Search

Objective:To determine zinc status and age-related changes in the immune function of healthy late-middle-aged men and women (aged 55–70 y).Design:Observational study.Setting:Population of Northern Ireland.Subjects:Apparently healthy, free-living individuals (45 men, 48 women) aged 55–70 y.Intervention:Zinc status markers were analysed by flame atomic absorption spectrometry and commercially available kits. Immune function was assessed by flow cytometry.Results:Serum and erythrocyte zinc concentrations were 13.0 (s.d. 1.40) μmol/l and 222 (s.d. 48.2) μmol/l, respectively. Serum alkaline phosphatase (ALP) concentrations were 76.8 (s.d. 16.1) U/l; women showed significantly higher concentrations of ALP (P=0.011). Women demonstrated (1) a significant inverse correlation in naive T lymphocytes, specifically naive T-helper lymphocytes (% expression, r=−0.364, P=0.007 and absolute count, r=−0.275, P=0.036) with age and (2) a significant positive correlation between late activation of T lymphocytes (% expression, r=0.299, P=0.019 and absolute count, r=0.260, P=0.039) with advancing age. Men demonstrated a significant positive correlation in the % expression of (CD3−/CD16+/CD56+) natural killer (NK) cells with age (r=0.316, P=0.017).Conclusions:Between the ages of 55 and 70 y, healthy individuals experience significant alterations in immune function; however, such changes appear largely sex specific. Given the reported importance of adequate zinc status in maintaining optimal immune function, further studies are required to explore the effect of enhanced zinc status on emerging immune deficiencies in cell-mediated immunity in healthy 55–70 y olds.Sponsorship:European Commission ‘Quality of Life and Management of Living Resources’, Fifth Framework Program, Contract no. QLK1-CT-2001-00168, and the Department of Education and Learning (DELNI), UK.European Journal of Clinical Nutrition (2005) 59, Suppl 2, S63–S67. doi:10.1038/sj.ejcn.1602301 [ABSTRACT FROM AUTHOR]

Aims The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects. Methods A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects. Results DNA damage was significantly ( P < 0.0001) and directly correlated to both FPG ( r = 0.540) and HbA1c ( r = 0.282), and was significantly ( P < 0.0001), independently and inversely correlated to plasma AA ( r = −0.449). In those subjects with both poor glycaemic control and low AA (< 48 µ m, the overall mean value for the study group), DNA damage was significantly ( P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean. Conclusions The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis often coexists with asthma in airway inflammatory conditions characterised by the infiltration of a range of immune cells. A potentially important role for ovarian hormones has been implicated in airway inflammation but the cellular target for such action is not known.Methods: Expression of oestrogen receptors (ER) and progesterone receptors (PR) was examined using immunohistochemistry in formalin fixed nasal polyp tissues from 47 subjects. The cells positive for ER or PR were confirmed by spatial location, dual immunolabelling, and histochemical staining.Results: Consistent with the known features of nasal polyps, CD4+ (T helper/inducer), CD8+ (cytotoxic/suppressor), CD68+ (macrophages), mast cells, eosinophils and neutrophils were all clearly detected by their relevant monoclonal antibodies or appropriate histochemical staining, but only mast cells tested positive for ER/PR labelling with their polyclonal and monoclonal antibodies. The frequencies for expression were 61.7% for ER positive and 59.6% for PR positive cells. The expression of ER/PR was independent of patient sex and age but was highly correlated with the numbers of mast cells (r = 0.973, p<0.001 for ER; r = 0.955, p<0.001 for PR). Fewer than 5% of mast cells were found to be negative for ER/PR expression.Conclusions: Mast cells alone, but not lymphocytes, macrophages, or other immune cells, express ER/PR in human upper airways. Numerous ER/PR positive mast cells exist in nasal polyps, indicating that this may be a major route for the involvement of sex hormones in airway inflammation when exposed to the higher and varying concentration of oestrogen and progesterone characteristic of females. [ABSTRACT FROM AUTHOR]

Three human cell lines of lymphoid (Molt-3 and Raji) or myeloid (HL-60) origin were maintained in vitro under zinc-sufficient or zinc-deficient conditions. Under these conditions, cell proliferation, viability and mode of death (apopiotic or necrotic) were assessed. All three cell types decreased their proliferative capacity and viability under conditions of zinc deficiency. Cell death in the HL-60 and Raji cultures occurred primarily via apoptosis, while most cells in zinc-deficient Molt-3 cultures died via necrosis. Apoptosis in zinc-deficient cultures of HL-60 and Raji cells was characterized by a slow decline in culture viability as cells with condensed and fragmented nuclear DNA appeared. These morphological changes were accompanied by an increase in cell buoyant density, which allowed separation of viable apoptotic cells from their non-apoptotic counterparts by means of percoli step density gradients. Necrosis in zinc-deficient Moli-3 cultures was characterized by rapid loss of cell culture viability as these cells underwent direct lysis. Intact necrotic cells were easily identified by the flocculated state of their chromatin as well as the decreased basophilia of their cytoplasm. Analysis of DNA from apoptotic HL-60 and Raji cells revealed that internucleosomal DNA degradation, indicative of endogenous endonuclease activation, had occurred, whereas the nuclear DNA of necrotic Molt-3 cells remained relatively unfragmented. The different modes of cell death evoked may reflect the relative sensitivities of cells of these lineages to zinc levels in vivo. [ABSTRACT FROM AUTHOR]