RESUMEN
Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.
Asunto(s)
Endometriosis , Neoplasias , Osteoartritis , Femenino , Humanos , Agonistas de Dopamina/farmacología , Dopamina/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Endometriosis/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias/metabolismo , Adyuvantes Inmunológicos/uso terapéutico , Osteoartritis/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismoRESUMEN
SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.
Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.
Asunto(s)
Animales , Ratas , Envejecimiento , Vasos Coronarios/anatomía & histología , Corazón/anatomía & histología , Riñón/irrigación sanguínea , Capilares/anatomía & histología , Inmunohistoquímica , Técnica del Anticuerpo Fluorescente , Ratas Wistar , Vasos Coronarios/fisiología , Factores de Crecimiento Endotelial Vascular/metabolismo , Corazón/fisiología , Riñón/anatomía & histología , Riñón/fisiología , MicrocirculaciónRESUMEN
ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.
RESUMEN
Schistosomiasis affects approximately 240 million people worldwide. In Brazil, it is estimated that 1.5 million people are infected with Schistosoma mansoni and up to 15% of diagnosed individuals develop kidney damage. Renal involvement in schistosomiasis mansoni is characterized by glomerular lesions, with a high incidence, especially in chronically infected patients living in areas of high endemicity. Renal damage occurs slowly and is often asymptomatic, with a long-term manifestation of chronic kidney disease, with progressive loss of kidney functions, and early detection of subclinical kidney disease is of great importance. The aim of this study was to investigate kidney damage in patients infected with S. mansoni through urinary biomarkers of kidney injury and their association with the different parasite loads found. The patients were divided into two groups based on the diagnosis of infection by S. mansoni by the Kato-Katz and IgG-ELISA-SEA method: group of individuals infected by S. mansoni, Kato-Katz positive (PG); and group of individuals not infected by S. mansoni, Kato-Katz-negative (NG). Urinary creatinine and albuminuria were determined by immunoturbidimetry and proteinuria by the colorimetric method. The urinary biomarkers of podocyte injury (VEGF and Nephrin) and glomerular inflammation (MCP-1) were quantified by immunoassay and expressed by the urinary creatinine ratio. Urinary VEGF showed significantly higher levels in PG compared to NG (p = 0.004), increasing at all intensities of infection including low parasite load (p = 0.020). Our results show increased signs of podocyte damage in patients with schistosomiasis mansoni regardless of the parasite load, evidenced by increased urinary VEGF levels. However, further studies are needed since data related to schistosomiasis glomerulopathy and its association with new urinary biomarkers of kidney injury are scarce in the literature.
Asunto(s)
Schistosoma mansoni , Esquistosomiasis mansoni , Animales , Biomarcadores , Brasil/epidemiología , Heces/parasitología , Humanos , Riñón , Carga de Parásitos , Prevalencia , Esquistosomiasis mansoni/parasitología , Sensibilidad y Especificidad , Factor A de Crecimiento Endotelial VascularRESUMEN
Abstract In this study, the effects of ozonetherapy on secondary wound healing were evaluated histologically and immuno-histochemically. Material and Methods: 8 healthy pigs were used in this study. Six wounds with 10 mm in diameter were created through the punch technique on the palatinal gingiva of each pig. Ozone gas was applied on only 3 wounds (test group) and the remaining 3 were left to natural healing (control group). Biopsy samples were taken from one of the wounds in each group on the third day, from another wound of each group on the seventh day, and from another one on the tenth day. Routine histological analysis and immuno-histochemical staining were performed to investigate transforming growth factor-beta (TGF-β) and (VEGF) expressions. Results: No statistical difference was found between the test and control groups in terms of collagen fibers, epithelial formation and inflammation scores. A VEGF expression found in the test group was statistically higher than control group samples taken on the 3rd and 7th day. There was no statistical difference between the test and control groups in terms of TGF-β expression on any of the sampling days. Conclusion: The topical application of ozone gas could be effective in the early stages of wound healing by increasing the amount of VEGF expression. Clinical Relevance: Topical application of ozone gas may be effective in the early stages of oral wound healing.
Asunto(s)
Animales , Ozono/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Encía/efectos de los fármacos , Encía/patología , Valores de Referencia , Porcinos , Factores de Tiempo , Biopsia , Inmunohistoquímica , Distribución Aleatoria , Reproducibilidad de los Resultados , Administración Tópica , Factor de Crecimiento Transformador beta/análisis , Factor de Crecimiento Transformador beta/efectos de los fármacos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is primarily a locoregional disease in which the cervical lymph nodes are the chief site of metastasis. The purpose of this study was to examine the relationship between lymphangiogenesis and clinicopathological aspects of HNSCC and its metastasis. METHODS: Fifty-two patients with HNSCC and metastatic lymph nodes from 21 of these subjects were analyzed by immunohistochemistry. RESULTS: The HNSCC samples were predominantly negative for vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)3. There was an association between the density of lymph vessels (measured by D2-40 staining) in the lymph nodes and advanced-stage tumors. There was no link between the expression of these proteins and survival rates. CONCLUSION: Although lymphatic spread is a significant event in the progression of HNSCC, the expression of VEGF-C, VEGF-D, and VEGFR3 does not correlate with clinicopathological characteristics, suggesting that other signaling pathways mediate lymphangiogenesis in HNSCC.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/secundario , Linfangiogénesis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Inmunohistoquímica , Metástasis Linfática , Vasos Linfáticos/patología , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Acute inflammation and angiogenesis are persistent features of several pathological conditions induced by biological agents leading to the resolution of local and systemic events. Glycoproteins derived from the protozoan Trypanosoma cruzi are suggested to mediate angiogenesis induced by inflammatory cells with still undescribed mechanisms. In this study, we investigated the effects of total antigen from trypomastigote forms of T. cruzi (Y strain), inoculated in sponges 24h after implantation in mice, on angiogenesis, inflammatory cell pattern and endogenous production of inflammatory and angiogenic mediators on days 1, 4, 7 and 14 post-implant. There was an increase in hemoglobin content and in the number of blood vessels associated with T. cruzi antigen stimuli on the 14th day, assessed by the hemoglobin of the implants and by morphometric analysis. However, these antigens were not able to increase type I collagen content on the 14th day. Parasite antigens also induced high production of vascular endothelial growth factor (VEGF) and inflammatory mediators TNF-alpha, CCL2 and CCL5 on the 7th day in sponges when compared to the unstimulated group. Neutrophils and macrophages were determined by measuring myeloperoxidase (MPO) and N-acetyl-ß-d-glucosaminidase (NAG) enzyme activities, respectively. Only NAG was increased after stimulation with antigens, starting from day 4 and peaking at day 7. Together, these data showed that antigens from the Y strain of T. cruzi are able to promote inflammatory neovascularization probably induced by macrophage-induced angiogenic mediators in T. cruzi antigen-stimulated sponges in Swiss mice.
Asunto(s)
Antígenos de Protozoos/inmunología , Inflamación/inmunología , Inflamación/parasitología , Neovascularización Patológica , Tapones Quirúrgicos de Gaza , Trypanosoma cruzi/inmunología , Acetilglucosaminidasa/metabolismo , Proteínas Angiogénicas/metabolismo , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Femenino , Inflamación/metabolismo , Inflamación/fisiopatología , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/parasitología , Ratones , Infiltración Neutrófila , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/parasitología , Peroxidasa/metabolismo , Factores de TiempoRESUMEN
Objetivos: presentar una revisión acerca de la terapia génica y los fármacos en estudios preclínicos como nuevos y posibles blancos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascular y el estado de los estudios clínicos de los mismos. Diseño del estudio: revisión de tema. Métodos: se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la OMS. Conclusiones: la terapia génica vinculada a la degeneración macular asociada a la edad neovascular muestra un avance científico importante en el campo de la farmacología ocular pudiendo proporcionar eficacia tras una sola inyección de un vector que puede expresar continuamente una proteína elegida. Existen estudios pre-clínicos que sugieren nuevos y diversos blancos farmacológicos para la degeneración macular relacionada a la edad mostrando un perfil de seguridad y eficacia significativo.
Objectives: to review gene therapy and drugs in preclinical studies as potential new targets for pharmacological treatment for agerelated macular degeneration neovascular and the state of development clinical trials. Study design: literature review. Methods: a search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject was performed and complemented with information found on www.clinicaltrials.gov and WHO platform of international clinical trials registers. Conclusions: the gene therapy linked to age-related macular degeneration shows a scientific important advance in the field of the ocular pharmacology being able to provide efficiency after a single injection of a vector that can express a chosen protein. There are preclinical studies that suggest new and different pharmacological targets for age-related macular degeneration showing a significant safety and efficacy profile.
Asunto(s)
Degeneración Macular/terapia , Neovascularización de la Córnea/terapia , Oftalmopatías/terapia , Degeneración Macular/tratamiento farmacológicoRESUMEN
BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogen-esis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.
Asunto(s)
Humanos , Serpinas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas del Ojo/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Hipotermia , Factores de Crecimiento Nervioso/metabolismo , Factores de Tiempo , ARN Mensajero/metabolismo , Línea Celular , Neovascularización FisiológicaRESUMEN
Objetivos: Presentar una revisión de los nuevos y posibles objetivos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascul r y el estado de los fármacos en estudios clínicos. Diseño del estudio: Revisión de tema. Métodos: Se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema, y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la O.M.S. Se procedió a sistematizar la información y se presenta en forma estructurada. Conclusiones: Las nuevas opciones terapéuticas para la degeneración macular relacionada la edad neovascular proporcionan múltiples objetivos farmacológicos, los cuales se alcanzan realizando modificaciones a moléculas ya elaboradas o con nuevos fármacos los cuales pueden actuar tanto como terapia adjunta a los actuales medicamentos antiangiogénicos (anti VEGF) mejorando su eficacia o con nuevas opciones sustitutivas. Meritorio destacar la vía de la tirosina-quinasa, la cual había sido abordada con los existentes anti VEGF, ahora se presentan nuevas opciones terapéuticas que actúan corriente abajo. Diversos fármacos se encuentran en estudios de efi cacia parcial, merecen especial mención Fovista® y conbercept de los cuales ya se encuentran en desarrollo estudios fase III.
Objectives: To present a review of new and potential targets for pharmacological treatment for neovascular age-related macular degeneration and the state of drugs in development of clinical studies. Study design: Literature review. Methods: A search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject is made and compliments the information found on www.clinicaltrials. gov and platform of international clinical trials registers of the W.H.O. Conclusions: N ew therapeutic options for neovascular age-related macular degeneration provide multiple targets, which are achieved by performing modifi cations to a molecule already developed or new drugs which can act both as an adjunct to current anti VEGF improving efficiency or new alternative options. Meritorious note the tyrosine kinase way, on which previously it has acted with existing anti VEGF, now presents new therapeutic options that act downstream. Several drugs are in partial effi cacy studies, deserve special mention Fovista and conbercept of which already studies are in development phase III.
Asunto(s)
Degeneración Macular/tratamiento farmacológico , Factores de Crecimiento Endotelial Vascular , Degeneración Macular/diagnósticoRESUMEN
El síndrome POEMS es un síndrome paraneoplásico raro asociado a discrasia de células plasmáticas. Se presenta el caso de un paciente masculino de 37 años de edad, quien consultó por presentar de 38.5 C°, precedida de escalofríos, predominio nocturno y frecuencia diaria/interdiaria, de tres meses de evolución; concomitante parestesias en región plantar bilateral, ascendente, con disminución de fuerza muscular simétrica en miembros inferiores. Durante su estancia hospitalaria se evidencia trombocitosis y eritrocitosis. Se realizó ecosonograma abdominal que evidencia hepatomegalia; tomografía computarizada (TC) de cuello que reportó adenopatías submandibulares, laterocervicales y parayugulares; TC de tórax donde se evidencia lesión ocupante de espacio de características osteolíticas expansivas a nivel de segunda costilla izquierda; electromiografía de miembros superiores e inferiores con radiculopolineuropatía de tipo mixto en miembros inferiores y polineuropatía sensitivo motora de tipo mixto en miembros superiores; electroforesis de proteínas con discreto aumento de gammaglobulinas, a expensas de IgG y aspirado de médula ósea con serie plasmática aumentada (3%) de apariencia madura. Se realizó biopsia de lesión en segundo arco costal izquierdo sin evidenciar atipias. En vista de hallazgos clínicos y paraclínicos se planteó síndrome POEMS.
POEMS syndrome is a rare paraneoplastic syndrome due to an underlying plasma cell disorder. We present a male patient of 37 years old with fever 38.5°C, preceded by chills, nocturnal predominance and daily frequency of three months of evolution, as well as paresthesias in plantar region, bilateral, ascendant with decrease in muscle strength of legs. During his hospitalization, he presented thrombocytosis and erythrocytosis. The abdominal ecosonography evidenced hepatomegaly; thorax computerized tomography evidenced space osteolytic occupying lesion in second left rib. The electromyography demonstrated radiculo polineuropathy in legs, and sensory motor polineuropathy in upper limbs. The protein electrophoresis with elevated of gammaglobulins ;bone marrow aspirate evidenced (3%) mature increased plasma cells. The biopsy of second rib evidenced no atypia.
Asunto(s)
Humanos , Masculino , Adulto , Células Plasmáticas , Síndrome POEMS , Policitemia/patología , Trombocitosis/patología , Factor A de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To investigate the vitreous level of vascular endothelial growth factor (VEGF) and kinase insert domain-containing receptor (KDR) in diabetic rats, and to explore the role of VEGF and KDR in diabetic retinopathy. METHODS: Eighty-four adult Wistar rats were randomly divided into two groups. Fifty-eight rats in group A were injected intraperitoneally with streptozotocin to induce diabetes and 20 rats in group B were injected with physiological saline. Blood glucose meter was used to detect the blood glucose level at 72 hours after injection; blood glucose level >16.67 mmol/L was considered to be successful modelling. Blood glucose level was assayed and body mass was measured on the same modelling day, one week, two weeks and four weeks after modelling. Four weeks after modelling, the vitreous was taken and the VEGF and KDR levels were detected by enzyme-linked immunosorbent assay (ELISA). The eyeballs were fixed with paraform and embedded by petrolin for haematoxylin and eosin (H & E) staining. RESULTS: Forty-two rats survived and 16 rats died in group A. No rats died in group B. The blood glucose at one week, two weeks and four weeks between the two groups had statistical differences (p < 0.05). The weight at one week and two weeks between the two groups was not different but there was statistical difference at four weeks between the two groups (p < 0.01). The ELISA results showed that the VEGF and KDR levels were 0.276 ± 0.026 ng/mL and 2.936 ± 0.295 ng/mL in group A, 0.231 ± 0.021 ng/mL and 2.394 ± 0.227 ng/mL in group B, respectively. The VEGF and KDR levels of group A were higher than those of group B (p < 0.05). CONCLUSIONS: The changes of VEGF and KDR levels in the vitreous of diabetic rats were related to the early retinopathy induced by diabetes.
OBJETIVO: Investigar el nivel vítreo del factor de crecimiento endotelial vascular (FCEV) y receptor con dominio inserto-quinasa (KDR) en ratas diabéticas, y explorar el papel de FCEV y KDR en la retinopatía diabética. MÉTODOS: Ochenta y cuatro ratas adultas Wistar fueron divididas aleatoriamente en dos grupos. A cincuenta y ocho ratas en el grupo A se les inyectó estreptozotocinapor vía intraperitonealpara inducir diabetes, mientras que a 20 ratas en el grupo B se les inyectó una solución salina fisiológica. Se usó un medidor de glucosa en sangre para detectar el nivel de glucosa en sangre a las 72 horas después de la inyección. Un nivel de glucosa en sangre > 16.67 mmol/L se consideró como un modelo exitoso. Se analizó el nivel de glucosa en sangre, y se midió la masa corporal en el mismo día del modelado, y una semana, dos semanas, y cuatro semanas después del modelado. Cuatro semanas después del modelado, se tomó el humor vítreo, y los niveles de FCEV y KDR fueron detectados mediante ensayo por inmunoabsorción ligado a enzimas (ELISA). Los globos oculares fueron fijados con para formaldehido e incrustados por petrolin para tinción (H & E) hematoxilina-eosina. RESULTADOS: Cuarenta y dos ratas sobrevivieron y 16 ratas murieron en el grupo A. Ninguna de las ratas en el grupo B murió. La glucosa en la sangre a la semana, las dos semanas, y las cuatro semanas entre los dos grupos tuvo diferencias estadísticas (p < 0.05). El peso a la semana y a las dos semanas entre los dos grupos no fue diferente, pero hubo diferencia estadística a las cuatro semanas entre los dos grupos (p < 0.01). Los resultados de ELISA mostraron que los niveles de FCEV y KDR fueron 0.276 ± 0.026 ng/mLy 2.936 ± 0.295 ng/mL en el grupo A, 0.231 ± 0.021 ng/mL y 2.394 ± 0.227 ng/mL en el grupo B, respectivamente. Los niveles de FCEV y KDR del grupo A fueron superiores a los del grupo B (p < 0.05). CONCLUSIONES: Los cambios de nivel FCEV y KDR en el humor vítreo de las ratas diabéticas estaban asociados con la retinopatía temprana inducida por diabetes.
Asunto(s)
Animales , Ratas , Cuerpo Vítreo/química , Receptores de Factores de Crecimiento Endotelial Vascular/análisis , Factores de Crecimiento Endotelial Vascular/análisis , Diabetes Mellitus Experimental/complicaciones , Retinopatía Diabética/etiología , Biomarcadores/análisis , Ratas Wistar , EstreptozocinaRESUMEN
Phyllocaulis boraceiensis mucus is known to be a compound capable of inducing cell proliferation and enhancing the wound healing process. The process of angiogenesis is a chain of mechanisms responsible for the formation of new vessels, which are are involved in cell proliferation, and factors that will act in the healing process. Our aim was to demonstrate that the angiogenesis process is enhanced in cultures of endothelial cells and fibroblasts treated with P. boraceiensis mucus. Experiments were carried out with 10(5) cells·mL(-1) of endothelial cells and fibroblasts treated with P. boraceiensis mucus in concentrations that have significant effects in proliferation assays, i.e. 0.012 µg·µL(-1) and 0.18 µg·µL(-1) , both of which cause extreme responses. Aliquots of 100 µL of cell suspensions were incubated for 1 h at 4 °C with 1 µL of antibodies specific for the cell markers vascular endothelial growth factor receptor 1 and cluster of differentiation 34, and negative isotype controls. Reading and expression analysis of cell markers was performed on a FACSCalibur flow cytometer. Expression levels of vascular endothelial growth factor receptor 1 and cluster of differentiation 34 expression were significantly increased in endothelial cells cultivated with 0.012 µg·µL(-1) P. boraceiensis mucus, suggesting that this compound is capable of enhancing angiogenesis.