Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals.

The serotonergic system may be involved in smoking behavior since the intake of nicotine increases serotonin secretion in the CNS. Moreover, evidence supporting the beneficial effect of selective serotonin reuptake for quitting smoking suggesting that the serotonin transporter (5-HTT) is a plausible target for the understanding and elucidation of smoking behavior. The transcriptional activity of its human gene (SLC6A4) is modulated by a polymorphism described in the second intron, the STin2 VNTR, which thus may interfere with 5-HTT synthesis. In this study was analyzed the polymorphism STin2 VNTR of 60 smokers male patients diagnosed for oral carcinoma, 61 male smokers without cancer and 65 non-smoker healthy blood donors. The STin2. 9 allele carriers were more present in smoker groups (with cancer and without cancer, respectively) than in the non-smoker (OR = 7.11, 95% CI = 0.83-60.91 and OR = 24.73; IC 95% = 3.17-192.66). Conversely, individuals carrying allele 10 were more prevalent in non-smokers compared with smokers (oral cancer patients and individuals without cancer, respectively), showing a protective factor of this allele (OR = 0.56; 95% CI = 0.24-1.33 and OR = 0.46; 95% CI = 0.20-1.07). This is the first report of a study assessing the importance of STin2 VNTR smoking behavior in Brazilian individuals and the association of STin2. 9 allele carriers in nicotine dependence. It is suggested that individuals with low serotonin concentration in the central nervous system, probably due to the presence of the allele for high expression of 5-HTT,especially STin2. 9, were more susceptible to nicotine dependence. Moreover, individuals with the 10 allele might have less risk for nicotine dependence.

Aumento dos níveis de LDLox induzem maior formação de células espumosas in vitro / Increased levels of oxLDL induce higher foam cells formation in vitro

Inúmeras evidências sustentam a hipótese de que a modificação oxidativa da LDL contribui para o desenvolvimento e progressão da aterosclerose em uma variedade de modelos animais e que as células espumosas constituem um evento crucial no desenvolvimento da lesão aterosclerótica. A LDL oxidada tem uma ação quimioatraente sobre os monócitos, induzindo a transformaçãode macrófagos em células espumosas. Neste trabalho, foi desenvolvido um protocolo simples e reproduzível de cultura de células mononucleares humanas, o qual foi utilizado para avaliação da capacidade aterogênica da LDL oxidada comparada à LDL nativa naformação de células espumosas com ativação espontânea dos macrófagos. A partir do sangue de 10 indivíduos normolipidêmicos, obteve-se a LDL por processo de ultracentrifugação sendo a mesma oxidada in vitro na presença de íons cobre. Monócitos diferenciaram-se em macrófagos e foram incubados com LDL nativa e oxidada em diferentes concentrações. Houve formação decélulas espumosas apenas em macrófagos estimulados com LDL oxidada, variando quantitativamente de acordo com a sua concentração.Concluiu-se que este protocolo de estudo, além de possibilitar a utilização de macrófagos humanos, permitiu a redução do tempo de incubação da cultura. Paralelamente, demonstrou-se que a formação de células espumosas é dependente da extensão do grau deoxidação da LDL

Much evidence sustains the hypothesis that oxidative modification of low-density lipoprotein (LDL) contributes to the development and progression of atherosclerosis and that foam cells constitute a crucial event in the development of the atheroscleroticlesion. Oxidized LDL (oxLDL) presents a chemotatic action on monocytes, inducing the transformation of macrophages into foam cells. In this work, a simple reproducible protocol for culturing human mononuclear cells was developed to evaluate the atherogeniccapacity of oxLDL compared to native LDL in the formation of foam cells. Monocytes differentiate into macrophages when stimulatedwith native and oxidized LDL at different concentrations. Foam cell formation only occurred in macrophages stimulated by oxLDL, which varied quantitatively according to its concentration. This study protocol, besides making the use of human macrophages possible, permitted a reduction in culture incubation time. Moreover, the study demonstrated that foam cell formation is dependent on the degree of LDL oxidation