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Clinica Chimica Acta - Verlag: Elsevier
'Clinica Chimica Acta' veröffentlicht Originalbeiträge auf dem Gebiet der Klinischen Chemie und der Laboratoriumsmedizin, wie die Anwendung der Chemie, Biochemie, Immunchemie, der biochemischen Aspekte der Hämatologie, Toxikologie und Molekularbiologie zur Untersuchung der menschlichen Erkrankungen, die sich in den Körperflüssigkeiten, Zellen oder Geweben zeigen.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 7 February 2012 Ying Yu, Jinhui Xu, Yuan Liu, Shanlei Qiao, Yun Chen BackgroundNodularins are an important class of hepatotoxic cyclic pentapeptides that most current methods are ill-suited to clinically monitor. Therefore, a liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay for the determination of nodularin-R in human plasma was validated and applied to clinical samples in this report.MethodsSample cleanup and enrichment were achieved using solid phase extraction. The concentration of nodularin-R in each sample was calculated using the relative abundance area ratio of nodularin-R and a stable isotope-labeled internal standard.ResultsThe validated calibration range was from 0.50 to 100 ng/ml. The intra- and inter-day precision were < 6.0 and 9.8%, respectively. The accuracy at the lower limit of quantification (LLOQ) was 2.0%, while for other QC levels, it was < 3.4%. The absolute concentrations determined by the LC/MS/MS assay were significantly lower than those measured using a commercial immunoassay. Finally, a variety of demographic factors were evaluated and the findings indicated that the elderly (> 50 y) and people living close to seashore or lakefront areas (? 10 km) were the most susceptible to nodularin-R (p = 0.79 × 10and 2.57 × 10, respectively).ConclusionsThis report was among the first to demonstrate that clinical monitoring of nodularin-R could be achieved using LC/MS/MS.
Highlights
? An LC/MS/MS assay for the determination of nodularin-R in human plasma was validated and applied. ? The LC/MS/MS assay was compared with a commercial immunoassay. ? Demographic factors (i.e., sex, age, body mass index (BMI) and area of residence) were evaluated. ? This report demonstrated that clinical monitoring of nodularin-R could be achieved using LC/MS/MS.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 7 February 2012 Marita Hanasand, Roald Omdal, Katrine B. Norheim, Lasse G. Gøransson, Cato Brede, ... BackgroundOxidative stress has been associated with many diseases and can among others be assessed as increased levels of advanced oxidation protein products (AOPP). Current AOPP methods suffer from poor reproducibility and accuracy due to precipitation of lipids in plasma samples. We therefore aimed to develop a robust method in which plasma lipids are solubilized.MethodsPlasma was diluted with citric acid, and AOPP measured as absorbance at 340 nm. The method was optimized and validated, and then used to analyze AOPP levels in plasma from healthy control subjects (HC), and in three patients groups; chronic kidney disease (CKD), primary Sjögren's Syndrome (pSS) and systemic lupus erythematosus (SLE).ResultsAOPP was detected with improved precision compared to established methods where lipids precipitate. Within- and between days variations were less than 1.4% and 2.2%, respectively. A control chart was established and the long-term reproducibility followed over six months.ConclusionsThis improved method detects plasma AOPP with significantly better reproducibility and accuracy compared to previously reported methods.Solubilization of plasma lipids before spectrophotometric measure of AOPP levels is novel. It prevents both loss of lipoproteins due to precipitation and overestimation as a result of light scattering.
Highlights
? Advanced oxidation protein products (AOPP) is a biomarker of oxidative stress. ? AOPP is detected in plasma as absorbance at 340 nm. ? Existing methods suffer from poor reproducibility due to plasma turbidity. ? Solubilization of plasma lipids result in improved method accuracy and precision.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 7 February 2012 Samir M. Awadallah, Manar F. Atoum, Nisreen A. Nimer, Suleiman A. Saleh BackgroundIschemia modified albumin (IMA) is an altered type of serum albumin that forms under conditions of oxidative stress. This study reports on the levels and clinical significance of IMA in patients with ?-thalassemia major.MethodsBlood specimens were collected from 166 subjects (101 ?-thalassemia major patients and 65 healthy controls). Serum levels of IMA, ferritin, malondialdehyde (MDA), ferroxidase, transaminases, total protein, and albumin were determined using conventional methods.ResultsSerum levels of IMA (ABSU) were significantly higher in patients than in controls (0.725 ± 0.155 vs 0.554 ± 0.154, p = 0.000). Similarly, higher levels were also observed for ferritin, MDA, ferroxidase, and transaminases. No significant differences were observed between patients and controls with respect to total protein and albumin. Spearman univariate analysis demonstrated significant correlation between IMA and ferritin, MDA, ferroxidase, and transaminases. Multiple linear regression analysis revealed significant association of IMA with ferritin and ferroxidase after adjusting for the other variables (r = 0.343, p = 0.002; r = 0.228, p = 0.029 respectively). MDA however, correlated significantly with ferritin only (r = 0.654, p = 0.000).ConclusionOur findings suggest that increased levels of IMA in thalassemic patients are likely to be a result of iron-induced oxidative stress and hence its potential significance as a new marker of oxidative stress in such patients.
Highlights
? Levels of ischemia modified albumin (IMA) are increased in ?-thalassemia major ? IMA correlated significantly with ferritin and ferroxidase in thalassemic patients ? Iron overload and oxidative stress induces the formation of IMA ? IMA is suggested as an additional marker for oxidative stress in thalassemia
Publication year: 2012 Source: Clinica Chimica Acta, Available online 7 February 2012 Simona Ferraro, Ilaria Ardoino, Patrizia Boracchi, Matteo Santagostino, Laura Ciardi, ... BackgroundNo information is available on the optimal sampling time to catch the highest increase for biomarkers whose elevation after ST-elevation myocardial infarction (STEMI) is prognostic for adverse events. This study aimed to investigate release kinetics and peak times of cardiac troponin I (cTnI), C-reactive protein (CRP), B-type natriuretic peptide (BNP), chromogranin A (CgA) and cystatin C (CyC) in STEMI patients undergoing primary percutaneous coronary intervention (PPCI).MethodsBlood concentrations of cTnI, CRP, BNP, CgA and CyC were measured before and 6 h, 24 h, and 48 h after PPCI in 84 STEMI patients. The averaged trajectory of marker kinetics was estimated by multivariable regression models adjusted for patient characteristics and orthogonal polynomials were used to describe related releases.ResultsFrom the estimated kinetics cTnI peaked at 10 h from symptoms, BNP at 28 h and CRP within 30 h. CyC concentrations did not change, whereas CgA concentrations increased from 6 to 48 h after PPCI. The amount of BNP release was found to be affected by the interaction between gender and age: females < 75 years had BNP concentrations fourfold higher than males.ConclusionsAccording to different release kinetics a single blood sampling for measuring all biomarkers is not recommended.
Highlights
? These biomarkers contribute information on myocardial infarction pathophysiology ? A multimarker approach may provide an accurate prognostic information. ? From our kinetics the simultaneous measurement of all markers is suboptimal. ? Our results warn about the need of specific sampling times for each marker ? This should increase the prognostic information gained by risk algorithms
Publication year: 2012 Source: Clinica Chimica Acta, Available online 4 February 2012 Junxian Zhang, Xueqiong Wu, Lilan Shi, Yan Liang, Zhensheng Xie, ... BackgroundThe diagnosis for smear-negative pulmonary tuberculosis (TB) is very difficult. Proteomic fingerprinting of sera is a potentially useful tool.MethodsThis study analyzed the results of the proteomic fingerprinting in sera obtained from active TB patients and controls using the surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and protein-chip technology. The peaks were detected and analyzed, and a diagnostic system was developed. The protein peak was identified using high performance liquid chromatography (HPLC)-tandem matrix-assisted laser desorption/ionization-TOF-MS (MALDI-TOF-MS).ResultsAround 50 protein peaks were found significantly different between the TB patients and the controls (P < 0.01). Three protein peaks atm/z5643, 4486 and 4360 were selected for system classification and the development of a decision model. The model distinguished the TB patients from the controls with a sensitivity of 96.9% and a specificity of 97.8%, respectively. The diagnostic accuracy was up to 97.3%. The one most discrepant protein peak atm/z5643 seen in sera of active TB patients was identified as orosomucoid.ConclusionsA diagnostic system for active TB was developed using mass spectrometry and protein chip technology and required only small-volume serum samples. One potential protein biomarker atm/z5643 was identified as orosomucoid.
Highlights
? The human sera were analyzed by mass spectrometry. ? The proteomic fingerprinting in sera was obtained. ? Around 50 significant protein peaks were found. ? Three protein peaks were selected for the development of a decision model. ? The protein peak at m/z 5643 was identified as orosomucoid.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 4 February 2012 J.R. Peña, K. Lewandrowski, E.L. Lewandrowski, K. Gregory, J.M. Baron, ... BackgroundPoint-of-care devices for performing a prothrombin time/ international normalized ratio (PT/INR) using capillary blood samples are being increasingly used to monitor patients receiving anticoagulation therapy. However, the performance of some devices has been shown to be suboptimal and there are only limited published data comparing specific devices to various central laboratory coagulation analyzers. We report an evaluation of the iSTAT PT/INR with a comparison to the Tcoag MDA II analyzer.MethodsWe obtained simultaneous capillary/venous samples on 20 healthy volunteers for a normal range study and on 50 anticoagulated patients for a clinical evaluation. Testing was performed by phlebotomists. We also obtained 68 near simultaneous capillary/venous test results for assessment of performance by non-laboratory personnel. The criteria for determining clinical equivalence of the iSTAT to the MDA II were (1) same clinical category (subtherapeutic INR < 2, therapeutic INR 2–3, and supratherapeutic INR > 3) or (2) paired values within ? 0.4 INR.ResultsForty nine of 50 patient sample pairs collected by phlebotomists showed acceptable clinical agreement. Sixty one (61) of 68 patient sample pairs collected by nurses showed acceptable agreement. In all discordant cases the differences were minor and would have resulted in either no or minimal change in therapy.ConclusionsThe iSTAT PT/INR compares well to the MDA II when performed by phlebotomists or nurses.
Highlights
? This is the first report comparing iSTAT point-of-care to MDAII core laboratory INR. ? Normal donors, warfarin patients, patients having a procedure, and additional patients with INR > 3 were studied. Correlation between i-STAT and MDAII INR was good. ? Using a locally-determined mean normal i-STAT PT reduced the i-STAT INR bias. Overall, the i-STAT INR compared well to the MDA II INR.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 1 February 2012 Robert Dupuis, Andrea Yuen, Federico Innocenti In preventing acute rejection in solid organ transplant patients, it is important to maintain a fine balance between preventing rejection and reducing adverse effects. Several immunosuppressive agents such tacrolimus, cyclosporine, sirolimus and everolimus require therapeutic drug monitoring. The study of germline variation of the genome has opened novel opportunities to individualize therapy. Among the currently available immunosuppressive agents, cyclosporine, tacrolimus and mycophenolic acid are in vitro substrates of the UGT1A and 2B families of glucuronidation enzymes. Mycophenolic acid, either given as mycophenolate mofetil or mycophenolate sodium, is the most frequently used antiproliferative immunosuppressant. Mycophenolic acid is a prodrug which is rapidly de-esterified in the gut wall, blood, liver and tissue to the active moiety, mycophenolic acid (MPA). MPA undergoes significant hepatic metabolism to several metabolites. The 7-hydroxyglucuronide MPA is the major metabolite and is inactive. This paper reviews the current status of the genetic associations between germline UGT variants and the pharmacokinetics and pharmacodynamics of mycophenolic acid. Our conclusive assessment of the studies conducted so far is that these germline markers are not ready to be used in the clinic to individualize mycophenolic acid dosing and improve outcome. Novel approaches are required to identify new genetic determinants of outcomes in transplantation.
Highlights
? Influence of UGT polymorphisms on mycophenolic acid pharmacokinetics and outcomes. ? Evidence on UGT polymorphisms inconclusive to use as clinical marker. ? Further study of UGT1A9 SNPs for utility of therapeutic drug monitoring. ? Further examine UGT2B7 and UGT1A8 SNPs for links to toxicity and infection.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 31 January 2012 Nakarin Kitkumthorn, Time Tuangsintanakul, Prakasit Rattanatanyong, Danai Tiwawech, Apiwat Mutirangura BackgroundRecently, we classified LINE-1 loci according to their methylation statuses and found that the percentage of hypomethylated LINE-1 loci (CC) can differentiate between the peripheral blood mononuclear cells (PBMCs) of oral cancer patients and normal controls with a higher specificity and sensitivity than overall methylation levels. Here, we evaluated the LINE-1 methylation levels and patterns in PBMCs from patients with cancers of the nasopharynx, lung, liver, bile duct, breast and colonMethodsCombined Bisulfite Restriction Analysis (COBRA) of LINE-1 loci was performed to examine the LINE-1 methylation statuses of PBMCs from 216 cancer patients with 6 different types of cancer compared with 144 normal controls.ResultsOnly colorectal and nasopharyngeal cancer samples were found to have lower levels of overall LINE-1 methylation compared with normal controls (p < 0.0001 andp = 0.0022). However, %CC in cancers of the colon, liver, lung and nasopharynx was significantly higher compared with normal controls (p < 0.0001,p < 0.0001,p = 0.01 andp = 0.001, respectively). Furthermore, ROC curve analyses of these four cancer types also demonstrated the potential of %CC as a biomarker for cancer diagnosis.ConclusionChanges in the levels and patterns of genome-wide methylation of PBMCs are associated with cancer risk. For LINE-1, %CC is a more effective tumour marker for determining cancer risk than overall methylation levels.
Highlights
? We improved measurement of LINE-1 methylation levels and patterns. ? Genome wide LINE-1 loci were differentiated into 4 methylation-status categories. ? The methylation-statuses were hyper-, hypo-, and 2 forms of partially methylation. ? Changes in LINE-1 methylation pattern could be observed regardless level. ? The number of hypomethylated loci was high in blood cells of cancer patients.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 2 February 2012 Moshe Israeli, Tirza Klein, Gunnar Brandhorst, Michael Oellerich The survival of a transplanted organ is dependent on avoidance of rejection, achieved through continuous immuno-supppression. Management of the transplant recipient confronts the clinician with a key challenge of post-transplant Immune monitoring. Early detection of an activated allo-immune response is a harbinger of incipient rejection. Thus, timely intervention may prevent acute and chronic injury to the transplanted organ. Similarly, over immune-suppression can lead to infections or malignancies, hence the importance of early detection of the precarious suppression. The need for non-invasive systemic immune monitoring of the transplant recipient is therefore imperative.This review describes the cellular immune function assay - a non-invasive diagnostic method for evaluation of the net state of the recipient's cellular immune function. We describe the background that brought about the need for a reliable diagnostic tool for serial immune monitoring, and we overview the main mile-stones in the assimilation of the assay and its implementation in the clinic.The arising conclusion presents a novel non-invasive diagnostic bio-marker for post-transplant immune monitoring which enables the clinician to intervene prior to manifestation of clinical complications. The usefulness of the assay in detecting a state of over-suppression has been consensually described in multiple publications while its contribution in detection and management of under-suppression conditions remains to be determined by means of prospective interventional studies. The cellular immune function assay can be useful and beneficial for patient care only if used for longitudinal monitoring through serial testing.
Highlights
? Long term Immuno-suppressive therapy after transplantation is not a panacea. ? Immune monitoring is a major challenge in managing a patient after transplantation. ? The cellular immunity assay measures the net state of the patient's immune function. ? Longitudinal immune function monitoring may improve outcome of organ transplants.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 1 February 2012 Yi-Tzu Cho, Yu-Syuan Chen, Jia-Lun Hu, Jentaie Shiea, Shih Meng Yeh, ... BackgroundMatrix-Assisted Laser Desorption Ionization/Time-of-Flight (MALDI-TOF) mass spectrometric analysis of albumin (ALB) biomarkers is an alternative approach toward the rapid diagnosis of proteinuria for screening a large numbers of samples. The aim of this study is to reveal if interfering factors in urinary dipstick approach would affect the results of diagnosing albuminuria by MALDI-TOF MS.MethodsThe effects of various interfering chemicals on the diagnosis of albumin in urine were examined using both MALDI-TOF mass spectrometric and dipstick approaches. Semi-quantification of albumin was performed by using MALDI-TOF MS.ResultsInterferences from various drugs, detergents, vitamins and their metabolites, alkaline, and blood, which often cause false-positive and false–negative results in conventional urinary dipstick analysis, are avoided when using this MALDI-TOF MS approach. It was found that the intensity of + 1 and + 2 albumin ions varies with the albumin concentration. A log/log plot of the intensity ratio vs. albumin concentration is then used as a calibration curve for semi-quantifying the albumin in urines.ConclusionsMALDI-TOF MS is an effective approach toward avoiding interferences caused by various chemical compounds during the rapid diagnosis of albumin in urine. Semi-quantification of albuminuria is also achieved by this MALDI-TOF MS approach.
Highlights
? MALDI-TOF MS can be used to sensitively characterize albumin in urine samples. ? We examined the effects of interfering chemicals on the albuminuria diagnosis. ? The matrix factors did not affect the detection of albumin through MALDI-TOF MS. ? MALDI-TOF MS is a rapid and unambiguous approach for screening albuminuria.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 30 January 2012 Tao Zhang, Xiaoyan Wu, Mingzhu Yin, Lijun Fan, Haiyu Zhang, ... BackgroundDiscrimination between epithelial ovarian cancer (EOC) and benign ovarian tumor (BOT) has always been difficult in clinical practice. We investigated the application of metabolomics in distinguishing EOC and BOT and tried to discover valuable biomarkers.MethodsPlasma metabolomic profiling was performed using ultra-performance liquid chromatography mass spectrometry (UPLC/MS). Partial least-squares discriminant analysis was employed to classify EOC and BOT, and reveal their metabolic differences. The area under the receiver-operating characteristic curve (AUC) was utilized to evaluate the predictive performance of the metabolic profiles for external validation set.ResultsThe metabolomic profiles consisting of 535 metabolites revealed a clear separation between EOC and BOT, with AUC of 0.86 for the external validation set. 6 metabolic biomarkers were identified, and the plasma concentrations of the 4 ascertained biomarkers (L-tryptophan, LysoPC(18:3), LysoPC(14:0), and 2-Piperidinone) were lower in EOC patients than those in BOT patients. Among them, tryptophan and LysoPC have been suspected to participate in cancer progression, and 2-Piperidinone might be a novel biomarker for EOC.ConclusionsMetabolomics could be used to discriminate EOC from BOT in clinical practice, and the identified metabolic biomarkers might be important on investigating the biological mechanisms of EOC.
Highlights
? Plasma metabolic profiles can discriminate malignant and benign ovarian tumor. ? Down-regulation of L-tryptophan was observed in malignant compared with benign ovarian tumor. ? Down-regulation of LysoPC metabolism was observed in plasma for ovarian cancer patients. ? 2-Piperidinone might be a novel biomarker for ovarian cancer.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 27 January 2012 Yizhao Chen, Qinde Liu, Sharon Yong, Tong Kooi Lee BackgroundAn isotope dilution mass spectrometry (IDMS) technique has been developed for high accuracy analysis of glucose in human serum. Currently, all the IDMS methods for glucose analysis are based on gas chromatography–mass spectrometry (GC-MS). In this study, isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) was investigated.MethodsNIST SRM 965b glucose in frozen human serum was analyzed by linear regression IDMS based on both LC-MS/MS and GC-MS. Serum samples were spiked with isotope labeled glucose and deproteinized by acetonitrile. For LC-MS/MS measurement, the supernate was injected directly after filtration and dilution. For GC-MS measurement, the supernate was evaporated to dryness and went through a two-step derivatization before injection.ResultsAll measurements had good precision with CVs of < 1%. Results from GC-MS agreed very well with results from LC-MS/MS, with a difference of < 0.7%. The final reporting values in this study, based solely on LC-MS/MS, were within the certified ranges. The relative expanded uncertainties were within the range of 1.37% to 1.73% for the 4 levels of glucose, which were comparable with uncertainties from the certificate.ConclusionsThe IDMS method based on LC-MS/MS is precise and accurate. It does not require lengthy derivatization steps and thus, greatly simplifies the sample preparation procedure.
Highlights
? Isotope dilution LC-MS/MS for high accuracy analysis of glucose in human serum. ? No derivatization of glucose and thus greatly simplifies sample preparation procedure. ? Certified reference material of glucose in frozen human serum from NIST was analyzed. ? Compared with ID GC-MS results and certified values, ID LC-MS/MS results are accurate and precise.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 27 January 2012 Der-Yuan Chen, Yi-Ming Chen, Joung-Liang Lan, Bor-Show Tzang, Chi-Chen Lin, ... BackgroundHuman parvovirus B19 (B19) infection has been reported as a possible cause of autoimmune diseases. The association of B19 infection with adult-onset Still's diseases (AOSD) remains unclear.MethodsIgM and IgG against B19-VP1/2 were determined using ELISA in 86 patients with AOSD, 58 patients with systemic lupus erythematosus (SLE) and 64 healthy controls. Anti-B19-VP1-unique region (VP1u) and anti-B19-nonstructural protein-1(NS1) antibodies were assessed by Western blot. B19 DNA was detected by nested PCR.ResultsForty-three (50.0%) of 86 AOSD patients, 27 (46.6%) of 58 SLE patients and 30 (46.9%) of 64 controls had positivity for anti-B19-VP1/2-IgG in the absence of anti-B19-VP1/2-IgM, indicating past infection. None of enrolled subjects had detectable circulating B19 DNA. Significantly higher positivity rates for anti-B19-VP1u and anti-B19-NS1 IgG were observed in AOSD patients (39.5% and 46.5% respectively) and SLE patients (34.5% and 36.2% respectively) than in healthy controls (14.1%, p < 0.005 for AOSD and p < 0.05 for SLE, and 15.6%, p < 0.001 for AOSD and p < 0.05 for SLE; respectively). AOSD patients and SLE patients with seropositive results for anti-B19-VP1/2 IgG, anti-B19-VP1u or anti-B19-NS1 antibodies had a higher frequency of leucopenia and thrombocytopenia when compared to those with seronegative results. AOSD patients with anti-B19-VP1u or anti-B19-NS1 antibodies were more likely to have arthritis in comparison with those without these antibodies.ConclusionsHigher seroreactivity for anti-B19-VP1u and anti-B19-NS1 IgG were associated with cytopenia in both AOSD and SLE patients with unique correlation to arthritis in the AOSD. Further studies are necessary to determine if these responses correlate with a common genetic risk in patients with AOSD and SLE.
Highlights
?AOSD patients reveal higher seroreactivity for anti-B19-VP1u and anti-B19-NS1 IgG.?Past B19 infection is associated with cytopenia and arthritis in AOSD patients.?Prompt detection of B19 infection in AOSD patients has therapeutic consequences.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 27 January 2012 P. Akila, V. Prashant, M.N. Suma, S.N. Prashant, T.R. Chaitra Macrophages are key players of the immune system and express a variety of surface receptors. CD163 is one such receptor which belongs to the scavenger receptor cysteine-rich super family (SRCR-SF) class B. It has four isoforms which differ in the structure of their cytoplasmic domains and putative phosphorylation sites. Expression of CD163 is tightly regulated with a general tendency of anti-inflammatory signals to induce its synthesis, while pro-inflammatory signals downregulate its expression. Previously the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes. However, it also plays a crucial role in the control of inflammatory processes by induction of anti-inflammatory pathways. Soluble CD163, which is generated via ectodomain shedding, serves as a potential diagnostic tool in variety of disease states, such as inflammation, atherosclerosis, transplant rejection and carcinoma. Recently, CD163 has been identified as a promising target for cell directed therapy. In this review we aim to summarize the current knowledge of CD163.
Highlights
? CD163 is a receptor belonging to scavenger receptor cysteine-rich superfamily class B ? It acts as a receptor for hemoglobin-haptoglobin complexes ? It plays a crucial role in the control of inflammatory processes ? Soluble CD163 serves as a potential diagnostic tool in variety of disease states ? CD163 has been identified as a promising target for cell directed therapy
Publication year: 2012 Source: Clinica Chimica Acta, Available online 25 January 2012 Duck-An Kim, Think-You Kim BackgroundTo find out whether serum level of anti-cyclic citrullinated peptides (anti-CCP) could be useful in the diagnosis of rheumatoid arthritis (RA).MethodsThe study was performed against 1,972 patients who visited Hanyang University Medical Center and were tested positive for anti-CCP.ResultsWhen test results were classified into 6 groups according to the anti-CCP level, diagnostic rates of RA in each group were distributed from 73.6% to 77.2%. The increase of serum level did not have any correlation with the diagnostic rate of RA.ConclusionsThe level of serum anti-CCP was not useful in the diagnosis of RA.
Highlights
? We studied in 1,972 patients who were tested positive for anti-CCP. ? The diagnostic rates of RA in 6 groups were distributed from 73.6% to 77.2%. ? The level of serum anti-CCP was not useful in the diagnosis of RA.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 25 January 2012 Madoka Yoshida, Takahiro Mikami, Kyohei Higashi, Ryotaro Saiki, Mutsumi Mizoi, ... BackgroundWe found previously that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good biomarkers for stroke. The aim of this study was to test whether 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, was increased in the urine of stroke patients.MethodsThe level of 3-HPMA in urine was measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Stroke (78 subjects) was divided into 52 cerebral infarction (CI) and 26 cerebral hemorrhage (CH) on the basis of clinical information including brain imaging.ResultsA major acrolein derivative in urine is 3-HPMA. Being different from the results of PC-Acro in plasma, 3-HPMA in urine decreased following stroke. The median value of ?mol 3-HPMA/g creatinine (Cre) for 90 control subjects was 2.83, while that for 78 stroke patients was 1.56. The degree of the decrease in 3-HPMA was similar in both CI and CH patients. Furthermore, the median value of ?mol 3-HPMA/g Cre in 56 patients with lesions > 1 cm in diameter (1.39) was significantly lower than that in 20 patients with lesion < 1 cm in diameter (2.16).ConclusionInverse correlation between stroke and urinary 3-HPMA was observed. The results suggest that stroke is aggravated when nervous system tissues have a reduced level of glutathione.
Highlights
? 3-HPMA in urine, acrolein conjugate of GSH, decreased following stroke. ? Decrease in 3-HPMA was parallel with the size of infarction. ? The results suggest that stroke is aggravated when GSH in nervous tissues is low.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 24 January 2012 Chun-Hou Liao, Hung-Yuan Li, Hong-Jeng Yu, Han-Sun Chiang, Mao-Shin Lin, ... BackgroundLow sex hormone-binding globulin (SHBG) is associated with metabolic syndrome (MetS), but its relationship with inflammation is unclear.MethodsThis cross-sectional study included 696 subjects (255 men, 235 pre-menopausal women, and 206 postmenopausal women). Body mass index, waist circumference, blood pressure, lipid profiles, plasma glucose, insulin, FSH, LH, total testosterone (TT), estradiol, SHBG, dehydroepiandrosterone sulfate (DHEA-S), and hs-CRP concentrations were measured. MetS was defined according to the updated National Cholesterol Education Program criteria with modification of waist circumference for Asians.ResultsSerum hs-CRP and SHBG were negatively correlated in men (r = ? 0.29, p < 0.001), pre-menopausal women (r = ? 0.38, p < 0.001), and postmenopausal women (r = ? 0.27, p < 0.001). In men, TT and hs-CRP showed a negative association (r = ? 0.25, p < 0.001), but the association was attenuated after adjusting for SHBG (r = ? 0.14, p = 0.039). Multivariate regression models showed that SHBG was independently associated with hs-CRP in men (r = ? 0.18, p = 0.009), pre-menopausal women (r = ? 0.15, p = 0.025), and postmenopausal women (r = ? 0.21, p = 0.005), adjusted for age, MetS components, insulin resistance, low-density lipoprotein-cholesterol, and serum sex hormone levels.ConclusionsSerum SHBG and hs-CRP concentrations were inversely correlated in men, pre-menoposal, and post-menopausal women independently.
Highlights
? Low sex hormone binding globulin (SHBG) predicts development of metabolic syndrome. ? SHBG is inversely correlated to C-reactive protein independent to traditional risk factors. ? SHBG is a novel independent marker of metabolic and inflammatory statuses in both men and women ? The role of SHBG in inflammation process needs further investigation.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 24 January 2012 M. Zaninotto, A. Vernocchi, F. Di Serio, M. Del Mar Viloria, Josè M. Hurtado, ... BackgroundSince cardiac troponins assay technology should comply with the recommendations of scientific societies (i.e. imprecision (10%) at the 99th percentile value observed in healthy subjects being the analytical qualifying aspect), the aim of the present study was to evaluate whether an improved troponin assay (Vitros Troponin I ES) provides data that meet the “guideline acceptable”criteria recently defined in a proposed scorecard.MethodsVitros Troponin I ES, an enhanced chemiluminescence immunoassay, was evaluated in a multicenter study considering: limit of blank (LOB, 60 relicates of 0 calibrators), limit of detection (LOD, 12 measurements for each of 5 serum pools), precision, linearity using control materials and serum plasma pool; matrix samples study matching serum and lithium-heparin plasma (n = 107 hospitalized patients); the 99th percentile limit in serum samples from 500 healthy Caucasian donors.ResultsLOB and LOD, 0.0029 ?g/L and 0.0030 ?g/L respectively; coefficients of variation (total CV%), obtained by running 3 levels of control materials and 10 serum pools, from 15.2% (x = 0.014 ?g/L) to 2.0% (x = 5.324 ?g/L); method, linear up to 70 ?g/L. No significant differences were found between serum and lithium-heparin matched sample (p = 0.48) values; 99th percentile limit of cTnI distribution in healthy donors, 0.021 ?g/L.ConclusionSince its analytical reliability meets the proposed performance and scorecard requirements, the Vitros TropI method can be considered “contemporary” and “guideline acceptable”.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 24 January 2012 Elisa Danese, Martina Montagnana, Anna Maria Minicozzi, Sara Bonafini, Orazio Ruzzenente, ... BackgroundTo date the role of resistin in colorectal cancer (CRC) is far from being elucidated. Aim of this study was to investigate the association between serum resistin levels and CRC in relation to known risk/protective factors including anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics.Methods40 CRC patients and 40 controls were enrolled. Body weight, height, waist circumference and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein (CRP) and resistin levels were measured. Metabolic Syndrome (MS) was defined according to the harmonized definition.ResultsResistin levels were significantly higher in CRC patients than in controls (p = 0.028) and gradually increased with tumor stage progression (p = 0.042). A high resistin level was statistically significant determinant of CRC after adjusting for age, sex, body mass index and lifestyle parameters (p = 0.029). Resistin showed a strong association with CRP levels (p ? 0.0001). In stepwise regression analysis CRP remained the only independent predictor of both resistin levels (p = 0.001) and CRC risk (p = 0.021).ConclusionsThese results clarify the nature of the association between resistin and CRC risk suggesting that the proinflammatory state of cancer, rather than the clinical diagnosis of CRC itself or its link with obesity and MS, may govern this association.
Highlights
? To date little is known about the resistin–colorectal cancer link ? We found a positive association between serum resistin level and colorectal cancer risk ? The association has found to be adiposity-independent ? The association has found to be dependent from the proinflammatory state of cancer
Publication year: 2012 Source: Clinica Chimica Acta, Available online 24 January 2012 S. Challouf, S. Ziadi, R. Zaghdoudi, F. Ksiaa, R. Ben Gacem, ... BackgroundAberrant methylation in the promoter of tumor-related genes is associated closely with epigenetically mediated gene silencing. The aim of the present study was to evaluate the methylation profile of Tunisian nasopharyngeal carcinoma (NPC) and to determine the clinicopathological features of tumors showing this epigenetic alteration.MethodsThirty-six archival NPC biopsies were investigated in comparison with 19 non-tumor nasopharyngeal tissue specimens. DNA methylation status of ten tumor-suppressor and related genes was analyzed by using methylation-specific PCR. The Epstein-Barr virus (EBV) presence was verified by PCR andin situhybridization and the LMP1 oncoprotein expression was analyzed by immunohistochemistry. Findings were then correlated with clinicopathological variables (Patients’ gender and age, tumor histolological subtype and stage).ResultsHypermethylation frequencies of the investigated genes in NPC biopsies were 75% for RASSFIA, 58.3% for SHP1, 47.2% for DAPK, 33.3% for P16, 31% for RAR?2, 19.4% for GSTP1 and TIMP3, 11% for APC and CDH1, and 5.5% for MGMT. In non-tumor nasopharyngeal samples, hypermethylation was detected in lower frequencies in 6 genes (SHP 26.3%, P16 21%, RAR?2 21%, DAPK 15.8%, TIMP3 10.5%, and GSTP 5.3%).Hypermethylation of RAR?2 promoter was more frequent in tumors with lymph node metastasis than those without metastasis (43.5%vs0%, p = 0.03). Methylation of RASSF1A was more frequently detected in non-keratinising NPC than in undifferentiated subtype (100%vs66.7%; p = 0.05). A trend toward positive association was found between an increased number of methylated genes and LMP1 expression (p = 0.07). However, no significant association was found for the remaining variables.ConclusionsThis study indicates that hypermethylation of multiple genes is a common alteration in nasopharyngeal carcinomas in Tunisian patients and that this epigenetic change may play a role in the nasopharyngeal carcinogenesis.
Highlights
? The authors investigated the methylation profile of ten tumor-related genes in a Tunisian series of nasopharyngeal carcinoma (NPC) in comparison with non-NPC nasopharyngeal specimens. ? A large proportion of cases with promoter methylation of multiple genes was found in NPC compared with the control group, underlining an important role of epigenetic alteration in the nasopharyngeal carcinogenesis. ? Hypermethylation of the promoter of several genes correlates with clinicopathological parameters, especially RAR?2 which correlates significantly with lymph node metastases. ? Moreover, a relationship between the viral oncoproteins LMP1 and the number of methylated genes was found suggesting a role of EBV in epigenetic alteration in NPC.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 20 January 2012 G. Gessoni, S. Valverde, F. Manoni BackgroundIn this study, we evaluated the GeneXpert HemosIL Factor II and Factor V assay, an innovative assay for the detection of Factor V Leiden (FVL) and prothrombin G20210A mutation (GPRO).Patients and MethodsWe evaluated 132 patients that were previously classified (with a concordant result) using two commercial real-time PCR assays supplied, by Applied Biosystems and Roche Molecular Biochemicals. The cohort comprised 75 normal subjects, 10 FVL homozygous, 35 FVL heterozygous, 7 GPRO heterozygous, 2 GPRO homozygous and 3 double heterozygous FVL and GPRO subjects. All of the samples were evaluated using the GeneXpert HemosIL Factor II and Factor V assay.ResultsAll of the samples were correctly identified using the GeneXpert HemosIL Factor II and Factor V assay; therefore, in this patient series, the specificity and sensitivity of the test under evaluation was 1.00.DiscussionWe have shown that the GeneXpert HemosIL Factor II and Factor V assay, a rapid fully automated assay, can accurately characterise the presence of FV G1691A and FII G20210A polymorphisms with specificity and sensitivity that are comparable to other current real-time PCR-based methods. The theoretical advantages of such an assay include improved standardisation across varying healthcare environments, more thorough sample manipulation and reduced human error.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 20 January 2012 Demao Yao, Jing Shi, Bingyin Shi, Na Wang, Wei Liu, ... BackgroundPromoter methylation is an alternative mechanism of gene silencing in human tumorigenesis. Although a number of methylated genes have been found in gastric cancer, useful methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown.MethodsUsing quantitative methylation-specific PCR (Q-MSP), we examined promoter methylation of 6 genes, includingCALCA,DAPK1,RARbeta,RASSF1A,TIMP3, andPAX6, and explored their association with clinical outcome in gastric cancer.ResultsWe found thatmost of genesinvestigated in the present study had significantly higher methylation level in tumor tissues than normal gastric tissues,including CALCA, RARbeta, RASSF1A, TIMP3, and PAX6. With more focus on specificity compared to sensitivity, all genes were hypermethylated in gastric cancer, ranging from 12.8% to 36.9%.Methylation of TIMP3 and PAX6 was strongly associated with differentiation and lymph node metastasis, respectively.Importantly,most of gene methylation, expect for DAPK1,was closely associated with poor survival in gastric cancer.ConclusionWe found that a panel of genes were specifically methylated in gastric cancer, and demonstrated the effect of promoter methylation of some genes on clinical outcome in gastric cancer, indicating these methylated genes may be as useful biomarkers for prognostic evaluation in this cancer.
Highlights
? Frequent gene methylation was found in gastric cancer. ? Gene methylation can affect clinical outcome in gastric cancer. ? Gene methylation may be used to evaluate prognosis of gastric cancer patients.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 20 January 2012 Kalle Günther, Francesca Malentacchi, Paolo Verderio, Sara Pizzamiglio, Chiara Maura Ciniselli, ... BackgroundAlthough important improvements of downstream molecularin vitrodiagnostics assays based on RNA from blood were made, the pre-analytical workflow is still poorly defined.MethodsWe performed a multicenter study within the EU-granted SPIDIA project to investigate blood collection and shipping influence on the following RNA quality parameters: yield, purity, integrity, RT-qPCR interference and IL1B, IL8, c-Fos and GAPDH gene expression. Two models were designed: ExpA. Ten laboratories collected blood from an own donor into two different tubes (with or without stabilizer) and extracted RNA at two different times; Exp B. Blood was drawn from a single donor and shipped to ten laboratories in two different tubes (with or without stabilizer) for RNA extraction.ResultsIn both models and collection tubes, reliable results were obtained for purity, yield, GAPDH expression, and interferences. A substantial variation in RIN (ExpA) and in transcription levels of IL1?, IL8 and c-Fos (ExpB) was observed for blood collected in unstabilized tubes. Overall the variability was higher among data obtained from unstabilized blood samples.ConclusionsWe defined the experimental setup for a larger ring trial throughout Europe. The chosen downstream analyses verified their potential, serving as adequate markers to test quality of blood RNA.
Highlights
? Multicenter pilot study for Proficiency Testing to develop a Pan-European ring trial ? PT is based on pre-analytical phase of RNA extraction from blood ? Evaluation of blood collection and blood and RNA shipping ? Setup of a panel of parameters to test quality of blood RNA
Publication year: 2012 Source: Clinica Chimica Acta, Available online 19 January 2012 Christiane Auray-Blais, Pamela Lavoie, Haoyue Zhang, René Gagnon, Joe T.R. Clarke, ... BackgroundMucopolysaccharidoses are complex lysosomal storage disorders caused by any of eleven different enzyme deficiencies resulting in the accumulation of substrates, mainly glycosaminoglycans (GAGs), in various tissues and biological fluids.MethodWe developed and validate da urine filter paper methodology for the analysis of GAGs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for mucopolysaccharidosis type I, type II and type VI patients. We focused on 2 objectives: first, its applicability to high-risk screening, and secondly, to facilitate the collection and shipping of samples to reference centers as part of diagnostic investigation, as well as from treated patients needing to be monitored for assessment of the efficacy of treatment. GAGs in urine dried onto filter paper were extracted and subjected to methanolysis to obtain the repeating disaccharides of the molecules. We devised a multiple reaction monitoring method in positive electrospray ionization mode.ResultsThe use of deuterated internal standards for dermatan sulfate (DS) and heparan sulfate (HS) reduced a troubling matrix effect. The resulting CVs were < 14%. Linearity assessment showed Pearson correlation coefficients of 0.999 and 0.997, for DS and HS, respectively. The stability on filter paper was good for DS and HS for up to 6 weeks at various temperatures.ConclusionWe devised a robust and efficient LC-MS/MS methodology for GAGS quantification in urine dried on filter paper and subjected to environmental conditions likely to be encountered during collection, storage and shipping of specimens from referring physicians to medical centers.
Highlights
? This LC-MS/MS technique allows quantification of GAGS for mucopolysaccharidoses. ? A methanolysis procedure is performed for dermatan and heparan sulfate analysis. ? Urine sample collected on filter paper facilitates collection, storage and shipment. ? This method allows adequate differentiation of MPS patients from healthy controls. ? It is a useful method for diagnosis, monitoring, evaluation of efficacy of treatment
Publication year: 2012 Source: Clinica Chimica Acta, Available online 19 January 2012 Garry Milman, David M. Schwope, David A. Gorelick, Marilyn A. Huestis Background?-Tetrahydrocannabinol (THC) in oral fluid (OF) implies cannabis intake, but eliminating passive exposure and improving interpretation of test results requires additional research.MethodsTen adult cannabis users smokedad libitumone 6.8% THC cigarette. Expectorated OF was collected for up to 22 h, and analyzed within 24 h of collection. THC, 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, and cannabinol were quantified by 2-dimensional-GCMS.ResultsEighty specimens were analyzed; 6 could not be collected due to dry mouth. THC was quantifiable in 95.2%, cannabidiol in 69.3%, cannabinol in 62.3%, and THCCOOH in 94.7% of specimens. Highest THC, cannabidiol, and cannabinol concentrations were 22370, 1000, and 1964 ?g/l, respectively, 0.25 h after the start of smoking; THCCOOH peaked within 2 h (up to 560 ng/l). Concentrations 6 h after smoking were THC (0.9-90.4 ?g/l) and THCCOOH (17.0-151 ng/l) (8 of 9 positive for both); only 4 were positive for cannabidiol (0.5-2.4 ?g/l) and cannabinol (1.0-3.0 ?g/l). By 22 h, there were 4 THC (0.4-10.3 ?g/l), 5 THCCOOH (6.0-24.0 ng/l), 1 cannabidiol (0.3 ?g/l), and no cannabinol positive specimens.ConclusionsTHCCOOH in OF suggests no passive contamination, and CBD and CBN suggest recent cannabis smoking. Seventeen alternative cutoffs were evaluated to meet the needs of different drug testing programs.
Highlights
? THC quantification with CBD and CBN in oral fluid suggests recent cannabis smoking. ? Quantification of multiple cannabinoids improves oral fluid interpretation results. ? Blood in expectorated oral fluid artificially increase cannabinoid concentrations. ? Low oral fluid volume due to dry mouth hinders quantitative analysis after smoking.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 15 January 2012 A. Lisowska, A. Tycinska, M. Knapp, R. Sawicki, P. Lisowski, ... ObjectiveThe aim of the study was to establish whether adiponectin may act as an independent risk factor of coronary artery disease (CAD) and if adiponectin has potential relations with a new marker of cardiovascular risk -intima-media thickness (IMT).Methods165 patients, who had undergone coronary angiography due to symptoms of CAD were enrolled. Selected clinical and biochemical risk factors were assessed, adiponectin concentrations and IMT were measured.ResultsA significantly lower adiponectin concentrations in the CAD group, as compared to the controls, were found. Adiponectin concentration did not correlate with a degree of coronary vessels changes advancement. No correlation between adiponectin concentrations and IMT values in the studied peripheral arteries were found. The value of 9.8ug/ml has been assigned as a cut-off value. Adiponectin concentrations < 9.8 ?g/ml had the highest positive predicitve value (PPV = 95.7%) and specificity (90.9), but low sensitivity (30.8). In the multilogistic regression analysis significant variables influencing the appearance of CAD were found: HDL-C (p = 0.011, OR = 0.88, 95%CI 0.80-0.97), IMT in CCA (p = 0.0048, OR== 5.25, 95%CI 1.65-16.75), IMT in CFA (p = 0.015, OR = 1.65, 95%CI 1.10-2.48 ), and adiponectin concentration < 9.8 ?g/ml (p = 0.032, OR = 28.95, 95%CI 1.31-641.48).ConclusionsAdiponectin is an independent risk factor of coronary artery disease occurence, but not its advancement. No correlation between adiponectin concentration and IMT values in peripheral arteries was shown.
Highlights
? We examine whether adiponectin may act as an independent risk factor of coronary artery disease (CAD) ? Lower adiponectin concentrations was found in the CAD group of patients ? Adiponectin concentration did not correlate with a degree of coronary vessels changes advancement. ? No correlation between adiponectin concentration and IMT values in peripheral arteries was shown.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 15 January 2012 Yan-Qiang Hou, Ping Xu, Mei Zhang, Deping Han, Liang Peng, ... BackgroundSepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS.Methods:Serum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, were quantitatively measured by enzyme-linked immunosorbent assay (ELISA).ResultsThe serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11 ± 2.58 ng/ml vs 2.62 ± 1.46 ng/ml, and 0.91 ± 0.56 ng/ml, respectively, p < 0.001). The area under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870-0.950), 0.992 (0.984-1.000) and 0.896 (0.820-0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r = 0.556, p = 0.005).ConclusionThe serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity.
Highlights
? Currently, there is no satisfactory biomarker to distinguish sepsis and SIRS. ? We found that serum DcR3 highly elevated in sepsis compared to normal. ? Serum DcR3 level is higher in sepsis than that in SIRS. ? Serum DcR3 might use in diagnosis of sepsis and differential diagnosis between sepsis and SIRS.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 15 January 2012 Steven Pauwels, Pieter Vermeersch, Johan Van Eldere, Koen Desmet BackgroundAn increasing number of publications points to the importance of voriconazole plasma monitoring. Our aim was to develop a fast and simple LC-MS/MS method for the quantification of plasma voriconazole.Methods20 ?L of plasma was extracted by adding a precipitation reagent containing the internal standard (d3-voriconazole). Analysis was performed on a Quattro Micro tandem mass spectrometer equipped with an Alliance HPLC 2795 separations module. MRM transitions werem/z350.0?281.4 for voriconazole andm/z353.0?284.4 ford3-voriconazole. Quantification was done by both linear calibration curves and multiplication of the response ratio by a predefined factor.ResultsA method using protein precipitation as only pretreatment with an analysis time of 2 min was developed. Within- and between-run precision, expressed as coefficient of variation, at 6 concentrations ranged from 2.8% to 11.7%. Accuracy, expressed as percentage of the theoretically added concentration, ranged from 89.0% to 109.0%. Linearity was demonstrated from 0.06 mg/L (0.17 ?M) to 20.0 mg/L (57.3 ?M).ConclusionsThe described method offers a simple and rapid analysis of voriconazole in human plasma for clinical routine. Quantification with a predefined factor permits omitting calibration to each run and thereby reduces workload, costs and turn-around-time.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 14 January 2012 Chien-Chih Chen, Jui-Jane Lin, Sheng-tien Hung, Peng-Ting Chun, Yiu-Kay Lai BackgroundThe novel technique of blood volume detection can improve the reliability and accuracy of a self-monitoring blood glucose system. Self-management of diabetes can be improved, and the glycemic range can be efficiently controlled.MethodsA total of 153 patients with diabetes mellitus participated in the clinical study. The accuracy, blood volume detection, interference, and altitude effect of the EGV1 self-monitoring blood glucose system were evaluated and compared among the fingerstick, alternative site testing, and venous blood.ResultsThe EGV1 self-monitoring blood glucose system with fingertip demonstrated an excellent correlation with venous blood (linear regression analysis: slope = 1.01, intercept = ? 0.8972 mg/dl, r = 0.96), and with other brands of glucose systems (linear regression analysis: slope = 0.99, intercept = + 3.5632 mg/dl, r = 0.94). The Clarke error grid analysis indicated that the results of fingertip and alternative sites were in the acceptable zones, A and B. The system required 0.6 ul of a blood sample to obtain an accurate reading, and was unaffected by several interferents and altitude.ConclusionsThe EGV1 self-monitoring blood glucose system using various blood samples demonstrated acceptable accuracy and reliability compared to the laboratory reference and other self-monitoring blood glucose systems.
Highlights
? EG V1 Self-monitoring blood glucose system with fingertip had a good correlation with venous blood and also with the other brand of glucose system. ? The Clarke error grid analysis showed the results of fingertip and alternative sites fell into the acceptable zones A and B. ? Bland-Altman plots added another element of evaluation showing that the system bias between EGV1 and YSI 2300 was better than Contour and YSI 2300. ? The system only needed 0.6 uL of blood sample to get accurate reading and showed no effect by several interferents and altitude.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 13 January 2012 Nader Rifai, Thomas M. Annesley, Jens P. Berg, Carlo Brugnara, Edgard Delvin, ...
Publication year: 2012 Source: Clinica Chimica Acta, Available online 13 January 2012 M. Mahler, A. Radice, W. Yang, C. Bentow, A. Seaman, ... BackgroundThe detection of anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) autoantibodies represents a serological hallmark in the diagnosis of small vessel vasculitis such granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). We evaluated novel chemiluminescence assays (CIAs) for PR3- and MPO-ANCA detection and to investigate their utility for disease activity monitoring.MethodsSera collected from GPA (n = 41) and MPA (n = 30) patients and various controls were tested by QUANTA LitePR-3 and MPO ELISA (INOVA Diagnostics) and by the QUANTA FlashPR3 and MPO CIAs (INOVA). Precision and linearity were analyzed following reference guidelines. The recently launched reference sera for PR3-and MPO-ANCA (Centers of Disease Control and prevention, CDC) were used to establish international units for the new assays. Disease activity was determined using the Birmingham Vasculitis Activity Score.ResultsThe international standards for PR3-and MPO-ANCA yielded results of 403 CU and 331 CU in the novel CIAs, respectively. The linearity analysis showed linear regression values > 0.97 with slopes between 0.96 and 1.04. Total variation obtained from the precision study showed CV% of ? 7.4 for PR3-ANCA and ? 12.8 for MPO-ANCA. Good agreement (Spearman rho ? 0.89) was observed between CIA and ELISA. PR3-ANCA determined by CIA, but not by ELISA, was correlated with disease activity. No correlation was found for MPO-ANCA.ConclusionThe novel PR3- and MPO-ANCA CIA show good precision, linearity and correlation to ELISA. In addition, PR3-ANCA showed correlation with disease activity.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 11 January 2012 Surajeet K. Patra, Sarika Arora BackgroundThe cachexia anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, weight loss, anorexia, early satiety, fatigue, weakness due to shifts in metabolism caused by tumour by-products and cytokines. Various neuropeptides like Leptin, neuropeptide Y, melanocortin, agouti-related peptides have been known to regulate appetite and body weight.MethodA comprehensive literature search was carried out on the websites of Pubmed Central (http://www.pubmedcentral.nih.gov/), National Library of Medicine (http://www.ncbl.nlm.nih.gov) and various other net resources.ResultData from observational studies shows that various cytokines (TNF-?, IL-6 and IL-1) are associated with metabolic changes resulting in cachexia in cancer patients. These cytokines may mimic the action of various neuropeptides resulting in anorexia, various metabolic effects resulting from enhanced catabolic state and weight loss.ConclusionThere is a need to understand and explore the role of various neuropeptides and cytokines in the pathophysiology of cancer-anorexia syndrome so that therapeutic measures may be designed for effective palliative care.
Highlights
? Cachexia anorexia syndrome- involuntary weight loss seen in malignancies and inflammatory diseases. ? Hyperalimentation is ineffective in counteracting wasting associated with these diseases. ? Cytokines (TNF-?, IL-6, IL-1) are associated cachexic changes in cancer patients. ? Orexigenic & anorexigenic neuropeptides decrease and increase sympathetic nervous activity. ? Cancer anorexia is due ‘hypothalamic resistance’ to peripheral signals indicating an energy deficit.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Yuki Tomonaga, Thomas Szucs, Patrice Ambühl, Stefan Nock, Martin Risch, ... BackgroundA majority of patients developing acute kidney injury (AKI) receive medical care from their primary care physicians prior to the occurrence of conditions that predispose them to this complication.MethodsTo characterize the uNGAL concentrations in primary care patients and to assess these concentrations with regard to different reference intervals, we conducted a multicenter, cross-sectional study with random selection of general practitioners (GP) from all GP offices in seven Swiss cantons. 1,000 adults (566 females; mean age 57 ± 17 years) were included.ResultsThe median absolute uNGAL was 21 ng/L. Elevated uNGAL (> 100 ng/L) together with normal kidney test results (eGFR and albuminuria) were found in 6.5% of all patients. Females had a significantly higher uNGAL than did males. Among a multitude of different clinical and laboratory variables, only age, gender, liver function parameters, WBC and CRP were significantly associated with uNGAL levels in a multivariate analysis. When examining the proposed KDIGO classification of chronic kidney disease, the uNGAL levels at the given eGFR stages changed with increasing albuminuria stages and vice versa.ConclusionsAge, gender, markers of inflammation and liver function, exert influences on uNGAL concentrations. A substantial proportion of patients exhibited normal kidney testing together with elevated uNGAL, potentially identifying patients with increased renal stress and at increased risk for the development of AKI.
Highlights
? 6.4% of primary care patients exhibit normal kidney testing but increased uNGAL ? Urinary NGAL (uNGAL) concentrations vary according to age and gender ? Creatinine (Cr) excretion accentuates gender and age difference in uNGAL/Cr ratio ? uNGAL concentrations are dependent on liver cell integrity and inflammation ? uNGAL reflects the different stages of the novel KDIGO CKD classification
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Ramin Vafadari, Willem Weimar, Carla C. Baan Cytokines of the IL-2 receptor family act via activation of the JAK-STAT (janus tyrosine kinase-signal transducer and activator of transcription) signaling pathway. These cytokines are pivotal for the development and function of lymphocyte subsets involved in immune response after organ transplantation including T, B and natural killer cells. The new small drug molecule and JAK1/3 inhibitor, tofacitinib, is currently being tested in phase II and III clinical trials for rheumatoid arthritis, psoriasis and in organ transplantation. This agent specifically targets the JAK-STAT signaling pathway. Here we discuss phosphospecific flow cytometry as a novel tool to monitor the JAK-STAT signaling pathway in kidney transplant patients and speculate that through the use of this pharmacodynamic tool the efficacy of immunosuppressive drugs can be assessed enabling optimization of the immunosuppressive therapy for individual transplant patients.List of abbreviationsCNI, Calcineurin inhibitor; IFN-?, Interferon-?; IL-2R, Interleukin-2 receptor; JAK, Janus tyrosine kinase; mAb, Monoclonal antibody; MFI, Median fluorescence intensity; MMF, Mycophenolate mofetil; NK cell, Natural killer cell; PBMC, Peripheral blood mononuclear cells; SCID, Severe combined immunodeficiency; SOCS, Suppressors of cytokine signaling; STAT, Signal transducer and activator of transcription; TAC, Tacrolimus; Treg, Regulatory T cell; TYK, Tyrosine kinase; ?c, Y-chain
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Karin Leander, Bruna Gigante, A. Silveira, M. Vikström, A. Hamsten, ... BackgroundHigh plasma levels of the adipokine NAMPT (or visfatin) have been associated with cardiovascular disease. However experimental data suggest that NAMPT, via Akt signaling, protects the myocardium against hypoxic insults. We studied whether theNAMPTrs1319501,AKT1rs3730358,p53rs1042522,Mdm2rs2279744 oreNOSrs1799983 SNP:s linked to NAMPT and Akt signaling associate with risk of myocardial infarction (MI).MethodsCases were 828 men and 346 women aged 45–70 who had suffered a first MI. Control individuals, 1062 men and 513 women, were randomly chosen from the study base. We employed unconditional logistic regression analysis.ResultsThe rs1319501 minor allele associated with MI among women aged 45–60; odds ratio (OR) under a recessive model of inheritan 2.96 (95% confidence interval [CI] 1.06-8.29). Replication analysis in an independent material yielded OR point estimates in the same direction. The rs3730358 minor allele associated with low MI risk in men aged 45–60 (OR dominant model: 0.72, 95% CI 0.53–0.97), an association completely attenuated by adjusting for inflammatory markers.ConclusionsTheNAMPTrs1319501 minor allele associates with increased MI risk in young women. In young men a protective effect of theAKT1rs3730358 minor allele was suggested, possibly related to an attenuated inflammation.
Highlights
? TheNAMPTrs1319501 associates with increased risk of MI in women aged 45–60. ? Carrying the minor allele atAKT1rs3730358 may protect men aged 45–60 against MI. ? The protective effect in men may be explained by an anti-inflammatory influence.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Li-nian Huang, Dong-sheng Wang, Yu-qing Chen, Wei Li, Feng-dan Hu, ... BackgroundTo assess the prognosis value of cyclin E expression in survival of patients with lung cancer (LC), we performed a systematic review of the literature with meta-analysis.MethodsElectronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association of cyclin E expression with survival of LC patients. Heterogeneity and publication bias were also assessed.ResultsFourteen studies (2606 cases) were eligible and subjected to analysis. Cyclin E over-expression was found to be a strong predictor of poor prognosis in LC patients (HR: 1.38, 95% CI: 1.07-1.79; P = 0.014). When only non-small cell lung cancer (NSCLC) was considered, the combined HR was 1.53 (95% CI: 1.19-1.97, P = 0.001). A significant association was also evident when the analysis was limited to studies involving adenocarcinoma (AD), but not squamous cell carcinoma (SQ). Publication bias was absent. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average.ConclusionCyclin E over-expression was associated with poor prognosis in LC in general and AD specifically.
Highlights
? We quantitatively summarized 14 studies by means of meta-analysis. ? The relation of cyclin E expression with lung cancer has been clarified. ? Cyclin E overexpression is a poor prognosis among lung cancer patients. ? Cyclin E overexpression is a poor prognosis among NSCLC patients. ? Significant association was observed in AD, but not in SQ.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Karin Leander, Bruna Gigante, A. Silveira, M. Vikström, A. Hamsten, ... BackgroundHigh plasma levels of the adipokine NAMPT (or visfatin) have been associated with cardiovascular disease. However experimental data suggest that NAMPT, via Akt signaling, protects the myocardium against hypoxic insults. We studied whether theNAMPTrs1319501,AKT1rs3730358,p53rs1042522,Mdm2rs2279744 oreNOSrs1799983 SNP:s linked to NAMPT and Akt signaling associate with risk of myocardial infarction (MI).MethodsCases were 828 men and 346 women aged 45–70 who had suffered a first MI. Control individuals, 1062 men and 513 women, were randomly chosen from the study base. We employed unconditional logistic regression analysis.ResultsThe rs1319501 minor allele associated with MI among women aged 45–60; odds ratio (OR) under a recessive model of inheritan 2.96 (95% confidence interval [CI] 1.06-8.29). Replication analysis in an independent material yielded OR point estimates in the same direction. The rs3730358 minor allele associated with low MI risk in men aged 45–60 (OR dominant model: 0.72, 95% CI 0.53–0.97), an association completely attenuated by adjusting for inflammatory markers.ConclusionsTheNAMPTrs1319501 minor allele associates with increased MI risk in young women. In young men a protective effect of theAKT1rs3730358 minor allele was suggested, possibly related to an attenuated inflammation.
Highlights
? TheNAMPTrs1319501 associates with increased risk of MI in women aged 45–60. ? Carrying the minor allele atAKT1rs3730358 may protect men aged 45–60 against MI. ? The protective effect in men may be explained by an anti-inflammatory influence.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 9 January 2012 Yuki Tomonaga, Thomas Szucs, Patrice Ambühl, Stefan Nock, Martin Risch, ... BackgroundA majority of patients developing acute kidney injury (AKI) receive medical care from their primary care physicians prior to the occurrence of conditions that predispose them to this complication.MethodsTo characterize the uNGAL concentrations in primary care patients and to assess these concentrations with regard to different reference intervals, we conducted a multicenter, cross-sectional study with random selection of general practitioners (GP) from all GP offices in seven Swiss cantons. 1,000 adults (566 females; mean age 57 ± 17 years) were included.ResultsThe median absolute uNGAL was 21 ng/L. Elevated uNGAL (> 100 ng/L) together with normal kidney test results (eGFR and albuminuria) were found in 6.5% of all patients. Females had a significantly higher uNGAL than did males. Among a multitude of different clinical and laboratory variables, only age, gender, liver function parameters, WBC and CRP were significantly associated with uNGAL levels in a multivariate analysis. When examining the proposed KDIGO classification of chronic kidney disease, the uNGAL levels at the given eGFR stages changed with increasing albuminuria stages and vice versa.ConclusionsAge, gender, markers of inflammation and liver function, exert influences on uNGAL concentrations. A substantial proportion of patients exhibited normal kidney testing together with elevated uNGAL, potentially identifying patients with increased renal stress and at increased risk for the development of AKI.
Highlights
? 6.4% of primary care patients exhibit normal kidney testing but increased uNGAL ? Urinary NGAL (uNGAL) concentrations vary according to age and gender ? Creatinine (Cr) excretion accentuates gender and age difference in uNGAL/Cr ratio ? uNGAL concentrations are dependent on liver cell integrity and inflammation ? uNGAL reflects the different stages of the novel KDIGO CKD classification
Publication year: 2012 Source: Clinica Chimica Acta, Available online 8 January 2012 Philippe Gonzalo, Matthieu Pecquet, Chantal Bon, Sylvie Gonzalo, Sylvie Radenne, ... BackgroundThe CDT assay used to detect chronic alcohol abuse is difficult with cirrhotic patients. This article describes the performances of several CDT assays in case of cirrhosis. The CDT-Capillarys assay by capillary zone electrophoresis was used for initial testing. Two additional methods were tested as putative confirmatory methods.Methods110 patients with known hepatic status had their CDT measured by the Capillarys2 or alternative methods. Self-reported alcohol intake was used to assess the performances of CDT assays.ResultsCapillarys2 performance was lower in case of cirrhosis, many electropherograms displaying various abnormalities. We used the proper separation of the di- and tri-sialotransferrin peaks to select reliable profiles. This selection led to the classification of cirrhotic and non-cirrhotic patients in abusers and abstainers with similar performances. However, no interpretation was available for 54% of the cirrhotic patients and neither the BioRad %CDT by HPLC test, nor the Siemens N-Latex CDT kit were suitable as confirmatory methods for these samples.ConclusionsAn attentive profile examination is required for the validation of Capillarys CDT results of cirrhotic patients. Reliability is significantly improved when samples with an improper separation are excluded. To date, no commercial test can confirm the excluded samples.
Highlights
? CDT assays are tricky and have decreased clinical performance in cirrhotic patients. ? Clinical performance of the CDT-Capillarys in case of cirrhosis is assessed. ? Selection of reliable CDT-Capillarys profiles from cirrhotic patients is achievable. ? Yet, many samples do not pass this selection and require a confirmatory method. ? Unfortunately, HPLC and immunonephelometry do not qualify for such samples.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 8 January 2012 Vanessa Fontana, Pamela S. Silva, Raquel F. Gerlach, Jose E. Tanus-Santos Growing experimental evidence indicates that matrix metalloproteinases (MMPs) are implicated in many cardiovascular diseases including hypertension and its chronic complications. It is now clear that MMPs have many more substrates other than components of the extracellular matrix. In fact, intracellular targets now include those associated with the cardiovascular system. Clinical studies have suggested that circulating MMPs may predict cardiovascular morbidity and mortality. It is highly probable that increased MMPs may predispose hypertensive patients to additional complications and clinical sequelae. In this article, we review the basic principles linking MMP activity with hypertension and summarize clinical studies examining two specific MMPs (MMP-2 and ? 9) in hypertension. We also discuss how antihypertensive drugs may affect MMPs and their endogenous inhibitors, ie, tissue inhibitors of matrix metalloproteinases (TIMPs). Circulating MMPs may predict increased risk of developing cardiovascular complications associated with hypertension. As such, patients could benefit from early pharmacologic intervention including use of MMP inhibitors.
Highlights
? Matrix metalloproteinases (MMPs) are implicated in many cardiovascular diseases. ? The circulating MMPs concentrations predict cardiovascular morbidity and mortality. ? We reviewed basic principles linking imbalanced MMPs activities with hypertension. ? The circulating MMPs levels may identify hypertensive patients are at increased risk. ? Such patients could benefit from the use of MMPs inhibitors.
Publication year: 2012 Source: Clinica Chimica Acta, Available online 8 January 2012 Chia-Ni Lin, Todd J. Emery, Randie R. Little, Steve E. Hanson, Curt L. Rohlfing, ...
Publication year: 2012 Source: Clinica Chimica Acta, Available online 8 January 2012 Chia-Ni Lin, Todd J. Emery, Randie R. Little, Steve E. Hanson, Curt L. Rohlfing, ...
Posted on 8 January 2012 | 10:47 pm
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