Search

Tangential flow filtration (TFF) is a central step in manufacturing of biopharmaceutics. Membrane clogging leads to decreased permeate flux, longer process time and potentially complete failure of the process. The effect of peristaltic pumping with tubings made of three different materials on protein particle formation during TFF was monitored via micro flow imaging, turbidity and photo documentation. At low protein concentrations, pumping with a membrane pump resulted in a stable flux with low protein particle concentration. Using a peristaltic pump led to markedly higher protein particle formation dependent on tubing type. With increasing protein particle formation propensity of the tubing, the permeate flux rate became lower and the process took longer. The protein particles formed in the pump were captured in the cassette and accumulated on the membrane leading to blocking. Using tubing with a hydrophilic copolymer modification counteracted membrane clogging and flux decrease by reducing protein particle formation. In ultrafiltration mode the permeate flux decrease was governed by the viscosity increase rather than by the protein aggregation; but using modified tubing is still beneficial due to a lower particle burden of the product. In summary, using tubing material for peristaltic pumping in TFF processes which leads a less protein particle formation, especially tubing material with hydrophilic modification, is highly beneficial for membrane flux and particle burden of the product., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to compare head-to-head the diagnostic and prognostic capabilities of galectin-3, soluble ST2 (sST2) and B-type natriuretic peptide (BNP) for heart failure (HF) in an emergency setting., Methods: We studied 251 consecutive patients with dyspnoea as a chief compliant presenting to an emergency department. The diagnosis of HF was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction. All-cause mortality was assessed at one year. Plasma concentrations of galectin-3 and BNP were measured with two commercially available assays from Abbott Diagnostics, plasma concentrations of sST2 were quantified with the Presage ST2 assay. The diagnostic and prognostic accuracies of galectin-3, sST2 and BNP were assessed by receiver operating characteristic (ROC) curve analysis., Results: Of the 251 patients, 137 had dyspnoea attributable to acute HF and 114 had dyspnoea attributable to other reasons. BNP had a higher area under the curve (AUC) for the diagnosis of HF (0.92; 95% CI, 0.87-0.95) than galectin-3 (0.57; 95% CI, 0.51-0.64) and sST2 (0.63; 95% CI, 0.56-0.69). Of the 137 patients with acute HF, 41 died and 96 survived during follow up. The AUC of BNP for the prediction of one-year all-cause mortality in HF patients (0.72; 95% CI, 0.63-0.79) was not different from the AUCs of galectin-3 (0.70; 95% CI, 0.62-0.78) and sST2 (0.75; 95% CI, 0.67-0.82)., Conclusions: In this study, galectin-3, sST2 and BNP were equally useful for the prediction of one-year all-cause mortality in patients with acute HF. However, in contrast to BNP, galectin-3 and sST2 were not useful as an aid in the diagnosis of acute HF in short of breath patients presenting to an emergency department., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Here we describe the determination of upper reference limits (URL) for galectin-3, high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in a single cohort of healthy blood donors using routine assays., Methods: For this reference value study, we used a cohort of 402 consecutive blood donors (64% were male and 36% were female). The median individuals' age was 35.0 years (range, 18.0-64.4). Individuals of this reference population were free of cardiovascular disease, diabetes mellitus, renal disease, cancer, current infection and chronic inflammatory disease. Plasma concentrations of galectin-3 were measured with the "routine Galectin-3" assay (Abbott Diagnostics), of hs-cTnI with the "STAT High Sensitive Troponin-I" assay (Abbott Diagnostics), and of hs-cTnT with the "Troponin T hs" assay (Roche Diagnostics). URLs were calculated by using a non-parametric percentile method., Results: The 97.5th percentile URL for galectin-3 was 16 ng/mL in males and 17 ng/mL in females; the 99 th percentile URL for hs-cTnI was 39 ng/L in males and 24 ng/L in females; and the 99 th percentile URL for hs-cTnT was 14 ng/L in males and 11 ng/L in females. Those individuals with hs-cTnI values ≥ 15 ng/L (n=8) were different from those individuals with hs-cTnT values ≥ 10 ng/L (n=7). Of the 402 individuals, none had galectin-3 values below the limit of detection (LOD, <1.0 ng/mL), 290 (72%) had hs-cTnI values below the LOD (i.e., 1.9 ng/L), and 359 (89%) had hs-cTnT values below the LOD (i.e., 5.0 ng/L)., Conclusion: Plasma concentrations of galectin-3, hs-cTnI and hs-cTnT and corresponding 99 th percentile URLs were rather low in our cohort of healthy blood donors compared with previously published data. In our reference population, analyte plasma concentrations above the LOD were detectable in 100% of the individuals with the Abbott galectin-3 assay, but only in less than 50% for both the Abbott hs-cTnI assay and the Roche hs-cTnT assay., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The biomarkers soluble ST2 (sST2), galectin-3, and growth-differentiation factor-15 (GDF-15) provide prognostic information in patients with heart failure (HF). The aim of this study was to evaluate to which extent plasma concentrations of these biomarkers are increased in HF compared with diverse non-cardiac conditions such as infectious disease or chronic kidney disease., Methods: We recruited 15 patients in each of the following clinical categories: HF without co-morbidity, pneumonia without co-morbidity, chronic obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy individuals as control group. In each of the 112 study participants, we measured plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF-15 (Roche assay)., Results: Compared to controls, the median sST2 concentration was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8-fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not significantly increased in renal disease. Compared to controls, the median galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia, ~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis (p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4-fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants, correlation analyses revealed a relatively strong association between galectin-3 and GDF-15 (correlation coefficient, 0.739; p<0.001)., Conclusion: Because increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific for a distinct disease group, the three biomarkers are not useful for diagnostic purposes. The results of our study are novel with respect to sST2, galectin-3 and GDF-15 as markers of inflammatory diseases and should encourage further studies., (Copyright © 2015. Published by Elsevier B.V.)

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).