Interventional left atrial appendage closure may affect metabolism of essential amino acids and bioenergetic efficacy.

BACKGROUND: Interventional closure of left atrial appendage (LAAC) represents an alternative for stroke prevention in patients with non-valvular atrial fibrillation. Whether LAAC may affect metabolomic pathways has not been investigated yet. This study evaluates the impact of LAAC on the metabolism of essential amino acids, kynurenine and creatinine. METHODS: Peripheral blood samples of prospectively enrolled patients undergoing successful LAAC were taken before (T0) and 6 months after (T1, mid-term follow-up). Targeted metabolomic profiling was performed using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements focusing on metabolism of essential amino acids. RESULTS: 44 patients with non-valvular AF (mean CHA2DS2-VASc score 4, mean HAS-BLED score 4) were enrolled. Changes in metabolites of essential amino acids, myocardial contraction and bioenergetic efficacy, such as phenylalanine (percentage change 8.2%, p = 0.006), tryptophan (percentage change 20.3%, p = 0.0006), tyrosine (percentage change 20.2%, p = 0.0001), creatinine (percentage change 7.2%, p > 0.05) and kynurenine (percentage change 8.3%, p = 0.0239) were found at mid-term follow-up. CONCLUSIONS: LAAC may affect the metabolism of essential amino acids and bioenergetic efficacy. ClinicalTrials.gov Identifier: NCT02985463.

Long term outcome of patients suffering from cancer and Takotsubo syndrome or myocardial infarction.

BACKGROUND: The pathophysiology of takotsubo syndrome (TTS) is unclear so far. There is strong association of the occurrence of TTS and malignant diseases. An association between malignant diseases and myocardial infarction (MI) was found recently and ascribed to common molecular and lifestyle mechanisms. AIM: To compare the outcome of patients with MI or TTS and malignant diseases in a matched cohort. METHODS: Patients with TTS or with MI (n = 138 per group) were matched for age and sex and assessed retrospectively and prospectively. Occurrence of malignant diseases and clinical outcome was followed up over 4 years. RESULTS: At the time of the index event, 8 (5.8%) MI patients and 17 (12.3%) TTS patients were already diagnosed with cancer. During follow up, the rate of patients who developed cancer was significantly higher in the TTS group than in the MI group (log rank P = 0.01). Mortality was higher in the TTS group, but also in the subgroup of TTS patients with cancer (log rank P < 0.05). In the multivariate analysis, male gender, renal impairment and the history of cancer was associated with an increased risk for death. CONCLUSIONS: Patients with TTS have more often malignant diseases than patients with MI. Cancer patients with TTS have a worse clinical outcome. The underlying mechanism is unclear yet, but the results point at TTS being the syndrome of an extracardiac disease rather than a disease of cardiac origin. Longer and closer follow up of patients with TTS and further studies addressing the mechanism of TTS are needed.

Percutaneous Closure of Left Atrial Appendage significantly affects Lipidome Metabolism.

Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.

Correction to: Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

Prevalence of cancer in Takotsubo cardiomyopathy: Short and long-term outcome.

BACKGROUND: Takotsubo Cardiomyopathy (TTC) is a transient disorder of ventricular wall dysfunction, mostly induced by physical or emotional stress. TTC may be associated with adverse cardiac events. The association of cancer and its clinical impact in TTC patients has not been described yet. METHODS: In 114 consecutive patients presenting with TTC between January 2003 and September 2015, we studied the frequency of cancer diagnosis, and compared the clinical course and the occurrence of a clinical endpoint of cancer and non-cancer patients during a follow up of 4.2years. RESULTS: Of the 114 patients, 16 (14.0%) had a malignancy already diagnosed at TTC, and further 11 patients received the diagnosis during follow up. Cancer patients had higher frequency of atrial fibrillation and lower hemoglobin levels at admission than patients without cancer. While the occurrence of in-hospital events was comparable, the diagnosis of cancer at TTC event or during follow up was predictive for a higher rate of the composite endpoint. In the Kaplan-Meier analysis, malignant diseases were strongly associated not only with overall mortality but also with worsened time of event-free survival during the long-term outcome. CONCLUSIONS: Prevalence of malignant diseases is high in TTC patients, and is a risk factor for worse outcome. Screening for malignancies should be recommended in all patients presenting with TTC. Further studies are needed to define the association on molecular levels.

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. OBJECTIVES: We aimed to study the effects of interventional LAAC on systemic metabolism. METHODS: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). RESULTS: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). CONCLUSIONS: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment.

OBJECTIVE: The primary objective of this single-centre, open-label, parallel-group study was to evaluate the pharmacokinetics and safety profile of the prandial glucose regulator repaglinide, following single and multiple dosing, in patients with type 2 diabetes with and without varying degrees of renal impairment. METHODS: The study comprised three screening visits, followed by a 7-day inpatient period. Thirty-four patients, with normal renal function (n = 12), mild-to-moderate renal dysfunction (n = 12) or severe renal dysfunction (n = 10), received a single 2-mg dose of repaglinide on day 1, followed by preprandial 2-mg doses with main meals (breakfast, lunch and dinner) on each of days 2-4. A final 2-mg dose of repaglinide was administered on day 5. RESULTS: Patients with mild-to-moderate renal impairment showed no significant differences in the pharmacokinetics of repaglinide, compared with patients with normal renal function. In the group of patients with severe renal dysfunction, the main pharmacokinetic finding was a longer half-life after multiple dosing. Rates of minor hypoglycaemia were similar in patients with severe, mild-to-moderate and no renal dysfunction. No major hypoglycaemic episodes occurred. CONCLUSION: Patients with type 2 diabetes and mild or moderate impairment of renal function may be treated with repaglinide without special precautions. If repaglinide is used in patients with severely impaired renal function, dose adjustment may be necessary if indicated by blood glucose measurements.

Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome.

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.

Vapor-Condensation Generation and STM Analysis of Fullerene Tubes.

Fullerene tubular structures can be generated by vapor condensation of carbon on an atomically flat graphite surface. Scanning tunneling microscope (STM) images revealed the presence of tubes with extremely small diameters (from 10 to 70 angstroms), most of which are terminated by hemispherical caps. Atomic resolution images of such structures showed that the tubes have a helical graphitic nature. The formation of the tubes under the quasi-free conditions suggests that the growth to tubular rather than spherical configurations is preferred for "giant fullerenes."

[Hydrophobicity and microbial production. 1. Selection of oleophilic microorganisms and qualitative characterization by several ecologically and technologically relevant activities]. / Hydrophobie und mikrobielle Leistung. 1. Selektion oleophiler Mikrooganismen und qualitative Charakterisierung durch einige ökologisch und technologisch relevante Leistungen.

From samples of different origin microorganisms were selected using the property of oleophily. All oleophilic isolates (30 strains are characterized in more detail) proved to be Gram-positive, nonsporogenic bacteria, obviously belonging to the group of coryneforms. They are growing on a broad spectrum of substrates, 11 strains are facultatively methylotrophic. They are utilizing methanol as well as n-alkanes and glucose without any supplines. 6 strains are able to degrade and decolorize triphenylmethane dyes, for example crystal violet and malachite green. Because of the degradative capacities, combined with the hydrophobic properties of the cell surface, the group of the oleophilic bacteria seems to be very promising in relation to the development of environmental technologies and ecological investigations.

[Preparation of preoral sustained-release preparations with a base of biodegradable polymers. 3. Preparation of matrix tablets with a base of poly-3-hydroxybutyric acid]. / Darstellung peroraler Retardarzneiformen auf der Basis von biologisch abbaubaren Polymeren. 3. Mitteilung4: Darstellung von Matrixtabletten auf der Basis von Poly-3-hydroxybuttersäure.

Poly-3-hydroxybutyric acid belongs to the biological polymers, which are produced by bacterials. The determination of the grain size, moisture content, flowability and the parameters for the direct compression was performed in regard of their use as auxillary substance for the preparation of solid sustained release dosage forms. The production of the matrix tablets was performed on the basis of a factorial design. The content of substance, an addition of Heweten 12 and the compression power served as factors. Caffeine was used as model drug. The in vitro release values show, that all three factors have an influence of the drug release. Optimized matrix tablets were produced on the basis of this result.

[Quantitative studies of the collagen content of the human amnion and chorion]. / Quantitative Untersuchungen über den Gehalt an Kollagen im menschlichen Amnion und Chorion.

The content of collagen in the amniotic and chorionic connective tissue was determined with the quantitative investigation method of hydroxyprolin. Significant differences do not exist between the amount of collagen in the amniotic and chorionic connective tissue. The difference in the tension stability must be based on the variegating pattern of the collagen fibrils.

[Evaluation of hearing improvement due to hearing aids]. / Bewertung des Hörerfolges bei Hörgeräteversorgung.

A method to assess the hearing improvement due to hearing aids is described. This method has been used routinely at a local hospital for 2 years on 200 patients. This method is based on the assessment of the speech reception threshold for sentences ("Marburger Satztest") in silence and in various noise levels (speech simulating noise). The following were used for the assessment of the hearing aid: the improvement of the speech reception threshold in silence with or without a hearing aid, the maximum tolerable noise level (i.e. the noise level at which everyday speech becomes subliminal for patients with hearing aids) and the noise level at which the speech reception threshold with the hearing aid is worse than without.