Soluble transferrin receptor and zinc protoporphyrin – competitors or efficient partners?

OBJECTIVES: Soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP) are both parameters of iron deficient erythropoiesis (IDE), the sTfR measurement is commonly regarded to be the more sensitive test. sTfR also reflects erythropoietic activity, it is increased in enhanced erythropoiesis. METHODS: We investigated the diagnostic accuracy of sTfR in assessment of iron deficiency (ID) and compared it with ZPP. The study was performed on 174 subjects, in which ID has been precisely staged. RESULTS: Individuals without ID and patients with storage iron depletion only, had normal sTfR values. Patients classified as IDE and patients with iron deficiency anemia had significantly increased sTfR. There was a good correlation between sTfR and hemoglobin (r = -0.86; P < 0.0001) and between sTfR and ZPP (r = 0.86; P < 0.0001). When diagnosing ID, ZPP was the more sensitive test. In mildly developed IDE associated with ZPP-ratios between 40 and 70 micromol/mol heme, the sTfR concentration was elevated in only 25% of the cases. Reliably elevated sTfR values were observed only in more advanced IDE, associated with ZPP > 70 mumol/mol heme. CONCLUSIONS: ZPP is not inferior to sTfR when diagnosing IDE. Given the good correlation between sTfR and ZPP and because ZPP is uninfluenced by the erythropoietic activity, sTfR and ZPP are not competitors, rather efficient partners in diagnosing anemias. By measuring ZPP and sTfR simultaneously, the diagnostic uncertainty inherent in each of them individually can be eliminated. In particular, the simultaneous determination of ZPP and sTfR enhances the diagnostic power of sTfR in assessment of the erythropoietic activity.     

Pulmonary function and bronchial reactivity in asthmatics during low-level formaldehyde exposure

This study evaluated whether formaldehyde, at concentrations similar to those found in the indoor environment, could produce adverse effects on the lower airway of 15 asthmatic persons with documented bronchial hyperresponsiveness who were exposed for 90 min in a climate chamber to clean air containing formaldehyde vapor at levels of 0.85 mg/m3, 0.12 mg/m3, and 0.008 mg/m3. No significant changes in forced expiratory volume in 1 sec (FEV1), airway resistance (Raw), specific airway resistance (SRaw), and flow-volume curves could be detected during formaldehyde exposure. Furthermore, histamine challenge tests performed immediately after formaldehyde exposure showed no evidence of changes in bronchial reactivity. No late reactions were registered during the first 14-16 hr after exposure. The results suggest that residential levels of formaldehyde are of minor importance in the emergence of pulmonary symptoms. Discrepancies between the present study and previous data may be due to differences in environmental conditions.     

Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure

BACKGROUND: Congestive heart failure (CHF) has previously been shown to be associated with insulin resistance and hyperinsulinemia. A beneficial effect of the non-selective beta-blocker carvedilol has been demonstrated in patients with CHF. However, whether the drug affects the insulin sensitivity (S(i)) is unknown. AIMS: To investigate whether treatment with carvedilol alters the S(i) in patients with CHF during a prospective, double-blinded, placebo-controlled study. METHODS AND RESULTS: The patients were randomized to receive either carvedilol (n=29) or matched placebo (n=17). Insulin and glucose responses were measured during a 0.3 g/kg intravenous glucose tolerance test, and S(i) was calculated according to Bergman's Minimal Model. Baseline S(i) values correlated significantly with body mass index (r=-0.42, P=0.002), plasma urate (r=-0.42, P=0.002), plasma HDL-cholesterol (r=0.39, P=0.003), maximal oxygen uptake (r=0.35, P=0.009), plasma triglycerides (r=-0.34, P=0.01) and weight (r=-0.29, P=0.03). During the study the insulin sensitivity was unchanged in the carvedilol group compared with placebo (2.63+/-1.45 to 2.38+/-1.64 vs. 2.81+/-2.36 to 2.48+/-1.84x10(-4) min(-1)/mUl(-1), P=0.83). CONCLUSION: Additional treatment with carvedilol is neutral with regard to influence the insulin sensitivity in patients with mild to moderate CHF.     

Effect of exercise on natriuretic peptides in plasma and urine in chronic heart failure

BACKGROUND: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in chronic heart failure (CHF). ANP is known to be increased during exercise in healthy subjects and CHF, while the response in BNP during exercise is less clear and does not exist in C-type natriuretic peptide (CNP) and aquaporin-2 (AQP2) in either healthy subjects or CHF. METHODS: Eleven patients with CHF and eleven healthy subjects performed a maximal aerobic exercise test. ANP and BNP in plasma were determined every 3 min and at maximum exercise by radioimmunoassay (RIA) and CNP and AQP2 in urine were determined before and after the exercise test by RIA. RESULTS: The absolute increase in BNP during exercise was higher in patients with CHF (CHF: 4.1 pmol/l; healthy subjects: 1.3 pmol/l, P<0.05) and was positively correlated to BNP at rest (P<0.05), while the absolute increase in ANP during exercise was the same in the two groups (CHF: 4.2 pmol/l; healthy subjects: 6.8 pmol/l, not significant, NS). In CHF, exercise did not change either u-CNP excretion (rest: 9.8 ng/mmol creatinine; after exercise: 8.8 ng/mmol, NS) or u-AQP2 (rest: 466 ng/mmol creatinine; after exercise: 517 ng/mmol creatinine, NS) as well as in healthy subjects where u-CNP (rest: 9.7 ng/mmol creatinine; after exercise: 9.2 ng/mmol creatinine) and u-AQP2 (rest: 283 ng/mmol creatinine; after exercise: 307 ng/mmol creatinine) were the same at rest and after exercise. CONCLUSION: The absolute increase in BNP during exercise is higher in patients with CHF compared to healthy subjects. It is suggested that this is a compensatory phenomenon to improve the exercise capacity in CHF, and that BNP is a more important factor in cardiovascular homeostasis during exercise in CHF than ANP.     

The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

CONTEXT: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. OBJECTIVES: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.     

Variability and effect sizes of intracranial current source density estimations during pain: Systematic review,experimental findings,and future perspectives

Pain arises from the integration of sensory and cognitive processes in the brain, resulting in specific patterns of neural oscillations that can be characterized by measuring electrical brain activity. Current source density (CSD) estimation from low‐resolution brain electromagnetic tomography (LORETA) and its standardized (sLORETA) and exact (eLORETA) variants, is a common approach to identify the spatiotemporal dynamics of the brain sources in physiological and pathological pain‐related conditions. However, there is no consensus on the magnitude and variability of clinically or experimentally relevant effects for CSD estimations. Here, we systematically examined reports of sample size calculations and effect size estimations in all studies that included the keywords pain, and LORETA, sLORETA, or eLORETA in Scopus and PubMed. We also assessed the reliability of LORETA CSD estimations during non‐painful and painful conditions to estimate hypothetical sample sizes for future experiments using CSD estimations. We found that none of the studies included in the systematic review reported sample size calculations, and less than 20% reported measures of central tendency and dispersion, which are necessary to estimate effect sizes. Based on these data and our experimental results, we determined that sample sizes commonly used in pain studies using CSD estimations are suitable to detect medium and large effect sizes in crossover designs and only large effects in parallel designs. These results provide a comprehensive summary of the effect sizes observed using LORETA in pain research, and this information can be used by clinicians and researchers to improve settings and designs of future pain studies.     

High frequency of MYC gene amplification is a common feature of radiation‐induced sarcomas. Further results from EORTC STBSG TL 01/01

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.