Serum ferritin concentration as an index of storage iron in rheumatoid arthritis

Serum ferritin concentration has been compared with semi-quantitative histochemical estimates of bone marrow iron deposits in 60 anaemic patients with rheumatoid arthritis. There was considerable variation in the visual assessment of iron stores made by different observers. Serum ferritin appears to be a particularly sensitive index of iron status when stores are low. The best means of detecting iron deficiency in rheumatoid arthritis are discussed.     

Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India

Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value < 1.5 were classified as pure ACD and patients with sTfR-F index value> 1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.     

Serum copper concentration as an index of cardiopulmonary injury in monocrotaline-treated rats

The pyrrolizidine alkaloid monocrotaline produces pulmonary inflammation, hemorrhage, fibrosis, and hypertension. In rats, monocrotaline pneumotoxicity can be ameliorated by cotreatment with inhibitors of angiotensin converting enzyme (ACE), such as CL242817. In the present study, serum and urine copper (Cu) concentrations were evaluated as indices of cardiopulmonary injury in rats sacrificed after six weeks of continuous administration of monocrotaline (0 to 3.6 mg per kg per day, in the drinking water) or CL242817 (60 mg per kg per day, in the feed), or both. Monocrotaline-treated rats exhibited dose-dependent increases in (1) pulmonary histopathology, (2) pulmonary endothelial dysfunction (decreased lung plasminogen activator activity, and increased prostacyclin and thromboxane production), (3) pulmonary hydroxyproline (collagen) content, and (4) cardiac right ventricular hypertrophy (an anatomic correlate of pulmonary hypertension). The severity of cardiopulmonary damage was accompanied by a dose-dependent elevation in serum Cu concentration. Serum iron concentration, in contrast, did not change. Urinary Cu concentration correlated roughly with that of serum, but the variability within groups was high. Cotreatment with the ACE inhibitor CL242817 not only ameliorated monocrotaline-induced right heart enlargement and lung hydroxyproline accumulation but also reduced the hypercupremia in monocrotaline-treated rats. Thus, serum copper concentration appears to be an accurate and minimally invasive index of monocrotaline pneumotoxicity in this model of pulmonary hypertension.     

Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: A conceptual framework

Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection.     

Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: A conceptual framework

Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection.     

Respiratory sinus arrhythmia as an index of emotional response in young adults

The relationship between respiratory sinus arrhythmia (RSA) and valence and arousal remains unclear. In the present study, the associations between emotion responses and tonic or task-related changes in RSA were assessed. Specifically, the sensitivities of changes in interbeat interval, RSA, and skin conductance to the valence and arousal values of emotional stimuli were examined. This study also explored the association between tonic RSA and subjective, expressive, and physiological emotional responses. Response measures were collected from 56 adults during baseline and film-viewing periods. Tonic RSA was not significantly related to any of the response measures. Increased skin conductance and decreased RSA were associated with arousal independent of valence. Interbeat interval was related to affective valence and not arousal. These findings suggest that RSA may be a useful adjunct to skin conductance measures in assessing emotional arousal.     

The utility of changes in cardiac weight as an index of drug-induced cardiotoxicity

The effects of toxic doses of various drugs and of food or water deprivation upon heart weights of mice were evaluated over a four day period to test the validity of the hypothesis that changes in cardiac weights are indicators of cardiotoxicity. Drugs included in the study were actinomycin-D, methotrexate, 5-fluorouracil, adriamycin, daunomycin, N-dimethyladriamycin, N-trifluoroacetyladriamycin-14-valerate, isoproterenol, atropine, and acetylsalicylic acid. Additional groups of mice served as vehicle controls, or were deprived of food or water for the duration of the experiment to control for the anorexia and dehydration accompanying treatment with antineoplastic drugs. Body weights were taken at the start of the experiment (day 0), day 2, and day 4 (just prior to sacrifice). Heart ventricle wet weights were determined immediately, and dry weights after thorough desiccation of the samples. Statistical evaluation of the weights revealed that there were no ventricular weight changes unique to any particular drug, and that decreases in heart weights correlated well with decreases in body weights, thereby reflecting the general toxicities of the drugs, including inanition, and not any specific cardiotoxicities.     

Clinical utility of serum soluble transferrin receptor levels and comparison with bone marrow iron stores as an index for iron-deficient erythropoiesis in a heterogeneous group of patients

AIM: To evaluate the correlation between raised soluble transferrin receptor (sTfR) and stainable marrow iron, and to define the utility of sTfR in discriminating between the presence or absence of iron-deficient erythropoiesis in patients with anaemia of chronic disease. METHODS: Seventy-six consecutive adult patients without accelerated erythropoiesis who had undergone bone marrow (BM) aspiration/trephine for various clinical reasons during 2003-2006 were studied. All patients had serum iron studies (iron, transferrin and ferritin) and sTfR performed within 1 week of BM aspiration/trephine. These 76 patients were assigned to three groups based on the iron status of the BM and sTfR level: patients with normal sTfR and normal BM iron stores (n = 49), patients with an elevated sTfR and normal BM iron stores (n = 13) and patients reduced or absent BM iron stores (n = 14). Means (95% confidence interval) for mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), red blood cell haemoglobin (RBC Hb) content and median (5th and 95th percentiles) for haemoglobin were then calculated. RESULTS: All patients with absent BM iron stores had an elevated sTfR level. Patients with normal BM iron stores and elevated sTfR levels had significantly lower Hb, MCV, MCHC and RBC Hb content than patients with normal BM iron stores and normal sTfR levels. CONCLUSION: sTfR is the most sensitive serum biochemical marker for the identification of iron-deficient erythropoiesis. Normal BM iron stores can coexist with elevated sTfR and decreased MCV and MCHC. sTfR levels correlate better than BM iron stores with decreased MCV and MCHC. Therefore, sTfR is a useful marker of iron-deficient erythropoiesis, due to both absent iron stores, and restricted iron supply due to anaemia of chronic disease. As a single investigation, however, sTfR does not discriminate between these two causes of iron-deficient erythropoiesis.     

Serum glutathione S-transferase B1 activity as an index of liver function in cystic fibrosis.

AIMS--To evaluate serum glutathione S-transferase B1 (GST B1), a highly sensitive test of hepatocellular function, as a means of identifying liver disease in patients with cystic fibrosis (CF). METHODS--The presence of liver disease was sought over a three year period in 60 children with CF, using a combination of clinical assessment, ultrasound examination, conventional biochemical tests of liver function (LFTs), and measurement of GST B1. RESULTS--Reference ranges for serum GST B1 were established in a paediatric control population. The 95% value (4.55 micrograms/l) was similar to the upper limit of normal previously derived in adults. Mean (SE) serum GST B1 activities were higher in the CF population (9.0 (1.14) micrograms/l) than in age matched controls (2.4 (0.15) micrograms/l). Ten patients with CF showed clinical signs of liver dysfunction. All but one had a serum GST B1 > 4.55 micrograms/l. Twelve other patients had elevated LFTs without clinically evident liver dysfunction, six had abnormal ultrasound scans and two showed both of these anomalies. Thirty patients with CF had neither biochemical, ultrasonographic nor clinical signs of liver disease. On review three years later, clinically important liver disease was reaffirmed in eight of the 10 index cases and had become apparent in a further eight, all of whom had elevated GST B1 activities. Five (36%) of the patients with elevated LFTs and two (33%) with isolated ultrasound changes continued to show these abnormalities. CONCLUSIONS--The limitations of conventional LFTs and ultrasound scans were evident from this study. The results suggest that elevated GST B1 activities may be a better predictor of hepatic dysfunction in CF than conventional LFTs.     

Serum IgD elevation is an early marker of B cell activation during infection with the human immunodeficiency viruses.

Serum IgD levels in individuals infected with the human immunodeficiency viruses (HIV) were studied as a means of monitoring the character and timing of B cell activation in individuals with this infection. Significantly increased levels of IgD were characteristic of homosexual men who were HIV seropositive but asymptomatic or mildly symptomatic. The hyper IgD globulinaemia became progressively more pronounced in patients with increasingly severe infection and reached its most marked level in patients with AIDS-related complex (ARC). In ARC patients, IgD levels were increased 8.8-fold above normal which was disproportionately greater than the 2.4-fold increase in IgG, the 1.8-fold increase in IgA and the 1.6-fold increase in IgM. IgD levels declined in AIDS patients (although remained elevated compared to controls). The data suggest that an unusual type of B cell activation is responsible for the unique pattern of hypergammaglobulinaemia seen in this disease and that the B cell activation occurs early in the pathogenesis of HIV infection, often before development of symptoms, and continues throughout the course of infection.