Adsorption/release behaviour of oligonucleotides on polymeric core-shell microspheres.
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Biomedical subjects
Publications and source records attributed to M Laus.
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We report the first study by inelastic (INS) and quasielastic neutron scattering of photoinduced changes in the reorientational and vibrational dynamics of a liquid crystalline side chain polymer. We use the cis-trans photoisomerization transition to take the system out of equilibrium and determine the quasielastic (QE) and inelastic scattering laws on two distinct time windows, corresponding to the time-of-flight (IN6) and backscattering (IN16) spectrometers at Institut Laue Langevin (ILL) (Grenoble). Our investigation was focused on the dynamics of the coupling between the mesogenic side chains and the polymeric main chain, which is connected to the extensive optical writing and memory effects that have been demonstrated in this complex material. We report data on the QE broadening and Debye-Waller factors, as a function of temperature across the glass transition (T(g)=293 K). We also studied the dynamical coupling of side and main chains. We report photoinduced changes on the static structure factor, on the purely elastic scattering fraction, on the low frequency vibrational dynamics (around the boson peak region). In particular, we find that on the space-time scales accessible to the INS techniques there is a time structure in the coupling, and that over longer times and distances the two dynamics are decoupled.
Cationic block copolymers, consisting of a poly(ethylene glycol) block and a block deriving from the poly(dimethylamino)ethyl methacrylate were prepared via a two-step procedure, based on the use of macroinitiators. By appropriately changing the experimental conditions and reacting the poly(dimethylamino)ethyl methacrylate block with iodo- or bromo-alkyl derivatives, a variety of ionic block copolymers with tuned physicochemical properties were prepared. These block copolymers are able to spontaneously self-assemble with plasmid DNA to produce oriented and shielded vectors, with physicochemical properties appropriate for in vivo applications. In addition, the formation of a complex between the cationic block copolymer and the plasmid DNA results in a nuclease resistance increase due to the stable nature of the complex.
The adsorption/release behaviour of oligodeoxynucleotides (ODNs) on double functional core-shell polymethylmethacrylate nanospheres, with a narrow size distribution, is described. The outer shell consists of alkyl or glycolic chains containing permanently-charged quaternary ammonium groups. Ion pair formation between negatively-charged ODN phosphate groups and positively-charged groups, present on the nanosphere surface, is the main mechanism of interaction. The amount of adsorbed ODN depends on both the ODN concentration and the nanosphere surface charge density. An adsorption-induced swelling mechanism is proposed in which a modification of the charged diffuse layer around the nanospheres increases the ODN binding site accessibility with increasing ODN concentration. Adsorption on the nanosphere surface prevents serum degradation of the ODNs. ODN release is negligible in the presence of culture medium but occurs gradually in the presence of serum. No significant cytotoxicity of the free nanoparticles was found in PBMC and CEM cells after 24 h at ODN concentrations required for antisense activity.
Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as drug delivery systems. Poly(vinyl alcohol)-based hydrogels containing different amounts of dextran or chitosan were prepared using the freezing-thawing method. Repeated freezing-thawing cycles of a poly(vinyl alcohol) (PVA) aqueous solution lead to the formation of crystallites which act as cross-linking sites, and a hydrogel with a high capacity to swell is obtained. The effects of the two different polysaccharides on the properties of the obtained materials were investigated by differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy. In addition the release with time of poly(vinyl alcohol) in aqueous medium, was monitored and evaluated. On the basis of the obtained results it seems that the presence of dextran favors the crystallization process of PVA, allowing the formation of a more ordered and homogeneous structure. Instead, chitosan seems to perturb the formation of PVA crystallites leading to a material with a less regular structure.
Nutritional support in the form of total parenteral nutrition (TPN) or enteral nutrition (EN) is successfully used in patients with pancreatitis, in whom the goal is to provide optimal nutrition while minimizing pancreatic exocrine activity. Controversy continues as to whether TPN or EN is more appropriate. Although TPN is traditionally preferred in acute pancreatitis, EN offers some advantages, being more physiologic, safer, and more cost-effective. A review of available animal and human studies suggests that elemental diets may be effective in patients with mild acute pancreatitis. In patients who have no clinical indication for restricting the gastrointestinal tract, EN may be preferred.
c-myb antisense oligonucleotides (AS ODNs) were reversibly immobilized to a novel polymeric core shell nanosphere and their cellular uptake and inhibitory effect on HL60 leukemia cell proliferation studied. The nanosphere surface was so designed as to directly bind ODNs via ionic interactions and reversibly release them inside the cells. Compared with the cellular uptake of free oligonucleotide, the use of AS ODN (immobilized to the nanospheres) produced a 50-fold increase in the intracellular concentration. Specifically, a single dose of 320 nM of AS ODN immobilized to the nanospheres was capable of inhibiting HL60 cell proliferation with the same degree of efficiency obtained using a 50-fold higher dose of free AS ODN. Flow cytometric experiments with fluoresceinated ODNs showed a temperature-dependent uptake, which was detectable as early as 2 h after the beginning of treatment. The inhibitory effect on cell proliferation was maintained for up to 8 days of culture. Moreover, the level of c-Myb protein decreased by 24% after 2 days and by 60% after 4 days of treatment, thus indicating a continuous and sustained release of non-degraded AS ODN from the nanospheres inside the cells.
STUDY DESIGN: A series of 10 patients surgically treated with prevascular or retrovascular extraoral retropharyngeal approach to the upper cervical spine is examined. OBJECTIVES: In orthopedic surgery, retropharyngeal approach may replace the transoral surgery, obviating the risks of infection and the uncomfortable postoperative course of cases in which median labiomandibular glossotomy was used to accomplish complex bone reconstruction. SUMMARY OF THE BACKGROUND DATA: The transoral approach is reported in literature as the classical anterior access to the upper cervical spine that provides direct exposure for anterior decompression of the spinal cord. The risks, the surgical limits, and the postoperative difficulties of transmucosal access suggest the use of an anterior extraoral retropharyngeal approach in orthopedic surgery. METHODS: The series includes four neoplastic lesions (osteoma, aneurismal bone cyst, giant cell tumor, solitary metastasis), three retropharyngeal ossifications resulting from diffuse idiopathic skeletal hyperostosis, and a single case of os odontoideum, craniocervical malformation, and postlaminectomy kyphosis. RESULTS: At follow-up evaluation, all patients achieved a satisfactory outcome, with good clinical and radiographic results; nasotracheal intubation obviated the need for tracheostomy. The wide surgical exposure allowed reconstruction with iliac strut bone grafts and internal fixation in six patients, avoiding the need of a halo device. The only complications were four instances of transient palsies of the marginal mandibular branch of the facial nerve. CONCLUSIONS: In the anterior surgery of the upper cervical spine, the prevascular approach allows a wide surgical exposure, with visualization similar to that obtained with median labiomandibular glossotomy. The retrovascular approach is indicated in selected cases, such as tumor adjacent to the vertebral artery and C1-C2 arthrodesis with bilateral transarticular screws according to Barbour.
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Twenty-five patients (16 with malignant soft-tissue tumors and 9 with suspected recurrence), previously studied with conventional radiography and Computed Tomography (CT), were examined with Magnetic Resonance (MR) imaging. MR findings were surgically and anatomo-histopathologically confirmed. Six more patients with benign lesions were examined for differential diagnosis. MR capabilities are here evaluated to detect and eventually characterize the lesion, and to assess its exact location. No false positives were found, and there was only one false negative, in a case of recurrent Malignant Fibrous Histiocytoma (MFH). In another case of MFH the infiltration of the adjacent vessels and nerves was not imaged. After a careful review of all the examinations, MR imaging appears to be able to provide much information for surgical planning about tumor extent and margins, thanks to its contrast resolution between tumor and surrounding anatomical structures. Therefore, MR imaging can be reasonably employed as the examination of choice when a soft-tissue tumor is clinically suspected, because of the multi-planar images it provides with and of its differential imaging parameters.
Osteosynthesis of the cervical spine with an anterior plate is indicated for reconstruction by a bone graft after somatectomy and in anterior fusion for unstable lesions such as fracture dislocations and fractures with severe deformity. In these situations traditional surgery with intersomatic wedged bone grafts may be insufficient and posterior surgery inadequate or risky. The authors report 11 cases of anterior osteosynthesis with a Louis plate, all of which were sufficiently stable to allow early mobilisation and minimal external orthosis. Fusion of the grafts occurred in all cases at long-term follow-up. The method involves a potential risk to the esophagus, which is in close contact with the plate. It must therefore be limited to cases in which the advantages outweigh the risks. The indications, technique, complications and results are discussed.
Correct orthopedic therapy for traumas of the cervical rachis requires perfect knowledge of the spatial balance of the fracture focus. The authors believe Computed Tomography (CT) to be the most suitable, and often indispensable, method for this purpose. Twenty-four patients were examined for traumatic pathology of the cervical rachis. In 7 cases with clinically minor traumas, the negative outcome of the traditional exam was considered reliable and sufficient for therapeutic purposes. The extant 17 patients were examined also by means of CT, either to better determine the characteristics of skeletal lesions already ascertained with traditional techniques or to assess the presence of clinically-suspected osteo-articular lesions, even with negative conventional X-rays. For 9 of these patients orthopedic treatment was considered sufficient, whereas 8 patients underwent surgery and were subsequently examined with CT, which allowed correct evaluation of postoperative pictures even in the presence of metal prostheses. In 10 cases CT demonstrated the presence of lesions which had not been diagnosed with traditional X-ray techniques.
Isolated traumatic cervical radicular lesions are rare. They constitute only 3% of the neurological lesions due to spinal trauma. A monolateral radicular lesion (Type A) is occasionally associated with medullary damage (Type B), resulting in a more complex neurological syndrome. Type A lesions are caused by flexion/rotation with fracture of the upper part of an articular facet and rotatory dislocation of the vertebra above, or by a pure monolateral dislocation. Reduction by halo traction followed by halo plaster gives good results even when the anatomical result is imperfect. Operative treatment of these lesions is required only in cases which cannot be reduced nonsurgically. Type B myelo-radicular lesions are caused by hyperextension-rotation injuries with displaced fractures of the facets and secondary subluxation. The treatment is surgical; reduction by a posterior approach with fixation by Roy-Camille plates, but must include radicular release by removal of the fractured joint mass.
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Solubility values of a selected group of nonsteroidal anti-inflammatory drugs have been determined in water and 1-octanol as a function of temperature. Thermodynamic functions of dissolution and partition have been calculated and discussed with respect to various physical parameters of each solute and the two solvents. The calculated solubility values show good agreement with the experimental values. The analysis of the experimental solubility values of these compounds in terms of solid-state contribution and solute-solvent interaction suggests the different importance of these parameters in promoting solubility of solid nonelectrolytes.
A study is presented of 25 cases of stenosis of the lumbar vertebral canal treated surgically by bilateral laminectomy at each affected level. The clinical and radiographic features are described, also the operative technique. Good results were obtained in 84% of the cases followed up for an average period of 3 years.
This is a study of 15 patients who have been operated on three or four times after an initial diagnosis of prolapsed lumbar disc. Four main causes have been distinguished; recurrent prolapse, spinal stenosis, arachnoiditis and vertebral instability. The final results of these multiple operations have been assessed as worthwhile in 73% of cases. Several factors in this case material have been identified as important in determining the satisfactory end results.