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Ali Modabber,1 Nassim Ayoub,1 Stephan Christian Möhlhenrich,1 Evgeny Goloborodko,1 Tolga Taha Sönmez,1 Mehrangiz Ghassemi,2 Christina Loberg,3 Bernd Lethaus,1 Alireza Ghassemi,1 Frank Hölzle1 1Department of Oral, Maxillofacial and Plastic Facial Surgery, 2Department of Orthodontics, 3Department of Diagnostic and Interventional Radiology, RWTH Aachen University Hospital, Aachen, Germany Background: The intention of mandibular reconstruction is to restore the complex anatomy with maximum possible functionality and high accuracy. The aim of this study was to evaluate the accuracy of computer-assisted surgery in primary mandibular reconstruction with an iliac crest bone flap compared with an osteomyocutaneous fibula flap. Materials and methods: Preoperative computed tomography data of the mandible and the iliac crest or fibula donor site were imported into a specific surgical planning software program. Surgical guides were manufactured using a rapid prototyping technique for translating the virtual plan, including information on the transplant dimensions and shape, into real-time surgery. Using postoperative computed tomography scans and an automatic surface-comparison algorithm, the actual postoperative situation was compared with the preoperative virtual simulation. Results: The actual flap position showed a mean difference from the virtual plan of 2.43 mm (standard deviation [SD] ±1.26) and a surface deviation of 39%

It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40-60). VEGFR-2 activity increased in the + Sr group from days 0-15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40-60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.

Objectives: This study was conducted to explore whether Hypericum perforatum L. (HPL) as a potent antioxidant protects against oxidative stress, cytokine production and caspase expression in muscle (soleus), brain and blood of sciatic nerve injury (SNI)-induced rats., Methods: Thirty-five rats were equally divided into five groups. The first and second were used as untreated control and sham control groups, respectively. The third, fourth and fifth were sham + HPL, SNI and SNI + HPL groups, respectively. The third and fifth groups received 30 mg/kg HPL via gastric gavage for 28 days., Key Findings: High levels of muscle, brain and red blood cell (RBC) lipid peroxidation, plasma cytokine (TNF-α, IL-1β and IL-2), muscle PARP, caspase 3 and 9 expression levels were decreased by HPL treatments. Plasma glutathione peroxidase (GPx) activity, α-tocopherol and melatonin, muscle, brain and RBC reduced glutathione (GSH) concentrations were decreased by SNI induction, whereas their values were increased by HPL treatments. β-carotene and retinol concentrations did not change in the five groups., Conclusion: HPL may play a role in preventing SNI-induced inflammatory, oxidative and apoptotic blood, muscle and brain damages through upregulation of the GSH and GPx values but downregulation of PARP, caspase level and cytokine production in SNI-induced rats., (© 2017 Royal Pharmaceutical Society.)

Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia/reperfusion (I/R) damage. 8 week-old male C57BL/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I/R, as revealed by specific staining for neutrophils and monocyte/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation in vivo. Disrupting chemokine heterodimers during myocardial I/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence.

Background: Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss ® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss ® in ethanol (EtOH) treated osteoblasts., Methods: The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss ® were assessed., Results: The application of PRGF and Bio-Oss ® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss ® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss ® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells., Conclusions: These results indicate that the simultaneous application of PRGF and Bio-Oss ® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective: To investigate the results of penile urethral reconstruction using amniotic membrane (AM) and buccal mucosa (BM) grafts, and the simultaneous use of both in a rabbit model., Materials and Methods: A total of 28 male rabbits were divided into 4 groups according to grafting style: group 1 (AM), group 2 (BM), group 3 (BM + AM), and group 4 (sham). A standardized urethral defect was created in the 3 initial groups. The sham group underwent only a ventral vertical urethral incision and primary re-suturation. AM grafts were used in group 1, and BM grafts were used in groups 2 and 3. AM grafts were affixed to the BM grafts in group 3 as a covering tissue. Urethrography and endoscopy were performed after the 1st and 2nd months of grafting. The penises were subjected to histopathologic and immunohistochemical assessment for fibroblast growth factor and vascular endothelial growth factor expression., Results: Dehiscence and fistula developed in group 1, whereas 2 fistulas were observed in group 2. No complications developed in group 3. Epithelization at urethras was observed at 4 weeks in all groups, but transformation to urothelial epithelialization occurred at 8 weeks. Marked amelioration and epithelial transformation were observed in group 3. The most prominent fibroblast growth factor expression was observed in group 3. Vascular endothelial growth factor expression was completely negative in group 3 at 8 weeks, indicating complete healing., Conclusion: The simultaneous use of AM and BM for ventral onlay penile urethroplasty provides better tissue healing and lower complication rates in comparison to BM alone. Further animal studies or clinical applications are needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF- α . The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF- α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF- α . The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF- α and IL-1 β . An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

Background: The objectives of this prospective randomized trial were to assess the impact of Peyton's four-step approach on the acquisition of complex psychomotor skills and to examine the influence of gender on learning outcomes., Methods: We randomly assigned 95 third to fifth year medical students to an intervention group which received instructions according to Peyton (PG) or a control group, which received conventional teaching (CG). Both groups attended four sessions on the principles of manual therapy and specific manipulative and diagnostic techniques for the spine. We assessed differences in theoretical knowledge (multiple choice (MC) exam) and practical skills (Objective Structured Practical Examination (OSPE)) with respect to type of intervention and gender. Participants took a second OSPE 6 months after completion of the course., Results: There were no differences between groups with respect to the MC exam. Students in the PG group scored significantly higher in the OSPE. Gender had no additional impact. Results of the second OSPE showed a significant decline in competency regardless of gender and type of intervention., Conclusions: Peyton's approach is superior to standard instruction for teaching complex spinal manipulation skills regardless of gender. Skills retention was equally low for both techniques.

Background: The aim of this study was to assess the impact of two teaching interventions (ultrasound and arthroscopy) in a peer teaching (PT) environment on anatomy examination scores and also to examine the influence of gender and learning style on these scores., Methods: We randomly assigned 484 second year medical students to one of three groups: musculoskeletal ultrasound (MSUS), arthroscopy (ASC) and control (CON). The MSUS- and the ASC-group attended two additional training sessions in ultrasound or arthroscopy; the CON-group received no additional lessons. Students were asked to complete Kolb's Learning Style Inventory test. We assessed differences in anatomical knowledge (multiple choice (MC) exam) and subjective evaluation with respect to gender and learning style., Results: There were no relevant differences between the three groups regarding the MC exam. Acceptance of the peer teaching concept was good. All students preferred ultrasound to arthroscopy and thought that they learned more from ultrasound despite the fact that they rated the instructors as less competent and needed more time to gain in-depth knowledge. There was no significant effect of gender on evaluation results. Arthroscopy was best enjoyed by accommodators according to Kolb's Inventory and least by divergers, who found that they had learned a lot through ultrasound. The improvement in spatial conceptualization was greatest for accommodators and worst for assimilators., Conclusion: Gender and learning style had no impact on quantitative parameters. Qualitative analysis, however, revealed differences for learning style and further evaluation is warranted to assess the impact on medical education., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: To evaluate and compare the success of amniotic membrane (AM) and buccal mucosa (BM) grafts and simultaneous use of both in penile augmentation urethroplasty in rabbits., Materials and Methods: A total of 12 New Zealand rabbits were divided into 3 groups by grafting style: Group 1 (AM), Group 2 (BM), and Group 3 (simultaneous use of BM and AM). In all animals, a standardized urethral defect was created. BM and AM were obtained from the rabbits. Solely AM grafts were affixed to the defects in Group 1, solely BM grafts were affixed to the urethral defects in Group 2, and simultaneous AM + BM grafts were affixed in Group 3. At 4 and 8 weeks, the penises were subject to histological assessment of subepithelial fibrosis, epithelial transformation, and inflammatory reaction., Results: Stenosis was detected in none of the groups. A dehiscence was developed in one rabbit in Group 1 and a fistula was developed in one rabbit in Group 2. After 4 weeks, minimal subepithelial fibrosis and inflammatory reaction were observed in Group 2, while subepithelial fibrosis was not in Groups 3. After 8 weeks, subepithelial connective tissue proliferation was moderate in Group 2, at both 4th and 8th weeks in Group 2. After 8 weeks, the best epithelial transformations were observed in Group 3., Conclusion: In an animal model, the simultaneous use of AM and BM grafts following acute urethral injury may be feasible for penile augmentation urethroplasty. Further study is needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Third-generation cephalomedullary nails currently represent the gold standard in the treatment of unstable trochanteric femur fractures. Recently, an extramedullary rotationally stable screw-anchor system (RoSA) has been developed. It was designed to combine the benefits of screw and blade and to improve stability using a locked trochanteric stabilizing plate (TSP). The purpose of this study was to compare the biomechanical behavior of RoSA/TSP and the proximal femoral nail antirotation (PFNA)., Methods: Standardized AO/OTA 31A2.2 fractures were induced by an oscillating saw in 10 paired human specimens (n = 20; mean age = 85 years; range: 71-96 years). The fractures were stabilized by either the RoSA/TSP (Koenigsee Implants, Allendorf, Germany) or the PFNA (DePuy Synthes, Zuchwil, Switzerland). Femurs were positioned in 25 degrees of adduction and 10 degrees of posterior flexion and were cyclically loaded with axial sinusoidal pattern at 0.5 Hz, starting at 300 N, with stepwise increase by 300 N every 500 cycles until bone-implant failure occurred. After every load step, the samples were measured visually and radiographically. Femoral head migration was assessed., Results: The stiffness at the load up to the clinically relevant load step of 1800 N (639 ± 378 N/mm (RoSA/TSP) vs. 673 ± 227 N/mm (PFNA); P = 0.542) was comparable, as was the failure load (3000 ± 787 N vs. 3780 ± 874 N; P = 0.059). Up to 1800 N, no femoral head rotation, head migration, or femoral neck shortening were observed either for RoSA/TSP or PFNA. Whereas failure of the PFNA subsumed fractures of the greater trochanter and the lateral wall, a posterior femoral neck fracture with a significantly increased femoral neck shortening (1.7 mm vs. 0 mm; P = 0.012) was the cause of failure with RoSA/TSP. This specific kind of failure was induced by a femoral neck weakening caused by the posterior TSP stabilizing screw., Conclusions: There was no significant difference in biomechanical properties between the RoSA/TSP and the PFNA for the fracture pattern tested. However, failure modes differed between the 2 implants with greater femoral neck shortening observed in the RoSA/TSP group.

Introduction: Locked minimally invasive plating and fourth generation nailing potentially could reduce the complication rate in the treatment of trochanteric femur fractures by its rotational stability and providing better lateral cortical support. The purpose of this study was (1) to compare the biomechanical properties of the Percutaneous compression plate (PCCP) and the Intertan nail (IT) with regards to implant failure and (2) to assess dynamic stability coefficients in an unstable AO/OTA 31A2.2 fracture model., Methods: In paired femurs, a standardised unstable trochanteric femur fracture was induced by an oscillating saw. The fractures were stabilised by either the PCCP (Orthofix, McKinney, TX, USA) or the IT (Smith & Nephew, Memphis, TN, USA). All femurs were loaded with 300N, followed by an increase in load until failure using 300N each time (2000 cycles each, 0.5Hz). After every load step the samples were assessed visually and radiographically. We measured migration and performed a survival analysis., Results: 16 fractures were induced in 8 paired human specimens (mean age: 84 years, 61-100 years). The mean stiffness (PCCP vs. IT: 249±124N/mm vs. 273±153N/mm; p=0.737) was comparable. The IT proved superior to the PCCP with regard to the number of cycles reached before failure occurred (PCCP vs. IT: 12,691±4733 vs. 15,313±4875 cycles; p=0.023). Except for a higher axial migration of the IT at failure point (PCCP vs. IT: 1.3mm vs. 4.3mm; p=0.028) there were no differences between the intra- and extramedullary implants, not even in terms of rotational stability along the femoral neck axis. A fracture of the femoral neck caused test abortion in both implants in most cases., Conclusion: This study showed a superiority of the IT compared with the PCCP with regards to number of cycles achieved under sequential load increases for unstable trochanteric femur fractures. The stiffness was comparable. Both implants showed a high rotational stability and a support of the lateral wall., Study Type: Biomechanical study., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The supraclavicular fasciocutaneous flap is a well-recognized flap in head and neck reconstruction. In this report, we describe for the first time a variation of this flap, the osteocutaneous supraclavicular (SOC) free flap, which was used to reconstruct a composite nasal defect. The defect arose after resection of a recurrent squamous cell carcinoma and involved dorsal nasal skin, cartilage, and the entire nasal bone. A 6 cm × 4 cm size flap including skin, subcutaneous tissue, and a vascularized cortico-periosteal segment of the clavicle was raised based on the transverse cervical artery. The flap survived with no complications. A satisfactory aesthetic outcome was achieved following two revision procedures. We believe that the incorporation of bone to the supraclavicular flap may expand its applications in reconstruction of composite nasal and facial defects., (© 2015 Wiley Periodicals, Inc.)

Purpose: Open fibrin gluing is reported to enable anatomical reconstruction with less soft tissue compromise than suture repair. Our main objective was to compare the complication rate, function, pain and disability of the two operative approaches of percutaneous suture using the Paessler technique and open fibrin gluing., Methods: Sixty-four patients (two centres, retrospective cohort study, 2000-2009) who had undergone acute Achilles tendon repair with either percutaneous suture (n = 27; 44 years) or open fibrin glue (n = 37; 45 years) took part in a follow-up examination after a median of 63 months (range, six to 180). Ankle range of motion, calf and ankle circumferences and return to work and sports activities were evaluated. Isokinetic und sonographic evaluation results were retrieved., Results: Complications were noted in 22 patients (34 %). Delayed wound healing without evidence of surgical site infection was found in three patients in the fibrin group and two patients in the suture group. Postoperative scar tenderness described as pain at the rim of the shoe was significantly more frequent in the suture group (p = 0.03). Re-rupture requiring re-operation occurred in one patient. Transient paresthesia of the heel occurred in 12 patients. No sural nerve lesions were reported. There was no significant difference between groups regarding lower leg circumference, disability, or function. Ultrasound and isokinetic measurements did not reveal a significant difference between the two methods., Conclusions: The present study suggests that open fibrin gluing is a reasonable alternative to percutaneous repair of acute ruptures of the Achilles tendon and both techniques can yield reliably good results.

Background: Orbital exenteration (OE) is a disfiguring procedure, which typically includes the removal of the entire eyeball including the globe, extraocular muscles, and periorbital soft tissues after malignancies excision or trauma. Several methods of orbital reconstruction have been attempted with varying success. In this report, we analyze results of the use of gracilis muscle free flap for reconstruction of OE defects and its feasibility for prosthetic rehabilitation., Methods: Nine consecutive patients treated at the China Medical University Hospital of Taichung during January 2009 to January 2013, who had gracilis free flap reconstruction after OEs, were retrospectively reviewed. Cancer in six patients and trauma in remaining three patients was the cause for OE., Results: Nine patients who underwent reconstruction with gracilis free tissue transfer had a successful outcome. There was not any donor or recipient site morbidity; however, one patient was deceased during follow-up period due to metastasis. The mean follow-up period was 23.5 months. Cosmetic results were acceptable both to patients and to surgeons., Conclusions: Gracilis free flap to repair OE defects may be a safe alternative for reconstruction. It provides a larger volume of well-vascularized tissue, greater placement flexibility, and minor donor site morbidity without any significant functional deficit., (© 2014 Wiley Periodicals, Inc.)

Skeletal muscles harbour a resident population of stem cells, termed satellite cells (SCs). After trauma, SCs leave their quiescent state to enter the cell cycle and undergo multiple rounds of proliferation, a process regulated by MyoD. To initiate differentiation, fusion and maturation to new skeletal muscle fibres, SCs up-regulate myogenin. However, the regulation of these myogenic factors is not fully understood. In this study we demonstrate that Nrf2, a major regulator of oxidative stress defence, plays a role in the expression of these myogenic factors. In both promoter studies with myoblasts and a mouse model of muscle injury in Nrf2-deficient mice, we show that Nrf2 prolongs SC proliferation by up-regulating MyoD and suppresses SC differentiation by down-regulating myogenin. Moreover, we show that IL-6 and HGF, both factors that facilitate SC activation, induce Nrf2 activity in myoblasts. Thus, Nrf2 activity promotes muscle regeneration by modulating SC proliferation and differentiation and thereby provides implications for tissue regeneration., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

This study aimed to evaluate the osteometric boundaries of the ilium, fibula, and scapula beyond which reconstruction of oromandibular and craniofacial defects, using these free flaps, may not be optimal. Fibula, scapula, and iliac bones were obtained bilaterally from 33 female and 27 male European adult cadavers (n = 60). Adapting classical anthropometric methods to surgical needs by modifying the measuring bone localizations and measurement points, a measuring system of osteometry and morphometry was used, to quantify the usable bone length of the iliac crest, fibula, and lateral border of the scapula and to localize an oval region (OR) in the ilium. The thin, translucent OR of ilium was localized 62.4 ± 5.6 mm posterior to the maximum concavity between the anterior superior (ASIS) and anterior inferior iliac spine and 26.7 ± 6 mm caudal to the intermediate line of the iliac crest. The available iliac crest was measured from ASIS to the posterior superior iliac spine (PSIS) 247.5 ± 12.6 mm, fibula supplied 170.2 ± 19.1 mm harvestable bone, and the lateral border of the scapula 94.3 ± 8.5 mm [Corrected]. The OR influenced the harvestable bone shape and volume of the ilium. Measuring of the localization points of OR, we found that the size of the OR was very variable and that the height of the neomandible reconstructed with iliac crest might alter with aging. Our findings contribute with knowledge of detailed morphometric measurements on commonly used donor bones to the planning strategies of volumetric defects in oral and maxillofacial region by precise osteometric localization method of OR and relativized length measurements., (© 2014 Wiley Periodicals, Inc.)

Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.

Introduction: Treatment of advanced lymphedema remains a challenge in reconstructive surgery. Microsurgical techniques seem to be effective in early stage lymphedema, however in advanced stages their role is not well established. In this study, we present a novel approach for advanced lymphedema combining excisional procedure (Charles) with transferring lymph node flap., Patients and Method: From 2010 to 2013, 24 patients (18 women, six men, mean age 53 years old) presented with late stage of lower extremity lymphedema. The modification of Charles procedure consisted of preserving the superficial venous system of the dorsum of the foot and the lesser saphenous vein, which were used for the venous anastomosis of the transferred lymph node flap. In 11 patients we transferred the inguinal lymph node flaps from the contralateral site, meanwhile in 13 patients supraclavicular lymph node flaps were used., Results: Maximum reduction of the lymphedema was achieved. No major complication was detected postoperatively. There were two patients with partial loss of the skin graft necessitated re-grafting. All the lymph node flaps survived well. The patients resumed normal daily activities within a period of 2 months. The mean follow-up was 14 months (3-26 months). During this period, no recurrence of the lymphedema was observed., Conclusion: The combination of the modified Charles procedure with vascularized transferring of lymph node flap is an effective method for treatment of advanced stage lymphedema., (© 2014 Wiley Periodicals, Inc.)

Introduction: Oxidative stress can impair fracture healing. To protect against oxidative damage, a system of detoxifying and antioxidative enzymes works to reduce the cellular stress. The transcription of these enzymes is regulated by antioxidant response element (ARE). The nuclear factor (erythroid-derived 2)-like2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes. Recently it has been shown that vascular endothelial growth factor (VEGF) prevents oxidative damage via activation of the Nrf2 pathway in vitro. Platelet-released growth factor (PRGF) is a mixture of autologous proteins and growth factors, prepared from a determined volume of platelet-rich plasma (PRP). It has already used to enhance fracture healing in vitro. The aim of the present study was to elucidate if platelets can lead to upregulation of VEGF and if platelets can regulate the activity of Nrf2-ARE system in primary human osteoblast (hOB) and in osteoblast-like cell line (SAOS-2)., Methods: Platelets and PRGF were obtained from healthy human donors. HOB and SAOS-2 osteosarcoma cell line were used. The ARE activity was analysed using a dual luciferase reporter assay system. We used Western blot to detect the nuclear accumulation of Nrf2 and the amount of cytosolic antioxidant Thioredoxin Reductase-1 (TXNRD-1), Heme Oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO1). Gene expression analysis was performed by real-time RT PCR. ELISA was used for the quantification of growth factors., Results: The activity of ARE was increased in the presence of PRGF up to 50%. Western blotting demonstrated enhanced nuclear accumulation of Nrf2. This was followed by an increase in the protein expression of the aforementioned downstream targets of Nrf2. Real-time RT PCR data showed an upregulation in the gene expression of the VEGF after PRGF treatment. This was confirmed by ELISA, where the treatment with PRGF induced the protein level of VEGF in both cells., Conclusions: These results provide a new insight into PRGF's mode of action in osteoblasts. PRGF not only leads to increase the endogenous VEGF, but also it may be involved in preventing oxidative damage through the Nrf2-ARE signalling. Nrf2 activation via PRGF may have great potential as an effective therapeutic drug target in fracture healing., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The scapula free flap is often the first choice for reconstruction of bony defects of the facial skeleton. However, the vascularised rib as part of a free rib osteomyocutaneous flap may be a suitable second choice. We have investigated the morphology and clinical dimensions of the 7th rib and the scapula, and the ability of the available bone to carry dental implants. The age and sex of the cadaver, and the donor side, were also recorded. The dimensions of the scapulas and 7th ribs (n=130 of each) from 65 cadavers were measured at 4 different points using osteometric methods. Examination showed that bone from the scapula and 7th rib were sufficient for placement of implants. The 7th rib gave reliable measurements for both height and width, and a consistent relation between compact and cancellous bone. Although the scapula provided adequate compact and cancellous bone, there were variations depending on the segment of bone chosen. Bones from male cadavers were more suitable for implantation. In both the scapula and the 7th rib ageing had a significant adverse effect in only one dimension. Most points of measurement have satisfactory bony dimensions for insertion of dental implants., (Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Functional nerve regeneration after reconstructive nerve surgery remains unsatisfying. In this study, vascular endothelial growth factor (VEGF) gene therapy combined with a hyaluronic acid (HA)-enriched microenvironment in nerve regeneration was investigated. Sciatic nerve was transected, and end-to-end neurorrhaphy was performed on 32 male Sprague-Dawley rats, which were randomly divided into four groups (n = 8 per group): nerve coaptation without treatment (group I); nerve coaptation covered with HA film sheath (group II); nerve coaptation with intramuscular VEGF gene in plasmid injection (group III); and nerve coaptation combined with HA film sheath and intramuscular VEGF gene in plasmid injection (group IV). Contralateral sciatic nerves were used as control. VEGF expression was verified from gluteal muscle biopsies surrounding the sciatic nerve by reverse transcriptase-PCR. Electrophysiological, histopathological, and electron microscopic evaluations were performed after 4 weeks. Mean peak amplitude of groups I-IV and nonoperated sciatic nerve were 4.5 ± 0.6 mV, 6.4 ± 0.4 mV, 6.7 ± 0.5 mV, 8.5 ± 0.4 mV, and 9.8 ± 0.5 mV, respectively. Mean myelinated axonal counts of groups I-IV and nonoperated sciatic nerve were 105 ± 24, 165 ± 19, 181 ± 22, 271 ± 23, and 344 ± 17, respectively. Treatment with HA film sheath coverage combined with intramuscular VEGF gene in plasmid injection yielded statistically significant higher peak amplitudes and myelinated axonal counts (P < 0.001). In addition, significantly less scar formation with HA administration (groups II and IV; P < 0.001) was found. Thus, it was found that VEGF might crucially regulate nerve regeneration processes and that HA can reduce the scar formation. This study showed that the combination of HA film sheath and VEGF gene may synergistically promote peripheral nerve regeneration., (Copyright © 2013 Wiley Periodicals, Inc.)

We investigated the effects of bisphosphonate (BP) on oxidative stress levels in blood of patients with cancer. In total, 19 patients with cancer and 21 healthy subjects were included in the study. BP was intravenously administrated to the participants for 6 weeks. The patients had higher lipid peroxidation (LP) levels in the plasma and erythrocyte samples but lower glutathione peroxidase (GSH-Px) and plasma vitamin E values. In patients treated with BP, calcium and LP levels decreased, but GSH-Px and vitamin E values improved. In conclusion, we observed that treatment with BP alleviated oxidative stress induced by cancer.

Cell transplantation therapy is considered a novel and promising strategy in regenerative medicine. Recent studies point out that paracrine effects and inflammation induced by transplanted cells are key factors for the improvement of myocardial function. The present study aims at differentiating paracrine effects from inflammatory reactions after cell transplantation. Therefore, in vitro induced apoptotic bodies were transplanted after myocardial infarction in a rat model. Eight weeks after transplantation, the functional results showed no improvement in left ventricular function. Histological analysis revealed no significant differences in the amount of infiltrated cells and collagen content did not differ among the four groups, which sustains the functional data. Surprisingly, angiogenesis increased in groups with apoptotic bodies derived from HUVEC and endothelial progenitor cells, but not from fibroblasts. A complex genetic analysis of apoptotic bodies indicated that miRNAs could be responsible for these changes. Our study demonstrates that inflammatory reaction is critical for scar remodelling and improvement of the heart function after late cell therapy, while neoangiogenesis alone is not sufficient to improve heart function., Competing Interests: Conflict of interests: No conflict of interest to declare., (Copyright © 2014, Applied Systems.)

Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration.

We assessed the morphological characteristics and dimensions of the ilium and fibula to evaluate the suitability of particular areas of bone for use as donor sites for dental reconstructions that carry implants. We measured the dimensions of 130 bilaterally harvested ilium and fibula bones from 65 adult cadavers using osteometric methods, and analysed the effects of age, sex, and side. Dimensions at measuring points, overall suitability for implantation, and relations among age, sex, and side, were evaluated statistically. We report observations of bone morphology involving cross-sections, and clinical relevance. Although the mean dimensions of the fibula and iliac crest were adequate, some segments would not support an implant 10 mm long and 3.5 mm wide. The overall suitability of parts of the iliac block fell to 30%. Fibular morphology is characterised by constant height and width, and relation of cortical and cancellous bone. Bony dimensions on the iliac fossa and fibula were significantly greater in men than in women. Age had a negative impact in one area of the iliac fossa, but nowhere on the iliac crest. Side was not significant. We found differences in dimensions and morphology between measuring points on the same bone. Precise knowledge about which areas of the donor sites can reliably provide sufficient bone to carry implants after reconstructions will allow greater flexibility and safety when reconstructions are designed., (Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Here, we aimed to clarify the role of CXC chemokine receptor (CXCR) 2 in macrophage migration-inhibitory factor (MIF)-mediated effects after myocardial ischemia and reperfusion. As a pleiotropic chemokine-like cytokine, MIF has been identified to activate multiple receptors, including CD74 and CXCR2. In models of myocardial infarction, MIF exerts both proinflammatory effects and protective effects in cardiomyocytes. Similarly, CXCR2 displays opposing effects in resident versus circulating cells., Approach and Results: Using bone marrow transplantation, we generated chimeric mice with Cxcr2(-/-) bone marrow-derived inflammatory cells and wild-type (wt) resident cells (wt/Cxcr2(-/-)), Cxcr2(-/-) cardiomyocytes and wt bone marrow-derived cells (Cxcr2(-/-)/wt), and wt controls reconstituted with wt bone marrow (wt/wt). All groups were treated with anti-MIF or isotype control antibody before they underwent myocardial ischemia and reperfusion. Blocking MIF increased infarction size and impaired cardiac function in wt/wt and wt/CXCR2(-/-) mice but ameliorated functional parameters in Cxcr2(-/-)/wt mice, as analyzed by echocardiography and Langendorff perfusion. Neutrophil infiltration and angiogenesis were unaltered by MIF blockade or Cxcr2 deficiency. Monocyte infiltration was blunted in wt/Cxcr2(-/-) mice and reduced by MIF blockade in wt/wt and Cxcr2(-/-)/wt mice. Furthermore, MIF blockade attenuated collagen content in all groups in a CXCR2-independent manner., Conclusions: The compartmentalized and opposing effects of MIF after myocardial ischemia and reperfusion are largely mediated by CXCR2. Although MIF confers protective effects by improving myocardial healing and function through CXCR2 in resident cells, thereby complementing paracrine effects through CD74/AMP-activated protein kinase, it exerts detrimental effects on CXCR2-bearing inflammatory cells by increasing monocyte infiltration and impairing heart function. These dichotomous findings should be considered when developing novel therapeutic strategies to treat myocardial infarction.

The vascularized iliac osteocutaneous flap has been used successfully for jaw reconstruction. To obtain a better contour of the reconstructed area in large upper and lower jaw resections, the transferred bone actually needs to be osteotomized. Single closing-wedge osteotomy of the iliac flap for mandibular reconstruction has been previously described. In this article, the modified multiple osteotomized perforator-based versatile free iliac osteocutaneous flap is described. Eleven cases were enrolled. Seven patients had wide anterior mandibular resections due to oral cavity and mandibular tumors; 3 patients had a defect due to explosive injury and 1 patient had complicated orbitomaxillary defect due to blast injury. Skin paddle was based on the perforators. In 8 patients, the bony segment was divided into 3 segments by 2 osteotomies, whereas in 2 patients the bony segment was divided into 4 segments by 3 osteotomies. In 10 cases, the flap was used for anterior mandibular defects, whereas in 1 case the flap was customized to fit an L-shaped defect at the naso-orbito-maxillary region. The overall flap success rate was 100%. No resorption or morbidity related to the osteotomy of the bony segments was observed. The size of perforator skin paddle was 6 to 8 × 15 to 18 cm. Physical and radiologic examinations showed proper bone healing without any additional complications. The modified multiple osteotomized free osteocutaneous iliac flap can provide a safe and versatile bony segment to be arranged and adapted to reconstruct complex mandibular and maxillofacial defects.

Background: Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI., Methods and Results: MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks). The efficiency of the anti-KC treatment was determined by the measurement of KC serum concentration and immunofluorescence staining, in each of the four groups. Surprisingly, we did not find any difference in neutrophil infiltration in the infarcted area between untreated and treated animals. Moreover, the heart function, infarct size, and neoangiogenesis were not different between the four groups. As expected, a comparable anti-CXCR2 treatment of mice before and after MI was able to significantly reduce neutrophil infiltration into the infarcted area and angiogenesis, but also to reduce the infarction size after long or "later" treatment., Conclusions: The major finding of our study is that KC, a potent neutrophil chemoattractant and an established angiogenic factor, failed to interfere in the post-infarction inflammatory response, in wound healing and scar formation after MI. Therefore, these aspects need to be carefully taken into account when devising therapeutic strategies for myocardial infarction and ischemic cardiomyopathy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Suitable and reproducible experimental models of translational research in reconstructive surgery that allow in-vivo investigation of diverse molecular and cellular mechanisms are still limited. To this end we created a novel murine model of acute hindlimb ischemia-reperfusion to mimic a microsurgical free flap procedure. Thirty-six C57BL6 mice (n = 6/group) were assigned to one control and five experimental groups (subject to 6, 12, 96, 120 hours and 14 days of reperfusion, respectively) following 4 hours of complete hindlimb ischemia. Ischemia and reperfusion were monitored using Laser-Doppler Flowmetry. Hindlimb tissue components (skin and muscle) were investigated using histopathology, quantitative immunohistochemistry and immunofluorescence. Despite massive initial tissue damage induced by ischemia-reperfusion injury, the structure of the skin component was restored after 96 hours. During the same time, muscle cells were replaced by young myotubes. In addition, initial neuromuscular dysfunction, edema and swelling resolved by day 4. After two weeks, no functional or neuromuscular deficits were detectable. Furthermore, upregulation of VEGF and tissue infiltration with CD34-positive stem cells led to new capillary formation, which peaked with significantly higher values after two weeks. These data indicate that our model is suitable to investigate cellular and molecular tissue alterations from ischemia-reperfusion such as occur during free flap procedures.

Recent studies have reported oxidative damage due to bisphosphonate (BP) in various cancer tissues and neurons, although basic fibroblast growth factor (bFGF) induced antioxidant effects in the cells. The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Twenty-eight rats were equally divided into four groups. The first group was used as control. The second, third and fourth groups intraperitoneally received BP (zoledronic acid), bFGF and BP + bFGF. At the end of 10 weeks, the rats were sacrificed, and oral epithelium samples were taken for analyses. In BP group, the lipid peroxidation levels were increased in the oral epithelium, while the activities of glutathione peroxidase (GSH-Px) and the concentrations of total antioxidant status (TAS) were decreased. In rats treated with bFGF, lipid peroxidation levels decreased, and the activities of GSH-Px and concentrations of TAS improved in the oral epithelium. However, zinc and copper levels were decreased in the oral epithelium by BP and bFGF treatments. Concentrations of vitamin E and reduced glutathione in the samples did not change in the groups. In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. However, zinc and copper levels were decreased by BP and bFGF treatments.

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

To improve skin flap healing, one promising strategy in reconstructive surgery might be to optimize platelet rich plasma (PRP) bioactivity and the ischemia-altered expression of genes. We studied both the effect of PRP on ischemic flaps, and whether in vivo bioluminescence imaging (BLI) is a suitable method for the longitudinal monitoring of angiogenesis in surgical wounds. Axial murine skin flaps were created in four experimental groups. In vivo measurements of VEGFR2 expression levels were made every other day until the 14th day. The local VEGF level and microvessel density were quantified on the 14th day via ELISA and immunohistochemistry, and flap survival rates were measured. We demonstrated that PRP and induced ischemia have a beneficial influence on angiogenesis and flap healing. Combining the two resulted in a significantly robust increase in angiogenesis and flap survival rate that was corroborated by bioluminescence imaging of VEGFR2 activity. This study shows that angiogenic effects of PRP may be potentialized by the stimulus of induced ischemia during free flap harvesting, and thus the two procedures appear to have a synergistic effect on flap healing. This study further demonstrates that BLI of modulated genes in reconstructive surgery is a valuable model for longitudinal in vivo evaluation of angiogenesis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1α (SDF-1α) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1α-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1α in infarcted myocardium. In addition, a significant increased density of CD31(+) vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation., (© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Background: The exponential growth of image-based diagnostic and minimally invasive interventions requires a detailed three-dimensional anatomical knowledge and increases the demand towards the undergraduate anatomical curriculum. This randomized controlled trial investigates whether musculoskeletal ultrasound (MSUS) or arthroscopic methods can increase the anatomical knowledge uptake., Methods: Second-year medical students were randomly allocated to three groups. In addition to the compulsory dissection course, the ultrasound group (MSUS) was taught by eight, didactically and professionally trained, experienced student-teachers and the arthroscopy group (ASK) was taught by eight experienced physicians. The control group (CON) acquired the anatomical knowledge only via the dissection course. Exposure (MSUS and ASK) took place in two separate lessons (75 minutes each, shoulder and knee joint) and introduced standard scan planes using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator combined with video tutorials. The theoretical anatomic learning outcomes were tested using a multiple-choice questionnaire (MCQ), and after cross-over an objective structured clinical examination (OSCE). Differences in student's perceptions were evaluated using Likert scale-based items., Results: The ASK-group (n = 70, age 23.4 (20-36) yrs.) performed moderately better in the anatomical MC exam in comparison to the MSUS-group (n = 84, age 24.2 (20-53) yrs.) and the CON-group (n = 88, 22.8 (20-33) yrs.; p = 0.019). After an additional arthroscopy teaching 1% of students failed the MC exam, in contrast to 10% in the MSUS- or CON-group, respectively. The benefit of the ASK module was limited to the shoulder area (p < 0.001). The final examination (OSCE) showed no significant differences between any of the groups with good overall performances. In the evaluation, the students certified the arthroscopic tutorial a greater advantage concerning anatomical skills with higher spatial imagination in comparison to the ultrasound tutorial (p = 0.002; p < 0.001)., Conclusions: The additional implementation of arthroscopy tutorials to the dissection course during the undergraduate anatomy training is profitable and attractive to students with respect to complex joint anatomy. Simultaneous teaching of basic-skills in musculoskeletal ultrasound should be performed by medical experts, but seems to be inferior to the arthroscopic 2D-3D-transformation, and is regarded by students as more difficult to learn. Although arthroscopy and ultrasound teaching do not have a major effect on learning joint anatomy, they have the potency to raise the interest in surgery.

Platelet-rich plasma (PRP) is a potent agent that improves soft tissue and bone healing. By the release of growth factors and cytokines, PRP is believed to locally boost physiologic healing processes. Recently, antimicrobial activity of PRP has been demonstrated against S. aureus strains. Major scientific effort is being put into the understanding and prevention of infections i.e. by delivery of antimicrobial substances. In previous studies we showed the ideal antibacterial activity-profile of the human beta-defensin 2 (hBD-2) for orthopaedic infections and therefore hypothesized that hBD-2 may be the effector of antimicrobial platelet action. Platelet concentrates were produced from human platelet phresis obtained from a hospital blood bank. They were screened by immunohistochemistry, Western Blot and ELISA for the human beta defensin-2. In vitro susceptibility to PRP was investigated by a standard disc diffusion test with or without pre-incubation of PRP with anti-hBD-2 antibody. SPSS statistical software was used for statistical analysis. PRP contains hBD-2 470 pg/10(9) platelets or 1786 pg/ml, respectively, (ELISA), which was confirmed by immunohistochemistry and Western Blot. In antimicrobial testing, PRP demonstrates effective inhibition of E. coli, B. megaterium, P. aeruginosa, E. faecalis and P. mirabilis. With this study we confirm the previously reported antimicrobial action of platelet concentrates i.e. PRP. In opposition to previously reported effects against gram positive bacteria our study focuses on gram negative and less common gram positive bacteria that do frequently cause clinical complications. We provide a possible molecular mechanism at least for E. coli and P. mirabilis for this effect by the detection of an antimicrobial peptide (hBD-2). This study may advocate the clinical use of PRP by highlighting a new aspect of platelet action.

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and β-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and β-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems., (Copyright © 2011 John Wiley & Sons, Ltd.)

Little is know about the pathophysiology of acute and degenerative tendon injuries. Although most lesions are uncomplicated, treatment is long and unsatisfactory in a considerable number of cases. Besides the common growth factors that were shown to be relevant for tendon integrity more recently protection against oxidative stress was shown to promote tendon healing. To improve tendon regeneration, many have advocated the use of platelet-rich plasma (PRP), a thrombocyte concentrate that can serve as an autologous source of growth factors. In this study, we investigated the effect of platelet-released growth factors (PRGF) on tenocytes. Tenocytes were isolated from the Achilles tendon of postnatal rats. Tenocyte cell cultures were stimulated with PRGF. We used a CyQuant assay and WST assay to analyse tendon cell growth and viability in different concentrations of PRGF. Migration and proliferation of cells grown in PRGF were assessed by a scratch test. A dual-luciferase assay was used to demonstrate the activation of the anti-oxidant response element (ARE) in tenocytes. A positive effect of PRGF could be shown on tendon cell growth and migratory capacity. PRGF activated the Nrf2-ARE pathway in a dose-dependent manner. Here, we provide evidence of a biological effect of PRGF on tenocytes by the promotion of tenocyte growth and activation of the Nrf2-ARE pathway. This is a novel aspect of the action of platelet concentrates on tendon growth.

Background: Fibroses of vessels and soft tissue are side effects of radiotherapy. The authors assumed that there was an immediate direct radiogenic damage of collagen of bone, periosteum and skin., Material and Methods: 15 porcine jaws samples (group 1) were exposed to a total dose of 60 Gy (cobalt-60, 2 Gy/day, five fractions/week). 15 jaws samples were stored accordingly (group 2, no irradiation, control). Collagen fragments of bone, periosteum and skin samples of groups 1 and 2 were isolated by ultrafiltration. Collagen types were characterized by SDS-PAGE measurement of the mature collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) by high-performance liquid chromatography (HPLC) and analysis of hydroxyproline (Hyp) was used to determine the ratio of the amount of collagen fragments from irradiated as opposed to nonirradiated samples., Results: The concentrations of HP, LP and Hyp in ultrafiltrates of probes of irradiated bone, periosteum and skin were markedly increased (average factors for bone: 3.69, 1.84, and 3.40, respectively; average factors for periosteum: 1.55, 1.41, and 1.77, respectively; average factors for skin: 1.55, 1.60, and 2.23, respectively) as compared to nonirradiated probes. SDS-PAGE did show collagen types I and V in nonirradiated bone, I and III in nonirradiated skin, and I in nonirradiated periosteum samples. In irradiated samples, smeared bands illustrated fragmentation of the collagen molecule., Conclusion: The increased concentrations of HP, LP and Hyp in ultrafiltrates indicated increased concentrations of split collagen. Direct and instant radiogenic damage of (extracellular matrix of) bone, periosteum and skin tissue collagen could be demonstrated.