Clinica Chimica Acta

Current research reports and chronological list of recent articles.


The international scientific journal Clinica Chimica Acta publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids, cells or tissues.

The publisher is Elsevier. The copyright and publishing rights of specialized products listed below are in this publishing house. This is also responsible for the content shown.

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Additional research articles see Current Chemistry Research Articles. Magazines with similar content (clinical chemistry):

 - Clinical Biochemistry.

 - Clinical Chemistry and Laboratory Medicine.

 - Clinical Chemistry Online.

 - Clinical Science.

 - Clinical Toxicology.

 - Journal of Medicinal Chemistry.

 - Journal of Laboratory Medicine.



Clinica Chimica Acta - Abstracts



FVIIa-antithrombin levels in early and late preeclampsia

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Luci Maria S. Dusse, Lara C. Godoi, Patricia N. Alpoim, Karina B. Gomes, Lirlandia P. Sousa, Luiza O. Perucci, Bashir Lwaleed, Maria G. Carvalho

Background Preeclampsia (PE) is associated with a hypercoagulability state. According to the gestational age (GA) at the onset of the disease, PE has been classified as early (GA<34weeks) and late (GA34weeks). It has been admitted that early PE is associated with ischemic placental lesions, while in late PE an adequate or slightly impaired placentation occurs, which suggests that the two clinical forms have distinct etiology. Tissue factor (TF) binds and activates plasma factor VII triggering the coagulation. The inhibitor antithrombin (AT), along with tissue factor pathway inhibitor, acts as an inhibitor of the FVIIa-TF pathway. Once the TF-FVIIa complex is formed, the binding and transfer of FVIIa to AT is facilitated and FVIIa activity is inhibited. Objective We evaluated the FVIIa-AT complex levels in pregnant women with early and late severe PE (sPE), in order to verify if this biomarker can be useful for discriminating the two forms of the disease. Methods We evaluated 26 pregnant with severe early PE and 19 pregnant with severe late PE. FVIIa-AT levels were measured by STACLOT® (Diagnostica Stago). Statistical analysis was done by Mann-Whitney test. Results Increased FVIIa-AT levels were found in early sPE [148.4pM (137.1)] compared to late sPE [95.9pM (66.5)] (P=0.046), which suggests a higher pro-coagulant state when PE onset occurs before 34weeks of gestation. Conclusion These pioneer data allow inferring the relevance of FVIIa-AT as a device for early sPE diagnosis. However, the clinical relevance of FVIIa-AT complex surely needs to be fully clarified.






Datum: 25.09.2017


Air bubbles and hemolysis of blood samples during transport by pneumatic tube systems

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Garrett R. Mullins, David E. Bruns

Background Transport of blood samples through pneumatic tube systems (PTSs) generates air bubbles in transported blood samples and, with increasing duration of transport, the appearance of hemolysis. We investigated the role of air-bubble formation in PTS-induced hemolysis. Methods Air was introduced into blood samples for 0, 1, 3 or 5min to form air bubbles. Hemolysis in the blood was assessed by (H)-index, lactate dehydrogenase (LD) and potassium in plasma. In an effort to prevent PTS-induced hemolysis, blood sample tubes were completely filled, to prevent air bubble formation, and compared with partially filled samples after PTS transport. We also compared hemolysis in anticoagulated vs clotted blood subjected to PTS transport. Results As with transport through PTSs, the duration of air bubble formation in blood by a gentle stream of air predicted the extent of hemolysis as measured by H-index (p<0.01), LD (p<0.01), and potassium (p<0.02) in plasma. Removing air space in a blood sample prevented bubble formation and fully protected the blood from PTS-induced hemolysis (p<0.02 vs conventionally filled collection tube). Clotted blood developed less foaming during PTS transport and was partially protected from hemolysis vs anticoagulated blood as indicated by lower LD (p<0.03) in serum than in plasma after PTS sample transport. Conclusions Prevention of air bubble formation in blood samples during PTS transport protects samples from hemolysis.






Datum: 25.09.2017


Neonatal screening parameters in infants with congenital Cytomegalovirus infection

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Roberta Rovito, Marjolein J. Korndewal, Peter C.J.I. Schielen, Aloys C.M. Kroes, Ann C.T.M. Vossen

Congenital Cytomegalovirus infection (cCMV) is the most common cause of congenital infections worldwide that can cause long-term impairment (LTI). The metabolic alterations due to cCMV are largely unknown. This study aims to assess the metabolites included in the neonatal screening in relation to cCMV and cCMV outcome, allowing the identification of prognostic markers for clinical outcome. Essential amino acids, hormones, carnitines and enzymes from Dried Blood Spots (DBS) were analyzed of 102 children with cCMV and 179 children without cCMV, and they were related to symptoms at birth and LTI at 6years of age. In this cohort, the neonatal screening parameters did not change in relation to cCMV, nor to symptoms at birth or LTI. However, metabolic changes were observed in children born preterm, with lower concentrations of essential amino acids in premature infants with cCMV compared to premature controls. Finally, a higher concentration of palmytoilcarnitine (C16) in the group with higher viral load was observed. Though these data demonstrate limitations in the use of neonatal screening data as predictors for long-term cCMV outcome, the metabolism of preterm neonates with cCMV merits further evaluation.






Datum: 25.09.2017


Urinary RNA-based biomarkers for prostate cancer detection

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Filippo Martignano, Lorena Rossi, Antonio Maugeri, Valentina Gallà, Vincenza Conteduca, Ugo De Giorgi, Valentina Casadio, Giuseppe Schepisi

Prostate cancer (PCa) is the commonest malignancy in the male population worldwide. Serum prostate specific antigen (PSA) test is the most important biomarker for the detection, follow-up and therapeutic monitoring of PCa. Defects in PSA specificity have elicited research for new biomarkers to improve early diagnosis and avoid false-positive results. This review evaluates urinary RNA-based biomarkers. Urine is a versatile body fluid for non-invasive biomarker detection in case of urological malignancies. The importance of RNA-based biomarkers has been demonstrated by the current use of PCA3, a long non coding RNA biomarker already approved by the Food and Drugs Administration. Through the years, other urinary RNA biomarkers have been evaluated, including the well-known TMPRSS2:ERG transcript, as well as many messenger RNAs, long non coding RNAs and micro-RNA. Validation of a specific urinary RNA-based marker or an algorithm of different biomarkers levels as diagnostic markers for PCa could be useful to avoid unnecessary prostate biopsies.






Datum: 25.09.2017


Heart-type fatty acid-binding protein in cardiovascular disease: A systemic review

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Yoichiro Otaki, Tetsu Watanabe, Isao Kubota

Fatty acid-binding proteins, whose clinical applications have been studied, are a family of proteins that reflect tissue injury. Heart-type fatty acid-binding protein (H-FABP) is a marker of ongoing myocardial damage and useful for early diagnosis of acute myocardial infarction (AMI). In the past decade, compared to other cardiac enzymes, H-FABP has shown more promise as an early detection marker for AMI. However, the role of H-FABP is being re-examined due to recent refinement in the search for newer biomarkers, and greater understanding of the role of high-sensitivity troponin. We discuss the current role of H-FABP as an early marker for AMI in the era of high sensitive troponin. H-FABP is highlighted as a prognostic marker for a broad spectrum of fatal diseases, viz., AMI, heart failure, arrhythmia, and pulmonary embolism that could be associated with poor clinical outcomes. Because the cut-off value of what constitutes an abnormal H-FABP potentially differs for each cardiovascular event and depends on the clinical setting, an optimal cut-off value has not been clearly established. Of note, several factors such as age, gender, and cardiovascular risk factors, which affect H-FABP levels need to be considered in this context. In this review, we discuss the clinical applications of H-FABP as a prognostic marker in various clinical settings.






Datum: 25.09.2017


Clinical, biochemical and molecular features of Iranian families with mucopolysaccharidosis: A case series

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Vahid Reza Yassaee, Feyzollah Hashemi-Gorji, Mohammad Miryounesi, Alireza Rezayi, Zeinab Ravesh, Fakhrolmolouk Yassaee, Shadab Salehpour

This study aims to ascertain the genetic variants which contribute to the most common types of MPS in eleven Iranian families. Clinical and biochemical features were obtained during initial examination and patients were further investigated for genetic defects in the MPS genes. Peripheral blood samples were obtained from all family members after obtaining written informed consent. Based on the patient's clinical diagnosis, three different genetic tests including Sanger sequencing of four genes (IDUA, IDS, SGSH, and GALNS), targeted panel (10 genes) and Whole Exome Sequencing (WES) techniques were applied to identify the causative variants. A total of 12 different mutations were identified in five genes, including nine novel mutations and three previously reported missense mutations. Sanger sequencing confirmation of the identified mutations determined one case of compound heterozygous in the NAGLU gene. In this study, novel mutations in MPS related genes were identified attempting to characterize the type and subtype of the disease using molecular approaches. Results of the study positively contribute to mutation spectrum of IDUA, IDS, SGSH, NAGLU, and GALNS genes in the Iranian cohort. It may also enrich genetic counseling for rapid risk assessment and disease management.






Datum: 25.09.2017


Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure patients

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Denise Traxler, Mitja Lainscak, Elisabeth Simader, Hendrik Jan Ankersmit, Borut Jug

Background Heat shock proteins (HSPs) represent intracellular mechanisms of stress response. Clinical implications of their (systemic) expression in patients with chronic heart failure (HF) remain inconclusive. Methods In outpatients with chronic stable HF plasma HSP27 levels were measured using ELISA. Patients were followed for a minimum of one year, and a multivariate Cox proportional hazard model was built for cardiovascular death or HF-associated hospitalisations. Results A total of 134 patients with chronic HF (mean age 71±10years, 34% female, mean LVEF 36±12%) were included. During a mean follow-up of 527±260days, 44 patients (33%) experienced an event. Mean time to event was 350±236days. In a Kaplan-Meier survival analysis HSP27 levels above the median (3820pg/ml) indicate a higher risk for an event (p=0.03). Increased HSP27 levels remained an independent predictor of events (HR, 2.33 CI 95% 1.12–4.87, p=0.024) even after adjustment for age, gender, NT-proBNP, LVEF, aetiology, smoking status, kidney function and NYHA class. Conclusions HSP27 is an independent predictor of prognosis in chronic HF. Our findings suggest that HSP27 may improve risk-stratification in chronic HF beyond known prognostic predictors.






Datum: 25.09.2017


Average glucose from hemoglobin A1c for altered red blood cell lifetimes: Predictions based on a model for hemoglobin A1c formation

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Ross Molinaro, Jay H. Herman, Douglas F. Stickle

Background A model for hemoglobin A1c (HbA1c) formation was used to predict the relationship between average glucose (AG) and %HbA1c under conditions of altered red blood cell lifetime (RCL). Methods Using a kinetic mass balance model for formation of HbA1c in red blood cells as a function of age (time in circulation), whole blood %HbA1c vs. glucose was calculated based on the nonlinear distribution of red blood cells as a function of age across RCL. Results Model calculations provided a close fit to the standard relationship of estimated average glucose to %HbA1c for normal RCL (r>0.999). Results for altered RCL were calculated assuming simple time-scale compression or expansion of the distribution of red blood cells as a function of RCL. For a given %HbA1c, the operative average glucose needed to have achieved a given %HbA1c was predicted to be altered by RCL according to average glucose×RCL=constant. Conclusions Model calculations estimate the extent to which standard reporting of AG vs. HbA1c underestimates or overestimates AG under conditions of altered RCL. Conditions of altered RCL may often be operative in patients with certain hemoglobin variants.






Datum: 25.09.2017


Association between serum periostin concentrations and outcome after acute spontaneous intracerebral hemorrhage

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Wen-Jian Ji, Xiao-Min Chou, Gang-Qun Wu, Yang-Fang Shen, Xiao-Gang Yang, Zhi-Feng Wang, Luo-Xin Lan, Xu-Gang Shi

Background Higher serum periostin concentrations are associated with mortality after head trauma. We further determined the relationship between periostin concentrations, severity, and clinical outcome in patients with intracerebral hemorrhage (ICH). Methods We prospectively included 128 controls and 128 consecutive patients with acute ICH within the first 24h after onset. At admission, we measured serum periostin concentrations. Results Serum periostin concentrations were significantly higher in the patients than in the controls. Serum periostin concentrations were positively related to National Institutes of Health Stroke Scale (NIHSS) score (r=0.526) and hematoma volume (r=0.586). An unfavorable outcome (defined as modified Rankin scale >2) was observed in 65 (50.8%) patients. Serum periostin [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002–1.013], NIHSS score (OR, 1.462; 95% CI, 1.209–1.767), hematoma volume (OR, 1.134; 95% CI, 1.047–1.227) and age (OR, 1.060; 95% CI, 1.015–1.108) emerged as independent predictors for 6-month unfavorable outcome. In terms of ROC AUC, serum periostin concentrations had significantly higher predictive value compared with age and showed similar predictive value compared with NIHSS score and hematoma volume. Conclusions High concentrations of serum periostin in acute ICH patients are associated with increasing severity and a poor functional prognosis.






Datum: 25.09.2017


Traditional approaches versus mass spectrometry in bacterial identification and typing

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Angela Sloan, Gehua Wang, Keding Cheng

Biochemical methods such as metabolite testing and serotyping are traditionally used in clinical microbiology laboratories to identify and categorize microorganisms. Due to the large variety of bacteria, identifying representative metabolites is tedious, while raising high-quality antisera or antibodies unique to specific biomarkers used in serotyping is very challenging, sometimes even impossible. Although serotyping is a certified approach for differentiating bacteria such as E. coli and Salmonella at the subspecies level, the method is tedious, laborious, and not practical during an infectious disease outbreak. Mass spectrometry (MS) platforms, especially matrix assisted laser desorption and ionization-time of flight mass spectrometry (MALDI-TOF-MS), have recently become popular in the field of bacterial identification due to their fast speed and low cost. In the past few years, we have used liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approaches to solve various problems hindering serotyping and have overcome some insufficiencies of the MALDI-TOF-MS platform. The current article aims to review the characteristics, advantages, and disadvantages of MS-based platforms over traditional approaches in bacterial identification and categorization.






Datum: 25.09.2017


Novel heterozygous mutations of the INSR gene in a familial case of Donohue syndrome

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Litao Qin, Xiaobo Li, Qiaofang Hou, Hongdan Wang, Guiyu Lou, Tao Li, Li Wang, Hongyan Liu, Xichuan Li, Shixiu Liao

Donohue syndrome (DS), a rare autosomal recessive disease which represents severe insulin resistance, pre- and postnatal growth retardation, hypertrichosis, and dysmorphic features, is caused by mutations in the insulin receptor (INSR) gene. Here, we have reported the clinical, molecular, and biochemical characterizations of a patient with DS. In this article, we have also reported a case with 2 novel INSR mutations and the DS phenotype. Using next-generation sequencing (NGS), we screened 27 known genes involved in inherited maturity-onset diabetes of the young (MODY) and identified compound heterozygous mutations in the INSR gene in the patient with DS, c.62T>G (p.L21R) and c.2563G>T (p.V855F). The positive correlation of these mutations with DS was further validated by Sanger DNA sequencing of his lineal consanguinity, indicating that these pathogenic mutations were inherited maternally and paternally, respectively. Therefore, our finding expanded the number of reported cases of this rare disease and the mutation spectrum of INSR mutation, suggesting that NGS is an accurate, rapid, and cost-effective method for the genetic diagnosis of this rare disease.






Datum: 25.09.2017


Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Marwa Ben Jdila, Abir Ben Issa, Boudour Khabou, Bochra Ben Rhouma, Fatma Kamoun, Leila Ammar-Keskes, Chahnez Triki, Faiza Fakhfakh

Introduction West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. Methods The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. Results The results revealed a complex genotype with more than one mutation in each patient including the known mutations c.1910C>G (P2, P3); c.2372A>C in P3 and c.2395C>G in P1 and novel variants including c.616G>A, shared by the three patients P1, P2 and P3; c.1403G>C shared by P2 and P3 and c.2288A>G in patient P1. Conclusions All the mutations were at somatic mosaic state and were de novo in the patients except ones (c.2372A>C). To our knowledge; the somatic mosaic state is described for the first time in patients with West syndrome. Five identified mutations were located in the C-terminal domain of the protein, while the novel mutation (c.616G>A) was in the catalytic domain. Bioinformatic tools predicted that this latter is the most pathogenic substitution affecting 3D protein structure and the secondary mRNA structure. Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability.






Datum: 25.09.2017


Folate and microRNA: Bidirectional interactions

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Emma L. Beckett, Martin Veysey, Mark Lucock

Low folate status is linked to increased risk of a number of conditions, including developmental disorders, some cancers, neurodegenerative and cardiovascular diseases. Some of the mechanisms of these associations are known, but much remains to be elucidated. Aberrant microRNA (miRNA) profiles are also signatures of these conditions, and as such, the association between folate status and miRNA are now being investigated. Potential associations are bidirectional, with miRNA linked to regulation of folate-mediated pathways, and folate linked to modulation of miRNA expression. miRNA are short non-coding RNA, involved in post-transcriptional regulation of gene expression via complementary binding to mRNA. Evidence is emerging that links folate levels to the regulation of miRNA levels, and miRNA to the regulation of the expression of enzymes involved in folate mediated one carbon metabolism. One carbon metabolism is the source of methyl groups for methylation reactions, including DNA methylation and is important in DNA synthesis and repair. miRNA may be modulated by DNA methylation and other epigenetic mechanisms directly, or indirectly via modulation of upstream signalling pathways. As such, there may be bi-directional associations between folate status and miRNA profiles. miRNA may also act as biomarkers for diagnosis or prognosis of conditions associated with folate status.






Datum: 25.09.2017


Association of post-procedural early (within 24h) increases in serum creatinine with all-cause mortality after coronary angiography

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Xiao-sheng Guo, Shi-qun Chen, Chong-yang Duan, Hua-long Li, Wei-jie Bei, Yong Liu, Ning Tan, Ping-Yan Chen, Ji-yan Chen

Background The majority of patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) are discharged early, with only early (within 24h) serum creatinine (SCr) data available without evidence of clinical prognosis. We aimed to systemically evaluate the association between post-procedural early increase in SCr and all-cause mortality following CAG. Methods We performed a retrospective sub-study analysis within a prospective observational study including 3091 consecutive patients with baseline and post-procedural early (within 24h) SCr data. The degree (mild, moderate, or large) of absolute and relative increases in SCr from baseline. The mean follow-up time was 2.49years. Result Moderate or large early increases in SCr were relatively rare (large increase: >1.0mg/dl [0.5%], >100% [0.4%]), whereas mild absolute and relative increases in SCr were more common (mild increase: 0.25 to 0.50mg/dl [4.5%], 25% to 50% [5.9%]). During the follow-up period, there were 136 post-procedural deaths (5.6%). After adjustment for confounders, mild absolute and relative increases in SCr were associated with increased mortality (hazard ratio [HR]: 1.9 and 1.8, respectively, both P <0.05). Moderate or large increases in SCr were associated with higher mortality, even higher than with pre-existing renal dysfunction (HR: 5.36 and 4.12 for moderate increase [0.5 to 1.0mg/dl] and estimated glomerular filtration rate<60ml/min). Conclusion Post-procedural mild, moderate, or large early increase in SCr, is associated with significantly increased long-term mortality. Although moderate or large increase in SCr following CAG was relatively rare, the prognosis is more serious, and is worse than that of pre-existing renal dysfunction. Clinical trial registration Predictive Value of Contrast Volume to Creatinine Clearance Ratio (PRECOMIN, ClinicalTrials.gov NCT01400295).






Datum: 25.09.2017


Rapid and simple analysis of disease-associated biomarkers of Taiwanese patients with schizophrenia using matrix-assisted laser desorption ionization mass spectrometry

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Tiao-Lai Huang, Li-Hua Lo, Jentaie Shiea, Hung Su

Background Matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) is an extremely sensitive analytical tool for characterizing biological compounds in bio samples. In this study, we applied MALDI-TOF MS to assess potential protein biomarkers in the peripheral blood mononuclear cells (PBMCs) of patients with schizophrenia in the acute phase, recovery phase and healthy controls in Taiwan. Methods We recruited 40 participants, including 20 pairs of patients diagnosed with schizophrenia in the acute phase, after four-week treatment with drug in the recovery phase, and 20 healthy controls. The schizophrenic patients were diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), and severity was assessed by a positive and negative symptom scale at baseline and at endpoint following four-week treatment with drug. The patients' PBMCs biomarkers were rapidly measured using a technique that combines MALDI-TOF MS and principle component analysis. A receiver operating characteristic curve was created for the evaluated biomarker. Results Significant differences in α-defensins 1–3 were found between the patients in acute phase with schizophrenia and the healthy controls, but not between the schizophrenic patients in recovery phase and healthy controls or between the schizophrenic patients in acute phase and in recovery phase. Conclusions α-Defensins can be biomarkers of Taiwanese patients with schizophrenia, thus supporting the hypothesis that the inflammatory response and immunity system is correlated with the pathophysiology of schizophrenia. Moreover, the result also implies that α-defensins may be related in schizophrenia-associated disease not in efficacy of drug-treatment.






Datum: 25.09.2017


Human platelet antigens are associated with febrile non-hemolytic transfusion reactions

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Ding-Ping Chen, Ying-hao Wen, Jang-Jih Lu, Ching-Ping Tseng, Wan-Ling Chen, Su-Wei Chang

Background Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reactions, and it could be reduced by transfusing patients with leukocyte-poor blood products. However, FNHTR still occur in certain patients transfused with leukocyte-poor red blood cell (LPR) products. It is examined whether human platelet antigen (HPA) could be a potential membrane antigen that plays a role in FNHTR. Methods A total of 120 inpatient subjects who transfused with LPR (60 in FNHTR group, 60 in control group) were typed for HPA-2, HPA-3, and HPA-15 using sequence specific primer-polymerase chain reaction (SSP-PCR) and electrophoresis. Results HPA-2 unmatched rate between donors and patients in FNHTR group was 18%, and only 3% unmatched rate was observed in control group (p =0.0082). FNHTR group was further classified according to the imputability. There was a significant difference (p =0.0041) between FNHTR (probable imputability, infection) group and control group, and more significant difference (p =0.0008) was seen between FNHTR (probable imputability, febrile neutropenia) group and control group. Conclusions Those results indicated that HPA-2 might play roles on inducing FNHTR in patients suffering from infectious diseases and febrile neutropenia. HPA-2 genotyping between donors and recipients might be worth integrating in pre-transfusion testing to increase transfusion safety.






Datum: 25.09.2017


Elevation of plateletcrit increasing the risk of non-alcoholic fatty liver disease development in female adults: A large population-based study

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Li-Ren Wang, Yi-Fan Zhou, Yu-Jie Zhou, Shu-Hao Zhang, Wen-Yue Liu, Sheng-Jie Wu, Sven Van Poucke, Ming-Hua Zheng

Background Non-alcoholic fatty liver disease (NAFLD) is the one of the most common form of chronic liver disease in China, so it is important to apply bio-marker in predict the development of NAFLD. Aims This study aims to evaluate association between plateletcrit (PCT) and non-alcoholic fatty liver disease (NAFLD) in Chinese female adults. Methods NAFLD was defined as per ultrasound in this study and 9737 NAFLD-free female subjects from Wenzhou People's Hospital were followed for five years in average in the study. The determination of NAFLD PCT quartiles (Q1 to Q4) were defined: 0–0.16, 0.17–0.18, 0.19–0.21, ≥0.22. With Q1 used as reference, 95% confidence intervals (CIs) and hazard ratios (HRs) in different models were computed across each quartile. Results From Q1 to Q4, the incidence ratios (95% CIs) were 8.30 (7.14–9.47), 11.51 (10.12–12.89), 12.68 (11.47–13.89) and 16.46 (15.03–17.88). Simply considering PCT, in the longitudinal population, values in Q2, Q3 and Q4 had HRs (95% CIs) are 1.51 (1.25–1.84), 1.72 (1.44–2.06) and 2.34 (1.96–2.79) versus Q1. After adjusting for all known confounding variables, values in Q2, Q3 and Q4 had HRs (95% CIs) of 1.31 (1.08–1.60), 1.30 (1.09–1.56) and 1.54 (1.29–1.84) in females compared with Q1. Conclusions We reported that elevated serum PCT levels are considered as an independently significant predictor for NAFLD development in females. The high PCT level contributes to the development of NAFLD.






Datum: 25.09.2017


Editorial board members

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473










Datum: 25.09.2017


High serum uric acid concentration predicts poor survival in patients with breast cancer

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Cai-Feng Yue, Pin-Ning Feng, Zhen-Rong Yao, Xue-Gao Yu, Wen-bin Lin, Yuan-Min Qian, Yun-Miao Guo, Lai-Sheng Li, Min Liu

Background Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. Methods A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Results Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15–3.94, p =0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p =0.013). Conclusions High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients.






Datum: 25.09.2017


MicroRNAs and bioactive compounds on TLR/MAPK signaling in rheumatoid arthritis

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Sali Sujitha, Mahaboobkhan Rasool

Rheumatoid arthritis (RA) is a chronic autoimmune mediated joint disease with severe complications affecting 1% of the population worldwide. Although the exact mechanism underlying the aggravation of RA remains unknown, its occurrence can lead to joint degradation and functional disability. Recent evidences have shown that the aberrant expression of microRNAs (miRNAs) play a prominent role in the furtherance of RA. Over the last decade, various intensive studies have validated different microRNAs to be good candidates for diagnostic purposes and for monitoring the disease progression in various inflammatory diseases. A deeper understanding of the molecular mechanism through which miRNAs amplify the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), pro-inflammatory mediators, growth factors and MMPs will act as potential therapeutic targets. More importantly, several studies have briefly reported the crucial role of TLR dependent MAPK signaling pathway, which mediates the pathological features of RA. In this review, we summarize the recent findings and provide a detailed report of the molecular mechanism of microRNA along with the role of TLR/MAPK signaling pathway in RA. However, the major aim of this review is to correlate the aberrantly expressed microRNAs in TLR/MAPK pathway with various well reported bioactive compounds that can modulate these signaling pathways in rheumatoid arthritis. Targeting miRNA expression using specific bioactive compounds might be a potent and an effective target in RA treatment by suppressing the TLR/MAPK pathway.






Datum: 25.09.2017


Urocortins: Actions in health and heart failure

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Miriam T. Rademaker, A. Mark Richards

The urocortins (Ucns), endogenous peptides belonging to the corticotropin-releasing factor (CRF) family, are increasingly recognized as having diverse and important multi-system functions, especially within the cardiovascular system. The biological actions of the three Ucns (Ucn1, Ucn2, Ucn3) are mediated via G-protein-coupled CRF receptors, with both peptides and receptors widely distributed throughout tissues and organs contributing to pressure/volume homeostasis including the heart, vasculature, kidneys and adrenals. The Ucns activate a variety of signaling cascades in cardiomyocytes, vascular smooth muscle cells and endothelial cells including, but not limited to, adenyl cyclase/cAMP and several kinase pathways, with downstream effects comprising vasodilation, augmented cardiac contractility, and protection against hypoxic injury. Increasing evidence suggests the Ucns may be clinically significant molecules in the pathogenesis, treatment and/or management of several conditions, with some of the most compelling data demonstrating a therapeutic potential for the peptides in the setting of heart failure. Circulating levels of the Ucns are elevated in this setting, and antagonism of the endogenous peptides exacerbates manifestations of the syndrome in animal models. All three Ucns exert salutary hemodynamic, neurohormonal and renal effects in experimental heart failure and recent clinical trials have demonstrated hemodynamic benefits of Ucn2 administration.






Datum: 25.09.2017


Nonalcoholic fatty liver disease associated with metabolic syndrome: Influence of liver fibrosis stages on characteristics of very low-density lipoproteins

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Diego Lucero, Verónica Miksztowicz, Gisela Gualano, Cristina Longo, Graciela Landeira, Estela Álvarez, Valeria Zago, Fernando Brites, Gabriela Berg, Eduardo Fassio, Laura Schreier

Background We evaluated possible changes in VLDLcharacteristics, and metabolic related factors, in MetS-associated NAFLD and accompanying liver fibrosis. Methods We studied 36 MetS patients with biopsy-proven NAFLD (MetS+NAFLD) and 24 MetS without ultrasound NAFLD evidence. Further, MetS+NAFLD was sub-divided according to fibrosis stage into, non-to-moderate (F0–F2, n=27) and severe (F3–F4, n=9) fibrosis. We measured: lipid profile, VLDL composition and size (size exclusion-HPLC), CETP and lipoprotein lipase (LPL) activities and adiponectin. Additionally, in MetS+NAFLD type IV collagen 7S domain was measured. Results MetS+NAFLD showed increased VLDL-mass, VLDL particle number, VLDL-triglyceride% and large VLDL-% (p<0.04). CETP activity tended to increase in MetS+NAFLD (p=0.058), while LPL activity was unchanged. Moreover, in MetS+NAFLD, adiponectin was decreased (p<0.001), and negatively correlated with VLDL-mass and VLDL particle number (p<0.05), independently of insulin-resistance. Within MetS+NAFLD group, despite greater insulin-resistance, patients with severe fibrosis showed lower plasma triglycerides, VLDL-mass, VLDL-triglyceride%, large VLDL-% and CETP activity (p<0.05), while type IV collagen was increased (p=0.009) and inversely correlated with large VLDL-% (p=0.045). Conclusions In MetS, NAFLD is associated with larger and triglyceride over-enriched circulating VLDLs, of greater atherogenicity. However, when NAFLD progresses to severe fibrosis, circulating VLDL features apparently improved, probably due to early alterations in hepatic synthetic function.






Datum: 25.09.2017


lncRNA PVT1 in cancer: A review and meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Dapeng Lu, Peng Luo, Qi Wang, Yuanyuan Ye, Baolong Wang

Objectives Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA that functions as an oncogenic molecule in different cancers. We conducted a systematic review and meta-analysis to determine its prognostic potential for malignant tumors. Materials and methods A literature survey was conducted by searching the PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wanfang electronic databases for articles published as of June 1, 2017. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to demonstrate the relationship between PVT1 expression and overall survival (OS) and disease-free survival (DFS) using RevMan 5.2 and Stata 12.0 software. A quality assessment of the included studies was performed according to the Newcastle–Ottawa scale. Results A total of 1443 patients from 15 studies were included in this meta-analysis. Elevated PVT1 expression was significantly correlated with poor overall survival (HR=2.03, 95% CI: 1.69–2.43) and disease-free survival (HR=1.55, 95% CI: 1.29–1.87). Statistical significance was also observed in a subgroup meta-analysis that was stratified by variance analysis, cancer type, sample size and PVT1 cut-off value. Additionally, increased PVT1 expression was significantly associated with positive lymph node metastasis (odds ratio (OR)=1.94, 95% CI: 1.03–3.68), positive distant metastasis (OR=3.85, 95% CI: 2.14–6.93), advanced tumor-node-metastasis stage (OR=3.19, 95% CI: 2.45–4.15) and poor differentiation grade (OR=1.57, 95% CI: 1.15–2.16), but not tumor size (P >0.05). Conclusion Elevated PVT1 expression was related to poor prognosis and might be a potential biomarkerof clinicopathological characteristics in different cancer types. More studies need to be conducted to verify the clinical value of PVT1 in human cancers.






Datum: 25.09.2017


The (in-)validity of volatile POCT parameters from patients beyond normothermia

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Michael A. Gruber, Stefan Felbermeir, Regina Lindner, Martin Kieninger

Background A common characteristic of all blood gas analyzers on the market is that measurements are processed at 37°C, not at the real patients´ temperature. Subsequently temperature-sensitive parameters can be mathematically corrected (alpha-stat method) or used directly (pH-stat method). National rules in Germany (Rili-BAEK) demand defined accuracy and precision without any restriction to samples´ temperatures or corrections. As consequence in the investigation at hand we tried to find out whether blood gas analyzers can fulfill the regulations for pCO2 and pO2 when normothermia of the matrix is not given. Methods Five matrices (blood from intensive care unit (ICU) patients, blood from healthy donors and 3 levels of bovine based quality control material) were tonometered at “high” and “low” partial pressures of O2 and CO2 within the RiLi-BAEK controlled range at 32, 37 and 40°C. One mL material was aspired into each blood gas (BG) syringe and analysis was accomplished immediately after. The procedure was repeated 10-fold for “high” and “low” gas concentrations and run on 4 different analyzers. At 18°C instead to the “high” one a “median” gas (n =10 as well) was employed. Every condition which constitutes of temperature (4), matrix (5), analyzer (4) and level of the partial pressure (2) led to a total of 1600 measurements. Results At 32°C or 37°C matrix temperature 7.5% to 27.5% of the pCO2(T) and between 14.5% and 28.1% of the pO2(T) results were outside the borders required by the RiLi-BAEK. At 18°C or 40°C the number of results beyond the allowed borders grows up to 82.5% for pCO2(T) and 73% for pO2(T) depending on the partial pressure (PP) level. Conclusions High precision in automated quality control (at a constant matrix temperature) is given in modern BGAnalyzers but is counteracted in practice by non normothermic patient's temperature and unavoidable sample handling effects.






Datum: 25.09.2017


Association between promoter polymorphism (−108C>T) of paraoxonase1 gene and it's paraoxonase activity in patients with Type2 diabetes in northern Iran

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Raheleh Shakeri, Safoura Khajeniazi, Abdoljalal Marjani

Type 2 diabetes mellitus (T2DM) is one of the diseases which depend on the obesity associated with insulin resistance. Various factors, such as a reduction in the activity of paraoxonase-1 enzyme (PON1), could affect T2DM. PON1 is a multifunctional enzyme with paraoxonase and arylesterase activities. The Activity of PON1 is influenced by various SNPs. The aim of presence study is to investigate the association between promoter polymorphism (−108C>T) of PON1 gene and its paraoxonase activity in patients suffering from Type 2 diabetes in Golestan Province, north of Iran. To this end, genomic DNA was extracted from whole blood then genotyping was carried out using PCR-RFLP and enzymatic activity of paraoxonase was measured in the serum of 90 healthy subjects and 90 diabetic patients. Data was analyzed using SPSS version 16. The relationship between the level of paraoxonase activity with polymorphisms of CC, CT, and TT was statistically significant in patients with T2DM. There was a significant association between polymorphism C-108>T of PON1 and type2 diabetes mellitus, with 24.4% of control group subjects and 15.5% of patients having CC genotype; p <0.05. The ratio for CT genotype in target and control groups was 51.1% and 61.1% respectively; p <0.05. TT genotype was 33.3% in patients and 14.4% in the control group; p <0.05. In the present study, the highest frequency belonged to CT genotype in both the control and the target groups, followed by CC genotype in control group and TT genotype in target group. Our findings revealed that paraoxonase activity of PON1 in the control group was significantly higher in comparison with diabetic patients.






Datum: 25.09.2017


Necessity of preoperative activated partial thromboplastin time test as a predictor for surgical hemorrhage in obstetric and gynecological patients in China

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Zhang Ge, Zhang Xia, Wang Yuefang, Ma Zhigui

Background On an international scale, the necessity of preoperative coagulation screen remains controversial, yet in China, coagulation screen is still a routine test before surgery required by the Ministry of Health of China. Methods A retrospective review of 26,807 patients >18y presenting with problems related to the areas of gynecology and obstetrics from March 2013 to July 2015 was performed, and the rate of major bleeding and the amount of blood lost during surgery were compared among groups of patients grouped according to the values of preoperative APTT, the departments the patients belonged to, or the measures for intervention. Results Groups with increased APTT had higher rates of major bleeding (9.80% & 26.14% vs 2.77%, P <0.001) and more blood loss (862.9 and 1455.6ml vs 194.0ml, P <0.001). And the same conclusion could be induced in both the obstetric and gynecological patients when they were taken into account separately. For obstetric patients, once those with high bleeding risks, e.g., placental abruption, placental implantation, or preoperative massive hemorrhage were excluded, groups with increased APTT would no longer demonstrated the higher rate of major bleeding (0.91% & 2.38% vs 0%, P =0.409 & 0.833) and would even have a lower amount of blood loss (202.76 and 228.09ml vs 322.13ml, P =0.003 and 0.027). In increased APTT patients without bleeding or bleeding tendency, FFP intervention would not make a difference in the rate of major bleeding (7.69% vs 8.37%, P =0.203) and the amount of blood loss (271.35ml vs 306.63, P =0.865). Conclusion For Chinese patients from the Obstetrics and Gynecology Departments, APTT is a good screen test to predict surgical hemorrhage.






Datum: 25.09.2017


Gamma-glutamyltransferase and risk of chronic kidney disease: A prospective cohort study

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Setor K. Kunutsor, Jari A. Laukkanen

Background Elevated serum gamma-glutamyltransferase (GGT) activity has been linked with an increased risk of chronic kidney disease (CKD) in Asian populations. We aimed to assess the prospective association of serum GGT with risk of CKD in a Caucasian population. Materials and methods We related GGT activity to the incidence of CKD in 2338 men aged 42–61years of the Kuopio Ischemic Heart Disease study with normal kidney function at baseline. Repeat measurements of GGT were used to correct for within-person variability. Results During a median follow-up of 25.6years, 221 men developed new-onset CKD. The age-adjusted regression dilution ratio of loge GGT was 0.70 (95% CI: 0.64–0.75). Gamma-glutamyltransferase was log-linearly associated with risk of CKD in age-adjusted analysis. In Cox regression analysis adjusted for age, the hazard ratio (95% CIs) for CKD per standard deviation increase in loge baseline GGT was 1.25 (1.09–1.43) which was attenuated to 1.01 (0.86–1.19) on further adjustment for several confounders. Conclusion Contrary to previous evidence of an independent association between elevated GGT and increased risk of CKD in Asian populations, initial evidence of an association between GGT and CKD in Caucasian men was confounded by body mass index, lifestyle factors, and lipids.






Datum: 25.09.2017


I index is not an accurate indicator of icteria in conjugated hyperbilirubinemia

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Nora Nikolac Gabaj, Marijana Miler, Roman Mihic

Introduction Serum indices have become a standard in assessing degree of endogenous interferences in serum and plasma samples. The aim of this study was to evaluate accuracy of I index in comparison with total bilirubin concentration in icteric samples with ranging amount of conjugated bilirubin. Materials and methods This study retrospectively analyzed data from laboratory information system. Total, conjugated bilirubin and I index are measured on Abbott Architect c8000 (N =900). Agreement between total bilirubin and I index in subgroups according to proportion of direct bilirubin (<50% and ≥50%) was investigated using Bland-Altman analysis. Results In samples where percentage of direct bilirubin accounts for <50% of total bilirubin there was no statistically significant constant difference, while small proportional difference was observed (2.5%) between total bilirubin and I index. In samples where percentage of direct bilirubin accounts for ≥50% of total bilirubin, significant constant (26.6) and proportional difference (22.2%) were observed between total bilirubin and I index. Conclusion I index is not accurate indicator of icteria if >50% of bilirubin is conjugated. Manufacturers should declare icteria interference with both, bilirubin concentration and value of I index.






Datum: 25.09.2017


Platelet to lymphocyte ratio in biliary tract cancer: Review and meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Lin-hua Zhou, Xiao-feng Luo

Background The platelet to lymphocyte ratio (PLR) has been found to predict clinical outcomes in multiple malignancies. The aim of this study was to assess the prognostic value of pretreatment PLR in biliary tract cancer (BTC). Methods We searched the MEDLINE, EMBASE, and Cochrane databases to identify studies evaluating the prognostic significance of pretreatment PLR in BTC. The end points were overall survival (OS), recurrence-free survival (RFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. Results A total of eleven studies comprising 2392 patients were included in the study. Pooled results showed that elevated PLR was significantly associated with decreased overall survival (HR: 1.59, 95% confidence interval [CI]: 1.42–1.78, p <0.001) and recurrence-free survival (HR: 1.53, 95% CI: 1.16–2.00, p =0.002). Subgroup analyses suggested that a high PLR predicted decreased OS in patient with BTC, regardless of sample size (<200 or ≥200), treatment methods (surgery, mixed, or chemotherapy), tumor stage (mixed or metastatic), analysis methods (univariate or multivariate), cut-off values (<150 or ≥150), and NOS score (<7 or ≥7). Conclusions Elevated pretreatment PLR may be an unfavorable prognostic factor for clinical outcomes in patients with biliary tract cancer.






Datum: 25.09.2017


DNA demethylation pattern of in-vitro fertilized and cloned porcine pronuclear stage embryos

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Xiaowei Nie, Qiang Liu, Ronggen Wang, Wenjie Sheng, Xiaokang Li, Manling Zhang, Yong Jin, Lihua Zhao, Daorong Hou, Ning Yang, Zhaoqiang Wu, Yifan Dai, Rongfeng Li

Recent studies in mice showed that the Ten-eleven translocation Enzymes (TET) family is involved in the active DNA demethylation. The isotype TET-3 is responsible for the conversion of 5mc (5-methylcytosine) to 5hmc (5-hydroxymethylcytosine) at the pronuclear stages of mouse embryo. This study was performed to investigate the pattern of methylation change and the role of TET family in the demethylation process of porcine in-vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) derived embryo. Bisulfite-sequencing PCR (BSP) and DNA glucosylation and digestion before quantitative PCR (qGluMS-PCR) were done to evaluate the exact change of methylation during porcine pronuclear stages. The results showed that the amount of 5hmc detected increased whereas 5mc decreased in IVF embryo from pronuclear stage 2 (PN2) to pronuclear stage 5 (PN5). In addition, Immunofluorescent staining showed that the 5hmc signal, also detected in oocytes, significantly increased in both pronucleus from fertilization to PN2. The amount of 5hmc continued to rise in male pronucleus but decreased to a very low level in female pronucleus from PN2 to PN5. The above results indicate that female pronucleus might undergo active demethylation only at early pronuclear stages. On the other hand, male pronucleus might undergo active demethylation throughout all pronuclear stages. The expression of three TET isotypes (TET-1, TET-2, TET-3) were tested and TET-3 was found to be the highest expressed isotype. High TET-3 concentrations observed mainly in male pronucleus using immunofluorescent staining, implying that TET-3 might be the main enzyme which catalyzes the conversion of 5mc to 5hmc. In contrast, no TET-3 signal was detected in female pronucleus through the pronuclear stages. The demethylation pattern of SCNT embryos resembled that of the male pronucleus of IVF embryos, suggesting that active demethylation might happen in porcine cloned embryo.






Datum: 25.09.2017


PSEN1 gene polymorphisms in Caucasian Alzheimer's disease: A meta-analysis

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): V. Ramakrishnan, R.S. Akram Husain, Shiek S.S.J. Ahmed

Background A meta-analysis was performed to assess PSEN1 gene polymorphisms (rs1800839 and rs17125721) in Alzheimer's disease (AD) risk. Methods A systematic electronic search was performed across databases to retrieve studies published before 31 January 2017. The association between the selected PSEN1 polymorphisms and AD was based on five genetic models using DerSimonian and Laird's method or Mantel-Haenszel's method. Results A total of 14 case–controlled studies were included. Results showed that rs1800839 polymorphism was significantly associated with AD in allelic OR=0.85 (95% CI [0.72–1.00]) and dominant OR=0.82 (95% CI [0.69–0.98]) genetic models, respectively. However, an insignificant association was found for rs17125721 polymorphism in all genetic models. Conclusions Meta-analysis of PSEN1 gene suggests that the rs1800839 polymorphism has potential influence on AD among Caucasians.






Datum: 25.09.2017


Macrophage migration inhibitory factor as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Yi-Hua Chen, Zhen-Yu Cheng, Lin-Hua Shao, Hua-Song Shentu, Bing Fu

Background Macrophage migration inhibitory factor (MIF) has been implicated in inflammation. We clarified whether serum MIF could be used as a marker of inflammation, brain damage and outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods Serum samples from 102 aSAH adults and 102 healthy controls were determined. The World Federation of Neurological Surgeons (WFNS) scale was used for neurological evaluation and radiological severity was estimated in accordance with the Fisher scale. Results Serum MIF, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and S100B concentrations were significantly higher in patients than in controls. Serum MIF concentrations correlated with WFNS scores and Fisher scores and serum concentrations of CRP, IL-6, TNF-α and S100B. Serum MIF was identified as an independent predictor for 6-month unfavorable outcome (defined as Extended Glasgow Outcome Scale score of 1–4). Area under receiver operating characteristic curve of serum MIF concentrations was similar to those of WFNS scores, Fisher scores and serum S100B concentrations and significantly exceeded those of serum CRP, IL-6 and TNF-α concentrations. Conclusions Serum MIF provides information about inflammation, brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.






Datum: 25.09.2017


Phosphorus and mortality risk in end-stage renal disease: A meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Yue Hou, Xiujiang Li, Liguang Sun, Zhihui Qu, Lili Jiang, Yujun Du

Background Studies on the association of abnormal serum phosphorus level with all-cause mortality in patients with end-stage renal disease (ESRD) have yielded inconsistent results. Objective To evaluate the association of abnormal serum phosphorus level with all-cause mortality in patients with ESRD requiring dialysis by conducting a meta-analysis. Methods Pubmed and Embase databases were searched through March 2017 to identify all observational studies that assessed the association between abnormal serum phosphorus level and all-cause mortality risk in patients with ESRD requiring dialysis. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the highest versus referent phosphorus category and lower versus referent phosphorus category, separately. Results Nine cohort studies were eligible for analysis. During 12 to 97.6months follow-up duration, 24,463 death events occurred among 1,992,869 ESRD patients. Meta-analysis showed that the pooled HR of all-cause mortality was 1.16 (95% CI 1.06–1.28) for the lower versus referent serum phosphorus category. Similarly, patients with highest serum phosphorus levels were associated with an increased risk of all-cause mortality (HR 1.39; 95% CI 1.31–1.47) compared with those in the referent phosphorus category. Subgroup analyses revealed that the effect of phosphorus on the all-cause mortality risk appeared to be stronger within 2years follow-up. Conclusions Both very high and very low values of phosphorus are independently associated with an increased risk for all-cause mortality in ESRD patients requiring dialysis. This meta-analysis highlighted a non-linear association of serum phosphorus with all-cause mortality among dialysis-dependent ESRD patients.






Datum: 25.09.2017


Implementation of point-of-care testing in a general internal medicine practice: A confirmation study

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Elizabeth-Lee Lewandrowski, Sunu Yeh, Jason Baron, J. Benjamin Crocker, Kent Lewandrowski

Background In a previous study we reported on the impact of point-of-care testing (POCT) on practice efficiency in an academic primary care practice that was established to develop new models of care delivery. Here we report a follow-on confirmation study in a more typical primary care practice in the community. Methods In this observational study with a retrospective comparison analysis we measured metrics of practice efficiency on two patient cohorts: those that did not receive POCT and those that did. Results In the patient cohort that received POCT there was a 99% reduction in letters to patients (p<0.001), a 75% decrease in calls to patients (not significant due to small numbers), a 50% reduction in follow-up tests per visit (p=0.044) and a 38% reduction in follow-up visits due to abnormal test results (p=0.178). Financial analysis including testing costs, revenues and efficiency gains to the practice demonstrated a net financial benefit of $11.90–14.74 per patient visit. Conclusions Our data confirm the earlier published findings that POCT can improve metrics of practice efficiency in a primary care practice.






Datum: 25.09.2017


Metabonomics screening of serum identifies pyroglutamate as a diagnostic biomarker for nonalcoholic steatohepatitis

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Suwen Qi, Depeng Xu, Qiaoliang Li, Ni Xie, Jun Xia, Qin Huo, Pu Li, Qiwen Chen, Si Huang

Objective A key step in managing non-alcoholic fatty liver disease (NAFLD) is to differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis (SS). Method Serum samples were collected from three groups: NASH patients (N =21), SS patients (N =38) and healthy controls (N =31). High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to analyse the metabolic profile of the serum samples. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) to identify novel metabolites. The potential biomarkers were quantitatively determined and their diagnostic power was further validated. Results A total of 56 metabolites were capable of distinguishing NASH from SS samples based on the OPLS-DA model. Pyroglutamate was found to be the most promising factor in distinguishing the NASH from SS groups. With an optimal cut-off value of 4.82mmol/L, the sensitivity and specificity of the diagnosis of NASH were 72% and 85%, respectively. The area under the receiver operating characteristic (AUROC) of the pyroglutamate levels of NASH versus SS patients was more than those of tumor necrosis factor-α, adiponectin and interleukin-8. Conclusion These data suggest that pyroglutamate may be a new and useful biomarker for the diagnosis of NASH.






Datum: 25.09.2017


Leptin concentrations and SCD-1 indices in classical homocystinuria: Evidence for the role of sulfur amino acids in the regulation of lipid metabolism

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Soraia Poloni, Poli Mara Spritzer, Roberta H. Mendes, Vânia D'Almeida, Kamila Castro, Fernanda Sperb-Ludwig, Johanna Kugele, Sara Tucci, Henk J. Blom, Ida V.D. Schwartz

Background We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU). Methods Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Sulfur amino acids (SAA) and their derivatives (total homocysteine, cysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, and glutathione), lipids (free fatty acids, acylcarnitines, triglycerides and lipoproteins), glucose, insulin, leptin, adiponectin, and isoprostanes were measured in plasma. Insulin resistance was evaluated by HOMA-IR. To estimate liver SCD-1 activity, SCD-16 [16:1(n7)/16:0] and SCD-18 [18:1(n9)/18:0] desaturation indices were determined. Results In HCU patients, SCD-16 index was significantly reduced (p=0.03). A trend of an association of SCD-16 index with cysteine was observed (r=0.624, p=0.054). HCU patients displayed lower lean mass (p<0.05), with no differences in fat mass percentage. Leptin and low-density lipoprotein concentrations were lower in HCU patients (p<0.05). Femur bone mineral density Z-scores were correlated with plasma cysteine (r=0.829; p=0.04) and total homocysteine (r=0.829; p=0.04) in HCU patients. Conclusions We report alterations in leptin and SCD-1 in HCU patients. These results agree with previous findings from epidemiologic and animal studies, and support a role for SAA on lipid homeostasis.






Datum: 25.09.2017


Accurate eGFR reporting for children without anthropometric data

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Emil den Bakker, Reinoud Gemke, Joanna A.E. van Wijk, Isabelle Hubeek, Birgit Stoffel-Wagner, Anders Grubb, Arend Bökenkamp

Introduction Reporting estimated glomerular filtration rate (eGFR) instead of serum concentrations is advised in current guidelines. Most creatinine-based eGFR equations for children require height, a parameter not readily available to laboratories. Combining height-dependent creatinine- and cystatin C-based eGFR improves performance. Recently, a height-independent creatinine-based eGFR equation has been developed. Aim To compare the combination of height-independent creatinine- and cystatin C-based equations with a combination of equations using anthropometric data. Methods Retrospective analysis of 408 pediatric inulin clearance studies with simultaneous height, creatinine, cystatin C and urea measurements. eGFR calculation using the recalibrated Schwartzcrea (height-dependent), FASage (height-independent) and the Schwartzcys equation. The means (Schwartzcrea +Schwartzcys)/2 and (FASage+Schwartzcys)/2 were compared with the CKiD3 equation incorporating cystatin C, creatinine, urea, height and gender in terms of %prediction error and accuracy. Results All three single parameter equations performed similarly (P30 accuracy around 80%). (FASage+Schwartzcys)/2 (P30 89.2%) and (Schwartzcrea +Schwartzcys)/2 (P30 89.0%), performed comparably to CKiD3 (P30 90.0%). If the difference between the creatinine- and the cystatine C based eGFR was <40%, P30 accuracy of the mean exceeded 90%. Conclusion Combining the height-independent FASage and SchwartzCys equations substantially improves accuracy and performs comparably to height-dependent equations. This allows laboratories to directly report eGFR in children.






Datum: 25.09.2017


A fast and simple method for simultaneous measurements of 25(OH)D, 24,25(OH)2D and the Vitamin D Metabolite Ratio (VMR) in serum samples by LC-MS/MS

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Neus Fabregat-Cabello, Jordi Farre-Segura, Loreen Huyghebaert, Stéphanie Peeters, Caroline Le Goff, Jean-Claude Souberbielle, Étienne Cavalier

Background Rapid, easy and reliable measurement of the major vitamin D metabolites is required in order to fulfill the needs of a clinical routine laboratory. To overcome these challenges, we have developed and validated a LC-MS/MS method for the quantification of 25-hydroxyvitamin D2 and D3, epi-25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. Methods Sample preparation was based on precipitation and centrifugation of 100μL of patient serum, followed by injection into the LC-MS/MS system. Samples from Vitamin D Standardization Program (n =80) and patient samples (n =281) have been compared with a reference LC-MS/MS method. For the analytical validation NIST and Labquality quality control materials were used. Results Mean intra-assay and inter-assay imprecision were <6.0 and 6.4% and mean recoveries were within 95–104%. LOQ's were 0.5μg/L for 24,25(OH)2D3, 1.1μg/L for 25(OH)D3 and epi-25(OH)D3 and 1.7μg/L for 25(OH)D2. A 3% bias obtained between the proposed and the reference method satisfies Vitamin D Standardization Program recommendations. Conclusions We present a rapid, easy, reliable and cost-effective method completely adequate for routine testing, which permits the measurement of the ratio of 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D, Vitamin D Metabolite Ratio (VMR), in serum samples.






Datum: 25.09.2017


Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Yasuko Yamamoto, Naoe Goto, Masao Takemura, Wakana Yamasuge, Kuniaki Yabe, Tsuyoshi Takami, Tatsuhiko Miyazaki, Tamotsu Takeuchi, Makoto Shiraki, Masahito Shimizu, Seiji Adachi, Koshiro Saito, Yuhei Shibata, Nobuhiko Nakamura, Takeshi Hara, Ginette Serrero, Kuniaki Saito, Hisashi Tsurumi

Background GP88 (progranulin; PGRN) is a secreted 88kDa glycosylated protein, with important functions, including inflammation and tumorigenesis. We assessed the significance of GP88 expression in survival outcomes of patients with malignant lymphoma (ML). Methods Serum samples from 254 previously untreated ML patients were examined to measure GP88 concentrations using a sandwich human GP88 ELISA kit. Immunohistochemical analyses were performed to examine GP88 tumor tissue expression. Results The median serum GP88 concentration of ML patients was 91.3ng/ml, and was significantly higher than that of the control group (median, 57.7ng/ml) (p<0.0001). Association between GP88 serum concentrations and overall survival (OS) was examined in patients with diffuse large B cell lymphoma (DLBCL) who had been stratified based on their serum GP88 concentrations. Kaplan Meier survival analysis showed that patients with serum GP88 concentrations of ≤116 and >116ng/ml, had 5-y OS rates of 70% and 50%, respectively (p=0.02). The immunohistochemical analyses of GP88 tumor expression revealed that DLBCL patients had lymphoma cells that were positive for GP88. Conclusions High serum GP88 concentrations are associated with poor prognosis in patients with DLBCL.






Datum: 25.09.2017


Preliminary evaluation of UF-5000 Body Fluid Mode for automated cerebrospinal fluid cell counting

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Michela Seghezzi, Barbara Manenti, Giulia Previtali, Maria Grazia Alessio, Paola Dominoni, Sabrina Buoro

Background Cellular analysis of cerebrospinal fluid (CSF) provides important diagnostic information in various medical conditions. The aim of this study was to evaluate the application of Sysmex UF-5000 body fluid mode in cytometric analysis of CSF compared to Light Microscopic (LM). Methods Eighty-one consecutive CSF samples were analyzed by UF-5000 body fluid mode and by LM. The study also included the evaluation of: limit of Blank (LoB), limit of Detection (LoD), limit of Quantitation (LoQ), carryover and linearity. Results For total nucleated cells (TNC-UF) and white blood cells (WBC-UF) LoB, LoD and LoQ were 1×106 cells/L, 1.8×106 cells/L and 1.9×106 cells/L respectively. For red blood cells (RBC) LoB was 2×106 cells/L, LoD was 3.5×106 cells/L and LoQ was 14×106 cells/L respectively. Linearity was excellent, carryover was negligible. The agreement between UF-5000 body fluid mode parameters and manual cell counts was good in all CSF samples with bias ranged between −0.5 and 25.1×106 cells/L. The ROC curve analysis showed an area under curve of 0.99 for both TNC-UF and WBC-UF parameters. Conclusions The UF-5000 body fluid mode offers rapid and accurate counts in clinically relevant concentration ranges, replacing the LM for most samples. However, in samples with abnormal cell counts or with abnormal scattergram the need for microscopic review remains.






Datum: 25.09.2017


Prognostic and clinical significance of VEGFR-3 in gastric cancer: A meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Hua Ge, Yan Yan, Lingfei Guo, Xueyan He, Xianzhi Yang

Background Recent studies have suggested that VEGFR-3 is involved in the development of gastric cancer, however, the results are contradictory. Hence, we conducted a meta-analysis to assess the correlation between VEGFR-3 and the clinicopathological characteristics of gastric cancer to assess its prognostic value. Methods An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, and Chinese CNKI. Correlations between VEGFR-3 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results Positive VEGFR-3 expression was not correlated with gender or tumor differentiation. However, high levels of VEGFR-3 expression were significantly associated with depth of invasion and lymph node metastasis. Moreover, VEGFR-3 expression was associated with poor three year and five year overall survival rates (OS) in GC patients. Conclusions Our meta-analysis found that VEGFR-3 expression was associated with depth of invasion and lymph node metastasis in gastric cancer. The results suggest that VEGFR-3 may be a useful prognostic biomarker for gastric cancer.






Datum: 25.09.2017


Short- and medium-term biological variation estimates of leukocytes extended to differential count and morphology-structural parameters (cell population data) in blood samples obtained from healthy people

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Sabrina Buoro, Anna Carobene, Michela Seghezzi, Barbara Manenti, Aurelio Pacioni, Ferruccio Ceriotti, Cosimo Ottomano, Giuseppe Lippi

Background Recent studies showed that some cell population data (CPD) parameters of neutrophils may be useful for diagnosing myelodysplastic syndromes and sepsis, for the differential diagnosis of acute promyelocytic leukemia, and some CPD parameters of lymphocytes may be a valuable tool for preliminary screening of B cell lymphoproliferative disease. Notwithstanding the knowledge, no information has been made available about their analytical quality specification. This study was aimed to define short- and medium-term biological variation (BV) estimates and reference change value (RCV) of leukocyte count, extended leukocyte differential and CPD. Methods The study population consisted of 43 healthy volunteers, who participated in the assessment of medium-term (21 volunteers; blood sampling once a week for 5 consecutive weeks) and short-term (22 volunteers; blood sampling once a day for 5 consecutive days) BV, using Sysmex XN. Outlier analysis was carried out before CV-ANOVA, to determine BV estimates and their confidence intervals. Results The medium-term and short-term within-subject BV (CVI) was comprised between 0.6–19.7% and 0.2–21.9%, whereas the medium-term and short-term between-subjects BV (CVG) was comprised between 1.2–61.5% and 1.1–58.5%. The RCVs were found to be similar for all the parameters, in both arms of the study, except for some CPD parameters. Conclusion This study allowed accurately estimating the BV of many leukocyte parameters, some of which have not been currently explored. The kinetics of some leukocyte turnover suggests the use of short-term BV data for calculating analytical goals and RCV.






Datum: 25.09.2017


Improved sensitivity of serum/plasma 1α,25-dihydroxyvitamin D quantification by DAPTAD derivatization

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Takayuki Ishige, Mamoru Satoh, Shoujiro Ogawa, Motoi Nishimura, Kazuyuki Matsushita, Tatsuya Higashi, Fumio Nomura

Background Although immunoassays have several limitations such as the cross-reactivities of antibodies, such techniques are widely used for serum/plasma 1,25(OH)2D quantification. An accurate method is required for the determination of the 1,25(OH)2D status. Methods We designed a serum/plasma 1,25(OH)2D quantification method using LC-MS/MS. Immunoaffinity extraction (IE) and the recently developed Cookson-type reagent 4-(4′-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) were used for sample preparation and derivatization, respectively. Analytical and pre-analytical validations were performed. Serum 1,25(OH)2D3 concentrations were determined in 232 healthy Japanese individuals. Results The intra- and inter-assay CVs for 1,25(OH)2D3 were 5.2% and 7.0%, respectively. The limit of quantification for 1,25(OH)2D3 was 7.1pg/ml. Rheumatoid factor (RF) at concentrations below 517IU/ml did not affect serum 1,25(OH)2D analysis. No significant differences were observed for various blood collection tubes, repeated freeze–thaw cycles, whole blood standing time, or serum storage time. A strong correlation between LC-MS/MS and radioimmunoassay (RIA) was observed (r=0.786), but serum 1,25(OH)2D concentrations obtained from RIA were 2-fold higher than those obtained from LC-MS/MS. Serum 1,25(OH)2D3 concentrations by LC-MS/MS were 18.7–53.9pg/ml. Conclusion A highly sensitive and selective LC-MS/MS-based serum/plasma 1,25(OH)2D quantification method was developed using IE and DAPTAD derivatization. This method will enable the accurate determination of serum/plasma 1,25(OH)2D concentrations in the clinical setting.






Datum: 25.09.2017


High serum adipocyte fatty acid binding protein level as a potential biomarker of aortic arterial stiffness in hypertensive patients with metabolic syndrome

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Ming-Chun Chen, Bang-Gee Hsu, Chung-Jen Lee, Chiu-Fen Yang, Ji-Hung Wang

Background The adipocyte-fatty-acid-binding protein (A-FABP) has been implicated in arterial stiffness, metabolic syndrome (MetS), and cardiovascular disease. We aimed to determine the relationship among serum A-FABP concentration, cardiometabolic risk factors, and central arterial stiffness in a hypertensive population. Methods Fasting blood samples and baseline characteristics were obtained from 110 hypertensive patients. Serum A-FABP concentrations were determined by enzyme immunoassay kit. High arterial stiffness was defined as carotid-femoral pulse wave velocity values >10m/s via the SphygmoCor system. Results Patients with MetS and high arterial stiffness accounted for 67.3% and 42.7% of the study population, respectively. Serum A-FABP was positively associated with MetS and high arterial stiffness (P=0.006 and P<0.001, respectively). Multivariable stepwise linear regression analysis of the significant variables of arterial stiffness revealed that logarithmically transformed A-FABP (log-A-FABP, β=0.278, P=0.002) was positively correlated arterial stiffness in hypertensive patients. Subgroup analysis revealed that log-A-FABP (β=0.327, P=0.003), age (β=0229, P=0.032), and triglyceride (β=0.307, P=0.004) were significantly positively correlated with arterial stiffness in hypertensive patients with MetS. Conclusions Elevated A-FABP concentration could be a predictor for MetS and arterial stiffness in hypertensive patients.






Datum: 25.09.2017


Gross deletions in FBN1 results in variable phenotypes of Marfan syndrome

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Jiacheng Li, Wei Wu, Chaoxia Lu, Yaping Liu, Rongrong Wang, Nuo Si, Fang Liu, Jian Zhou, Shuyang Zhang, Xue Zhang

Background A mutation in FBN1 is primarily attributed to Marfan syndrome (MFS). So far, >1800 unique FBN1 mutations have been identified, with the vast majority being single-nucleotide substitutions, small deletions, and insertions. The rearrangement of large fragments of FBN1 accounts for only 1.7% of all variants. The aim of this study was to investigate the characteristics of large genomic rearrangements in FBN1 among MFS patients and to evaluate the correlations between genotype and phenotype. Methods Systematic sequencing of the disease-related genes FBN1, TGFBR1, and TGFBR2, was carried out previously for 26 unrelated patients with MFS. No small mutations were found. Subsequently, multiplex ligation-dependent probe amplification was performed for the detection of copy number variations in these patients. The breakpoints were determined by gap PCR and sequencing. Transcription level analysis was conducted in patients whose RNA sample was available. Results Four gross deletions were identified in FBN1. Three deletions (exons 6, 48–53, and 49–50) were predicted to be in-frame deletions; the remaining deletion (exons 1–36) was expected to induce the loss of one copy of the FBN1 gene. The breakpoints of these four deletions were cloned, and revealed deletion sizes of 16,551, 10,346, 4563, and 187,047bp, respectively. Patients with in-frame deletions of exons 48–53 and 49–50 showed severe clinical phenotypes; Patient with an exon 6 deletion showed mild potential MFS phenotypes. And the patient had classic MFS with a deletion of exons 1–36. Conclusions We characterized four large genomic rearrangements in FBN1. FBN1 haploinsufficiency correlated with a classic MFS phenotype, while in-frame deletions between exons 24–53 of FBN1 tended to cause severe clinical phenotypes.






Datum: 25.09.2017


Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Mehmet Aslan, Ufuk Duzenli, Ramazan Esen, Yasemin Usul Soyoral

Background The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Methods Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Results Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; p <0.001). Moreover, obese subjects have lower levels of TAC than in those in healthy subjects (p <0.001). In the Pearson's correlation analysis, enzyme activity of prolidase was positively related with TOS (p <0.001, r =0.529) and OSI (p<0.001, r =0.519) as well as BMI (p<0.001, r =0.692) and inversely related with TAC (p <0.05, r =0.405) in obese subjects. Conclusions Increased serum prolidase activity and decreased antioxidant levels are likely to be a results of increased of oxidative stress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects.






Datum: 25.09.2017


Tanshinone IIA increases aquaporins expression in human amniotic epithelial WISH cells by stimulating GSK-3β phosphorylation

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Ying Hua, Shengdi Ding, Huihui Cheng, Hui Luo, Xueqiong Zhu

Background A recent study found that Salvia miltiorrhiza extract substantially increased amniotic fluid index in women with oligohydramnios. Abnormal aquaporin (AQP) expression is associated with oligohydramnios. This study aims to investigate the effect of tanshinone IIA, the major lipophilic component in the root of Salvia miltiorrhiza, on the function and expression of AQPs in human amniotic epithelial WISH cells and the molecular mechanism underlying the effect. Methods WISH cells were treated with tanshinone IIA. Cell proliferation and swelling were determined by cell counting kit-8 assay and measurement of cell size, respectively. A human phospho-MAPK antibody array was used to screen tanshinone IIA-associated signaling molecules. The protein expression of AQPs, glycogen synthase kinase 3β (GSK-3β), and phosphorylated GSK-3β (p-GSK-3β) was analyzed by Western blot. Result Tanshinone IIA significantly inhibited WISH cell proliferation at ≥50μM (P <0.05) and the IC50 was 35μM. Cell size was significantly increased by the treatment with 35μM tanshinone IIA for 24h (P <0.05). WISH cells expressed AQP1, AQP3, AQP8, and AQP9 predominantly in cytoplasm. The dose of tanshinone IIA to maximally induce AQP1 and AQP3 expression was 35μM; for AQP8 and AQP9, the dose of maximal stimulation was 5μM (All P <0.05). Tanshinone IIA (35μM)-mediated up-regulation of AQP8, AQP9, AQP1, and AQP3 peaked at 6, 12, 24, and 24hours of treatment, respectively. Tanshinone IIA increased p-GSK-3β level significantly (P <0.05). Blockade of GSK-3β expression by siRNA and inhibition of GSK-3β activity by lithium chloride significantly reduced tanshinone IIA-induced AQP1 and AQP3 expression (All P <0.05). Conclusion Tanshinone IIA increases AQPs expression in WISH cells by stimulating p-GSK-3β. AQP8 responds to tanshinone IIA the most rapidly compared with AQP9, AQP1, and AQP3 in WISH cells.






Datum: 25.09.2017


Preoperative platelet count improves the prognostic prediction of the FIGO staging system for operable cervical cancer patients

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Ru-ru Zheng, Xiao-xiu Huang, Chu Jin, Xin-xin Zhuang, Le-chi Ye, Fei-yun Zheng, Feng Lin

Background Increased platelet has been identified as an independent and unfavorable prognostic indicator in various cancers including cervical cancer. In our study, the prognostic value of preoperative platelet count combining with FIGO (International Federation of Gynecology and Obstetrics) stage in patients with operable cervical cancer was investigated. Methods A large cohort study including 800 operable cervical cancer patients was conducted from May 2005 to December 2012. Cancer-related biomarkers such as platelet count, hematocrit, hemoglobin, RDW was evaluated together with FIGO staging system in stage IA1–IIA2 cervical cancer patients. The prediction validity of platelet together with FIGO stage was then evaluated by receiver operating characteristic (ROC) curve, and the areas under the curve (AUCs) were compared by Z test. Results Univariate cox proportional hazard analysis demonstrated that hematocrit, platelet count, hemoglobin, FIGO stage, tumor differentiation, PLN (pelvic lymph node metastasis), LVSI (vascular lymph node invasion) were associated with overall survival (OS) and disease free survival (DFS), instead of RDW (red cell distribution width), age and histological subtype. Multivariate analysis demonstrated that preoperative platelet and FIGO stage were independent predictors for OS and DFS in cervical cancer. Furthermore, significant improvements were found after the combination of platelet count and FIGO stage in predicting OS and DFS for cervical cancer patients (P =0.0128 and P =0.0385, respectively). Conclusions Combination of platelet count and FIGO stage improved the prediction performance of FIGO staging and provide additional risk stratification for operable cervical cancer patients.






Datum: 25.09.2017


Establishing age-specific reference intervals for anti-Müllerian hormone in adult Chinese women based on a multicenter population

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Xinqi Cheng, Qiong Zhang, Min Liu, Shijun Li, Zhihua Tao, Kiyoshi Ichihara, Songlin Yu, Kai Zhang, Pengchang Li, Jianhua Han, Ling Qiu

Aim of this study Anti-Müllerian hormone (AMH) is useful for the assessment of ovarian reserve and treatment of individualized in vitro fertilization (IVF). The aim of this study is to establish AMH reference interval for adult Chinese women on the Beckman Beckman DxI 800 platform. Material and methods From May to September 2013, serum from 1169 apparently healthy adult females from five representative cities in China (Beijing, Hangzhou, Guangzhou, Dalian and Urumqi) were collected, and AMH was analyzed on the platform of Beckman DxI 800 automated chemiluminescence immunoassay. Multiple regression analysis was used to investigate the effects of region, sex, age, body mass index (BMI), systolic blood pressure (SBP), exercise on AMH. Age specific reference interval for AMH was established. Results The main factor affecting AMH levels was age (B=0.756, P<0.001). The AMH reference intervals for adult Chinese women aged 19–24years, 25–29years, 30–34years, 35–39years, 40–44years, 45–49years and ≥50years were 0.74–16.06, 0.67–11.64, 0.50–9.99, 0.09–8.33, 0.04–4.09, 0.01–1.46 and <0.01–0.18ng/ml, respectively. The linear, quadratic and cubic models could either provide good fit regression model to describe the decline of AMH with age (R2 =0.40). Conclusion This study firstly established age-specific reference intervals for AMH in Chinese women based on multicenter population.






Datum: 25.09.2017


Cell-free DNA induced apoptosis of granulosa cells by oxidative stress

Publication date: October 2017
Source:Clinica Chimica Acta, Volume 473

Author(s): Yichun Guan, Wenjuan Zhang, Xingling Wang, Pengfei Cai, Qi Jia, Wenjie Zhao

Background Cell-free DNA is a DNA fragment that is produced by cell apoptosis which can affect the micro-environment of cell apoptosis. The levels of Cell-free DNA have been associated with successful rate of in vitro fertilization-embryo transfer (IVF-ET) and embryonic development. Our aim is to determine the relationship between cell-free DNA and embryo quality. The mechanisms of cell-free DNA in granulose and the apoptosis will be determined also. Methods The study enrolled patients who were undergone IVF for the first time and grouped the patients as pregnant (n =130) and non-pregnant (n =59). The relationship was determined by statistical analysis between the levels of cell-free DNA in the follicular fluid and clinical data of IVF patients. Flow cytometry was done to detect the rate of granulosa cell apoptosis and intracellular reactive oxygen species (ROS) level. Western blotting and fluorescent quantitative PCR detected the apoptosis-related gene expressions. Results Clinical data statistics showed that cell-free DNA levels were positively correlated with granulosa cell apoptosis and negatively correlated with embryo quality and pregnancy rates. High levels of cell-free DNA lead to increased ROS in granulosa cells and activated caspase through Fas/FasL that induced apoptosis. Conclusion High levels of cell-free DNA triggers granulosa cell apoptosis and influences oocyte maturation embryo development and pregnancy rates in IVF treatments. Cell-free DNA can be as a secondary criteria and predictive marker for the quality control of IVF embryo.






Datum: 25.09.2017






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