Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy

Angiogenesis is a process of development and of growth of new capillary blood vessels from pre-existing vessels. When pathological, it contributes to the development of numerous types of tumors, and the formation of metastases. In order to grow, carcinoma need new blood vessels to form so that they can feed themselves. Therefore, nowadays the concept according to which the development of cancer is angiogenesis dependent is generally recognized. This concept makes the control of tumoral angiogenesis one of the promising therapeutic ways in cancerology. The transition from the latent phase to the invasive and metastatic phase of a cancer is linked to what is called the angiogenic switch. It implies complex cellular and molecular interactions between cancerous cells, endothelial cells and the components of the extra-cellular matrix and namely the existence of specific proteins secreted by the tumoral cells able to stimulate the proliferation of capillary endothelial cells. Among them, VEGF, Vascular Endothelial Growth Factor was found in several types of tumors. It has shown a tumoral angiogenic activity in vitro and in vivo, and thus is a privileged target for the control of angiogenesis in an anti-tumoral goal. The role of VEGF in tumoral angiogenesis has been extensively studied. It has been proved to undergo as well autocrine as paracrine stimulation of tumoral angiogenesis. During the last few years, several members of the VEGF family have been described namely the VEGF-A, B, C, D, E and placenta growth factor (PlGF) among which VEGF-A (121 aminoacids) plays a role of prime importance in angiogenesis. VEGF is a 45 kDA glycoprotein, homodimeric, basic, and able to bind heparin. The three-dimensional structure of VEGF has been recently determined, by X-rays diffraction, and NMR spectroscopy. The different forms of the VEGF bind to receptors that exhibit a tyrosine-kinase activity (RTK). The specific action of the VEGF on the endothelial cells is mainly regulated by two types of RTK of the VEGF family, VEGFR1, or Flt-1, and VEGFR2, or KDR/Flk-1. Mutagenesis studies have shown that only a small number of VEGF residues are important and essential for the binding with RTK. Data described to date from the studies of VEGF/RTK interactions agree to the hypothesis that KDR receptor is the main human receptor responsible for the VEGF activity in both physiological and pathological vascular development, and VEGF-KDR signalling pathway has been validated as a priority target for the development of anti- and pro- angiogenic agents. Therefore angiogenesis mediated by VEGF constitutes a new target for anti-cancer therapy which has explored through different ways of intervention aiming at the blocking of the tumoral angiogenesis. The main ones are: -Struggle against the stroma degradation and invasion by the neo-vessels -Inhibition of activated endothelial cells. -Inhibition of angiogenic factors production and of their receptors. -Inhibition of the VEGF signal pathway, by peptides blocking the bond between VEGF and its receptors through the inhibition of intracellular transduction of VEGF signal. In conclusion, this bibliographic study allows to situate works of medicinal chemistry in the context of present knowledge concerning the vascular endothelial growth factor (VEGF) and its role in angiogenesis.     

Strategies for the implementation of a new pedagogical proposal at the Nursing School of the Federal University of Bahia

This article reflects on the process of designing the Pedagogical Project for the Nursing School from Federal University of Bahia. The socialization of this experience intends to contribute with other nursing institutions which, in order to meet new curricular requirements (DCENF--National Curricular Guidelines for Nursing, Medicine, and Nutrition Undergraduate Programs), are going to experience similar processes or which are presently going through the same process. This article includes some historical features and the legal basis for changes, by presenting the reasons for the current proposal, as well as its curricular organization, the main challenges and some strategies for overcoming them. Although some aspects which still need further attention from the faculty are presented, such as interdisciplinary program contents, academic management, the evaluation process and the implementation of the proposal, the authors come to the conclusion that this debate is to be continued. As this process is a dynamic one and is still under construction, other challenges might come up that demand the use of new strategies for their (re)orientation.     

Updating of the distribution of Aedes albopictus in Brazil (1997-2002)

Updating regarding the distribution of Aedes albopictus in Brazil is presented for the period from 1997 to 2002. Data from the yellow fever and dengue information system of the National Health Foundation is utilized. It can be seen that this species is present in 20 of the 27 Brazilian states.     

Prevalence of sexual disorders in those young males who later become drug abusers

The purpose of this study was to learn about the frequency of sexual disorders in young males who later become substance abusers. We interviewed 228 men treated in 10 drug centers for substance abuse. The questionnaire that we used was designed to assess the onset of erectile dysfunction (ED) or of premature ejaculation (PE). Only those subjects who became substance users between the ages of 17 to 29 were taken into consideration. Of the 228 subjects recruited, only 130 met the inclusion criteria (mean age 33). These male patients had a prevalence of ED of 20.3% (cl 99% 12.3-31.2), whereas the prevalence of ED of age-matched males in the general population is 2.1% (cl 99% 0.36-5.46; p < 0.000001). The prevalence of PE in the sample prior to drug use was 37.5%. Sexual desire was in the normal range in nearly all subjects. The prevalence of ED in the men of our sample is higher than in age-matched individuals of the general population. These data suggest a new hypothesis: sexual disorders or the conviction that one has a sexual problem is a possible risk factor among men for drug abuse and addiction.     

Family history of ischemic heart disease and risk of acute myocardial infarction

BACKGROUND: Several aspects of the relation between family history of ischemic heart disease (IHD) and risk of acute myocardial infarction (AMI) need further quantification. METHODS: A case-control study was conducted in Italy in 1995-1999 on 378 men and 129 women with a first nonfatal AMI, and 297 male and 181 female controls in a hospital for selected acute conditions. Odds ratios (OR) of AMI according to family history of IHD were estimated using unconditional logistic regression, adjusting for other AMI risk factors and family size. RESULTS: The overall OR for those having > or =1 first-degree relatives with IHD was 2.1, and 3.8 for > or =2 relatives. The OR for those with an affected parent or sibling were similar. The OR were also similar across strata of sex, age at diagnosis of the proband or the relative, and selected AMI risk factors, which were risk factors also in those with a positive family history. CONCLUSIONS: Family history of IHD is an independent risk factor for AMI, and intervention on modifiable risk factors may be beneficial also in those with a family history of the disease.     

First epidemic of aseptic meningitis due to echovirus type 13 among Spanish children

Echoviruses are the commonest cause of aseptic meningitis (AM). Echovirus type 13 (EV-13) was the second enterovirus serotype associated with different local outbreaks of AM in Spain between February and October 2000. It was the first time that an epidemic AM caused by this virus was recognized in Spain. The index case appeared in the Canary Islands (Canarias). The EV-13 virus was isolated from 135 patients, predominantly from cerebrospinal fluid (CSF). All isolates were from children under 13 years. The age specific peak incidence was in infants under 1 year. Most patients had fever, headache and other meningeal signs. This enterovirus serotype, not previously detected in Spain, caused severe illness with a high attack rate.     

Cavernous hemangioma of the tricuspid valve: minimally invasive surgical resection

Cardiac hemangioma is a rare, benign vascular tumor, occurring with an incidence of 1% to 2% of all detected benign heart neoplasms. Hemangioma of the tricuspid valve has never been previously reported. We describe the successful excision of this tumor through a right anterolateral mini-thoracotomy in a 49-year-old woman. Competency of the valve was confirmed intraoperatively and at discharge by transesophageal echocardiography.