The genetics of nicotine dependence:Relationship to Pancreatic cancer

Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

儿童脑脊液内IGF-I、IGF-II、IGF-结合蛋白-1及IGF结合蛋白-3浓度的早期发育性变化

IGF-I and IGF-II are ubiquitously expressed growth factors that have profoun d effects on the growth and differentiation of many cell types and tissues, incl uding cells of the CNS. In biologic fluids, most IGFs are bound to one of six IG F binding proteins (IGFBPs 1-6). Increasing evidence strongly supports a role f or IGF-I in CNS development, as it promotes neuronal proliferation and survival . However, little is known about IGF-I and its homolog IGF-II and their carrie r proteins, IGFBPs, during the neonatal period in which brain size increases dra matically, myelination takes place, and neurons show limited capacity to prolife rate. Herein, we have determined the concentrations of IGF-I, IGF-II, IGFBP-I , and IGFBP-3 in cerebral spinal fluid (CSF) samples that were collected from children who were 1 wk to 18 y of age. The concentrations of IGF-I, IGFBP-I, and IGFBP-3 in CS F from children < 6mo of age were significantly higher than in older children, w hereas IGF-II was higher in the older group. This is in contrast to what is obs erved in the peripheral circulation, where IGF-I and IGFBP-3 are low at birth and rise rapidly during the first year, reaching peak levels during puberty. Hig her concentrations of IGF-I, IGFBP-I, and IGFBP-3 in the CSF of very young ch ildren suggest that these proteins might participate in the active processes of myelination and synapse formation in the developing nervous system. We propose t hat IGF-I and certain IGFBPs are likely necessary for normal CNS development du ring critical stages of neonatal brain growth and development.

Impaired T-cell differentiation in diabetic foot ulceration

Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly understood.Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing.However,few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes.In this study,we analysed the T-cell receptor(TCR)repertoire diversity in TCR-αβ^(+)T cells.We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers.Our results showed that diabetic individuals,especially those with foot ulcers,have a significantly lower naive T-cell number and a poorer TCR-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,which was even more pronounced in patients with acute foot ulceration.Moreover,the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients.In conclusion,effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers.This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.