Iron absorption in breast-fed infants: effects of age,iron status,iron supplements,and complementary foods

BACKGROUND: Iron supplements are often recommended for older breast-fed infants, but little is known about factors affecting iron absorption from human milk or supplements. OBJECTIVE: We investigated the effects of age, iron status, and iron intake on iron absorption in healthy, term, breast-fed infants. DESIGN: Twenty-five infants were randomly assigned to receive either 1) iron supplements (1 mg x kg(-1) x d(-1)) from 4 to 9 mo of age, 2) placebo from 4 to 6 mo and iron supplements from 6 to 9 mo, or 3) placebo from 4 to 9 mo. Infants were exclusively breast-fed to 6 mo and partially breast-fed to 9 mo of age. Iron absorption was assessed by giving (58)Fe with mother's milk at 6 and 9 mo. Blood samples were obtained at 4, 6, and 9 mo, and complementary food intake was recorded at 9 mo. RESULTS: At 6 mo, mean (+/-SD) fractional iron absorption from human milk was relatively low (16.4 +/- 11.4%), with no significant difference between iron-supplemented and unsupplemented infants. At 9 mo, iron absorption from human milk remained low in iron-supplemented infants (16.9 +/- 9.3%) but was higher (P = 0.01) in unsupplemented infants (36.7 +/- 18.9%). Unexpectedly, iron absorption at 9 mo was not correlated with iron status but was significantly correlated with intake of dietary iron, including supplemental iron. CONCLUSIONS: Changes in the regulation of iron absorption between 6 and 9 mo enhance the infant's ability to adapt to a low-iron diet and provide a mechanism by which some, but not all, infants avoid iron deficiency despite low iron intakes in late infancy.     

Breast-feeding protects against celiac disease

BACKGROUND: Celiac disease, or permanent gluten-sensitive enteropathy, is an immunologic disease strictly dependent on exposure to wheat gluten or related proteins in rye and barley. OBJECTIVE: The aim of this study was to explore whether breast-feeding and the mode of introducing dietary gluten influence the risk of celiac disease in childhood. DESIGN: A population-based incident case-referent study of Swedish children, 627 cases with celiac disease and 1254 referents, was conducted; 78% of the matched sets were included in the final analyses. A questionnaire was used to assess patterns of food introduction to infants. Models were built, based on current epidemiologic and immunologic knowledge of celiac disease, to study the potential influence of dietary patterns on disease risk and were evaluated by conditional logistic regression in multivariate analyses. RESULTS: The risk of celiac disease was reduced in children aged <2 y if they were still being breast-fed when dietary gluten was introduced [adjusted odds ratio (OR): 0.59; 95% CI: 0.42, 0.83]. This effect was even more pronounced in infants who continued to be breast-fed after dietary gluten was introduced (OR: 0.36; 95% CI: 0.26, 0.51). The risk was greater when gluten was introduced in the diet in large amounts (OR: 1.5; 95% CI: 1.1, 2.1) than when introduced in small or medium amounts. In older children, these risk factors were of no or only minor importance. CONCLUSIONS: The gradual introduction of gluten-containing foods into the diet of infants while they are still being breast-fed reduces the risk of celiac disease in early childhood and probably also during the subsequent childhood period.     

Iron status of infants fed low-iron formula: no effect of added bovine lactoferrin or nucleotides

BACKGROUND: The appropriate level of iron fortification in infant formula remains undetermined. OBJECTIVES: We compared hematologic indexes and iron-status indicators in infants who were either breast-fed or fed formula with concentrations of 2 or 4 mg Fe/L and evaluated the effects of providing part of the iron as bovine lactoferrin and of adding nucleotides. DESIGN: Healthy term infants were exclusively breast-fed (n = 16) or fed formula (n = 10-12) from age 4 +/- 2 wk to 6 mo. Anthropometric measures were taken monthly, and blood samples were taken at 1, 4, and 6 mo. Hematologic indexes; indicators of iron, zinc, and copper status; and erythrocyte fatty acids were assessed. RESULTS: No significant differences in hematology or iron status were observed between groups at 4 and 6 mo of age. Although 34% of all infants had a hemoglobin concentration <110 g/L at 6 mo, the absence of iron deficiency or defective erythropoiesis suggests that this hemoglobin cutoff is too high for this age group. Neither the source or the concentration of iron in formula nor fortification with nucleotides had any significant effect on serum zinc or copper, and nucleotide fortification did not affect erythrocyte fatty acids. CONCLUSIONS: A concentration of 1.6 mg Fe/L formula meets the iron requirement of healthy term infants aged 相似文献   

Modulation of post-operative insulin resistance by pre-operative carbohydrate loading

Insulin resistance develops as a response to virtually all types of surgical stress. There is an increasing body of evidence that suggests that insulin resistance in surgical stress is not beneficial for outcome. A recent large study in intensive-care patients showed that aggressive treatment of insulin resistance using intravenous insulin reduced mortality and morbidity substantially. Similarly, in burn patients, intensive insulin and glucose treatment has been shown to improve N economy and enhance skin-graft healing. In surgical patients insulin resistance has been characterized in some detail, and has been shown to have many similarities with metabolic changes seen in patients with type 2 diabetes. This finding may be important since insulin resistance has been shown to be one independent factor that influences length of stay. When patients about to undergo elective surgery have been treated with glucose intravenously or a carbohydrate-rich drink instead of overnight fasting, insulin resistance was reduced by about half. A small meta-analysis showed that when post-operative insulin resistance was reduced by pre-operative carbohydrates, length of hospital stay was shortened. Overnight intravenous glucose at high doses improved post-operative N economy. This type of treatment has also been shown repeatedly to reduce cardiac complications after open-heart surgery. Furthermore, if the carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger and anxiety are markedly reduced. In summary, preventing or treating insulin resistance in surgical stress influences outcome. Fasting overnight is not an optimal way to prepare patients for elective surgery. Instead, pre-operative carbohydrates have clinical benefits.     

Knowledge of osteoporosis in a Swedish municipality--a prospective study

BACKGROUND: As a part of the Vadstena Osteoporosis Prevention Project, the knowledge of osteoporosis was examined before the intervention program started, after 5 and 10 years. METHODS: At baseline (in 1989) 15% of the population in two Swedish municipalities was randomly invited to the study. The participants in the study group were invited for examination by forearm bone densitometry and a questionnaire concerning lifestyle and risk factors for osteoporosis and also knowledge of osteoporosis, while the subjects in the control group were examined only by questionnaire. Follow-ups were made in 1994 and in 1999. Meanwhile education about osteoporosis was given to the study group, to the public, and to various professionals in the study community. RESULTS: There was a difference in the level of knowledge between the groups prior to the intervention. The rate of increment did not differ significantly between the groups for the study period. Previous participants had 0.58 higher score than new participants in the study group in 1994 (P = 0.031) and 0.76 higher score in 1999 (P < 0.001) regarding the total number of correct answers. The women in the study group had 0.63 higher score than the men in 1994 (P = 0.016) and 1.03 higher score in 1999 (P < 0.001) regarding the total number of correct answers. CONCLUSION: There was no significant effect of a general intervention program concerning the knowledge of osteoporosis in participants in the intervention area compared to the control area.     

Respiratory health among bleachery workers exposed to ozone and chlorine dioxide

OBJECTIVES: This study investigated the possibility of occupational exposure to ozone increasing the risk of obstructive airway disease among bleachery workers. : Bleachery workers (N = 129) from two Swedish pulp mills using ozone for bleaching were studied together with referents (N = 80) from adjacent paper mills. The pulp mills had previously used chlorine dioxide as the bleaching agent. Testings included spirometry, methacholine challenge testing, and questionnaires. Area samplings showed sporadic ozone levels exceeding 0.9 ppm. RESULTS: There was a greater prevalence of wheezing (25%) among the bleachery workers with a history of gassings (from ozone, chlorine, or sulfur dioxide) than among those without gassings (18%) and among the referents (13%). Among the current smokers the fraction with a slightly increased bronchial responsiveness to methacholine was greater among the bleachery workers reporting gassings than among those that had not been gassed. For the period from 1992 to 1996, when the mills were using ozone, there was an increased incidence rate of wheezing among the workers in the bleachery (incidence rate ratio 2.3, 95% confidence interval 1.6-5.8). CONCLUSIONS: Repeated exposure to irritants increases the risk of asthma-like symptoms. This finding reinforces the view that repeated peak exposures to irritants must be prevented in pulp mills.     

SYT-SSX is critical for cyclin D1 expression in synovial sarcoma cells: a gain of function of the t(X;18)(p11.2;q11.2) translocation

The SYT-SSX fusion gene has been implicated in the malignant tumor cell growth of synovial sarcoma, but the underlying molecular mechanisms are still poorly understood. Here we demonstrate that SYT-SSX is critical for the protein level of cyclin D1 in synovial sarcoma cells. Antisense oligonucleotides to SYT-SSX mRNA rapidly and drastically decreased cyclin D1 and subsequently inhibited cell growth. This effect is specific for SYT-SSX, without involving the wild-type genes SYT or SSX. The decrease in cyclin D1 expression, which occurred shortly after inhibition of SYT-SSX expression, was found to be primarily dependent on an increased degradation of the cyclin D1 protein, as assessed by pulse-chase experiments using [(35)S]methionine. Furthermore, transfection of mouse fibroblasts with SYT-SSX cDNA increased the stability of cyclin D1. Because treatment with a proteasome inhibitor restored cyclin D1 expression, it seems like SYT-SSX interferes with ubiquitin-dependent degradation of cyclin D1. However, SYT-SSX-regulated cyclin D1 expression was proven to be independent of the glycogen synthetase kinase-3beta pathway. Taken together, our study provides evidence that SYT-SSX stabilizes cyclin D1 and is critical for cyclin D1 expression in synovial sarcoma cells. SYT-SSX-dependent expression of cyclin D1 may be an important mechanism in the development and progression of synovial sarcoma and also raises the possibility for targeted therapy.     

Mechanisms of Interferon-alpha induced apoptosis in malignant cells

Interferon alpha (IFNalpha) has been used in the treatment of several types of cancer for almost 30 years, yet the mechanism(s) responsible for its anti-tumoral action remains unknown. A variety of cellular responses, including inhibition of cell growth and induction of apoptosis are induced by IFNs, and apoptotic induction by this cytokine has been proposed to be of importance for both its anti-tumoral in addition to its anti-viral responses. The aim of the present study was to delineate the pathways activated during IFNalpha-induced apoptosis in malignant cell lines. We found that apoptosis induced by IFNalpha was associated with activation of caspases-1, -2, -3, -8 and -9 and that this activation was a critical event. Caspase-3 activation was dependent on activity of caspases-8 and -9, moreover, activation of caspase-8 seems to be the upstream event in IFNalpha-induced caspase cascade. We also found loss of mitochondrial membrane potential as well as release of cytochrome c post IFN-treatment, clearly implicating the involvement of mitochondria in IFN-mediated apoptosis. Furthermore, IFNalpha-induced apoptosis was found to be independent on interactions between the Fas-receptor and its ligand. These studies form the basis for further investigations aiming to improve IFN therapy and the development of future strategies to overcome the IFN resistance observed in some malignancies.     

Cost-effectiveness analysis of screening for celiac disease in the adult population.

BACKGROUND: Celiac disease (CD) is common and, when undiagnosed, may result in increased mortality, suggesting that mass screening could be justified. The authors examined the cost-effectiveness (CE) of such an approach, assuming a higher mortality rate in undiagnosed CD and that adhering to a gluten-free diet (GFD) reduces the mortality rate. METHODS: The authors developed a state transition Markov model, evaluating the CE of screening an entire population at the age of 18. Screening strategies included no screening v. screening by IgA antiendomysial antibodies (EMA), IgA human antitissue transglutaminase antibodies (TTG), and TTG verified by EMA. All strategies were examined with and without evaluation for IgA deficiency, and they all included an intestinal biopsy. Effects of variables were examined using sensitivity analysis. Effectiveness was assessed by life expectancy for each strategy and the incremental average CE ratio for each. RESULTS: Base-case analysis revealed US$49,491 and US$572,616 per life year gained for screening compared to no screening using EMA or TTG, respectively. The CE of screening with EMA was most influenced by the prevalence of CD and the standardized mortality ratio (SMR) for untreated CD patients. Screening was cost-effective in populations with a relatively high prevalence of CD or when the SMR for untreated CD patients was higher than 1.5. The model was insensitive to changes in the cost of serological markers and diagnostic endoscopy. CONCLUSION: Assuming an SMR of 1.5 or higher for untreated CD patients, mass screening for CD is cost-effective in populations with a relatively high prevalence of CD over a wide range of ages at screening. From a CE perspective, EMA is the preferred serological marker for mass screening. Screening for CD would be justified only if the uncertainties regarding the validity of our assumptions are substantiated.     

The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells.

PURPOSE: Uveal melanoma has a high mortality rate due to a high incidence of metastasis (up to 50%), which preferentially occurs in the liver. Conventional chemotherapy, being the only therapeutic option today against metastatic uveal melanoma, has not proved to be effective. Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents. EXPERIMENTAL DESIGN: We previously reported data indicating that the insulin-like growth factor-1 receptor (IGF-IR) is a metastasis predictor as well as a therapeutic target for uveal melanoma. In the present study, we made use of the cyclolignan picropodophyllin (PPP), which is an inhibitor of the IGF-IR. RESULTS: We showed that PPP efficiently blocks growth and viability of uveal melanoma cells in cultures and causes tumor regression in xenografted mice. In addition, treatment with PPP inhibited several mechanisms involved in metastasis, including tumor cell adhesion to extracellular matrix proteins, activity and expression of matrix metalloproteinase 2, and cell migration as well as invasion through basement membranes and endothelial cell layers. Furthermore, PPP significantly delayed establishment of uveal melanoma tumors and drastically reduced the incidence of liver metastasis in mice. CONCLUSIONS: Our data suggest that IGF-IR is crucial for growth and survival as well as invasion and metastasis of uveal melanoma cells. Targeting this receptor may therefore comprise a strategy to treat ongoing disease (today incurable) as well as a strategy to prevent development of metastases in patients with primary disease.