Low Serum Hepcidin Levels in Patients with Ulcerative Colitis - Implications for Treatment of Co-existent Iron-Deficiency Anemia.

Ulcerative colitis (UC) is often associated with anemia. Hepcidin, the central regulator of iron homeostasis, is known to be induced by inflammation and suppressed by anemia. It is not clear how hepcidin is affected in those with UC, when both inflammation and anemia may co-exist.Such knowledge may hold implications for treatment. Hematological and iron-related parameters, C-reactive protein (CRP), growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE) (erythroid regulators of hepcidin) levels were estimated in blood from those with UC and in control subjects. Values for hematological and iron-related parameters showed evidence of iron-deficiency and resultant anemia, in patients with UC. The presence of UC was significantly associated with inflammation. Serum levels of ERFE, but not of GDF-15, were significantly higher in patients with UC than in control patients, while hepcidin levels were significantly lower. Serum hepcidin concentrations in patients with UC correlated positively with serum iron, ferritin and GDF-15, and negatively with serum ERFE. The iron status and serum hepcidin levels in UC patients with co-existent anemia were significantly lower and serum ERFE values significantly higher than in those with UC without anemia. The effect of anemia on hepcidin predominated over that of inflammation in patients with UC, resulting in suppressed hepcidin levels. This effect is possibly mediated through erythroferrone. We suggest that a serum hepcidin-guided approach may be useful to guide use of oral iron supplements to treat co-existent iron-deficiency anemia in patients with UC and other chronic inflammatory diseases.

Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin.

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1-/-) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.

Impaired pancreatic beta-cell function after a single dose of oral iron: A before-and-after (pre-post) study.

BACKGROUND: Although in vitro and animal studies have shown that iron loading in pancreatic beta cells impairs insulin secretion, no human studies have documented the acute effects of oral iron on beta-cell insulin secretory capacity. In the present study, we determined beta-cell insulin secretory capacity at baseline and after a single oral dose of iron (ferrous sulphate, 120 mg elemental iron) in healthy male individuals. METHODS: Fifteen healthy male volunteers underwent an oral glucose tolerance test (OGTT) to document baseline glucose tolerance and insulin secretion kinetics (baseline OGTT). One week later, the same subjects underwent a second OGTT, 2 h after an oral dose of ferrous sulphate (120 mg of elemental iron) (post-iron OGTT). Changes in disposition index, insulin secretion kinetics, glucose tolerance, insulin resistance, insulin clearance and iron-related parameters in serum were determined. RESULTS: Compared to baseline OGTT, the areas under the curve (AUC) for serum iron and transferrin saturation increased by 125% and 118%, respectively, in the post-iron OGTT. The disposition index decreased by 20% (p = 0.009) and the AUC for glucose concentrations increased by 5.7% (p < 0.001) during the post-iron OGTT. The insulin secretion rate was marginally lower during the first hour (-3.5%, p = 0.63), but became significantly higher during the second hour (22%, p = 0.005) of the post-iron OGTT. Insulin resistance and insulin clearance rate were not affected by iron intake. CONCLUSIONS: The decrease in disposition index and glucose tolerance observed after the oral dose of iron points to an acute iron-induced impairment in pancreatic beta-cell insulin secretory capacity.

Gift authorship: Look the gift horse in the mouth.

Unmerited authorship in research papers is widely acknowledged to constitute research misconduct. In different contexts, it has been called "gift", "honorary", or "guest" authorship. Although several attempts have been made to address the issue, it remains a significant problem in research. In this paper, we discuss accepted criteria that qualify a person to be an author on a research publication and define what constitutes "gift authorship". We also look at the scenario in India and try to identify the circumstances that have fostered this practice in academia in the country. Finally, we discuss the adverse effects of this practice on the research enterprise as a whole, and possible remedial measures.

Evidence of dysregulated iron homeostasis in newly diagnosed diabetics, but not in pre-diabetics.

AIM: Diabetes mellitus has been reported to be associated with increased serum levels of ferritin. The basis of this association is unclear. It is also not precisely known whether other iron-related parameters, including hepcidin (the central regulator of systemic iron homeostasis), are affected under these circumstances. This study attempted to determine this. METHODS: Adult men (normoglycemic or newly diagnosed with diabetes or pre-diabetes) were recruited. Anthropometric, metabolic, and hematological and iron-related parameters in blood were measured. Indices of insulin resistance (HOMA-IR) and pancreatic beta cell function (HOMA-ß) were calculated. RESULTS: Subjects in the 3 groups were similar in age, and anthropometric and hematological parameters. Serum ferritin and hepcidin levels were higher in diabetics, than in pre-diabetics and in control subjects. These elevations seen were not linked to the presence of inflammation. HOMA-IR was higher in diabetics, and HOMA-ß lower in diabetics and pre-diabetics, than in control subjects. HOMA-IR and serum ferritin were positively correlated with one another. CONCLUSION: Elevated levels of serum ferritin and hepcidin in newly diagnosed diabetics (but not pre-diabetics) indicate dysregulated iron homeostasis, with the former positively associated with insulin resistance in these patients.

Calculated values of serum LDL-cholesterol (LDL-C) - for better or worse?

BACKGROUND AND AIMS: The use of Friedewald's formula to calculate serum low-density lipoprotein cholesterol (LDL-C) is well-known to have limitations. A modification of it, in 2013, has been proposed to be superior. However, it was not known whether LDL-C values (calculated by the modified formula) meet laboratory performance criteria for their estimation. This study aimed to evaluate this. METHODS AND RESULTS: LDL-C values were calculated for 129,821 lipid profiles, using both Friedewald's formula and its modified version. Kappa statistics and intra-class correlation coefficient (ICC) were used to determine degree of agreement between directly measured and calculated values for LDL-C. Bias and total percentage error of the values were calculated. LDL-C concentrations calculated by the modified formula showed a greater degree of agreement with directly measured values (kappa = 0.713) than those calculated by Friedewald's formula (kappa = 0.595). Both the formulae produced values with negative biases (-3.47 for the modified formula and -7.62 for Friedewald's formula) and total percentage errors above the recommended limit of 12% (15.57% for the modified formula and 21.77% for Friedewald's formula). ICC showed that values calculated by the modified formula showed a greater degree of agreement with directly measured values, across a range of LDL-C values. CONCLUSION: Calculated LDL-C values, using the modified formula, showed better agreement with directly measured values, and less bias and percentage total error than those obtained by use of Friedewald's formula. However, the percentage total error with use of the modified formula exceeded the recommended limit for LDL-C.

Development of insulin resistance preceded major changes in iron homeostasis in mice fed a high-fat diet.

Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) have been associated with dysregulation of iron metabolism. The basis for this association is not completely understood. To attempt to investigate this, we studied temporal associations between onset of insulin resistance (IR) and dysregulated iron homeostasis, in a mouse model of T2DM. Male C57Bl/6 mice (aged 8 weeks) were fed a high-fat diet (HFD; 60% energy from fat) or a control diet (CD; 10% energy from fat) for 4, 8, 12, 16, 20 and 24 weeks. Development of IR was documented, and various metabolic, inflammatory and iron-related parameters were studied in these mice. HFD-feeding induced weight gain, hepato-steatosis and IR in the mice. Onset of IR occurred from 12 weeks onwards. Hepatic iron stores progressively declined from 16 weeks onwards. Accompanying changes included a decrease in hepatic hepcidin (Hamp1) mRNA expression and serum hepcidin levels and an increase in iron content in the epididymal white adipose tissue (eWAT). Iron content in the liver negatively correlated with that in the eWAT. Factors known to regulate hepatic Hamp1 expression (such as serum iron levels, systemic inflammation, and bone marrow-derived erythroid regulators) were not affected by HFD-feeding. In conclusion, the results show that the onset of IR in HFD-fed mice preceded dysregulation of iron homeostasis, evidence of which were found both in the liver and visceral adipose tissue.

Enhanced insulin signaling and its downstream effects in iron-overloaded primary hepatocytes from hepcidin knock-out mice.

BACKGROUND: Increased body iron stores have been implicated in the pathogenesis of diabetes mellitus. However, the molecular mechanisms involved are unclear. The liver plays a central role in homeostasis of iron and glucose in the body. Mice deficient in hepcidin (the central regulator of systemic iron homeostasis) (Hamp1-/- mice) accumulate iron in the liver in vivo. The effects of such iron loading on hepatic insulin signaling and glucose metabolism are not known. METHODS: Hepatocytes isolated from Hamp1-/- mice were studied for markers of insulin signaling (and its downstream effects), glucose production, expression of gluconeogenic and lipogenic enzymes, and markers of AMPK (AMP-activated protein kinase) activation and oxidative stress. These parameters were studied both in the absence and presence of insulin, and also with the use of an iron chelator. RESULTS: Akt in the insulin signaling pathway was found to be activated in the Hamp1-/- hepatocytes to a greater extent than wild-type (WT) cells, both under basal conditions and in response to insulin. Incubation of the Hamp1-/- hepatocytes with an iron chelator attenuated these effects. There was no evidence of oxidative stress or AMPK activation in the Hamp1-/- hepatocytes. Glucose production by these cells was similar to that by WT cells. Gene expression of key gluconeogenic enzymes was decreased in these cells. In addition, they showed evidence of increased lipogenesis. CONCLUSIONS: Hepatocytes from Hamp1-/- mice showed evidence of greater sensitivity to the effects of insulin than WT hepatocytes. This may explain the insulin-sensitive phenotype that has been reported in classical hemochromatosis.

Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease.

BACKGROUND: Perturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved. METHODS: Patients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters. RESULTS: Patients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter-1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 µg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 µg/dL. CONCLUSIONS: In patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease.

Establishing Goals of Care for Patients With Stroke and Feeding Problems: An Interdisciplinary Trigger-Based Continuous Quality Improvement Project.

BACKGROUND: Few patients with dysphagia because of stroke receive early palliative care (PC) to align treatment goals with their values, as called for by practice guidelines, particularly before enteral access procedures for artificial nutrition. MEASURES: To increase documented goals of care (GOC) discussions among acute stroke patients before feeding gastrostomy tube placement. INTERVENTION: We undertook a rapid-cycle continuous quality improvement process with interdisciplinary planning, implementation, and performance review to operationalize an upstream trigger for PC referral prompted by the speech and language pathology evaluation. OUTCOMES: During a six-month period, 21 patients underwent gastrostomy tube placement; 52% had preprocedure GOC discussions postintervention, with the rate of compliance increasing steadily from 13% (11/87, preintervention) to 100% (2/2) in the final two months. CONCLUSIONS/LESSONS LEARNED: We effectively increased documented GOC discussions before feeding gastrostomy tube placement among stroke patients. Systems-based tools and education will enhance this upstream trigger model to ensure early PC for stroke patients.

Increased intracellular iron in mouse primary hepatocytes in vitro causes activation of the Akt pathway but decreases its response to insulin.

BACKGROUND: An iron-overloaded state has been reported to be associated with insulin resistance. On the other hand, conditions such as classical hemochromatosis (where iron overload occurs primarily in the liver) have been reported to be associated with increased insulin sensitivity. The reasons for these contradictory findings are unclear. In this context, the effects of increased intracellular iron per se on insulin signaling in hepatocytes are not known. METHODS: Mouse primary hepatocytes were loaded with iron in vitro by incubation with ferric ammonium citrate (FAC). Intracellular events related to insulin signaling, as well as changes in gene expression and hepatocyte glucose production (HGP), were studied in the presence and absence of insulin and/or forskolin (a glucagon mimetic). RESULTS: In vitro iron-loading of hepatocytes resulted in phosphorylation-mediated activation of Akt and AMP-activated protein kinase. This was associated with decreased basal and forskolin-stimulated HGP. Iron attenuated forskolin-mediated induction of the key gluconeogenic enzyme, glucose-6-phosphatase. It also attenuated activation of the Akt pathway in response to insulin, which was associated with decreased protein levels of insulin receptor substrates 1 and 2, constituting insulin resistance. CONCLUSIONS: Increased intracellular iron has dual effects on insulin sensitivity in hepatocytes. It increased basal activation of the Akt pathway, but decreased activation of this pathway in response to insulin. GENERAL SIGNIFICANCE: These findings may help explain why both insulin resistance and increased sensitivity have been observed in iron-overloaded states. They are of relevance to a variety of disease conditions characterized by hepatic iron overload and increased risk of diabetes.

Gene-gene interaction between DRD4 and COMT modulates clinical response to clozapine in treatment-resistant schizophrenia.

Clozapine is the drug of choice for treatment-resistant schizophrenia. However, its use is associated with variable clinical responses and serious adverse effects. Polymorphisms in genes encoding proteins involved in synaptic neurotransmission may account for such variability. Here, we studied independent and epistatic genetic associations of polymorphisms in DRD4 (120-bp duplication) and COMT (Val158Met) with clinical response to clozapine in people with treatment-resistant schizophrenia. We studied 93 participants who were on stable doses of clozapine for at least 12 weeks. A total score of less than or equal to 35 on the Brief Psychiatric Rating Scale was defined as a clinical response. The genetic associations were tested using logistic regression analyses. Neither polymorphism studied was found to be independently associated with response to clozapine. However, a statistically significant gene-gene interaction was observed between the polymorphisms. Participants with the COMT Val/Met or Met/Met genotype, who also had one or two DRD4 120-bp alleles (120/240 and 120/120), showed significantly better clinical response to clozapine. Our results highlight the importance of investigating gene-gene interactions, while studying the pharmacogenetics of clozapine.

Decreased hepatic iron in response to alcohol may contribute to alcohol-induced suppression of hepcidin.

Hepatic Fe overload has often been reported in patients with advanced alcoholic liver disease. However, it is not known clearly whether it is the effect of alcohol that is responsible for such overload. To address this lacuna, a time-course study was carried out in mice in order to determine the effect of alcohol on Fe homoeostasis. Male Swiss albino mice were pair-fed Lieber-DeCarli alcohol diet (20 % of total energy provided as alcohol) for 2, 4, 8 or 12 weeks. Expression levels of duodenal and hepatic Fe-related proteins were determined by quantitative PCR and Western blotting, as were Fe levels and parameters of oxidative stress in the liver. Alcohol induced cytochrome P4502E1 and oxidative stress in the liver. Hepatic Fe levels and ferritin protein expression dropped to significantly lower levels after 12 weeks of alcohol feeding, with no significant effects at earlier time points. This was associated, at 12 weeks, with significantly decreased liver hepcidin expression and serum hepcidin levels. Protein expressions of duodenal ferroportin (at 8 and 12 weeks) and divalent metal transporter 1 (at 8 weeks) were increased. Serum Fe levels rose progressively to significantly higher levels at 12 weeks. Histopathological examination of the liver showed mild steatosis, but no stainable Fe in mice fed alcohol for up to 12 weeks. In summary, alcohol ingestion by mice in this study affected several Fe-related parameters, but produced no hepatic Fe accumulation. On the contrary, alcohol-induced decreases in hepatic Fe levels were seen and may contribute to alcohol-induced suppression of hepcidin.

Indomethacin induces endoplasmic reticulum stress, but not apoptosis, in the rat kidney.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice. However, their use is often associated with adverse effects in the gastrointestinal tract and kidney. Our earlier work with indomethacin, a prototype NSAID, has shown that it induced oxidative stress in the kidney in rats, an event that has been postulated to contribute to pathogenesis of its adverse effects in this organ. Endoplasmic reticulum (ER) stress responses have been shown to occur in response to oxidative stress. We investigated whether this occurred in the rat kidney, in response to indomethacin. For this, Wistar rats were orally gavaged with indomethacin (20mg/kg). Markers of ER stress were studied in the kidneys 1, 12 and 24h later. GRP78, p-PERK and nuclear sXBP-1, all markers of ER stress, were found to be increased in the rat kidney at 12h, in response to indomethacin; levels of these markers fell by 24h. The effects seen at 12h were attenuated by pre-treatment with zinc, a known anti-oxidant, which has earlier been shown to ameliorate indomethacin-induced oxidative stress. Activation of an ER stress response was not associated with induction of apoptosis, as measured by markers of apoptosis such as release of cytochrome c from mitochondria into the cytosol, activation of caspases 3 and 9, cleavage of poly-ADP ribose polymerase and the presence of DNA laddering. We conclude that indomethacin-induced oxidative stress activated ER stress, but did not lead to apoptosis in the rat kidney.

Do medical students require education on issues related to plagiarism?

In the course of our professional experience, we have seen that many medical students plagiarise. We hypothesised that they do so out of ignorance and that they require formal education on the subject. With this objective in mind, we conducted a teaching session on issues related to plagiarism. As a part of this, we administered a quiz to assess their baseline knowledge on plagiarism and a questionnaire to determine their attitudes towards it. We followed this up with an interactive teaching session, in which we discussed various aspects of plagiarism. We subjected the data obtained from the quiz and questionnaire to bivariate and multivariate analysis. A total of 423 medical students participated in the study. Their average score for the quiz was 4.96±1.67 (out of 10). Age, gender and years in medical school were not significantly associated with knowledge regarding plagiarism. The knowledge scores were negatively correlated with permissive attitudes towards plagiarism and positively correlated with attitudes critical of the practice. Men had significantly higher scores on permissive attitudes compared to women . In conclusion, we found that the medical students' knowledge regarding plagiarism was limited. Those with low knowledge scores tended to have permissive attitudes towards plagiarism and were less critical of the practice. We recommend the inclusion of formal instruction on this subject in the medical curriculum, so that this form of academic misconduct can be tackled.

Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea.

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

Indomethacin inhibits activation of endothelial nitric oxide synthase in the rat kidney: possible role of this effect in the pathogenesis of indomethacin-induced renal damage.

The clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with adverse effects in the kidney. Indomethacin, an NSAID that has been shown to induce oxidative stress in the kidney, was used to study the pathogenesis of renal damage induced by the drug in a rat model. Experimental animals were given indomethacin (20mg/kg) by oral gavage, sacrificed 1, 12 or 24h (h) later and the kidneys studied. Evidence of glomerular and tubular damage in the kidney was found in response to the drug. Renal tissue nitrite levels, a surrogate marker of nitric oxide (NO) synthesis, were significantly decreased at 12 and 24h. Indomethacin did not affect protein and mRNA levels of endothelial nitric oxide synthase (eNOS) or inducible NOS (iNOS). However, it significantly reduced the ratio of dimeric (active) to monomeric (inactive) eNOS in the kidney, 12 and 24h after drug administration. This was associated with reductions in heme content, both in renal tissue and in NOS. Heme oxygenase 1 (HO-1) mRNA (at 1 and 12h), protein (at 12 and 24h) and activity (at 1, 12 and 24h) were elevated in response to indomethacin. Nuclear translocation of Nrf2 (at 12h) and p38 MAPK signaling (at 12h and 24h), both of which are known to induce HO-1, also occurred in response to the drug. In summary, our results show that indomethacin reduced levels of activated eNOS in the kidney. This effect is possibly mediated by heme depletion, secondary to HO-1 induction that occurred downstream of Nrf2 and p38 MAPK signaling. We postulate that reduced renal eNOS activity may result in decreased NO levels, and hence reduced renal perfusion, leading to glomerular and tubular injury with subsequent renal damage.

Expression of iron-related proteins in the duodenum is up-regulated in patients with chronic inflammatory disorders.

Mechanisms responsible for derangements in Fe homeostasis in chronic inflammatory conditions are not entirely clear. The aim of the present study was to test the hypothesis that inflammation affects the expression of Fe-related proteins in the duodenum and monocytes of patients with chronic inflammatory disorders, thus contributing to dysregulated Fe homeostasis. Duodenal mucosal samples and peripheral blood monocytes obtained from patients with chronic inflammatory disorders, namely ulcerative colitis (UC), Crohn's disease (CD) and rheumatoid arthritis, were used for gene and protein expression studies. Hb levels were significantly lower and serum C-reactive protein levels were significantly higher in patients in the disease groups. The gene expression of several Fe-related proteins in the duodenum was significantly up-regulated in patients with UC and CD. In patients with UC, the protein expression of divalent metal transporter 1 and ferroportin, which are involved in the absorption of dietary non-haem Fe, was also found to be significantly higher in the duodenal mucosa. The gene expression of the duodenal proteins of interest correlated positively with one another and negatively with Hb. In patients with UC, the gene expression of Fe-related proteins in monocytes was found to be unaffected. In a separate group of patients with UC, serum hepcidin levels were found to be significantly lower than those in the control group. In conclusion, the expression of Fe-related proteins was up-regulated in the duodenum of patients with chronic inflammatory conditions in the present study. The effects appeared to be secondary to anaemia and the consequent erythropoietic drive.