Clinical Chemistry and Laboratory Medicine (CCLM)

Published by De Gruyter

Volume 41 Issue 8

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Contents
Journal Overview

October 7, 2005

SIBioC 2003 35th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, Florence, Italy, 14–17 October 2003

Page range: A37-A60

June 1, 2005

Vitamins and Trace Elements: The Distances between Deficiency and Repletion and between Care and Prevention

Jean-Louis Guéant, Layachi Chabraoui

Page range: 977-978

June 1, 2005

Factors Affecting Intestinal Absorption of Highly Lipophilic Food Microconstituents (Fat-Soluble Vitamins, Carotenoids and Phytosterols)

Patrick Borel

Page range: 979-994

Abstract

Highly lipophilic food microconstituents (HLFMs) with octanol-water partition coefficients log 10 p c > 8 include the fat-soluble vitamins (A, E, D and K) and phytochemicals with potential health benefits, the carotenoids and phytosterols. It has been assumed that these compounds have the same metabolism in the human upper gastrointestinal tract and that they follow the same fate as lipids. However, a literature review shows that the metabolism of HLFMs in the upper gastrointestinal tract depends on each HLFM species. For example, some HLFM esters are hydrolyzed mainly by pancreatic lipase, others by bile salt-stimulated lipase; some HLFMs are apparently absorbed by passive diffusion, others by a transporter. Also, although some factors (HLFM molecular species, fat, food matrix) affect absorption efficiency of most HLFMs, other factors (fibers, microconstituents) apparently affect absorption only of some HLFMs. The mnemonic acronym SLAMENGHI, previously proposed to list the factors affecting the bioavailability of carotenoids, was used here to review current knowledge of the factors suspected to affect the intestinal absorption of HLFMs. The available data reveal numerous gaps in the knowledge of the metabolism of HLFMs and the factors that affect their absorption. These gaps need to be filled to be able to formulate HLFMs so as to promote greater absorption efficiency.

June 1, 2005

Protective Effects of Antioxidant Micronutrients (Vitamin E, Zinc and Selenium) in Type 2 Diabetes Mellitus

Patrice Faure

Page range: 995-998

Abstract

Type 2 diabetes (T2D) is a major cause of vascular complications affecting heart, kidney, retina and peripheral nerves. Hyperglycaemia leads to oxidative stress that plays an important role in vascular degenerative lesions observed in diabetes. In this Review we consider whether vitamin E, zinc or selenium are involved in the pathogenesis of diabetes. Concerning vitamin E, major epidemiological studies do not give the expected results in preventing cardiovascular outcomes. The mechanisms of free radical overproduction in diabetes could explain these results. Superoxide anion overproduction originates from mitochondria; in these conditions antioxidant enzymes are more relevant to reduce oxygen species than vitamin E. Zinc has numerous targets to modulate insulin activity, including its antioxidant capacity. Zinc status is decreased in most T2D patients. The effect of zinc supplementation on antioxidant status is raised when complications are associated. Selenium is a major antioxidant trace element and is the co-factor of glutathione peroxidase (Se GSHpx). Low Se GSHpx activity, observed in diabetic patients, is associated with thrombosis and cardiovascular complications.

June 1, 2005

Biofactors in the Mediterranean Diet

Mariette Gerber

Page range: 999-1004

Abstract

This Review covers the sources and the main effects on human health of well-known micronutrients such as minerals and vitamins and also of microconstituents contained in the Mediterranean diet. Vitamins were first identified because of deficiency diseases still present in certain parts of the world. Hydrosoluble vitamins, among them folic acid and vitamin C, also play a role in chronic degenerative diseases, not only the main cause of mortality in the Western world but also increasingly common in developing countries. Hydrosoluble vitamins are well represented in the Mediterranean diet, more so than vitamin A, a liposoluble vitamin obtained primarily from animal foods. Vitamin E is important for antioxidant and cellular functions. The Mediterranean diet is also rich in provitamins A, such as α-and β-carotene and β-cryptoxanthine. Microconstituents are non-nutritional compounds known to protect plants and more recently suspected to have a protective effect in humans. They play a role in the antioxidant defense of the organism, but their effect on various enzyme activities appears even more promising and is still under investigation. It is nevertheless difficult to isolate the effect of the numerous biofactors present in the Mediterranean diet from the foods themselves, especially because of the possible synergy between the various biofactors.

June 1, 2005

The Effect of Selenium on Immune Functions of J774.1 Cells

Nadia Safir, Albrecht Wendel, Rachid Saile, Layachi Chabraoui

Page range: 1005-1011

Abstract

The J774.1 macrophage cell line was used as a tool to investigate the influence of selenium on macrophage function. In vitro selenium supplementation enhanced phagocytosis, degranulation by the release of β-glucuronidase after N-formyl-methionyl-leucyl-phenylalanine (FMLP) or cytochalasin B, and the production of superoxide anion after phorbol myristate acetate stimulation of these cells, while the release of nitric oxide was not affected by the selenium status. Selenium supplementation enhanced significantly (p < 0.05) the release of tumor necrosis factor (5-fold), interleukin-1 (3-fold) and interleukin-6 (2.5-fold) after 10 μg/ml lipopolysaccharide stimulation compared to selenium-deficient cells.

June 1, 2005

Effects of Vitamin B12 and Folate Deficiencies on DNA Methylation and Carcinogenesis in Rat Liver

Laurent Brunaud, Jean-Marc Alberto, Ahmet Ayav, Philippe Gérard, Farès Namour, Laurent Antunes, Marc Braun, Jean-Pierre Bronowicki, Laurent Bresler, Jean-Louis Guéant

Page range: 1012-1019

Abstract

Deficiencies of the major dietary sources of methyl groups, methionine and choline, lead to the formation of liver cancer in rodents. The most widely investigated hypothesis has been that dietary methyl insufficiency results in abnormal DNA methylation. Vitamin B 12 and folate also play important roles in DNA methylation since these two coenzymes are required for the synthesis of methionine and S-adenosyl methionine, the common methyl donor required for the maintenance of methylation patterns in DNA. The aim of this study was to review the effects of methyl-deficient diets on DNA methylation and liver carcinogenesis in rats, and to evaluate the role of vitamin B 12 status in defining carcinogenicity of a methyl-deficient diet. Several studies have shown that a methyl-deficient diet influences global DNA methylation. Evidence from in vivo studies has not clearly established a link between vitamin B 12 and DNA methylation. We reported that vitamin B 12 and low methionine synthase activity were the two determinants of DNA hypomethylation. Choline- or choline/methionine-deficient diets have been shown to cause hepatocellular carcinoma in 20–50% of animals after 12–24 months. In contrast, the effect of vitamin B 12 withdrawal, in addition to choline, methionine and folate, induced hepatocellular carcinoma in less than 5% of

June 1, 2005

Trace Elements, Innate Immune Response and Parasites

Maria Teresa Rivera, Andrea Pereira De Souza, Tania Cremonini Araujo-Jorge, Solange Lisboa De Castro, Jean Vanderpas

Page range: 1020-1025

Abstract

Micronutrient deficiencies and infectious disease often coexist and show complex interactions leading to mutually reinforced detrimental clinical effects. Such a combination is predominantly observed in underprivileged people of developing countries, particularly in rural regions. Several micronutrients such as trace elements (zinc, iron, selenium) modulate immune function and influence the susceptibility of the host to infection. Nevertheless, the effect of individual micronutrients on components of innate immunity is difficult to design and interpret. Micronutrient deficiency, in general, has a widespread effect on nearly all components of the innate immune response. Chagas' disease is a pertinent model to study interaction of nutrition, immunity and infection, as it implies many components of innate immunity. An important question is whether alterations on micronutrient intake modify the course of infection. Some interactions of trace elements with innate immunity and acute inflammatory response are reviewed in this article with a special focus on selenium deficiency and Trypanosoma cruzi infection

June 1, 2005

Clinical B12 Deficiency in One Case of Recurrent Spontaneous Pregnancy Loss

Mirande Candito, Sarah Magnaldo, Jacques Bayle, Jean-François Dor, Yves Gillet, André Bongain, Emmanuel Van Obberghen

Page range: 1026-1027

Abstract

Moderate hyperhomocysteinaemia (HHcy) and the homozygous mutation C677T in the 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene are associated with increased risk of recurrent pregnancy loss. This HHcy is currently reported as a consequence of folate rather than of vitamin B 12 -deficient status. We describe one case of recurrent early pregnancy loss with HHcy caused by B 12 deficiency. A 38-year old woman had four episodes of early spontaneous pregnancy loss. Biological data: no haemostasis disorders, HHcy (25.9 μmol/l), normal folate (5 ng/ml), B 12 deficiency (<150 pg/ml) and the MTHFR C677T homozygote genotype. A bone marrow biopsy gave evidence of moderate megaloblastosis. Parenteral B 12 therapy led to normal homocysteine level within 2 months and to a successful pregnancy. In conclusion, vitamin B 12 deficiency is one of the causes of recurrent pregnancy loss associated with HHcy, and serum B 12 should be measured systematically in this circumstance.

June 1, 2005

Low Frequency of Mutated Methylenetetrahydrofolate Reductase 677 C→T and 1298 A→C Genetics Single Nucleotide Polymorphisms (SNPs) in Sub-Saharan Populations

Charles E. Adjalla, Emile K. Amouzou, Ambaliou Sanni, Idrissia Abdelmouttaleb, Nicodème W. Chabi, Fares Namour, Batoma Soussou, Jean-Louis Guéant

Page range: 1028-1032

Abstract

5,10-Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are two of the key enzymes in the folate/vitamin B 12 -dependent remethylation of homocysteine to methionine. The frequencies of MTHFR single nucleotide polymorphisms (SNPs), 677C → T, 1298A → C, 1317T → C and of MTR, 2756A → G , have been widely studied in Caucasians, but they have never been reported simultaneously in a large population from Sub-Saharan Africa. Presently, we report the prevalence of these SNPs and their relationship to homocysteine in 240 subjects recruited in West Africa. The frequencies of the mutant genotypes 677TT (0.8%) and 1298CC (2%) were lower than that usually observed in Caucasians, while the frequency of the mutant 1317CC was higher (16%). We formed a systematic association of the mutated MTHFR 677C → T SNP with a 1298A/1317T common haplotype. The MTHFR mutant genotype 677TT was associated with an intermediate hyperhomocysteinemia (92.4±6.0 μmol/l) higher than that described in Caucasians. The 2756A → G SNP in the MTR was similarly distributed in Africans compared to Caucasians. In conclusion, the MTHFR 677TT or 1298CC genotypes are much rarer in Africans than in Caucasians. The 677TT low frequency may be related to the high effect of this mutation on homocysteine metabolism in the environmental conditions of this African region.

June 1, 2005

A Two-Step Method for the Extraction of High-Quality RNA from Endoscopic Biopsies

Thomas Wex, Gerhard Treiber, Uwe Lendeckel, Peter Malfertheiner

Page range: 1033-1037

Abstract

The use of molecular techniques such as quantitative RT-PCR depends on the quality of cellular RNA. In particular, RNA extraction from endoscopic biopsies is difficult with respect to yield, and especially integrity. Endoscopic biopsies taken from the gastric antrum, corpus and duodenum were subjected to various RNA extraction protocols, and the RNA was used for quantitative RT-PCR. The subsequent use of two methods, (i) a phenol/chloroform extraction and (ii) a columnbased extraction method, resulted in a yield of 4.5 μg total RNA per biopsy with reliable quality in 80% of samples. The quantitative RT-PCR analysis revealed that only RNA samples that clearly show both 18S-and 28S-RNA bands in agarose gel electrophoresis were suitable for quantitative RT-PCR as shown by expression of corpus-specific pepsinogen C-mRNA and the duodenum-specific multi-drug resistance protein-1 (mdr-1)-mRNA. In partially degraded RNA, pepsinogen C, mdr-1, or β-actin mRNAs were still detectable, but the quantitative determination gave inconsistent data. The two-step method described here is a suitable option for extracting high-quality RNA from endoscopic biopsies when other standard protocols fail.

June 1, 2005

Assay for Cross-Linked Carboxyterminal Telopeptide of Type I Collagen (ICTP) Unlike CrossLaps Assay Reflects Increased Pathological Degradation of Type I Collagen in Rheumatoid Arthritis

Mirja-Liisa Sassi, Sari Åman, Markku Hakala, Reijo Luukkainen, Juha Risteli

Page range: 1038-1044

Abstract

We compared the ability of assay for cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and CrossLaps assay to reflect increased pathological degradation of type I collagen in serum and synovial fluid samples of patients with rheumatoid arthritis (RA; n = 40). ICTP and CrossLaps concentrations were correlated with each other and with markers of collagen synthesis (PINP and PIIINP, amino terminal propeptides of type I and type III procollagens, respectively) and with markers of inflammation, i.e. , C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum ICTP was increased in half of the RA patients, whereas CrossLaps assays were increased only occasionally. Serum ICTP correlated with the other markers of collagen metabolism as well as with CRP and ESR. Serum CrossLaps correlated only with PINP and ICTP, but not with serum PIIINP, CRP or ESR. Two patients had false-positive reactions in the CrossLaps assay due to the rheumatoid factor. The ICTP and CrossLaps antigens were clearly separate peaks in gel filtration analysis. The CrossLaps assay is able to detect the same ICTP antigen, but not vice versa . The ICTP assay reflects increased matrix metalloproteinase-mediated collagen degradation in joints in RA. In contrast, the physiological cathepsin K-mediated bone resorption measured by the CrossLaps assay was only occasionally increased.

June 1, 2005

Stimulatory Effect of Homocysteine on Interleukin-8 Expression in Human Endothelial Cells

Jürgen Geisel, Verena Jödden, Rima Obeid, Jean Pierre Knapp, Marion Bodis, Wolfgang Herrmann

Page range: 1045-1048

Abstract

Elevated plasma homocysteine is an independent risk factor for atherosclerosis. An important initial step of atherosclerosis is the adhesion and infiltration of monocytes to the lesion site. It has been shown that the pro-inflammatory cytokine interleukin-8 can rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin. The objective of the present study was to investigate the effect of homocysteine on interleukin-8 production in human endothelial cells. Cells were incubated with various concentrations of homocysteine for 20 h. The gene expression was determined by real-time PCR and the interleukin-8 protein was measured by immunoassay analysis. Homocysteine enhanced the expression of interleukin-8 in a dose-dependent manner (181% of controls at 2.5 mmol/l homocysteine). Stimulation of gene expression was associated with a parallel increase in interleukin-8 protein synthesis (160% of controls at 5.0 mmol/l homocysteine). By co-incubation of endothelial cells with homocysteine and copper sulfate, a further elevation of interleukin-8 expression (251% of controls) was observed, whereas copper sulfate alone had no stimulatory effect. In conclusion, the present study demonstrated that homocysteine altered endothelial cell function by stimulating interleukin-8 expression, suggesting a contribution of homocysteine to the initiation and progression of atherosclerosis. The formation of homocysteine-induced oxidation products might serve as one of the underlying mechanisms of this effect.

June 1, 2005

Sensitive and Specific Photometric Determination of Mannitol in Human Serum

Hendrik Graefe, Barbara Gütschow, Hartmut Gehring, Leif Dibbelt

Page range: 1049-1055

Abstract

Mannitol is an osmotically active polyalcohol often present in fluids used for irrigation of exposed tissue during minimal invasive surgery. Since this polyol normally is not detected in human plasma to any significant extent, it may be used as a laboratory marker of absorption of mannitol-containing irrigative fluids during surgery. For this aim, we developed a photometric assay of mannitol in human blood or serum that may be performed in a near-patient setting. Following deproteinization of the sample with trichloroacetic acid, the supernatant is mixed with NAD+ and a commercially available preparation of mannitol 2-dehydrogenase and is incubated at pH7.8 and at 37 °C for 30 to 60 minutes. At the end of the incubation period the solution is appropriately diluted and the concentration of NADH formed by oxidation of mannitol is determined photometrically at 340 nm. The limit of detection of serum mannitol with this assay is 0.05 mmol/l, the linear range of measurement extends to about 3 mmol/l. At analyte concentrations of 0.48, 1.38 and 3.48 mmol/l, coefficients of inter-assay variation of 12.1, 6.7 and 4.9%, respectively, were obtained. The analytical recovery of mannitol added to serum samples was close to 100%. Of 27 polyalcohols, monosaccharides and oligosaccharides tested, none exhibited a measurable substrate activity and only D-fructose significantly inhibited the oxidation of mannitol at sample concentrations above 10 mmol/l; the enzymatic reaction, however, was strongly affected by EDTA. The suitability of the assay as a routine diagnostic tool for detection and quantification of intraoperatively absorbed irrigation fluid was demonstrated by analyzing mannitol in serum samples obtained from 24 patients undergoing transurethral prostatectomy.

June 1, 2005

Assessment of Hypolactasia and Site-Specific Intestinal Permeability by Differential Sugar Absorption of Raffinose, Lactose, Sucrose and Mannitol

Jan Hessels, Harry H. M. Eidhof, Jan Steggink, Wilfried W. H. Roeloffzen, Kalung Wu, Guy Tan, Jan van de Stadt, Leo van Bergeijk

Page range: 1056-1063

Abstract

The sugar absorption test is a non-invasive test for investigating intestinal permeability by simultaneous measurement of four probe sugars. In this study, we evaluated the utility of raffinose, lactose, sucrose and mannitol as probe sugars and calculated their urinary recovery as a percentage of ingested dose (mol/mol) and the recovery ratios of raffinose/mannitol, lactose/raffinose and sucrose/raffinose. The reference ranges for these ratios, established from 39 healthy volunteers, are 0.005–0.015, 0.13–0.63 and 0.09–0.47, respectively. This sugar absorption test was performed in three patient groups. i) In 109 patients with aspecific gastrointestinal symptoms of whom intestinal histology was studied by duodenal biopsies: the urinary raffinose/mannitol recovery ratio highly correlated with gradation of duodenal damage; the sensitivity and specificity of the raffinose/mannitol ratio for detection of intestinal damage were 93% and 91%, respectively, using a cut-off level of 0.020. ii) In 70 patients in whom intestinal lactase activity was investigated by the lactose tolerance test: the urinary lactose/raffinose recovery ratio provided high diagnostic accuracy for hypolactasia (sensitivity 81% and specificity 89% at a cut-off level of 0.70). In analogy with the lactose/raffinose ratio, we suppose that the sucrose/raffinose ratio can be used as a marker of hyposucrasia. iii) In 40 patients with localized small intestinal damage, Crohns disease of the ileum (n = 21) and celiac disease with histologically proven duodenal damage (n = 19): the raffinose/mannitol recovery ratio was increased in 100% of patients with celiac disease and in 81% of patients with Crohns disease; increased lactose/raffinose recovery ratio (hypolactasia) and increased sucrose/raffinose (hyposucrasia) were present in 89% and 95% of celiac patients and 19% and 0% of Crohn's disease patients, respectively. The combination of the raffinose/mannitol ratio and sucrose/raffinose ratio appears to be an indication of the distribution of intestinal damage.

June 1, 2005

Human Plasminogen Is Highly Susceptible to Peroxynitrite Inactivation

Alejandro Gugliucci

Page range: 1064-1068

Abstract

It has been shown that diabetic patients have up to three-fold increases in plasma nitrated tyrosine. We hypothesize that nitration of plasminogen could impair its catalytic properties and be a factor in diabetic thrombogenicity. To test this hypothesis, in this study we addressed the effects of the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) on human streptokinase-induced plasmin activity. Given the link between glycation and oxidation we also explored whether peroxynitrite enhances the effect of fructose (1–5 mmol/l) and glucose (5–50 mmol/l) on plasminogen. We provide evidence that plasminogen, but not antithrombin III, is quickly inactivated by exogenously generated peroxynitrite (0–20 mmol/l SIN-1), in a timeand dose-dependent manner. The effect occurs even when the molar ratio of other plasma proteins and key antioxidants is respected. In our system, peroxynitrite did not enhance the effect of the sugars. Preincubation of the sugars with peroxynitrite also failed to produce any effect. This suggests that in conditions and times approaching the in vivo situation, plasminogen is more susceptible to peroxynitrite damage than to carbonyl damage. Plausibly, nitration of tyrosine should play a critical role in either conformational or functional changes. If proven in ulterior in vivo studies, this factor would provide another mechanism by which nitrosative stress participates in diabetic complications.

June 1, 2005

Analytical and Clinical Evaluation of a New Urinary Tumor Marker: Bladder Tumor Fibronectin in Diagnosis and Follow-up of Bladder Cancer

Nilgun Mutlu, Levent Turkeri, Kaya Emerk

Page range: 1069-1074

Abstract

Bladder cancer is the fourth most common malignant neoplasm in men and the tenth most common in women. Cystoscopy presents the gold standard for detection and monitoring of bladder cancer. However, it is an invasive and expensive procedure. Therefore, development of biomarkers for the purposes of screening, diagnosis and prediction of the prognosis in bladder cancer is required. Bladder tumor fibronectin is one of the new urinary tumor markers. The aim of this study is to evaluate the diagnostic performance of urinary bladder tumor fibronectin in detecting and monitoring bladder cancer. A total of 75 patients with the diagnosis of bladder cancer, 20 patients with the diagnosis of benign prostatic hyperplasia, 7 patients with the diagnosis of prostate cancer between the years 1996–2000, and 28 age-matched healthy individuals, were enrolled in the study. The patients were diagnosed by cystoscopy, with histopathological evaluation of the tumor, as having superficial or invasive bladder cancer. Patients were followed-up clinically with data pertinent to disease recurrence and progression. Bladder tumor fibronectin (BTF; ng/ml) was determined by solid phase, two-site chemiluminescent immunometric commercial diagnostic assay developed for the Immulite automated immunoassay system (Diagnostic Products Corporation, Los Angeles, CA, USA). All measured values were normalized by urinary creatinine, and the obtained data were evaluated by receiver-operating characteristics (ROC) curve analysis. Optimal cut-off was established at 43.4 ng/mg. This cut-off rendered overall sensitivities of 72% and specificity of 82.1%. The analytical evaluation of the BTF test displayed promising results in terms of a non-invasive in vitro test in the diagnosis of bladder cancer. Although it was not satisfactory in prediction of recurrence or progression of the disease, it correlated well with the stage, one of the most reliable prognostic factors. In conclusion, the urinary bladder tumor fibronectin test warrants further clinical evaluation.

June 1, 2005

Biological Variation of Lipoprotein(a) in a Diabetic Population. Analysis of the Causes and Clinical Implications

Cristina Hernández, Gemma Francisco, Pilar Chacón, Jordi Mesa, Rafael Simó

Page range: 1075-1080

Abstract

The aims of the present study were to evaluate the biological variability of lipoprotein(a) (Lp(a)) in diabetic patients and to investigate the biological sources of this variability. Lp(a) was measured by ELISA in four serum specimens collected in 3-month intervals from 70 patients. The other parameters analyzed were: total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, HbA and albumin excretion rate. The overall biological within-subject variance (CVb) was 31.7%, and it was inversely correlated with Lp(a) serum levels. According to the initial ranges of Lp(a) serum levels (<15, 15–30 and >30mg/dl) the CVb were 42.3%, 24.1% and 23.7%, respectively. In multivariate analysis the total intra-individual coefficient of variation (CVt) of triglycerides and the CVt of the albumin excretion rate (AER) were independently associated with the CVb of Lp(a) (R 2 =0.54). The intra-individual biological variation of Lp(a) produced a misclassification of 20% of diabetic patients for cardiovascular risk attributable to this lipoprotein. In conclusion, the higher biological variability of Lp(a) observed in diabetic patients suggests that a single determination could be inaccurate to assess the cardiovascular risk associated with this lipoprotein, at least in those patients in whom serum levels are near the cut-off considered as risk for cardiovascular disease (>30 mg/dl). Finally, triglycerides and AER are the main factors influencing Lp(a) serum levels in the diabetic population.

June 1, 2005

Relationship of Dehydroepiandrosterone and Its 7-Hydroxylated Metabolites to Thyroid Parameters and Sex Hormone-Binding Globulin (SHBG) in Healthy Subjects

Richard Hampl, Martin Hill, Radovan Bílek, Luboslav Stárka

Page range: 1081-1086

Abstract

The concentrations of four immunomodulatory steroids, namely dehydroepiandrosterone (DHEA), its sulfate and its 7-hydroxylated metabolites, and sex hormone-binding globulin (SHBG) and major laboratory parameters of thyroid function were determined in sera from 104 healthy females and 48 males, screened for iodine deficiency in one region of the Czech Republic. The mutual relationships of the laboratory parameters were investigated by using four statistical approaches: correlation analysis, principal component analysis, canonical correlation and linear model relationship. In addition to expected correlations among thyroid parameters and substrate-product relationships among the steroids, several new relationships were revealed: The only thyroid parameter tightly correlating with SHBG was free triiodothyronine. The latter hormone was also associated with one of the 7-OH-DHEA epimers, namely with 7β-OH-DHEA. Thyroid hormones are known to possess thermogenic properties, as does another 7-oxygenated DHEA metabolite, 7-oxo-DHEA, the major metabolite of which is 7β-OH-DHEA. It may indicate a link between the two thermogenic factors. The results should serve for further investigation of changes in the thyroid hormone concentrations, together with SHBG and dehydroepiandrosterone metabolites, under various pathological situations.

June 1, 2005

Comparability of Eight Immunoassay Procedures for the Determination of CA 15-3 and Related Markers

Petr Stern, Vladimir Bartos, Jaroslava Vavrova, Drahomira Bezdickova, Martina Pechova, Jana Uhrova, Bedrich Friedecky, Ludek Sprongl, Tomas Zima, Vladimir Palicka

Page range: 1087-1094

Abstract

MUC1 mucins are tumour markers that are frequently indicated and examined, particularly as part of the treatment of breast cancer. Relatively large differences were observed in external quality assessment (EQA) between the results that were obtained by different immunoassay technologies. Thus, we compared eight routinely employed immunoassay sets for the determination of MUC1 mucins in the serum: six closed automated systems (AxSYM, Centaur, ECi Vitros, Elecsys 2010, Immulite 2000 and Kryptor), and two IRMA kits (ELSA CIS and IRMA-mat Byk-Sangtec). Using all analytical systems, we measured identical groups of clinical samples complete with selected calibrator and control samples. The repeatability of measurements (presented as coefficients of variation) ranged from 0.7% (Kryptor) to 6.9% (Immulite 2000). Even though the cut-off values differ among various systems, no similar clinical efficacy appears to be attained. In the region of cut-off values, the highest specificity that was set as a standard was found for the AxSYM analyser, while the sensitivity was highest for the Elecsys 2010. Data from Bland-Altman differential plots suggest the presence of significant individual differences among individual samples, mainly in the region of high concentrations of MUC1 mucins. The parameters of Passing-Bablok regression show significant systematic differences between some of the analytical systems as well as an increase of the differences with increasing MUC1 mucin concentrations. The effect of the combination of antibodies used on the extent of differences among results obtained with individual systems is more obvious than the effect of the matrix of analysed materials.

June 1, 2005

Reference Values of Serum Total Sialic Acid for Healthy Adult Subjects and Comparison of Two Different Calibrators for Quantitation of Total Sialic Acid in High Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection

Jarkko Romppanen, Eeva-Liisa Romppanen, Toivo Halonen, Matti Eskelinen, Kari Punnonen

Page range: 1095-1096

June 1, 2005

A Simple Method for the Classification of Proteinuria

Massimo Gai, Daria Motta, Francesca Bertinetto, Elisabetta Mezza, Alberto Jeantet, Vincenzo Cantaluppi, Giorgina B. Piccoli, Giacomo Lanfranco

Page range: 1097-1098

July 27, 2005

Meetings and Awards

Page range: 1099-1101

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 8. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

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clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
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