Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.     

Mammakarzinom zwischen Krankheits- und Managementaspekten

Ohne Zusammenfassung     

Bildgebung der Nasennebenhöhlen (NNH) in der heutigen Zeit

CT is accepted as the gold standard for pathological-anatomical evaluation of paranasal sinus disease, CT is especially considered an obligatory part of planning surgical procedures. Indications for paranasal sinus CT include trauma, malignant disease, and chronic sinusitis, which accounts for the major part of examinations. Due to the benign character of the disease and the relatively moderate age of the patients involved, the radiation dose of paranasal sinus CT plays an important role. The use of a low-dose spiral CT technique and the reformation of coronal images out of the axial CT data instead of an additional direct coronal scan allow the effective dose of paranasal sinus CT to be reduced to the order of a chest radiogram. MRI is the preferred imaging modality in malignant disease or complications of inflammatory sinus disease that extend beyond the limits of the paranasal sinuses. The clinical value of other imaging modalities, including plain film radiography, ultrasound, or scintigraphy, is limited to special indications.     

Endokrine Therapie des metastasierten Mammakarzinoms

One of the characteristics of breast cancer is its hormone dependency, which provides a number of effective approaches for treatment. Endocrine therapies usually have a good tolerability and oral application is convenient. Third generation aromatase inhibitors are well established in the treatment of metastatic breast cancer, having overtaken Tamoxifen. In the adjuvant setting, the ATAC trial is beginning to demonstrate the superiority of anastrozol compared to Tamoxifen. A new set of trials, coordinated by the International Breast Intervention Study Group, will compare the anti-hormones in healthy postmenopausal women with a moderate risk of developing breast cancer and in women after surgery for ductal carcinoma in situ. This article will discuss the various options for endocrine therapy in metastatic breast disease. The indications for endocrine manipulation as well as the various drugs will be discussed.     

Innovationen in der gynäkologischen Endoskopie

After the triumph of endoscopy in gynaecology, new developments can be seen more with the invention and optimisation of instruments than with the introduction of new surgical techniques. The endoscopic surgeon is very much dependent on sophisticated and precise instruments to perform high quality operations in an acceptable time. In hysteroscopy, optical systems have more and more been miniaturised with concomitant enhanced quality. A new and safe technique for hysteroscopic sterilisation has been developed and bipolar resectoscope systems have been created. In laparoscopy, optical systems, bipolar instruments, morcellators and a monopolar loop electrode have also been markedly improved. New modes of energy application such as the BiClamp technique and reusable ultrasound dissectors are helpful in improving the quality of coagulation and reduce operative time.     

Winkelstabile Plattenfixation

There are fundamental biomechanical differences between fixed-angle plate systems, also referred to as internal fixators, and conventional plate-screw fixation systems. Fixed-angle systems have rapidly gained widespread acceptance in recent years for almost all indications and anatomical sites. This contribution presents tips and tricks on their implantation and on the management of complications. Much of the information has already been presented elsewhere, in print or orally. Some of it is based on the authors’ own experience in their hospitals. The tips and tricks presented here are intended to help surgeons find pragmatic solutions to intraoperative problems.