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1.
ObjectiveDuring the last 10 years we have experienced an increasing number of referrals due to hyperferritinemia. This is probably due to increased awareness of hereditary hemochromatosis, and the availability of a genetic test for this condition. Most of these referred patients were over-weight middle-aged men with elevated ferritin levels, but without the hemochromatosis-predisposing gene mutations. We evaluated the relationship between hyperferritinemia and the metabolic syndrome in 40 patients. MethodsForty consecutive patients referred for hyperferritinemia were investigated. The examination programme included medical history, clinical investigation and venous blood samples drawn after an overnight fast. This resulted in 34 patients with unexplained hyperferritinemia, which were further examined. Liver biopsy was successfully performed in 29 subjects. Liver iron stores were assessed morphologically, and by quantitative phlebotomy in 16 patients. ResultsThe majority of the patients had markers of the metabolic syndrome, and 18 patients (52%) fulfilled the IDF-criteria for the metabolic syndrome. Mean body mass index was elevated (28,8±4,2), mean diastolic blood pressure was 88,5±10,5 mmHg, and mean fasting insulin C-peptide 1498±539 pmol/l. Liver histology showed steatosis and nuclear glycogen inclusions in most patients (19 out of 29). Only four patients had increased iron stores by histology, of which two could be explained by alcohol consumption. Fourteen of 16 patients normalized ferritin levels after phlebotomy of a cumulative blood amount corresponding to normal iron stores. Ferritin levels were significantly related to insulin C-peptide level (p<0.002) and age (p<0.002). ConclusionThe present results suggest that liver steatosis and insulin resistance but not increased iron load is frequently seen in patients referred for suspected hemochromatosis on the basis of hyperferritinemia. The ferritin level seems to be positively associated to insulin resistance. 相似文献
2.
There have been inconsistent reports on the relationship between iron status and coronary artery diseases (CAD), and little data on this relationship in non-Caucasian populations. We assessed dietary iron by questionnaire and measured serum iron and ferritin levels in 270 Saudi male subjects without established CAD, 130 of whom were angiogram negative. Serum lipid profile, glucose, high sensitivity-C reactive protein (hs-CRP), serum soluble intercellular adhesion molecules-1 (sICAM-1), and caeruloplasmin were measured in all subjects. The angiogram negative patients, had lower serum ferritin (p<0.05) and iron (p<0.0001) levels than the 140 subjects without reported cardiovascular diseases (CVD). Serum iron correlated with serum triglycerides (p<0.0001) and total cholesterol (p<0.05) levels for this latter group and the groups combined. Serum ferritin correlated with serum total cholesterol and low-density lipoprotein (LDL)-cholesterol in the combined group (p<0.05), and was correlated with blood glucose and serum LDL-cholesterol (p<0.05) in the subjects without reported CVD. After adjustment for confounding variables, serum iron levels remained a significant correlate with total calorie intake and serum triglycerides. Serum ferritin also correlated significantly with cholesterol intake and fasting serum total cholesterol. Dietary iron was significantly related to dietary cholesterol and fiber, age, smoking habits, and serum total cholesterol level. Hence, indices of iron status were related to several coronary risk factors in the Saudi population. 相似文献
3.
Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit. 相似文献
5.
BackgroundDistortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB. MethodsThree groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm 3 (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin. ResultsA total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection. ConclusionIron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients. 相似文献
6.
Context: Improved biomarkers would facilitate the diagnosis and treatment of autism spectrum disorders (ASD). Objective: Our objective was to examine the levels of Nogo-A and glial fibrillary acidic protein (GFAP) in children with ASD. Materials and methods: Serum concentrations of GFAP and Nogo-A were determined by enzyme-linked immunosorbent assay. Results: In this preliminary study, we found that serum Nogo-A was not found significantly different between groups, while serum levels of GFAP were significantly lower in ASD than controls. Discussion and conclusions: It will be of great interest to determine other potential causes of elevated serum levels of GFAP, and whether this elevation has any phenotypic effect. 相似文献
7.
The recent discovery of hepcidin, the key iron regulatory hormone, has changed our view of iron metabolism, which in turn is long known to be linked with insulin resistant states, including type 2 diabetes mellitus and the Metabolic Syndrome (MetS). Serum ferritin levels are often elevated in MetS (Dysmetabolic hyperferritinemia - DHF), and are sometimes associated with a true mild-to-moderate hepatic iron overload (dysmetabolic iron overload syndrome - DIOS). However, the pathophysiological link between iron and MetS remains unclear. This study was aimed to investigate, for the first time, the relationship between MetS and hepcidin at population level. We measured serum hepcidin levels by Mass Spectrometry in 1,391 subjects from the Val Borbera population, and evaluated their relationship with classical MetS features. Hepcidin levels increased significantly and linearly with increasing number of MetS features, paralleling the trend of serum ferritin. In multivariate models adjusted for relevant variables including age, C-Reactive Protein, and the HFE C282Y mutation, ferritin was the only significant independent predictor of hepcidin in males, while in females MetS was also independently associated with hepcidin. Overall, these data indicate that the fundamental iron regulatory feedback is preserved in MetS, i.e. that hepcidin tends to progressively increase in response to the increase of iron stores. Due to recently discovered pleiotropic effects of hepcidin, this may worsen insulin resistance and contribute to the cardiovascular complications of MetS. 相似文献
8.
Introduction Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA). Methods Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis. Results Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement. Conclusions Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients. 相似文献
9.
BackgroundThe iron status in human body and its association with liver function in adolescents was rarely studied. The objective was to investigate the association among the levels of serum ferritin, uric acid and alanine aminotransferase (ALT) in adolescents. Methods and ResultsA total of 2090 adolescents negative for hepatitis B surface antigen from one junior high school (786, 12–13 years), three senior high schools (973, 15–16 years) and one college (331, 18–19 years) participated in this survey. Anthropometric and biochemical measurements, including complete blood count, ALT, serum ferritin and uric acid were performed. An ALT>42 U/L was defined as elevated, a ferritin level >200 µg/L was defined as hyperferritinemia. A uric acid level >460 µmol/L in males and >340 µmol/L in females was defined as hyperuricemia. The chi-squared test, linear regression and multivariate logistic regression were used for the data analysis. Elevated ALT levels were detected in 76 (3.6%) students and were more prevalent in males than females (6.4% vs. 2.0%, p<0.001). The univariate analysis found gender, age group, body mass index, ferritin level, uric acid level and white blood cell count all to be significantly associated with elevated ALT. Linear regression showed a positive correlation among log(ferritin), uric acid level and ALT level. Elevated ALT occurred more frequently at ferritin level >100 µg/L. The logistic regression analysis found that body mass index, hyperferritinemia and hyperuricemia were significant factors associated with the ALT elevation, but gender, age, and white blood cell count were not. ConclusionsHyperferritinemia and hyperuricemia are two independently significant factors associated with ALT elevation among obese adolescents. More studies are needed to corroborate any hypothesis related to these phenomena. 相似文献
11.
Background and ObjectivesThere is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN. Materials and MethodsWe compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients. ResultsEach serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g), compared to patients with less proteinuria. ConclusionsSerum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases. 相似文献
12.
Introduction Toll-like receptors (TLRs) mediate signaling that triggers activation of the innate immune system, whereas heme oxygenase (HO)-1 (an inducible heme-degrading enzyme that is induced by various stresses) suppresses inflammatory responses. We investigated the interaction between TLR and HO-1 in an inflammatory disorder, namely Behçet's disease. Methods Thirty-three patients with Behçet's disease and 30 healthy control individuals were included in the study. Expression levels of HO-1, TLR2 and TLR4 mRNA were semiquantitatively analyzed using a real-time PCR technique, and HO-1 protein level was determined by immunoblotting in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes. In some experiments, cells were stimulated with lipopolysaccharide or heat shock protein-60; these proteins are known to be ligands for TLR2 and 4. Results Levels of expression of HO-1 mRNA were significantly reduced in PBMCs from patients with active Behçet's disease, whereas those of TLR4, but not TLR2, were increased in PBMCs, regardless of disease activity. Moreover, HO-1 expression in PBMCs from patients with Behçet's disease was repressed in the presence of either lipopolysaccharide or heat shock protein-60. Conclusion The results suggest that upregulated TLR4 is associated with HO-1 reduction in PBMCs from patients with Behçet's disease, leading to augmented inflammatory responses. 相似文献
13.
Sirtuin 1 (Sirt1) is a class III histone deacetylase (HDAC) that modulates gene expression and is involved in the regulation of proinflammatory cytokines. Interleukin-23 (IL-23) is produced by activated macrophages and dendritic cells and could fuel the progression of rheumatoid arthritis (RA). The goal of our study was to evaluate serum IL-23 levels and both Sirt1 activity and expression in peripheral blood mononuclear cells (PBMCs) in patients with RA compared to healthy controls (HC) and to determine the relationship between Sirt1 activity/expression and IL-23 levels. We assessed apoptosis in PBMCs of RA patients and its association with Sirt1 expression and serum IL-23. Serum IL-23 levels were increased in RA patients in comparison with controls. We found a positive correlation between the levels of serum IL-23 and serum IL-6 in RA patients. Decreased cytoplasmic Sirt1 activity was observed in RA patients with severe disease compared to HC. The expression of Sirt1 protein was significantly decreased in PBMCs of RA patients compared to HC using western blotting. Serum IL-23 levels correlated positively with the cytoplasmic Sirt1 activity in RA patients. Apoptosis rate of PBMCs isolated from RA patients was increased compared to HC and correlated negatively with the expression of Sirt1 protein and serum IL-23 levels. Levels of serum IL-23 and Sirt1 activity and expression were disturbed in RA parallel to increased PBMC apoptosis. Our findings might provide the rationale for the development of new therapeutic approaches in RA. 相似文献
14.
IntroductionIn a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. MethodsA protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. ResultsProtein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. ConclusionUrine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. 相似文献
16.
目的分析继发性噬血细胞综合征(HPS)患者的实验室指标及临床特点,以提高对该病的认识。方法对2005年6月~2015年6月在广西肿瘤防治研究所治疗的32例继发性HPS患者的病因、临床表现、实验室特征、治疗及预后等进行分析。结果 32例患者中,血液系统肿瘤17例,单纯感染13例,自身免疫性疾病2例。临床上以发热(100%)、肝脾(87.5%)及淋巴结(43.8%)肿大为主要表现。实验室检查以血细胞减少(100%)、铁蛋白升高(96.9%)、自然杀伤细胞活性降低或缺失(96.9%)为主,纤维蛋白原降低(68.8%),甘油三酯升高(56.3%),81.3%的患者骨髓涂片检查可见噬血细胞现象。结论继发性HPS可由多种病因引起,临床表现多样,对可疑患者及时进行相关实验室检查有助于早期明确诊断;合并多脏器衰竭、DIC的患者预后不良。 相似文献
17.
Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients’ sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases. 相似文献
18.
Serum surfactant protein (SP)-A offers a useful clinical marker for interstitial lung disease (ILD). However, SP-A is occasionally elevated in non-ILD pulmonary patients. The present study was conducted to investigate factors that affect serum SP- A levels in respiratory medicine. Serum SP-A, serum SP-D, serum Klebs von den Lungen (KL)-6 and pulmonary function tests were evaluated in 929 patients (current smokers, n=255; ex-smokers, n=242; never-smokers, n=432) without ILD or pulmonary alveolar proteinosis. Serum SP-A was significantly higher in current smokers than in never- or ex-smokers (p<0.01 and p<0.05, respectively). Serum SP- A was significantly higher in chronic obstructive pulmonary disease (COPD) and pulmonary thromboembolism than in other diseases (p<0.01). Serum SP-A correlated positively with amount of smoking (p<0.01) and negatively with forced expiratory volume in 1 s/forced vital capacity (p<0.05). Serum SP-D and KL-6 were unaffected by smoking. Smoking should be taken into account when evaluating serum SP-A levels, and different baseline levels of serum SP-A should be established for smokers and non-smokers. Serum SP-A may also represent a useful marker for predicting COPD in the preclinical stage. 相似文献
19.
Steatohepatitis is a common finding in chronic hepatitis C virus (HCV) infection. As in other forms of steatohepatitis, oxidative damage may play an outstanding role. However, there are conflicting results relative to the role of iron on hepatic lipogenesis. Proinflammatory cytokines up-regulate ferritin expression, probably reflecting a defensive mechanism against increased oxidative stress, capable to open haem ring and release reactive iron. On the contrary, some adipokines, such as adiponectin, are associated with low ferritin levels. The aim of this study is to analyse the relationships of the amount of liver steatosis with serum iron, transferrin and ferritin as well as with proinflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, and adiponectin levels. We included 82 HCV infected patients and assessed the amount of liver fat by histomorphometry and its relationships with serum iron, ferritin and transferrin, adiponectin and TNF-α and IL-6. Liver steatosis was observed in 67 patients out of 82; in the remaining 15 patients, no steatosis at all was found. Patients with steatosis showed significantly higher serum ferritin levels than patients without steatosis ( Z?=?2.14; p?=?0.032). When patients were classified in quartiles according to the intensity of steatosis, we observed that both TNF-α (KW?=?10.6; p?=?0.014) and IL-6 (KW?=?15.2; p?=?0.002) were significantly different among the four groups. Patients with more intense steatosis (highest quartile) showed the highest TNF-α and IL-6 values. Patients with severe hepatitis had higher levels of serum iron than patients with mild to moderate hepatitis. Serum iron also showed a correlation with the proportion of fibrosis ( ρ?=?0.30; p?=?0.007). Serum iron levels are related with biochemical and histological parameters derived from liver inflammation in HCV-associated liver disease. Serum ferritin is higher among those with intense steatosis and also shows a (non-significant) trend to be associated with the more severe forms of hepatitis. 相似文献
20.
Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses. 相似文献
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