º dia após a injeção de antifator de crescimento endotelial vascular.

RESUMO

Abstract Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.

RESUMO

Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.

RESUMO

AIM: Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4. METHODOLOGY: Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP). RESULTS: The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling. CONCLUSION: Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.

Assuntos

RESUMO

Brown adipose tissue (BAT) remains active in adults, oxidizing fatty acids or glucose and releasing energy in the form of heat. Brown adipocytes and enhanced thermogenesis are targets for treating obesity and its comorbidities. BAT shows high synthesis activity and secretes several signaling molecules. The brown adipokines, or batokines, take action in an autocrine, paracrine, and endocrine manner. Batokines have a role in the homeostasis of the cardiovascular system, central nervous system, white adipose tissue, liver, and skeletal muscle and exert beneficial effects on BAT. The systemic function of batokines gives BAT an endocrine organ profile. Besides, the batokines Fibroblast Growth Factor-21, Vascular Endothelial Growth Factor A, Bone Morphogenetic Protein 8, Neuregulin 4, Myostatin, and Interleukin-6 emerge as targets to treat obesity and its comorbidities, deserving attention. This review outlines the role of six emerging batokines on BAT and their cross-talk with other organs, focusing on their physiological significance and diet-induced changes.

Assuntos

RESUMO

OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Assuntos

RESUMO

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease that affects motor neurons and promotes progressive muscle atrophy. Vascular Endothelial Growth Factor A (VEGF-A) plays multiple roles in the central nervous systems (CNS). The purpose of this study was to evaluate the association between single nucleotide polymorphism (SNP) VEGF-A rs28357093 and ALS. METHODS AND RESULTS: This case-control study was conducted in 101 ALS patients and 119 healthy individuals. Genotyping was performed by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP). The statistical analysis was carried out using the RStudio® and SNPStats© software's. Analysis of genetic inheritance models was performed by logistic regression. Our findings demonstrated a strong association between VEGF- A rs28357093 and ALS in all genetic inheritance models, with a 9-fold increased risk for A/C - C/C genotypes (95%CI = 3.70-21.88; p < 0.001). CONCLUSIONS: The mutant allele was more frequent in ALS patients (p < 0.001) and this finding could be associated with ALS risk. This first study from the Brazilian central population was conducted to provide new insight into the pathogenesis of ALS.

Assuntos

RESUMO

SUMMARY OBJECTIVE: The polycystic ovary syndrome is the most common endocrine disorder, characterized by the dysregulation of ovarian angiogenesis. This alteration can be related to changes in the activities of the vascular endothelial growth factor (VEGF) gene. Single-nucleotide polymorphisms have been observed in the promoter, intronic, and untranslated regions of the VEGF gene, and several studies have suggested that these polymorphisms may be associated with the risk of polycystic ovary syndrome. This study aimed to investigate the association between rs2010963 and rs833061 polymorphisms and haplotypes of VEGF in the etiology of polycystic ovary syndrome. METHODS: A total of 210 women, 102 diagnosed with polycystic ovary syndrome and 108 controls, participated in this study. The genotyping of the samples was performed by PCR-RFLP and real-time PCR for rs2010963 and rs833061 polymorphisms, respectively. The statistical analyses were performed by the chi-square test and logistic regression model. RESULTS: The clinical characteristics of the patients showed that 75.8% of the patients did not become pregnant, 36.3% had a family history of polycystic ovary syndrome, 58.6% were obese, and about 60% had clinical characteristics of hyperandrogenism. There were no associations between the distribution of rs2010963 (OR 1.24; 95%CI 0.60-2.57; p=0.56) and rs833061 (OR 0.78; 95%CI 0.32-1.92; p=0.59) in patients and controls. CONCLUSIONS: The patients with polycystic ovary syndrome have similar rates of VEGF polymorphisms rs2010963 and rs833061 on the general population.

RESUMO

SUMMARY OBJECTIVE: The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andβ-human chorionic gonadotropin in each subgroup. METHODS: Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42-56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%. RESULTS: One-way analysis of variance revealed a significant correlation between the different subgroups and β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). β-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value. CONCLUSIONS: Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.

RESUMO

ABSTRACT Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

RESUMO Objetivos: Avaliar a sensibilidade ao contraste em pacientes virgens de tratamento com retinopatia diabética proliferativa de não alto risco, submetidos a panfotocoagulação retiniana com injeções intravítreas de ranibizumabe versus pan­fotocoagulação isolada. Métodos: Sessenta olhos de 30 pa­cientes foram randomizados em dois grupos: um submetido a panfotocoagulação com injeções de ranibizumabe (grupo estudo), e o outro submetimedo a panfotocoagulação isolada (grupo controle). Todos olhos foram tratados em 3 sessões de laser, seguindo recomendação do Early Treatment Diabetic Retinopathy Study (ETDRS). Avaliação da sensibilidade ao contraste foi realizada sob condições fotópicas (85 cd/m2) com tabela Visual Contrast Test Sensitivity 6500, permitindo avaliação de cinco frequências espaciais medidas com redes senoidais: 1.5, 3.0, 6.0, 12.0 e 18.0 ciclos por grau de ângulo visual (cpd). Foram realizadas medidas dos limiares de sensibilidade ao contraste intra e entre grupos na visita inicial, no 1º, 3º, e 6º mês de seguimento. Resultados: Cinquenta e oito olhos, 28 do grupo estudo e 30 do grupo controle, atingiram o término do estudo. Análise comparativa da SC entre os grupos mostrou diferença estatisticamente significante, nas baixas frequências espaciais, no 1º mês em 1.5 cpd (p=0,001) e 3.0 cpd (p=0,04), no 3º mês em 1.5 cpd (p=0,016) e no 6º mês em 3.0 cpd (p=0,026) a favor do grupo estudo. Conclusão: O tratamento com panfotocoagulação associada a injeção de ranibizumabe parece causar menos danos a sensibilidade ao contraste quando comparada com panfotocoagulação isolada em olhos com retinopatia diabética proliferativa de não alto risco. Dessa forma, os resultados apresentados podem justificar a associação do ranibizumabe à panfotocoagulação nestes pacientes.