المؤلفون: Pietrangelo, Antonello

المصدر: Gastroenterology (00165085); Aug2010, Vol. 139 Issue 2, p393-408.e2, 0p

مصطلحات موضوعية: HEMOCHROMATOSIS, GENETIC disorder treatment, GENETIC disorder diagnosis, IRON metabolism disorders, TRANSFERRIN, ERYTHROPOIESIS, GENETIC polymorphisms, MICRONUTRIENTS

مستخلص: In the late 1800s, hemochromatosis was considered an odd autoptic finding. More than a century later, it was finally recognized as a hereditary, multi-organ disorder associated with a polymorphism that is common among white people: a 845G→A change in HFE that results in C282Y in the gene product. Hemochromatosis is now a well-defined syndrome characterized by normal iron-driven erythropoiesis and the toxic accumulation of iron in parenchymal cells of liver, heart, and endocrine glands. It can be caused by mutations that affect any of the proteins that limit the entry of iron into the blood. In mice, deletion of the iron hormone hepcidin and any of 8 genes that regulate its biology, including Hfe, transferrin receptor 2 (Tfr2), and hemojuvelin (Hjv) (which all sense the accumulation of iron that hepcidin corrects) or ferroportin (Fpn) (the cellular iron exporter down-regulated by hepcidin), cause iron overload but not organ disease. In humans, loss of TfR2, HJV, and hepcidin itself or FPN mutations result in full-blown hemochromatosis. Unlike these rare instances, in white people, homozygotes for C282Y polymorphism in HFE are numerous, but they are only predisposed to hemochromatosis; complete organ disease develops in a minority, when these individuals abuse alcohol or from other unidentified modifying factors. HFE gene testing can be used to diagnose hemochromatosis, but analyses of liver histology and clinical features are still required to identify patients with rare, non-HFE forms of the disease. The role of hepcidin in the pathogenesis of hemochromatosis reveals its similarities to endocrine diseases such as diabetes and indicates new approaches to diagnosis and management of this common disorder in iron metabolism. [ABSTRACT FROM AUTHOR]

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المؤلفون: Garuti, Cinzia, Tian, Yinghua, Montosi, Giuliana, Sabelli, Manuela, Corradini, Elena, Graf, Rolf, Ventura, Paolo, Vegetti, Alberto, Clavien, Pierre–Alain, Pietrangelo, Antonello

المصدر: Gastroenterology (00165085); Jul2010, Vol. 139 Issue 1, p315-322.e1, 0p

مصطلحات موضوعية: HEMOCHROMATOSIS, KUPFFER cells, LIVER transplantation, LABORATORY mice, MICRONUTRIENTS, POLYMERASE chain reaction, STANDARD deviations, HISTOPATHOLOGY

مستخلص: Background & Aims: Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver—the source of the iron regulatory hormone hepcidin—in pathogenesis in mice. Methods: We exchanged livers between Hfe wild-type (+/+) and Hfe null (−/−) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. Results: At 6–8 months after OLT, Hfe ^−/− mice that received Hfe ^−/− livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe ^+/+ mice that received Hfe ^−/− livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe ^+/+ livers into Hfe ^−/− mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. Conclusions: In Hfe ^−/− mice, transplantation of livers from Hfe ^+/+ mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. [Copyright &y& Elsevier]

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المؤلفون: Biesalski, Hans K.

المصدر: Gastroenterology (00165085); Nov2009 Supplement, Vol. 137 Issue 5, pS92-S104, 0p

مصطلحات موضوعية: THERAPEUTIC use of vitamin E, MICRONUTRIENTS, ANTIOXIDANTS, OXIDATIVE stress, PARENTERAL feeding, LOW density lipoproteins, UNSATURATED fatty acids

مستخلص: Patients with parenteral nutrition depend on an adequate supply of micronutrients, in particular, antioxidant vitamins and cofactors such as selenium. In cases of oxidative stress (eg, chronic inflammation, sepsis, lung distress syndrome, and organ failure), there is a higher need for antioxidants. One of the most important antioxidant vitamins is vitamin E. For very low birth weight infants the plasma level is an indicator for adequate supply and for safety. Safe and effective blood levels are between 23 and 46 μmol/L, maintained with a dose of 2.8 IU/kg body weight (1–2 mg/day). For safety reasons a plasma level of 80 μmol/L should not be exceeded. For adults, 10 IU/day (9.1 mg/day) are recommended. Whether this dose is sufficient to ensure body stores and sufficient antioxidant activity is controversial. If parenteral lipid emulsions are supplied there is an additional need for vitamin E to protect the lipids (polyunsaturated fatty acids) from lipid peroxidation and to deliver additional vitamin E. Dietary guidelines for healthy adults recommend an intake of polyunsaturated fatty acids equal to 10% of total energy and an intake of α-tocopherol greater than 0.4 mg/g of polyunsaturated fatty acids. Randomized clinical trials are performed using special formulations of vitamin E solutions because vitamin E is available only in lipid emulsions to protect lipids, but not in an isolated solution for parenteral supply. [Copyright &y& Elsevier]

: Copyright of Gastroenterology (00165085) is the property of W B Saunders and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Nielsen, Forrest H.

المصدر: Gastroenterology (00165085); Nov2009 Supplement, Vol. 137 Issue 5, pS55-S60, 0p

مصطلحات موضوعية: MICRONUTRIENTS, PARENTERAL feeding, BORON, BONE growth, SILICON, WOUND healing, PHYSIOLOGICAL effects of fluorides, OSTEOPENIA

مستخلص: Boron may be beneficial for bone growth and maintenance, central nervous system function, and the inflammatory response, and silicon may be beneficial for bone maintenance and wound healing. Fluoride is not an essential element but amounts provided by contamination may be beneficial for bone strength. Fluoride toxicity may be a concern in parenteral nutrition. Further studies are warranted to determine whether there are optimal amounts of boron and silicon that should be delivered to typical and special population patients receiving parenteral nutrition. In addition, further studies are needed to determine whether providing the dietary guideline of adequate intake amounts of fluoride parenterally would prevent or treat parenteral nutrition osteopenia. [Copyright &y& Elsevier]

: Copyright of Gastroenterology (00165085) is the property of W B Saunders and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Hardy, Gil

المصدر: Gastroenterology (00165085); Nov2009 Supplement, Vol. 137 Issue 5, pS29-S35, 0p

مصطلحات موضوعية: PARENTERAL feeding, MANGANESE, MICRONUTRIENTS, NEUROTOXICOLOGY, MAGNETIC resonance imaging, BIOCHEMISTRY, SUPEROXIDE dismutase, DRUG dosage

مستخلص: Micronutrient requirements are not fully understood. Parenteral nutrition (PN) usually contains the trace element (TE) manganese (Mn) from fixed-concentration TE supplements. Multiple TE formulations may not be optimal in pediatric and home PN. Moreover, most PN products contain Mn as a ubiquitous contaminant. Excessive Mn can lead to Parkinson-like symptoms resulting from hypermanganesemia. A survey of 40 Australasian hospitals that contributed data on 108 patients to the annual home PN register and a systematic review of the literature were conducted to establish the scope of the potential problem of Mn toxicity in PN patients. Exposure to Mn doses 5–6 times current daily requirements, together with the TE contamination that is reported in PN products, can lead to neurotoxicity. Whole-blood levels are more accurate for monitoring and correlate well with signal intensity of magnetic resonance imaging. Current TE formulations restrict prescribing options. The regulatory mechanisms of Mn homeostasis are bypassed via the parenteral route so elimination via the hepatobiliary system is impaired, resulting in tissue or brain accumulation. Published dosage recommendations may be excessive and official guidelines require revision. Variability in clinical practices necessitates that individual TE additives are more widely available and multiple TE products reformulated. More frequent monitoring for any brain accumulation is recommended. The scarcity of PN-associated Mn deficiency, plus the growing evidence for Mn toxicity, leads to the conclusion that it is unnecessary for Mn to be prescribed routinely for pediatric or long-term PN patients. [Copyright &y& Elsevier]

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المؤلفون: Buchman, Alan L., Howard, Lyn J., Guenter, Peggi, Nishikawa, Reid A., Compher, Charlene W., Tappenden, Kelly A.

المصدر: Gastroenterology (00165085); Nov2009 Supplement, Vol. 137 Issue 5, pS1-S6, 0p

مصطلحات موضوعية: MICRONUTRIENTS, PARENTERAL feeding, MALNUTRITION, CHRONICALLY ill

مصطلحات جغرافية: EUROPE, UNITED States

الشركة/الكيان: AMERICAN Medical Association

مستخلص: This research workshop in 2009 grew out of a concern in the United States, Europe, and other countries with advanced medicine that it was time to revisit the parenteral requirements for a number of micronutrients. Critical questions sought to be answered included the following: Were there micronutrients not routinely added that should be part of a parenteral nutrition (PN) formula? Were other micronutrients present but in inappropriate amounts? How are various micronutrient requirements altered in the critically or chronically ill? [Copyright &y& Elsevier]

: Copyright of Gastroenterology (00165085) is the property of W B Saunders and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)