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1.
Int. j. morphol ; 40(2): 420-424, 2022. ilus
Article in Spanish | LILACS | ID: biblio-1385609

ABSTRACT

RESUMEN: La angiogénesis es el proceso de formación de vasos sanguíneos a partir de otros formados previamente. Existen varios factores que están involucrados en el proceso, así como agentes capaces de modular distintas etapas de esta. Si bien, se ha observado que Celecoxib es capaz de inhibir la angiogénesis en distintos modelos, aún no se ha observado la potencial capacidad antiangiogénica de este agente cuando es microencapsulado en PLGA. Se incubaron huevos fertilizados y a las 48 horas se dividieron en 4 grupos para ser instilados con PBS (control), PLGA, Celecoxib 1000 ppm o Celecoxib 1000 ppm + PLGA. Se realizó un conteo de los vasos sanguíneos a las 48, 72 y 96 horas post aplicación de la solución a estudiar. Los resultados muestran que tanto Celecoxib como Celecoxib+PLGA reducen los vasos sanguíneos, manteniendo el mismo efecto a las 48, 72 y 96 horas y no existen diferencias significativas entre los dos tratamientos. Esto podría ser explicado por la concentración de Celecoxib usada o el margen de tiempo analizado, pudiendo encontrarse diferencias posteriores a este rango de tiempo o con concentraciones distintas.


SUMMARY: Angiogenesis is the process of blood vessel formation from previously formed ones. There are several factors involved in the process, as well as agents capable of modulating different stages of it. Although, it has been observed that Celecoxib is capable of inhibiting angiogenesis in different models, the potential antiangiogenic capacity of this agent has not yet been observed when it is microencapsulated in PLGA. Fertilized eggs were incubated and at 48 hours they were divided into 4 groups to be instilled with PBS (control), PLGA, Celecoxib 1000ppm or Celecoxib 1000 ppm + PLGA. A blood vessel count was performed at 48, 72 and 96 hours after application of the solution to be studied. The results show that both Celecoxib and Celecoxib + PLGA reduce blood vessels, maintaining the same effect at 48, 72 and 96 hours and there are no significant differences between the two treatments. This could be explained by the concentration of Celecoxib used or the time frame analyzed, being able to find differences after this time range or with different concentrations.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Celecoxib/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Capsules
2.
Chinese Journal of Lung Cancer ; (12): 291-294, 2022.
Article in Chinese | WPRIM | ID: wpr-928811

ABSTRACT

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
.


Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , Bevacizumab/therapeutic use , Brain/metabolism , Consensus , Lung Neoplasms/drug therapy , Necrosis/etiology , Radiation Injuries/etiology , Vascular Endothelial Growth Factor A/metabolism
3.
China Journal of Chinese Materia Medica ; (24): 737-744, 2022.
Article in Chinese | WPRIM | ID: wpr-927957

ABSTRACT

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.


Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , China , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/metabolism
4.
Braz. j. med. biol. res ; 54(3): e10291, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153518

ABSTRACT

The vascular network expansion and functioning are important factors affecting normal intra-uterine fetal development. This study addressed the previously reported antiangiogenic potential of beta-2-glycoprotein I (β2GPI) in vivo in the chick embryo model of angiogenesis. The effects of two naturally occurring β2GPI forms on the development of the chorioallantoic membrane (CAM) vessels and the chicken embryo were investigated. β2GPI monomers and dimers were obtained by fractioned purification and characterized using SDS-PAGE, immunoblot, and ELISA. The egg exposure was performed by injection of small volumes of 2.5 µg/mL solutions of the β2GPI subfractions. Angiogenesis was evaluated through quantitative measurements of vascular architecture parameters in the captured CAM images, using computational analysis of texture contrasts and computer vision techniques. Quantitative information was assigned to the CAM vasculature modifications. In vivo, the β2GPI dimer completely halted the formation of CAM vessels and led to embryo death after 48 h of exposure. The β2GPI monomer allowed the embryo to develop up to the 10th day, despite early changes of CAM vessels. The impaired normal vessel growth proceeded as a self-limited effect. The β2GPI monomer-exposed eggs showed reduced vascularization on the 6th day of incubation, but embryos were viable on the 10th day of incubation, with ingurgitated CAM vessels implying sequelae of the angiogenesis inhibition. Both subfractions impaired CAM vasculature development. The β2GPI dimer proved to be largely more harmful than the β2GPI monomer. β2GPI modification by cleavage or dimerization may play a role in angiogenesis control in vivo.


Subject(s)
Chickens , Chorioallantoic Membrane , Chick Embryo , Neovascularization, Physiologic , Angiogenesis Inhibitors/pharmacology , beta 2-Glycoprotein I
5.
Medwave ; 20(8): e8024, 2020.
Article in English, Spanish | LILACS | ID: biblio-1128871

ABSTRACT

INTRODUCCIÓN: La degeneración macular asociada a la edad es la principal causa de ceguera en personas mayores en el mundo. El tratamiento más eficaz consiste en inyecciones intravítreas de fármacos anti factor del crecimiento vascular endotelial (anti-VEGF). Sin embargo, no existe consenso sobre su frecuencia de administración, siendo pro re nata y treat and extend los protocolos más utilizados, pero existe controversia sobre su efectividad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos observacionales. Concluimos que no es posible establecer con claridad si el protocolo treat and extend en comparación a pro re nata es superior en términos de ganancia visual, disminución del grosor de la retina, número de inyecciones ni en el desarrollo de efectos adversos serios a los 12 meses, debido a que la certeza de la evidencia existente es muy baja.


INTRODUCTION: Age-related macular degeneration is the leading cause of blindness in older people in the world. One of the most effective treat-ments consists of injection intravitreal of anti-endothelial vascular growth factor (anti-VEGF) drugs. However, there is no con-sensus on their frequency of administration, being the treat and extend and the pro re nata the most commonly used regimens, but there is still controversy regarding their effectiveness. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that together included two primary studies, both observational studies. We concluded that we are uncertain whether the treat and extend regimen is superior in terms of visual gain, decrease in retinal thickness, number of injections and serious adverse effects at 12 months in comparison with the pro re nata regimen, because the certainty of the existing evidence has been assessed as very low.


Subject(s)
Humans , Aged , Angiogenesis Inhibitors/administration & dosage , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Macular Degeneration/drug therapy , Drug Administration Schedule , Visual Acuity/drug effects , Databases, Factual , Angiogenesis Inhibitors/pharmacology , Intravitreal Injections , Macular Degeneration/pathology
6.
Rev. bras. ginecol. obstet ; 41(11): 668-672, Nov. 2019. graf
Article in English | LILACS | ID: biblio-1057879

ABSTRACT

Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2mm2, a significantly higher value compared with Group II (49.4mm2, p = 0.023) and Group III (48.6mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1mg/kg/day and at the dose of 10 mg/kg/day.


Resumo Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamentemenor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesãomédia do Grupo I foi de 69,2mm2, valor significativamentemaior em relação ao Grupo II (49,4mm2, p = 0,023) e Grupo III (48,6mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1mg/kg/dia quanto na dose de 10 mg/kg/dia.


Subject(s)
Humans , Animals , Female , Thalidomide/pharmacology , Angiogenesis Inhibitors/pharmacology , Disease Models, Animal , Endometriosis/pathology , Endometrium/pathology , Biomarkers/analysis , Rats, Wistar , Proliferating Cell Nuclear Antigen/analysis , Cell Proliferation/drug effects , Dose-Response Relationship, Drug
7.
Arq. bras. oftalmol ; 82(1): 38-44, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-973869

ABSTRACT

ABSTRACT Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.


RESUMO Objetivo: Avaliar os efeitos do ranibizumabe em associação com o amfenac nas células de melanoma uveal humano e explorar a capacidade desses compostos em sensibilizar as células de melanoma uveal à radioterapia. Métodos: Células de melanoma uveal humano do tipo 92.1 foram cultivadas e submetidas ao tratamento proposto (ranibizumabe, amfenac e a combinação de ambos). Ensaios de proliferação, migração e invasão com as células de melanoma uveal do tipo 92.1 foram avaliados após tratamento com ranibizumabe (125 mg/ml), amfenac (150 nM) e a combinação de ambos. Além disso, as taxas de proliferação foram avaliadas após tratamento com ranibizumabe e amfenac com subsequente exposição das células a diferentes doses de radiação (0 Gy, 4 Gy e 8 Gy). Resultados: Ensaio de proliferação: células tratadas com ranibizumabe e amfenac combinados apresentaram taxas de proliferação inferiores em comparação ao grupo controle (p=0,016), do que as tratadas apenas com ranibizumabe (p=0,033). Ensaio de migração: foi observada uma taxa de migração significativamente mais baixa nas células tratadas com amfenac do que no grupo controle (p=0,014) e do que nas tratadas com ranibizumabe (p=0,044). Ensaio de invasão: não houve diferenças significativas entre os grupos estudados. Exposição à irradiação: no grupo da dose de 4 Gy, não houve diferença significante entre os grupos. No grupo da dose de 8 Gy, o tratamento com ranibizumabe, afenac e sua combinação antes da aplicação da radiação de 8 Gy levou a uma redução acentuada nas taxas de proliferação (p=0,009, p=0,01 e p=0,034, respectivamente) em comparação aos grupos controle. Conclusão: A combinação de ranibizumabe e amfenac reduziu a taxa de proliferação das células de melanoma uveal; no entanto, apenas o amfenac diminuiu significativamente a migração celular. A radiossensibilidade das células de melanoma uveal do tipo 92.1 aumentou após a administração de ranibizumabe, amfenac e sua combinação. Mais investigações são necessárias para determinar se esta é uma estratégia de pré-tratamento viável para tornar grandes tumores passíveis de radioterapia.


Subject(s)
Humans , Phenylacetates/pharmacology , Angiogenesis Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Ranibizumab/pharmacology , Melanoma/drug therapy , Melanoma/radiotherapy , Radiation Tolerance , Uveal Neoplasms/drug therapy , Uveal Neoplasms/radiotherapy , Antineoplastic Combined Chemotherapy Protocols , Cell Movement/drug effects , Cell Movement/radiation effects , Reproducibility of Results , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Dose-Response Relationship, Radiation
8.
Rev. bras. oftalmol ; 77(3): 128-132, May-June 2018. tab
Article in Portuguese | LILACS | ID: biblio-959090

ABSTRACT

Resumo Objetivo: O objetivo desse trabalho é avaliar o perfil de aplicações intravítreas do Ranibizumab em uma população de adultos atendidos no Instituto Benjamin Constant, no ano de 2015, levando em consideração o efeito sobre a acuidade visual e a espessura macular após tratamento. O objetivo secundário é apresentar as principais indicações desse tipo tratamento no serviço de olhos acima citado. Métodos: Foi realizado um estudo retrospectivo seccional, em indivíduos acima de 20 anos entre os meses de março a agosto de 2015, para analisar a acuidade visual e espessura foveal pré e pós tratamento. A dose do anti-VEGF utilizada foi de 0,05ml por aplicação com intervalo de quatro semanas entre elas. A aferição da acuidade visual assim como o OCT pós tratamento foram realizados em torno de trinta dias após a última aplicação. As análises estatísticas foram feitas com uso do software SPSS versão 21 e o nível de significância estatística foi de 95% com um valor de p <0,05. Resultado: O estudo mostrou que a principal afecção relacionada a esse tratamento foi a retinopatia diabética não proliferativa associada ao edema macular (32,8%). Após o tratamento indicado com Ranibizumab, houve uma melhora da acuidade visual média de 0,70 para 0,59 (logMAR) e uma regressão da espessura macular, visto no OCT, de 408,1µm para 337,2 µm (valor de p <0,05). Conclusão: Pode-se concluir portanto, que o tratamento com Ranibizumab na população estudada contribuiu para uma melhor qualidade de vida dos pacientes, pois a maioria dele apresentou uma melhora estatisticamente significativa na acuidade visual após as aplicações.


Abstract The objective of this work is to evaluate the profile of intravitreal applications of Ranibizumab in a population of adults attended at the Benjamin Constant Institute in the year of 2015, taking into account the effect on visual acuity and macular thickness after the treatment. The secondary objective is to present the main indications of this type of treatment in the eye care mentioned above. A retrospective cross-sectional study was performed in individuals over 20 years of age between March and August of 2015 to analyze visual acuity and foveal thickness before and after treatment. The dose of anti-VEGF used was 0.05 ml per application with an interval of four weeks between them. Visual acuity assessment as well as OCT post treatment were performed around 30 days after the last application. Statistical analyses were performed using SPSS software version 21 and the level of statistical significance was of 95% with a value of p <0.05. The study showed that the main condition related to this treatment was non-proliferative diabetic retinopathy associated with macular edema (32.8%). After treatment indicated with Ranibizumab, there was an improvement in the average visual acuity from 0.70 to 0.59 (logMAR) and a regression of the macular thickness, seen in the OCT, from 408.1μm to 337.2μm (p < 0.05). It can be concluded, therefore, that treatment with Ranibizumab in the studied population contributed to a better quality of life of the patients, since most of them presented a statistically significant improvement in the visual acuity after the applications.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Macular Edema/drug therapy , Macular Edema/diagnostic imaging , Intravitreal Injections , Ranibizumab/administration & dosage , Retina/diagnostic imaging , Fluorescein Angiography , Visual Acuity , Retinal Neovascularization , Retrospective Studies , Choroidal Neovascularization , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Tomography, Optical Coherence , Diabetic Retinopathy , Ranibizumab/therapeutic use , Ranibizumab/pharmacology , Fovea Centralis/diagnostic imaging , Macula Lutea/diagnostic imaging , Macular Degeneration
9.
Rev. bras. oftalmol ; 77(1): 34-37, jan.-fev. 2018. tab, graf
Article in Portuguese | LILACS | ID: biblio-899102

ABSTRACT

Resumo Objetivo: O tratamento com anti-angiogêncios é uma das modalidades mais utilizadas em patologias relacionadas ao edema macular. A injeção intravítrea de um inibidor do VEGF-A tem alta efetividade, porém está relacionada com efeitos adversos, como o aumento da pressão intraocular. O objetivo deste estudo foi avaliar a variação da pressão intraocular (PIO) em pacientes que se submeteram a injeções intravítreas de ranibizumabe, a variação de acordo com facia e com história de injeções prévias. Métodos: Este foi um estudo um estu-do observacional transversal. Foram incluídos todos os pacientes submetidos a injeções intravítreas com diagnóstico de degeneração macular relacionada à idade exsudativa, oclusão de veia central da retina com edema macular, ou edema macular diabético. A pressão intraocular foi aferida antes da injeção, imediatamente após e 30 minutos após a injeção com tonômetro portátil. Resultados Foram realizadas 143 injeções intravítreas, restando para a análise 96 injeções realizadas em 55 participantes. A comparação entre a PIO antes e 30 minutos após a injeção intravítrea mostrou-se estatisticamente significativa com PIO final maior que a inicial (p<0,0001) em pacientes com edema macular diabético. Pacientes fácicos e afácicos não mostraram diferenças significativas com relação a variação da PIO. Quando analisados apenas os participantes que haviam recebido injeções prévias, não foi encontrado uma variação significativa. Conclusão: Concluímos neste estudo que existe uma diferença significativa entre a pressão intraocular antes e 30 minutos após a injeção intravítrea de ranibizumabe em pacientes com edema macular diabético, mos-trando que esse período de tempo não foi suficiente para a regressão da PIO ao valor pré-injeção. Não encontramos diferenças significativas entre outros grupos, comparação entre fácicos e afácicos, nem em pacientes que haviam recebido injeções prévias.


Abstract Objective: Treatment with anti-angiogenic drugs is one of the most widely used modalities of treatment of macular edema related conditions. Intravitreal injection of a VEGF-A inhibitor is highly effective, but is related to adverse effects such as increased intraocular pressure. The objective of this study was to evaluate intraocular pressure (IOP) variation in patients who underwent intravitreal injections of ranibizumab, variation according to phakic/aphakic and history of previous injections. Methods: This was a cross-sectional observational study. All patients submitted to intravitreal injections with diagnosis of exudative age-related macular degeneration, retinal central vein occlusion with macular ede-ma, or diabetic macular edema were included. The IOP was measured before the injection, immediately after and 30 minutes after the injection with a portable tonometer. Results: 143 intravitreal injections were performed, with 96 injec-tions performed in 55 participants. The comparison between IOP before and 30 minutes after intravitreal injection showed to be statistically significant with higher than initial IOP (p <0.0001) in patients with diabetic macular edema. Phakic and aphakic patients did not show significant differences regarding IOP variation. When only those participants who had received previous injections were analyzed, no significant variation was found. Conclusion: We conclude in this study that there is a significant difference between intraocular pressure before and 30 minutes after intravitreal injection of ranibizumab in patients with diabetic macular edema, showing that this period of time was not sufficient for regression of IOP at the pre-injection value . We did not find significant differences between other groups, comparing phakic and aphakic patients, nor in patients who had received previous injections.


Subject(s)
Humans , Male , Female , Aged , Ocular Hypertension/chemically induced , Angiogenesis Inhibitors/pharmacology , Intravitreal Injections/methods , Ranibizumab/pharmacology , Intraocular Pressure/drug effects , Tonometry, Ocular/instrumentation , Tonometry, Ocular/methods , Retinal Vein Occlusion/drug therapy , Macular Edema/drug therapy , Cross-Sectional Studies , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Ranibizumab/adverse effects , Ranibizumab/therapeutic use , Intraocular Pressure/physiology , Macular Degeneration/drug therapy
10.
Colomb. med ; 48(2): 88-93, Apr,-June 2017. tab, graf
Article in English | LILACS | ID: biblio-890860

ABSTRACT

Abstract Case description: Five-year-old female patient with hereditary hemorrhagic telangiectasia. Clinical Findings: Deterioration of cardiopulmonary function with higher oxygen requirements secondary to pulmonary arteriovenous shunts, epistaxis. Treatment and Outcome: The patient was treated with the monoclonal antibody bevacizumab, which inhibits the vascular endothelial growth factor, with good clinical outcome. Clinical Relevance: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations in different organs, making its clinical presentations varied. Systemic therapeutic options for a generalized disease are limited. The monoclonal antibody bevacizumab, seems to be a good option in this disorder. Although reported as successful in adult population, its use in pediatric population has not yet been reported. Here we report the use of bevacizumab in a 5-year-old female patient with hereditary hemorrhagic telangiectasia, showing clinical benefits and good outcome.


Resumen Descripción del caso: Paciente de cinco años de sexo femenino con telangiectasia hemorrágica hereditaria. Hallazgos Clínicos: Deterioro de la función cardiopulmonar con mayores requerimientos de oxígeno secundario a shunt pulmonar arteriovenoso, epistaxis. Tratamiento y resultado: La paciente fue tratada con el anticuerpo monoclonal bevacizumab, que inhibe el factor de crecimiento endotelial vascular, con buen resultado clínico. Relevancia clínica: La telangiectasia hemorrágica hereditaria es un trastorno autosómico dominante caracterizado por malformaciones arteriovenosas en diferentes órganos, lo que hace que sus presentaciones clínicas varíen. Las opciones terapéuticas sistémicas para la enfermedad generalizada son limitadas. El anticuerpo monoclonal bevacizumab, parece ser una buena opción en este trastorno. Aunque se ha reportado como exitoso en la población adulta, su uso en población pediátrica aún no ha sido reportado. Aquí se informa el uso de bevacizumab en una paciente de 5 años de edad con telangiectasia hemorrágica hereditaria, mostrando beneficios clínicos y buen resultado.


Subject(s)
Child, Preschool , Female , Humans , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Telangiectasia, Hereditary Hemorrhagic/physiopathology , Treatment Outcome , Angiogenesis Inhibitors/pharmacology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Bevacizumab/pharmacology
11.
Arq. bras. oftalmol ; 80(2): 74-77, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-838797

ABSTRACT

ABSTRACT Purpose: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. Methods: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. Results: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. Conclusions: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.


RESUMO Objetivo: Acredita-se que a nicotinamida (NIC) seja capaz de diminuir a angiogênese induzida pelo fator de crescimento endotelial vascular (VEGF). Investigar os efeitos da nicotinamida sobre a secreção de citocinas pró-angiogênicas e pró-inflamatórias em linhagens de células de melanoma uveal humano (UM). Métodos: Duas linhagens de células humanas de UM (92,1 e OCM-1) foram tratadas com NIC (10 mmol/L) ou apenas com meio de cultura por 48 horas. O sobrenadante das culturas obtido após a administração de nicotinamida foi comparado com o sobrenadante das culturas controle quanto à expressão de 20 fatores pró-angiogênicos e pró-inflamatórios, pela técnica de enzyme-linked immunosorbent assay (ELISA). Resultados: Sete citocinas pró-angiogênicas foram detectadas nas condições de controle em ambas as linhagens de células de UM. O tratamento com nicotinamida promoveu uma redução significativa da secreção das seguintes citocinas angiogênicas: Angiogenina, ANG2, EGF e VEGF-A em células 92.1; bFGF em células OCM-1; PIGF em ambas as linhagens celulares. Quanto às proteínas pró-inflamatórias, a expressão de MCP-1 e IL-8 foi significativamente reduzida com a administração de nicotinamida em relação às culturas de células que não receberam o tratamento. Conclusões: Nicotinamida apresenta propriedades anti-inflamatórias e anti-angiogênicas em modelo experimental in vitro. Tais efeitos sugerem a possibilidade de utilizar esta substância na quimioprevenção do UM. Entretanto, estudos com modelos experimentais in vivo são necessários para melhor avaliar o benefício do tratamento do UM com nicotinamida.


Subject(s)
Humans , Uveal Neoplasms/metabolism , Cytokines/drug effects , Niacinamide/pharmacology , Angiogenesis Inhibitors/pharmacology , Melanoma/metabolism , Anti-Inflammatory Agents/pharmacology , Ribonuclease, Pancreatic/drug effects , Uveal Neoplasms/blood supply , Cytokines/metabolism , Fibroblast Growth Factor 2/drug effects , Interleukin-8/drug effects , Chemokine CCL2/drug effects , Cell Line, Tumor , Angiopoietin-2/metabolism , Epidermal Growth Factor/drug effects , Placenta Growth Factor/drug effects , Melanoma/blood supply
12.
Int. j. morphol ; 35(1): 148-156, Mar. 2017. ilus
Article in English | LILACS | ID: biblio-840946

ABSTRACT

The combined antiretroviral therapy (cART), a multidrug combination regimen, usually consisting Nucleoside Reverse Transcriptase Inhibitors, non- Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors has altered the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining malignancies (nADMs). The speculation is rife; does cART induce or promote the progression of nADMs such as breast cancer? This study was therefore designed to investigate of the effects of some antiretroviral drugs (at clinically relevant concentrations) on the expression of anti-angiogenic gene; VEGF165b in two human breast cell lines; MCF-7 and MCF-10A by Real Time qPCR and immuno-fluorescence. All of the antiretroviral drugs and combinations tested produced patterns of slight up or downregulation of VEGF165b mRNA expression but the alterations did not attain statistical significance. They also did not alter VEGF165bprotein localisation in both cell lines. The findings reported here suggest that antiretroviral drugs probably do not influence the angiogenic pathway in the development of breast cancer in patients under the combined antiretroviral regimen.


El tratamiento antirretroviral combinado (TARc), un régimen de combinación de múltiples fármacos, consistiendo generalmente en inhibidores nucleósidos de la transcriptasa reversa, inhibidores no-nucleósidos de la transcriptasa reversa e inhibodres de proteasa que alteran el patrón de mortalidad que afecta a infectados por el VIH incluyendo neoplasias definidas como no HIV (nADMs). La especulación es moneda corriente; TARc induce o promueve la progresión de nADMs como cáncer de mama? Por lo tanto, este estudio se diseñó para investigar los efectos de algunos de los fármacos antirretrovirales (en concentraciones clínicamente relevantes) sobre la expresión del gen anti-angiogénico; VEGF165b en dos líneas celulares de mama humana; MCF-7 y MCF-10A por PCR tiempo real e inmunofluorescencia. Todos los fármacos antirretrovirales y las combinaciones probadas pueden regular en forma ligera hacia arriba o hacia abajo la expresión de ARNm producidos por VEGF165b pero las alteraciones no fueron estadísticamente significativos. Además, no se alteran los niveles de proteína VEGF165b, para la localización en ambas líneas celulares. Los resultados aquí presentados sugieren que los medicamentos antirretrovirales probablemente no influyen en la vía angiogénica en el desarrollo del cáncer de mama en pacientes bajo el régimen antirretroviral combinado.


Subject(s)
Humans , Female , Adenocarcinoma/metabolism , Angiogenesis Inhibitors/pharmacology , Breast Neoplasms/metabolism , Protease Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Epithelial Cells , Immunohistochemistry , MCF-7 Cells , Polymerase Chain Reaction , Vascular Endothelial Growth Factor A
13.
Biol. Res ; 50: 41, 2017. tab, graf
Article in English | LILACS | ID: biblio-950889

ABSTRACT

BACKGROUND: The marine environment is a rich source of bioactive natural products. Many of the marine bioactive compounds have been derived successfully from molluscs. Euchelus asper is a marine mollusc which is commonly found in the intertidal rocky regions of the Mumbai coast. The present study was focused on evaluating the anti-angiogenic and anti- proliferative activities of methanolic extract of Euchelus asper (EAME). METHODS: The anti-angiogenic activity of EAME (50-800 µg/mL) was assessed by chick chorio-allantoic membrane (CAM) model wherein multiple parameters in the CAM blood vessels were analysed through morphometric and histo-logical investigations. In vitro testing of EAME (5-20 µg/mL) included its cytotoxicity against three different cancer cell lines, its effect on cell proliferation by wound healing assay as well as their relevant molecular mechanisms. Statistical analysis was carried out by two-tailed student's t test for two unpaired groups. RESULTS: Analysis of CAM revealed that the extract is effective in reducing the branching points of the 1st order blood vessels or capillaries of CAM. Histological analysis of CAM showed significant decrease in capillary plexus and compartmentalization along with increase in mesodermal blood vessels, thus establishing its anti-angiogenicity. Further, EAME exhibited moderate but significant cytotoxicity against A549 non-small cell lung carcinoma cell line. We also demonstrated that the cytotoxicity of EAME in A549 was associated with its apoptotic activity by subG1 phase arrest. Lastly, EAME significantly reduced A549 proliferation by reducing the expression of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9). CONCLUSION: Overall, our study suggested that EAME has potential to inhibit tumour angiogenic and proliferative activity and may be a potential source for development of new anti-cancer pharmaceuticals.


Subject(s)
Animals , Chick Embryo , Biological Products/pharmacology , Angiogenesis Inhibitors/pharmacology , Cell Proliferation/drug effects , Gastropoda/chemistry , Biological Products/isolation & purification , Angiogenesis Inhibitors/isolation & purification , Cell Line, Tumor/drug effects
14.
Biol. Res ; 49: 1-9, 2016. ilus, graf, tab
Article in English | LILACS | ID: biblio-950845

ABSTRACT

BACKGROUND: Cancer, being the foremost challenge of the modern era and the focus of world-class investigators, gargantuan research is in progress worldwide to explore novel therapeutic for its management. The exploitation of natural sources has been proven to be an excellent approach to treat or minify the excessive angiogenesis and proliferation of cells. Similarly, based the ethnomedicinal uses and literature survey, the current study is designed to explore the anti-tumor and anti-angiogenic potentials of Rumex hastatus. Anti-tumor and anti-angiogenic activities were carried out using potato-disc model and chorioallantoic membrane (CAM) assay respectively. Moreover, R. hastatus was also assessed for antibacterial activity against Agrobacterium tumefaciens (tumor causing bacterial strain). The positive controls used in anti-tumor, anti-angiogenic and antibacterial activities were vincristine sulphate, dexamethasone and cefotaxime respectively. RESULTS: The crude saponins (Rh.Sp), methanolic extract (Rh.Cr) and other solvent extracts like n-hexane (Rh.Hex), chloroform (Rh.Chf), ethylacetate (Rh.EtAc) and aqueous fraction (Rh.Aq) exhibited notable anti-tumor and anti-angiogenic activities. In potato tumor assay, the chloroform and saponin fractions were observed to be the most effective showing 86.7 and 93.3 % tumor inhibition at 1000 µg/ml with IC50 values 31.6 and 18.1 µg/ml respectively. Similarly, these two samples i.e., chloroform and saponins also excelled among the entire test samples in anti-angiogenic evaluation exhibiting 81.6 % (IC50 = 17.9 µg/ml) and 78.9 % (IC50 = 64.9 µg/ml) at 1000 µg/ml respectively. In contrast, the antibacterial investigations revealed a negligible potential against A. tumefaciens. CONCLUSION: Based on our results we can claim that R. hastatus possesses both anti-tumor and anti-angiogenic potentials. In all of the solvent fractions, Rh.Chf and Rh.Sp were most effective against tumor and angiogenesis while having negligible activity against A. tumefaciens. It can be concluded that Rh.Chf and Rh.Sp might be potential targets in the isolation of natural product having anti-neoplastic action.


Subject(s)
Saponins/pharmacology , Plant Extracts/pharmacology , Agrobacterium tumefaciens/drug effects , Angiogenesis Inhibitors/pharmacology , Rumex/chemistry , Antineoplastic Agents/pharmacology , Plant Tumors , Saponins/isolation & purification , Solvents/chemistry , Time Factors , Microbial Sensitivity Tests , Reproducibility of Results , Analysis of Variance
15.
Rev. chil. cardiol ; 35(2): 127-132, 2016. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-796798

ABSTRACT

Introducción: El ácido acetilsalicílico (AAS) es ampliamente utilizado en el manejo de patología cardiovascular. En modelos "in vitro" el AAS restringe la angiogénesis, atribuyéndose este efecto al bloqueo de ciclooxigenasa-1, manteniendo íntegra la zona adhe-rente endotelial, citotoxicidad directa y otras vías de señalización. Hipótesis: El AAS en concentración terapéutica antiplaquetaria utilizada en humanos ejerce un efecto antiangiogénico en modelo de membrana alantocorió-nica de pollo (MAC). Objetivo: Comparar la capacidad antiangiogénica del AAS en distintas concentraciones en MAC utilizando como punto de comparación la angiogénesis fisiológica de la MAC. Método: Se incubaron 46 huevos fecundados de gallinas White Leghorn, en cámara temperada a 37°C, provenientes del Instituto de Salud Pública de Chile. Mediante procedimiento descrito por Ribatti (2006), se instiló sobre filtro de metilcelulosa 10uL de Dimetilsulfóxido al 0.1% + m199, sin fármaco al control, asociado a AAS y ácido salicílico (AS) a los grupos de estudio en concentraciones 2mM y 5 mM. Posteriormente se fijó y analizó la muestra en forma ciega. Resultados: El promedio de vasos del control fue 21.8. Para el grupo AAS 2mM y 5mM fue 11.3 y 10, siendo para el grupo AS 2mM y 5mM 15.6 y 12.4. El análisis estadístico mediante ANOVA y t-Student muestra que todos los grupos que recibieron fármacos tuvieron una disminución significativa en el numero de vasos sanguíneos en relación al grupo control. No hubo diferencias significativas entre ambo grupos de AAS. El AS demostró tener mayor potencia antiangiogénica dosis dependiente. Discusión: En este estudio se demuestra que el AAS ejerce un efecto antiangiogénico en concentración terapéutica en condiciones fisiológicas de un modelo "in vivo".


Background: Acetylsalicylic acid (ASA) is widely used in the treatment of various cardiovascular disorders. In vitro, AAS decreases angiogenesis, through cyclo-oxigenase-1 blockade while keeping active the adherent endothelial zone, direct toxicity and other signaling pathways. Hypothesis: AAS at therapeutic anti plaquetary doses exerts an anti-angiogenic effect in the alanto choronic chicken membrane (ACM) Method: 46 fertilized eggs form White Leghorn hens were incubated at 37oC. 10 uL of 0.1% Dimethyl sulfoxide +Ml 19 with no drug were used as control, while experimental groups received ASA and Salicylic acid (SA), 2mM. After fixation, samples were analyzed in a blind fashion Results: The mean number of vessels was 21.8 for controls, 11.3 and 10 for ASA 2mM and ASA 5mM, respectively. Corresponding values for SA 2 and SA 5mM were 15.6 and 12.4, respectively. Thus, a statistically significant (ANOVA and Student's t) decrease in the number of vessels was observed in both ASA groups. SA showed had a greater potential for anti-angiogenesis in a dose dependent way. Conclusion: This study shows that ASA in therapeutic concentrations has an anti-angiogenic effect in a physiologic model in vivo.


Subject(s)
Animals , Chick Embryo , Aspirin/pharmacology , Neovascularization, Physiologic/drug effects , Angiogenesis Inhibitors/pharmacology , Chorioallantoic Membrane , Chickens
16.
Arq. bras. oftalmol ; 78(3): 194-196, May-Jun/2015. graf
Article in English | LILACS | ID: lil-753023

ABSTRACT

ABSTRACT Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has been suggested as a potential healing therapeutic following glaucoma surgery. Here, we aimed to improve the bioavailability of bevacizumab when used as an adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab-methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients diagnosed with primary open angle glaucoma underwent DS with a subconjunctival injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4% methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro using size-exclusion high performance liquid chromatography (HPLC). Intraocular pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab was detected in BMM for up to 72 h. Moreover, all surgical blebs remained expanded with hyaline material during the first week. A significant IOP reduction (mean ± SD= -10.3 ± 5.4 mmHg, P<0.001) and diffuse blebs were observed at the final follow-up period. Although CECC was slightly reduced (-7.4%), no complications were observed. In conclusion, bevacizumab was released from BMM, and the use of this innovative mixture yielded good results following DS with no complications. Further studies are required to determine its efficacy prior to establishing BMM as an adjunct treatment for penetrating and non-penetrating glaucoma surgeries.


RESUMO O bevacizumabe (um agente anti-fator de crescimento endotelial vascular) tem sido sugerido como potencial modulador cicatricial na cirurgia do glaucoma. Este estudo objetivou melhorar a biodisponibilidade do bevacizumabe, investigando a viabilidade de uma nova mistura de bevacizumabe-metilcelulose (BMM) como terapia adjuvante para a esclerectomia profunda não-penetrante (DS). Dez olhos sem cirurgias prévias de 10 pacientes com glaucoma primário de ângulo aberto foram submetidos à DS associada à uma injeção subconjuntival de 0,3 ml da mistura de bevacizumabe-metilcelulose (bevacizumabe 3,75 mg incorporado em metilcelulose 4%) no sítio cirúrgico. A liberação de bevacizumabe foi avaliada in vitro através de cromatografia líquida de alta performance por exclusão de tamanho (HPLC). A pressão intraocular (PIO), a morfologia da ampola de filtração, a contagem de células endoteliais da córnea (CECC) e as complicações foram estudadas aos seis meses de seguimento. O bevacizumabe foi detectado a partir da mistura de bevacizumabe-metilcelulose por meio do HPLC até 72 horas. Além disso, todas as ampolas cirúrgicas permaneceram expandidas com material hialino durante a primeira semana. Uma redução significativa da pressão intraocular (média ± DP= -10,3 ± 5,4 mmHg, P<0,001) e ampolas difusas foram observadas ao final do período de seguimento. Embora a contagem de células endoteliais da córnea se mostrou discretamente diminuída (-7,4%), nenhuma complicação foi observada. Neste estudo, o bevacizumabe foi liberado da mistura de bevacizumabe-metilcelulose e o uso desta nova mistura se associou com bons resultados cirúrgicos e nenhuma complicação. Estudos futuros serão necessários para determinar sua eficácia, antes de se estabelecer a mistura de bevacizumabe-metilcelulose como um tratamento adjuvante às cirurgias penetrantes e não-penetrantes para o glaucoma.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors/pharmacology , Bevacizumab/pharmacology , Glaucoma, Open-Angle/surgery , Methylcellulose/pharmacology , Angiogenesis Inhibitors/therapeutic use , Blister , Bevacizumab/therapeutic use , Chemotherapy, Adjuvant/methods , Drug Combinations , Drug Liberation , Feasibility Studies , Follow-Up Studies , Glaucoma, Open-Angle/drug therapy , Intraocular Pressure , Methylcellulose/therapeutic use , Pilot Projects , Prospective Studies , Slit Lamp , Wound Healing/drug effects
17.
Korean Journal of Ophthalmology ; : 424-432, 2015.
Article in English | WPRIM | ID: wpr-219865

ABSTRACT

PURPOSE: To evaluate the effects of bevacizumab on expression of B-cell leukemia/lymphoma (Bcl)-2 and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress conditions. METHODS: RPE cells were treated with H2O2 (0, 100, 200, 300, and 400 microM) and bevacizumab at or above the doses normally used in clinical practice (0, 0.33, 0.67, 1.33, and 2.67 mg/mL). Cell apoptosis was measured using flow cytometry with annexin V-fluorescein isothiocyanate. The expression of Bcl-2 mRNA was determined using reverse transcription polymerase chain reaction. RESULTS: Under low oxidative stress conditions (H2O2 100 microM), cell apoptosis was not significantly different at any concentration of bevacizumab, but Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL). Under moderate oxidative stress conditions (H2O2 200 microM), Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL), but cell apoptosis increased only at 2.67 mg/mL of bevacizumab. Under high oxidative stress (300 microM) conditions, cell apoptosis increased at high concentrations of bevacizumab (1.33 and 2.67 mg/mL), but it did not correlate with Bcl-2 expression. CONCLUSIONS: Withdrawal of vascular endothelial growth factor can lead to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2 under oxidative stress conditions. Since oxidative stress levels of each patient are unknown, repeated injections of intravitreal bevacizumab, as in eyes with age-related macular degeneration, might influence RPE cell survival.


Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , Apoptosis/drug effects , Bevacizumab/pharmacology , Cell Line , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Expression Regulation/physiology , Hydrogen Peroxide/toxicity , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Retinal Pigment Epithelium/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors
18.
Journal of Korean Medical Science ; : 979-987, 2015.
Article in English | WPRIM | ID: wpr-70183

ABSTRACT

Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.


Subject(s)
Animals , Humans , Mice , Rats , Acer/metabolism , Angiogenesis Inhibitors/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival , Extracellular Signal-Regulated MAP Kinases/metabolism , Hep G2 Cells , Human Umbilical Vein Endothelial Cells/drug effects , MAP Kinase Signaling System/drug effects , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/metabolism , Neoplasm Invasiveness/pathology , Neovascularization, Pathologic/drug therapy , Nitric Oxide Synthase Type III/metabolism , Phosphorylation/drug effects , Plant Extracts/pharmacology , Rats, Sprague-Dawley , Transcription Factors/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors
19.
Braz. dent. j ; 25(5): 435-441, Sep-Oct/2014. tab, graf
Article in English | LILACS | ID: lil-731060

ABSTRACT

This study compared the physicochemical properties and interfacial adaptation to canal walls of Endo-CPM-Sealer, Sealapex and Activ GP with the well-established AH Plus sealer. The following analyses were performed: radiopacity, pH variation and solubility using samples of each material and scanning electron microscopy of root-filled bovine incisors to evaluate the interfacial adaptation. Data were analyzed by the parametric and no-parametric tests (α=0.05). All materials were in accordance with the ANSI/ADA requirements for radiopacity. Endo-CPM-Sealer presented the lowest radiopacity values and AH Plus was the most radiopaque sealer (p=0.0001). Except for ActiV GP, which was acidic, all other sealers had basic chemical nature and released hydroxyl ions. Regarding solubility, all materials met the ANSI/ADA recommendations, with no statistically significant difference between the sealers (p=0.0834). AH Plus presented the best adaptation to canal walls in the middle (p=0.0023) and apical (p=0.0012) thirds, while the sealers Activ GP and Endo-CPM-Sealer had poor adaptation to the canal walls. All sealers, except for ActiV GP, were alkaline and all of them fulfilled the ANSI/ADA requirements for radiopacity and solubility. Regarding the interfacial adaptation, AH Plus was superior to the others considering the adaptation to the bovine root canal walls.


Este estudo comparou as propriedades físico-químicas e a adaptação interfacial às paredes do canal dos cimentos Endo-CPM-Sealer, Sealapex e Activ GP com o bem estabelecido cimento AH Plus. As seguintes análises foram realizadas: radiopacidade, variação de pH e de solubilidade utilizando amostras de cada material, e microscopia eletrônica de varredura utilizando incisivos bovinos obturados para avaliar a adaptação interfacial. Os dados foram analisados utilizando testes paramétricos e não-paramétricos (α=0,05). Todos os materiais estavam de acordo com os requerimentos da ANSI/ADA para radiopacidade, sendo que o Endo-CPM-Sealer apresentou os menores valores de radiopacidade e o AH Plus foi o cimento mais radiopaco (p=0,0001). Exceto o Activ GP, que foi ácido, todos os outros cimentos apresentaram natureza química básica e liberaram íons hidroxila. Com relação à solubilidade, todos os materiais estavam de acordo com as recomendações da ANSI /ADA, sem diferença significante entre os cimentos (p=0,0834). O AH Plus apresentou a melhor adaptação às paredes do canal nos terços médio (p=0,0023) e apical (p=0,0012), enquanto que os cimentos Activ GP e Endo-CPM-Sealer apresentaram uma pobre adaptação às paredes do canal. Em conclusão, todos os cimentos, exceto o Activ GP, foram alcalinos e todos preencheram os requerimentos da ANSI/ADA para radiopacidade e solubilidade. Com relação à adaptação interfacial, o AH Plus foi superior aos demais para adaptação às paredes do canal radicular de incisivos bovinos.


Subject(s)
Animals , Female , Humans , Mice , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Dextrans/pharmacology , Growth Inhibitors/pharmacology , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/pathology , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Culture Media, Conditioned/pharmacology , Dose-Response Relationship, Drug , Dextrans/chemistry , Dextrans/therapeutic use , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Growth Inhibitors/therapeutic use , Mice, Inbred BALB C , Mice, Nude , Necrosis , Phenylacetates/pharmacology , Phenylacetates/therapeutic use , Xenograft Model Antitumor Assays/statistics & numerical data
20.
Rev. Esc. Enferm. USP ; 48(spe): 45-52, 08/2014. tab
Article in English | LILACS, BDENF | ID: lil-731291

ABSTRACT

Objective To explore beliefs, values and practices related to the use of medicinal plants among low-income black families. Method The research method was ethnography and the participant observation process was done in a low-income community in the peripheral area of the City of São Paulo. Twenty black women were interviewed. Results Two cultural sub-themes, I do use medicines that I learned to make with my mother and with religious practitioners to care for diseases and Home medicines are to treat problems that are not serious, and the cultural theme I do use home medicines to treat simple diseases because I always have them at my disposal, they are free and I don’t need a medical prescription represent beliefs, values, and practices related to the use of medicinal plants among low-income black families. Conclusion The development of such practices, which can hide ethnic and social vulnerability, reveals the resilience of low-income black women in the process of confronting problems during the health-illness process. .


Objetivo Explorar las creencias, valores y prácticas sobre el uso de las plantas medicinales entre las familias negras de bajos ingresos. Método El método de investigación fue la etnografía y el proceso de observación participante fue desarrollado en una comunidad de bajos ingresos en las afueras de la Ciudad de São Paulo. Se entrevistó a veinte mujeres negras. Resultados Dos subtemas culturales Uso remedios que aprendí a hacer con mi madre y con los religiosos para cuidar de enfermedades y Remedios caseros se utilizan para resolver problemas que no son graves y el tema cultural Uso remedio casero para resolver enfermedades simples porque tengo todo lo que necesito, es gratuito y no necesita una receta médica simbolizam las prácticas de las mujeres. Conclusión Estas prácticas, que pueden estar enmascarando vulnerabilidades étnicas y sociales, ponen de manifiesto la resiliencia de las mujeres negras de bajos ingresos en el confrontamiento de los problemas del proceso salud-enfermedad. .


Objetivo Explorar crenças, valores e práticas relativas ao uso das plantas medicinais entre famílias negras de baixa renda. Método Pesquisa etnográfica cujo processo de observação participante foi desenvolvido em uma comunidade de baixa renda da periferia da Cidade de São Paulo. Vinte mulheres negras foram entrevistadas. Resultados Dois subtemas culturais, Uso remédios que aprendi a fazer com minha mãe e com os religiosos para cuidar das doenças e Remédios caseiros servem para resolver problemas que não são graves, e o tema cultural Uso remédio caseiro para resolver doenças simples, pois tenho sempre que preciso, é de graça e não precisa de receita médica representam as crenças, valores e práticas relativos ao uso das plantas medicinais entre famílias negras de baixa renda. Conclusão O desenvolvimento dessas práticas, que pode estar mascarando vulnerabilidades étnicas e sociais, revela a resiliência das mulheres negras de baixa renda no enfrentamento dos problemas que encontram no processo saúde-enfermidade. .


Subject(s)
Humans , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Endothelium, Vascular/drug effects , Sulindac/analogs & derivatives , Sulindac/pharmacology , Angiogenesis Inhibitors/pharmacology , Cell Cycle/drug effects , Cell Division/drug effects , Cell Line , Dose-Response Relationship, Drug , Endothelium, Vascular/cytology , Endothelium, Vascular/ultrastructure , Microscopy, Electron , Umbilical Veins
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