Publications by authors named "Patrick Altmann"

18 Publications

  • Page 1 of 1

Predisposing Factors for Sexual Dysfunction in Multiple Sclerosis.

Front Neurol 2021 9;12:618370. Epub 2021 Feb 9.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) has a detrimental impact on individual health-related quality of life (HRQoL). It is not clear whether SD in multiple sclerosis (MS) is an independent symptom or merely a byproduct of other symptoms such as depression or anxiety. This cross-sectional study of 93 pwMS determines risk factors for SD in MS based on prevalence, HRQoL, and associated disease outcomes. Diagnosis of SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (measured by Expanded Disability Status scale, EDSS), depression and anxiety [Hospital Anxiety and Depression Scale (HADS)], and HRQoL [Multiple Sclerosis Quality of Life-54 (MSQoL-54)]. Multivariate regression models were performed to determine independent risk factors for SD in pwMS. Almost half of the participants in this study (46%) reported SD. HRQoL was significantly poorer in patients with MS suffering from SD (median [IQR] MSQoL-54 scores: physical subscale 52 [41-68] vs. 81 [69-89], < 0.001; mental subscale 50 [38-82] vs. 86 [70-89], < 0.001). In the multivariate model, EDSS was the only independent risk factor for SD (OR 18.1 for EDSS ≥4 [95% CI 3.3-31.4, < 0.001]), while depression and anxiety were not. We conclude that the risk for SD is growing with increasing EDSS and is independent of depression or anxiety. Screening for SD becomes particularly relevant in patients with growing disability.
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http://dx.doi.org/10.3389/fneur.2021.618370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900565PMC
February 2021

Phonon-Mediated Interlayer Charge Separation and Recombination in a MoSe/WSe Heterostructure.

Nano Lett 2021 Feb 16. Epub 2021 Feb 16.

Dipartimento di Fisica, Politecnico di Milano, Piazza L. da Vinci 32, I-20133 Milano, Italy.

Monolayer transition metal dichalcogenides bear great potential for photodetection and light harvesting due to high absorption coefficients. However, these applications require dissociation of strongly bound photogenerated excitons. The dissociation can be achieved by vertically stacking different monolayers to realize band alignment that favors interlayer charge transfer. In such heterostructures, the reported recombination times vary strongly, and the charge separation and recombination mechanisms remain elusive. We use two color pump-probe microscopy to demonstrate that the charge separation in a MoSe/WSe heterostructure is ultrafast (∼200 fs) and virtually temperature independent, whereas the recombination accelerates strongly with temperature. quantum dynamics simulations rationalize the experiments, indicating that the charge separation is temperature-independent because it is barrierless, involves dense acceptor states, and is promoted by higher-frequency out-of-plane vibrations. The strong temperature dependence of the recombination, on the other hand, arises from a transient indirect-to-direct bandgap modulation by low-frequency shear and layer breathing motions.
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http://dx.doi.org/10.1021/acs.nanolett.0c04955DOI Listing
February 2021

Quantifying the risk of disease reactivation after interferon and glatiramer acetate discontinuation in multiple sclerosis: The VIAADISC score.

Eur J Neurol 2020 Dec 28. Epub 2020 Dec 28.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background And Purpose: There is a lack of evidence guiding discontinuation of disease-modifying therapy (DMT) in relapsing multiple sclerosis (RMS). Thus, the objective of this study was to generate and validate a risk score for disease reactivation after DMT discontinuation in RMS.

Methods: We drew a generation and validation dataset from two separate prospectively collected observational databases including RMS patients who received interferon-β or glatiramer acetate for ≥12 months, then discontinued DMT for ≥6 months and had ≥2 years of follow-up available. In the generation sample (n = 168), regression analysis was performed to identify clinical or magnetic resonance imaging (MRI) variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model and applied to the validation sample (n = 98).

Results: The variables included in the final model as independent predictors of disease reactivation were age at discontinuation, MRI activity at discontinuation, and duration of clinical stability (all p < 0.001). The resulting score was able to robustly identify patients at high (83%-85%), moderate (36%-38%), and low risk (7%) of disease reactivation within 5 years after DMT discontinuation in both cohorts.

Conclusions: The composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.
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http://dx.doi.org/10.1111/ene.14705DOI Listing
December 2020

Serum neurofilament light chain withstands delayed freezing and repeated thawing.

Sci Rep 2020 11 17;10(1):19982. Epub 2020 Nov 17.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Serum neurofilament light chain (sNfL) and its ability to expose axonal damage in neurologic disorders have solicited a considerable amount of attention in blood biomarker research. Hence, with the proliferation of high-throughput assay technology, there is an imminent need to study the pre-analytical stability of this biomarker. We recruited 20 patients with common neurological diagnoses and 10 controls (i.e. patients without structural neurological disease). We investigated whether a variation in pre-analytical variables (delayed freezing up to 24 h and repeated thawing/freezing for up to three cycles) affects the measured sNfL concentrations using state of the art Simoa technology. Advanced statistical methods were applied to expose any relevant changes in sNfL concentration due to different storing and processing conditions. We found that sNfL concentrations remained stable when samples were frozen within 24 h (mean absolute difference 0.2 pg/ml; intraindividual variation below 0.1%). Repeated thawing and re-freezing up to three times did not change measured sNfL concentration significantly, either (mean absolute difference 0.7 pg/ml; intraindividual variation below 0.2%). We conclude that the soluble sNfL concentration is unaffected at 4-8 °C when samples are frozen within 24 h and single aliquots can be used up to three times. These observations should be considered for planning future studies.
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http://dx.doi.org/10.1038/s41598-020-77098-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672085PMC
November 2020

Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis.

Mult Scler J Exp Transl Clin 2020 Oct-Dec;6(4):2055217320966344. Epub 2020 Oct 29.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: PIRA (progression independent of relapse) has emerged as a term to quantify the proportion of disability worsening due to non-inflammatory neurodegenerative processes in multiple sclerosis (MS).

Objective: To determine the impact of PIRA on retinal thinning, a biomarker of neuroaxonal degeneration in MS, in comparison to traditional disability worsening and relapse.

Methods: In a 4-year, prospective observational study including 171 relapsing MS (RMS) patients, retinal thinning was determined by annual spectral-domain optical coherence tomography measuring macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and peripapillary-retinal-nerve-fibre-layer (pRNFL). PIRA was defined as an expanded disability status scale (EDSS) or symbol digit modalities test (SDMT) worsening confirmed after 24 weeks with no relapse in the 30 days before or after the disability worsening.

Results: Each PIRA event was associated with a mean additional loss of GCIPL (1.8 µm) and pRNFL (1.9 µm), similar to the impact of EDSS and SDMT worsening. Overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3 µm) and pRNFL (1.4 µm).

Conclusions: PIRA is associated with retinal thinning, likely reflecting neurodegenerative processes, not directly associated with focal inflammation. It might be a clinical measure to identify MS patients with ongoing MS-associated neurodegeneration.
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http://dx.doi.org/10.1177/2055217320966344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604994PMC
October 2020

Longitudinal measurement of cerebrospinal fluid neurofilament light in anti-N-methyl-D-aspartate receptor encephalitis.

Eur J Neurol 2020 Nov 3. Epub 2020 Nov 3.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background And Purpose: Biomarkers reflecting the course of patients suffering from anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) are urgently needed. Neurofilament light chains (NfL) have been studied as potential markers for neuroaxonal injury mainly in neuroinflammatory diseases, but so far there have been only in a few small reports on anti-NMDARE. We aimed to compare the longitudinal course of cerebrospinal fluid (CSF)-NfL levels and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies with clinical parameters in six patients with anti-NMDARE.

Methods: Longitudinal measurement of CSF-NfL levels and CSF anti-NMDAR antibodies in six patients suffering from anti-NMDARE was performed.

Results: The major finding of this study is that most of our patients showed highly elevated NfL, with peak levels considerably delayed to clinical nadir. High NfL levels were associated with hippocampal atrophy but not with tumors detected. Furthermore, we did not find a clear relationship between NfL levels, CSF antibody titer, and CSF inflammatory markers.

Conclusions: CSF-NfL levels do not predict short-term outcome but rather are associated with intensive care unit stay and extreme delta brushes. However, high CSF-NFL levels were associated with long-term outcome. Our data suggest early aggressive immunotherapy to avoid primary and secondary neuroaxonal damage.
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http://dx.doi.org/10.1111/ene.14631DOI Listing
November 2020

Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis.

J Neurol 2020 Sep 14. Epub 2020 Sep 14.

Medizinische Universitat Wien, Wien, Austria.

Introduction: Treatment with disease-modifying therapies (DMT) in patients with clinically isolated syndrome (CIS) represents standard care in multiple sclerosis (MS) patients nowadays. Since a proportion of patients may show no evidence of disease activity (NEDA) after some time of treatment, the question might arise about the risks of stopping DMT.

Methods: We present a cohort of 49 patients who started DMT immediately after CIS and had no evidence of disease activity (NEDA-3) for at least five years before discontinuation of therapy. Thereafter, patients underwent clinical and MRI follow-up for at least five consecutive years.

Results: Of 49 patients discontinuing DMT, 53% (n = 26) had NEDA for at least further five years, while 47% (n = 23) showed either a relapse/disease progression (18.4%, n = 9), MRI activity (14.3%, n = 7) or both (14.3%, n = 7). The main predictive factor for sustained NEDA was age at DMT termination. Patients aged > 45 years had a significantly lower risk of disease reactivation (13% vs. 54% in patients aged < 45 years, p < 0.001) after DMT discontinuation.

Discussion: In CIS patients with immediate DMT after their first clinical episode, older age at the time of DMT discontinuation is the main predictive factor for sustained NEDA status.
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http://dx.doi.org/10.1007/s00415-020-10074-4DOI Listing
September 2020

Inner nuclear layer and olfactory threshold are interlinked and reflect inflammatory activity in multiple sclerosis.

Mult Scler J Exp Transl Clin 2020 Jul-Sep;6(3):2055217320945738. Epub 2020 Aug 24.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS).

Objective: The study aims to investigate (a) whether there is an association of INL and OT in MS and (b) if changes in INL and OT follow a time pattern in relation to MS relapse.

Methods: We assessed INL by optical coherence tomography and OT by Sniffin' Sticks in three different cohorts: a cross-sectional MS cohort ( = 260), a longitudinal, 3-year cohort of MS ( = 141) and healthy controls ( = 30), and a longitudinal, 24-weeks cohort with acute MS relapse ( = 28) and stable MS controls ( = 27).

Results: Cross-sectionally, INL and OT were strongly correlated with number but not localization of relapse in the previous 12 months and INL correlated with OT. Longitudinally, INL was thicker and OT score was lower short term in times of relapse activity, but not long term and independent of relapse localization. In acute MS relapse, INL and OT were altered compared with stable MS, again, independent of relapse localization resolving over 12-24 weeks with faster approximation to stable MS after escalation of disease-modifying treatment.

Conclusions: INL and OT are interlinked markers of short-term inflammatory activity, following a nearly congruent time pattern and independent of relapse localization, possibly reflecting a proinflammatory state within the central nervous system.
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http://dx.doi.org/10.1177/2055217320945738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448136PMC
August 2020

Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis.

Mult Scler Relat Disord 2020 Oct 17;45:102403. Epub 2020 Jul 17.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objective: To examine and validate thresholds for inter-eye differences in peripapillary retinal nerve fibre (pRNFL) and ganglion cell + inner plexiform layer (GCIPL) thicknesses for identifying unilateral optic neuritis in MS.

Methods: In this two-centre, cross-sectional study, optical coherence tomography was performed in 340 patients with clinically isolated syndrome (CIS) and MS. Cut-off values of inter-eye difference for identification of eyes with a history of unilateral ON were evaluated by receiver-operating characteristics analysis.

Results: For pRNFL ≥5 µm, sensitivity was 69% and specificity 68%, while for GCIPL ≥4 µm sensitivity was 67% and specificity 78%. The areas under the curve (AUC) were 0.72 (95% confidence interval: 0.64 - 0.79) for pRNFL and 0.78 (95%CI: 0.72 - 0.85) for GCIPL, indicating GCIPL as the superior model (p<0.001). When analysing only CIS patients, GCIPL inter-eye difference ≥4 µm also remained significant, while pRNFL inter-eye difference did not.

Interpretations: Inter-eye differences of ≥4 μm for GCIPL and to a lesser degree ≥5 μm for RNFL are robust thresholds for identifying unilateral optic nerve lesions. These thresholds could be used to demonstrate previous symptomatic and possibly asymptomatic ON and might be included into a new version of the diagnostic criteria.
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http://dx.doi.org/10.1016/j.msard.2020.102403DOI Listing
October 2020

Macular ganglion cell-inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis.

Mult Scler 2020 Jul 2:1352458520935724. Epub 2020 Jul 2.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Macular ganglion cell-inner plexiform layer (mGCIPL) is an emerging biomarker of neuroaxonal degeneration in multiple sclerosis (MS).

Objective: We aimed to determine cut-off values of mGCIPL thinning for discriminating between progressing and stable patients in relapsing multiple sclerosis (RMS).

Methods: This is a 3-year prospective longitudinal study on 183 RMS patients with annual optical coherence tomography. Best possible cut-off values of baseline mGCIPL and annual loss of macular ganglion cell-inner plexiform layer (aLmGCIPL) for discriminating clinically progressing (physical progression or cognitive decline) from stable patients were defined by receiver operating characteristics analysis and tested using multivariate regression models.

Results: Baseline mGCIPL thickness <77 µm was associated with an increased risk (hazard ratio: 2.7, 95% confidence interval (CI): 1.5-4.7,  < 0.001) of disability progression. An aLmGCIPL cut-off ⩾1 µm accurately identified clinically progressing patients (87% sensitivity at 90% specificity) and was a strong predictor of clinical progression (odds ratio: 18.3, 95% CI: 8.8-50.3).

Conclusion: We present evidence that cross-sectionally measured mGCIPL thickness and annualized thinning rates of mGCIPL are able to identify clinically progressing RMS with high accuracy.
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http://dx.doi.org/10.1177/1352458520935724DOI Listing
July 2020

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome.

J Neuroinflammation 2020 Mar 17;17(1):86. Epub 2020 Mar 17.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.

Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.

Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability.

Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
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http://dx.doi.org/10.1186/s12974-020-01737-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079539PMC
March 2020

Do elevated autoantibodies in patients with multiple sclerosis matter?

Acta Neurol Scand 2019 Mar 3;139(3):238-246. Epub 2018 Dec 3.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Objectives: The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort.

Material & Methods: In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels.

Results: The 18.8% of the MS cohort showed elevated serum autoantibody levels, but only 10.2% of all MS patients were diagnosed with a further autoimmune disease (AI). Patients with elevated serum autoantibodies (AABS) were not significantly more often diagnosed with a clinical manifest AI as compared to patients with negative autoantibodies (P = 0.338). MS patients with disease duration of more than 10 years showed no significant increase of positive autoantibodies as compared to patients with a more recent disease onset (P = 1). MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease course (P = 0.428).

Conclusions: According to our data, elevated serum autoantibodies do not have the potential to serve as a prognostic tool for disease severity in patients with MS Since MS patients with positive serum AABS did not significantly more often suffer from clinical manifest AIs than MS patients with negative serum AABS, the role of routine testing of serum AABS in MS patients should be critically called into question.
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http://dx.doi.org/10.1111/ane.13054DOI Listing
March 2019

Intravalley Spin-Flip Relaxation Dynamics in Single-Layer WS.

Nano Lett 2018 11 16;18(11):6882-6891. Epub 2018 Oct 16.

Department of Physics , Politecnico di Milano , Piazza Leonardo da Vinci 32 , I-20133 Milano , Italy.

In monolayer (1L) transition metal dichalcogenides (TMDs) the valence and conduction bands are spin-split because of the strong spin-orbit interaction. In tungsten-based TMDs the spin-ordering of the conduction band is such that the so-called dark excitons, consisting of electrons and holes with opposite spin orientation, have lower energy than A excitons. The transition from bright to dark excitons involves the scattering of electrons from the upper to the lower conduction band at the K point of the Brillouin zone, with detrimental effects for the optoelectronic response of 1L-TMDs, since this reduces their light emission efficiency. Here, we exploit the valley selective optical selection rules and use two-color helicity-resolved pump-probe spectroscopy to directly measure the intravalley spin-flip relaxation dynamics in 1L-WS. This occurs on a sub-ps time scale, and it is significantly dependent on temperature, indicative of phonon-assisted relaxation. Time-dependent ab initio calculations show that intravalley spin-flip scattering occurs on significantly longer time scales only at the K point, while the occupation of states away from the minimum of the conduction band significantly reduces the scattering time. Our results shed light on the scattering processes determining the light emission efficiency in optoelectronic and photonic devices based on 1L-TMDs.
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http://dx.doi.org/10.1021/acs.nanolett.8b02774DOI Listing
November 2018

Epidemiology of Multiple Sclerosis in Austria.

Neuroepidemiology 2017 19;49(1-2):40-44. Epub 2017 Aug 19.

Clinic for Neurology 2, Med Campus III, Kepler University Clinic Linz, Linz, Austria.

Background: To assess the incidence rate and prevalence ratio of multiple sclerosis (MS) in Austria.

Methods: Hospital discharge diagnosis and MS-specific immunomodulatory treatment prescriptions from public health insurances, covering 98% of Austrian citizens with health insurance were used to extrapolate incidence and prevalence numbers based on the capture-recapture method.

Results: A total of 1,392,629 medication prescriptions and 40,956 hospitalizations were extracted from 2 data sources, leading to a total of 13,205 patients. The incidence rate and prevalence ratio of MS in Austria based on the capture-recapture method were 19.5/100,000 person-years (95% CI 14.3-24.7) and 158.9/100,000 (95% CI 141.2-175.9), respectively. Female to male ratio was 1.6 for incidence and 2.2 for prevalence.

Conclusions: Incidence rates and prevalence ratios of MS in our study are within the upper range of comparable studies across many European countries as well as the United States.
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http://dx.doi.org/10.1159/000479696DOI Listing
May 2018

Non-professional marathon running: RAGE axis and ST2 family changes in relation to open-window effect, inflammation and renal function.

Sci Rep 2016 Sep 22;6:32315. Epub 2016 Sep 22.

Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University Vienna, Austria.

Conflicting data exist on the relevance of marathon (M) and half marathon (HM) running for health. The number of non-professional athletes finishing M and HM events is steadily growing. In order to investigate molecular changes occurring in amateur athletes, we enrolled 70 non-professional runners finishing a single M (34) or HM (36) event at baseline, the finish line and during recovery, and 30 controls. The measurement of the Receptor for Advanced Glycation Endproducts, Interleukin 1 receptor antagonist, ST2 and cytokeratin 18 was combined with molecules measured during clinical routine. Results were analyzed in the light of blood cell analysis, lactate measurements, correction for changes in plasma volume and body composition assessments. There were intrinsic differences in body mass index, abdominal body fat percentage and training time between M and HM runners. C-reactive protein changes in M and HM runners. While soluble RAGE, AGEs and ST2 increased immediately after the race in HM runners, HMGB1 increased in HM and M after the race and declined to baseline after a recovery period. We give insights into the regulation of various molecules involved in physical stress reactions and their possible implications for the cardiovascular system or renal function.
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http://dx.doi.org/10.1038/srep32315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032027PMC
September 2016

The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats.

Exp Neurol 2015 May 19;267:230-42. Epub 2015 Mar 19.

Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address:

After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.
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http://dx.doi.org/10.1016/j.expneurol.2015.03.013DOI Listing
May 2015

Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia.

F1000Res 2014 19;3:131. Epub 2014 Jun 19.

Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.

The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia. Neurological evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted to analyze neuroprotective signal-transduction in human primary glia cells and neurons. Neuronal sprouting assays were performed and neurotrophic factors in both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively. Neurological examinations revealed improvement after stroke in both treatment groups. Co-incubation of human astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes elicit neuroprotective effects on rats that have undergone ischemic stroke.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215751PMC
http://dx.doi.org/10.12688/f1000research.4219.2DOI Listing
November 2014

Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction.

Basic Res Cardiol 2011 Jun 17;106(4):645-55. Epub 2011 Mar 17.

Department of Thoracic Surgery, Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University Vienna, Währinger Gürtel 18-20, Vienna, Austria.

Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling.
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http://dx.doi.org/10.1007/s00395-011-0173-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105227PMC
June 2011