Regeneration of dendritic cells in aged mice

Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration.     

Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients

BACKGROUND: Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients; it has been attributed to increased oxidative stress, dyslipidemia, malnutrition, and chronic inflammation. Activation of neutrophils is a well-recognized feature in dialysis patients, and superoxide-anion production by neutrophil NADPH oxidase may contribute significantly to oxidative stress. OBJECTIVE: The aim of the study was to compare the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients. DESIGN: Thirty-two patients undergoing hemodialysis were recruited and randomly assigned to groups to receive dietary supplementation with RGJ, vitamin E, or both or a control condition without supplementation or placebo. Blood was obtained at baseline and on days 7 and 14 of treatment. RESULTS: RGJ consumption but not vitamin E consumption reduced plasma concentrations of total cholesterol and apolipoprotein B and increased those of HDL cholesterol. Both RGJ and vitamin E reduced plasma concentrations of oxidized LDL and ex vivo neutrophil NADPH oxidase activity. These effects were intensified when the supplements were used in combination; in that case, reductions in the inflammatory biomarkers intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 also were observed. CONCLUSIONS: Regular ingestion of concentrated RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concentrations of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a reduction in cardiovascular risk.     

Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations

Objectives. We examined pregnant women''s use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa.Methods. Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005.Results. At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home.Conclusions. Pregnant women''s tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.Tobacco use is widely recognized as one of the leading threats to global health.¹ Historically, the prevalence of smoking among women in the developing world has been very low, in part because of strong cultural constraints against women''s smoking; approximately 50% of men in developing nations smoke cigarettes, compared with 9% of women.² Averting an increase in the prevalence of smoking among women in developing nations is widely recognized as a significant public health opportunity.^3,4Pregnant women are a priority population for tobacco control efforts because both cigarette smoking and smokeless tobacco use during pregnancy pose serious risks to fetal health. Smoking during pregnancy may cause preterm delivery, low birthweight, and sudden infant death syndrome; smokeless tobacco use during pregnancy has been associated with stillbirth, preterm birth, and reduced birthweight.^5–8 Maternal tobacco use is also likely to expose infants and children to secondhand smoke (SHS) and to provide a role model for children''s use of tobacco. Intervening during pregnancy is also important because of the health risks to the woman, who potentially has many years of remaining life. For cigarette smoking, these health risks include lung and other cancers, coronary heart disease and stroke, and chronic obstructive pulmonary disease; health risks from smokeless tobacco products include oral and pancreatic cancer.^9,10The US National Institute of Child Health and Human Development''s Global Network for Women''s and Children''s Health Research consists of 10 research units chosen for scientific merit that are focused on improving maternal and children''s health in the developing world. To determine whether pregnant women''s tobacco use and SHS exposure are emerging public health issues, the Global Network undertook an investigative survey of pregnant women''s knowledge, attitudes, and behaviors regarding tobacco use and SHS exposure. Here we report findings on pregnant women''s experimentation with and use of tobacco products, their perceptions of the social acceptability of tobacco use by women, and their and their young children''s exposure to SHS.     

Heptavalent-pneumococcal conjugate vaccine (Prevenar). Differences in effectiveness between populations

This article reviews the publications on the effectiveness of heptavalent-pneumococcal conjugate vaccine (PCV7) in the prevention of invasive pneumococcal disease (IPD) in children under five years of age. It also analyses the characteristics of the vaccine and its impact on the epidemiology of IPD in different places. Before the introduction of PCV7, the percentage of cases of IPD due to vaccine serogroups oscillated between 89% in the United States and 43% in Asia. In Spain it was 68%. Active laboratory-based surveillance shows that the introduction of PCV7 has had a highly variable impact on the incidence of IPD, with falls oscillating between 91% in the United States and 12% in Navarre, Spain. The global effectiveness of VNC7v in published studies varies between 31% and 89%, chiefly depending on the patterns of pneumococcal serotypes in each place. Numerous studies show a variable replacement capacity of the pneumococci, which means the effect of the vaccine can be reduced, as non-vaccine serotypes occupy the space left by the vaccine ones. A study in Navarre has found a risk of IPD due to non-vaccine serotypes that is 6 times higher in vaccinated children than in unvaccinated ones. In places where less than 70% of the serotypes that cause IPD are represented in the VNC7v, the effectiveness of its introduction in the vaccination will probably be slight and the routine vaccination schedule serotypes fast. In these cases, VNC7v could be reserved for children with IPD risk factors.     

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality

An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality.     

Role of bone gammagraphy in the diagnosis of secondary osteomalacia in a patient treated with tenofovir

It is reported a HIV infected patient under antiretroviral therapy including tenofovir therapy who was referred to the Nuclear Medicine Department to complete bone pain study. A bone scan was performed at 3 hours after the injection of 740 MBq of 99mTc-MDP, revealing an abnormal distribution with characteristic changes compatible with osteomalacia. In further analysis, a secondary hyperparathyroidism and osteomalacia were diagnosed in the context of Fanconi syndrome, an infrequent complication described in patients under treatment with tenofovir.