36 research outputs found
Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance
Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is an autosomal dominant and the third most common inherited muscle disease. Cardiac involvement is currently described in several muscular dystrophies (MD), but there are conflicting reports in FSHD1. Mostly, FSHD1 is recognized as MD with infrequent cardiac involvement, but sudden cardiac deaths are reported in single cases. The aim of this study is to investigate whether subclinical cardiac involvement in FSHD1 patients is detectable in preserved left ventricular systolic function applying cardiovascular magnetic resonance (CMR). Methods: We prospectively included patients with genetically confirmed FSHD1 (n = 52, 48 ± 15 years) and compared them with 29 healthy age-matched controls using a 1.5 T CMR scanner. Myocardial tissue differentiation was performed qualitatively using focal fibrosis imaging (late gadolinium enhancement (LGE)), fat imaging (multi-echo sequence for fat/water-separation) and parametric T2- and T1-mapping for quantifying inflammation and diffuse fibrosis. Extracellular volume fraction was calculated. A 12-lead electrocardiogram and 24-h Holter were performed for the assessment of MD-specific Groh-criteria and arrhythmia. Results: Focal fibrosis by LGE was present in 13 patients (25%,10 men), fat infiltration in 7 patients (13%,5 men). T2 values did not differ between FSHD1 and healthy controls. Native T1 mapping revealed significantly higher values in patients (global native myocardial T1 values basal: FSHD1: 1012 ± 26 ms vs. controls: 985 ± 28 ms, p < 0.01, medial FSHD1: 994 ± 37 ms vs. controls: 982 ± 28 ms, p = 0.028). This was also evident in regions adjacent to focal fibrosis, indicating diffuse fibrosis. Groh-criteria were positive in 1 patient. In Holter, arrhythmic events were recorded in 10/43 subjects (23%). Conclusions: Patients with FSHD1 and preserved left ventricular ejection fraction present focal and diffuse myocardial injury. Longitudinal multi-center trials are needed to define the impact of myocardial changes as well as a relation between myocardial injury and arrhythmias on long-term prognosis and therapeutic decision-making. Trial Registration: ISRCTN registry with study ID ISRCTN13744381
Impact of Media Heat Treatment on Cell Morphology and Stability of L. acidophilus, L. johnsonii and L. delbrueckii subsp. delbrueckii during Fermentation and Processing
Manufacturers of starter cultures and probiotics aim to provide preparations with the highest possible amount of living cells and assurance of long-term storage stability. Thereby the industrial economy and thus an efficient outcome of the processes is of utmost importance. Earlier research has shown that the sterilization procedure of the microbial culture medium tremendously impacts growth performance of heating product-sensitive Lactobacillus strains. Thus, three different strains, i.e., L. acidophilus NCFM, L. johnsonii La-2801 and L. delbrueckii subsp. delbrueckii La-0704, were investigated for the influence of media heat pretreatment on cell morphology and stability during fermentation and further freeze drying and storage. The data indicate a relationship between the heating time of the culture medium, which is associated with an increase in browning reactions, and the cultural characteristics of the three strains. The resulting characteristic cell sizes of the cultures could be a major reason for the different stability properties during processing and storage that were observed. Besides the obvious relevance of the results for the production of starter cultures and probiotics, the pleomorphic phenomenon described here could also be a subject for other biotechnological processes, where heat-mediated media conversions, and thereby related cellular effects, could be a topic. Future studies have to show if further functional properties are influenced by the cell morphology and which cellular mechanisms lead to the observed pleomorphism
Progressive myocardial injury in myotonic dystrophy type II and facioscapulohumeral muscular dystrophy 1: a cardiovascular magnetic resonance follow-up study
AIM: Muscular dystrophy (MD) is a progressive disease with predominantly muscular symptoms. Myotonic dystrophy type II (MD2) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) are gaining an increasing awareness, but data on cardiac involvement are conflicting. The aim of this study was to determine a progression of cardiac remodeling in both entities by applying cardiovascular magnetic resonance (CMR) and evaluate its potential relation to arrhythmias as well as to conduction abnormalities. METHODS AND RESULTS: 83 MD2 and FSHD1 patients were followed. The participation was 87% in MD2 and 80% in FSHD1. 1.5 T CMR was performed to assess functional parameters as well as myocardial tissue characterization applying T1 and T2 mapping, fat/water-separated imaging and late gadolinium enhancement. Focal fibrosis was detected in 23% of MD2) and 33% of FSHD1 subjects and fat infiltration in 32% of MD2 and 28% of FSHD1 subjects, respectively. The incidence of all focal findings was higher at follow-up. T2 decreased, whereas native T1 remained stable. Global extracellular volume fraction (ECV) decreased similarly to the fibrosis volume while the total cell volume remained unchanged. All patients with focal fibrosis showed a significant increase in left ventricular (LV) and right ventricular (RV) volumes. An increase of arrhythmic events was observed. All patients with ventricular arrhythmias had focal myocardial changes and an increased volume of both ventricles (LV end-diastolic volume (EDV) p = 0.003, RVEDV p = 0.031). Patients with supraventricular tachycardias had a significantly higher left atrial volume (p = 0.047). CONCLUSION: We observed a remarkably fast and progressive decline of cardiac morphology and function as well as a progression of rhythm disturbances, even in asymptomatic patients with a potential association between an increase in arrhythmias and progression of myocardial tissue damage, such as focal fibrosis and fat infiltration, exists. These results suggest that MD2 and FSHD1 patients should be carefully followed-up to identify early development of remodeling and potential risks for the development of further cardiac events even in the absence of symptoms. Trial registration ISRCTN, ID ISRCTN16491505. Registered 29 November 2017 - Retrospectively registered, http://www.isrctn.com/ISRCTN16491505
Involvement of Sulfur in the Biosynthesis of Essential Metabolites in Pathogenic Fungi of Animals, Particularly Aspergillus spp. : Molecular and Therapeutic Implications
Fungal sulfur uptake is required for incorporation into the sidechains of the amino acids cysteine and methionine, and is also essential for the biosynthesis of the antioxidant glutathione (GSH), S-adenosylmethionine (SAM), the key source of methyl groups in cellular transmethylation reactions, and S-adenosylhomocysteine (SAH). Biosynthesis of redox-active gliotoxin in the opportunistic fungal pathogen Aspergillus fumigatus has been elucidated over the past 10 years. Some fungi which produce gliotoxin-like molecular species have undergone unexpected molecular rewiring to accommodate this high-risk biosynthetic process. Specific disruption of gliotoxin biosynthesis, via deletion of gliK, which encodes a Îł-glutamyl cyclotransferase, leads to elevated intracellular antioxidant, ergothioneine (EGT), levels, and confirms crosstalk between the biosynthesis of both sulfur-containing moieties. Gliotoxin is ultimately formed by gliotoxin oxidoreductase GliT-mediated oxidation of dithiol gliotoxin (DTG). In fact, DTG is a substrate for both GliT and a bis-thiomethyltransferase, GtmA. GtmA converts DTG to bisdethiobis(methylthio)gliotoxin (BmGT), using 2 mol SAM and resultant SAH must be re-converted to SAM via the action of the Methyl/Met cycle. In the absence of GliT, DTG fluxes via GtmA to BmGT, which results in both SAM depletion and SAH overproduction. Thus, the negative regulation of gliotoxin biosynthesis via GtmA must be counter-balanced by GliT activity to avoid Methyl/Met cycle dysregulation, SAM depletion and trans consequences on global cellular biochemistry in A. fumigatus. DTG also possesses potent Zn2+ chelation properties which positions this sulfur-containing metabolite as a putative component of the Zn2+ homeostasis system within fungi. EGT plays an essential role in high-level redox homeostasis and its presence requires significant consideration in future oxidative stress studies in pathogenic filamentous fungi. In certain filamentous fungi, sulfur is additionally indirectly required for the formation of EGT and the disulfide-bridge containing non-ribosomal peptide, gliotoxin, and related epipolythiodioxopiperazines. Ultimately, interference with emerging sulfur metabolite functionality may represent a new strategy for antifungal drug development
Detektion mittels Kardialer Magnetresonanztomographie
Since the following abstract refers to the study contents of the “top journal”
publication with first authorship and corresponding contribution listed below,
it has been taken directly from: Schmacht L, Traber J, Grieben U, Utz W,
Dieringer MA, Kellman P, Blaszczyk E, von Knobelsdorff-Brenkenhoff F, Spuler
S, Schulz-Menger J. Cardiac involvement in Myotonic Dystrophy type 2 patients
with preserved ejection fraction – Detection by Cardiovascular Magnetic
Resonance. Circulation: Cardiovascular Imaging. 2016;9:e004615.
doi:10.1161/CIRCIMAGING.115.004615. Background: Myotonic dystrophy type 2
(DM2) is a genetic disorder characterized by skeletal muscle symptoms,
metabolic changes, and cardiac involvement. Histopathologic alterations of the
skeletal muscle include fibrosis and fatty infiltration. The aim of this study
was to investigate whether subclinical cardiac involvement in DM2 is already
detectable in preserved left ventricular function by cardiovascular magnetic
resonance. Methods and Results: Twenty-seven patients (mean age, 54 ± 10
years; 20 females) with a genetically confirmed diagnosis of DM2 were compared
with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance
imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-
separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]),
and 1H magnetic resonance spectroscopy were performed. Extracellular volume
fraction was calculated. Conduction abnormalities were diagnosed based on Groh
criteria (Groh et al. 2008, doi:10.1056/NEJMoa062800). LGE located
subepicardial basal inferolateral was detectable in 22 % of the patients.
Extracellular volume was increased in this region and in the adjacent medial
inferolateral segment (P = 0.03 compared with healthy controls). In 21 % of
patients with DM2, fat deposits were detectable (all women). The control group
showed no abnormalities. Myocardial triglycerides were not different in LGE-
positive and LGE-negative subjects (P = 0.47). Six patients had indicators for
conduction disease (60 % of LGE-positive patients and 12.5 % of LGE-negative
patients). Conclusions: In DM2, subclinical myocardial injury was already
detectable in preserved left ventricular ejection fraction. Extracellular
volume was also increased in regions with no focal fibrosis. Myocardial
fibrosis was related to conduction abnormalities.Da sich die folgende Zusammenfassung auf die Studieninhalte der
“Topjournal”-Publikation mit Erstautorenschaft und entsprechendem unten
aufgefĂĽhrten Eigenanteil bezieht, ist sie inhaltlich dieser entnommen und ins
Deutsche ĂĽbersetzt worden. Ich verweise auf: Schmacht L, Traber J, Grieben U,
Utz W, Dieringer MA, Kellman P, Blaszczyk E, von Knobelsdorff-Brenkenhoff F,
Spuler S, Schulz-Menger J. Cardiac involvement in Myotonic Dystrophy type 2
patients with preserved ejection fraction – Detection by Cardiovascular
Magnetic Resonance. Circulation: Cardiovascular Imaging. 2016;9:e004615.
doi:10.1161/CIRCIMAGING.115.004615. Einleitung: Die Myotone Dystrophie Typ 2
(DM2) ist eine genetische Erkrankung, die sowohl durch eine muskuläre
Symptomatik, als auch durch metabolische Veränderungen und eine kardiale
Mitbeteiligung charakterisiert ist. Der Skelettmuskel dieser Patienten ist
histopathologisch durch Fibrosen und Fettinfiltrationen gekennzeichnet. Die
vorliegende Studie sollte untersuchen, ob myokardiale subklinische
Veränderungen bei DM2 auch bei erhaltener linksventrikulärer Pumpfunktion
mittels Kardiovaskulärer Magnetresonanztomographie (Kardio-MRT) zu detektieren
sind. Methoden und Ergebnisse: Es wurden 27 Patienten (mittleres Alter 54 ± 10
Jahre, 20 weiblich) mit genetisch gesicherter DM2 mittels 1,5 T Kardio-MRT
untersucht und einer Kontrollgruppe bestehend aus 17 Probanden gleichen Alters
und Geschlechtes gegenĂĽbergestellt. Zur myokardialen Gewebedifferenzierung
wurden T1 und T2 Mapping, Fett-/Wasserbildgebung, Late Gadolinium Enhancement
(LGE) zur Darstellung fokaler Fibrosen, sowie Protonen-
Magnetresonanzspektroskopie durchgeführt. Die extrazelluläre Volumenfraktion
wurde berechnet. Basierend auf den Groh-Kriterien (Groh et al. 2008,
doi:10.1056/NEJMoa062800) wurden Störungen im kardialen Reizleitungssystem
evaluiert. Bei 22 % der Patienten wurden im Kardio-MRT fokale Fibrosen
detektiert, welche vorwiegend subepikardial basal inferolateral lokalisiert
waren. Sowohl in diesem als auch in dem benachbarten, medial inferolateralen
Segment war die extrazelluläre Volumenfraktion im Vergleich zur Kontrollgruppe
erhöht (p = 0,03). Bei 21 % der Patienten mit DM2 waren fokale
Fettdepositionen nachweisbar (nur bei weiblichen Probanden). Die
Kontrollgruppe zeigte keine Auffälligkeiten. Der Gehalt an myokardialen
Triglyzeriden unterschied sich nicht zwischen Patienten mit und ohne fokalen
Fibrosen (p = 0,47). Hinweise für eine Überleitungsstörung wiesen sechs
Patienten auf (60 % der LGE-positiven und 12,5 % der LGE-negativen Patienten).
Fazit: Bei DM2 war eine subklinische myokardiale Mitbeteiligung bereits bei
erhaltener linksventrikulärer Pumpfunktion mittels Kardio-MRT nachweisbar. Die
extrazelluläre Volumenfraktion war auch in Regionen ohne fokale Fibrosen
erhöht. Myokardiale Fibrose war mit kardialen Überleitungsstörungen
assoziiert
Influence of Media Heat Sterilization Process on Growth Performance of Representative Strains of the Genus <i>Lactobacillus</i>
Lactic acid bacteria (LAB) are widely applied microorganisms in food, feed, and beverage applications, where they can provide essential functionality for product modification, increase product shelf life, or act as beneficial organisms after consumption. Among these, strains of the genus Lactobacillus are often used as starters, probiotics, or biopreservatives. For all these types of bacterial preparations, a transportable shelf-stable form of concentrated bacteria, preserving their intrinsic properties, is essential for commercial distribution. Former studies revealed a relationship between the culture medium, cellular morphology, and the robustness of Lactobacillus acidophilus NCFM (name derived from North Carolina Food Microbiology) cultures. Due to these insights, a multitude of Lactobacillus strains representative of the genus were screened regarding their sensitivity to thermal medium pretreatment possibly accompanied by the alteration of their chemical composition, such as the formation of Maillard reaction products (MRPs). This study reveals a quite diverse and different growth behavior of those strains in the form of altered or non-altered cell concentrations and the size distributions of the populations, whereby five strains of the L. delbrueckii group in particular showed increased cell concentrations combined with decreased mean cell volumes. The results are of both scientific and industrial relevance, as they highlight the necessity to consider and understand the effects of media sterilization for the applied production strain
Tradition as a Stepping Stone for a Microbial Defined Water Kefir Fermentation Process: Insights in Cell Growth, Bioflavoring, and Sensory Perception
A process development from a traditional grain-based fermentation to a defined water kefir fermentation using a co-culture of one lactic acid bacterium and one yeast was elaborated as a prerequisite for an industrially scalable, controllable, and reproducible process. Further, to meet a healthy lifestyle, a low ethanol-containing product was aimed for. Five microbial strains—Hanseniaspora valbyensis, Dekkera bruxellensis, Saccharomyces cerevisiae, Liquorilactobacillus nagelii, and Leuconostoc mesenteroides—were used in pairs in order to examine their influence on the fermentation progress and the properties of the resulting water kefir products against grains as a control. Thereby, the combination of H. valbyensis and L. mesenteroides provided the best-rated water kefir beverage in terms of taste and low ethanol concentrations at the same time. As a further contribution to harmonization and reduction of complexity, the usage of dried figs in the medium was replaced by fig syrup, which could have been proven as an adequate substitute. However, nutritional limitations were faced afterward, and thus, an appropriate supplementation strategy for yeast extract was established. Finally, comparative trials in 5-L scale applying grains as well as a defined microbial consortium showed both water kefir beverages characterized by a pH of 3.14, and lactic acid and aromatic sensory properties. The product resulting from co-culturing outperformed the grain-based one, as the ethanol level was considerably lower in favor of an increased amount of lactic acid. The possibility of achieving a water kefir product by using only two species shows high potential for further detailed research of microbial interactions and thus functionality of water kefir.DFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische Universität Berli
Differential sympathetic regulation of automatic, conductile, and contractile tissue in dog heart
Cardiac fibrosis in aortic stenosis and hypertensive heart disease assessed by magnetic resonance T1 mapping
BACKGROUND: Continuous pressure overload may lead to subclinical myocardial tissue changes in patients with hypertensive heart disease (HHD) and aortic stenosis (AS). The study aim was to detect interstitial fibrosis using quantitative cardiovascular magnetic resonance. METHODS: Fifteen patients with HHD (arterial Hypertension + septal wall thickness >/=13 mm), 33 with AS (eight mild, 15 moderate, 10 severe), and 60 healthy controls were enrolled. Native T1 maps (modified Look-Locker inversion recovery) were obtained in a basal, mid-ventricular, and apical shortaxis slice of the left ventricle to assess cardiac fibrosis. Focal fibrosis was assessed with late gadolinium enhancement (LGE). RESULTS: Patients with HHD and controls did not differ regarding the native myocardial T1 values, both per slice and per segment. In AS patients, apical native T1 values were lower than in controls, and there was a trend towards higher T1 values in the septum in severe AS (1172.6 +/- 62.0 ms versus 1152.9 +/- 43.9 ms). Five HHD patients and 11 AS patients had non-ischemic fibrosis in LGE images. Native T1 times did not differ between LGE-positive and LGEnegative groups (both with inclusion and exclusion of segments with LGE). CONCLUSIONS: T1 mapping did not reveal any evidence of abnormal interstitial fibrosis in HHD subjects with mild hypertrophy. In severe AS, a trend towards more interstitial fibrosis was present, but absolute differences were small for decision making
Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times
OBJECTIVE: Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time. MATERIALS AND METHODS: Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 x 1.4 x 6, 1.6 x 1.6 x 6, 1.7 x 1.7 x 6 mm3), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart. RESULTS: Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p < 0.001). The global partition coefficient was 0.43 +/- 0.3 for 0.2 and 0.1 mmol gadobutrol (p = 0.079). CONCLUSION: Related to the tested MOLLI technique at 3T, very small variations in spatial resolution (voxel sizes between 1.4 x 1.4 x 6 and 1.7 x 1.7 x 6 mm3) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts