Immunochemiluminometric Assay Research Articles

Diagnostic value of stimulated urine luteinizing hormone after triptorelin stimulation test in girls with CPP.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were involved. The triptorelin stimulation test at 8:30 a.m.were performed. Two consecutive 12-hour urine samples were collected after the test, defined as first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in CPP group were higher than those in PPP group. When first 12-hour ULH/Cr was ≥ 287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When second 12-hour ULH/Cr was ≥ 152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When the compliance of blood sampling in girls with precocious puberty is poor, first 12-hour ULH/Cr ≥ 288 IU/mol (or second 12-hour ≥ 153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

The Correlation Between C-Peptide and Severity of Peripheral Atherosclerosis in Type 2 Diabetes Mellitus.

One of the major issues affecting global health is Diabetes mellitus (DM), not only in terms of the disease itself but also its complications. Macrovascular complications are both common and serious, affecting many patients. This study aimed to assess fasting C-peptide levels and correlate them with the severity of the peripheral arterial disease complicating type 2 DM (T2DM). This study included 200 participants who were categorized into two groups: Group I (n=100, patients with T2DM complicated by femoropopliteal arterial atherosclerosis) and Group II (n=100, healthy age- and sex-matched individuals serving as controls). Fasting C-peptide levels were estimated using an immunochemiluminometric assay. Fasting C-peptide levels were significantly higher in Group I than in the control group. Fasting C-peptide levels were positively correlated with the severity of atherosclerosis. In addition, the receiver operating characteristic (ROC) curve analysis revealed that fasting C-peptide levels served as a specific and sensitive marker for detecting the severity of this disease. Fasting C-peptide levels can be used as a sensitive and specific indicator of the severity of femoropopliteal arteriosclerosis that complicates T2DM.

A single blood sample for stimulated LH assayed by ICMA is useful for monitoring the treatment efficacy of triptorelin depot in girls

Background: There is still no consensus on the optimal monitoring method to evaluate the hypothalamic-pituitary-gonadal axis (HPGA) inhibition. Methods: There were 124 girls treated with triptorelin depot due to puberty disorders, including 77 central precocious puberty and 47 early puberty. After treatment, triptorelin stimulation tests were performed, and blood samples were collected at 0, 20, 40 and 60 min. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured by immunochemiluminometric assay (ICMA). Results: Peak LH (PLH), peak FSH and estradiol in 124 girls were significantly decreased after treatment, while 2 cases had inadequate treatment efficacy. Areas under the receiver operating characteristic curves (AUC) of PLH and peak FSH after stimulation for the diagnosis of HPGA suppression were 0.984 and 0.121. When the cut-off value of PLH was ≤ 2.25 IU/L, the sensitivity was 96.7% and specificity was 100.0%. There was no difference in AUC between PLH and a single LH at 20, 40, or 60 min (p > 0.05). When LH were ≤ 2.34 IU/L, ≤ 2.21 IU/L and ≤ 2.00 IU/L at 20, 40 and 60 min, respectively, the sensitivity were 99.1%, 96.7% and 98.4%, and the specificity were all 100.0%. The correlation coefficients between PLH and LH at 20, 40 or 60 min were 0.947, 0.975 and 0.961. Conclusion: A single blood sample for stimulated LH at 20 min, 40 min, or 60 min assayed by ICMA during triptorelin stimulation test is useful for monitoring the treatment efficacy of triptorelin depot in girls with puberty disorders.

Linoleic acid-derived oxylipins and isoprostanes plasma levels are influenced by 1,25-Dihydroxyvitamin D levels in middle-aged sedentary adults: The FIT-AGEING study

IntroductionVitamin D – concretely its active form 1,25-dihydroxyvitamin D (1,25(OH)2D) – maintains several physiological processes. Oxylipins are oxidized lipids derived from ω-6 and ω-3 polyunsaturated fatty acids involved in inflammation. Little is known about the association of 1,25(OH)2D with inflammatory parameters in middle-aged populations – who could be at risk of vitamin D deficiency –. The aim of this study was to investigate the relationship between 1,25(OH)2D plasma levels with circulating white blood cells, platelets counts and oxylipins levels. Materials and methodsA total of 74 (53 % women) middle-aged (40–65 years old) adults were recruited for this cross-sectional study. 1,25(OH)2D plasma levels were measured using an immunochemiluminometric assay. White blood cells and platelets were analyzed by hemocytometry. ω-6 and ω-3 oxylipins plasma levels were measured using liquid chromatography - tandem mass spectrometry. Simple and multiple linear regression models, and Pearson correlation analyses, were performed to study the association of 1,25(OH)2D levels with WBC and platelets counts, and oxylipins, respectively. Results1,25(OH)2D plasma levels were positively related with linoleic acid-derived oxylipins and isoprostanes plasma levels, whereas an inverse relationship with dihomo-γ-linolenic acid/linoleic acid and arachidonic acid/linoleic acid ratios was unveiled. No significant associations were observed for circulating ω-3 oxylipins, white blood cells levels or platelets count. ConclusionsLinoleic acid-derived oxylipins and isoprostanes plasma levels may be influenced by 1,25(OH)2D plasma levels. Further investigations are needed to elucidate the impact of other vitamin D forms upon circulating oxylipins levels.

Асоційовані зміни гормонального статусу та скелетної м’язової тканини у жінок старших вікових груп

У статті наведені причини розвитку саркопенії у людей старших вікових груп — синдрому, що характеризується прогресивним і генералізованим зниженням скелетної м’язової маси, сили та її функції. Висвітлено дані літератури щодо впливу соматотропного гормона на скелетну м’язову тканину, а також результати дослідження, проведеного на базі ДУ «Інститут геронтології імені Д.Ф. Чеботарьова НАМН України». Метою дослідження було вивчити зв’язок між показниками скелетної мускулатури та рівнем соматотропного гормона, загального та вільного тестостерону. Стан знежиреної маси всього тіла, верхніх та нижніх кінцівок оцінювали за допомогою двофотонної рентгенівської абсорбціометрії (Prodigy, GEHC Lunar, Madison, WI, США). Силу скелетної мускулатури оцінювали за допомогою кистьового пружинного динамометра, що пацієнт стискає кистю витягнутої верхньої кінцівки. Для визначення функціональних можливостей скелетних м’язів оцінювали швидкість ходьби обстежених жінок за чотириметровим тестом. Визначення рівня загального та вільного тестостерону та соматотропного гормона в сироватці крові обстежених жінок проведено за допомогою імунохемілюмінесцентного методу з використанням обладнання Immulite 2000 виробництва компанії Siemens DPC (США). Під час дослідження встановлено зв’язок рівня соматотропного гормона та апендикулярної знежиреної маси; рівня загального, вільного тестостерону, соматотропного гормона та сили скелетної мускулатури; рівня загального, вільного тестостерону та функціональних можливостей скелетної м’язової тканини.

Early detection of pregnancy after IVF and embryo transfer with hyperglycosylated HCG versus Elecsys HCG+β assay

Research questionIs measurement of hyperglycosylated HCG (hHCG) superior to beta-HCG (HCG+β) for early pregnancy detection after IVF and embryo transfer? DesignBlood samples were collected on day 4 (+1), 7 (+1) and 11 (+2) after embryo transfer from women aged 18–45 years undergoing first or second fresh or frozen IVF embryo transfer cycles. Biochemical pregnancy was assessed on-site by HCG determination on day 11; clinical pregnancy was assessed by ultrasound on day 21 (+4/–3). Serum hHCG (immunochemiluminometric assay) and HCG+β (Elecsys® HCG+β assay) concentrations were measured. Performance of hHCG and HCG+β for predicting pregnancy was evaluated and cut-offs selected. ResultsIn total, 155 women were enrolled and underwent IVF and embryo transfer. Area under the curve (AUC) (95% CI) on day 4 was not significantly different for hHCG (AUC 0.88; 95% CI 0.83 to 0.94) and HCG+β (AUC 0.90; 95% CI 0.84 to 0.95), as was predictive performance on day 7 and 11, with higher AUC estimates compared with day 4. Applying cut-offs derived according to Youden's index on day 4 (hHCG, 100 pg/ml; HCG+β, 1.30 mIU/ml), both biomarkers demonstrated high negative predictive values for ruling out pregnancy (hHCG, 83.8%; HCG+β, 82.8%) and high positive predictive values for ruling in pregnancy (hHCG, 89.0%; HCG+β, 84.9%) on day 21. Diagnostic performance improved from day 4 to day 11. ConclusionsPredictive performance for early pregnancy post-IVF embryo transfer of day-5 blastocysts was not significantly different for hHCG and HCG+β; hHCG superiority over HCG+β was not shown.

Relationship of sedentary time, physical activity and fitness with 1,25-dihydroxyvitamin D in middle-aged sedentary adults: The FIT-AGEING study.

Potential interactions between sedentary behaviour, physical activity (PA), and physical fitness with 25-hydroxyvitamin D (25(OH)D) status have been previously suggested. However, data are scarce concerning the association between these predictors of general health and the main active metabolite of vitamin D, the 1,25-dihidroxyvitamin D (1,25(OH)2D). This study aimed to analyse the relationship of sedentary time, PA levels, and physical fitness (i.e., maximal oxygen uptake (VO2max) and muscular strength) with 1,25(OH)2D in middle-aged sedentary adults. A total of 73 (39 women) middle-aged sedentary adults (53.7±5.1years old) participated in this cross-sectional study. Sedentary time and PA intensity levels were objectively measured with triaxial accelerometers for 7 consecutive days. VO2max was determined by a maximum treadmill test. Lower and upper limb muscular strength was assessed by an isokinetic strength test and by a handgrip strength test, respectively. 1,25(OH)2D plasma levels were measured using a DiaSorin Liaison® immunochemiluminometric assay. No significant relationships were found between objectively measured sedentary time, PA levels or physical fitness (i.e., VO2max, extension and flexion peak torque, and hand grip strength) and 1,25(OH)2D (all P>0.05). All results persisted after controlling for age, sex, fat mass or energy, vitamin D, calcium, and phosphorus intake. In summary, our results show that vitamin D status is not affected by physical activity habits and sedentary behaviour in middle-aged sedentary adults.

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents.

Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 ± 2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at pFWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?

Background: Measurements of both basal (b) calcitonin (CT) and calcium (Ca)-stimulated CT (Ca-sCT) levels are performed to identify medullary thyroid cancer (MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules (CT screening). Novel immunochemiluminometric assays, which are highly sensitive and specific for monomeric CT and avoid cross-reactivity, have been introduced over the past decade. No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and, therefore, still indicated for the early detection of MTC. Methods: Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT. Regardless of Ca-sCT levels, all patients had an operation applying a uniform surgical protocol, including thyroidectomy and systematic lymph node dissection. Recently published sex-specific cutoff levels for the differentiation of MTC and other C-cell pathologies (C-cell hyperplasia [CCH]) were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic (ROC) analysis. In addition, CT cutoff levels to predict lateral lymph node metastasis were evaluated for bCT compared with Ca-sCT. Follow-up for all patients was documented and correlated with initial CT levels. Results: MTC was identified in 76 (50.1%) patients, in 21/76 (27.6%) with lymph node and in 4 (5.3%) with distant metastasis. Using predefined cutoff levels, patients could effectively be subdivided into a group above the cutoff level with definitive diagnosis of MTC (100%) and below (gray zone) with a significant overlap of CCH and MTC (all classified as pT1a; males: 19/58 [37.5%], females: 7/41 [17.1%]). The areas under the ROC curve (AUC) were excellent for the diagnosis of MTC in all tests. Determination of bCT proved to be superior for both diagnosing MTC in males (AUC for bCT: 0.894; AUC for Ca-sCT: 0.849) and females (bCT: 0.935; Ca-sCT: 0.868) and also for diagnosing lymph node metastasis in the lateral compartment (males: bCT: 0.925; Ca-sCT: 0.810; females: bCT: 0.797; Ca-sCT: 0.674). Combining both tests did not improve diagnostic accuracy. Using a cutoff level of >85 pg/mL for females and >100 pg/mL for males, the sensitivity for diagnosing lateral neck lymph node metastasis was 100%. Below these cutoff levels, no patient showed persistent or recurrent disease (median follow-up: 46 [ ± 27] months). Conclusions: Predefined sex-specific bCT cutoff levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis. Ca-sCT did not improve preoperative diagnostics. bCT levels >43 and >100 pg/mL for males and of >23 and >85 pg/mL for females are relevant for advising patients and planning the extent of surgery.

Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases.

The different mechanisms that trigger the autoimmune attack to the thyroid between Hashimoto's thyroiditis (HT) and Graves' disease (GD) are still unclear. The aim of this study was to recognize thyroid antigens specific CD8+ T-cell epitopes and explore the relationship between these epitopes and thyroid autoantibodies, duration and classification in these two diseases. Free thiiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, TgAb, and TPOAb were all measured by immunochemiluminometric assays, while TRAb was tested by radioimmunoassay. HLA class I peptide affinity algorithms were applied to predict candidate thyroid autoantigen peptides that blind to HLA-A*0201. The ELISpot assay was used to detect Tg-, TPO-, and TSHR-specific CD8+ T cells. We demonstrated that TG-6 was a novel HLA-A*0201-restricted CTL epitope in GD. TG-6, TG-7, TG-10, TG-11, and TPO-6 were immunodominant in GD patients compared with HT patients (TG-6: 38.5 vs. 8%, P = 0.034; TG-7, TG-10, TG-11, and TPO-6: 23.1 vs. 0%, P = 0.034). The immunodominance of TG-6 in GD patients was more evident than healthy controls (HC) (TG-6: 35.8 vs. 0%, P = 0.011), but there was no statistically significant difference between HT patients and HC. Subgroup analyses revealed the T-cell responsiveness to TG-6 was stronger in TgAb-negative HT patients (0 vs. 40%, P = 0.033). However, there was no correlation showed for TPOAb, TRAb, medication and duration in both HT and GD patients. We report for the first time that both diseases, HT and GD, recognize different antigen-specific CD8-positive T cells. Tg maybe the dominant thyroid autoantigen contributing to breaking tolerance in GD. It could improve our knowledge of autoimmune thyroid diseases pathogenesis as well as offer new therapeutical tools in terms of peptide vaccine therapy.

Ultrasonic cardiogram and MiRNA-21 analysis of cardiac dysfunction in patients with cardiac arrest following cardiopulmonary resuscitation

PurposeTo explore correlations between the serum level of miRNA-21 expression and cardiac dysfunction severity after cardiopulmonary resuscitation (CPR) using ultrasonic cardiogram. MethodsThirty-nine patients with cardiopulmonary arrest receiving successful CPR and forty-one healthy participants were recruited in the study. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunochemiluminometric assays was used to examine the serum miRNA-21 level and the concentration of cardiac troponins T and I, respectively. Indices of Electrocardiogram (ECG) and cardiac dysfunction measured by ultrasound of patients in the case group were used to assess cardiac function after CPR. Furthermore, the correlation between the serum level of miRNA-21 expression and severity of cardiac dysfunction was analyzed by Spearman correlation analysis. ResultsAs compared to the control group, the serum level of miRNA-21 expression, as well as cardiac troponin T and I levels in the case group were significantly higher (p = 0.000). The miRNA-21 expression level in the patients at IV grade of cardiac function were substantially higher than patients at III grade (p = 0.015). There was no significant difference in level of cardiac troponins T and I between patients at III grade and patients at IV grade (p > 0.05). Further, Spearman correlation analysis revealed that the level of miRNA-21 expression was negatively correlated with cardiac function index in the ultrasound imaging: E peak, E/A value, LVEF and LVEDD (r = 0.617, 0.535, 0.612, 0.573, P = 0.012, 0.009, 0.008, 0.011), but was positively correlated with the level of cardiac troponins T and I (r = 0.546,0.582, P = 0.006,0.007) and the severity of cardiac dysfunction (r = 0.859, p < 0.05). ConclusionThe level of miRNA-21 is higher after CPR is closely related to the severity of cardiac dysfunction that is measured by ultrasound, suggesting that it may serve as a potential biomarker.

Amniotic fluid and umbilical cord serum erythropoietin in term and prolonged pregnancies

ObjectiveErythropoietin - a hormone regulating erythropoiesis - is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (≥ 37 gestational weeks) and prolonged pregnancies (≥ 41 gestational weeks) with labor induction. Study designThis prospective cohort study comprised 93 singleton pregnancies at 37+0-42+1 gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as ≤ 3 IU/L, and abnormal value as ≥ 27 IU/L. Normal umbilical cord serum erythropoietin was defined as < 40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman’s rank correlation coefficient. The Chi-square test, Fisher’s exact test and the Mann-Whitney U test were utilized to determine differences in the study groups. ResultsAmniotic fluid erythropoietin levels correlated with gestational age (r = 0.261, p = 0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p = 0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r = 0.513, p < 0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r = 0.250, p = 0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome. ConclusionsIn vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome.

Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients: Cross sectional study.

Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003–1.034]), total cholesterol (P = .038 [CI: 1.004–1.164]), fibrosis grade (P < .001 [CI: 0.000–0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus–host interaction.

The Dynamic Trends of Urinary LH and FSH Assayed by ICMA During Triptorelin Stimulation Tests in Girls - a Pilot Study.

Gonadotropin-releasing hormone stimulation test is a gold standard for evaluating the function of the hypothalamic-pituitary-gonadal axis (HPGA) in children. These tests are usually uncomfortable because of multi-venipunctures. A urine specimen is a good alternative because it is noninvasive and convenient. More studies have shown the correlation between sera and urine LH and FSH levels under different physiological and pathological conditions. The study investigated the dynamic trends of urine LH (uLH) and FSH (uFSH) assayed by immunochemiluminometric assays (ICMA) during triptorelin stimulation tests in girls. The triptorelin stimulation tests were performed in 52 girls with disorders of puberty. The time 0 hour was regarded as the start time of the test (8:30 am). The day before the tests, urine samples were collected at 12 hours diurnal (-24 hours ~ -12 hours) and nocturnal (-12 hours ~ 0 hour) time points. On the day of the testing, the first 12 hours (0 hour ~ 12 hours), the second 12 hours (12 hours ~ 24 hours), the third 12 hours (24 hours ~ 36 hours), the fourth 12 hours (36 hours ~ 48 hours), the third and fourth overnight urine samples were also collected. The LH and FSH levels were assayed by ICMA, and uLH and uFSH were corrected for creatinine (Cr). The HPGA in 41 girls was activated but it was nonactivated in 11 girls. In girls with HPGA activated, uLH/Cr or uFSH/Cr was significantly elevated within 24 hours, and gradually dropped to baseline after 48 hours. When HPGA was nonactivated in girls, there were the same dynamic trends but much lower amplitude of uLH/Cr or uFSH/Cr, which dropped to baseline after 24 hours. The stimulated uLH and uFSH assayed by ICMA are valuable for evaluating the function of HPGA in girls, and the valuable time window is within 24 hours.

Effects of Storage Conditions on Urinary LH and FSH Measurement Using Immunochemiluminometric Assay.

Urine is a good alternative body fluid for gonadotropin studies. There was limited information about the effects of different storage conditions on urinary gonadotropin measurement by using immunochemiluminometric assay (ICMA). ICMA was used to determine gonadotropin in urine stored under different conditions, such as different pH, storage time, and cycles of freeze-thaw. Luteinizing hormone (LH) level was not significantly affected at pH 2.5 to 10.5 or being stored at 4°C for 3 days. Follicular stimulating hormone (FSH) level was not significantly changed at pH 3.5 to 10.5 or throughout 49-day storage at 4°C in the absence of glycerol. LH was significantly decreased after freeze-thawing twice, while FSH was resistant to freeze-thaw procedures. LH and FSH can be determined by ICMA in normal urine pH range (4.6 ~ 8.0). Urine LH is more sensitive to long-term storage and multiple freeze-thaw procedures than FSH.

PROTEIN MARKERS OF CARDIONECROSIS IN THE DYNAMICS OF ACUTE CORONARY SYNDROME

The aim of this study was to compare and analyze the effectiveness of protein markers of myocardial necrosis - heart-type fatty acid-binding protein (H-FABP) and the MB fraction of creatine phosphokinase (CPK-MB) in the dynamics of acute coronary syndrome. Material and methods. A total of 49 patients (57.1 ± 11,0 years) were examined, including 36 male patients (73.5 %) who were admitted to the City Clinical Hospital No. 34 of Novosibirsk with suspected acute coronary syndrome. The content of H-FABP in whole venous blood was evaluated for all patients upon admission to the hospital with the means of the immunochromatographic rapid test «CardioPBFA» (NPO «Biotest», Novosibirsk) with a sensitivity of 15 ng/ml. Determination of CPK-MB was carried out repeatedly in the first 48 hours from the beginning of the clinical manifestations of the disease, using immunochemiluminometric assay. Results and discussion. It was revealed that in patients with myocardial infarction (MI), CPK-MB content after 6-24 hours and also after 24-48 hours from the onset of pain was significantly higher than in patients without MI. H-FABP content 15 ng/ml and more, determined in the majority of patients in the first 6 hours from the onset of pain, was recorded much more often in MI presence than in MI absence. Using partial correlation analysis, it was determined that age influenced the association of MI with CPK-MB 6-24 hours after the onset of pain (which is probably due to the increase in the influence of a number of factors modulating the level of protein cardiac markers with age), and the correlation of MI with CPK-MB in 24-48 hours from the onset of pain did not depend on this factor ( r = 0.322; p = 0.46). In the regression model (χ² = 13.6; p = 0.001) it was revealed that H-FABP content 15 ng/ml and more regardless of age ( p = 0.006) is associated with the presence of MI in the patients, which confirms information about the high significance of identifying this H-FABP level in early diagnosis of myocardial infarction.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension.

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

Abstract 2268: Serum insulin and glucose, indices of insulin resistance, and risk of lung cancer

Abstract Background: Although insulin is crucial in human growth and development, it also harbors antiapoptotic properties and acts as a growth factor by stimulating mitosis through the Akt pathway, which could lead to tumor growth and promotion. Insulin has been positively associated with several cancer sites, but no studies to date have examined fasting serum insulin concentrations and risk of lung cancer. Methods: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was a randomized, double-blind intervention trial conducted among 29,133 male smokers in southwest Finland. Participants were randomly assigned to one of four groups in a 2x2 factorial design (α-tocopherol alone, β-carotene alone, both supplements, or placebo). 196 lung cancer cases and 395 subcohort members were sampled from the larger cohort. Fasting serum collected at enrollment (5-12 years prior to diagnosis) was analyzed for insulin using a double-antibody immunochemiluminometric assay, and for glucose using a hexokinase assay. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by quartiles of insulin, glucose, and surrogate indices of insulin resistance (insulin:glucose molar ratio and homeostasis model assessment of insulin resistance [HOMA-IR]). Multivariable models adjusted for age, BMI, family history of lung cancer, and pack-years of smoking. Results: Insulin was positively associated with risk of lung cancer (Q4 vs. Q1 HR: 2.10, 95% CI: 1.12, 3.94). A similar association was seen with HOMA-IR (Q4 vs. Q1 HR: 1.83, 95% CI: 0.99, 3.38). We observed no statistically significant associations with glucose or the insulin:glucose molar ratio (P-trend=0.55 and P-trend = 0.27, respectively). Insulin and HOMA-IR were associated with lung cancer risk regardless of stage, although the findings were stronger for the lower stage cancers (Q4 vs. Q1 insulin, stage I-II HR=2.85, 95% CI: 1.14, 7.15, P-trend=0.01; stage III-IV HR=0.94, 95% CI: 0.93 - 4.06, P-trend=0.23; HOMA-IR stage I-II HR=2.25, 95% CI 0.89-5.69, P-trend=0.02, stage III-IV HR=1.78, 95% CI=0.87 - 3.61, P-trend=0.34). Findings were similar across histologic subtypes of lung cancer. Conclusion: Higher fasting serum insulin and insulin resistance appear to be associated with an increased risk of lung cancer. In addition, elevated insulin concentrations may be more strongly associated with lower stage lung malignancies, suggesting a role for insulin in stimulating the growth of early pulmonary cancers. Citation Format: Ilona Argirion, Stephanie J. Weinstein, Satu Männistö, Demetrius Albanes, Alison M. Mondul. Serum insulin and glucose, indices of insulin resistance, and risk of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2268. doi:10.1158/1538-7445.AM2017-2268

Lead and cadmium exposure, higher thyroid antibodies and thyroid dysfunction in Chinese women

BackgroundExposure to lead(Pb) or cadmium(Cd) has been related to decreasing thyroxine in many previous studies. The underlying mechanisms have not been clarified. Heavy metal-induced thyroid autoimmunity in pregnant women has been found, despite having been rarely explored in the general population. ObjectivesWe aimed to determine whether the blood levels of lead(BPb) or cadmium(BCd) related to the levels of sera antibodies to thyroid proteins and thyroid dysfunction in the general population. MethodsOur study included 5628 Chinese adults and was based on the 2014 SPECT-China study. Thyroid dysfunction and subclinical thyroid dysfunction were defined by total triiodothyronine (TT3), total thyroxine(TT4) and thyroid stimulating hormone (TSH).Thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies (TGAb), TT3, TT4, and TSH were measured by immunochemiluminometric assays. BPb and BCd levels were tested by atomic absorption spectrometry. Linear and logistic regression models were used to analyze the associations. ResultsAfter adjustment for age, body mass index, smoking status (men only) and drinking status, the natural log(ln) BPb was positively related to the lnTPOAb (B = 0.062, P < 0.05) and to the lnTSH (B = 0.047, P < 0.01) in women. The lnBCd in women was positively related to the lnTGAb (B = 0.046, P < 0.05). In the adjusted logistic regression models, the BCd of women was positively related to their hypothyroid status and TGAb tertiles. The ORs of women in the middle and higher TPOAb tertiles were 1.38 (P < 0.001) and 1.35 (P < 0.001) times greater for every ln-unit increase in BPb, respectively. In men, no continuous correlation was found among variables. ConclusionsIn women, BPb and BCd levels were related to higher TSH and hypothyroid status, respectively, suggesting a Pb and Cd induction of sex-biased thyroid autoimmunity.

Abstract B53: Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium

Abstract Background: African Americans (AAs) are known to have a higher prevalence of vitamin D deficiency than European Americans (EAs). Aside from darker skin pigmentation being a major contributing factor, few studies have investigated determinants of blood levels of 25-hydroxyvitamin D (25OHD) in AA women. Recent evidence suggests that differences in levels between AAs and EAs were largely eliminated after accounting for levels of vitamin D binding protein (VDBP). In the current study, we conducted a comprehensive investigation of associations between genetic and non-genetic factors, including circulating VDBP levels, and serum 25OHD levels in AA and EA women. Study population and methods. Data and biospecimens were examined in the context of the African American Breast Cancer Risk and Epidemiology (AMBER) consortium. For this analysis, levels were measured in 1,756 healthy controls from two case-control studies in AMBER, the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS), and included 909 AA and 847 EA women. Blood samples collected at the time of enrollment were used for 25OHD measurement by DiaSorin Liasion immunochemiluminometric assay and VDBP measurement by Assaypro Gc-Globulin ELISA assays. Epidemiological data were collected from questionnaires and harmonized across studies. Genotype data for 25,248 typed and imputed germline variants in vitamin D-related pathways were available as a part of exome genotyping array from AAs in the consortium. Percent of European ancestry in AAs was estimated based on genotype data of ancestry informative markers. Univariate analyses and generalized linear regression analyses were conducted to relate serum 25OHD levels with genetic and non-genetic factors and between AA and EA women. Results: AA women had markedly lower 25OHD levels than EA women (14.2 ng/ml vs. 21.1 ng/ml, p&amp;lt;0.0001), yet had similar levels of VDBP (344 ug/ml vs. 336 ug/ml, p=0.25), which is different from the previous study in AAs showing much lower VDBP levels in AAs than in EAs. Also different is that VDBP levels with were not affected by the two GC polymorphisms rs4588 and rs7041. In AAs, a higher percent of European ancestry was also associated with higher 25OHD levels (p=0.03). Race was the strongest determinant of 25OHD levels, followed by body mass index (BMI), physical activity (walking for exercise), season of blood collection, multivitamin use, dietary vitamin D intake, cigarette smoking and study. Accounting for VDBP levels had little impact on racial difference in 25OHD levels. In analysis of germline variants with serum 25OHD levels, none of the index genome-wide association study (GWAS) variants identified in EAs, including rs2282679 and rs7041 in GC, were significant in AAs in our study. Conclusion: VDBP levels had little impact on notable differences in blood 25OHD levels between AAs and EAs. In addition to race, obesity, season of assessment, and several lifestyle factors were also important determinants of 25OHD levels. Genetic determinants of 25OHD levels in AAs are likely different from those in EAs, which warrants further investigation. Citation Format: Song Yao, Chi-Chen Hong, Ting-Yuan David Cheng, Gary Zirpoli, Stephen A. Haddad, Katherine L. Lunetta, Elisa V. Bandera, Andrew F. Olshan, Julie R. Palmer, Christine B. Ambrosone. Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B53.