The osteogenic differentiation improvement of human mesenchymal stem cells on titanium grafted with polyNaSS bioactive polymer.

Osseointegration of metallic implants used in orthopedic surgery requires that osteoprogenitor cells attach and adhere to the surface, then proliferate, differentiate into osteoblasts, and finally produce mineralized matrix. Because the ability of progenitor cells to attach to a scaffold surface during early stages is important in the development of new tissue structures, we developed in our laboratory, a strategy involving grafting of implants with a polymer of sodium styrene sulfonate (polyNaSS) used as a scaffold which enables human mesenchymal stem cells (hMSCs) interactions. In the present study, we investigated the cellular response of hMSCs to polyNaSS surfaces of titanium (Ti). In particular, cell proliferation, cell viability, cell differentiation, and cell spreading were evaluated. Results showed that cell proliferation and cell viability did not differ with any statistical significance between modified and unmodified Ti surfaces. Interestingly, culture of MSCs on polyNaSS surfaces resulted in a significant increase of cell spreading and cell differentiation compared with the other tested surfaces. These results suggest that titanium surface grafted with polyNaSS is a suitable scaffold for bone tissue engineering.

Spiral plasmonic nanoantennas as circular polarization transmission filters.

We present simulation and experimental results for easily fabricated spiral plasmonic antenna analogues providing circular polarization selectivity. One circular polarization state is concentrated and transmitted through a subwavelength aperture, while the opposite circular state is blocked. The spectral bandwidth, efficiency, and extinction ratios are tunable through geometric parameters. Integration of such structures onto a focal plane array in conjunction with linear micropolarizers enables complete Stokes vector imaging, that, until now, has been difficult to achieve. An array of these structures forms a plasmonic metamaterial that exhibits high circular dichroism.

Ultra-high extinction ratio micropolarizers using plasmonic lenses.

The design of a new type of plasmonic ultra-high extinction ratio micropolarizing transmission filter is presented along with an experimental demonstration. A pair of dielectric coated metal gratings couple incident TM polarized light into surface plasmons, which are fed into a central metal-insulator-metal (MIM) waveguide, followed by transmission through a sub-wavelength aperture. Extinction ratios exceeding 10¹¹ are predicted by finite element simulation. Good absolute agreement for both the spectral and polarization response is obtained between measurement and simulations using measured geometric parameters. The filters can be easily fabricated and sized to match the pixel pitch of current focal plane arrays.

Cell therapy of burns.

Severe burns remain a life-threatening local and general inflammatory condition often with serious sequelae, despite remarkable progress in their treatment over the past three decades. Cultured epidermal autografts, the first and still most up-to-date cell therapy for burns, plays a key role in that progress, but drawbacks to this need to be reduced by using cultured dermal-epidermal substitutes. This review focuses on what could be, in our view, the next major breakthrough in cell therapy of burns - use of mesenchymal stromal cells (MSCs). After summarizing current knowledge, including our own clinical experience with MSCs in the pioneering field of cell therapy of radiation-induced burns, we discuss the strong rationale supporting potential interest in MSCs in treatment of thermal burns, including limited but promising pre-clinical and clinical data in wound healing and acute inflammatory conditions other than burns. Practical options for future therapeutic applications of MSCs for burns treatment, are finally considered.

Transitions towards either slow-oxidative or fast-glycolytic phenotype can be induced in the murine WTt myogenic cell line.

Contraction and energy metabolism are functions of skeletal muscles co-regulated by still largely unknown signals. To help elucidating these interconnecting pathways, we are developing new cellular models that will allow to control the switch from a neonatal to an adult slow-oxidative or fast-glycolytic phenotype of myofibers, during in vitro differentiation. Thus, our purpose was to direct the differentiation of the newly characterized WTt clone, from a mixed towards either fast or slow phenotype, by modifying amounts of two transcription factors respectively involved in control of glycolytic and oxidative energy metabolism, namely HIF-1alpha and PPARdelta. Our data support the idea that HIF-1alpha protein stabilization would favor expression of fast phenotypic markers, accompanied or not by a decreased expression of slow markers, depending on treatment conditions. Conversely, PPARdelta over-expression appears to enhance the slow-oxidative phenotype of WTt myotubes. Furthermore, we have observed that expression of PGC-1alpha, a coregulator of PPAR, is also modified in this cell line upon conditions that stabilize HIF-1alpha protein. This observation points to the existence of a regulatory link between pathways controlled by the two transcription factors HIF-1alpha and PPARdelta. Therefore, these cells should be useful to analyze the balance between oxidative and glycolytic energy production as a function of phenotypic transitions occurring during myogenic maturation. The newly characterized murine WTt clone will be a good tool to investigate molecular mechanisms implicating HIF-1alpha and PPARdelta in the coordinated metabolic and contractile regulations involved in myogenesis.

Principles of operative treatment of malleolar fractures today.

Ankle fractures continue to be a common injury. They involve various mechanisms of injury and produce, when treated correctly, fairly good results. Although non-displaced stable malleolar fractures are treated safely by conservative means, displaced unstable fractures are still the domain of open reduction and internal fixation (ORIF), as recommended by the AO Group. The principles of the operative treatment of these fractures are discussed in this paper, illuminating the surgical technique and biomechanics of lateral, medial and posterior malleolar fractures. Even though there have been no fundamental changes in the treatment of these fractures in the last several years, new implants such as angular-stable plates and new surgical techniques such as the minimally invasive plate osteosynthesis (MIPO) technique help to treat these fractures more individually, depending on the type of fracture, quality of bone and soft tissue conditions.

[Genital elephantiasis: reconstructive treatment of penoscrotal lymphoedema with a myocutaneous M. gracilis flap. Experiences from a District Hospital in Ethiopia]. / Genitale Elephantiasis: Rekonstruktive Behandlung des penoskrotalen Lymphödems durch myokutane M. gracilis-Lappenplastik. Erfahrungen aus einem District Hospital in Athiopien.

BACKGROUND: Genital elephantiasis is an illness leading to serious functional and aesthetic as well as psychosocial impairment. Since the 19th century there have been articles describing methods for surgical ablative treatment of penoscrotal lymphoedema. However, most of these methods ignore the creation a new drainage for the lymph. We now describe a new technique using a myocutaneous M. gracilis muscle flap for the reconstruction of the soft tissue damage resulting from radical excision, thus ensuring drainage of the lymph into the deep muscle compartment of the thigh. PATIENTS AND METHOD: In the District Hospital "Mettu-Karl Hospital" in the Ethiopian rain forest region of Illubabor, during a period of 6 months the described surgical procedure was applied to 9 patients suffering from severe forms of this grotesquely disfiguring disease. Two patients presented with combined penoscrotal oedema, while the other 7 patients were suffering from isolated scrotal lymphoedema alone. All patients benefited from reconstruction with a myocutaneous M. gracilis muscle flap after radical excision of the affected tissue. All patients were evaluated after 3 and 12 months postoperatively in the presence of a translator. RESULTS: All nine patients showed a functionally and aesthetically satisfying result after 3 months without postoperative occurrence of infection. The evaluation 12 months postoperatively showed no recurrence of genitoscrotal lymphoedema. All patients reported on having regained normal ability for sexual intercourse and no occurrence of urinary tract infections since the operation. Concerning fertility, no statements could be made. A significant improvement in the quality of life was observed by the regained ability to walk and work and consequently the reintegration of the patients into their socio-economic environment. CONCLUSION: Radical excision of the affected tissue followed by transferring a functioning lymphatic drainage into the deep muscle compartment of the ipsilateral thigh using a proximally based myocutaneous gracilis muscle flap treats genital lymphoedema without recurrence. Satisfying aesthetic and functional results are achieved. The described surgical technique is still successfully being performed by two Ethiopian surgeons trained in this procedure.

Novel murine clonal cell lines either express slow or mixed (fast and slow) muscle markers following differentiation in vitro.

We have investigated whether the phenotype of myogenic clones derived from satellite cells of different muscles from the transgenic immortomouse depended on muscle type origin. Clones derived from neonatal, or 6- to 12-week-old fast and slow muscles, were analyzed for myosin and enolase isoforms as phenotypic markers. All clones derived from slow-oxidative muscles differentiated into myotubes with a preferentially slow contractile phenotype, whereas some clones derived from rapid-glycolytic or neonatal muscles expressed both fast and slow myosin isoforms. Thus, muscle origin appears to bias myosin isoform expression in myotubes. The neonatal clone (WTt) was cultivated in various medium and substrate conditions, allowing us to determine optimized conditions for their differentiation. Matrigel allowed expressions of adult myosin isoforms, and an isozymic switch from embryonic alpha- toward muscle-specific beta-enolase, never previously observed in vitro. These cells will be a useful model for in vitro studies of muscle fiber maturation and plasticity.

Interactions of enolase isoforms with tubulin and microtubules during myogenesis.

Enolase is a glycolytic enzyme, expressed as cell-type specific isoforms in higher vertebrates. Herein we demonstrated for the first time that enolase isoforms interact with microtubules during muscle satellite cell differentiation. While in undifferentiated myoblasts the ubiquitous alphaalpha enolase isoform, expressed at high level, exhibited extensive co-localization with microtubules, the muscle-specific betabeta isoform, expressed at low level, did not. During differentiation, the level of beta subunit increased significantly; the alpha and beta enolase immunoreactivities were detected both in cytosol and along the microtubules. We identified tubulin from muscle extract as an interacting protein for immobilized betabeta enolase. ELISA and surface plasmon resonance measurements demonstrated the direct binding of enolase isoforms to tubulin with an apparent KD below the micromolar range, and indicated that the presence of 0.8 mM 2-phosphoglycerate abolished the interaction. Our data showed that, at various stages of myogenic differentiation, microtubules were decorated by different enolase isoforms, which was controlled by the abundance of both partners. We suggest that the binding of enolase to microtubules could contribute to the regulation of the dynamism of the cytoskeletal filaments known to occur during the transition from myoblast to myotubes.

Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine.

PURPOSE: To compare the frequency of seizures and status epilepticus and their response to first-line drugs in patients with idiopathic generalized epilepsies receiving carbamazepine or phenytoin to those receiving other drugs or no treatment. METHODS: We performed a retrospective chart review of all cases of idiopathic generalized epilepsies treated by the authors between 1985 and 1994. We compared seizure frequency and mean intravenous benzodiazepine dose required to control absence status epilepticus, intraindividually in subjects on carbamazepine or phenytoin before and after discontinuation of these compounds, and interindividually to subjects without treatment or receiving other drugs. RESULTS: Bouts of absence or tonic-clonic status epilepticus and seizures in subjects treated with phenytoin or carbamazepine at therapeutic concentrations were considerably more frequent and proved intractable to treatment with valproic acid or benzodiazepines, compared with a cohort of subjects also with idiopathic generalized epilepsies, but naive to, or receiving subtherapeutic or therapeutic doses of other agents. CONCLUSIONS: Our observations strongly suggest that therapeutic concentrations of phenytoin and carbamazepine exacerbate idiopathic generalized epilepsies. Subjects in whom absence is one of the seizure types seem at a particularly high risk for responding paradoxically. These findings underscore the value of accurate classification of seizures and particularly the syndromic approach to diagnosis and point to the potential for iatrogenic complications with indiscriminate use of antiseizure drugs.