Cervical disc arthroplasty with the Baguera C prosthesis: clinical and radiological results of a 10-year follow-up study.

PURPOSE: We evaluated the long-term safety, mobility and complications of cervical total disc arthroplasty with the Baguera®C prosthesis over 10 years. METHODS: We included 91 patients treated by arthroplasty for cervical degenerative disc disease. A total of 113 prostheses were implanted (50 one-level, 44 two-level and 19 hybrid constructs). They were assessed for complications, clinically, with NDI and SF-12 questionnaires and by independent radiologists for ROM, HO, disc height and adjacent level degeneration. RESULTS: No spontaneous migration, loss of fixation, subsidence, vascular complication or dislocation were observed. The reoperation rate was 1%. About 82.7% of the patients were pain free. About 9.9% were taking occasional grade I painkillers. Motricity and sensitivity were preserved in 98.8% and 96.3%. The NDI showed an average functional disability of 17.58%, 26% lower than preoperatively. The SF-12 scores were close to normal health. The average ROM at the treated level was 7.4°. Motion was preserved in 86.6%. Lack of motion was observed in 13.4%. Grades II and III H0 were present in 53.7% and 31.7%, respectively, Grade IV was present in 13.4%. Motion was preserved in 100% of the grades 0-III. The preoperative adjacent level disc height of 4.3 mm remained stable during all the follow-ups at 4.4 mm and 4.2 mm, respectively, at 5 and 10 years. CONCLUSIONS: After 10 years, cervical arthroplasty with the Baguera®C prosthesis presents excellent safety and functional results and low complications. Motion was preserved in 86.6%, with a 7.4° ROM. Although common, HO did not hinder motion. Adjacent disc height preservation confirms some adjacent level degeneration protection.

Co-assembly of precision polyurethane ionomers reveals role of and interplay between individual components.

Industrial and household products, such as paints, inks and cosmetics usually consist of mixtures of macromolecules that are disperse in composition, in size and in monomer sequence. Identifying structure-function relationships for these systems is complicated, as particular macromolecular components cannot be investigated individually. For this study, we have addressed this issue, and have synthesized a series of five sequence-defined polyurethanes (PUs): one neutral-hydrophobic, one single-charged hydrophilic, one single-charged hydrophobic and two double-charged amphiphilic PUs (one symmetric and one asymmetric). These novel precision PUs - that were prepared by using stepwise coupling-deprotection synthetic protocols - have a defined composition, size and monomer sequence, where the chosen sequences were inspired by those that are abundantly formed in the production of industrial waterborne PU dispersions. By performing dynamic light scattering experiments (DLS), self-consistent field (SCF) computations and cryogenic transmission electron microscopy (cryo-TEM), we have elucidated the behavior in aqueous solution of the individual precision PUs, as well as of binary and ternary mixtures of the PU sequences. The double-charged PU sequences ('hosts') were sufficiently amphiphilic to yield single-component micellar solutions, whereas the two more hydrophobic sequences did not micellize on their own, and gave precipitates or ill-defined larger aggregates. Both the neutral-hydrophobic PU and the hydrophilic single-charged PU were successfully incorporated in the host micelles as guests, respectively increasing and reducing the micelle radius upon incorporation. SCF computations indicated that double-charged symmetric PUs stretch whilst double-charged asymmetric PUs are expelled from the core to accommodate hydrophobic PU guests within the micelles. For the ternary mixture of the double-charged symmetric and asymmetric hosts and the neutral-hydrophobic guest we have found an improved colloidal stability, as compared to those for binary mixtures of either host and hydrophobic guest. In another ternary mixture of precision PUs, with all three components not capable of forming micelles on their own, we see that the ensemble of molecules produces stable micellar solutions. Taken together, we find that the interplay between PU-molecules in aqueous dispersions promotes the formation of stable micellar hydrocolloids.

Micellization of Sequence-Controlled Polyurethane Ionomers in Mixed Aqueous Solvents.

While the impact of compositional parameters such as block length and ionic content on the micellization of (polymeric) amphiphiles is widely investigated, the influence of monomer sequence has received far less attention until recently. Here, we report the synthesis of two sequence-controlled polyurethane ionomers (PUIs) prepared via a stepwise coupling-deprotection strategy, and compare their solution association in aqueous-organic mixtures. The two PUIs are highly similar in mass and overall composition, yet differ markedly in the sequence of building blocks. PUI-A2 comprises a polytetrahydrofuran (pTHF) block connected to an alternation of isophorone diamine (IPDA) and dimethylolpropionic acid (DMPA) units that together are also arranged in a blockwise manner. The result is a macromolecular structure with a comparatively hydrophobic tail (pTHF) and a hydrophilic headgroup, which structure is reminiscent of those of traditional surfactants, albeit much larger in size. PUI-S2 instead resembles a bolaamphiphilic architecture with a pTHF midblock connected on either end to a singly charged segment comprising DMPA and IPDA. We detect micellization below a threshold cosolvent volume fraction (φsolv) of 0.4 in aqueous-organic mixtures with tetrahydrofuran (THF), ethanol, and isopropyl alcohol. We use scattering tools to compare the aggregation number (N agg) and hydrodynamic radius (R h) of PUI-S2 and PUI-A2 micelles. Irrespective of the solvent composition, we observe in the micellar window of φsolv < 0.4, lower N agg for PUI-S2 micelles compared to PUI-A2, which we attribute to packing restraints associated with its bolaamphiphilic architecture. The increase in micellar size with increasing φsolv is much more pronounced for PUI-S2 than for PUI-A2. The micellar mass decreases with increasing φsolv for both PUIs; the effect is modest for PUI-S2 compared to PUI-A2 and is not observed in the most apolar cosolvent studied (THF). Upon the approach of the micellization boundary φsolv ≈ 0.4, both types of PUI micelles become less compact in structure, as (in most cases) PUIs are released and as micellar dimensions increase.

Sequence of Polyurethane Ionomers Determinative for Core Structure of Surfactant-Copolymer Complexes.

The core of micelles self-assembled from amphiphiles is hydrophobic and contains little water, whereas complex coacervate core micelles co-assembled from oppositely charged hydrophilic polymers have a hydrophilic core with a high water content. Co-assembly of ionic surfactants with ionic-neutral copolymers yields surfactant-copolymer complexes known to be capable of solubilizing both hydrophilic and hydrophobic cargo within the mixed core composed of a coacervate phase with polyelectrolyte-decorated surfactant micelles. Here we formed such complexes from asymmetric (PUI-A2) and symmetric (PUI-S2), sequence-controlled polyurethane ionomers and poly(N-methyl-2-vinylpyridinium iodide)29-b-poly(ethylene oxide)204 copolymers. The complexes with PUI-S2 were 1.3-fold larger in mass and 1.8-fold larger in radius of gyration than the PUI-A2 complexes. Small-angle X-ray scattering revealed differences in the packing of the similarly sized PUI micelles within the core of the complexes. The PUI-A2 micelles were arranged in a more ordered fashion and were spaced further apart from each other (10 nm vs. 6 nm) than the PUI-S2 micelles. Hence, this work shows that the monomer sequence of amphiphiles can be varied to alter the internal structure of surfactant-copolymer complexes. Since the structure of the micellar core may affect both the cargo loading and release, our findings suggest that these properties may be tuned through control of the monomer sequence of the micellar constituents.

Supramolecular surface functionalization via catechols for the improvement of cell-material interactions.

Optimization of cell-material interactions is crucial for the success of synthetic biomaterials in guiding tissue regeneration. To do so, catechol chemistry is often used to introduce adhesiveness into biomaterials. Here, a supramolecular approach based on ureido-pyrimidinone (UPy) modified polymers is combined with catechol chemistry in order to achieve improved cellular adhesion onto supramolecular biomaterials. UPy-modified hydrophobic polymers with non-cell adhesive properties are developed that can be bioactivated via a modular approach using UPy-modified catechols. It is shown that successful formulation of the UPy-catechol additive with the UPy-polymer results in surfaces that induce cardiomyocyte progenitor cell adhesion, cell spreading, and preservation of cardiac specific extracellular matrix production. Hence, by functionalizing supramolecular surfaces with catechol functionalities, an adhesive supramolecular biomaterial is developed that allows for the possibility to contribute to biomaterial-based regeneration.

Increased admission and fasting glucose are associated with unfavorable short-term outcome after intra-arterial treatment of ischemic stroke in the MR CLEAN pretrial cohort.

BACKGROUND: Limited data are available on the impact of fasting glucose on outcome after intra-arterial treatment (IAT). We studied whether hyperglycemia on admission and impaired fasting glucose (IFG) are associated with unfavorable outcome after IAT in acute ischemic stroke. METHODS: Patients were derived from the pretrial registry of the MR CLEAN-trial. Hyperglycemia on admission was defined as glucose>7.8mmol/L, IFG as fasting glucose>5.5mmol/L in the first week of admission. Primary effect measure was the adjusted common odds ratio (acOR) for a shift in the direction of worse outcome on the modified Rankin Scale at discharge, estimated with ordinal logistic regression, adjusted for common prognostic factors. RESULTS: Of the 335 patients in which glucose on admission was available, 86 (26%) were hyperglycemic, 148 of the 240 patients with available fasting glucose levels (62%) had IFG. Median admission glucose was 6.8mmol/L (IQR 6-8). Increased admission glucose (acOR 1.2, 95%CI 1.1-1.3), hyperglycemia on admission (acOR 2.6, 95%CI 1.5-4.6) and IFG (acOR 2.8, 95%CI 1.4-5.6) were associated with worse functional outcome at discharge. CONCLUSION: Increased glucose on admission and IFG in the first week after stroke onset are associated with unfavorable short-term outcome after IAT of acute ischemic stroke.

Synthesis and evaluation in rats of homologous series of [(18)F]-labeled dopamine D 2/3 receptor agonists based on the 2-aminomethylchroman scaffold as potential PET tracers.

BACKGROUND: Agonist positron emission tomography (PET) tracers for dopamine D2/3 receptors (D2/3Rs) offer greater sensitivity to changes in endogenous dopamine levels than D2/3R antagonist tracers. D2/3R agonist tracers currently available for clinical research are labeled with the short-lived isotope carbon-11, which limits their use. We aimed to develop high-affinity D2R agonists amenable for labeling with the longer-living fluorine-18. Here, we report the evaluation as potential PET tracers of two homologous series of [(18)F]fluorinated tracers based on the 2-aminomethylchroman-7-ol (AMC) scaffold: (R)-2-((4-(2-fluoroalkoxy)benzylamino)methyl)chroman-7-ols (AMC13 homologues) and (R)-2-((2-(4-(4-(fluoroalkoxy)phenyl)piperazin-1-yl)ethylamino)methyl)chroman-7-ols (AMC15 homologues). We varied the length of the (18)F-fluoroalkyl chain in these structures to balance brain penetration and non-specific binding of the radioligands by adjusting their lipophilicity. METHODS: The tracers were evaluated in brain slices of Sprague-Dawley rats by in vitro autoradiography and in living rats by microPET imaging and ex vivo autoradiography. PET data were analyzed with one- and two-tissue compartmental models (1TCM/2TCM), simplified reference tissue model (SRTM), and Logan graphical analysis. Specificity of binding was tested by blocking D2/3R with raclopride. RESULTS: Homologues with a shorter fluoroalkyl chain consistently showed greater D2/3R-specific-to-total binding ratios in the striatum than those with longer chains. The fluoroethoxy homologue of AMC13 ([(18)F]FEt-AMC13) demonstrated the highest degree of D2/3R-specific binding among the evaluated tracers: mean striatum-to-cerebellum uptake ratio reached 4.4 in vitro and 2.1/2.8 in vivo/ex vivo (PET/autoradiography). Striatal binding potential (BPND) relative to cerebellum was 0.51-0.63 depending on the estimation method. Radiometabolites of [(18)F]FEt-AMC13 did not enter the brain. In vitro, application of 10 µmol/L raclopride reduced D2/3R-specific binding of [(18)F]FEt-AMC13 in the striatum by 81 %. In vivo, pre-treatment with 1 mg/kg (2.9 µmol/kg) raclopride led to 17-39 % decrease in D2/3R-specific binding in the striatum. CONCLUSIONS: Varying the length of the [(18)F]fluoroalkyl chain helped improve the characteristics of the original candidate tracers. Further modifications of the current lead [(18)F]FEt-AMC13 can provide an agonist radiopharmaceutical suitable for D2/3R imaging by PET.

Synthesis and evaluation in rats of the dopamine D2/3 receptor agonist 18F-AMC20 as a potential radioligand for PET.

UNLABELLED: Dopamine D(2/3) receptor (D(2/3)R) agonist PET tracers are better suited for the imaging of synaptic dopaminergic neurotransmission than D(2/3)R antagonists and may also offer the opportunity to study in vivo the high-affinity state of D(2/3)R (D(2/3)RHigh). With the aim to develop (18)F-labeled D2/3R agonists suitable for widespread clinical application, we report here on the synthesis and in vitro and in vivo evaluation of a D(2/3)R agonist ligand from the aminomethyl chromane (AMC) class-(R)-2-[(4-(18)F-fluorobenzylamino)methyl]chroman-7-ol ((18)F- AMC20: ). METHODS: In vitro affinities of AMC20: toward dopaminergic receptor subtypes were measured in membrane homogenates prepared from HEK293 cells expressing human dopamine receptors. Agonism of AMC20: was assessed in the arrestin recruitment assay in Chinese hamster ovary-K(1) cells expressing the long isoform of D(2)R (D(2)RLong). D(2/3)R-specific binding of (18)F- AMC20: was evaluated in brain slices of Sprague-Dawley rats by in vitro autoradiography and in living rats by in vivo small-animal PET imaging and ex vivo autoradiography. PET data were analyzed with 1- and 2-tissue compartmental models, the simplified reference tissue model, and Logan graphical analysis. Specificity of binding was tested by blocking D(2/3)R with raclopride (coincubation with 10 µM in vitro, administration of 1.0 mg/kg in vivo). RESULTS: In membrane homogenates, AMC20: demonstrated picomolar affinity at D(2)RHigh (mean inhibition constant [K(i)] = 85 pM) and excellent selectivity against the low-affinity state of D(2)R (D(2)RLow) (mean K(i) = 84 nM, 988-fold selectivity) and D(1)-like receptors (mean K(i) = 5,062 nM at D1R). The efficacy of AMC20: was 90% of that of dopamine in the arrestin recruitment assay. Up to 70% of total binding of (18)F- AMC20: in the D2/3R-rich striatum in rat brain slices was D(2/3)R-specific; in living rats, the uptake ratio between the striatum and the D(2/3)R-poor cerebellum reached 2.0-2.5, depending on the measurement method. Radiometabolites of (18)F- AMC20: did not enter the brain. Striatal binding potential of (18)F- AMC20: varied between 0.49 and 0.59 depending on the estimation method. Pretreatment with 1 mg of raclopride per kilogram reduced the apparent specific binding of (18)F- AMC20: in the striatum. CONCLUSION: (18)F- AMC20: shows specific binding to D(2/3)R in the striatum of living rats. Further optimization of the chemical structure of (18)F- AMC20: can lead to (18)F-labeled D(2/3) agonist PET tracers more suitable for in vivo clinical application.

[Laminoplasty for cervical spondylotic myelopathy]. / Place de la laminoplastie dans le traitement de la myélopathie cervicale d'origine arthrosique.

Cervical spondylotic myelopathy (CSM) is a common condition. Uninstrumented laminectomy may be complicated by postoperative instability, whereas anterior or posterior decompression with fusion may be associated with stiffness and adjacent segment disease. Cervical laminoplasty, initially oriented towards pediatric patients and ossification of the posterior longitudinal ligament, becomes an interesting surgical alternative to decompress and reconstruct cervical anatomy without fusion. Eighteen patients (12 men, 6 women), mean age 64.2 who presented with CSM were treated surgically using multilevel laminoplasty, and reviewed after 1 month, 6 months, 1 year and 2 years. Clinical evaluation was performed based on the Benzel-JOA and Nurick scores. The preoperative mean Benzel-JOA score was 13.55; Preoperative mean Nurick score was 1.88. Preoperative MRI was carried-out in 16/18 patients. Intramedullary hyperintensity in T2 was observed in 6 patients. The operation was performed on 2 levels (4 patients) 3 levels (11 patients) and 4 levels (3 patients). We used the open-door hinged laminoplasty technique, using metallic implants, without bone graft. At one month FU, mean JOA score was 15.44, and Nurick dropped to 1.05. At 6 months, mean JOA was 16.28 and Nurick was 0.71. At one year, the mean JOA score was 16.16, and Nurick was 0.83. At 2 years, mean JOA was 17.5, and Nurick was 0.25. One infection, one dural tear and one transient episode of C5 paresthesia were observed. We conclude that spinal cord decompression by open-door laminoplasty for CSM allows significant clinical improvement observed progressively in the two years following surgery.

[Longterm results of cervical arthroplasty with disc prosthesis. A literature review]. / Résultats à long terme de l'arthroplastie cervicale par prothese de disque. Revue de la littérature.

Cervical arthroplasty has now been performed for over 10 years. Despite the large number of implanted artificial discs, the quality of the published studies is weak, and very few report a follow up exceeding two years. We reviewed the literature on cervical total disc replacement, focusing on publications reporting a follow-up of more than two years. The selection of patients, the type of implant and the surgical technique seem to influence greatly the quality of the clinical and radiological results. The occurrence of heterotopic ossifications around the implant seems to be the rule rather than the exception. Wear debris are likely to be observed in the vicinity of the prosthesis. Most long term studies also report a progressive decrease in the range of motion of the prosthesis, although without influence on the clinical evolution. It seems reasonable to say that cervical disc prosthesis is not inferior to discectomy and fusion, and that these implants allow a short term preservation of cervical mobility, but the efficacy in preventing adjacent segment disease or a favourable costleffectiveness ratio have yet to be demonstrated. A more widespread use of cervical disc prosthesis can only be suggested when these questions have been answered by long term follow-up studies.

Synthesis and characterization of a novel series of agonist compounds as potential radiopharmaceuticals for imaging dopamine D2/3 receptors in their high-affinity state.

Imaging of dopamine D2/3 receptors (D2/3R) can shed light on the nature of several neuropsychiatric disorders in which dysregulation of D2/3R signaling is involved. Agonist D2/3 tracers for PET/SPECT imaging are considered to be superior to antagonists because they are more sensitive to dopamine concentrations and may selectively label the high-affinity receptor state. Carbon-11-labeled D2/3R agonists have been developed, but these short-lived tracers can be used only in centers with a cyclotron. Here, we report the development of a series of novel D2R agonist compounds based on the 2-aminomethylchromane (AMC) scaffold that provides ample opportunities for the introduction of longer-lived [(18)F] or [(123)I]. Binding experiments showed that several AMC compounds have a high affinity and selectivity for D2/3R and act as agonists. Two fluorine-containing compounds were [(18)F]-labeled, and both displayed specific binding to striatal D2/3R in rat brain slices in vitro. These findings encourage further in vivo evaluations.

Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors.

For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [(123)I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [(123)I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.

Cost-effectiveness of two endovascular treatment strategies vs intravenous thrombolysis.

OBJECTIVE: To assess the cost-effectiveness of endovascular treatment against intravenous thrombolysis (IVT) when varying assumptions concerning its effectiveness. METHODS: We developed a health economic model including a hypothetical population consisting of patients with ischemic stroke, admitted within 4.5 h from onset, without contraindications for IVT or intra-arterial treatment (IAT). A decision tree and life table were used to assess 6-month and lifetime costs (in Euros) and effects in quality-adjusted life years treatment with IVT alone, IAT alone, and IVT followed by IAT if the patient did not respond to treatment. Several analyses were performed to explore the impact of considerable uncertainty concerning the clinical effectiveness of endovascular treatment. RESULTS: Probabilistic sensitivity analysis demonstrated a 54% probability of positive incremental lifetime effectiveness of IVT-IAT vs IVT alone. Sensitivity analyses showed significant variation in outcomes and cost-effectiveness of the included treatment strategies at different model assumptions. CONCLUSIONS: Acceptable cost-effectiveness of IVT-IAT compared to IVT will only be possible if recanalization rates are sufficiently high (>50%), treatment costs of IVT-IAT do not increase, and complication rates remain similar to those reported in the few randomized studies published to date. Large randomized studies are needed to reduce the uncertainty concerning the effects of endovascular treatment.

Prevention of scar tissue formation in spinal surgery: state of the art and review of the literature.

Recurrent radicular pain after lumbar micro-discectomy may lead to reduced quality of life of the patient. Lumbar epidural fibrosis is believed to be one of the mechanisms involved in the genesis of the pain. The use of absorbable gel temporarily separating disc remnants, muscle or bone structures from the nerve roots could reduce the amount of scar tissue surrounding the nerve, reduce tethering and therefore pain, improve outcomes and facilitate revision surgery. The author reviews the literature on prevention techniques for lumbar epidural fibrosis. The most recent studies on new compounds are encouraging in terms of safety and clinical efficacy.

[Treatment of symptomatic degenerative lumbar spinal stenosis by a percutaneous stand-alone lumbar interspinous implant. Preliminary experience with the Aperius device]. / Traitement de la sténose lombaire dégénérative symptomatique par mise en place percutanée d'implant interépineux. Expérience préliminaire avec l'implant Aperius.

BACKGROUND AND PURPOSE: Surgery for degenerative spinal stenosis classically involves decompression by laminectomy or foraminotomy. The use of interspinous process devices has been described for these indications in recent years. This study evaluates the efficacy and morbidity of a percutaneous interspinous device to define whether this technique would be a suitable alternative to classical surgery. METHOD: Twenty-two patients with degenerative lumbar spinal stenosis were studied prospectively. Pre- and postoperative symptoms were assessed using the Visual Analogic Score (VAS), the Zurich Claudication Questionnaire (ZCQ), physical activity, and patient satisfaction. The implant was positioned under biplanar fluoroscopic control after progressive distraction of the interspinous space using trocars. The patients were reviewed after 7 days, 6 weeks, and 6 months. RESULTS: All patients showed improved gait perimeter: 90 % could walk more than 1000 m 6 months after surgery, whereas only 50 % could walk this distance preoperatively. The mean symptom severity scores of 2.71 and physical activity scores of 2.38 improved to 1.87 (p=0.0003) and 1.53 (p<0.0001), respectively, after 6 months. The VAS decreased 3.5 points (p=0.0008) 6 months after surgery for leg pain. Ninety-one percent of the patients declared they were satisfied with the operation. CONCLUSION: The Aperius stand-alone and percutaneous interspinous device proved to be effective and safe in treating symptomatic lumbar spinal stenosis. This could be a good alternative to classic decompression surgery, but long-term follow-up studies are needed as well as subgroup analysis to define which patients could benefit from this technique.

Vasodilator efficacy of nitric oxide depends on mechanisms of intracellular calcium mobilization in mouse aortic smooth muscle cells.

BACKGROUND AND PURPOSE: Reduction of intracellular calcium ([Ca(2+)](i)) in smooth muscle cells (SMCs) is an important mechanism by which nitric oxide (NO) dilates blood vessels. We investigated whether modes of Ca(2+) mobilization during SMC contraction influenced NO efficacy. EXPERIMENTAL APPROACH: Isometric contractions by depolarization (high potassium, K(+)) or alpha-adrenoceptor stimulation (phenylephrine), and relaxations by acetylcholine chloride (ACh), diethylamine NONOate (DEANO) and glyceryl trinitrate (GTN) and SMC [Ca(2+)](i) (Fura-2) were measured in aortic segments from C57Bl6 mice. KEY RESULTS: Phenylephrine-constricted segments were more sensitive to endothelium-derived (ACh) or exogenous (DEANO, GTN) NO than segments contracted by high K(+) solutions. The greater sensitivity of phenylephrine-stimulated segments was independent of the amount of pre-contraction, the source of NO or the resting potential of SMCs. It coincided with a significant decrease of [Ca(2+)](i), which was suppressed by sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) inhibition, but not by soluble guanylyl cylase (sGC) inhibition. Relaxation of K(+)-stimulated segments did not parallel a decline of [Ca(2+)](i). However, stimulation (BAY K8644) of L-type Ca(2+) influx diminished, while inhibition (nifedipine, 1-100 nM) augmented the relaxing capacity of NO. CONCLUSIONS AND IMPLICATIONS: In mouse aorta, NO induced relaxation via two pathways. One mechanism involved a non-cGMP-dependent stimulation of SERCA, causing Ca(2+) re-uptake into the SR and was prominent when intracellular Ca(2+) was mobilized. The other involved sGC-stimulated cGMP formation, causing relaxation without changing [Ca(2+)](i), presumably by desensitizing the contractile apparatus. This pathway seems related to L-type Ca(2+) influx, and L-type Ca(2+) channel blockers increase the vasodilator efficacy of NO.

Paraoxonase 1 gene transfer lowers vascular oxidative stress and improves vasomotor function in apolipoprotein E-deficient mice with pre-existing atherosclerosis.

BACKGROUND AND PURPOSE: Transgenesis of human paraoxonase 1 (PON1), a HDL-associated enzyme that destroys lipid peroxides, has been reported to reduce early atherogenesis in mice. The present study explored the therapeutic potential of human PON1 gene transfer in old apolipoprotein E-deficient (apoE(-/-)) mice with advanced atherosclerosis. EXPERIMENTAL APPROACH: ApoE(-/-) mice (18 months, regular chow) were transfected with PON1 adenovirus (AdPON1, n=10) or control adenovirus (AdRR5, n=10). Non-transfected apoE(-/-) (n=9) and C57Bl/6J (WT, n=6) mice served as controls. Three weeks later, plaque size and composition, and endothelial cell (EC) and smooth muscle cell (SMC) function were assessed in the aorta. KEY RESULTS: PON1 gene transfer raised total PON1 serum activity 13-15 fold during the 3-week study period, without affecting hypercholesterolaemia or lesion size. However, PON1 decreased the oxLDL content of the plaque. Plaque-free thoracic aorta rings from apoE(-/-) mice displayed, like rings from WT mice, complete relaxation to acetylcholine (ACh, 86+/-2%), ATP (90+/-2%) or UTP (83+/-3%). In contrast, in plaque-bearing segments amplitude (55+/-7%, 68+/-8%, 52+/-8% respectively) and sensitivity were decreased. EC function was completely (ATP, UTP) or largely (ACh) restored by AdPON1. Furthermore, apoE(-/-) SMCs released less intracellular calcium than WT upon sarco-endoplasmic reticulum calcium ATPase (SERCA) inhibition by cyclopiazonic acid. This defect was also restored by AdPON1 transfection. CONCLUSIONS AND IMPLICATIONS: These data indicate that AdPON1 gene transfer improved vascular wall oxidative stress, EC function, and SMC Ca(2+) homeostasis in segments with pre-existing atherosclerosis, independently of an effect on plaque size.

[Balloon kyphoplasty for treatment of vertebral osteoporotic compression fractures]. / Traitement des fractures vertébrales ostéoporotiques avec kyphoplastie par ballonnet.

Kyphoplasty, the newest of the tools treating vertebral osteoporotic compression fractures (VOCF) is the evolution of vertebroplasty, allowing not only pain control and strengthening of the fractured vertebra, but also offering the possibility to restore vertebral height with a lower risk of complications. We present our series of 41 consecutive VOCF treated by kyphoplasty in 30 patients between October 2003 and March 2006. Systematic spinal X rays and CT scan have be performed, occasionally followed by bone scintigraphy or spinal MRI. The mean preoperative duration of symptoms before surgery was 52 days. Pain control after the operation was considered excellent in all cases and all patients were mobilized the day after surgery. Kyphoplasty allowed a 50% restoration of vertebral height in 66% of the treated vertebras. The results were better when surgery was performed within the first three months after the fracture. The mean vertebral deformity correction by comparison of the pre- and postoperative Cobb angles was 9.7 degrees. One patient showed cement leakage in the spinal canal without neurological deterioration. The mean postoperative stay was 2.5 days. We found kyphoplasty to be a safe technique allowing immediate pain control after VOCF, with minimal risks of cement leakage or pulmonary embolism. Vertebral height and deformity correction are best achieved with early surgery, but pain control is always excellent even with a delayed procedure.

[Epidural neurostimulation for chronic pain following abdominal hernia repair]. / Neuromodulation antalgique pour douleur chronique pariétale après cure chirurgicale d'éventration.

We report the case of a patient presenting with midline abdominal herniation treated surgically followed by progressively growing abdominal pain resistant to conventional pain treatments. Epidural neurostimulation finally gave satisfactory results. We suggest that epidural neurostimulation can be a valuable tool in treating carefully selected patients with otherwise intractable pain. It is essential to rule out any local complication and to check that conventional analgesia is ineffective, that the psychiatric evaluation is satisfactory and that TENS provides a benefit in pain control. To our knowledge this is to be the first report of epidural neurostimulation for the treatment of chronic pain following repair of midline herniation.