Modeling of Immunosenescence and Risk of Death from Respiratory Infections: Evaluation of the Role of Antigenic Load and Population Heterogeneity

It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to describe and investigate the mechanism underlying the age pattern of the mortality rate caused by infectious diseases and to determine the cause-specific hazard rate as a function of immune system characteristics. For these purposes we develop a three-compartment model explaining observed risk-of-death. The model incorporates up-to-date knowledge about cellular mechanisms of aging, disease dynamics, population heterogeneity in resistance to infections, and intrinsic aging rate. The results of modeling show that the age-trajectory of mortality caused by respiratory infections may be explained by the value of antigenic load, frequency of infections and the rate of aging of the stem cell population (i.e. the population of T-lymphocyte progenitor cells). The deceleration of infection-induced mortality at advanced age can be explained by selection of individuals with a slower rate of stem cell aging. Parameter estimates derived from fitting mortality data indicate that infection burden was monotonically decreasing during the twentieth century, and changes in total antigenic load were gender-specific: it experienced periodic fluctuations in males and increased approximately two-fold in females

Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies

Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells

Single-electron tunneling in InP nanowires

We report on the fabrication and electrical characterization of field-effect devices based on wire-shaped InP crystals grown from Au catalyst particles by a vapor-liquid-solid process. Our InP wires are n-type doped with diameters in the 40-55 nm range and lengths of several microns. After being deposited on an oxidized Si substrate, wires are contacted individually via e-beam fabricated Ti/Al electrodes. We obtain contact resistances as low as ~10 kOhm, with minor temperature dependence. The distance between the electrodes varies between 0.2 and 2 micron. The electron density in the wires is changed with a back gate. Low-temperature transport measurements show Coulomb-blockade behavior with single-electron charging energies of ~1 meV. We also demonstrate energy quantization resulting from the confinement in the wire.Comment: 4 pages, 3 figure

Risk factors for colorectal cancer in subjects with family history of the disease.

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population

Selected physical activities and the risk of endometrial cancer.

The relationship between various indicators of physical activity and endometrial cancer risk was analysed using data of a case-control study conducted in 1988-1991 in Switzerland and Italy on 274 histologically confirmed cases and 572 controls admitted to hospital for acute, non neoplastic, non hormone-related diseases. Using a self-rated assessment of total physical activity, there was a systematic tendency for the cases to report more frequently 'low' or 'very low' physical activity. The relative risks were similar for 'very high' or 'moderately high' physical activity, but increased in the two lowest levels, with point estimates, in various decades of age, between 1.3 and 2.3 for 'moderately low' and over 2.5 for 'very low' physical activity. Although the association was apparently stronger at older ages, all the trends in risk were significant. Allowance for major identified potential distorting factors, including body mass index and a measure of total energy intake, could explain only in part the association, and the inverse trends in risk remained statistically significant. When selected types of physical activity were analysed, no association was observed with climbing stairs or walking, but the risk estimates for the lowest level of activity was over 4 for housework, and between 1.5 and 1.9 for sport and leisure and occupational activity. Thus, the present findings suggest that a moderate or high physical activity is an indicator of reduced endometrial cancer risk, although this observation still requires epidemiologic confirmation and clearer definition from a pathogenic point of view

Maize and Risk of Cancers of the Oral Cavity, Pharynx, and Esophagus in Northeastern Italy

The relationship between maize consumption and risk of cancer of the upper digestive tract was investigated in 107 patients with oral cancer, 107 with pharyngeal cancer, 68 with esophageal cancer, and 505 hospital controls who permanently resided in Pordenone Province in the northeastern part of Italy. The analysis was restricted to males. The population of this province has a high incidence of these neoplasms and shows particularly elevated levels of alcohol and tobacco use, in addition to high maize consumption. Highly significant associations with frequent intake of maize emerged for oral cancer, pharyngeal cancer, and esophageal cancer (odds ratios = 3.3, 3.2, and 2.8, respectively). The risk elevation could not be explained in terms of differences in education, occupation, tobacco use, or consumption of fresh fruits and vegetables. The unfavorable effect of maize on risk of cancer of the upper digestive tract, however, was evident only in those individuals who reported heavy drinking (i.e., ≥42 alcoholic drinks/wk). The present findings are likely to be related to the fact that maize can cause deficiencies of various micronutrients (chiefly, niacin and riboflavin) and agree with previous observations from Africa, the People's Republic of China, the United States, and Italy. [J Natl Cancer Inst 82:1407-1411, 1990

Oral contraceptives, hormone replacement therapy and the risk of colorectal cancer.

The relationship between oral contraceptives (OCs), menopausal hormone replacement therapy (HRT) and the risk of colorectal cancer was investigated in a case-control study conducted in northern Italy between 1985 and 1992 on 709 women with incident colorectal cancer and 992 controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract, non-hormone-related disorders. A reduced risk of colorectal cancer was observed in women who had ever used OCs [multivariate odds ratio (OR) = 0.58; 95% confidence interval (CI): 0.36-0.92]. The OR was 0.52 (95% CI 0.27-1.02) for use over 2 years. For women ever using HRT, the multivariate OR was 0.40 (95% CI 0.25-0.66). The risk was inversely related to duration of use, with ORs of 0.46 for 2 years or less and 0.25 for more than 2 years of use. No consistent pattern of trends was observed with time since first or last use. This study provides further evidence that OC and HRT do not increase, and possibly decrease, the risk of colorectal cancer. These results, if confirmed, would have important implications for the ultimate risk-benefit assessment of female hormone preparations