Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain is the most compartmentalized organ. It is also highly aerobic. Because nerve cells grow but do not regenerate, the brain is the organ best suited for the accumulation of metabolic errors colocalized in specific areas of the brain over an extended period. Alzheimer's disease (AD) is primarily a neurological disorder of the elderly. It is suggested that this disorder results from the accumulation of such errors, and that AD onset aluminum and iron contribute to but do not necessarily initiate the onset of the disease. In vitro and in vivo evidence summarized here suggests that this is effected by interfering in the utilization of glucose and glucose-6-phosphate, and sequestration of iron by ferritin. beta-amyloid precusor proteins (beta-APPs) are normal components of the human brain and some other tissues. Proteolysis of these, presumably by serine proteases, generates a 39 to 42 amino acid long peptide, the alpha-amyloid (beta-AP). In AD brains, beta-AP aggregates into plaque, the hallmark of AD brains. Some of the alpha-APPs also contain a 56 amino acid long segment which inhibits serine proteases. We show that in vitro, at pH 6.5, aluminum activates beta-chymotrypsin 2-fold and makes it dramatically resistant to protease inhibitors such as bovine pancreatic trypsin inhibitor (bPTI) or its mimic present in the beta-amyloid precursor proteins (beta-APPs). Iron and oxygen are reported to favor cross-linking of beta-AP in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Iron and aluminum homeostasis in neural disorders. 784 99

In screening a rat pancreatic islet cDNA library by differential hybridization for transcripts increased by glucose, the H chain of ferritin, an iron storage protein, was identified. An ELISA for rat ferritin showed that the insulin cell contains a surprisingly high amount of ferritin comparable to that of iron storage tissues. Most of the ferritin was located in the beta cell, as judged from colocalization of ferritin and insulin by immunohistochemical staining of the pancreas. Islets maintained for 24 h in culture medium containing 20 mM glucose are capable of releasing insulin in response to stimulation with glucose, but islets maintained at 1 mM glucose are incapacitated in response to glucose (see ref 1). Immunoassayable ferritin was threefold higher in 20 mM glucose islets than in 1 mM glucose islets and the glucose-stimulated increase in H ferritin mRNA was confirmed by probing Northern blots of islet RNA with authentic H and L chain cDNAs. This showed that H ferritin mRNA was four- to eightfold higher in 20 mM-glucose islets than in 1 mM glucose islets, whereas L ferritin mRNA was decreased 75-90% in 20 mM glucose islets relative to 1 mM glucose islets. The physiological reason for the abundance of (apo)ferritin in the beta cell is not readily apparent because the islet contains very little iron. Whether or not ferritin is used to handle another metal such as zinc, which is plentiful in the beta cell, is unknown. Another potential reason for ferritin in the beta cell is that ferritin has antioxidant properties and the beta cell is particularly sensitive to oxygen radicals. Regardless of its physiologic purpose, the high amount of ferritin can explain why iron is preferentially retained in the insulin cell and causes diabetes in diseases of iron overloading.
 ...
PMID:Large amount of (apo)ferritin in the pancreatic insulin cell and its stimulation by glucose. 805 Jun 78

An elevated serum ferritin concentration recently has been shown to be associated with coronary artery disease and its risk factors, including blood glucose concentration. The purpose of this study is to establish the prevalence of elevated levels of serum ferritin in patients with non-insulin-dependent diabetes mellitus (NIDDM) without hemochromatosis and to determine whether or not deferoxamine is of therapeutic value in treating such patients. The level of serum ferritin was measured in consecutive eligible patients with NIDDM seen at routine outpatient visits. Five patients with an elevated serum ferritin were treated with deferoxamine, 1 g intramuscularly, twice a week for 12 weeks. The level of serum ferritin was measured every 4 weeks, and the level of glycosylated hemoglobin was measured at baseline, at the end of the treatment, and 12 weeks after treatment was completed. The level of serum ferritin was elevated in 34 of 102 (33%) patients with NIDDM. The level of serum ferritin remained elevated in 30 of 32 (94%) of these patients on repeat testing. In three of the five patients treated with deferoxamine, the level of serum ferritin was normalized, but no patient had an appreciable change in dosage of medication for diabetes or glycemic control. Non-insulin-dependent diabetes is a condition frequently associated with elevated levels of serum ferritin. Treatment with deferoxamine intramuscularly was not effective in improving control of glucose in our patient group.
 ...
PMID:Non-insulin-dependent diabetes mellitus and elevated serum ferritin level. 821 68

Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
 ...
PMID:Tissue iron loading and histopathological changes in hypotransferrinaemic mice. 827 72

Although polymorphonuclear (PMNL) glucose consumption as an index of metabolic response to phagocytosis in the production of free radical species is depressed in hemodialyzed patients, substantial interindividual differences are registered. Studies evaluating to what variables these differences are related are, however, lacking. In the present study, the relation of several factors to PMNL functional capacity in the breakdown of glucose to CO2 by the hexose monophosphate shunt (HMS) is considered in an individual and multifactorial regression analysis. Starting from a database, collected in 126 stabilized hemodialysis patients, PMNL HMS-response to standard quantities of latex and zymosan was correlated to 14 numerical parameters: time since the start of dialysis, hematocrit, serum creatinine, phosphorus, ferritin, albumin, parathormone, albumin before and after administration of desferrioxamine, residual creatinine clearance, PCR, TACurea, Kt/V and age. In addition, the non-numeric parameters of sex, biocompatibility of dialyzers, and primary diagnosis were also considered. A significant correlation was found for time on dialysis (P < 0.001), hematocrit (P < 0.001), ferritin (P < 0.05), PTH (P < 0.001) and aluminum (P < 0.05). The highest correlation coefficients were found for time on dialysis (latex: N = 126, r = 0.50, P < 0.001; zymosan: N = 126, r = 0.58, P < 0.001). Multivariate correlation analysis of one clinical parameter together with time on dialysis to PMNL response showed that the correlation was strongly weakened or disappeared for ferritin, aluminum and PTH, but not for hematocrit. Our data indicate that time since the start of dialysis is an important, but not unique factor, influencing polymorphonuclear functional capacity in a hemodialysis population.
 ...
PMID:Contributing factors to the inhibition of phagocytosis in hemodialyzed patients. 835 62

Deferoxamine has been proposed as a potentially important therapy for individuals with NIDDM and mild elevations in serum ferritin. Previously, iron chelation therapy with intravenous deferoxamine over a 5-13-wk period has been reported to normalize serum ferritin and markedly improve glycemic control. To confirm these results and to study potential beneficial effects of deferoxamine on insulin secretion, 9 individuals with NIDDM and elevated serum ferritin levels were treated twice weekly with deferoxamine infusion, following a previously described protocol. Although 8 of 9 subjects achieved normal or near-normal serum ferritin values after deferoxamine therapy, we found little evidence that it produced beneficial effects on glycemic control. Fasting glucose levels pre- and post-deferoxamine therapy were unchanged (11.6 +/- 1.2 and 11.3 +/- 1.5 mM, respectively, P = 0.80). GHb levels declined slightly after deferoxamine therapy (9.3 +/- 0.7 vs. 8.8 +/- 0.7%, P < 0.05); however, this effect was small and was not associated with elimination of or even substantial reduction in insulin or oral hypoglycemic therapy. Deferoxamine therapy did not significantly alter fasting insulin or C-peptide levels, nor stimulated insulin or C-peptide responses to intravenous arginine or glucose. During follow-up studies 1.5-8 mo after deferoxamine therapy, serum ferritin levels again were elevated in 5 of 8 subjects who showed an initial response. Thus, although deferoxamine therapy reduced serum ferritin levels in our subjects, we were unable to confirm a previous report that this effect was associated with any meaningful improvement in glycemic control or insulin secretion.
 ...
PMID:No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin. 845 4

We report a case of aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation (BMT). A 29-year-old man was diagnosed as having aplastic anemia at the age of 8. At the age of 28, BMT was performed from his HLA-identical sister. Total volume of blood transfusion before BMT was about 28,000 ml, and in three months after BMT was 8,000 ml. The transplantation was successful, but one month after BMT, dry eyes, skin pigmentation and hepatomegaly appeared. Serum bile duct enzymes and ferritin also increased remarkably. Moreover after thirteen months, glucose tolerance impaired seriously. Abdominal computed tomography (CT) revealed atrophic pancreas and an increased CT density in the liver and the tail of the pancreas. A large amount of iron deposition were also found in liver and stomach biopsy specimens. We concluded that diabetes mellitus was due to secondary hemochtomatosis in the present case. There is a possibility that tissue damage due to iron deposits may have been accelerated through BMT in this patient with a history of many blood transfusions.
 ...
PMID:[Aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation]. 853 29

ENDOREM (Guerbet, Sulzbach) is a superparamagnetic contrast agent for magnetic resonance imaging of the liver and spleen. The contrast agent consists of dextran-coated iron oxide particles with a size distribution between 120 and 180 nm and an iron concentration of 0.2 mol/l. Before ENDOREM received approval in Germany and other European countries, clinical trials were performed in Japan, the USA, and Europe. At a dose of 10 micromol Fe/kg (Japan, USA) and 15 micromol Fe/kg (Europe). ENDOREM was slowly infused in 100 ml of glucose 5% over approximately 30 min in 163 (Japan), 213 (USA), and 467 patients (Europe). The rate of side effects ranged between 6.1% (Japan) and 10.3% (Europe). The most frequent side effect was lower back pain. However, infusion was stopped or medication was necessary because of lower back pain in only very few cases. Transient increases of serum iron and ferritin and decreases of iron binding capacity occurred. No clinically relevant changes of heart rate and arterial blood pressure were observed. With the recommended biphasic infusion (2 ml/min over 10 min and 4 ml/min over 20 min) and at a dose of 15 micromol Fe/kg in 100 ml of glucose 5% ENDOREM is a well tolerated contrast agent
 ...
PMID:[The endorem tolerance profile]. 858 33

Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.
 ...
PMID:Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction. 862 11

This study relates to the diffusive transport characterization of hollow fibre membranes used in implantable bio-hybrid organs and other immunoisolatory devices. Techniques were developed to accurately determine the mass transfer coefficients for diffusing species in the 10(2)-10(5) MW range, validated and then used to study one membrane type known to effectively immunoisolate both allografts and xenografts in vivo. Low-molecular-weight diffusing markers included glucose, vitamin B12 and cytochrome C; higher-molecular-weight molecules were bovine serum albumin, immunoglobulin G, apoferritin and a range of fluorescein-tagged dextrans. Overall and fractional mass transfer coefficients through the hollow fibres were determined using a resistance-in-series model for transport. A flowing dialysis-type apparatus was used for the small-molecular-weight diffusants, whereas a static diffusion chamber was used for large-molecular-weight markers. For diffusion measurements of small-molecular-weight solutes, convective artefacts were minimized and the effect of boundary layers on both sides of the membrane were accounted for in the model. In measuring diffusion coefficients of large-molecular-weight species, boundary layer effects were shown to be negligible. Results showed that for small-molecular-weight species (< 13,000 MW) the diffusion coefficient in the membrane was reduced relative to diffusion in water by two to four times. The diffusion rate of large-molecular-weight species was hindered by several thousand-fold over their rate of diffusion in water.
 ...
PMID:Transport characterization of membranes for immunoisolation. 874 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>