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Biomedical subjects

Simin Nikbin Meydani

Publications and source records attributed to Simin Nikbin Meydani.

At least 19 recordsLinked to original sources
PubMed2006

Age and vitamin E-induced changes in gene expression profiles of T cells.

T cells are vulnerable to age-associated changes. Vitamin E has been shown to improve T cell functions in the old. We studied gene expression profiles of T cells to better understand the underlying mechanisms of age and vitamin E-induced changes in T cell function. Young and old C57BL mice were fed diets containing 30 (control) or 500 (supplemented) ppm of vitamin E for 4 wks. Gene expression profiles of T cells were assessed using microarray analysis with/without anti-CD3/anti-CD28 stimulation. Genes associated with cytokines/chemokines, transcriptional regulation, signal transduction, cell cycle, and apoptosis were significantly up-regulated upon stimulation. Higher SOCS3 and lower growth factor independent 1 (Gfi-1) expression in old T cells may contribute to age-associated decline in proliferation. Higher Gadd45 and lower Bcl2 expression may contribute to increased apoptosis in old T cells. Vitamin E supplementation resulted in higher expression of genes involved in cell cycle regulation (Ccnb2, Cdc2, Cdc6) in old T cells. Vitamin E supplementation resulted in higher up-regulation of IL-2 expression in young and old T cells and lower up-regulation of IL-4 expression in old T cells following stimulation. These findings suggest that aging has significant effects on the expression of genes associated with signal transduction, transcriptional regulation, and apoptosis pathways in T cells, and vitamin E has a significant impact on the expression of genes associated with cell cycle and Th1/Th2 balance in old T cells. Further studies are needed to determine whether these changes are due to the effects of aging at a single-cell level or to the shift in the ratio of naïve:memory T cells with age.

Age Factors↗
PubMed2006

An aged host promotes the evolution of avirulent coxsackievirus into a virulent strain.

The emergence of new, more pathogenic viruses necessitates elucidation of factors that promote viral evolution. Aging, a potential factor, is associated with increased susceptibility to viral infections. We used the enterovirus coxsackievirus B3 (CVB3) to investigate the effects of host age on pathogenicity and viral gene sequence. Old mice infected with a normally amyocarditic strain of CVB3, CVB3/0, had significantly higher mean heart viral titers compared with CVB3/0-infected adult mice. To determine whether a change in the CVB3/0 viral population could contribute to the higher titers observed in the old infected mice, CVB3/0 was passed once through an old or adult host and the changes in pathogenicity and viral genome were examined after subsequent infection of old or adult mice. Adult mice infected with CVB3/0 that was passed through an old host (CVB3/0(Old)) exhibited significantly higher heart viral titers, pathology, and weight loss than adult mice infected with either stock CVB3/0 or CVB3/0 passed through an adult host (CVB3/0(Adult)). Sequence analysis of virus isolated from CVB3/0(Old)-infected mice revealed 13 specific and reproducible nucleotide changes. These changes result in a sequence that matches the virulent CVB3/20 strain and are associated with promoting cardiovirulence. In contrast, we observed only one nucleotide change, low heart viral titers, and no heart and liver pathology in adult mice infected with CVB3/0(Adult). These results demonstrate that the aged host promotes rapid selection of a pathogenic variant of CVB3 from an avirulent strain and introduces a host-virus paradigm for studies of viral infection in the aged.

Aging↗
PubMed2006

Nutritional, immunological and health status of the elderly population living in poor neighbourhoods of Quito, Ecuador.

The number of elderly people is increasing in less-developed countries. Although nutritional deficiencies and infectious diseases are generally more prevalent in resource-poor countries, the health and nutritional status of the elderly in South America in general, and in Ecuador, in particular, remains largely unstudied. The objective of the present study was to assess the nutritional, immunological and health status of elderly Ecuadorians. A cross-sectional study was conducted to evaluate a sample of elderly Ecuadorians with 24 h dietary recalls, biochemical and anthropometric measurements, delayed type hypersensitivity skin response and a health questionnaire. The 145 elders who enrolled had a mean age of 74.3 (SD 6.9) years. Of the subjects, 52 % exhibited BMI >or=25 kg/m(2), whereas 9.1 % had BMI <or=20 kg/m(2). Means of dietary intakes were below recommendations for most nutrients; exceptions were carbohydrate, fat, Fe and Se. Serum nutrient levels indicated that 50, 44, 43, 19 and 18 % of participants had deficiencies of Zn, Fe, vitamins B12 and D, and folate, respectively. The mean number of positive responses to seven recall antigens was 2.1 (SD 1.7) with an induration diameter of 9.9 (SD 7) mm, which are substantially lower than those reported for elders in developed countries. During the previous 6 months, 54 and 21 % of subjects reported at least one episode of respiratory infection or diarrhoea, respectively. Of these, 47 % sought care at a hospital or from a physician and 96 % from a relative or friend. In conclusion, while few elderly Ecuadorians were underweight, obesity was common. Micronutrient deficiencies were prevalent and may contribute to reduced immunological responses in this population.

Aged↗
PubMed2006

Effect of concomitant consumption of fish oil and vitamin E on T cell mediated function in the elderly: a randomized double-blind trial.

OBJECTIVES: To determine if concomitant consumption of fish oil and vitamin E would modify the vitamin E level needed for improving T cell mediated function in elderly. METHODS: A randomized and double-blind study was conducted using 40 healthy male and female elderly subjects (>65 y) who were randomly assigned to one of 4 groups (n = 10/group). All the subjects received 5 g of fish oil daily containing 1.5 g eicosapentaenoic acid (EPA) and 1 g docosahexaenoic acid (DHA), and a capsule containing different doses of dl-alpha-tocopherol (0, 100, 200 or 400 mg/day) for 3 mo. Plasma vitamin E and fatty acid levels, and in vivo [delayed-type hypersensitivity skin response (DTH) and T cell sub-population analysis] and ex vivo [mitogen-stimulated peripheral blood mononuclear cells (PBMC) proliferation and interleukin (IL)-2 production] immune functions were determined at baseline and after supplementation. RESULTS: The control group (fish oil only) did not show a statistically significant change in either DTH or PBMC proliferation. DTH response, however, was significantly increased from baseline in all groups supplemented with fish oil plus vitamin E and a significant positive correlation between DTH response and plasma concentrations of alpha-tocopherol was observed. PBMC proliferation was only significantly increased in the group supplemented with fish oil plus 200 mg vitamin E. However, the changes caused by fish oil plus vitamin E in either DTH or PBMC proliferation were not significantly different from those observed in control group. Plasma levels of alpha-tocopherol were significantly increased in all three fish oil plus vitamin E groups and the increase in plasma alpha-tocopherol level was less profound than that previously reported when vitamin E was given alone. CONCLUSIONS: The immuno-enhancing effect of vitamin E in the elderly is dampened when it is concomitantly consumed with fish oil. This may be due to the smaller increase in plasma concentrations of vitamin E in the presence of fish oil.

Aged↗
PubMed2005

Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2.

Impairment of endothelium-dependent vasodilation is associated with the initiation and development of atherosclerosis. Vasodilator prostanoids constitute a protective mechanism in maintaining normal vasomotor function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations (10-60 micromol/L) on the production of the vasodilator prostanoids prostaglandin I(2) (PGI(2); prostacyclin) and prostaglandin E(2)(PGE(2)) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10-40 micromol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10-40 micromol/L) upregulation of cytosolic phospholipase A(2) (cPLA(2)) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10-60 micromol/L) inhibited cyclooxygenase (COX) activity but did not affect the expression of either COX-1 or COX-2, indicating that the effect of vitamin E on COX activity was post-translational. Thus, vitamin E had opposing effects on the 2 key enzymes in prostanoid biosynthesis; at the concentrations used in this study, this resulted in a net increase in the production of vasodilator prostanoids. The vitamin E-induced increase in PGI(2) and PGE(2) production may contribute to its suggested beneficial effect in preserving endothelial function.

Aorta↗
PubMed2005

Vitamin E and immune response in the aged: molecular mechanisms and clinical implications.

Nutritional status has been indicated as a contributing factor to age-related dysregulation of the immune response. Vitamin E, a lipid-soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed-type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)-2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T-cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell-dividing and IL-producing capacities of naive T cells, but not memory T cells. The vitamin E-induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naive T-cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

Aging↗
PubMed2005

Aging, nutritional status, and infection in the developing world.

The fast rate of increase in the number of older people in less-developed countries threatens to further strain the limited health resources of these countries. However, very little is known about their health status and the risk factors that contribute to it. In this article, we review the burden of infectious diseases in elderly people in less-developed countries, discuss the contribution of nutrition and immune response to morbidity and mortality, identify gaps in current knowledge, and suggest strategies to address this fast-growing public health problem.

Adult↗
PubMed2004

Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial.

CONTEXT: Respiratory tract infections are prevalent in elderly individuals, resulting in increased morbidity, mortality, and use of health care services. Vitamin E supplementation has been shown to improve immune response in elderly persons. However, the clinical importance of these findings has not been determined. OBJECTIVE: To determine the effect of 1 year of vitamin E supplementation on respiratory tract infections in elderly nursing home residents. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial was conducted from April 1998 to August 2001 at 33 long-term care facilities in the Boston, Mass, area. A total of 617 persons aged at least 65 years and who met the study's eligibility criteria were enrolled; 451 (73%) completed the study. INTERVENTION: Vitamin E (200 IU) or placebo capsule administered daily; all participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals. MAIN OUTCOME MEASURES: Incidence of respiratory tract infections, number of persons and number of days with respiratory tract infections (upper and lower), and number of new antibiotic prescriptions for respiratory tract infections among all participants randomized and those who completed the study. RESULTS: Vitamin E had no significant effect on incidence or number of days with infection for all, upper, or lower respiratory tract infections. However, fewer participants receiving vitamin E acquired 1 or more respiratory tract infections (60% vs 68%; risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.00; P =.048 for all participants; and 65% vs 74%; RR, 0.88; 95% CI, 0.75-0.99; P =.04 for completing participants), or upper respiratory tract infections (44% vs 52%; RR, 0.84; 95% CI, 0.69-1.00; P =.05 for all participants; and 50% vs 62%; RR, 0.81; 95% CI, 0.66-0.96; P =.01 for completing participants). When common colds were analyzed in a post hoc subgroup analysis, the vitamin E group had a lower incidence of common cold (0.67 vs 0.81 per person-year; RR, 0.83; 95% CI, 0.68-1.01; P =.06 for all participants; and 0.66 vs 0.83 per person-year; RR, 0.80; 95% CI, 0.64-0.98; P =.04 for completing participants) and fewer participants in the vitamin E group acquired 1 or more colds (40% vs 48%; RR, 0.83; 95% CI, 0.67-1.00; P =.05 for all participants; and 46% vs 57%; RR, 0.80; 95% CI, 0.64-0.96; P =.02 for completing participants). Vitamin E had no significant effect on antibiotic use. CONCLUSIONS: Supplementation with 200 IU per day of vitamin E did not have a statistically significant effect on lower respiratory tract infections in elderly nursing home residents. However, we observed a protective effect of vitamin E supplementation on upper respiratory tract infections, particularly the common cold, that merits further investigation.

Aged↗
PubMed2004

Mechanism of age-associated up-regulation in macrophage PGE2 synthesis.

Many physiological functions of the body change during the aging process. Dysregulated immune and inflammatory responses have been well documented in both humans and animals. The investigation into the cellular and molecular mechanism underlying these disorders has provided compelling evidence that up-regulated cyclooxygenase (COX)-2 and its product, particularly prostaglandin (PG)E2, play a critical role in the age-associated dysregulation of the immune and inflammatory responses. In particular, several studies have shown that increased PGE2 production in old macrophages (Mphi) contributes to the suppression of T cell function with aging. Furthermore, interventions targeted at decreasing PGE2 production have been shown to enhance T cell-mediated function. COX-2 and its catalytic products are also suggested to play a key role in age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Administration of anti-inflammatory drugs which inhibit COX activity has been shown, by some investigators, to be beneficial in preventing and treating these diseases. It is, thus, important to understand the underlying mechanisms of age-related COX-2 up-regulation and to delineate the factors, which contribute to this age-related change. This review focuses on the regulation of PGE2 production in murine Mphi; the age-associated changes in COX-2 expression; and its implication for certain disorders observed in the aged immune system and brain. Increased PGE2 production has been shown to be mainly due to an increase in COX activity, which is, in turn, due to an increase in COX-2 protein and mRNA expression. Elevated COX-2 mRNA represents a higher transcription rate rather than an altered stability of COX-2 mRNA. Upon stimulation, Mphi from old mice generate more ceramide, a sphingolipid, than those from young mice. Ceramide has been shown to induce, by itself, and also augment, LPS-stimulated COX-2 expression and PGE2 production. Several lines of evidence indicate that the higher ceramide levels in old Mphi are an important contributor to the age-associated up-regulation of COX-2 in Mphi. Ceramide up-regulates COX-2 transcription by increasing activation of transcription factor NF-kappaB. Further understanding of molecular mechanisms involved in COX-2 up-regulation will help in delineating fundamental age-related changes, which lead to the development of immune and neurological disorders in the aged.

Aging↗
PubMed2004

Yogurt and gut function.

In recent years, numerous studies have been published on the health effects of yogurt and the bacterial cultures used in the production of yogurt. In the United States, these lactic acid-producing bacteria (LAB) include Lactobacillus and Streptococcus species. The benefits of yogurt and LAB on gastrointestinal health have been investigated in animal models and, occasionally, in human subjects. Some studies using yogurt, individual LAB species, or both showed promising health benefits for certain gastrointestinal conditions, including lactose intolerance, constipation, diarrheal diseases, colon cancer, inflammatory bowel disease, Helicobacter pylori infection, and allergies. Patients with any of these conditions could possibly benefit from the consumption of yogurt. The benefits of yogurt consumption to gastrointestinal function are most likely due to effects mediated through the gut microflora, bowel transit, and enhancement of gastrointestinal innate and adaptive immune responses. Although substantial evidence currently exists to support a beneficial effect of yogurt consumption on gastrointestinal health, there is inconsistency in reported results, which may be due to differences in the strains of LAB used, in routes of administration, or in investigational procedures or to the lack of objective definition of "gut health." Further well-designed, controlled human studies of adequate duration are needed to confirm or extend these findings.

Adult↗
PubMed2004

Vitamin E and gene expression in immune cells.

Aging is associated with dysregulation of immune cells, particularly T cells. Previous studies indicated that vitamin E improves T cell function, in part by a direct effect on T cells. We studied gene expression profile of T cells to better understand the underlying mechanisms of aging- and vitamin E-induced changes in T cell function. Young and old C57BL mice were fed diets containing 30 (control) or 500 (E) ppm of vitamin E for 4 weeks. T cells were purified from splenocytes by negative selection using magnetic beads (anti-Mac-1 and anti-MHC class II), then cultured with media or stimulated with anti-CD3 and anti-CD28. Gene expression profile was assessed using microarray analysis. Genes showing more than two-fold changes, P < 0.05 by ANOVA, and with at least one present call were selected. Aging had significant effects on genes involved in signal transduction, transcriptional regulation, and apoptosis pathways in T cells, while vitamin E had a significant effect on genes associated with the regulation of cell cycle.

Aging↗
PubMed2004

Vitamin E and respiratory infection in the elderly.

Respiratory infections are prevalent in the elderly, resulting in increased morbidity, mortality, and utilization of health care services. Contributing to the increased incidence of infection with age is the well-described decline in immune response, which has been correlated with patterns of illness in the elderly. For example, there are higher morbidity and mortality from cancer, pneumonia, and post-operative complications in those who have diminished, delayed-type hypersensitivity skin test responses. Nutritional status is an important determinant of immune function. We have shown in double-blind, placebo-controlled trials that vitamin E supplementation significantly improved immune response, including DTH and response to vaccines. Furthermore, subjects receiving vitamin E in the 6-month trial had a 30% lower incidence of infectious diseases. That study, however, was not powered to demonstrate statistical significance, and the infections were self-reported. To overcome these limitations, we conducted a double-blind, placebo-controlled trial to determine the effect of one-year supplementation with 200 IU/day vitamin E on the incidence and duration of respiratory infections in 617 elderly nursing home residents. The results of this clinical trial show that vitamin E supplementation significantly reduces the incidence rate of common colds and the number of subjects who acquire a cold among elderly nursing home residents. A nonsignificant reduction in the duration of colds was also observed. Because of the high rate and more severe morbidity associated with common colds in this age group, these findings have important implications for the well being of the elderly as well as for the economic burden associated with their care.

Aged↗
PubMed2004

Vitamin E supplementation reverses the age-associated decrease in effective immune synapse formation in CD4+ T cells.

Aging is associated with impairment of T cell function. We demonstrate here that age-associated declines in T cell signaling are due to the inability to form effective immune synapses at the site of the T cell receptor and antigen interaction. On the basis of our previous research with vitamin E (VE), we hypothesized that VE supplementation of old CD4(+) T cells enhances effective immune synapse formation through increased translocation of signaling proteins. Using confocal microscopy, we found that when exposed to antigen-presenting cells, CD4(+) T cells from old mice have a lower percentage of effective immune synapses compared to those from young mice. Furthermore, we show that in vitro and in vivo VE supplementation increases the percentage of old CD4(+) T cells capable of forming a functional immune synapse. Further studies are under way to determine the mechanisms of age and VE-induced enhancement of effective immune synapse formation.

Aging↗
PubMed2004

The effect of vitamin E on secondary bacterial infection after influenza infection in young and old mice.

Mortality from influenza is high in the elderly. Deaths are mainly due to secondary complications, including Staphylococcus aureus (SA) infections. Vitamin E (E) supplementation reduces influenza in aged mice. This study determined the efficacy of E supplementation on secondary bacterial infections after influenza in young and old mice. C57BL/6 mice were fed diets containing 30 or 500 ppm E for 4 weeks. Priming with influenza significantly increased SA in the lungs of infected mice fed control diet. Age did not have a significant effect on SA infection alone or SA infection after influenza infection. E supplementation did not have a significant effect on SA infection alone. However, E supplementation abolished the priming effect of influenza on SA.

Aging↗
PubMed2004

Effect of concomitant consumption of fish oil and vitamin E on production of inflammatory cytokines in healthy elderly humans.

A beneficial effect of fish oil in reducing inflammatory and cardiovascular diseases has been suggested. This effect occurs in part through fish oil's inhibition of synthesis of pro-inflammatory cytokines. Epidemiologic studies have shown a link between increased intake of vitamin E in diet and reduced risk of cardiovascular disease. Since pro-inflammatory cytokines have been indicated in pathogenesis of cardiovascular diseases, the current study was designed to determine the effect of concomitant consumption of fish oil and vitamin E on interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha production by peripheral blood mononuclear cells (PBMCs). Healthy elderly subjects consumed fish oil plus different doses of vitamin E for 3 months. The results indicated that, in general, fish oil inhibited production of pro-inflammatory cytokines and vitamin E did not interfere with this effect of fish oil; rather its supplementation might further contribute to the fish oil-induced inhibition of these cytokines, in particular at the 200 mg/d dose.

Aged↗
PubMed2004

Effect of vitamin E on prostacyclin (PGI2) and prostaglandin (PG) E2 production by human aorta endothelial cells: mechanism of action.

Vitamin E has been suggested to reduce the risk of cardiovascular diseases. Prostanoids are vasoactive molecules, the change in whose production contributes to homeostasis and pathophysiology of the cardiovascular system. In the current study, we determined the effect of vitamin E on production of vasodilative PGI(2) and PGE(2) by human aorta endothelial cells (HAECs) and its underlying mechanism. Results showed that vitamin E increased production of both prostanoids by HAECs. This effect of vitamin E is due to increased release of substrate arachidonic acid, which in turn results from increased expression of phospholipase A(2) (PLA(2)).

Aorta↗
PubMed2003

Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity.

We have shown that the age-associated increase in lipopolysaccharide (LPS)-stimulated macrophages (M phi) prostaglandin E(2) (PGE(2)) production is because of ceramide-induced up-regulation of cyclooxygenase (COX)-2 transcription that leads to increased COX-2 expression and enzyme activity. To determine the mechanism of the age-related and ceramide-dependent increase in COX-2 transcription, we investigated the role of various transcription factors involved in COX-2 gene expression. The results showed that LPS-initiated activations of both consensus and COX-2-specific NF-kappa B, but not AP-1 and CREB, were significantly higher in M phi from old mice than those from young mice. We further showed that the higher NF-kappa B activation in old M phi was because of greater I kappa B degradation in the cytoplasm and p65 translocation to the nucleus. An I kappa B phosphorylation inhibitor, Bay 11-7082, inhibited NF-kappa B activation, as well as PGE(2) production, COX activity, COX-2 protein, and mRNA expression in both young and old M phi. Similar results were obtained by blocking NF-kappa B binding activity using a NF-kappa B decoy. Furthermore, NF-kappa B inhibition resulted in significantly greater reduction in PGE(2) production and COX activity in old compared with young M phi. Addition of ceramide to the young M phi, in the presence or absence of LPS, increased NF-kappa B activation in parallel with PGE(2) production. Bay 11-7082 or NF-kappa B decoy prevented this ceramide-induced increase in NF-kappa B binding activity and PGE(2) production. These findings strongly suggest that the age-associated and ceramide-induced increase in COX-2 transcription is mediated through higher NF-kappa B activation, which is, in turn, because of a greater I kappa B degradation in old M phi.

Aging↗