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81.
Gábor Zsurka Felicitas Becker Markus Heinen Hans-Jürgen Gdynia Holger Lerche Wolfram S. Kunz Yvonne G. Weber 《Seizure》2013,22(6):483-486
PurposeThe group of the rare progressive myoclonic epilepsies (PME) include a wide spectrum of mitochondrial and metabolic diseases. In juvenile and adult ages, MERRF (myoclonic epilepsy with ragged red fibres) is the most common form. The underlying genetic defect in most patients with the syndrome of MERRF is a mutation in the tRNALys gene, but mutations were also detected in the tRNAPhe gene.MethodHere, we describe a 40 year old patient with prominent myoclonic seizures since 39 years of age without a mutation in the known genes who underwent intensive clinical, genetic and functional workup.ResultsThe patient had a slight mental retardation and a severe progressive hearing loss based on a defect of the inner ear on both sides. Ictal electroencephalography (EEG) showed bilateral occipital and generalized spikes and polyspikes induced and aggravated by photostimulation. A cranial magnetic resonance imaging (cMRI) detected a global cortical atrophy of the brain and mild periventricular white matter lesions. The electromyography (EMG) was normal but the muscle biopsy showed abundant ragged red fibres. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed a novel heteroplasmic mutation (m.4279A>G) in the tRNAIle gene which was functionally relevant as tested in single skeletal muscle fibre investigations.ConclusionMutations in tRNAIle were described in patients with chronic progressive external ophthalmoplegia (CPEO), prominent deafness or cardiomyopathy but, up to now, not in patients with myoclonic epilepsy. The degree of heteroplasmy of this novel mitochondrial DNA mutation was 70% in skeletal muscle but only 15% in blood, pointing to the diagnostic importance of a skeletal muscle biopsy also in patients with myoclonic epilepsy. 相似文献
82.
83.
Cholesterol is important for cell membrane structure and functions as well as for production of steroid hormones and bile acids. It is transported through the body as lipoprotein particles of varying density and composition. Cholesterol homeostasis is maintained through finely tuned mechanisms regulating dietary uptake, hepatic biosynthesis and secretion as well as plasma clearance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cellular uptake of plasma low-density lipoprotein-cholesterol (LDL-C) by promoting LDL receptor (LDLR) degradation. Two nonsense single-nucleotide polymorphisms (SNPs) at the PCSK9 locus have been associated with life-long hypocholesterolemia and a remarkable reduction of the risk for coronary heart disease (CHD) in African-Americans. These loss-of-function SNPs presumably render PCSK9 less capable of inducing LDLR catabolism, effectively increasing LDLR availability and allowing efficient removal of plasma LDL-C. The combined frequency of heterozygosity for these nonsense SNPs is approximately 3-4% in populations of African descent. Homozygosity for either SNP, which would aggravate hypocholesterolemia, is reportedly rare. Whether such an aggravation would represent a health risk is still a matter of debate. From an evolutionary point of view, the cardioprotective effect of these nonsense SNPs may be a secondary phenotype made evident by the dyslipidemia-inducing lifestyle of today's North America. Their relatively high frequency in African-Americans must be interpreted in the context of the ancestral environment of these subjects in Africa, where diet and lifestyle were presumably less predisposing to atherosclerosis and where parasitic infections were major causes of morbidity and mortality before reproductive age. Parasites feed on host cholesterol for successful infection. The nonsense PCSK9 SNPs may have been positively selected because they reduced susceptibility to severe parasitic infections through cholesterol restriction. If so, these SNPs should be significantly more frequent in Sub-Saharan Africa where parasitic diseases, malaria in particular, have been and still are major selective forces. 相似文献
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85.
Controlling residual solvent levels is a major concern in pharmaceutical freeze-drying from co-solvent systems. This review provides an overview of the factors influencing this process and estimates their potential to reduce residual solvents in freeze-dried products. Decreased solvent contents are potentially correlated with the lower solid content, complete excipient crystallization, higher water solubility, and smaller molecular sizes of the solvent. Although no general rule can be derived for the selection of appropriate freezing conditions, the freezing stage appears to play a major role in subsequent volatile retention. In contrast, diverse secondary drying conditions do not appear to impact the amount of solvent retained in lyophilisates, and modification of this stage is thus not assumed to be expedient. Co-solvents are strongly entrapped in an amorphous product matrix as soon as the local moisture content decreases below a certain level. Thus, the moisture content in the dried product layer adjacent to the sublimation interface might be a key factor. Therefore, extension of the high moisture content period during the primary drying phase as well as a postlyophilization humidification of the dried products are presumably promising approaches to promote solvent release. 相似文献
86.
87.
Pierre Kunz Paul Mick Sascha Gross Gerhard Schmidmaier Felix Zeifang Marc-André Weber Christian Fischer 《Journal of orthopaedic research》2020,38(5):1150-1158
Supraspinatus (SSP) tendon tears represent a common indication for shoulder surgery. Yet, prediction of postoperative function and tendon retear remains challenging and primarily relies on morphologic magnetic resonance imaging (MRI)-based parameters, supported by patients' demographic data like age, gender, and comorbidities. Considering continuously high retear rates, especially in patients with larger tears and negative prognostic factors, improved outcome prediction could be of high clinical value. Contrast-enhanced ultrasound (CEUS) enables an assessment of dynamic perfusion of the SSP muscle. As a potential surrogate for muscle vitality, CEUS might reflect functional properties of the SSP and support improved outcome prediction after tendon repair. Fifty patients with isolated SSP tendon tears were prospectively enrolled. Preoperatively, SSP muscle perfusion was quantified by CEUS and conventional morphologic parameters like tear size, fatty infiltration, and tendon retraction were assessed by MRI. At six months follow-up, shoulder function, tendon integrity, and muscle perfusion were reassessed. The predictive value of preoperative CEUS for postoperative shoulder function and tendon integrity was evaluated. 35 patients entered the statistical analysis. Preoperative CEUS-based assessment of SSP perfusion significantly correlated with early postoperative shoulder function (Constant, r = 0.48, p < 0.018) and tendon retear (r = 0.67, p < 0.001). CEUS-based subgroup analysis identified patients with exceptionally high, respectively low risk for tendon retear. CEUS-based assessment of the SSP seemed to predict early shoulder function and tendon retear after SSP repair and allowed to identify patient subgroups with exceptionally high or low risk for tendon retear. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:1150-1158, 2020 相似文献
88.
Stefan Polenz Willy Kunz Benjamin Braun Andrea Franke Elena Lpez Frank Brückner Christoph Leyens 《Materials》2021,14(12)
Ceramic matrix composites (CMCs) are refractory ceramic materials with damage-tolerant behavior. Coming from the space industry, this class of materials is increasingly being used in other applications, such as automotive construction for high-performance brake discs, furnace technology, heat coatings for pipe systems and landing flaps on reusable rocket sections. In order to produce CMC faster and more cost-efficiently for the increasing demand, a new additive manufacturing process is being tested, which in the future should also be able to realize material joints and higher component wall thicknesses than conventional processes. The main features of the process are as follows. A ceramic fiber bundle is de-sized and infiltrated with ceramic suspension. The bundle infiltrated with matrix material is dried and then applied to a body form. During application, the matrix material is melted by laser radiation without damaging the fiber material. For the initial validation of the material system, samples are pressed and analyzed for their absorption properties using integrating sphere measurement. With the results, a suitable processing laser is selected, and initial melting tests of the matrix system are carried out. After the first validation of the process, a test system is set up, and the first test specimens are produced to determine the material parameters. 相似文献
89.
Krüger S Graf J Kunz D Stickel T Merx MW Hanrath P Janssens U 《European journal of heart failure》2005,7(4):475-478
BACKGROUND: Human Urotensin II (hU-II) is the most potent vasoconstrictor known to date. HU-II receptors are predominant in the human heart and arterial vessels, suggesting hU-II to be of importance as a cardiovascular mediator. METHODS: We studied 32 consecutive patients (60+/-12 years) with chronic heart failure (CHF) and 10 control subjects (54+/-12 years, n.s.) with cardiopulmonary exercise testing. Blood samples for the measurement of plasma hU-II and big-endothelin-1 (big-ET1) were obtained at rest and at peak exercise. RESULTS: Peak VO(2) was significantly higher in controls than in CHF patients (19.8+/-3.8 vs. 14.7+/-3.6 ml min(-1) kg(-1), P<0.001). Big-ET1 levels were increased in CHF compared to controls at rest (2.8+/-1.8 vs. 1.7+/-0.1 fmol/ml, P<0.01) and at peak exercise (2.7+/-1.7 vs. 1.6+/-0.2 fmol/ml, P<0.005). HU-II concentrations were comparable in patients with CHF and controls at rest (2990+/-1104 vs. 3290+/-508 pg/ml, n.s.) and peak exercise (3063+/-1185 vs. 3213+/-1188 pg/ml, n.s.). Resting hU-II levels demonstrated no correlation with peak VO(2) in controls or CHF patients. CONCLUSIONS: The measurement of circulating plasma levels of hU-II does not seem to be very helpful in studying the effects of hU-II in human cardiovascular regulation. A local paracrine or autocrine mediator effect of hU-II in CHF is possible. 相似文献
90.
J. Chr Reidemeister W. Isselhard W. Hasselkus R. Olbrisch U. Müller W. Stock 《Basic research in cardiology》1973,68(1):21-38
Zusammenfassung Ein Verfahren zur Verlängerung der tolerierbaren Ischämiezeit des Myokards stellt der vonBretschneider 1964 angegebene Herzstillstand durch Natrium- und Kalziumentzug und Procaingabe dar. Bisher waren der Sauerstoffverbrauch, der anaerobe Stoffwechsel, die Elektrolytbilanzen, sowie die histologisch morphologischen Veränderungen während der Kardioplegie am Hundeherzen untersucht worden. Für die sichere klinische Anwendung mußte die Erholung des Stoffwechsels nach einem solchen induzierten Herzstillstand analysiert werden. Eine erste Versuchsreihe zeigte, daß am isolierten Kaninchenherzen nach 60 min Ischämie bei 18 °C mit dieser Methode zwar eine gerade ausreichende postischämische Erholung des Stoffwechsels möglich ist, daß aber erhebliche Substratverluste mit der Reperfusion auftreten. Die zweite Versuchsreihe am Hundeherzen in situ ergab eine vollständige Erholung des Stoffwechsels innerhalb der ersten 5 min nach einer Ischämie von 60 min bei 25 °C mit der Methode vonBretschneider. Dabei tritt kein Substratverlust mit der Wiederdurchblutung des Koronarsystems auf. Die Summe der Adeninnucleotide bleibt auch während der 60 min Ischämie völlig konstant.Ein Vergleich der Veränderungen der Substrate und Metabolite des Stoffwechsels während der Kardioplegie mit den anderen bisher auch klinisch verwendeten Verfahren ergibt eindeutig die längsten tolerierbaren Ischämiezeiten bei Anwendung dieser Herzstillstandsmethode, so daß die Methode nach dem augenblicklichen Stand der Kenntnisse als das beste Verfahren zur Durchführung eines induzierten Herzstillstandes, d. h. einer notwendigen Myokardischämie gewertet werden muß.
Mit 3 Abbildungen und 2 Tabellen 相似文献
Summary In 1964Bretschneider introduced a cardioplegia by sodium and calcium depletion and application of procaine which was a new principle for prolongation of the tolerable ischemic period of the myocardium. Untill now the oxygen consumption, the anaerobic metabolism, the electrolyte balances and the histologic changes during this cardioplegia had been investigated in dogs. For a safe clinical use the recovery period after such an induced cardiac arrest had to be evaluated.In a first group of experiments a sufficient postischemie recovery was found after a 60 min period of ischemia at 18 °C with his method of cardiac arrest in isolated rabbit hearts. But a considerable ammount of metabolites was lost during reperfusion with blood.A second group of experiments showed a complete postischemic recovery during the first five minutes after a 60 min period of ischemia at 25 °C introduced by the method ofBretschneider in dogs in situ. There was no loss of metabolites during reperfusion of the coronary system with blood. The sum of adenine nucleotides remained constant throughout a 60 min period of ischemia.The changes of primary substrates and metabolites during this artificial cardiac arrest compared with other clinically introduced methods of cardioplegia showed the longest tolerable ischemic period with the cardiac stand still according toBretschneider. This method must be regarded in the moment as the safest method of induced cardiac arrest for a necessary period of myocardial ischemia.
Mit 3 Abbildungen und 2 Tabellen 相似文献