54 research outputs found
Development of a test system to analyze different hip fracture osteosyntheses under simulated walking
The mechanical complications of osteosyntheses after hip fractures are previously investigated by mostly static or dynamic uniaxial loading test systems. However, the physiologic loading of the hip joint during a normal gait is a multiplanar, dynamic movement. Therefore, we constructed a system to test osteosyntheses for hip fractures under physiologic multiplanar loading representative of normal gait. To evaluate the testing system, 12 femora pairs were tested under 25,000 cycles with two standard osteosyntheses (Proximal Femoral Nail Antirotation/Gamma3 Nail). For angular movement, the varus collapse to cut out (proportional to(CO)) (proportional to(CO) = 4.8 degrees +/- 2.1 degrees for blade and proportional to(CO) = 7.8 degrees +/- 3.8 degrees for screw) was the dominant failure mode, and only slight rotational angle shifts (proportional to(Rot)) (proportional to(Rot) = 1.7 degrees +/- 0.4 degrees for blade and proportional to(Rot) = 2.4 degrees +/- 0.3 degrees for screw) of the femoral head around the implant axis were observed. Angular displacements in varus direction and rotation were higher in specimens reinforced with screws. Hence, the cut out model and the migration directions showed a distinction between helical blade and hip screw. However, there were no significant differences between the different implants. The new setup is able to create clinical failures and allows to give evidence about the anchorage stability of different implant types under dynamic gait motion pattern
Radioprotective effect of lidocaine on neurotransmitter agonist-induced secretion in irradiated salivary glands.
Previously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy.
Rabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy.
The uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca(2+) influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect.
Lidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands
Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes
Background: Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart. Methods: CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel. Results: In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA. Conclusion: By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.</p
The Degree of t-System Remodeling Predicts Negative Force-Frequency Relationship and Prolonged Relaxation Time in Failing Human Myocardium
The normally positive cardiac force-frequency relationship (FFR) becomes flat or negative in chronic heart failure (HF). Here we explored if remodeling of the cardiomyocyte transverse tubular system (t-system) is associated with alterations in FFR and contractile kinetics in failing human myocardium. Left-ventricular myocardial slices from 13 failing human hearts were mounted into a biomimetic culture setup. Maximum twitch force (F), 90% contraction duration (CD90), time to peak force (TTP) and time to relaxation (TTR) were determined at 37 degrees C and 0.2-2 Hz pacing frequency. F-1(Hz)/F-0.(5)(Hz) and F-2(Hz)/F-0.(5)(Hz) served as measures of FFR, intracellular cardiomyocyte t-tubule distance (Delta TT) as measure of t-system remodeling. Protein levels of SERCA2, NCX1, and PLB were quantified by immunoblotting. F-1(Hz)/F-0.(5)(Hz) (R-2 = 0.82) and F-2(Hz)/F-0.(5)(Hz) (R-2 = 0.5) correlated negatively with Delta TT, i.e., samples with severe t-system loss exhibited a negative FFR and reduced myocardial wall tension at high pacing rates. PLB levels also predicted F-1(Hz)/F-0.(5)(Hz), but to a lesser degree (R-2 = 0.49), whereas NCX1 was not correlated (R-2 = 0.02). CD90 correlated positively with Delta TT (R-2 = 0.39) and negatively with SERCA2/PLB (R-2 = 0.42), indicating that both the t-system and SERCA activity are important for contraction kinetics. Surprisingly, Delta TT was not associated with TTP (R-2 = 0) but rather with TTR (R-2 = 0.5). This became even more pronounced when interaction with NCX1 expression was added to the model (R-2 = 0.79), suggesting that t-system loss impairs myocardial relaxation especially when NCX1 expression is low. The degree of t-system remodeling predicts FFR inversion and contraction slowing in failing human myocardium. Moreover, together with NCX, the t-system may be important for myocardial relaxation
Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression
Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base
Is the rotation of the femural head a potential initiation for cutting out? A theoretical and experimental approach
We conclude the center-center position in the head of femur of any kind of lag screw or blade is to be achieved to minimize rotation of the femoral head and to prevent further mechanical complications
Acute hypothalamo-pituitary-adrenal axis response to LPS-induced endotoxemia: expression pattern of kinin type B1 and B2 receptors
A practical guide for investigating cardiac physiology using living myocardial slices
Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories. Here, we provide a practical guide on how to use LMS to interrogate multiple aspects of cardiac function, structure and biochemistry. We discuss issues that should be considered to conduct successful experiments, including experimental design, sample preparation, data collection and analysis. We describe how laboratory setups can be adapted to accommodate and interrogate this multicellular research model. These adaptations can often be achieved at a reasonable cost with off-the-shelf components and operated reliably using well-established protocols and freely available software, which is essential to broaden the utilization of this method. We will also highlight how current measurements can be improved to further enhance data quality and reliability to ensure inter-laboratory reproducibility. Finally, we summarize the most promising biomedical applications and envision how living myocardial slices can lead to further breakthroughs
Organ-specific extravasation of albumin-bound Evans blue during nonresuscitated hemorrhagic shock in rats
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