Ioannis Stratos

Fragestellung: Traumatische Weichteilschäden und deren Folgezustände bestimmen wesentlich die Prognose komplexer Verletzungen. Bei zusätzlich vorliegendem Diabetes mellitus Typ II und dadurch bedingten Begleitpathologien wie Angio- und Neuropathie wird von einer verzögerten Regeneration[for full text, please go to the a.m. URL]

Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demon...

Introduction The management of a patient suffering from blunt abdominal trauma (BAT) remains a challenge for the emergency physician. Within the last few years, the standard therapy for hemodynamically stable patients with BAT has transitioned to a non-operative approach. The purpose of this study is to evaluate the outcome of patients with BAT and to determine the reasons for failure of non-operative management (NOM). Materials and methods Analysis of 176 consecutive patients treated for BAT was conducted in a German level 1 trauma center from 2004 to 2011. Abdominal injuries were classified according to the American Association for the Surgery of Trauma (AAST). Patients included were demonstrated to have objective abdominal trauma with either free fluid on focused assessment with sonography for trauma (FAST) or computed tomography (CT), or proven organ injury. Results Patients, 142 of 176 (80.7%), with BAT were initially managed non-operatively, with a success rate of 90%. The rat...

Elevated peak bone mass in early adulthood reduces the risk for osteoporotic fractures at old age. As sports participation has been correlated with elevated peak bone masses, we aimed to establish a training program that would efficiently stimulate bone accrual in healthy young mice. We combined voluntary treadmill running with sprint interval training modalities that were tailored to the individual performance limits and were of either high or intermediate intensity. Adolescent male and female STR/ort mice underwent 8 weeks of training before the hind legs were analyzed for cortical and trabecular bone parameters and biomechanical strength. Sprint interval training led to increased running speeds, confirming an efficient training. However, males and females responded differently. The males improved their running speeds in response to intermediate intensities only and accrued cortical bone at the expense of mechanical strength. High training intensities induced a significant loss of...

Erythropoietin (EPO) is a pleiotropic cytokine with neuroprotective, anti-inflammatory, and muscle regenerative properties. The purpose of our study was to analyze the regenerative capacity of systemically applied EPO in a combined muscle-nerve injury model. We performed a crush injury to the left soleus muscle in 84 male Wistar rats. Using an instrumented clamp, the muscle was crushed over its complete length. Simultaneously, the ipsilateral sciatic nerve was sham manipulated or crushed. Upon induction of the trauma, animals received either EPO (E) (single application of 5,000 IU/kg body weight intraperitonial) or vehicle solution (K). After in vivo assessment of mechanical pain according to Frey, thermal hyperalgesia, latency of nerve conduction velocity, and strength of the soleus muscle were analyzed at days 1, 7, and 42 postinjury (n = 7 per group). Cell proliferation and apoptosis were assessed by means of histology and immunohistochemistry. Combined muscle-nerve injury showed...

Insufficient skeletal muscle regeneration after injury often impedes the healing process and is accompanied by functional deficiencies or pain. The aim of our study was to provide evidence that vitamin D improves muscle healing after muscle injury. Therefore, we used male rats and induced an injury of the soleus muscle. After crush injury, animals received either 8.3 mg/kg (332,000 IU/kg) body weight vitamin D or vehicle solution, s.c. After assessment of muscle force at days 1, 4, 14, and 42 after injury, sampling of muscle tissue served for analysis of proliferation, apoptosis, satellite cells, and prolyl-4-hydroxylase-β expression. Vitamin D application caused a significant increase in cell proliferation and a significant inhibition of apoptosis at day 4 after injury compared to control animals. The numbers of satellite cells were not influenced by the vitamin D application, but there was an increase in prolyl-4-hydroxylase-β expression, indicative of increased extracellular matrix proteins. This cellular turnover resulted in a faster recovery of contraction forces at day 42 in the vitamin D group. Current data support the hypothesis that vitamin D promotes the regenerative process in injured muscle. Thus, vitamin D treatment may represent a promising therapy to optimize recovery after injury.

Abstract Insufficiency of skeletal muscle regeneration often impedes the healing process with functional deficiencies and scar formation. We therefore tested the hematopoietic growth factor G-CSF with respect to its efficacy to improve functional muscle regeneration ...

Closed soft tissue injury (CSTI) induces local inflammation and progressive microvascular dysfunction. The aim of the study was to evaluate and compare the microvascular changes systematically in a precompartmental tissue injury by oxygen-to-see (O2C), a combined laser Doppler flowmetry and spectrophotometry system, and intravital fluorescence microscopy (IVM). Fourteen Wistar rats were subjected to a trauma and a control group (both n = 7). CSTI was performed on the left lower limb by means of a standardized impact device. Controls received a sham CSTI. Capillary blood flow (QRBC), oxygen saturation (sO2), and postcapillary filling pressure (rHb) were measured noninvasively by O2C assessed in 2-mm and 8-mm depth underneath the skin. Measurements were done before and after trauma and hourly up to 24 hours. IVM of the soleus muscle was performed after 24 hours. Before CSTI, O2C parameters did not reveal a difference between both groups. Up to 2 hours after trauma, QRBC was significantly increased in 8-mm tissue depth. No significant changes of sO2 and rHb were noted compared with controls. In 2-mm depth, significantly reduced QRBC and rHb levels were observed compared with 8 mm but with no significant changes after CSTI. IVM showed a significant increase of postcapillary blood flow with decreased functional capillary density, increased macromolecular leakage, and increased nicotinamide adenine dinucleotide hydride. After CSTI in rats, there was an immediate increase of compartmental capillary blood flow with a slight increase of muscle oxygen saturation and unchanged postcapillary venous filling pressures as sign of a redistribution of blood between soft and muscle tissue. The severity of pathologic changes in the compartment was not reflected by O2C but by IVM.

Muscle injury and degenerative muscle disease is a disabling condition in sport medicine and a challenging problem in orthopedic surgery. Upon traumatic or degenerative changes in the structure of the muscle, regeneration befalls mainly by increased proliferation of satellite cells. If the injury is extensive fibrosis and scar tissue formation occurs. Till now various alternative therapeutic ways have been proposed

Although muscle regeneration after injury is accompanied by apoptotic cell death, prolonged apoptosis inhibits muscle restoration. The goal of our study was to provide evidence that inhibition of apoptosis improves muscle function following blunt skeletal muscle injury. Therefore, 24 rats were used for induction of injury to the left soleus muscle using an instrumented clamp. All animals received either 3.3 mg/kg i.p. of the pan-caspase inhibitor Z-valinyl-alanyl-dl-aspartyl-fluoromethylketone (z-VAD.fmk) (n = 12 animals) or equivalent volumes of the vehicle solution DMSO (n = 12 animals) at 0 and 48 h after trauma. After assessment of the fast twitch and tetanic contraction capacity of the muscle at days 4 and 14 post injury, sampling of muscle tissue served for analysis of cell apoptosis (cleaved caspase 3 immunohistochemistry), cell proliferation (BrdU immunohistochemistry) as well as of muscle tissue area and myofiber diameter (HE planimetric analysis). Muscle strength analysis after 14 days in the z-VAD.fmk treated group revealed a significant increase in relative muscle strength when compared to the DMSO treated group. In contrast to the DMSO treated injured muscle, showing a transient switch towards a fast-twitching muscle phenotype (significant increase of the twitch-to-tetanic force ratio), z-VAD.fmk treated animals showed an enhanced healing process with a faster restoration of the twitch-to-tetanic force ratio towards the physiological slow-twitching muscle phenotype. This enhancement of muscle function was accompanied by a significant decrease of cell apoptosis and cell proliferation at day 4 as well as by a significant increase of muscle tissue area at day 4. At day 14 after injury z-VAD.fmk treated animals presented with a significant increase of myofiber diameter compared to the DMSO treated animals. Thus, z-VAD.fmk could provide a promising option in the anti-apoptotic therapy of muscle injury.

Insufficiency of skeletal muscle regeneration is often accompanied with functional deficiencies. The goal of our study was to assess the restoration of peripheral muscle upon injury of different severity. Blunt crush injury of the soleus muscle in rats was induced by a clamp and stepwise amplified in severity by rising the locking level of the clamp, resulting in three different groups (1× lock; 2× lock; 3× lock; n = 30 animals per group). After assessment of the fast twitch and tetanic contraction capacity at days 1, 4, 7, 14, and 42 postinjury sampling of muscle tissue served for analysis of cell proliferation, including satellite cells, apoptosis, and leukocyte infiltration. Contraction force analysis demonstrated significantly higher values of relative muscle strength in the 1× lock group compared to the two other groups over 42 days. Calculation of the twitch-to-tetanic force ratio revealed significantly higher mean values at days 1, 7, and 14 in the animals of group 2× lock and 3× lock, indicating a transformation toward a fast-twitching muscular phenotype. Moreover, cell proliferation during the first 4 days was found dependent on the severity of muscle injury in that the higher the severity the higher the proliferation. At the same time, cell apoptosis was found increased, and at day 1 the local leukocyte infiltration was significantly higher in the 3× lock compared to the 1× lock group. These data indicate that severity of injury correlates with local repair responses, which, however, are not necessarily sufficient to fully restore muscle function. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:950–957, 2010

Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated for the first time the EPO-dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 ± 1.5% was reduced by EPO to 17.2 ± 0.8%. Contraction force analysis in the EPO-treated animals revealed significantly improved muscle strength with 10–20% higher values of twitch and tetanic forces over the 42-day observation period. EPO-treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU-positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase-3-positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

ADInstruments data acquisition for life science. Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats. Ioannis Stratos, 1 Robert Rotter, 2 Christian Eipel, 1 Thomas Mittlmeier, 2 and Brigitte Vollmar 1. ...