Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major / Fator de crescimento endotelial vascular e hipertensão pulmonar em crianças com talassemia beta maior

Abstract Objective: The purpose of this study was to illustrate the association between vascular endothelial growth factor level and pulmonary artery hypertension in children with β-thalassemia major. Method: This case-control study was conducted on 116 children with β-thalassemia major; 58 of them had pulmonary artery hypertension. They were compared to 58 healthy children who were age and sex-matched (control group). Serum levels of vascular endothelial growth factor and echocardiographic assessment were done for all children. Results: Vascular endothelial growth factor serum level was significantly higher in children with β-thalassemia major with pulmonary artery hypertension than in those without pulmonary artery hypertension, as well as in control groups (p < 0.001). Vascular endothelial growth factor serum level had a significant positive correlation with pulmonary artery pressure and serum ferritin, as well as a significant negative correlation with the duration of chelation therapy. Logistic regression analysis revealed that elevated vascular endothelial growth factor (Odd Ratio = 1.5; 95% Confidence Interval, 1.137-2.065; p = 0.005) was an independent risk factor of pulmonary artery hypertension in such children. Vascular endothelial growth factor serum level at a cutoff point of >169 pg/mL had 93.1% sensitivity and 93.1% specificity for the presence of pulmonary artery hypertension in children with β-thalassemia major. Conclusion: Elevated vascular endothelial growth factor serum level is associated with pulmonary artery hypertension in children with β-thalassemia.

Resumo: Objetivo: A finalidade deste estudo foi exemplificar a associação entre o nível de fator de crescimento endotelial vascular e a hipertensão arterial pulmonar em crianças com talassemia beta maior. Método: Este estudo caso-controle foi realizado em 116 crianças com talassemia beta maior; 58 das quais apresentaram hipertensão arterial pulmonar em comparação com 58 crianças saudáveis pareadas por idade e sexo (grupo de controle). Os níveis séricos do fator de crescimento endotelial vascular e a avaliação ecocardiográfica foram realizados em todas as crianças. Resultados: O nível sérico do fator de crescimento endotelial vascular foi significativamente maior em crianças com talassemia beta maior com hipertensão arterial pulmonar que as crianças sem hipertensão arterial pulmonar e os grupos de controle (p < 0,001). O nível sérico do fator de crescimento endotelial vascular apresentou uma correlação positiva significativa com a pressão arterial pulmonar e a ferritina sérica e correlação negativa significativa com a duração da terapia de quelação. A análise de regressão logística revelou que o fator de crescimento endotelial vascular elevado (RC = 1,5; IC de 95%: 1,137-2,065; p = 0,005) foi um fator de risco independente de hipertensão arterial pulmonar nessas crianças. O nível sérico do fator de crescimento endotelial vascular no ponto de corte > 169 (pg/mL) apresentou 93,1% de sensibilidade e 93,1% de especificidade na presença de hipertensão arterial pulmonar em crianças com talassemia beta maior. Conclusão: O nível sérico do fator de crescimento endotelial vascular elevado está associado à hipertensão arterial pulmonar em crianças com talassemia beta.

Effect of FOLFOX6 chemotherapy on serum VEGF expression in advanced colorectal cancer patients

SUMMARY OBJECTIVE: To explore the effect of FOLFOX6 chemotherapy on serum vascular endothelial growth factor (VEGF) expression in advanced colorectal cancer patients. METHODS: A retrospective analysis of 81 patients with advanced colorectal cancer who visited our hospital from March 2014 to February 2016 was performed. All the patients were treated with FOLFOX6 chemotherapy. On day 1, patients received oxaliplatin 100 mg/m2 ivgtt (2h), calcium folinate 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus and 5 fluorouracil 2500 mg/m2 ivgtt (5h). The treatment course was 2 weeks, and 4 treatment courses were required. The changes in the levels of VEGF and CRP and quality of life before and after 4 courses of chemotherapy were observed and therapeutic effects and adverse reactions after chemotherapy were evaluated. RESULTS: After treatment, the total efficiency of chemotherapy was 82.72% (67/81) with 24 cases in complete remission, 25 cases in partial response, 18 cases in stable disease and 14 cases in progressive disease. The levels of CRP and VEGF after the treatment were significantly lower than those before treatment (5.69±0.77) mg/L vs. (7.99±1.36) mg/L; (443.26±21.55) pg/mL vs. (542.83±20.44) pg/mL] (P<0.05). The KPS grade after treatment was significantly higher than that before treatment (57.84±4.6) point vs. (50.99±3.73) point] (P<0.05). Among them, 3 cases developed a rash, 5 cases experienced hair loss, and 9 cases developed nausea and vomiting. CONCLUSION: FOLFOX6 chemotherapy can decrease serum VEGF expression in patients with advanced colorectal cancer and enhance the curative effect with high safety, which is good for the improvement of patients' survival.

RESUMO OBJETIVO: Explorar o efeito da quimioterapia Folfox6 na expressão do fator de crescimento endotelial vascular sérico (VEGF) em pacientes com câncer colorretal avançado. MÉTODOS: Uma análise retrospectiva de 81 pacientes com câncer colorretal avançado que visitaram nosso hospital de março de 2014 a fevereiro de 2016 foi realizada. Todos os pacientes foram tratados com quimioterapia Folfox6. No dia 1, os doentes receberam oxaliplatina 100 mg / m2 ivgtt (2h), folinato de cálcio 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus e 5 fluorouracil 2.500 mg/m2 ivgtt (5h). O curso de tratamento foi de duas semanas e foram necessários quatro cursos de tratamento. Foram observadas as alterações nos níveis de VEGF e CRP e qualidade de vida antes e após quatro cursos de quimioterapia e avaliados os efeitos terapêuticos e reações adversas após a quimioterapia. RESULTADOS: Após o tratamento, a eficácia total da quimioterapia foi de 82,72% (67/81), com 24 casos em remissão completa, 25 casos em resposta parcial, 18 casos em doença estável e 14 casos em doença progressiva. Os níveis de CRP e VEGF após o tratamento foram significativamente inferiores aos do tratamento (5,69 ± 0,77) mg / L vs. (7,99 ± 1,36) mg / L; (443,26 ± 21,55) pg / mL vs. (542,83 ± 20,44) pg / mL] (P < 0,05). O grau de KPS após o tratamento foi significativamente maior do que antes do tratamento (57,84 ± 4,6 pontos) vs. (50,99 ± 3,73 pontos)] (P < 0,05). Entre eles, três casos desenvolveram erupção cutânea, cinco casos sofreram perda de cabelo e nove casos desenvolveram náuseas e vômitos. CONCLUSÃO: A quimioterapia Folfox6 pode, obviamente, diminuir a expressão de VEGF no soro em pacientes com câncer colorretal avançado e melhorar o efeito curativo com alta segurança, o que é bom para a melhoria da sobrevivência dos pacientes.

Serum concentration of vascular endothelial growth factor and depth of trophoblastic invasion in ampullary ectopic pregnancy

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia

We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia was associated with increased blood levels of anti-inflammatory and pro-inflammatory cytokines.

Influence of VEGF-C936T genetic variant on age-related macular degeneration / Influência da variante genética VEGF-C936T na degeneração macular relacionada à idade

ABSTRACTPurpose:To evaluate the association between the VEGF-C936T polymorphism and serum vascular endothelial growth factor (VEGF) levels, lifestyle, and demographic parameters in patients with age-related macular degeneration (AMD).Methods:A total of 183 individuals were enrolled in the present study, including 88 patients with AMD receiving clinical and pharmacological treatment (study group, SG) and 95 individuals without AMD as controls (control group, CG). The presence of the VEGF-C936T polymorphism and serum VEGF levels were determined using polymerase chain reaction/restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. Significance was set at P<0.05 for all statistical analyses.Results:The homozygous wild-type genotype (CC) and the C allele were predominant in both groups (P=0.934 and P=0.938, respectively). Serum VEGF levels (assessed in 57% and 31% of patients in the SG and CG, respectively) were comparable between groups (SG, 307.9 ± 223.6 pg/mL; CG, 305.1 ± 212.3 pg/mL; P=0.955). A significantly higher prevalence of smoking (44% vs 25%; P=0.01) and hypertension (66% vs 48%; P=0.025) was observed in the SG than in the CG. The distribution of alcohol consumption and dyslipidemia was similar between groups (P>0.05).Conclusions:In the present study group of Brazilian patients, the VEGF-C936T polymorphism was not found to be associated with age-related macular degeneration. However, smoking and systemic arterial hypertension (SAH) were found to be potential independent risk factors for the development of age-related macular degeneration. Comparable serum VEGF levels in both study groups may reflect the efficacy of pharmacological treatment of AMD.

RESUMOObjetivo:Avaliar a associação entre o polimorfismo VEGF-C936T, níveis séricos de VEGF (vascular endothelial growth factor), hábitos de vida e antecedentes pessoais em pacientes com degeneração macular relacionada à idade (DRMI).Métodos:Foram estudados 183 indivíduos: 88 pacientes com degeneração macular relacionada à idade, em tratamento clínico e medicamentoso (Grupo Estudo - GE) e 95 indivíduos sem sinais clínicos da doença (Grupo Controle - GC). O polimorfismo VEGF-C936T e os níveis séricos de VEGF foram analisados por PCR/RFLP e ELISA, respectivamente. Admitiu-se nível de significância para P<0.05.Resultados:O genótipo homozigoto selvagem (CC) prevaleceu em ambos os grupos (P=0,934), assim como o alelo C (P=0,938). Os níveis séricos de VEGF, analisados em 57% de SG e em 31% de CG, apresentaram valores semelhantes entre pacientes e controles (GE=307,9 ± 223,6 pg/mL; GC=305,1 ± 212,3 pg/mL; P=0,955). Notou-se maior frequência de tabagismo (44%) e hipertensão arterial sistêmica (66%) em GE versus GC (25%; 48%; P=0,01; P=0,025, respectivamente). A distribuição de etilismo e dislipidemia foi semelhante entre os grupos (P>0,05).Conclusões:Em nosso estudo com pacientes brasileiros, o polimorfismo VEGF-C936T não se associa com degeneração macular relacionada à idade, por outro lado, tabagismo e HAS são potencialmente fatores de risco independentes para a doença, enquanto níveis de VEGF semelhantes em ambos os grupos podem refletir o sucesso do tratamento farmacológico.

Correlation between vascular endothelial growth factor expression and presence of lymph node metastasis in advanced squamous cell carcinoma of the larynx / Correlação entre expressão do fator de crescimento endotelial e presença de metástase linfática nos carcinomas epidermoides avançados de laringe

Introduction: Squamous cell carcinoma is the most common neoplasm of the larynx, and its evolution depends on tumor staging. Vascular endothelial growth factor is a marker of angiogenesis, and its expression may be related to increased tumor aggressiveness, as evidenced by the presence of cervical lymphatic metastases. Objectives: To evaluate the expression of the vascular endothelial growth factor marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4) and correlate it with the presence of cervical lymph node metastases. Methods: Retrospective clinical study and immunohistochemical analysis of vascular endothelial growth factor through the German scale of immunoreactivity in products of non-glottic squamous cell carcinomas. Results: This study analyzed 15 cases of advanced non-glottic laryngeal tumors (T3/T4), four of which exhibited cervical lymphatic metastases. There was no correlation between vascular endothelial growth factor expression and the presence of cervical metastases. Conclusion: Although vascular endothelial growth factor was expressed in a few cases, there was no correlation with the spread of cervical lymph metastases. .

Introdução: O carcinoma de células escamosas é a neoplasia mais frequente da laringe e seu prognóstico depende do estadiamento. A progressão da doença está relacionada a fatores intrínsecos celulares do câncer, não conhecidos. O VEGF (vascular endothelial growth factor) é um marcador de angiogênese e sua expressão pode estar relacionada a uma maior agressividade tumoral, evidenciada pela presença de metástases linfáticas cervicais. Objetivos: Avaliar a expressão do marcador VEGF em carcinoma de células escamosas da laringe avançados (T3/T4), não glóticos e correlacionar quanto à presença de metástases linfáticas cervicais. Método: Estudo clínico retrospectivo de análise imunohistoquimica do VEGF através da escala Germânica de imunorreatividade em produtos de carcinomas epidermóides não glóticos. Resultados: Analisados 15 casos de tumores avançados de laringe (T3/T4) não glóticos, sendo sete com presença de metástases linfáticas cervicais. Não houve correlação entre a expressão do VEGF e a presença de metástases cervicais. Conclusão: O VEGF foi pouco expressado nos casos estudados e não foi observada sua correlação com a disseminação de metástase linfática cervical. .

Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion

Unexplained recurrent spontaneous abortion [URSA] is one of the main complications of pregnancy which is usually defined as three or more consecutive pregnancy losses before the 20[th] week of gestation without a known cause. Vascular endothelial growth factor [VEGF] is a potent angiogenic factor and shown, along with its receptors [VEGFR1, 2], to play important roles in several physiologic processes including reproduction. The aim of the present study was to analyze gene expression of VEGF and VEGF receptors in endometrium of patients with a history of URSA compared with normal fertile women. In addition, serum VEGF concentration was assessed and compared between the two groups at the same time. In this case control study, endometrial and blood samples were obtained between day 19[th] and 24[th] of menstrual cycle [window of implantation] from 10 women with a history of URSA [case group] and 6 fertile women who had at least one successful pregnancy [control group]. Expression of VEGF and VEGFRs was studied by reverse transcription- polymerase chain reaction [RT-PCR] and then quantified by real time PCR. Normalization of expression levels was done by comparison with beta-actin expression level as an internal control. Relative VEGF, VEGFR1 and VEGFR2 expression quantities were compared between the two groups. Enzyme linked immunosorbent assay [ELISA] was used for serum VEGF assay. VEGF, VEGFR1 and VEGFR2 gene expression was detected in endometrial samples of both groups. The mean relative expression of VEGF gene was lower in the case group compared with control women, however, both VEGF receptors were expressed higher in endometrium of the case group. In addition, the serum level of VEGF was significantly higher in the case group compared with the controls. Alteration in gene expression of VEGF and its receptors in endometrium and changes of serum VEGF might play important roles in pathogenesis of unexplained RSA

[ effect of aerobic exercise on the levels of vascular endothelial growth factor and glucose in hypertensive postmenopausal women: a randomized clinical trial]

Methods of lifestyle modification, including exercise can prevent cardiovascular disease in hypertensive patients through augmentation of endothelial function. The aim of this study was to determine the effect of 6 weeks of aerobic exercise on the plasma levels of vascular endothelial growth factor [VEGF] and glucose in hypertensive postmenopausal women. In this clinical trial, 20 stage 1 hypertensive postmenopausal women [50-55 years old] were randomly divided into two groups of exercise training and control. Training program consisted of 6 weeks of 45-60min aerobic exercise at 50-65% of maximum heart rate, for 45-60min persession, and 3 sessions per week. The control group did not participate in any training program. Blood pressure [BP] and plasma levels of VEGF and glucose was measured before and 48h after the last training session. Data were analyzed using Kolmogorov-Smirnov, levene, and paired t-tests. p<0.05 was considered statistically significant. Systolic and diastolic BP was significantly reduced in the exercise training group after 6 weeks [p<0.001]. In addition, 6 weeks of aerobic exercise significantly increased VEGF [p<0.002] and decreased glucose level [p<0.001]. According to the results of this study, regular aerobic exercise training is associated with a decrease in blood glucose and also an increase in VEFG in hypertensive postmenopausal women

Expression Characteristics of KAI1 and Vascular Endothelial Growth Factor and Their Diagnostic Value for Hepatocellular Carcinoma

BACKGROUND/AIMS: We tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC). METHODS: The protein and mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled para-carcinoma tissues were analyzed by Western blot and real-time polymerase chain reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC, benign liver disease or in healthy controls were quantitatively detected by enzyme-linked immunosorbent assay. RESULTS: The expression level of KAI1 was downregulated, while the expression level of VEGF was upregulated in the tissues or serum of the patients with HCC. The expression level of serum KAI1 in HCC patients was correlated with TNM staging, intrahepatic metastasis, lymph node or peritoneal metastasis, and portal vein thrombus. In addition to the factors that were correlated with KAI1 expression, VEGF expression was also closely related to the alpha-fetoprotein level of the patients. The area under the receiver operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and 0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was 86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the negative predictive value were improved to 91.86%, 84.68%, and 78.79% according to the combined detection of KAI1 and VEGF, respectively. CONCLUSIONS: A combined detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and form a reliable panel of diagnostic markers for HCC.

Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers / Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers.

Clear cell renal carcinoma is the most frequent type of renal carcinoma. Recently, attention has been focused in the expression of angiogenic factors by these tumors, which would justify in part their capacity to grow, invade and disseminate, stating a worse evolution of those patients with an unfavorable angiogenic profile. 83 samples of nephrectomy with a diagnosis of clear cell renal cell carcinoma were studied. Clinical and pathological data were collected. Tumors were studied to assess immunohistochemical expression of the following markers: VEGF-A, HIF-1α, CD34 and Ki67. Results indicated a direct linear relationship between expressions of these four markers. Besides, the expression of HIF-1α was directly related to Furhman grade, invasion of the renal vein and tumor stage. Likewise, tumor proliferation index, assessed with Ki67, was directly related to the presence of necrosis, capsular invasion and advanced tumor stage. Regarding the expression of CD34, vascular density was inversely related to tumor necrosis and overall survival. These findings are controversial compared with the available literature. Then, a research scenery would be open, where the importance of generating prospective and more standardized studies are highlighted to determine the role of these angiogenic factors in tumor evolution and prognostic evaluation of these tumors.

Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p<0.05) than normotensive subjects. Serum concentrations of VEGF, PlGF and NO were significantly decreased (p<0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p<0.05), systolic blood pressure (r = -0.822, p<0.005), diastolic blood pressure (r = -0.714, p<0.005) and was positively correlated with VEGF (r = 0.464, p<0.005) and PlGF (r = 0.546, p<0.005). VEGF and PlGF showed significant (p<0.005) negative correlation with systolic and diastolic blood pressure and PlGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and PlGF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.

Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05) and better left ventricle function (p<0.01). CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients. .

Association between baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios and response to metronomic chemotherapy using cyclophosphamide and celecoxib in patients with advanced breast cancer.

BACKGROUND: Metronomic chemotherapy (MCT) with cyclophosphamide (Cy) and celecoxib (Cel) has therapeutic efficacy and low toxicity profile in advanced breast cancer patients (ABCP), but no reliable biomarkers of response have been found yet that allow patient selection for treatment. AIM: To investigate the potential role as biomarkers of pro‑ and antiangiogenic parameters and evaluate their response in ABCP receiving metronomic Cy 50 mg p.o./day + Cel 400 mg p.o./day. MATERIALS AND METHODS: Serum levels of vascular endothelial growth factor‑C (VEGF‑C), soluble VEGF receptors 2 and 3 (sVEGFR‑2, sVEGFR‑3), were measured at different time points in 13/15 patients included in a phase II trial of MCT with Cy+Cel. RESULTS: Serum levels of sVEGFR‑2 and sVEGFR‑3 increased significantly during treatment (P = 0.0392; P = 0.0066, respectively). VEGF‑C showed no significant modifications. Previous determinations of VEGF and TSP‑1 in the same patients were utilized. VEGF/sVEGFR‑2, VEGF/TSP‑1, and VEGF‑C/sVEGFR‑3 ratios decreased significantly along the treatment (P = 0.0092; P = 0.0072; P = 0.0141, respectively). Nonsignificant variations were observed for VEGF‑C/sVEGFR‑2 ratio. Baseline values of VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios were associated with time to progression (TTP) (P = 0.0407; P = 0.0394, respectively) meanwhile baseline VEGF was marginally significant (P = 0.0716). Patients with values lower than the 50th percentile for both ratios showed longer TTP. CONCLUSIONS: We have identified the baseline VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios as potential biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding warrants its confirmation in a higher number of patients.

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic ...

Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

PURPOSE: To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. METHODS: Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. RESULTS: The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. CONCLUSION: Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.

Bronchial asthma and airway remodeling markers

Abstract: Asthma is an inflammatory disease with extracellular matrix remodeling and collagen deposition. Vascular alterations have been suggested to contribute to airway hyper responsiveness. Vascular endothelial growth factors and metalloproteinases are mediators of airway inflammation and remodeling in asthma. There are few data regarding the potential effects of anti-asthma treatment on indices of air way remodeling

Objective: This study investigates the role of VEGF, MMP-9 in the pathogenesis of asthma and their role as index of remodeling, markers of inflammation in symptomatic bronchial asthma on low dose ICS. Also we evaluate the role of adding long acting B[2] agonist for 6 weeks in airway remodeling for the symptomatic asthmatic patients on low dose ICS

Methods: VEGF and MMP-9 were measured in sputum of healthy control, and bronchial asthma patients before and after the addition of long acting B[2] agonists. Also we evaluated whether VEGF correlated with MMP-9 in symptomatic bronchial asthma receiving low or moderate dose of ICS

Results: Levels of VEGF and MMP-9 are significantly higher in sputum of bronchial asthma than in healthy controls. The mean level of VEGF, MMP-9 in sputum of bronchial asthma patients on low to moderate dose of ICS was 2500 pg/ml +/- 750, 33.3 ng/ml +/- 16.7. After 6 weeks of treatment with long acting B[2] agonists there was a reduction in the mean levels of both VEGF, MMP-9 1750 pg/ml +/- 250, 27.4 ng/ml +/- 13. Also there was a significant correlation between the levels of VEGF and MMP-9 in healthy subjects and patients with bronchial asthma. There was a significant correlation between both VEGF MMP-9 and the sputum eosinophils and neutrophil in patients with bronchial asthma before adding long acting B[2] agonists

Conclusion: Symptomatic patients with bronchial asthma on a low dose ICS have elevated levels of VEGF, MMP-9. There was an interrelationship between VEGF and MMP-9, this finding suggests that VEGF signaling regulates MMP-9 expression, and plays a critical role in the maintenance of asthma. VEGF, MMP-9 could be considered as important markers of airway remodeling in asthma. The addition of regular long acting B[2] agonist to low or moderate dose ICS in symptomatic bronchial asthma patients had a beneficial effect on the air way remodeling markers in a way that they may potentate the anti-inflammatory effects of ICS on inflammatory cells

Prognostic utility of vascular enothelial growth factor [VEGF] in case of endometriosis

Endometriosis call defined as a non-neoplastic disease in which an endometrium-like tissue implants itself outside the uterine cavity conserving its histological and functional structure. VEGF concentration elevates in peritoneal fluid of patients with endometriosis which indicate that VEGF is also modulated in the serum of these patients. The aim of this study is to determine the behavior of VEGF in plasma and peritoneal fluids of patients with endometriosis, also correlation between VEGF level and stage of endometriosis. This study was carried out on 60 infertile patients. They were divided after laparoscopy into two groups, study group including 40 endometriosis patients and control group including 20 patients without endometriosis. The study group was subdivided in two subgroups according to stage of endometriosis first subgroup [a] including 20 patients with minimal to mild endometriosis and subgroup [b] including 20 patients with moderate to severe endometriosis. VEGF levels were measured by enzyme Linked immunosorbent assay [ELISA] in serum and peritoneal fluid of all patients. The mean VEGF level were significantly increased in serum and peritoneal fluid samples of cases with endometriosis compared with control cases, this increase was statistically significant in patients with moderate to severe stage. Also VEGF levels in peritoneal fluids was greater than that of the serum levels which was also significant in With moderate to severe stage. Conclusions: VEGF is present ill amount in the serum and peritoneal fluid of women with endometriosis. This increase correlates with the stage of the disease

Serum and plasma vascular endothelial growth factor in healthy dogs / Fator de crescimento do endotélio vascular no soro e plasma de cães saudáveis

Vascular endothelial growth factor (VEGF) is an angiogenic factor with a key role in physiological and pathological process. It can be measured in several organic fluids, including serum and plasma samples. The aim of this work was to investigate the concentration of serum and plasma VEGF of healthy dogs in order to recommend optimal handling of biological samples for accurate measurement of VEGF. Blood samples of thirty dogs were collected into sterile EDTA tube for plasma analysis and into clot activator tubes for serum analysis. The tubes were centrifuged within 90 minutes of collection at 1400 xg for 10 minutes. VEGF concentration was determined using the quantitative method (ELISA). Serum VEGF level was 26.5 + 13.3pg/mL and plasma VEGF was 11.7 + 16.4 pg/mL (p = 0.0003). There was a positive correlation between serum VEGF and platelets (r = 0.37, p = 0.03) and a negative correlation between serum VEGF and hemoglobin (r = -0.38, p = 0.03) and between plasma VEGF and  hemoglobin (r = -0.34, p = 0.06). When compared with serum samples it was concluded that plasma samples could be used as an optimal fluid for measuring VEGF in dogs.

O fator de crescimento do endotélio vascular (VEGF) é um fator angiogênico com papel importante em processos patológicos e fisiológicos. O VEGF pode ser quantificado em diversos fluidos orgânicos, incluindo amostras de soro e plasma. O presente trabalho investigou a concentração do VEGF no soro e no plasma de cães saudáveis a fim de recomendar o manejo ótimo de amostras biológicas para a determinação dos níveis do VEGF. Amostras de sangue de 30 cães saudáveis foram coletadas em tubos estéreis contendo EDTA para análise do plasma e em tubos com ativador de coagulação para análise do soro. Os tubos foram centrifugados após 90 minutos da coleta a 1.400 x g por 10 minutos. A concentração do VEGF foi determinada com o método quantitativo de ELISA. O nível sérico médio de VEGF foi de 26,5+13,3pg/mL e o plasmático foi 11,7 + 16.4 pg/mL (p = 0,0003). Houve correlação positiva entre o VEGF do soro com as plaquetas (r = 0,37, p = 0,03) e correlação negativa entre o VEGF do soro com hemoglobina (r = -0,38, p = 0,03) e entre VEGF do plasma com hemoglobina (r = -0,34, p = 0,06). A comparação dos resultado obtidos nos exames de plasma e soro indicou que amostras de plasma podem ser utilizadas como ótimo fluido para quantificação do VEGF de cães.

Mobilização de células progenitoras endoteliais com o exercício em sadios: uma revisão sistemática / Mobilization of endothelial progenitor cells with exercise in healthy individuals: a systematic review / Movilización de células progenitoras endoteliales con el ejercicio en sanos: una revisión sistemática

O exercício físico mobiliza Células Progenitoras Endoteliais (CPE) para o sangue periférico. Entretanto, esse efeito parece depender de características do exercício, como duração e intensidade. O objetivo do presente trabalho foi verificar, por meio de revisão sistemática, o impacto de uma única sessão de exercício aeróbico sobre a mobilização de CPE em indivíduos sadios e os potenciais mecanismos envolvidos. A busca bibliográfica foi realizada nas bases de dados eletrônicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus e Medline, em maio de 2011. Dos 178 estudos inicialmente identificados, 12 atenderam aos critérios de inclusão e foram classificados quanto à qualidade mediante critérios da escala PEDro. A magnitude e a duração da resposta de mobilização das CPE foram maiores após a realização de exercícios de longa/ultralonga duração e estão correlacionadas com níveis plasmáticos de fator de crescimento endotélio vascular (VEGF). O pico de mobilização dessas células em resposta a uma sessão de exercício máximo ou submáximo, com duração de até uma hora, ocorre no período imediatamente após o esforço até uma hora após sua interrupção. Um possível mecanismo é a biodisponibilidade do Óxido Nítrico (NO). A idade dos indivíduos e a intensidade do exercício parecem interferir na resposta de mobilização das CPE. Exercícios de longa/ultralonga duração promovem mobilização mais acentuada das CPE quando comparados a exercícios máximos ou submáximos. Os mecanismos envolvem a liberação do VEGF em exercícios de longa/ultralonga duração e a biodisponibilidade de NO em exercícios máximo e submáximo com até uma hora de duração.

Physical exercise mobilizes endothelial progenitor cells (EPCs) to peripheral blood. However, this effect seems to depend on exercise characteristics, such as duration and intensity. The aim of this systematic review was to verify the impact of a single bout of aerobic exercise on the mobilization of EPCs in healthy individuals, and the potential mechanisms involved. The bibliographic search was conducted on the following electronic databases in May 2011: SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus and Medline. Of the 178 articles initially identified, 12 met the inclusion criteria and were classified regarding quality according to the PEDro scale. The magnitude and duration of the EPC mobilization response were higher after long/ultralong duration exercises, and they are correlated with vascular endothelial growth factor (VEGF) plasma levels. The EPC mobilization peak in response to a maximal or submaximal single bout of exercise lasting up to one hour occurs immediately after the exercise or within the first hour after it. One possible mechanism is nitric oxide (NO) bioavailability. The individuals' age and exercise intensity seem to interfere with the EPC mobilization response. Long/ultralong duration exercises promote more pronounced EPC mobilization as compared with maximal or submaximal exercises. The mechanisms involve VEGF release in long/ultralong duration exercises and NO bioavailability in maximal or submaximal exercises lasting less than one hour.

El ejercicio físico moviliza Células Progenitoras Endoteliales (CPE) hacia la sangre periférica. Entre tanto, ese efecto parece depender de características del ejercicio, como duración e intensidad. El objetivo de este estudio fue verificar, por medio de revisión sistemática, el impacto de una única sesión de ejercicio aeróbico sobre la Movilización de CPE en individuos sanos y los potenciales mecanismos envueltos. La búsqueda bibliográfica fue realizada en las bases de datos electrónicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus y Medline, en mayo de 2011. De los 178 estudios inicialmente identificados, 12 respondieron a los criterios de inclusión y fueron clasificados en cuanto a la calidad mediante criterios de la escala PEDro. La magnitud y la duración de la respuesta de Movilización de las CPE fueron mayores después de la realización de ejercicios de larga/ultra larga duración y están correlacionadas con niveles plasmáticos de factor de crecimiento endotelio vascular (VEGF). El pico de Movilización de esas células en respuesta a una sesión de ejercicio máximo o submáximo, con duración de hasta una hora, ocurre en el período inmediatamente después del esfuerzo y hasta una hora después de su interrupción. Un posible mecanismo es la biodisponibilidad del Óxido Nítrico (NO). La edad de los individuos y la intensidad del ejercicio parecen interferir en la respuesta de Movilización de las CPE. Ejercicios de larga/ultra larga duración promueven Movilización más acentuada de las CPE cuando son comparados a ejercicios máximos o submáximos. Los mecanismos envuelven la liberación del VEGF en ejercicios de larga/ultra larga duración y la biodisponibilidad de NO en ejercicios máximo y submáximo con hasta una hora de duración.

Effects of perinatal nicotine exposure on the development of albino rat's alveoli with special reference to the role of the vascular endothelial growth factor

Nicotine is one of the most toxic and addictive agents in cigarette smoke. Maternal cigarette smoking may affect lung development and maturation of the fetus. Recently, it has been reported that blood vessels promote alveolar growth during development and contribute toward the maintenance of alveolar structures throughout postnatal life. The aims of this study were to determine the effects of perinatal nicotine exposure on the histological structures of the developing alveoli of offspring with special reference to the role of vascular endothelial growth factors [VEGF]. Ten healthy pregnant rats were divided equally into control [I] and treated [II] groups. Rats of group II were subjected to a daily subcutaneous injection of 1 mg/kg of nicotine from the seventh day of gestation until the end of the experiment. Their offspring were subdivided into two subgroups at 2 and 21 postnatal days. At the time of sacrifice, all rats were anesthetized with ether and lung samples were processed for light and electron microscopic examination. Also, an immunohistochemical study was carried out for VEGF. The alveolar diameter, thickening of interalveolar septa, number of vacuolated interstitial cells, and the surface area of VEGF immunoexpression were determined and analyzed statistically. In the nicotine-exposed groups, widening in alveoli and thinning of interalveolar septa in the offspring were observed. Also, the same offspring showed a reduction in VEGF immunoexpression. All these results were confirmed statistically especially at 3 weeks of age or at the time of weaning. Also, swelling in pneumocyte type I and deformed blood air barriers with a subsequent statistical increase in the number of vacuolated interstitial cells [pneumocyte type II] were observed. In the current work, it was found that perinatal exposure to nicotine altered lung development, an effect that may be mediated by decreased VEGF. Thus, avoidance of maternal smoking during pregnancy and lactation is highly recommended