Alkaline phosphatase dual-binding sites for collagen dictate cell migration and microvessel assembly in vitro.

Interactions between cell types, growth factors, and extracellular matrix components involved in angiogenesis are crucial for new vessel formation leading to tissue regeneration. This study investigated whether cocultures of fibroblasts and endothelial cells (ECs; from macro- or microvasculature) play a role in the formation of microvessel-like structures by ECs, as well as modulate fibroblast differentiation and growth factors production (vascular endothelial cell growth factor, basic fibroblast growth factor, active transforming growth factor-β1, and interleukin-8), which are important for vessel sprouting and maturation. Data obtained revealed that in vitro coculture systems of fibroblasts and human ECs stimulate collagen synthesis and growth factors production by fibroblasts that ultimately affect the formation and distribution of microvessel-like structures in cell cultures.

Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies.

RNA-binding proteins (RBPs) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the underlying disease mechanisms remain unclear. In an unbiased screen in Drosophila for RBPs that genetically interact with TDP-43, we found that downregulation of the mRNA export factor Ref1 (fly orthologue to human ALYREF) mitigated TDP-43 induced toxicity. Further, Ref1 depletion also reduced toxicity caused by expression of the C9orf72 GGGGCC repeat expansion.

Author Correction: Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity.

The original version of this Article contained an error in the author affiliations. The affiliation of Alice Chen-Plotkin with the Department of Neurology, Perelman School of Medicine, Philadelphia, PA, 19104 USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity.

TDP-43 is the major disease protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-TDP). Here we identify the transcriptional elongation factor Ell-a shared component of little elongation complex (LEC) and super elongation complex (SEC)-as a strong modifier of TDP-43-mediated neurodegeneration. Our data indicate select targets of LEC and SEC become upregulated in the fly ALS/FTLD-TDP model.

TDP-43 Promotes Neurodegeneration by Impairing Chromatin Remodeling.

Regulation of chromatin structure is critical for brain development and function. However, the involvement of chromatin dynamics in neurodegeneration is less well understood. Here we find, launching from Drosophila models of amyotrophic lateral sclerosis and frontotemporal dementia, that TDP-43 impairs the induction of multiple key stress genes required to protect from disease by reducing the recruitment of the chromatin remodeler Chd1 to chromatin.

Human endothelial cell-based assay for endotoxin as sensitive as the conventional Limulus Amebocyte Lysate assay.

Endotoxin, also known as lipopolysaccharide (LPS) produced by bacteria can be present in any liquid or on any biomaterial even if the material is sterile. Endotoxin in mammals can cause fever, inflammation, cell and tissue damage and irreversible septic shock and death. In the body, endothelial cells making up the blood vasculature and endothelial cells in vitro rapidly react to minute amounts of endotoxin resulting in a rapid induction of the cell adhesion molecule E-selectin.

In vitro evaluation of biomimetic chitosan-calcium phosphate scaffolds with potential application in bone tissue engineering.

This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan-calcium phosphate (Cs-CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone.

Photoactivatable caged cyclic RGD peptide for triggering integrin binding and cell adhesion to surfaces.

We report the synthesis and properties of a photoactivatable caged RGD peptide and its application for phototriggering integrin- and cell-binding to surfaces. We analysed in detail 1) the differences in the integrin-binding affinity of the caged and uncaged forms by quartz crystal microbalance (QCM) studies, 2) the efficiency and yield of the photolytic uncaging reaction, 3) the biocompatibility of the photolysis by-products and irradiation conditions, 4) the possibility of site, temporal and density control of integrin-binding and therefore human cell attachment, and 5) the possibility of in situ generation of cell patterns and cell gradients by controlling the UV exposure. These studies provide a clear picture of the potential and limitations of caged RGD for integrin-mediated cell adhesion and demonstrate the application of this approach to the control and study of cell interactions and responses.

Human endothelial and osteoblast co-cultures on 3D biomaterials.

Increasingly, in vitro experiments are being used to evaluate the cell compatibility of novel biomaterials. Single cell cultures have been used to determine how well cells attach, grow, and exhibit characteristic functions on these materials and the outcome of such tests is generally accepted as an indicator of biocompatibility. However, organs and tissues are not made up of one cell type and the interaction of cells is known to be an essential factor for physiological cell function.

The rapid anastomosis between prevascularized networks on silk fibroin scaffolds generated in vitro with cocultures of human microvascular endothelial and osteoblast cells and the host vasculature.

The survival and functioning of a bone biomaterial upon implantation requires a rapidly forming and stably functioning vascularization that connects the implant to the recipient. We have previously shown that human microcapillary endothelial cells (HDMEC) and primary human osteoblast cells (HOS) in coculture on various 3-D bone biomaterial scaffolds rapidly distribute and self-assemble into a morphological structure resembling bone tissue. Endothelial cells form microcapillary-like structures containing a lumen and these were intertwined between the osteoblast cells and the biomaterial.

[In vitro trials with single and co-cultures of osteoblasts and endothelial cells : evaluation of new biomaterials for bone reconstruction and regeneration].

Many different types of bone substitute biomaterials are being developed for different applications in the body. The current dogma is that if osteoblasts and endothelial cells grow and exhibit normal cell functions on these materials in vitro as single cultures or in co-cultures, then the biomaterials are suitable for implantation for bone reconstruction and regeneration. Generally, only in vivo animal studies will prove whether this is the case.

Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials.

The survival and functioning of a bone biomaterial requires a rapid and stable vascularization after implantation. However, the mechanisms involved in the context of the complex healing microenvironment are poorly understood. To evaluate the vascularization potential of bone biomaterials, angiogenic stimuli were added to human dermal microvascular endothelial cells (HDMEC) growing on three-dimensional (3-D) bone biomaterials consisting of porous hydroxyapatite, porous calcium phosphate, porous nickel-titanium, successfully being used in humans, and also silk fibroin nets.

Nasal cheek flap in ethmoidal and skull base tumour surgery: results and complications.

Surgery is the treatment of choice for the management of malignant nasal/ethmoidal tumours, followed, in most cases, by external radiotherapy. Two main procedures are adopted to resect these tumours depending upon stage and extension: ethmoidectomy and medial maxillectomy, via a transfacial approach, or craniofacial resection with a combined transcranial and transfacial approach. The nasal cheek flap technique allows complete nasal swing thus obtaining a wide access to both the nasal fossae and the ethmoidal labyrinth.

Oropharyngeal carcinoma during pregnancy: clinical and psycho-oncological aspects.

Cancer is uncommon in pregnancy, occurring in approximately one out of 1000 pregnancies, although it has been noted that one out of 118 women diagnosed with cancer is pregnant at the time of diagnosis. In the last 10 years, two oropharyngeal carcinomas, (1 squamous cell carcinoma and 1 adenoid cystic carcinoma) which developed during pregnancy, have been diagnosed and treated in our Department. No cases of oropharyngeal cancer, during pregnancy, have so far been reported in the literature with the exception of one case of oral cancer.

13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group.

Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours. 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC. Synergism between retinoids and interferon in tumoural cell lines have been demonstrated.

beta-carotene supplementation in patients radically treated for stage I-II head and neck cancer: results of a randomized trial.

This study was aimed at evaluating the efficacy of beta-carotene in improving survival (S) and in disease-free survival (DFS) and reducing the incidence of second primary tumors (SPT) in patients with a radically treated stage I-II squamous head and neck tumors. Eligible patients were randomly allocated to receive beta-carotene (n=104) or no treatment (n=110). beta-carotene was administered at the dose of 75 mg/day for 3-month cycles within one month intercycle intervals for a 3-year period.

[Endoscopic follow-up of translaryngeal Fantoni tracheostomy].

Dilatational tracheotomy techniques are widely used in the long-term management of the respiratory tract in patients in intensive care units (ICU). The translaryngeal tracheotomy technique (TLT) was first described by Fantoni in 1993 and rapidly asserted itself, especially in Europe. This technique basically differs from the other percutaneous techniques in that it involves a progressive, retrograde, dilatation of the trachea in a single session conducted from inside the trachea, working outward, simultaneously exerting a counter-pressure on the pre-tracheal soft tissues with the fingers.

[Complications of tracheostomy in critically ill patients: comparison of dilation and surgical techniques].

The tracheotomy, one of the oldest surgical procedures, has in recent years been the focus of particular attention given the undoubted, and not always justified, increase in indications, and by the introduction of dilatational tracheotomy techniques, particularly in critically patients. The present work compares the standard surgical tracheotomy with the more recent percutaneous techniques (Ciaglia dilatational tracheotomy and Fantoni translaryngeal tracheotomy). In particular, the relationship between the technique adopted, timing and complications were analyzed for 215 tracheotomies performed at different Intensive Care Units at our Hospital between 1993 and 1998 (106 performed using the standard surgical technique, 51 with the Ciaglia technique and 58 with the Fantoni technique).

[Hyperbaric oxygen therapy application in otorhinolaryngology and head and neck surgery: state of the art and review of literature].

Hyperbaric Oxygen Therapy (HOT) encompasses an extensive research area in which new indications, some of which are now well-codified, have emerged both in the fields of medical and surgical pathology. Its utilization in carefully targeted clinical situations, in which its true efficacy can be demonstrated, is first of all connected with medicolegal responsibility, in suspected iatrogenic accidents; its application must furthermore be subordinated to a favourable cost/benefit ratio for the health service employing it. In otorhinolaryngology and head and neck surgery, HOT is a strategic therapeutic weapon in several applications.

Pectoralis major myocutaneous flap: analysis of complications in difficult patients.

The purpose of this study was to assess and discuss the effects of old age and systemic diseases on complications related to the use of a pectoralis major myocutaneous flap (PMMF) for reconstruction in head and neck surgery. Eighty-four consecutive patients, operated on between January 1992 and December 1998, were included in the study. Of these patients, 47 were in relatively good condition, while 37were old and frail or affected by systemic diseases.

Enlarged approach to the anterior cervical spine.

In this report a new enlarged approach to the anterior cervical spine is presented. A 66-year-old female, having a large C3-C4-C5 chordoma, recurrent after surgery and following radiotherapy, underwent a surgical resection. The approach allows a wide retraction of the nasopharynx, oropharynx and larynx from the midline, only sacrificing the superior laryngeal nerve on one side.

Is pressure dressing necessary after ear surgery?

Compressive bandages carry intrinsic risks and complications. The purpose of this study was to assess whether compressive head bandages are necessary after ear surgery to prevent complications such as hematoma or wound infection. A prospective, randomized, controlled study was conducted from August 1, 1993, to June 1, 1999.

[Equilibrium and orthognathodontic surgery: correlations in a group of patients undergoing treatment].

Background: The aim of this study was to evaluate the main parameters provided by the static stabilometric test (mean X, mean Y, mean velocity, length of tracing, standard deviation of velocity, ellipse area) in the follow-up of patients suffering from skeletal occlusive pathology undergoing orthognathodontic surgery to confirm the re-establishment of postural equilibrium.

Methods: Fifteen patients with skeletal dysgnathia were correlated with a group of 10 healthy subjects. The same parameters were analysed in the dysgnathic subjects at 6 and 12 months after surgical correction.

New options for aerodigestive tract replacement after extended pharyngolaryngectomy.

Objectives: Assess the results of a new type of reconstruction of the aerodigestive tract after extended pharyngolaryngectomy.

Study Design: Follow-up of a total of eight patients who had surgery using ileocolic free graft.

Methods: The surgical technique is described.

A multicenter trial of specific local nasal immunotherapy.

Objective: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters.

Study Design: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months.

Methods: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen.