TIBC Levels Research Articles

Iron Overload in Very Low Birth Weight Infants: Serum Ferritin and Adverse Outcomes

Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants. Iron indices were measured in VLBW infants (weight 300microg/L was considered elevated. Data was analysed using SPSS Version 14.0. Associations were assessed using Mann Whitney U tests for non-parametric variables and p< 0.05. Ferritin levels were elevated in 31% (n=14). The mean ferritin level was 270microgms/L. The mean total Iron was within normal limits at 16.64umol (11-34umol). However mean Transferrin and TIBC levels were below normal at 1.75g/dl (2-3g/dl) and 42.35umol (50-85umol) respectively. 19 MRIs had been conducted at term. Of 6 MRIs conducted in the high ferritin group, 3 were abnormal and 3 were normal. In the low ferritin group 13 MRIS were conducted at term, 10 were normal and 3 were abnormal. In this group of healthy VLBW infants there was a 31% of iron overload at time of starting routine iron supplementation. ELBW and lower gestational age were risk factors for developing iron overload which seems to be associated with number of transfusions required. VLBW infants with high ferritin longer on both NCPAP and 02.

Abstract B8: Correlation of the expression of hepcidin mRNA and the serum iron, ferritin, and TIBC levels in hepatocellular carcinoma

Abstract Background: The present study correlated the expression of hepcidin mRNA and the levels of serum iron, ferritin, and TIBC in hepatocellular carcinoma (HCC). Methods: Samples of cancerous and noncancerous liver tissue were taken from patients with HCC who underwent hepatectomy. Expression of hepcidin mRNA was evaluated by realtime PCR, and compared in tumors differing in their degree of differentiation and number of tumors. Correlations between hepcidin expression and the serum concentration of hepcidin were evaluated, together with the expression of the serum concentration of biochemical markers of iron metabolism. Results: Hepcidin mRNA expression in non-cancerous and cancerous tissues was 1791.6 (34.3- 25187.4) and 58.7 (1.93235.8), respectively (P &amp;lt; 0.0001). There were no significant differences in hepcidin expression among tumors differing in their degree of differentiation and number of tumors. The serum concentration of hepcidin did not correlate with hepcidin-mRNA expression. The serum iron level was found to be normal (125.4 ± 21.4 mg/dL). The serum ferritin level was also found to be normal 193.5(14.0-232.9 ng/mL). TIBC was (284.8 ±28.3 ng/mL). There were significant correlations between the serum levels of hepcidin and iron, hepcidin-25 and ferritin and hepcidin and TIBC. Conclusion: The serum hepcidin concentration was correlated with the levels of serum iron and ferritin, but not with the level of hepcidin mRNA expression in either cancerous or non- cancerous liver tissue. Hepcidin is produced in patients with HCC, from non-cancerous liver tissue, even though production is inhibited in cancerous tissue. Expression of hepcidin mRNA is constitutively suppressed in cancerous, but not in non-cancerous liver tissue of patients with HCC. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B8.

Preliminary results from The Ovarian Nutrition Education (ONE) study

Guidelines for cancer prevention suggest that a diet high in fruit and vegetables and low in animal protein is associated with a reduction of risk for most cancers and may improve cancer survival. The aim of this study was to determine if fruit/vegetable concentrate supplementation is associated with similar improvements in plasma biomarkers and anthropometric indicators than a diet high in fiber and low in fat among a sample of ovarian cancer survivors. Initially there were a total of 52 women (85% White; Mean age = 53 years) participants with an adherence rate of roughly 73%. Twenty‐seven women were randomized to Juice Plus diet and 24 were randomized to the WHEL study diet. Mixed‐effects regression models revealed that there were no significant between‐group changes in anthropometric measures (i.e., BMI, weight, hip, waist, upper arm) (all p &gt; 0.05), whereas, significant between‐group differences were observed for improvements in Serum Albumin and TIBC levels (all p &lt; 0.05). Near significant between‐group differences were observed for vitamin B12 (p &lt; 0.10). These improvements were observed among Juice Plus participants. More research is needed to determine if the improvements observed by Juice Plus participants translates into meaningful clinical outcomes such as reductions in recurrence and survival. Support: NSA (TN, USA)

Patients with Waldenstrom's Macroglobulinemia Are Often Hypoferremic That Is Refractory to Oral Iron Repletion and Responsive to Parental Iron Infusions, and Demonstrate Elevated Levels of Hepcidin.

Abstract 2952Poster Board II-928 Background:Patients with Waldenstrom's macroglobulinemia (WM) often present with anemia, that can occur independent of bone marrow disease involvement, serum IgM levels, and in the absence of any hemolysis (Treon, Blood 2009). Iron deficiency is commonly observed in WM patients, and is often oral iron refractory. Parenteral administration of iron (Ferrlicit) in such patients can lead to improvements in hematocrit in patients who are oral iron refractory as shown below in Table 1:(n=5)Pre-TreatmentPost-Treatmentp=Hct (%)29.7 (range 27.4-33.8)34.2 (range 30.7-35.6)0.03097As such, we investigated mechanisms by which oral iron uptake could be impaired in patients with WM. Hepcidin is a peptide which acts as a master regulator of iron homeostasis by binding to and disabling the only known iron-export protein, ferroportin, resulting in the inhibition of iron transfer from enterocytes and macrophages into the circulation. We therefore sought to delineate the role of Hepcidin in WM patients presenting with and without anemia, and in those patients who did not respond to oral iron intake. Patients and Methods:Serum levels of Hepcidin were determined in 53 previously untreated patients with WM [Median Age: 63; BM Involvement 40%; Beta 2 Microglobulin (B2M) 2.6 g/L; Hematocrit 34.2%; Iron 67 ug/dL; TIBC 321 ug/dL] along with 20 healthy donors [Median Age: 63.5, Female N=8, Male N=12] using the Hepcidin-P competitive ELISA for hepcidin-25, the biologically-active form of the hormone [Intrinsic LifeSciences, La Jolla, CA USA]. Of the patients examined, 45 were anemic, 12 were hypoferremic [<37-170 mg/dL]. All but 5 individuals had normal TIBC levels [210-480 mg/dL]. Results:Serum Hepcidin levels were elevated among all WM patients [107.5 ng/mL, range 11.3-689 ng/mL] versus healthy donors [91.8 ng/mL, range 12.2-211.6 ng/mL; p=.04]. Levels of Hepcidin positively correlated with BM disease involvement (p=0.004; Spearmans rho=0.4), and inversely with hematocrit (p=0.08; Spearman's rho=-.24) [Figure 1,2]. [Display omitted] Among the 45 WM patients who demonstrated anemia, the median level of Hepcidin was higher at 118.5 ng/mL [Range 11.3-689 ng/mL; p=0.025 versus healthy donors]. Among 5 WM patients who failed to respond to oral iron repletion and who subsequently responded to parenteral iron (Table 1), the median Hepcidin level was 189.1 (range 40.6-444.1 ng/mL). Among non-anemic WM patients, hepcidin levels were lower [66.5 ng/mL; range 31.7-401.8 ng/mL; p=0.35 versus anemic WM patients), though these patients demonstrated a lower bone marrow disease burden (30% vs. 50%; p=0.03). Conclusions:Hepcidin levels are elevated in patients with WM, and show a positive correlation with bone marrow disease burden, and an inverse relationship with hematocrit. Importantly, higher levels of Hepcidin may be associated with refractoriness to oral iron intake. Further studies addressing the role of Hepcidin in the management of WM related anemia are warranted. Disclosures:No relevant conflicts of interest to declare.

Intravenous Iron Versus Erythropoiesis-Stimulating Agents: Friends or Foes in Treating Chronic Kidney Disease Anemia?

Patients with chronic kidney disease (CKD), especially those requiring maintenance hemodialysis treatments, may lose up to 3 g of iron each year because of frequent blood losses. Higher doses of erythropoiesis-stimulating agents (ESAs) may worsen iron depletion and lead to an increased platelet count (thrombocytosis), ESA hyporesponsiveness, and hemoglobin variability. Hence, ESA therapy requires concurrent iron supplementation. Traditional iron markers such as serum ferritin and transferrin saturation ratio (TSAT) (ie, serum iron divided by total iron-binding capacity [TIBC]), may be confounded by non-iron-related conditions. Whereas serum ferritin <200 ng/mL suggests iron deficiency in CKD patients, ferritin levels between 200 and 1,200 ng/mL may be related to inflammation, latent infections, malignancies, or liver disease. Protein-energy wasting may lower TIBC, leading to a TSAT within the normal range, even when iron deficiency is present. Iron and anemia indices have different mortality predictabilities, in that high serum ferritin but low iron, TIBC, and TSAT levels are associated with increased mortality, whereas hemoglobin exhibits a U-shaped risk for death. The increased mortality associated with targeting hemoglobin above 13 g/dL may result from iron depletion-associated thrombocytosis. Intravenous (IV) iron administration may not only decrease hemoglobin variability and ESA hyporesponsiveness, it may also reduce the greater mortality associated with the much higher ESA doses that have been used in some patients when targeting higher hemoglobin levels.

IRON STATUS IN FEBRILE SEIZURE: A CASE-CONTROL STUDY

Objective Data on the relationship between iron deficiency anemia and febrile convulsions are controversial. The aim of this study was to determine the association between iron deficiency anemia and febrile convulsions among children. Materials & Methods This case-control study was conducted during 2006-2007, on 90 children with febrile seizures (case) and 90 febrile children without seizures (control) referred to the Amirkola children hospital (a referral hospital in the north of Iran). Two groups were matched for age and sex. In all children hemoglobin (Hb) level, hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and plasma ferritin (PF) were determined and the data collected were analyzed statistically using the t-test. Results The mean PF and TIBC levels were not significantly different in the febrile seizure compared to the reference group; neither were differences in Hb levels statistically significant between two groups. However MCV and MCH were significantly higher in the febrile seizure group (p Conclusion Plasma ferritin levels were not significantly lower in children with febrile seizures in comparison with the children in control group. It seems that iron insufficiency does not play a role in pediatric febrile seizures.

Is soluble transferrin receptor a good marker of iron deficiency anemia in chronic kidney disease patients?

Anemia in patients with chronic renal failure is multifactorial with an absolute or functional iron deficiency present in 60–80% of patients. In this study, 102 patients of stage 5 chronic kidney disease (CKD) were enrolled. Thirty six age- and sex-matched anemic patients without any known renal disease were taken as controls. Their sTfR levels were measured with anemia profile.(Fe, TIBC, Ferritin, TSAT). The patients were followed up twice, at four weeks and six months. There was a significant statistical difference in the mean sTfR levels in patients when compared to controls (P < 0.01).The mean level of sTfR in CKD patients was 3.23 ± 2.07 mg/l while in controls this was 5.16 ± 3.64 mg/l. sTfR had no statistically significant correlation with the levels of hemoglobin, iron, ferritin, TIBC and TSAT. We conclude that owing to complexity of iron metabolism in CKD, sTfR can not be used as a reliable marker of iron deficiency anemia.

Almost Normal Transferrin Saturation in Thalassemic Patients on Deferasirox May Predict Better Outcome

Iron overload is a serious consequence of the repeated blood transfusions required in the treatment of Thalassaemia major patients. Transferrin saturation (TfS) above 75% is a marker of iron overload of any cause. In thalassemia TfS levels can reach 80% to 100% and even higher. Most of the Non Transferrin Bound Iron (NTBI) is chelated by iron chelators. The fraction of NTBI, which in thalassemia is referred to as ‘‘directly chelatable iron”, has also recently been termed labile plasma iron (LPI). Labile iron appears in plasma and interstitial fluids when the transferrin binding capacity is surpassed. Iron chelators are agents designed to remove LPI and iron from the cells. There are now 3 different classes of iron chelators used mainly as monotherapy and one combination regimen with Desferrioxamine (DFO) and Deferiprone (DFP). Deferasirox (DFS) is a new active oral chelator. The mode of action of each chelator is different and the choice is individualized.Aim: To evaluate the effect of 4 different types of chelation therapy on TfS.Methods: Serum iron (Fe, normal range 60–180μg/dl), Total Iron Binding Capacity (TIBC, normal range 155–300μg/dl), TfS (which was calculated by the formula (serum Fex100/TIBC) and serum Ferritin were measured in 100 thalassaemia patients (46M/54F, median age 30,4 ± 8,4 years (range 18–54 years). All patients were regularly transfused (pre-transfusion hemoglobin: 9,7g/dl) and well chelated. Twenty-nine of the above-mentioned 100 patients were on DFS (Group A), 32 on DFP (Group B), 25 on combination therapy (Group C) and 14 on DFO (Group D). Median duration of therapy was 16±7 months for group A and 5,2±2,8, 3,4±2,1 and 29,8±4,3 years for groups B, C and D respectively. T-test was used in statistical analysis to compare means.Results: All patients of groups B, C and D had low levels of TIBC below normal values (40±26, 67±35 and 104±39μg/dl respectively) but patients on DFS (A) had values in the normal range (292±114μg/dl). Patients on DFS had the lowest TfS (103±46%), followed by patients on DFO (251±132%). The DFP group had the highest TfS value 1245±1510%, while the combined therapy group's value was 531±545%. Group's A ferritin was 1617±1363 ng/ml while ferritin of groups B, C and D were 1210±799, 1683±1950 and 1058±514 ng/ml respectively. Although TfS differed significantly between groups (T-test: A vs B, A vs C and A vs D: p=0,0001, p=0,0006 and p= 0,001 respectively) differences in ferritin were not statistically significant.Conclusions: TfS can theoretically be used to predict with whatever type of treatment applied, the NTBI and consequently the LPI. Very high TfS values may mean a great amount of circulating toxic NTBI which is not successfully chelated. In our patients TfS was found lowest in those on DFS. Differences in TIBC and TfS can be explained by the different mode of action of the three chelators used. Further comparative studies are needed to conclude whether DFS therapy, leads to not only the lowest TfS levels but also to the lowest LPI values. In that case it could be considered a more “reasonable” therapy than other chelators

Insights into the ethnic differences in serum ferritin between black and white US adult men

Although higher serum ferritin (SF) concentrations have been consistently observed among blacks, despite their lower hemoglobin (Hb) concentrations compared with whites, few studies attempted to explain this SF difference. To determine the possible factors contributing to the observed SF difference between blacks and whites, 1,938 non-Hispanic white (NHW) and 1,616 non-Hispanic black (NHB) male subjects, aged 20-65 years were selected from the third National Health and Nutrition Examination Survey (NHANES III). Multiple regression analysis was used to examine the contribution of dietary, biochemical, and socioeconomic variables to the observed SF difference between the two groups. NHB subjects showed a continuing, significantly higher SF concentration compared with NHW subjects at each age group. Age, serum total protein, mean cell volume (MCV), and gamma glutamyl transferase (GGT) were positively associated with SF, whereas percent energy from carbohydrate and fat, calcium intake, serum alpha-carotene, and iron binding capacity (TIBC) were inversely associated with SF (P < 0.01). After excluding subjects with abnormal serum total protein, TIBC and GGT levels from the analysis (the final regression model), the SF difference dropped to 3.95 microg/l (initial difference = 37.1 microg/l) between NHWs and NHBs. The results suggest that the oft-noted black-white SF difference is a result of factors including overall nutrition and health, iron status, and hepatic well-being. Higher SF, low Hb, and reduced TIBC level observed in blacks are consistent with the definition of anemia of chronic disease (ACD). Future investigations are needed to confirm the role of ACD in the black-white SF difference.

Supplementing iron bioavailability enhanced mung bean.

Iron deficiency anaemia is a major public health problem. The high incidence is either due to insufficient intake of iron or poor bio availability. Enhancing the bio availability is as important as increasing the intake. The absorption could be enhanced by including ascorbic acid and beta carotene containing fruits and vegetables into recipes of iron containing food preparations. The effect of supplementation of iron bio-availability enhanced mung bean preparations was studied on 75 women who were compared against 75 who served as controls and another 75 who consumed regular traditional recipes. The methodology included identification of suitable mung bean variety, assessing iron in vitro bio availability, mapping the anaemic women, estimating their iron levels, supplementation for one year and studying the effect of supplementation. Mung bean supplementation had increased serum protein levels from 5.36 to 6.73 g/dl, serum iron levels had increased from 16.6 to 46.7 microg/dl. The TIBC levels decreased from 555 to 508 microg/dl while serum ferritin levels increased from 3.56 to 5.94 microg/dl and Hb levels from 7.54 to 8.29 g/dl. Thus, improving the bioavailability of iron of food preparations, will improve the iron status of women.

Coefficient of variation of R–R intervals in electrocardiogram is a sensitive marker of anemia induced by autonomic neuropathy in type 1 diabetes

The present study investigated the relationship between hemoglobin (Hb) levels and autonomic failure using a sensitive marker, coefficient of variation of R–R intervals in electrocardiogram (CVR-R) in order to clarify a cause of normocytic normochromic anemia in type 1 diabetic patients without overt nephropathy. We recruited 46 patients with type 1 diabetes and measured creatinine clearance (Ccr), HbA1c, albuminuria, Hb levels and CVR-R of all patients. In addition, the status of diabetic retinopathy and neuropathy were also evaluated. Serum erythropoietin (EPO), Fe, total iron binding capacity, lactate dehydrogenase, total bilirubin levels and number of reticulocytes and mean corpuscular volume were also measured to distinguish types of anemia. To survey the statistical correlation existing between Hb and body mass index (BMI), Ccr, HbA1c, albuminuria or retinopathy, multiple regression analysis was performed. Serum EPO, Fe, TIBC, LDH and TB levels and number of reticulocytes and MCV were within normal limits. Multiple regression analysis disclosed that HbA1c, nephropathy evaluated by albuminuria and Ccr, and retinopathy has no concern with Hb level. There is only significant relationship between Hb levels and CVR-R. Similar results were obtained even if we analyzed a group of male and female separately. We conclude that CVR-R has the strong relationship on anemia without overt nephropathy in type 1 diabetes, indicating that autonomic failure contributes on the progression of anemia via a poor response of EPO to anemia.

Metabolic Syndrome in HD Patients: Association with Body Composition, Nutritional Status, Inflammation and Serum Iron

Insulin resistance and metabolic syndrome (MeS) are common in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Such metabolic and clinical abnormalities may lead to an increased risk for cardiovascular disease. The study group included 22 well-nourished and 20 middle- to moderate-malnourished, stable ESRD patients, with median dialysis duration of 48 months (IQR 24.5-82.0). To determine nutritional status, body composition, inflammatory biomarkers and the presence of MeS subjective global assessment (SGA), anthropometrical measurements (BMI and waist circumference), bioelectrical impedance analysis (BIA), and biochemical parameters [the levels of serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, TIBC, transferrin saturation (TSAT), ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein (hs-CRP)] were used. All parameters were evaluated by comparisons between two groups, with MeS (Group 2) and without it (Group 1). Logistical regression analysis was used to evaluate the correlation between measured variables and the presence of MeS in HD patients. Independent variables for MeS were identified by backward multivariate regression analysis. To identify the independent predictors for insulin resistance index (HOMA-IR) multivariate regression analysis was conducted, after linear regression analysis. After adjustment for confounding variables, a model consisting of serum levels of iron, transferrin saturation (TSAT), and BMI which accounted for 62% of the variance in MeS, determined only BMI as an independent marker (according to ATP-III criteria). But, serum glucose level, iron, waist and total fat mass accounted for 68% of the variance in MeS, according to IDF criteria. Glucose level was an independent predictor. BMI and iron, as independent variables, contributed to 29% of the variance in IR HOMA, the sensitive marker of MeS. The present study demonstrated that serum iron participated together with independent predictors, glucose and BMI, in the pathogenesis of IR and MeS of ESRD patients on maintenance HD.

Polymorphisms in the Transferrin 5′ Flanking Region Associated with Differences in Total Iron Binding Capacity: Possible Implications in Iron Homeostasis

ABSTRACTWe have identified five single nucleotide polymorphisms (SNPs) upstream (5′) of the transferrin coding region. One polymorphism is in the 5′ UTR at nt +49, and four are in the promoter region at nt −34, −551, −617, and −739, numbering from the start of transcription. The −34 and −617 SNPs are tightly but not completely linked. The −34 polymorphism lies between a conserved Sp1 site and the TATA box. The −617 polymorphism is within the DRII enhancer region. Five haplotypes have been defined from these SNPs by the identification of at least one homozygous individual, and two other haplotypes were deduced from heterozygous individuals. The total iron-binding capacity associated with each transferrin haplotype was haplotype 2 > 1 > 4 > 3. Transferrin promoter haplotype 2 had a significantly higher mean TIBC and haplotype 3 had a significantly lower mean TIBC than the more common haplotype 1. Persons with haplotype 4, which includes the −34T and −617A minor alleles, have a lower mean TIBC but the difference was not statistically significant. In normal individuals, the differences in the haplotypes were not found to be associated with differences in transferrin saturation and ferritin levels. There was no difference in the extent of increase in the mean TIBC levels in individuals with iron deficiency anemia in regard to their haplotype. Furthermore, there was no difference in the relative frequencies of the transferrin haplotypes in the iron-deficient population. In hemochromatosis patients who were homozygous for the C282Y HFE mutation, no particular haplotype was associated with a significant difference in transferrin saturation or ferritin levels. In White patients with Parkinson's disease, a disorder in which there is abnormal iron deposition in the brain, the presence of transferrin haplotype 3 was in slight excess over the normal White population.

Total Iron-Binding Capacity–Estimated Transferrin Correlates With the Nutritional Subjective Global Assessment in Hemodialysis Patients

We examined the value of transferrin concentrations in estimating nutritional status as determined by the subjective global assessment (SGA) score. Fifty-nine hemodialysis patients (37 men and 22 women, aged 59+/-16 years, dialyzed for 3.6+/-3.9 years) were selected by predetermined criteria. All received erythropoietin (EPO) and oral iron therapy. SGA evaluation was conducted twice by both a dietitian and a physician. Serum iron, total iron-binding capacity (TIBC; which is linearly correlated with transferrin), transferrin saturation ratio, ferritin, albumin, total protein, and cholesterol were measured. Twenty-seven (46%) patients were well nourished (group A), 20 (34%) were moderately nourished (group B), and 12 (20%) were poorly nourished (group C) according to the SGA. TIBC values were 276+/-47 mg/dL, 217+/-54 mg/dL, and 176+/-41 mg/dL, respectively (P < 0.00001), and thus directly correlated with the state of nutrition. The relationship between TIBC and nutritional status was independent of age and number of years on hemodialysis. Serum ferritin values were 104+/-93 ng/mL, 161+/-154 ng/mL, and 363+/-305 ng/mL, respectively (P < 0.0003), and thus inversely correlated with the state of nutrition. Transferrin saturation ratios were slightly higher in the severely malnourished patients. The number of years on dialysis were a determinant of nutritional status. These values were 2.4+/-2.4 years for group A, 3.9+/-4.0 years for group B, and 5.7+/-3.9 years for group C (P < 0.05). The average age of the poorly nourished patients was 10 years older than the well-nourished patients. Serum iron values were lower but transferrin saturation ratios were higher in the severely malnourished patients. The required EPO doses were higher in the poorly nourished patients. We suggest that transferrin values are superior to other laboratory tests in assessing nutrition and will supplement SGA criteria. Serum ferritin may be useful as a predictor of illness. Older patients who have been on dialysis longer warrant special concern. Malnutrition may be an indicator of EPO resistance in dialysis patients. Finally, since a decreased TIBC level in poorly nourished patients may erroneously increase the transferrin saturation ratio, our findings may have implications in making the diagnosis and treatment of anemia and iron deficiency in malnourished dialysis patients.

Systemic toxicity of a bitumen upgrading product in the rat following subchronic dermal exposure

The subchronic toxicity following dermal exposure to a synthetic fuel, heavy gas oil No. 2 fraction of bitumen upgrading product (B-HGO II) was studied in the rat. B-HGO II was applied on the dorsal skin of rats at doses of 8, 20, 50 and 125 mg/kg bw/day daily for 13 weeks. Control animals received normal saline and positive controls received a medium-boiling coal liquefaction product (CLP) at 125 mg/kg bw/day. Both male and female rats in the treatment groups had reduced body weight gain, and males in the highest dose group were terminated in the 5th week due to overt toxicity. Increased liver weight relative to body weight was observed in males and females starting at 8 mg/kg. Increased relative heart and spleen weights were observed in males and females starting at the two intermediate doses (20, 50 mg/kg). Increased relative kidney weight was detected in males at 50 mg/kg and females at 125 mg/kg. Increased serum cholesterol was observed in both sexes starting at 50 mg/kg while elevated serum glucose was present in females starting at 8 mg/kg. Significant changes in AH, APDM and EROD activities were observed in treated rats of both sexes. Reduced red blood cell counts were detected in males starting at 8 mg/kg and females at 20 mg/kg. Microscopic examination of blood smears, spleen and hemosiderin accumulation patterns, as well as analysis of FEP and serum TIBC levels indicated that the cause of anemia was primarily intravascular hemolysis and secondarily iron deficiency. Marked thymic atrophy and thyroid abnormalities were the most prominent histological changes followed by changes in bone marrow (myelofibrosis) and liver. Both B-HGO II and CLP (positive control) caused kidney changes characterized by cytoplasmic inclusions and lesions in the tubular cells, which were observed in 50 mg/kg males but not in the females. B-HGO II was considered to be toxic at a subchronic dermal exposure level as low as 8 mg/kg/day.

Effect of ferrous fumarate on the iron status and physical work capacity of women

The effect of iron supplementation (ferrous fumarate) on the iron status and physical work capacity was studied in anaemic middle class Maharastrian women. It was observed that 60% of the subjects were suffering from mild to moderate iron deficiency anaemia. The serum iron, ferritin, TIBC and transferrin saturation levels in the anaemic subjects were not only significantly lower than the levels observed in the non anaemics, but also lower than the normal values. Although the calorie and nutrient intake of the two groups was observed to be similar, it was significantly lower than the RDA suggesting no association between the diet intake and blood parameters observed. The non-anaemics had significantly better scores on the Harvard step test (used to assess the physical work capacity) in comparison to the anaemic subjects. After iron supplementation not only was a significant increase in the haematological and biochemical parameters noted (Hb + 5g/dl, serum ferritin + 35.6 ng/ml, transferrin saturation + 16%, serum iron + 45.4 mcg/dl), but also the anaemics physical work performance showed significant improvement. The above values (after supplementation) were also found to be significantly higher than the non anaemic values.

Regulation of ferritin and transferrin synthesis in hepatocytes depending on iron status of rats

In order to examine the control mechanism of ferritin (Fr) and transferrin (Tf) synthesis depending on intracellular iron levels, the rate of 14C-leucine incorporation into those proteins was investigated by cell culture of isolated hepatocytes obtained from iron deficient, iron injected and control rats. The effects of iron (ferric ammonium citrate: FeAc) and (diferric Tf: 2FeTf) or desferrioxamine (Dfo) in culture media were also examined. Serum iron, TIBC and Hb levels of iron deficient rats, which were fed an iron deficient diet for 2 and 4 weeks were significantly lower than the control. However serum iron and TIBC levels of iron injected rats which had received 30 and 45 mg iron as iron dextran 18 h before sacrifice were approximately ten times higher than the control group. The time course of 14C-leucine incorporation into Fr and Tf was investigated at the 60, 120 and 180 minutes stages of the culture. Fr synthesis was increased by the amounts of iron injected, whereas Tf synthesis showed a negative response to iron. The 14C activities in Fr and Tf detected from culture media were proportional to those in hepatocytes. The percentage of nonglycosylated Fr was 82.0-91.4% for total Fr in the culture media in every experiment, which was measured by the affinity of glycosylated Fr to Con A-Sepharose (Con A). This result suggested the leakage of cytosol Fr through the cell membrane instead of specific secretion of the sialyl protein. The efficiency of Fr and Tf synthesis was positively or negatively proportional to cellular iron contents respectively. And the curves of 14C-leucine incorporation into both proteins, calculated as the sum of those in hepatocytes and culture media intersected at the point between the 30 mg iron injected and control groups. The addition of FeAC or 2FeTf into the culture media had an indistinct effect on Fr and Tf synthesis, whereas there was a significant decrease for Fr and a slight increase for Tf formations in the Dfo supplement. These results showed the influence of cellular iron levels in Fr and Tf synthesis.

Haematological changes during parenteral nutrition of malnourished patients with an enteral disease.

The present study assesses the blood haemoglobin concentration, the mean corpuscular haemoglobin concentration and the mean corpuscular volumes, as well as the serum iron levels and the total iron binding capacities in 28 malnourished patients with an enteral disease before and after 10-12 days of pre-operative parenteral nutrition of three different kinds: one with glucose, a second with glucose and fat as energy source, and a third rich in amino acids. About half of the patients in each group also received intramuscular iron supplementation of 1.79 mmol every 2 days. Before the nutritional therapy, 54% of the patients had a subnormal serum iron level; on average, serum iron was 10.5 (SD 7.4) mumol/l. In spite of this, 50% of the patients had a TIBC level less than normal and 43% of the patients within the normal range. Ninety-three percent of the patients had an anaemia which, in most cases, was normochromic and normocytic. On average, blood haemoglobin was 110 (SD 12) g/l. After 10-12 days of parenteral nutrition, the blood haemoglobin concentration decreased independently of the quality of the intravenous alimentation, the serum iron level and the intramuscular iron supplementation. The fall in the blood haemoglobin level was on average 11.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional factors in the aetiopathogenesis of amoebic liver abscess in man

AbstractThirty‐seven patients with amoebic liver abscess and 20 controls were studied for their nutritional status. Their dietary history suggested deficient intake of total calories, protein, fat, Vitamin A and β carotene. No significant difference was observed in the levels of iron intake in patients and controls.Biochemical parameters suggested a hypoproteinemic state associated with low levels of cholesterol, VLDLc, HDLc, Vitamin A, β carotene, iron and TIBC in the patients in comparison to controls. The protein electrophoresis pattern showed an increase in α1, α2, and γ fractions in patients compared with controls, whereas the albumin fraction was reduced.On the basis of these findings and previously published experimental studies, it is suggested that amoebic liver abscess in human subjects is associated with undernutrition due to a poorly balanced diet. Thus, undernutrition may facilitate invasive amoebiasis in man.

Iron stores in users of oral contraceptive agents

A comparison of serum ferritin and other parameters of iron status was made between 46 women taking oral contraceptive agents (OCAs) for two or more years continuously and 71 women who never took OCAs. The mean serum ferritin level for the OCA users was 39.5 +/- 21.5 ng/ml and the control group mean level was 25.4 +/- 15.96 ng/ml, which is significantly different at p less than 0.001. Serum transferrin, serum iron, TIBC, MCH and MCHC levels were significantly greater for the OCA users group. Significantly lower RBC and hematocrit levels were found for OCA users while other parameters, hemoglobin, MCV and percent transferrin saturation, were not significantly different. No major differences in subject characteristics and dietary traits were evidenced, except a difference in reported menstrual cycle losses and a higher heme iron content in the diet of the OCA users.