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nfcorpus-corpus-MED-4113 | null | Good riddance: Thymocyte clonal deletion prevents autoimmunity.
Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4114 | null | Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an...
Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4115 | null | The rise and fall of horror autotoxicus and forbidden clones.
Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4163 | null | Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed.
OBJECTIVE: The health benefits of vegetarian diets are well-recognized; however, long-term adherence to these diets may be associated with nutrient inadequacies, particularly vitamins B12 and D, calcium, iron, zinc, and protein. The dietary reference intakes (DRIs) expert panels recommended adjustments to the iron, zinc, and calcium DRIs for vegetarians to account for decreased bioavailability, but no adjustments were considered necessary for the protein DRI under the assumption that vegetarians consume about 50% of protein from animal (dairy/egg) sources. This study examined dietary protein sources in a convenience sample of 21 young adult vegetarian women who completed food logs on 4 consecutive days (3 weekdays and 1 weekend day). METHODS: The daily contribution percentages of protein consumed from cereals, legumes, nuts/seeds, fruits/vegetables, and dairy/egg were computed, and the protein digestibility corrected amino acid score of the daily diets was calculated. RESULTS: The calculated total dietary protein digestibility score for participants was 82 ± 1%, which differed significantly (P < 0.001) from the DRI reference score, 88%, and the 4-d average protein digestibility corrected amino acid score for the sample was 80 ± 2%, which also differed significantly (P < 0.001) from the DRI reference value, 100%. The analyses indicated that animal protein accounted for only 21% of dietary protein. CONCLUSION: This research suggests that the protein DRI for vegetarians consuming less than the expected amounts of animal protein (45% to 50% of total protein) may need to be adjusted from 0.8 to about 1.0 g/kg to account for decreased protein bioavailability. Copyright © 2011 Elsevier Inc. All rights reserved. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4164 | null | Evidence that protein requirements have been significantly underestimated.
PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4224 | null | Growth Factors and their receptors in cancer metastases.
Metastatic, rather than primary tumours are responsible for ninety percent cancer deaths. Despite significant advances in the understanding of molecular and cellular mechanisms in tumour metastases, there are limitations in preventive treatment of metastatic tumours. Much evidence arising from laboratory and clinical studies suggests that growth factors and their receptors are implicated in cancer metastases development. We review the origin and production of growth factors and their receptors in all stages of cancer metastases including epithelial-mesenchymal transition, cancer cell invasion and migration, survival within the circulation, seeding at distant organs and metastatic tumour angiogenesis. The functions of growth factors and their receptors are also discussed. This review presents the efforts made in understanding this challenge to aid in the development of new treatment strategies for cancer metastases. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4226 | null | Mechanisms of breast cancer bone metastasis.
Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4228 | null | Circulating insulin-like growth factor (IGF) peptides and prostate cancer risk: a systematic review and meta-analysis
Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3; and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide, were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I2 > 75%), partly explained by study design: the magnitude of associations was smaller in prospective versus retrospective studies, and for IGFBP-3 the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4216 | null | Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial.
High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4211 | null | Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap...
Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively). |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4212 | null | Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women.
Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4886 | null | Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.
OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4220 | null | Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States).
OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4612 | null | Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.
Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4222 | null | Growth Hormone Receptor Deficiency is Associated With a Major Reduction in Pro-aging Signaling, Cancer and Diabetes in Humans
Life span extending mutations in growth signaling pathways protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian subjects with mutations in the growth hormone receptor gene leading to severe growth hormone receptor (GHR) and IGF-I deficiencies and combined this information with surveys to identify the cause and age of death for subjects who died before this period. The individuals with GHR deficiency (GHRD) exhibited only one non-lethal malignancy and no cases of diabetes, in contrast to 17% cancer and 5% diabetes prevalence in the controls. A possible explanation for the very low incidence of cancer may be revealed by in vitro studies: serum from GHRD subjects reduced DNA breaks but increased apoptosis in human mammary epithelial cells (HMECs) treated with hydrogen peroxide. We also observed reduced insulin concentrations (1.4 μU/ml vs. 4.4μU/ml in unaffected relatives) and a very low homoeostasis model assessment of insulin resistance (HOMA-IR) index (0.34 vs. 0.96 in unaffected relatives) in GHRD individuals, indicating increased insulin sensitivity, which could explain the absence of diabetes in these subjects. Incubation of HMECs with GHRD serum also resulted in reduced expression of RAS, PKA and TOR, and up-regulation of SOD2, changes that promote cellular protection and life span extension in model organisms. These results provide evidence for a role of evolutionarily conserved pathways in promoting aging and diseases in humans and identify a candidate drug target for healthy life span extension. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4223 | null | Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies
Summary Background Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Methods Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0·05 was considered significant. Findings IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1·28 (95% CI 1·14–1·44; p<0·0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1·38 (95% CI 1·14–1·68) for oestrogen-receptor-positive tumours and 0·80 (0·57–1·13) for oestrogen-receptor-negative tumours (p for heterogeneity=0·007). Interpretation Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours. Funding Cancer Research UK. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4225 | null | Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53.
BACKGROUND: Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be effectively protected from cancers. The mechanisms that underlie this protection are quite complex and still largely unclear. AIM: To critically analyse the literature in order to propose a unifying hypothesis that can account for this cancer protection in centenarians. METHODS: Review of the scientific literature regarding three main players in tumourigenesis such as IGF-1, inflammation and p53, and centenarians. RESULTS: Centenarians appear to be characterised by low IGF-1-mediated responses and high levels of anti-inflammatory cytokines such as IL-10 and TGF-beta, a condition that results in protection from cancer. Both inflammation and IGF-1 pathway converge on the tumour suppressor p53. Accordingly, some studies indicate that genetic variants of p53 are associated with human longevity by providing protection from cancer mortality. CONCLUSIONS: The available data let us to hypothesise that among other possible mechanisms, well-preserved p53-mediated responses are likely a key factor contributing to protection from cancer in centenarians. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4227 | null | Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality.
Epidemiologic and biological data strongly support the existence of a strict link between cancer and aging. In spite of the relevance of the problem, there were numerous pitfalls in epidemiologic investigation until a few years ago. An apparent decrease of cancer incidence in old age was revealed to be a misconception based on lack of sufficient appreciation for changing population size. But not all problems are solved by using age-specific cancer incidence, as recently stressed by some authors. At very advanced ages a slowing of the rate of increase of age-specific cancer incidence is clearly demonstrated. These findings apparently clash with the majority of biological data and suggest that some mechanism may develop at advanced ages capable of decreasing cancer susceptibility. In this paper, it will be shown that just a slowing-down kinetics is predicted for cancer incidence by using a mathematical model of mortality kinetics recently proposed in the gerontologic field. The slowing of the increasing rate or even a decreasing trend of cancer incidence of an aging population is compatible with a continuously accelerating pace of loss of physiological capacity of the single subjects, as with advancing age there is a selection of individuals with better physiological functions. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4897 | null | Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies.
Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4953 | null | Protein intake and ovulatory infertility
Objective To evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. Study Design 18,555 married women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an eight year period. Dietary assessments were related to the incidence of ovulatory infertility. Results During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk [RR] (95% CI; P, trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 – 1.90; 0.03). The corresponding RR (95% CI; P, trend) for vegetable protein intake was 0.78 (0.54 – 1.12; 0.07). Further, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P = 0.007). Conclusions Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-4954 | null | Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy.
BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of "high beef consumers" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of "high beef consumers" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity. |
nfcorpus-queries-PLAIN-1398 | null | IGF-1 |
nfcorpus-corpus-MED-2494 | null | Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment
Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2495 | null | Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int...
We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2496 | null | Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population.
Persistent organic pollutants (POPs) exert harmful effects on cognitive, endocrine and immune functions and bioaccumulate in the environment and human tissues. The aim of this study was to investigate the body burden of several POPs in the adult population (n=246) and their association to diet and other lifestyle factors in a Swedish national survey. Serum concentrations of several polychlorinated biphenyls (PCBs), and the pesticides hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), chlordane compounds and dichlorodiphenyldichloroethylene (DDE) were determined by liquid-liquid extraction, silica column cleanup and gas chromatography high resolution mass spectrometry. Diet was assessed using 4-day food records and complementary dietary and lifestyle factors by questionnaire. Fish intake was additionally assessed by plasma fatty acid composition. Clustering of the compounds revealed that PCBs were separated into two clusters, one including low-chlorinated PCB 28 and 52, and the other high-chlorinated mono- and di-ortho PCBs, suggesting similarities and dissimilarities in exposure sources and possibly also toxicokinetics. Men had 24% and 32% higher levels of PCB 138-180 and chlordane compounds, respectively, compared with women. This may partly be explained by elimination of the POPs among women reporting a history of breastfeeding. The proportion of very long-chain n-3 fatty acids in plasma were positively correlated with the pollutants: r=0.24 (PCB 28), r=0.33 (PCB 118), r=0.35 (PCB 138-180), r=0.29 (HCB), r=0.18 (β-HCH), r=0.34 (chlordane compounds), r=0.34 (p,p'-DDE), p≤0.005. Individuals consuming fatty Baltic fish≥1 time per months had 45% higher serum levels of PCB 118 compared with non-consumers. Levels of PCB 28 were associated with the age of the residential building. To conclude, the population-distributed approach of surveying dietary habits, lifestyle factors and POP body burdens, made it possible to identify personal characteristics associated with the POP body burdens in Sweden. Copyright © 2012 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2493 | null | Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease?
There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body’s first line of defense. Thus, the consequences of early-life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2497 | null | Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants.
The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2644 | null | p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene.
Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2646 | null | Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA...
BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2651 | null | Alkylphenols in human milk and their relations to dietary habits in central Taiwan.
The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-118 | null | Alkylphenols in human milk and their relations to dietary habits in central Taiwan.
The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2652 | null | Xeno-estrogenic compounds in precipitation.
The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2653 | null | Nonylphenol and octylphenol in human breast milk.
Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2655 | null | Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial
Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2659 | null | European bans on surfactant trigger transatlantic debate.
U.S. and European regulators and researchers disagree over risks of a common class of surfactants. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2661 | null | Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy).
This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2662 | null | Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7).
A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-4551 | null | Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He...
Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2643 | null | Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action
The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2645 | null | Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment.
The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2656 | null | Effects of intestinal microflora and the environment on the development of asthma and allergy.
The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2657 | null | Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis.
BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2658 | null | Alkylphenols--potential modulators of the allergic response.
The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2660 | null | Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men.
BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2649 | null | Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study
Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-3028 | null | Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes
OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2913 | null | Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children
The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-3021 | null | Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans.
The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-3012 | null | Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment.
The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-3033 | null | Smoking and lung cancer risk in American and Japanese men: an international case-control study.
Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
nfcorpus-corpus-MED-2906 | null | Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines.
BACKGROUND: Different chemical forms of mercury occur naturally in human milk. The most controversial aspect of early post-natal exposure to organic mercury is ethylmercury (EtHg) in thimerosal-containing vaccines (TCV) still being used in many countries. Thus exclusively breastfed infants can be exposed to both, fish derived methylmercury (MeHg) in maternal diets and to EtHg from TCV. The aim of the study is to evaluate a new analytical method for ethyl and methyl mercury in hair samples of breastfed infants who had received the recommended schedule of TCV. METHODS: The hair of infants (<12 months) that had been exposed to TCV (Hepatitis B and DTaP) was analysed. A method coupling isothermal gas chromatography with cold-vapor atomic fluorescence spectrometry was used for MeHg which can also speciate EtHg in biological matrices. RESULTS: In 20 samples of infants' hair, all but two samples showed variable amounts of MeHg (10.3 to 668 ng/g), while precise and reliable concentrations of EtHg (3.7 to 65.0 ng/g) were found in 15 of the 20 samples. A statistically significant inverse association (r=-05572; p=0.0384) was found between hair-EtHg concentrations and the time elapsed after the last TCV shot. CONCLUSIONS: The analytical method proved sensitive enough to quantify EtHg in babies' hair after acute exposure to thimerosal in vaccine shots. Provided that the mass of hair was above 10mg, organic-mercury exposure during early life can be speciated, and quantified in babies' first hair, thus opening opportunities for clinical and forensic studies. Copyright © 2011 Elsevier B.V. All rights reserved. |
nfcorpus-queries-PLAIN-1409 | null | industrial toxins |
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