Polytraumaversorgung in der Luftrettung in Zeiten der COVID-19-Pandemie: Auswirkungen und Entwicklung der Fallzahlen

Notfall + Rettungsmedizin - Sowohl innerklinisch als auch präklinisch kam es durch das SARS-CoV-2-Virus zu Veränderungen in der Patientenversorgung. Durch das Herunterfahren des...     

Vision and visual cortical maps in mice with a photoreceptor synaptopathy: Reduced but robust visual capabilities in the absence of synaptic ribbons

How little neurotransmission in the visual system is sufficient to promote decent visual capabilities? This question is of key importance for therapeutic approaches to restore vision in patients who suffer from degenerative retinal diseases. In the retinae of mice, mutant for the presynaptic scaffolding protein Bassoon (Bsn), signal transfer at photoreceptor ribbon synapses is severely disturbed due to impaired ribbon attachment to the active zone. We have used two different behavioural tasks and optical imaging of intrinsic signals to probe vision in young and adult Bsn?/? mice and their wild-type littermates. Here we show that while visual acuity was significantly reduced in mutants compared to controls, vision guided behavioural decisions and optical imaging revealed essentially unperturbed cortical signals and retinotopy in spite of the photoreceptor synaptopathy. In addition, both vision and visual cortical maps were adult-like at 4 weeks of age. These results show that (i) while Bassoon-dependent fast exocytosis is essential for normal vision surprisingly good visual performance can be achieved in the absence of synaptic ribbons, (ii) both the development and maintenance of visual cortical maps is independent of synaptic ribbons and (iii) visual development in the mutants is completed at 4 weeks of age indicating that later developing ectopic synapses do not affect vision. Thus, the central visual system can make use of slow and weak retinal signals to subserve surprisingly robust vision.     

Targeted three‐dimensional immunohistochemistry reveals localization of presynaptic proteins Bassoon and Piccolo in the rat calyx of Held before and after the onset of hearing

Bassoon and Piccolo contribute to the cytomatrix of active zones (AZ), the sites of neurotransmitter release in nerve terminals. Here, we examined the 3D localization of Bassoon and Piccolo in the rat calyx of Held between postnatal days 9 and 21, the period of hearing onset characterized by pronounced structural and functional changes. Bassoon and Piccolo were identified by immunohistochemistry (IHC) on slices of the brainstem harboring calyces labeled with membrane‐anchored green fluorescent protein (mGFP). By using confocal microscopy and 3D reconstructions, we examined the distribution of Bassoon and Piccolo in calyces delineated by mGFP. This allowed us to discriminate calyceal IHC signals from noncalyceal signals located in the spaces between the calyceal stalks, which could mimic a calyx‐like distribution. We found that both proteins were arranged in clusters resembling the size of AZs. These clusters were located along the presynaptic membrane facing the principal cell, close to or overlapping with synaptic vesicle (SV) clusters. Only about 60% of Bassoon and Piccolo clusters overlapped, whereas the remaining clusters contained predominantly Bassoon or Piccolo, suggesting differential targeting of these proteins within a single nerve terminal and potentially heterogeneous AZs functional properties. The total number of Bassoon and Piccolo clusters, which may approximate the number of AZs, was 405 ± 35 at P9 and 601 ± 45 at P21 (mean ± SEM, n = 12). Normalized to calyx volume at P9 and P21, the density of clusters was similar, suggesting that the absolute number of clusters, not density, may contribute to the functional maturation associated with hearing onset. J. Comp. Neurol. 518:1008–1029, 2010. © 2009 Wiley‐Liss, Inc.     

A novel glucokinase activator modulates pancreatic islet and hepatocyte function

The glucose-sensing enzyme glucokinase (GK) plays a key role in glucose metabolism. We report here the effects of a novel glucokinase activator, LY2121260. The activator enhanced GK activity via binding to the allosteric site located in the hinge region of the enzyme. LY2121260 stimulated insulin secretion in a glucose-dependent manner in pancreatic beta-cells and increased glucose use in rat hepatocytes. In addition, incubation of beta-cells with the GK activator resulted in increased GK protein levels, suggesting that enhanced insulin secretion on chronic treatment with a GK activator may be due to not only changed enzyme kinetics but also elevated enzyme levels. Animals treated with LY2121260 showed an improved glucose tolerance after oral glucose challenge. These results support the concept that GK activators represent a new class of compounds that increase both insulin secretion and hepatic glucose use and in doing so may prove to be effective agents for the control of blood glucose levels in patients with type 2 diabetes.     

Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats

OBJECTIVE: Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. METHODS: Therefore, we characterized TG (n=35) vs. wild-type (WT) control rats (n=39) under physiological conditions (37 degrees C, stimulation rate <8 Hz). Twitch force, intracellular Ca2+ transients ([Ca2+]i), and SR Ca2+ content were measured in isolated muscles. The contribution of transsarcolemmal Ca2+ influx (I(Ca)) through L-type Ca2+ channels (LTCC) and reverse mode NCX (I(Na/Ca)) to Ca2+ cycling were studied in isolated myocytes. RESULTS: With increasing frequency, force increased in TG muscles by 168+/-35% (8 Hz; P<0.05) and SR Ca2+ content increased by maximally 118+/-31% (4 Hz; P<0.05). In WT, there was a flat force-frequency response without changes in SR Ca2+ content. Relaxation parameters of force and [Ca2+]i decay were accelerated at each frequency in TG vs. WT by approximately 10%. At prolonged rest intervals (<240 s), force and SR Ca2+ content increased significantly more in TG. Consequently, absolute SR Ca2+ content measured in myocytes was increased approximately 2-fold in TG. Transsarcolemmal Ca2+ fluxes estimated by I(Ca) (at 0 mV -10.2+/-1.1 vs. -16.9+/-1.3 pA/pF) and I(Na/Ca) (0.17+/-0.02 vs. 0.46+/-0.05 pA/pF) were decreased in TG vs. WT (P<0.05), whereas NCX and LTCC protein expression was only slightly reduced (P=n.s.). CONCLUSION: In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased.