Publications by authors named "Robert Zimmermann"

207 Publications

Posttraumatic Active Intraneural Pseudoaneurysm: A Fast, Exact, and Decisive Diagnosis.

Ultraschall Med 2021 May 28. Epub 2021 May 28.

Department of Radiology, Innsbruck Medical University, Innsbruck, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1495-5356DOI Listing
May 2021

Pyoderma Gangrenosum After Hand Surgery: A Case Report.

Wounds 2021 Feb;33(2):E14-E16

Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, Austria.

Introduction: Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis that can be triggered after minor trauma or surgery and mimics a fulminating infection. It is commonly associated with a systemic disease, such as inflammatory bowel disease, metabolic syndrome, rheumatologic or hematological disorders, and malignancies. The typical clinical appearance is hemorrhagic nodules, which rapidly progress into extremely painful, irregular, red to violaceous ulceration with undermined border and purulent necrotic bases. The treatment of PG is nonsurgical. Unnecessary surgical procedures may incite a pathergic response, worsening the disease dramatically and potentially resulting in a limb amputation.

Case Report: A report of PG, originally misdiagnosed as an infection after a carpal tunnel release, is presented.

Conclusions: This case emphasizes the importance of early recognition of PG to provide a timely diagnosis and avoid unnecessary surgeries, which can result in devastating consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Lead Discovery of SARS-CoV-2 Main Protease Inhibitors through Covalent Docking-Based Virtual Screening.

J Chem Inf Model 2021 04 30;61(4):2062-2073. Epub 2021 Mar 30.

DiSTABiF, University of Campania Luigi Vanvitelli, Via Vivaldi 43, Caserta 81100, Italy.

During almost all 2020, coronavirus disease 2019 (COVID-19) pandemic has constituted the major risk for the worldwide health and economy, propelling unprecedented efforts to discover drugs for its prevention and cure. At the end of the year, these efforts have culminated with the approval of vaccines by the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) giving new hope for the future. On the other hand, clinical data underscore the urgent need for effective drugs to treat COVID-19 patients. In this work, we embarked on a virtual screening campaign against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M chymotrypsin-like cysteine protease employing our in-house database of peptide and non-peptide ligands characterized by different types of warheads acting as Michael acceptors. To this end, we employed the AutoDock4 docking software customized to predict the formation of a covalent adduct with the target protein. verification of the inhibition properties of the most promising candidates allowed us to identify two new lead inhibitors that will deserve further optimization. From the computational point of view, this work demonstrates the predictive power of AutoDock4 and suggests its application for the screening of large chemical libraries of potential covalent binders against the SARS-CoV-2 M enzyme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jcim.1c00184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029447PMC
April 2021

Iron Store of Repeat Plasma and Platelet Apheresis Donors.

Clin Lab 2021 Feb;67(2)

Background: Repeat apheresis donation causes a noticeable loss of whole blood: through routine blood tests with every donation as well as through residual blood left within the used apheresis set. While the effect of blood loss on donor iron stores has been widely researched for whole blood donations, fewer and especially contradictory results exist for apheresis donors.

Methods: A retrospective analysis of the donor blood samples (Department of Transfusion Medicine, University Hospital Erlangen) of the past 11 years (n = 52.976) was performed. Serum ferritin and hemoglobin were used to detect iron deficiency. Values at admission were compared to values measured at the donations. To investigate the impact of the donation frequency, this frequency was calculated for every single donor (for the whole duration of 11 years as well as for each individual year). Correlation and regression analyses between frequency and iron parameters were performed. A special group were long-time repeat donors, whose changes in ferritin values were analyzed in comparison to the first-ever ferritin value before the first donation.

Results: All donor groups show significantly lower mean ferritin and hemoglobin values after repeated donations than at admission. Interestingly, there are much more iron-depleted females in the control group than there are iron-depleted males. The correlation and regression analysis showed a significant relationship between donation frequency and iron-deficiency in males, but not in females. The analysis of the long-time repeat donors showed that the relative ferritin value dropped more in males than in females. When comparing iron-depleted long-time donors, females tend to be iron-depleted much more often even before the first donation.

Conclusions: Repeat apheresis donation has a noticeable effect on the iron store of the blood donor, leading to a high percentage of iron-deficient donors, especially in women. The very small correlation between donation frequency and iron depletion for females is most likely due to the fact that women tend to be iron-deficient even before the first donation. Because of the natural variation of inter-donation-intervals, the calculated donation frequency might not be that exact. As a result, the correlation between donation frequency and iron stores might be higher than suggested by this work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.200506DOI Listing
February 2021

Charged particle guiding and beam splitting with auto-ponderomotive potentials on a chip.

Nat Commun 2021 Jan 15;12(1):390. Epub 2021 Jan 15.

Department Physik, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Staudtstraße 1, 91058, Erlangen, Germany.

Electron and ion beams are indispensable tools in numerous fields of science and technology, ranging from radiation therapy to microscopy and lithography. Advanced beam control facilitates new functionalities. Here, we report the guiding and splitting of charged particle beams using ponderomotive forces created by the motion of charged particles through electrostatic optics printed on planar substrates. Shape and strength of the potential can be locally tailored by the lithographically produced electrodes' layout and the applied voltages, enabling the control of charged particle beams within precisely engineered effective potentials. We demonstrate guiding of electrons and ions for a large range of energies (from 20 to 5000 eV) and masses (from 5 · 10 to 131 atomic mass units) as well as electron beam splitting for energies up to the keV regime as a proof-of-concept for more complex beam manipulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20592-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810984PMC
January 2021

Orientation Preference Maps in Microcebus murinus Reveal Size-Invariant Design Principles in Primate Visual Cortex.

Curr Biol 2021 Feb 3;31(4):733-741.e7. Epub 2020 Dec 3.

University of Geneva, Department of Basic Neurosciences, Rue Michel Servet 1, Geneva 1211, Switzerland. Electronic address:

Orientation preference maps (OPMs) are a prominent feature of primary visual cortex (V1) organization in many primates and carnivores. In rodents, neurons are not organized in OPMs but are instead interspersed in a "salt and pepper" fashion, although clusters of orientation-selective neurons have been reported. Does this fundamental difference reflect the existence of a lower size limit for orientation columns (OCs) below which they cannot be scaled down with decreasing V1 size? To address this question, we examined V1 of one of the smallest living primates, the 60-g prosimian mouse lemur (Microcebus murinus). Using chronic intrinsic signal imaging, we found that mouse lemur V1 contains robust OCs, which are arranged in a pinwheel-like fashion. OC size in mouse lemurs was found to be only marginally smaller compared to the macaque, suggesting that these circuit elements are nearly incompressible. The spatial arrangement of pinwheels is well described by a common mathematical design of primate V1 circuit organization. In order to accommodate OPMs, we found that the mouse lemur V1 covers one-fifth of the cortical surface, which is one of the largest V1-to-cortex ratios found in primates. These results indicate that the primate-type visual cortical circuit organization is constrained by a size limitation and raises the possibility that its emergence might have evolved by disruptive innovation rather than gradual change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2020.11.027DOI Listing
February 2021

Validation of a SARS-CoV-2 RNA RT-PCR assay for high-throughput testing in blood of COVID-19 convalescent plasma donors and patients.

Transfusion 2021 02 9;61(2):368-374. Epub 2020 Nov 9.

Department of Transfusion Medicine and Hemostaseology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Background: The frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia in blood donors is uncertain. Thus, assays for SARS-CoV-2 RNA detection in blood, validated on commercially available polymerase chain reaction (PCR) systems, are required to allow a good comparability of data.

Study Design And Methods: The cobas SARS-CoV-2 dual-target reverse transcriptase PCR (RT-PCR) assay, licensed for respiratory swab SARS-CoV-2 RNA testing, was validated for detection of viral RNA in blood. For the validation panel, SARS-CoV-2-positive plasma samples were prepared by spiking SARS-CoV-2-positive respiratory specimens in negative human plasma. The 95% limit of detection (LOD95) was determined by probit analysis. For clinical validation, coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donors and patients with COVID-19 with a severe disease course treated in an intensive care unit (ICU) were included.

Results: The validation of the SARS-CoV-2 RT-PCR assay for blood demonstrated high sensitivity and specificity and intra- and inter-assay precision and efficiency. The LOD95 for SARS-CoV-2 RNA was 5.0 genome copies/mL (95% confidence interval [CI], 3.3-12 copies/mL) for target 1 and 4.3 genome copies/mL (95% CI, 2.9-10 copies/mL) for target 2. In a cohort of 39 CCP donors with 66 CCP donations no SARS-CoV-2 RNA in plasma was detected. Screening of 25 blood samples of 19 ICU patients with COVID-19 showed six positive results for SARS-CoV-2 RNA in at least one target of the assay.

Conclusion: The SARS-CoV-2 RNA assay, only licensed for respiratory swabs, performed on a PCR system for high-throughput testing, showed a good assay performance for blood testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16178DOI Listing
February 2021

Detection of REEs with lightweight UAV-based hyperspectral imaging.

Sci Rep 2020 10 15;10(1):17450. Epub 2020 Oct 15.

Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institute Freiberg for Resource Technology, 09599, Freiberg, Germany.

Rare earth elements (REEs) supply is important to ensure the energy transition, e-mobility and ultimately to achieve the sustainable development goals of the United Nations. Conventional exploration techniques usually rely on substantial geological field work including dense in-situ sampling with long delays until provision of analytical results. However, this approach is limited by land accessibility, financial status, climate and public opposition. Efficient and innovative methods are required to mitigate these limitations. The use of lightweight unmanned aerial vehicles (UAVs) provides a unique opportunity to conduct rapid and non-invasive exploration even in socially sensitive areas and in relatively inaccessible locations. We employ drones with hyperspectral sensors to detect REEs at the earth's surface and thus contribute to a rapidly evolving field at the cutting edge of exploration technologies. We showcase for the first time the direct mapping of REEs with lightweight hyperspectral UAV platforms. Our solution has the advantage of quick turn-around times (< 1 d), low detection limits (< 200 ppm for Nd) and is ideally suited to support exploration campaigns. This procedure was successfully tested and validated in two areas: Marinkas Quellen, Namibia, and Siilinjärvi, Finland. This strategy should invigorate the use of drones in exploration and for the monitoring of mining activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74422-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562707PMC
October 2020

EthoLoop: automated closed-loop neuroethology in naturalistic environments.

Nat Methods 2020 10 29;17(10):1052-1059. Epub 2020 Sep 29.

University of Geneva, Department of Basic Neurosciences, Geneva, Switzerland.

Accurate tracking and analysis of animal behavior is crucial for modern systems neuroscience. However, following freely moving animals in naturalistic, three-dimensional (3D) or nocturnal environments remains a major challenge. Here, we present EthoLoop, a framework for studying the neuroethology of freely roaming animals. Combining real-time optical tracking and behavioral analysis with remote-controlled stimulus-reward boxes, this system allows direct interactions with animals in their habitat. EthoLoop continuously provides close-up views of the tracked individuals and thus allows high-resolution behavioral analysis using deep-learning methods. The behaviors detected on the fly can be automatically reinforced either by classical conditioning or by optogenetic stimulation via wirelessly controlled portable devices. Finally, by combining 3D tracking with wireless neurophysiology we demonstrate the existence of place-cell-like activity in the hippocampus of freely moving primates. Taken together, we show that the EthoLoop framework enables interactive, well-controlled and reproducible neuroethological studies in large-field naturalistic settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41592-020-0961-2DOI Listing
October 2020

Long-term outcome after hand and forearm transplantation - a retrospective study.

Transpl Int 2020 12 10;33(12):1762-1778. Epub 2020 Nov 10.

Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria.

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756600PMC
December 2020

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2.

ChemMedChem 2021 01 16;16(2):340-354. Epub 2020 Oct 16.

Institute for Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128, Mainz, Germany.

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL ) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL . Moreover, we report the discovery of isoindolines as a new class of potent PL inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL are valuable starting points for the development of new pan-coronaviral inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cmdc.202000548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894572PMC
January 2021

Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL).

Bioorg Med Chem 2020 08 4;28(16):115610. Epub 2020 Jul 4.

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria; BIOTECHMED Graz, A-8010, Austria. Electronic address:

High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure-activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2020.115610DOI Listing
August 2020

Dipeptidyl peptidase 3 modulates the renin-angiotensin system in mice.

J Biol Chem 2020 10 16;295(40):13711-13723. Epub 2020 Jun 16.

Institute of Biochemistry, Graz University of Technology, NAWI Graz, Graz, Austria. Electronic address:

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4-12 amino acid residues. It has been associated with several pathophysiological processes, including blood pressure regulation, pain signaling, and cancer cell defense against oxidative stress. However, the physiological substrates and the cellular pathways that are potentially targeted by DPP3 to mediate these effects remain unknown. Here, we show that global DPP3 deficiency in mice (DPP3) affects the renin-angiotensin system (RAS). LC-MS-based profiling of circulating angiotensin peptides revealed elevated levels of angiotensin II, III, IV, and 1-5 in DPP3 mice, whereas blood pressure, renin activity, and aldosterone levels remained unchanged. Activity assays using the purified enzyme confirmed that angiotensin peptides are substrates for DPP3. Aberrant angiotensin signaling was associated with substantially higher water intake and increased renal reactive oxygen species formation in the kidneys of DPP3 mice. The metabolic changes and altered angiotensin levels observed in male DPP3 mice were either absent or attenuated in female DPP3 mice, indicating sex-specific differences. Taken together, our observations suggest that DPP3 regulates the RAS pathway and water homeostasis by degrading circulating angiotensin peptides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA120.014183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535908PMC
October 2020

Thrombin Generation in Fresh and Frozen-Thawed Platelet Poor Plasma - Is there a Difference?

Clin Lab 2020 Jun;66(6)

Background: Applicability of thrombin generation tests to clinical routine has been sought for many years. The aim of this study was to compare thrombin generation measured in fresh platelet poor plasma (f-PPP) and frozen-thawed platelet poor plasma (ft-PPP) to prove the consistency of results.

Methods: In this prospective study, thrombin generation was measured in twenty-fold repetitions in 3.2% citrate PPP obtained from male healthy blood donors aged 19 - 39 years (n = 54 donations). The tests were performed with fresh PPP and repeated after storing the PPP at -60°C. In two subgroup analyses, the effect of higher and lower normal baseline platelet counts on the Calibrated Automated Thrombogram (CAT) assay and the influence of ABO blood groups on thrombin generation were analyzed.

Results: Referring to the parameters of thrombin generation most frequently used in studies, peak thrombin of f-PPP and ft-PPP agreed in about 50% of the samples. Endogenous thrombin potential (ETP) of f-PPP and ft-PPP agreed in nearly two-thirds of the samples. A slightly but significantly slower kinetic was found in the thrombin generation of ft-PPP compared with f-PPP. At least in f-PPP, ETP correlates with baseline platelet counts of the whole blood sample. Peak thrombin was significantly higher in non-O blood groups compared to O blood group.

Conclusions: A low level of agreement between the results of f-PPP and ft-PPP is shown. In terms of practicability of sample collection using semi-automated thrombin-generation assays ft-PPP should be preferred over f-PPP. We therefore recommend using ft-PPP in clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2019.190834DOI Listing
June 2020

Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease.

Theranostics 2020 15;10(14):6337-6360. Epub 2020 May 15.

Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.

Monoacylglycerol lipase (Mgll), a hydrolase that breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG) to produce arachidonic acid (ARA), is a potential target for neurodegenerative diseases, such as Alzheimer's disease (AD). Increasing evidence shows that impairment of adult neurogenesis by perturbed lipid metabolism predisposes patients to AD. However, it remains unknown what causes aberrant expression of Mgll in AD and how Mgll-regulated lipid metabolism impacts adult neurogenesis, thus predisposing to AD during aging. Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce β-amyloid accumulation. Mgll expression was assessed in both human AD patient post-mortem hippocampal tissues and 3xTg-AD mouse model. In addition, we used both the 3xTg-AD animal model and the S436A genetic knock-in mouse model to identify that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway, involving atypical protein kinase C (aPKC)-stimulated Ser436 phosphorylation of histone acetyltransferase CBP through biochemical methods. Furthermore, we performed adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway. Finally, we performed adult neurosphere assays using both animal models to study the role of the aPKC-CBP mediated Mgll repression in determining adult neural stem/progenitor cell (NPC) fate. Here, we demonstrate that aging-dependent induction of Mgll is observed in the 3xTg-AD model and human AD patient post-mortem hippocampal tissues. Importantly, we discover that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway. The accumulation of Mgll in the 3xTg-AD mice reduces the genesis of newborn neurons and perturbs spatial memory. However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD. In addition, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and S436A animal models are responsible for their NPC neuronal differentiation deficits. Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.44962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255032PMC
May 2021

Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 08 1;1865(8):158730. Epub 2020 May 1.

Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, A-8010 Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address:

Vitamin A is stored as retinyl esters (REs) in lipid droplets of hepatic stellate cells (HSCs). To date, two different pathways are known to facilitate the breakdown of REs: (i) Hydrolysis of REs by neutral lipases, and (ii) whole lipid droplet degradation in autolysosomes by acid hydrolysis. In this study, we evaluated the contribution of neutral and acid RE hydrolases to the breakdown of REs in human HSCs. (R)-Bromoenol lactone (R-BEL), inhibitor of adipose triglyceride lipase (ATGL) and patatin-like phospholipase domain-containing 3 (PNPLA3), the hormone-sensitive lipase (HSL) inhibitor 76-0079, as well as the serine-hydrolase inhibitor Orlistat reduced neutral RE hydrolase activity of LX-2 cell-lysates between 20 and 50%. Interestingly, in pulse-chase experiments, R-BEL, 76-0079, as well as Orlistat exerted little to no effect on cellular RE breakdown of LX-2 cells as well as primary human HSCs. In contrast, Lalistat2, a specific lysosomal acid lipase (LAL) inhibitor, virtually blunted acid in vitro RE hydrolase activity of LX-2 cells. Accordingly, HSCs isolated from LAL-deficient mice showed RE accumulation and were virtually devoid of acidic RE hydrolase activity. In pulse-chase experiments however, LAL-deficient HSCs, similar to LX-2 cells and primary human HSCs, were not defective in degrading REs. In summary, results demonstrate that ATGL, PNPLA3, and HSL contribute to neutral RE hydrolysis of human HSCs. LAL is the major acid RE hydrolase in HSCs. Yet, LAL is not limiting for RE degradation under serum-starvation. Together, results suggest that RE breakdown of HSCs is facilitated by (a) so far unknown, non-Orlistat inhibitable RE-hydrolase(s).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2020.158730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279957PMC
August 2020

Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice.

J Lipid Res 2020 07 29;61(7):995-1003. Epub 2020 Apr 29.

Institute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address:

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endolysosomal system. Surprisingly, little is known about the physiological regulation of BMP. In this study, we investigated the effects of nutritional and metabolic factors on BMP profiles of whole tissues and parenchymal and nonparenchymal cells. Tissue samples were obtained from fed, fasted, 2 h refed, and insulin-treated mice, as well as from mice housed at 5°C, 22°C, or 30°C. These tissues exhibited distinct BMP profiles that were regulated by the nutritional state in a tissue-specific manner. Insulin treatment was not sufficient to mimic refeeding-induced changes in tissue BMP levels, indicating that BMP metabolism is regulated by other hormonal or nutritional factors. Tissue fractionation experiments revealed that fasting drastically elevates BMP levels in hepatocytes and pancreatic cells. Furthermore, we observed that the BMP content in brown adipose tissue strongly depends on housing temperatures. In conclusion, our observations suggest that BMP concentrations adapt to the metabolic state in a tissue- and cell-type-specific manner in mice. Drastic changes observed in hepatocytes, pancreatic cells, and brown adipocytes suggest that BMP plays a role in the functional adaption to nutrient starvation and ambient temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.RA119000516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328040PMC
July 2020

Lysophosphatidylcholines inhibit human eosinophil activation and suppress eosinophil migration in vivo.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 07 11;1865(7):158686. Epub 2020 Mar 11.

Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address:

Eosinophils are important multifaceted effector cells involved in allergic inflammation. Following allergen challenge, eosinophils and other immune cells release secreted phospholipases, generating lysophosphatidylcholines (LPCs). LPCs are potent lipid mediators, and serum levels of LPCs associate with asthma severity, suggesting a regulatory activity of LPCs in asthma development. As of yet, the direct effects of LPCs on eosinophils remain unclear. In the present study, we tested the effects of the major LPC species (16:0, 18:0 and 18:1) on eosinophils isolated from healthy human donors. Addition of saturated LPCs in the presence of albumin rapidly disrupted cholesterol-rich nanodomains on eosinophil cell membranes and suppressed multiple eosinophil effector responses, such as CD11b upregulation, degranulation, chemotaxis, and downstream signaling. Furthermore, we demonstrate in a mouse model of allergic cell recruitment, that LPC treatment markedly reduces immune cell infiltration into the lungs. Our observations suggest a strong modulatory activity of LPCs in the regulation of eosinophilic inflammation in vitro and in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2020.158686DOI Listing
July 2020

Monoacylglycerol Lipase Inhibition Protects From Liver Injury in Mouse Models of Sclerosing Cholangitis.

Hepatology 2020 05 30;71(5):1750-1765. Epub 2019 Dec 30.

Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background And Aims: Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2-arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis, a disease so far lacking effective pharmacological therapy.

Approach And Results: To this aim we analyzed the effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding to induce sclerosing cholangitis in wild-type (WT) and knockout (MGL ) mice and tested pharmacological inhibition with JZL184 in the multidrug resistance protein 2 knockout (Mdr2 ) mouse model of sclerosing cholangitis. Cholestatic liver injury and fibrosis were assessed by serum biochemistry, liver histology, gene expression, and western blot characterization of BA and FA synthesis/transport. Moreover, intestinal FAs and fecal microbiome were analyzed. Transfection and silencing were performed in Caco2 cells. MGL mice were protected from DDC-induced biliary fibrosis and inflammation with reduced serum liver enzymes and increased FA/BA metabolism and β-oxidation. Notably, pharmacological (JZL184) inhibition of MGL ameliorated cholestatic injury in DDC-fed WT mice and protected Mdr2 mice from spontaneous liver injury, with improved liver enzymes, inflammation, and biliary fibrosis. In vitro experiments confirmed that silencing of MGL decreases prostaglandin E accumulation in the intestine and up-regulates peroxisome proliferator-activated receptors alpha and gamma activity, thus reducing inflammation.

Conclusions: Collectively, our study unravels MGL as a metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for sclerosing cholangitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317927PMC
May 2020

Multi-Sensor Spectral Imaging of Geological Samples: A Data Fusion Approach Using Spatio-Spectral Feature Extraction.

Sensors (Basel) 2019 Jun 21;19(12). Epub 2019 Jun 21.

Division "Exploration Technology", Helmholtz Institute Freiberg for Resource Technology, Helmholtz-Zentrum Dresden-Rossendorf, Chemnitzer Straße 40, 09599 Freiberg, Germany.

Rapid, efficient and reproducible drillcore logging is fundamental in mineral exploration. Drillcore mapping has evolved rapidly in the recent decade, especially with the advances in hyperspectral spectral imaging. A wide range of imaging sensors is now available, providing rapidly increasing spectral as well as spatial resolution and coverage. However, the fusion of data acquired with multiple sensors is challenging and usually not conducted operationally. We propose an innovative solution based on the recent developments made in machine learning to integrate such multi-sensor datasets. Image feature extraction using orthogonal total variation component analysis enables a strong reduction in dimensionality and memory size of each input dataset, while maintaining the majority of its spatial and spectral information. This is in particular advantageous for sensors with very high spatial and/or spectral resolution, which are otherwise difficult to jointly process due to their large data memory requirements during classification. The extracted features are not only bound to absorption features but recognize specific and relevant spatial or spectral patterns. We exemplify the workflow with data acquired with five commercially available hyperspectral sensors and a pair of RGB cameras. The robust and efficient spectral-spatial procedure is evaluated on a representative set of geological samples. We validate the process with independent and detailed mineralogical and spectral data. The suggested workflow provides a versatile solution for the integration of multi-source hyperspectral data in a diversity of geological applications. In this study, we show a straight-forward integration of visible/near-infrared (VNIR), short-wave infrared (SWIR) and long-wave infrared (LWIR) data for sensors with highly different spatial and spectral resolution that greatly improves drillcore mapping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s19122787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631011PMC
June 2019

The α/β-hydrolase domain-containing 4- and 5-related phospholipase Pummelig controls energy storage in .

J Lipid Res 2019 08 4;60(8):1365-1378. Epub 2019 Jun 4.

Research Group Molecular Physiology Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany

Triglycerides (TGs) are the main energy storage form that accommodates changing organismal energy demands. In , the TG lipase Brummer is centrally important for body fat mobilization. Its gene () encodes the ortholog of mammalian adipose TG lipase, which becomes activated by α/β-hydrolase domain-containing 5 (ABHD5/CGI-58), one member of the paralogous gene pair, α/β-hydrolase domain-containing 4 () and In , the () gene encodes the single sequence-related protein to mammalian ABHD4/ABHD5 with unknown function. We generated deletion mutant flies, that were short-lived as a result of lipid metabolism changes, stored excess body fat at the expense of glycogen, and exhibited ectopic fat storage with altered TG FA profile in the fly kidneys, called Malpighian tubules. TG accumulation in mutants was not associated with increased food intake but with elevated lipogenesis; starvation-induced lipid mobilization remained functional. Despite its structural similarity to mammalian ABHD5, Puml did not stimulate TG lipase activity of Bmm in vitro. Rather, Puml acted as a phospholipase that localized on lipid droplets, mitochondria, and peroxisomes. Together, these results show that the ABHD4/5 family member Puml is a versatile phospholipase that regulates body fat storage and energy metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M092817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672044PMC
August 2019

Reduction of exposure to plasticizers in stored red blood cell units.

Perfusion 2020 01 31;35(1):32-38. Epub 2019 May 31.

Department of Pediatric Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Introduction: Plastic can be toxic and hazardous to an organism's health, but it is being widely used in our daily lives. Di-2-ethylhexyl-phthalate is the most common plasticizer in medical devices made of polyvinylchloride and is commonly found in soft bags storing red blood cell units. Di-2-ethylhexyl-phthalate and its degradation product mono-2-ethylhexyl-phthalate can migrate into human body fluids, for example, blood and tissues. The aim of the study was to assess the concentration of plasticizers in red blood cell units according to storage time and after mechanical rinsing using a cell salvage device.

Methods: Levels of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate were analysed in 50 unwashed red blood cell units using liquid chromatography coupled with tandem mass spectrometry. In addition, phthalate concentrations were measured before and after mechanical rinsing in six more washed red blood cell units with storage times ranging between 36 and 56 days. A linear regression model was determined by the daily increase of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate in the stored red blood cell units subject to their storage time (range = 4-38 days), and the effect of mechanical rinsing on their phthalate concentration was calculated.

Results: A linear correlation was found between storage time of unwashed red blood cell units and the concentration of di-2-ethylhexyl-phthalate (p < 0.001) or mono-2-ethylhexyl-phthalate (p < 0.001). Stored red blood cell units older than 14 days had significantly higher concentrations of both contaminants than red blood cell units of shorter storage time (p < 0.001). Mechanical rinsing in washed red blood cell units attained a reduction in the di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate concentration by a median of 53% (range = 18-68%; p = 0.031) and 87% (range = 68-96%; p = 0.031), respectively.

Conclusion: Leaching of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate into red blood cell units depends on the duration of storage time. Plasticizers can be significantly reduced by mechanical rinsing using cell salvage devices, and thus, red blood cell units can be regenerated with respect to chemical contamination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0267659119851403DOI Listing
January 2020

Fast 2D Laser-Induced Fluorescence Spectroscopy Mapping of Rare Earth Elements in Rock Samples.

Sensors (Basel) 2019 May 14;19(10). Epub 2019 May 14.

Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institute Freiberg for Resource Technology, Chemnitzer Str. 40, 09599 Freiberg, Germany.

Due to the rapidly increasing use of energy-efficient technologies, the need for complex materials containing rare earth elements (REEs) is steadily growing. The high demand for REEs requires the exploration of new mineral deposits of these valuable elements, as recovery by recycling is still very low. Easy-to-deploy sensor technologies featuring high sensitivity to REEs are required to overcome limitations by traditional techniques, such as X-ray fluorescence. We demonstrate the ability of laser-induced fluorescence (LIF) to detect REEs rapidly in relevant geological samples. We introduce two-dimensional LIF mapping to scan rock samples from two Namibian REE deposits and cross-validate the obtained results by employing mineral liberation analysis (MLA) and hyperspectral imaging (HSI). Technique-specific parameters, such as acquisition speed, spatial resolution, and detection limits, are discussed and compared to established analysis methods. We also focus on the attribution of REE occurrences to mineralogical features, which may be helpful for the further geological interpretation of a deposit. This study sets the basis for the development of a combined mapping sensor for HSI and 2D LIF measurements, which could be used for drill-core logging in REE exploration, as well as in recovery plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s19102219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567338PMC
May 2019

Lack of monoacylglycerol lipase prevents hepatic steatosis by favoring lipid storage in adipose tissue and intestinal malabsorption.

J Lipid Res 2019 07 2;60(7):1284-1292. Epub 2019 May 2.

Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Monoacylglycerol lipase (MGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. To examine the role of MGL in hepatic steatosis, WT and MGL KO (MGL) mice were challenged with a Western diet (WD) over 12 weeks. Lipid metabolism, inflammation, and fibrosis were assessed by serum biochemistry, histology, and gene-expression profiling of liver and adipose depots. Intestinal fat absorption was measured by gas chromatography. Primary adipocyte and 3T3-L1 cells were analyzed by flow cytometry and Western blot. Human hepatocytes were treated with MGL inhibitor JZL184. The absence of MGL protected mice from hepatic steatosis by repressing key lipogenic enzymes in liver (Srebp1c, Pparγ2, and diacylglycerol -acyltransferase 1), while promoting FA oxidation. Liver inflammation was diminished in MGL mice fed a WD, as evidenced by diminished epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (F4/80) staining and C-C motif chemokine ligand 2 gene expression, whereas fibrosis remained unchanged. Absence of MGL promoted fat storage in gonadal white adipose tissue (gWAT) with increased lipogenesis and unchanged lipolysis, diminished inflammation in gWAT, and subcutaneous AT. Intestinal fat malabsorption prevented ectopic lipid accumulation in livers of MGL mice fed a WD. In vitro experiments demonstrated increased adipocyte size/lipid content driven by PPARγ. In conclusion, our data uncover that MGL deletion improves some aspects of nonalcoholic fatty liver disease by promoting lipid storage in gWAT and fat malabsorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M093369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602129PMC
July 2019

Hepatocyte-specific deletion of lysosomal acid lipase leads to cholesteryl ester but not triglyceride or retinyl ester accumulation.

J Biol Chem 2019 06 25;294(23):9118-9133. Epub 2019 Apr 25.

From the Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstrasse 31/II,

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl ester (CE) and retinyl ester (RE) and triglyceride (TG). Mice globally lacking LAL accumulate CE most prominently in the liver. The severity of the CE accumulation phenotype progresses with age and is accompanied by hepatomegaly and hepatic cholesterol crystal deposition. In contrast, hepatic TG accumulation is much less pronounced in these mice, and hepatic RE levels are even decreased. To dissect the functional role of LAL for neutral lipid ester mobilization in the liver, we generated mice specifically lacking LAL in hepatocytes (hep-LAL-ko). On a standard chow diet, hep-LAL-ko mice exhibited increased hepatic CE accumulation but unaltered TG and RE levels. Feeding the hep-LAL-ko mice a vitamin A excess/high-fat diet (VitA/HFD) further increased hepatic cholesterol levels, but hepatic TG and RE levels in these mice were lower than in control mice. Performing activity assays with lysosome-enriched fractions from livers of mice globally lacking LAL, we detected residual acid hydrolytic activities against TG and RE. Interestingly, this non-LAL acid TG hydrolytic activity was elevated in lysosome-enriched fractions from livers of hep-LAL-ko mice upon VitA/HFD feeding. In conclusion, the neutral lipid ester phenotype in livers from hep-LAL-ko mice indicates that LAL is limiting for CE turnover, but not for TG and RE turnovers. Furthermore, hydrolase activity assays revealed the existence of non-LAL acid hydrolytic activities for TG and RE. The corresponding acid lipase(s) catalyzing these reactions remains to be identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA118.007201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556574PMC
June 2019

Astroglial monoacylglycerol lipase controls mutant huntingtin-induced damage of striatal neurons.

Neuropharmacology 2019 05 23;150:134-144. Epub 2019 Mar 23.

Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Universitario de Investigación Neuroquímica (IUIN), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) and Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, 28040 Madrid, Spain. Electronic address:

Cannabinoids exert neuroprotection in a wide array of preclinical models. A number of these studies has focused on cannabinoid CB receptors in striatal medium spiny neurons (MSNs) and the most characteristic MSN-degenerative disease, Huntington's disease (HD). Accruing evidence supports that astrocytes contribute to drive HD progression, and that they express CB receptors, degrade endocannabinoids, and modulate endocannabinergic transmission. However, the possible role of the astroglial endocannabinoid system in controlling MSN integrity remains unknown. Here, we show that JZL-184, a selective inhibitor of monoacylglycerol lipase (MGL), the key enzyme that deactivates the endocannabinoid 2-arachidonoylglycerol, prevented the mutant huntingtin-induced up-regulation of the pro-inflammatory cytokine tumor necrosis factor-α in primary mouse striatal astrocytes via CB receptors. To study the role of astroglial MGL in vivo, we injected stereotactically into the mouse dorsal striatum viral vectors that encode mutant or normal huntingtin under the control of the glial fibrillary acidic protein promoter. We observed that, in wild-type mice, pharmacological blockade of MGL with JZL-184 (8 mg/kg/day, i.p.) conferred neuroprotection against mutant huntingtin-induced striatal damage, as evidenced by the prevention of MSN loss, astrogliosis, and motor coordination impairment. We next found that conditional mutant mice bearing a genetic deletion of MGL selectively in astroglial cells (MGL mice) were resistant to mutant huntingtin-induced MSN loss, astrogliosis, and motor coordination impairment. Taken together, these data support that astroglial MGL controls the availability of a 2-arachidonoylglycerol pool that ensues protection of MSNs in the mouse striatum in vivo, thus providing a potential druggable target for reducing striatal neurodegeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropharm.2019.03.027DOI Listing
May 2019

Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans.

J Lipid Res 2019 05 20;60(5):1020-1031. Epub 2019 Mar 20.

Institute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz Graz, Austria. Electronic address:

Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSDs, however, are scarce, and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and FA composition in the liver and plasma, similar to what has been observed in LSDs. Notably, distinct changes in the BMP FA profile enable a clear distinction between lipid overload and drug-induced LSDs. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSDs. In humans, nonalcoholic fatty liver disease and liver cirrhosis affect the serum BMP FA composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the gene, leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M093351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495172PMC
May 2019

Clotting factor activity in fresh frozen plasma after thawing with a new radio wave thawing device.

Transfusion 2019 05 18;59(5):1857-1861. Epub 2019 Mar 18.

Department of Transfusion Medicine and Hemostaseology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen, Germany.

Background: Massive hemorrhage usually results in rapid need of blood products. Patients in need of fresh frozen plasma (FFP) might benefit from shorter thawing times using a novel radio wave device. So far, only one study on the prototype has been published. Activities of clotting factors after thawing FFP with the radio wave device and with a system using water cushions were compared. This is the first study analyzing the quality of FFP using the fully developed radio wave thawing device UFT100.

Study Design And Methods: Thirty FFP units were thawed with the UFT100 and the Plasmatherm machine. Various clotting factors and inhibitors were analyzed before freezing, immediately after thawing, and after a 48-hour storage period at +4°C.

Results: After thawing, all factor activities were within normal ranges regardless of the thawing procedure. We observed significant differences in nearly all clotting factor activities regarding time as effector, whereas thawing with the Plasmatherm machine led to a significant decrease (>10%) only in factor V activity compared to the UFT100.

Conclusions: Immediately after rapid thawing with the UFT100, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity. The UFT100 does not deteriorate FFP quality compared to a conventional system. Regardless of the thawing system, the postthaw refrigerated storage caused a decrease in several clotting factors and inhibitors (factors V, VIII, and IX; von Willebrand factor activity; protein S and C activity) and a significant increase of factor XI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.15246DOI Listing
May 2019

HPA Frequencies in the Syrian Population.

Clin Lab 2019 Mar;65(3)

Background: Exposure to allogenic Human Platelet Antigens (HPAs) can lead to antibody formation causing different immunological reactions. Frequencies of common HPA antigens differ between ethnic groups and should be known to calculate potential alloimmunization risk. Syrian refugees are the largest group of applicants for asylum in Germany in 2017. However, no study on HPA antigen frequencies in the Syrian population exists.

Methods: DNA from blood samples of 96 volunteers with Syrian origin was isolated. The genotype of HPA-1, -2, -3, -4, -5, -6, -9, and -15 was determined using a commercialized polymerase chain reaction kit with sequence-specific primers (SSP-PCR). Data were compared with data formerly obtained from the German population and diverse other studies.

Results: In Syrian population, the gene frequencies of HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b, -6a/6b, -9a/9b, and -15a/15b were 0.837/0.163, 0.875/0.125, 0.630/0.370, 1.000/0.000, 0.837/0.130, 1.000/0.000, 1.000/0.000, and 0.457/0.543, respectively.

Conclusions: There are no significant differences between HPA antigen frequencies in the Syrian and German population. Therefore, we do not see a need for special precaution in the selection of blood products or in pregnancy of interethnic couples with regard to HPA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2018.180838DOI Listing
March 2019