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1.
PIVKA-II: A biomarker for diagnosing and monitoring patients with pancreatic adenocarcinoma.
Tartaglione, S, Mancini, P, Viggiani, V, Chirletti, P, Angeloni, A, Anastasi, E
PloS one. 2021;(5):e0251656
Abstract
BACKGROUND Pancreatic adenocarcinoma (PDAC) is an incurable cancer without adequate tumor markers. Our previous study has showed a better diagnostic performance of Protein Induced by Vitamin K Absence II (PIVKA-II) compared to currently used PDAC biomarkers. To corroborate our previous data with a larger sample size and to assess a possible role of PIVKA-II in predicting surgical success. Additionally, to further evaluate the hypothesis of a direct PIVKA-II production by PDAC cells, we examined PIVKA-II tissue expression in a case of PDAC using immunofluorescence. METHODS We enrolled 76 newly diagnosed PDAC patients and selected 11 patients to determine PIVKA-II levels also after surgical resection. An immunofluorescence (IF) study of PIVKA-II tissue expression was carried out in one of them. PIVKA-II serum values were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Belgium). RESULTS PIVKA-II serum levels were above the cut-off at baseline in 71 patients (94%) with a median value of 464 mAU/Ml (range 27-40783 mAU/mL); the sensitivity and specificity were 78.67% and 90.67% respectively. Patients with pre-operative PIVKA-II positivity showed a significant decrease (P < 0.015) of median PIVKA-II serum concentrations after surgery: 820 (91-40783) mAU/mL at diagnosis vs 123 (31-4666) mAU/mL post-operatively. IF assay on PDAC sections demonstrated PIVKA-II expression in cancer cells. CONCLUSION These data are the first showing a decreased PIVKA-II serum levels after surgery in PDAC patients and reporting PIVKA-II expression in PDAC tissue. Further studies are needed to confirm these findings and to determine PIVKA-II usefulness in diagnosing and monitoring PDAC patients.
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2.
Postprandial regulation of prouroguanylin in humans of a healthy weight and those who are overweight or with obesity.
Patterson, M, Ward, H, Halvai, D, Holm Nilsen, HA, Reeves, S
Peptides. 2020;:170179
Abstract
Uroguanylin is a peptide gut hormone proposed to have a role in signalling post meal satiety. Uroguanylin circulates as its pro-hormone, prouroguanylin. There has been limited investigation of the regulation of prouroguanylin by food; therefore we investigated prouroguanylin regulation following meals. In separate experiments we investigated the effects of high calorie (1451 kcal) and medium calorie (725 kcal), high fat meals, on plasma prouroguanylin concentrations. We then examined the effect of a 722.5 kcal high carbohydrate breakfast on prouroguanylin concentrations, comparing the response in healthy weight adults versus those who are overweight/ with obesity. The 1451 kcal meal increased prouroguanylin concentrations, versus fasting at 60 (P < 0.05), 90 (P < 0.01) and 120 (P < 0.001) minutes. After the 725 kcal meal hormone concentrations rose more slowly and were significant versus fasting concentrations at 120 min (P < 0.01). The high carbohydrate breakfast 722.5 kcal, led to an initial suppression of hormone concentrations at 30 min. post meal (P < 0.05) followed by an increase in concentrations until they were significant versus fasting at 120 min. (P < 0.01). Participants overweight/ with obesity had lower fasting prouroguanylin concentrations (P < 0.05), but post meal concentrations did not differ between the groups. Our results suggest there is a delayed increase in prouroguanylin concentrations following, large and regular sized mixed macronutrient meals rich in fat or carbohydrate. Fasting levels are suppressed in people who are overweight/ with obesity, but the post meal response remains intact. There may be potential to target post meal release of prouroguanylin in obesity.
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3.
The N-Terminus Makes the Difference: Impact of Genotype-Specific Disparities in the N-Terminal Part of The Hepatitis B Virus Large Surface Protein on Morphogenesis of Viral and Subviral Particles.
Jiang, B, Wen, X, Wu, Q, Bender, D, Carra, G, Basic, M, Kubesch, A, Peiffer, KH, Boller, K, Hildt, E
Cells. 2020;(8)
Abstract
The N-terminus of the hepatitis B virus (HBV) large surface protein (LHB) differs with respect to genotypes. Compared to the amino terminus of genotype (Gt)D, in GtA, GtB and GtC, an additional identical 11 amino acids (aa) are found, while GtE and GtG share another similar 10 aa. Variants of GtB and GtC affecting this N-terminal part are associated with hepatoma formation. Deletion of these amino-terminal 11 aa in GtA reduces the amount of LHBs and changes subcellular accumulation (GtA-like pattern) to a dispersed distribution (GtD-like pattern). Vice versa, the fusion of the GtA-derived N-terminal 11 aa to GtD causes a GtA-like phenotype. However, insertion of the corresponding GtE-derived 10 aa to GtD has no effect. Deletion of these 11aa decreases filament size while neither the number of released viral genomes nor virion size and infectivity are affected. A negative regulatory element (aa 2-8) and a dominant positive regulatory element (aa 9-11) affecting the amount of LHBs were identified. The fusion of this motif to eGFP revealed that the effect on protein amount and subcellular distribution is not restricted to LHBs. These data identify a novel region in the N-terminus of LHBs affecting the amount and subcellular distribution of LHBs and identify release-promoting and -inhibiting aa residues within this motive.
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4.
Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.
Molina-Vega, M, Castellano-Castillo, D, Sánchez-Alcoholado, L, Plaza-Andrade, I, Perera-Martin, G, Cabrera-Mulero, A, Fernández-García, JC, Ramos-Molina, B, Cardona, F, Tinahones, FJ
Biomolecules. 2020;(5)
Abstract
Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist.
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5.
Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study.
Yan, C, Hu, J, Yang, J, Chen, Z, Li, H, Wei, L, Zhang, W, Xing, H, Sang, G, Wang, X, et al
Clinical biochemistry. 2018;:32-36
Abstract
BACKGROUND Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects. METHODS This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method. RESULTS The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P < 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females. CONCLUSIONS The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries.
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6.
Serum procalcitonin and calcitonin normal values before and after calcium gluconate infusion.
Giovanella, L
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2012;(3):169-70
Abstract
AIM: To evaluate and compare serum procalcitonin (PCT) and calcitonin (hCT) levels before and after stimulation with intravenous calcium gluconate in selected thyroid healthy subjects. METHODS There were enrolled 78 healthy blood donors with no history of thyroid disease, renal disease, neuroendocrine tumours, infections or inflammatory diseases, and taking no proton-pump inhibitors medication. Serum PCT and hCT were measured before and after intravenous injection of 2.5 mg/kg calcium gluconate. RESULTS Undetectable basal PCT values were found in all subjects while a marginal increase occurred only in 2 male subjects after stimulation. The basal and stimulated 95th percentile hCT values were 7.80 pg/mL and 102 pg/mL in males and 5.20 pg/mL and 78.5 pg/mL in females, respectively. CONCLUSIONS Our data suggest that calcium gluconate physiologically stimulate the release of mature hCT molecule from the parafollicular C-cells with no or minimal effects on the PCT release. Our preliminary results form a reliable reference platform for basal and calcium-stimulated PCT measurements in clinical studies.
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7.
Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines.
Carr, BI, Wang, Z, Wang, M, Wei, G
Digestive diseases and sciences. 2011;(6):1876-83
Abstract
PURPOSE DCP is a useful HCC tumor marker, which reflects a defect in vitamin K metabolism. We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also. EXPERIMENTAL DESIGN HCC patients who had both elevated AFP and DCP were included. A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose. RESULTS A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose. No toxicities were found up to 1,000 mg/infusion. In the phase II cohort, 93% of patients had tumor marker responses by decreased DCP levels, but only 22% had responses by decreased AFP levels. CT scans showed 11% of patients had PRs, 59% had stable tumors and 29.6% had tumor progression. Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis. CONCLUSIONS Vitamin K1 was non-toxic at high doses, strongly inhibited plasma DCP levels, but weakly suppressed AFP levels. The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth, as DCP levels were decreased in patients without AFP change, and were suppressed in vitro at 1% of the vitamin K1 concentration needed to inhibit AFP.
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8.
How does short-term low-dose simvastatin influence serum prohepcidin levels in patients with end-stage renal disease? A pilot study.
Li, XY, Chang, JP, Su, ZW, Li, JH, Peng, BS, Zhu, SL, Cai, AJ, Zhang, J, Jiang, Y
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2010;(3):308-14
Abstract
Anemia is a common clinical problem in end-stage renal disease (ESRD). Despite adequate erythropoiesis-stimulating agent (ESA) supplementation, some ESRD patients still have suboptimal hemoglobin levels, and iron deficiency and inflammation are recognized as the two most common causes. Hepcidin, a newly discovered key regulator of iron homeostasis, is found to be accumulated in ESRD. As it controls iron uptake and release, better reflecting real-time iron demand and availability, hepcidin might become a target in the management of iron deficiency and ESA resistance in dialysis patients. For their pleiotropic functions apart from lipid-modulation, statins are also used as anti-inflammatory or immune-modulating agents. In this study, we applied simvastatin for the purpose of influencing serum prohepcidin level in a group of maintenance hemodialysis patients. Thirty-three ESRD patients undergoing hemodialysis were enrolled and assigned to experimental and hemodialysis control groups according to their lipid profile. Nineteen healthy adults were chosen as a normal control group. The subjects in the experimental group took 20 mg simvastatin orally per night for eight weeks, and those in the hemodialysis control group took no statins or any other lipid-modulating drugs. Before and after the experiment, the serum prohepcidin concentrations, plasma IL-6, and serum C-reactive protein (CRP), ferritin, hemoglobin, albumin, total cholesterol, glycerinate, and LDL and HDL cholesterol levels were determined. Of the 33 hemodialysis patients, the serum prohepcidin concentration was (175.8 +/- 52.9) ng/mL, significantly higher than that in the normal control group (149.5 +/- 24.2) ng/mL (P = 0.048). In the experimental group, the serum prohepcidin level was (156.7 +/- 51.9) ng/mL before treatment, and (190.6 +/- 49.6) ng/mL after eight weeks (P = 0.127). In the hemodialysis control group, the serum prohepcidin level was (190.6 +/- 49.6) ng/mL at the beginning, and (193.5 +/- 36.0) ng/mL after eight weeks (P = 0.728). In the experimental group, after taking simvastatin for eight weeks the serum total cholesterol and triglyceride levels had lowered by 18.6% (P = 0.004) and 55.1% (P = 0.007), respectively. The plasma IL-6, serum CRP, ferritin, hemoglobin, albumin, and LDL and HDL cholesterol levels in both the hemodialysis group remained unchanged. According to our preliminary study, eight weeks of 20 mg simvastatin did not significantly change the serum prohepcidin, high-sensitive CRP, or IL-6 concentrations in the group of maintenance hemodialysis patients.
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9.
Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial.
Müller, F, Christ-Crain, M, Bregenzer, T, Krause, M, Zimmerli, W, Mueller, B, Schuetz, P, ,
Chest. 2010;(1):121-9
Abstract
BACKGROUND Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP. METHODS This was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. RESULTS A total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P < .05) and PCT serum levels (adjusted odds ratio, 3.72; P < .001) were independent predictors. Overall, a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures. CONCLUSIONS Initial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources.
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10.
Serum vasopressin response in patients with intradialytic hypotension: a pilot study.
Rho, M, Perazella, MA, Parikh, CR, Peixoto, AJ, Brewster, UC
Clinical journal of the American Society of Nephrology : CJASN. 2008;(3):729-35
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Abstract
BACKGROUND AND OBJECTIVES Arginine vasopressin (AVP), an endogenous hormone with vasopressor properties, may be inadequately secreted during episodes of intradialytic hypotension (IDH). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS To evaluate this, we performed a prospective, observational pilot study of 20 chronic hemodialysis patients assessing the baseline AVP level and trend of AVP with ultrafiltration in patients with a diagnosis of IDH compared with patients without IDH. Ten symptomatic IDH patients and 10 controls were enrolled and matched for age, gender, and dialysis vintage. AVP levels were obtained hourly throughout the dialysis session and during hypotensive episodes. RESULTS We observed that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients (5.0 +/- 1.8) compared with controls (6.4 +/- 6.0) (P = 0.5) despite hypotensive events. CONCLUSIONS This study suggests that symptomatic IDH patients are unable to mount an appropriate increase in AVP secretion in the setting of hypotension. These findings support the possibility of AVP as a mechanism driven therapy for patients with symptomatic IDH.