Publications by authors named "Olivier Gauthier"

66 Publications

Biphasic Calcium Phosphate Microparticles Mixed With Autologous Blood: Application for the Reconstruction of a Large Mandibular Bone Defect in a Dog.

J Vet Dent 2020 Dec 19;37(4):201-209. Epub 2021 Feb 19.

560854Azurvet Veterinary Referal Center, Saint Laurent du Var, France.

Large mandibular bone defects can be difficult to treat in dogs, with a high risk of mal or nonunion due to instability and risk of infection. This case report describes the use of autologous clotted blood mixed with biphasic calcium phosphate microparticles to fill a defect in a nonunion fracture and promote bone regeneration in a dog using a 2-stage surgical approach. This new method was designed and tried in a dog with a chronic, unstable mandibular fracture associated with a large sequestrum. Initial treatment involved debridement of the lesion, then the oral wound and oral vestibule were reconstructed in 2 layers. Four weeks later a second stage surgery allowed placement of a pre-contoured maxillofacial plate to bridge the defect, which was filled with a blood/biphasic calcium phosphate compound implant. Cone-beam computed tomography was used prior to the initial surgery for preoperative planning and 3-D printing of a mandibular template for plate contouring. CT was subsequently used to document the healing process, using a bone density measurement tool to assess bone regeneration. Radiographic evidence suggestive of osseointegration was observed within 6 months with effective filling of the defect and restoration of alveolar ridge continuity. A return to normal and atraumatic occlusion was considered excellent. Cone-beam computed tomography was found useful to document radiographic evidence of osseointegration, bone regrowth and remodeling. This case report is to serve as a proof-of-concept study and should be followed by a prospective evaluation.
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http://dx.doi.org/10.1177/0898756421990909DOI Listing
December 2020

The Use of Biphasic Calcium Phosphate Substitute (BCP) in Mandibular Defects in Dogs: Use of CBCT to Evaluate Bone Healing.

J Vet Dent 2020 Dec 8;37(4):210-219. Epub 2021 Feb 8.

Azurvet Veterinary Referal Center, Saint Laurent du Var, France.

This study aimed to assess the use of cone beam computed tomography (CBCT) to follow-up bone healing of mandibular bone defects in dogs, filled with a combination of autologous blood and millimetric BCP granules. CBCT was performed ≥4 weeks postoperatively. CBCT gray-scale values were measured from multiplanar reconstructions of the defects and compared to that of normal contralateral mandibular bone and to pure BCP/blood composite time 0 (T0) value. Other parameters, determined by affecting grades according to specific criteria included: bone ridge margin restoration; biomaterial homogeneity; bone-biomaterial interface. Results: 8 dogs with 14 defects were included. Median age was 7.2 years (1-15 years). Follow-up CBCT was performed 1 to 7.5 months postoperatively (mean 3.3 months). Defect CBCT gray-scale values at follow-up were significantly greater than T0 (p < 0.05). Ratios of maximum and minimum densities of the defects to contralateral mandibular bone followed a linear correlation with time (p < 0.05). The bone ridge margin was adequately restored in all the defects and significantly correlated with time (p = 0.03). Biomaterial homogeneity was fair to good in 11 defects and significantly correlated with the bone ridge margin parameter (p = 0.05) and time (p = 0.006). There was no significant correlation with the bone-material interface. The latter was satisfactory in 12 defects and significantly correlated with time (p = 0.01) but not with the other parameters. The biomaterial was more homogeneous in smaller defects and with increasing time. CBCT allowed effective assessment of bone healing via the measurement of CBCT gray-scale values and assessment of multiple radiological variables.
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http://dx.doi.org/10.1177/0898756421989120DOI Listing
December 2020

Stable mercury concentrations of tropical tuna in the south western Pacific ocean: An 18-year monitoring study.

Chemosphere 2021 Jan 21;263:128024. Epub 2020 Aug 21.

Univ Brest, CNRS, IRD, Ifremer, LEMAR, F-29280, Plouzané, France.

Global anthropogenic mercury (Hg) emissions to the atmosphere since industrialization are widely considered to be responsible for a significant increase in surface ocean Hg concentrations. Still unclear is how those inputs are converted into toxic methylmercury (MeHg) then transferred and biomagnified in oceanic food webs. We used a unique long-term and continuous dataset to explore the temporal Hg trend and variability of three tropical tuna species (yellowfin, bigeye, and skipjack) from the southwestern Pacific Ocean between 2001 and 2018 (n = 590). Temporal trends of muscle nitrogen (δN) and carbon (δC) stable isotope ratios, amino acid (AA) δN values and oceanographic variables were also investigated to examine the potential influence of trophic, biogeochemical and physical processes on the temporal variability of tuna Hg concentrations. For the three species, we detected significant inter-annual variability but no significant long-term trend for Hg concentrations. Inter-annual variability was related to the variability in tuna sampled lengths among years and to tuna muscle δN and δC values. Complementary AA- and model-estimated phytoplankton δN values suggested the influence of baseline processes with enhanced tuna Hg concentrations observed when dinitrogen fixers prevail, possibly fuelling baseline Hg methylation and/or MeHg bioavailability at the base of the food web. Our results show that MeHg trends in top predators do not necessary capture the increasing Hg concentrations in surface waters suspected at the global oceanic scale due to the complex and variable processes governing Hg deposition, methylation, bioavailability and biomagnification. This illustrates the need for long-term standardized monitoring programs of marine biota worldwide.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128024DOI Listing
January 2021

Collateral effects of targeting the nucleus pulposus via a transpedicular or transannular surgical route: a combined X-ray, MRI, and histological long-term descriptive study in sheep.

Eur Spine J 2021 Feb 18;30(2):585-595. Epub 2020 Sep 18.

INSERM UMR 1229, RMeS, Regenerative Medicine and Skeleton, School of Dental Surgery, ONIRIS, Université de Nantes, 1-Place Alexis Ricordeau, 44042, Nantes Cedex I, France.

Purpose: In the context of regenerative medicine strategies, based in particular on the injection of regenerative cells, biological factors, or biomaterials into the nucleus pulposus (NP), two main routes are used: the transpedicular approach (TPA) and the transannular approach (TAA). The purpose of our study was to compare the long-term consequences of the TPA and the TAA on intervertebral disc (IVD) health through a longitudinal follow-up in an ovine model.

Methods: The TPA and the TAA were performed on 12 IVDs from 3 sheep. Six discs were left untreated and used as controls. The route and injection feasibility, as well as the IVD environment integrity, were assessed by MRI (T2-weighted signal intensity), micro-CT scan, and histological analyses (Boos' scoring). The sheep were assessed at 1, 3, and 7 months.

Results: Both the TPA and the TAA allowed access to the NP. They both induced NP degeneration, as evidenced by a decrease in the T2wsi and an increase in the Boos' scores. The TPA led to persistent end-plate defects and herniation of NP tissue (Schmorl's node-like) after 7 months as well as the presence of osseous fragments in the NP.

Conclusions: The TPA induced more severe lesions in IVDs and vertebrae compared to the TAA. The lesions induced by the TPA are reason to consider whether or not this route is optimal for studying IVD regenerative medicine approaches.
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http://dx.doi.org/10.1007/s00586-020-06602-5DOI Listing
February 2021

The marine intertidal zone shapes oyster and clam digestive bacterial microbiota.

FEMS Microbiol Ecol 2020 08;96(8)

Univ Brest, CNRS, IRD, Ifremer, LEMAR, F-29280 Plouzané, France.

Digestive microbiota provide a wide range of beneficial effects on host physiology and are therefore likely to play a key role in marine intertidal bivalve ability to acclimatize to the intertidal zone. This study investigated the effect of intertidal levels on the digestive bacterial microbiota of oysters (Crassostrea gigas) and clams (Ruditapes philippinarum), two bivalves with different ecological niches. Based on 16S rRNA region sequencing, digestive glands, seawater and sediments harbored specific bacterial communities, dominated by operational taxonomic units assigned to the Mycoplasmatales,Desulfobacterales and Rhodobacterales orders, respectively. Field implantation modified digestive bacterial microbiota of both bivalve species according to their intertidal position. Rhodospirillales and Legionellales abundances increased in oysters and clams from the low intertidal level, respectively. After a 14-day depuration process, these effects were still observed, especially for clams, while digestive bacterial microbiota of oysters were subjected to more short-term environmental changes. Nevertheless, 3.5 months stay on an intertidal zone was enough to leave an environmental footprint on the digestive bacterial microbiota, suggesting the existence of autochthonous bivalve bacteria. When comparing clams from the three intertidal levels, 20% of the bacterial assemblage was shared among the levels and it was dominated by an operational taxonomic unit affiliated to the Mycoplasmataceae and Spirochaetaceae families.
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http://dx.doi.org/10.1093/femsec/fiaa078DOI Listing
August 2020

Evaluation of a Single Intra-Articular Injection of Autologous Adipose Tissue for the Treatment of Osteoarthritis: A Prospective Clinical Study in Dogs.

Vet Comp Orthop Traumatol 2020 Jul 21;33(4):258-266. Epub 2020 Apr 21.

Department of Small Animal Surgery and Anesthesia, ONIRIS Nantes Atlantic College of Veterinary Medicine, Nantes, France.

Objective:  The aim of this study was to investigate the safety, feasibility and clinical efficacy of a single intra-articular injection of autologous and purified micro-fragmented adipose tissue for the treatment of osteoarthritis (OA) in dogs.

Study Design:  Twenty-one client-owned dogs with radiographically confirmed OA were recruited into this prospective study. Lameness and discomfort were evaluated by physical examination at day 0 and then 14, 30, 60 and 180 days after injection. Kinetic data and temporospatial parameters were obtained using a pressure-sensing walkway. Peak vertical force, vertical impulse and percentages of body weight distribution were determined. Owner perception data regarding their own dog's physical activity were also collected using the Canine Brief Pain Inventory.

Results:  Radiographic scores for OA from days 0 to 180 were similar, except in two dogs. No major side effects were noted after injection. Lameness and Canine Brief Pain Inventory scores were significantly lower at all time points compared with day 0. Post-injection results demonstrated gradual improvement of kinetic data up to day 180 compared with pre-treatment values: vertical impulse (>2.25%), peak vertical force (>5.32%) and percentages of body weight distribution (>3.6%). In dogs with elbow OA, gait analysis values significantly increased at all time points compared with day 0.

Conclusion:  Regenerative autologous adipose tissue injection therapy is a promising alternative to traditional analgesics treatment in patients with OA, associated with significant reductions in pain and lameness, delayed disease progression and improved quality of life.
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http://dx.doi.org/10.1055/s-0040-1708524DOI Listing
July 2020

Tailored Three-Dimensionally Printed Triply Periodic Calcium Phosphate Implants: A Preclinical Study for Craniofacial Bone Repair.

ACS Biomater Sci Eng 2020 01 22;6(1):553-563. Epub 2019 Nov 22.

INSERM, U 1229, Laboratoire Regenerative Medicine and Skeleton (RMeS), 1 place Alexis Ricordeau, Nantes F - 44042, France.

Finding alternative strategies for the regeneration of craniofacial bone defects (CSD), such as combining a synthetic ephemeral calcium phosphate (CaP) implant and/or active substances and cells, would contribute to solving this reconstructive roadblock. However, CaP's architectural features (i.e., architecture and composition) still need to be tailored, and the use of processed stem cells and synthetic active substances (e.g., recombinant human bone morphogenetic protein 2) drastically limits the clinical application of such approaches. Focusing on solutions that are directly transposable to the clinical setting, biphasic calcium phosphate (BCP) and carbonated hydroxyapatite (CHA) 3D-printed disks with a triply periodic minimal structure (TPMS) were implanted in calvarial critical-sized defects (rat model) with or without addition of total bone marrow (TBM). Bone regeneration within the defect was evaluated, and the outcomes were compared to a standard-care procedure based on BCP granules soaked with TBM (positive control). After 7 weeks, de novo bone formation was significantly greater in the CHA disks + TBM group than in the positive controls (3.33 mm and 2.15 mm, respectively, P=0.04). These encouraging results indicate that both CHA and TPMS architectures are potentially advantageous in the repair of CSDs and that this one-step procedure warrants further clinical investigation.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064275PMC
January 2020

Ultrasonography-Guided Perineural Injection of the of the 7 and 8th Cervical Nerves in Horses: A Cadaveric Descriptive Pilot Study.

Front Vet Sci 2020 25;7:102. Epub 2020 Feb 25.

INRA/ENVA, UMR 957, Biomechanics and Equine Locomotor Pathology Research Unit, Centre for Imaging and Research in Equine Locomotor Disorders (CIRALE), National Veterinary School of Alfort, Maisons-Alfort, France.

To describe the feasibility and dye diffusion of selective perineural injection of the 7 and 8th cervical nerve (C7 and C8) under ultrasonographic guidance in horses. Prospective experimental pilot cadaver study. Four equine cadavers of similar body weight (420-480 kg) and neck conformation. Five C7 and five C8 were perineurally injected with a dye solution. Anatomic dissections including vertebral canal opening were conducted to confirm nerve dye staining and describe the extent of color diffusion. The of the spinal cervical nerves was visualized in all cadavers. All the injections were successful in staining a portion of the nerve trunk. Eight had a uniform transversal staining of the nerve trunk that longitudinally covered a distance >2 cm. One C7 and one C8 nerve trunk showed incomplete transversal staining with a more concentrated color on its half cranial aspect and a longitudinal coverage of <2 cm. Five injections resulted in dye extending proximally and medially into the epidural space. Volume had no appreciable effect on the extent of nerve staining. A greater proportion of epidural diffusion was found with injections done within less than one cm distally to the articular processes. All injections were considered to be selective for the targeted nerve. Ultrasonography-guided perineural injection of C7 and C8 is a feasible technique that may have multiple applications in multimodal analgesia in horses. Further clinical study will be necessary to determine the appropriate drug, dosage, and volume to inject and to confirm its usefulness.
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http://dx.doi.org/10.3389/fvets.2020.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052177PMC
February 2020

A Self-Setting Hydrogel of Silylated Chitosan and Cellulose for the Repair of Osteochondral Defects: From Characterization to Preclinical Evaluation in Dogs.

Front Bioeng Biotechnol 2020 29;8:23. Epub 2020 Jan 29.

Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, France.

Articular cartilage (AC) may be affected by many injuries including traumatic lesions that predispose to osteoarthritis. Currently there is no efficient cure for cartilage lesions. In that respect, new strategies for regenerating AC are contemplated with interest. In this context, we aim to develop and characterize an injectable, self-hardening, mechanically reinforced hydrogel (Si-HPCH) composed of silanised hydroxypropymethyl cellulose (Si-HPMC) mixed with silanised chitosan. The cytocompatibility of Si-HPCH was tested using human adipose stromal cells (hASC). , we first mixed Si-HPCH with hASC to observe cell viability after implantation in nude mice subcutis. Si-HPCH associated or not with canine ASC (cASC), was then tested for the repair of osteochondral defects in canine femoral condyles. Our data demonstrated that Si-HPCH supports hASC viability in culture. Moreover, Si-HPCH allows the transplantation of hASC in the subcutis of nude mice while maintaining their viability and secretory activity. In the canine osteochondral defect model, while the empty defects were only partially filled with a fibrous tissue, defects filled with Si-HPCH with or without cASC, revealed a significant osteochondral regeneration. To conclude, Si-HPCH is an injectable, self-setting and cytocompatible hydrogel able to support the and viability and activity of hASC as well as the regeneration of osteochondral defects in dogs when implanted alone or with ASC.
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http://dx.doi.org/10.3389/fbioe.2020.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025592PMC
January 2020

Preliminary evaluation of an osteochondral autograft, a prosthetic implant, and a biphasic absorbable implant for osteochondral reconstruction in a sheep model.

Vet Surg 2020 Apr 9;49(3):570-581. Epub 2020 Jan 9.

Department of Small Animal Surgery, Oniris Nantes-Atlantic College of Veterinary Medicine Food Science and Engineering, Nantes, France.

Objective: To determine the ability of three implants to enhance the healing of osteochondral defects: (1) a biphasic construct composed of calcium phosphate (CaP) and chitosan/cellulosic polymer, (2) a titanium-polyurethane implant, and (3) an osteochondral autograft.

Study Design: Experimental study.

Animals: Ten adult female sheep.

Methods: In five sheep, an 8-mm diameter osteochondral defect was created on the medial femoral condyle of a stifle and filled with a synthetic titanium-polyurethane implant. In five sheep, a similar defect was filled with an osteochondral autograft, and the donor site was filled with a biphasic construct combining CaP granules and a chitosan/cellulosic polymer. Sheep were monitored daily for lameness. Stifle radiographs and MRI were evaluated at 20 weeks, prior to animals being humanely killed. Surgical sites were evaluated with histology, microcomputed tomography, and scanning electron microscopy.

Results: Clinical outcomes were satisfactory regardless of the tested biomaterials. All implants appeared in place on imaging studies. Osteointegration of prosthetic implants varied between sites, with limited ingrowth of new bone into the titanium structure. Autografts and biphasic constructs were consistently well integrated in subchondral bone. All autografts except one contained a cartilage surface, and all biphasic constructs except one partially restored hyaline cartilage surface.

Conclusion: Biphasic constructs supported hyaline cartilage and subchondral bone regeneration, although restoration of the articular cartilage was incomplete.

Clinical Impact: Biphasic constructs may provide an alternative treatment for osteochondral defects, offering a less invasive approach compared with autologous grafts and eliminating the requirement for a prosthetic implant.
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http://dx.doi.org/10.1111/vsu.13373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154554PMC
April 2020

Reconstruction of segmental mandibular defects: Current procedures and perspectives.

Laryngoscope Investig Otolaryngol 2019 Dec 22;4(6):587-596. Epub 2019 Nov 22.

Laboratoire Regenerative Medicine and Skeleton RMeS, France INSERM, U 1229 Nantes France.

Background: The reconstruction of segmental mandibular defects remains a challenge for the reconstructive surgeon, from both a functional and an esthetic point of view.

Methods: This clinical review examines the different techniques currently in use for mandibular reconstruction as related to a range of etiologies, including the different bone donor sites, the alternatives to free flaps (FFs), as well as the contribution of computer-assisted surgery. Recent progress and the perspectives in bone tissue engineering (BTE) are also discussed.

Results: Osseous FF allows reliable and satisfying outcomes. However, locoregional flap, distraction osteogenesis, or even induced membrane techniques are other potential options in less favorable cases. Obtaining an engineered bone with satisfactory mechanical properties and sufficient vascular supply requires further investigations.

Conclusions: Osseous FF procedure remains the gold standard for segmental mandible reconstruction. BTE strategies offer promising alternatives.
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http://dx.doi.org/10.1002/lio2.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929581PMC
December 2019

In vivo resorption of injectable apatitic calcium phosphate cements: Critical role of the intergranular microstructure.

J Biomed Mater Res B Appl Biomater 2020 02 29;108(2):367-376. Epub 2019 Apr 29.

CEISAM, Université de Nantes, CNRS, UMR 6230, Nantes, France.

The in vivo resorption rate of two injectable apatitic calcium phosphate cements used in clinics (Graftys® HBS and NORIAN®) was compared, using a good laboratory practice (GLP) study based on an animal model of critical-sized bone defect. To rationalize the markedly different biological properties observed for both cements, key physical features were investigated, including permeability and water-accessible porosity, total porosity measured by mercury intrusion and gravimetry, and microstructure. Due to a different concept for creating porosity between the two cements investigated in this study, a markedly different microstructural arrangement of apatite crystals was observed in the intergranular space, which was found to significantly influence both the mechanical strength and in vivo degradation of the two calcium phosphate cements.
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http://dx.doi.org/10.1002/jbm.b.34395DOI Listing
February 2020

Extracellular hemoglobin combined with an O -generating material overcomes O limitation in the bioartificial pancreas.

Biotechnol Bioeng 2019 05 29;116(5):1176-1189. Epub 2019 Jan 29.

Immuno-Endocrinology Unit (IECM), Oniris, INRA, Université Bretagne Loire, Nantes, France.

The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O supply after transplantation remains a major challenge. In this study, we address the O limitation by combining silicone-encapsulated CaO (silicone-CaO ) to generate O with an extracellular hemoglobin O -carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O -diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O species produced by silicone-CaO . While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O provider with hemoglobin as an effective strategy to overcome O limitations in tissue engineering.
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http://dx.doi.org/10.1002/bit.26913DOI Listing
May 2019

Delivery systems of local anesthetics in bone surgery: are they efficient and safe?

Drug Discov Today 2018 11 26;23(11):1897-1903. Epub 2018 Jun 26.

CEISAM, CNRS UMR 6230, University of Nantes, Nantes, France; Faculty of Pharmaceutical Sciences, University of Nantes, Nantes, France. Electronic address:

Management of postoperative pain following bone surgery includes administration of local anesthetics (LAs). Smart delivery systems, including triggered systems, have been designed to provide a continuous release of LA in situ. However, these systems can provide a high level of LA locally. This review will examine the state-of-the-art regarding the LA delivery systems optimized for management of postoperative pain in bone surgery and will discuss the potential adverse effects of LAs on the overall pathways of bone healing, including the inflammation response phase, hemostasis phase, tissue repair phase and remodeling phase. There is a clinical need to document these effects and the potential impacts on the clinical outcome of the patient.
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http://dx.doi.org/10.1016/j.drudis.2018.06.019DOI Listing
November 2018

Evaluation of a hydrogel membrane on bone regeneration in furcation periodontal defects in dogs.

Dent Mater J 2018 Sep 20;37(5):825-834. Epub 2018 Jun 20.

INSERM, UMR-S 1229, RMeS, Faculty of Dental Surgery, University of Nantes.

The aim of the study was to evaluate bone regeneration using a canine model with surgically created periodontal defects filled for 12 weeks using a stratified biomaterial consisting in a biphasic calcium phosphate (BCP) covered with a crosslinking hydrogel acting as polymer membrane of silated hydroxypropyl methylcellulose (Si-HPMC) as the tested new concept. Bilateral, critical-sized, defects were surgically created at the mandibular premolar teeth of six adult beagle dogs. The defects were randomly allocated and: (i) left empty for spontaneous healing or filled with: (ii) BCP and a collagen membrane; (iii) BCP and hydrogel Si-HPMC membrane. At 12 weeks, the experimental conditions resulted in significantly enhanced bone regeneration in the test BCP/Si-HPMC group. Within the limits of this study, we suggest that the hydrogel Si-HPMC may act as an occlusive barrier to protect bone area from soft connective tissue invasion and then effectively contribute to enhance bone regeneration.
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http://dx.doi.org/10.4012/dmj.2017-238DOI Listing
September 2018

Pain Management After Bone Reconstruction Surgery Using an Analgesic Bone Cement: A Functional Noninvasive In Vivo Study Using Gait Analysis.

J Pain 2018 10 15;19(10):1169-1180. Epub 2018 May 15.

CEISAM, CNRS UMR 6230, University of Nantes, Nantes, France.

Postoperative pain after bone reconstruction is a serious complication that could jeopardize the global success of a surgery. This pain must be controlled and minimized during the first 3 to 4 postoperative days to prevent it from becoming chronic. In this study, a critical-size bone defect was created at the femoral distal end of rats and filled by an injectable calcium phosphate cement (CPC) loaded or not with local anesthetics (bupivacaine or ropivacaine). A functional evaluation of the gait was performed using the CatWalk system to compare the postoperative pain relief enhanced by the different CPCs after such a bone filling surgery. The results demonstrated significant pain relief during the short-term postoperative period, as shown by the print area and intensity parameters of the operated paw. At 24hours, the print area decreased by 65%, 42%, and 24%, and the intensity decreased by 25%, 9%, and 1% for unloaded, ropivacaine-loaded, and bupivacaine-loaded CPCs, respectively, compared with the preoperative values. Bupivacaine-loaded CPC provided an earlier return to full functional recovery than ropivacaine-loaded CPC. Moreover, the CPCs retained their biologic and mechanical properties. For all these reasons, anesthetic-loaded CPCs could be part of the global pain management protocol after bone reconstruction surgery such as iliac crest bone grafting procedures.

Perspective: Bupivacaine-loaded CPC provided an earlier return to full gait function than ropivacaine-loaded CPC, with preserved bone filling properties. Such analgesic CPCs deserve further in vivo investigation and may be part of the global pain management protocol after bone reconstruction or bone augmentation surgery such as iliac crest bone grafting.
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http://dx.doi.org/10.1016/j.jpain.2018.04.014DOI Listing
October 2018

Combination of blood and biphasic calcium phosphate microparticles for the reconstruction of large bone defects in dog: A pilot study.

J Biomed Mater Res A 2018 07 24;106(7):1842-1850. Epub 2018 Mar 24.

Université Côte d'Azur, CNRS, Inserm, iBV, France.

We previously reported that biphasic calcium phosphate (BCP) microparticles embedded in a blood clot induces ectopic bone formation in mice and repairs a critical femoral defect in rat. The present pilot study aimed to evaluate in dog and in two models of large defects the efficacy of this composite named "blood for reconstruction of bone" (BRB). We show here that BRB is a cohesive biomaterial easy to prepare from dog autologous blood and to mold to fill large bone defects. First in a model of cylindrical femoral condyle defect, the BRB was compared with BCP particles alone. After 8 weeks, this revealed that the amount of mature bone was slightly and significantly higher with BRB than with BCP particles. Second, in a model consisting in a 2 cm-long critical interruptive defect of the ulna, the BRB was compared with autologous bone. After 6 months, we observed that implantation of BRB can induce the complete reconstruction of the defect and that newly formed bone exhibits high regenerative potential. Comparison with the results obtained with autologous bone grafting strongly suggests that the BRB might be an efficient biomaterial to repair large bone defects, as an alternative or in addition to autologous bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1842-1850, 2018.
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http://dx.doi.org/10.1002/jbm.a.36384DOI Listing
July 2018

Trends and seasonality of river nutrients in agricultural catchments: 18years of weekly citizen science in France.

Sci Total Environ 2018 May 27;624:845-858. Epub 2017 Dec 27.

Laboratoire des Sciences de l'Environnement Marin (LEMAR UMR 6539 CNRS UBO IRD IFREMER), Institut Universitaire Européen de la Mer, Université de Bretagne Occidentale, 29280 Plouzané, France.

Agriculture and urbanization have disturbed three-quarters of global ice-free land surface, delivering huge amounts of nitrogen and phosphorus to freshwater ecosystems. These excess nutrients degrade habitat and threaten human food and water security at a global scale. Because most catchments are either currently subjected to, or recovering from anthropogenic nutrient loading, understanding the short- and long-term responses of river nutrients to changes in land use is essential for effective management. We analyzed a never-published, 18-year time series of anthropogenic (NO and PO) and naturally derived (dissolved silica) riverine nutrients in 13 catchments recovering from agricultural pollution in western France. In a citizen science initiative, high-school students sampled catchments weekly, which ranged from 26 to 1489km. Nutrient concentrations decreased substantially over the period of record (19 to 50% for NO and 14 to 80% for PO), attributable to regional, national, and international investment and regulation, which started immediately prior to monitoring. For the majority of catchments, water quality during the summer low-flow period improved faster than during winter high-flow conditions, and annual minimum concentrations improved relatively faster than annual maximum concentrations. These patterns suggest that water-quality improvements were primarily due to elimination of discrete nutrient sources with seasonally-constant discharge (e.g. human and livestock wastewater), agreeing with available land-use and municipal records. Surprisingly, long-term nutrient decreases were not accompanied by changes in nutrient seasonality in most catchments, attributable to persistent, diffuse nutrient stocks. Despite decreases, nutrient concentrations in almost all catchments remained well above eutrophication thresholds, and because additional improvements will depend on decreasing diffuse nutrient sources, future gains may be much slower than initial rate of recovery. These findings demonstrate the value of citizen science initiatives in quantifying long-term and seasonal consequences of changes in land management, which are necessary to identify sustainable limits and predict recovery timeframes.
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http://dx.doi.org/10.1016/j.scitotenv.2017.12.176DOI Listing
May 2018

A straightforward approach to enhance the textural, mechanical and biological properties of injectable calcium phosphate apatitic cements (CPCs): CPC/blood composites, a comprehensive study.

Acta Biomater 2017 10 30;62:328-339. Epub 2017 Aug 30.

Université de Nantes, CNRS, UMR 6230, CEISAM, UFR Sciences et Techniques, 2, rue de la Houssinière, BP 92208, 44322 NANTES Cedex 3, France. Electronic address:

Two commercial formulations of apatitic calcium phosphate cements (CPCs), Graftys® Quickset (QS) and Graftys® HBS (HBS), similar in composition but with different initial setting time (7 and 15min, respectively), were combined to ovine whole blood. Surprisingly, although a very cohesive paste was obtained after a few minutes, the setting time of the HBS/blood composite dramatically delayed when compared to its QS analogue and the two blood-free references. Using solid state NMR, scanning electron microscopy and high frequency impedance measurements, it was shown that, in the particular case of the HBS/blood composite, formation of a reticulated and porous organic network occurred in the intergranular space, prior to the precipitation of apatite crystals driven by the cement setting process. The resulting microstructure conferred unique biological properties to this material upon implantation in bone defects, since its degradation rate after 4 and 12weeks was more than twice that for the three other CPCs, with a significant replacement by newly formed bone.

Statement Of Significance: A major challenge in the design of bone graft substitutes is the development of injectable, cohesive, resorbable and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with initial mechanical properties as close as bone ones. Thus, we describe specific conditions in CPC-blood composites where the formation of a 3D clot-like network can interact with the precipitated apatite crystals formed during the cement setting process. The resulting microstructure appears more ductile at short-term and more sensitive to biological degradation which finally promotes new bone formation. This important and original paper reports the design and in-depth chemical and physical characterization of this groundbreaking technology.
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http://dx.doi.org/10.1016/j.actbio.2017.08.040DOI Listing
October 2017

The transpedicular surgical approach for the development of intervertebral disc targeting regenerative strategies in an ovine model.

Eur Spine J 2017 08 3;26(8):2072-2083. Epub 2017 Jul 3.

Laboratory for Regenerative Medicine and Skeleton (RMeS), Team STEP (Skeletal Physiopathology and Joint Regenerative Medecine), School of Dental Surgery, INSERM (Institut National de la Santé et de la Recherche Médicale) UMRS 1229, 1-Place Alexis Ricordeau, Nantes Cedex I, 44042, France.

Purpose: To investigate the suitability of the transpedicular approach (TPA) in a sheep model of IVD regenerative strategies METHODS: 24 IVD from four sheep were used. TPA and biopsies of the Nucleus pulposus (NP) were performed in 18 IVD (6 IVD control). Seven discographies were performed to assess the feasibility of injecting contrast agent. MRI, micro-CT scan, and histological analyses were performed and the accuracy of the TPA was evaluated. The effects on the vertebra and endplates were analyzed.

Results: 83% of our biopsies or injections were located in the NP. Osseous fragments in IVD were observed in 50%. We observed two cases (11%) of rostral endplate fracture and five cases (27%) of breaching of the cortical pedicle and encroachment into the spinal canal. Two cases of perivertebral venous embolism and two of backflow through the canal of the TPA inside the vertebra were noted. Significant damage occurred to the bone structure of the vertebra and to the rostral endplate on which the IVD had been inserted.

Conclusions: TPA induces damage to the endplates, and it may lead to neurological impairment and leakage of injected materials into the systemic circulation. These adverse effects must be fully considered before proceeding with TPA for IVD regenerative strategies.
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http://dx.doi.org/10.1007/s00586-017-5199-zDOI Listing
August 2017

Neu5Gc and α1-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs.

Diabetes 2017 04 12;66(4):987-993. Epub 2017 Jan 12.

IECM, Immuno-endocrinology, EA4644 Oniris, University of Nantes, USC1383 INRA, Oniris, Nantes, France

Xenocell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type 1 diabetes for addressing organ shortage. In humans, however, natural and elicited antibodies specific for pig xenoantigens, α-(1,3)-galactose (GAL) and -glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xenoislet rejection. We obtained double-knockout (DKO) pigs lacking GAL and Neu5Gc. Because Neu5Gc mice exhibit glycemic dysregulations and pancreatic β-cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities to quantities obtained from control wild-type pigs. In contrast to wild-type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in cytidine monophosphate--acetylneuraminic acid hydroxylase KO mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities, and immunostaining of insulin and glucagon was similar to that from wild-type pancreata. Blood glucose, insulin, C-peptide, the insulin-to-glucagon ratio, and HOMA-insulin resistance in fasted adult DKO pigs and blood glucose and C-peptide changes after intravenous glucose or insulin administration were similar to wild-type pigs. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies.
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http://dx.doi.org/10.2337/db16-1060DOI Listing
April 2017

Laparoscopic Evaluation of Umbilical Disorders in Calves.

Vet Surg 2016 Nov 29;45(8):1041-1048. Epub 2016 Sep 29.

Center for Research and Preclinical Investigation, ONIRIS, Nantes, France.

Objective: To describe a laparoscopic technique for evaluating umbilical disorders in calves, including feasibility, visualization of umbilical structures, and related complications.

Study Design: Prospective clinical study.

Animals: Male calves (15 Holstein, 2 Montbeliard) with umbilical disorders (n=17).

Methods: Calves <2 months old with obvious umbilical disease were assessed by clinical examination and ultrasonography of the umbilical structures. Laparoscopic evaluation was performed in dorsal recumbency under subarachnoid lumbosacral anesthesia and sedation. An open insertion technique with short 60 mm cannulas was used after creating 2 portals 10 cm cranial to the umbilicus (one 5 cm left of midline for the laparoscope and one 5 cm right of midline as an instrument portal). After laparoscopy, abnormal tissues were resected by laparotomy during the same anesthetic period.

Results: Laparoscopic evaluation of umbilical structures was performed quickly (mean surgery time 7.1 ± 2.5 minutes). Umbilical structures could be completely visualized in all calves without intraoperative complications. In addition to abnormalities previously detected on ultrasound, laparoscopy enabled detection of adhesions 7 calves that were not suspected on ultrasound, as well as focal enlargements of the umbilical arteries and urachus close to the bladder in 5 calves. Laparoscopy failed to detect abnormalities observed with ultrasound or laparotomy in 4 calves, including small hernias and omphalitis.

Conclusion: Laparoscopic evaluation of umbilical structures was performed safely and quickly in young calves and allowed complete evaluation of intra-abdominal umbilical structures and may, therefore, be a useful adjunct to physical examination and ultrasound to fully assess the abdomen in calves.
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http://dx.doi.org/10.1111/vsu.12559DOI Listing
November 2016

Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption.

Sci Rep 2016 09 19;6:33527. Epub 2016 Sep 19.

INSERM, U791, LIOAD, Nantes, F-44042, France.

Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.
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http://dx.doi.org/10.1038/srep33527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027597PMC
September 2016

Comparison of medetomidine-morphine and medetomidine-methadone for sedation, isoflurane requirement and postoperative analgesia in dogs undergoing laparoscopy.

Vet Anaesth Analg 2017 Jan 23;44(1):17-27. Epub 2017 Feb 23.

School of Clinical Veterinary Science, University of Bristol, Langford, UK.

Objective: To compare the effects of intravenous (IV) medetomidine-morphine and medetomidine-methadone on preoperative sedation, isoflurane requirements and postoperative analgesia in dogs undergoing laparoscopic surgery.

Study Design: Randomized, crossover trial.

Animals: Twelve adult Beagle dogs weighing 15.1 ± 4.1 kg.

Methods: Dogs were administered medetomidine (2.5 μg kg) IV 5 minutes before either methadone (MET) or morphine (MOR) (0.3 mg kg) IV. Anaesthesia was induced with propofol, maintained with isoflurane in oxygen, and depth was clinically assessed and adjusted by an anaesthetist blinded to the treatment. Animals underwent laparoscopic abdominal biopsies. Sedation and nausea scores, pulse rate (PR), respiratory rate (f), noninvasive systolic arterial blood pressure (SAP), rectal temperature (RT) and pain scores were recorded before drug administration, 5 minutes after medetomidine injection and 10 minutes after opioid administration. Propofol dose, PR, f, SAP, oesophageal temperature (T), end-tidal carbon dioxide and end-tidal isoflurane concentration (Fe'Iso) were recorded intraoperatively. Pain scores, PR, f, SAP and RT were recorded 10 minutes after extubation, every hour for 6 hours, then at 8, 18 and 24 hours. The experiment was repeated with the other drug 1 month later.

Results: Nine dogs completed the study. After opioid administration and intraoperatively, PR, but not SAP, was significantly lower in MET. Fe'Iso was significantly lower in MET. Temperature decreased in both treatments. Pain scores were significantly higher in MOR at 3 hours after extubation, but not at other time points. Two dogs required rescue analgesia; one with both treatments and one in MOR.

Conclusion And Clinical Relevance: At the dose used, sedation produced by both drugs when combined with medetomidine was equivalent, while volatile anaesthetic requirements and PR perioperatively were lower with methadone. Postoperative analgesia was deemed to be adequate for laparoscopy with either protocol, although methadone provided better analgesia 3 hours after surgery.
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http://dx.doi.org/10.1111/vaa.12394DOI Listing
January 2017

Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study.

Biomed Res Int 2016 10;2016:5498271. Epub 2016 May 10.

Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire (LIOAD), Group STEP "Skeletal Tissue Engineering and Physiopathology", School of Dental Surgery, 44042 Nantes, France; Department of Pharmacy, University Hospital of Nantes, 44093 Nantes, France; Pharmacy Faculty, University of Nantes, 44093 Nantes, France.

Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.
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http://dx.doi.org/10.1155/2016/5498271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877459PMC
February 2017

A simple and effective approach to prepare injectable macroporous calcium phosphate cement for bone repair: Syringe-foaming using a viscous hydrophilic polymeric solution.

Acta Biomater 2016 Feb 26;31:326-338. Epub 2015 Nov 26.

Université de Nantes, INSERM UMRS 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, 1 place Alexis Ricordeau, BP 84215, 44042 Nantes Cedex 1, France; CHU de Nantes, Nantes University Hospital, PHU 4 OTONN, 1 Pl A. Ricordeau Nantes, France. Electronic address:

Unlabelled: In this study, we propose a simple and effective strategy to prepare injectable macroporous calcium phosphate cements (CPCs) by syringe-foaming via hydrophilic viscous polymeric solution, such as using silanized-hydroxypropyl methylcellulose (Si-HPMC) as a foaming agent. The Si-HPMC foamed CPCs demonstrate excellent handling properties such as injectability and cohesion. After hardening the foamed CPCs possess hierarchical macropores and their mechanical properties (Young's modulus and compressive strength) are comparable to those of cancellous bone. Moreover, a preliminary in vivo study in the distal femoral sites of rabbits was conducted to evaluate the biofunctionality of this injectable macroporous CPC. The evidence of newly formed bone in the central zone of implantation site indicates the feasibility and effectiveness of this foaming strategy that will have to be optimized by further extensive animal experiments.

Statement Of Significance: A major challenge in the design of biomaterial-based injectable bone substitutes is the development of cohesive, macroporous and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with adequate initial mechanical properties without the use of complex processing and additives. Thus, we propose a simple and effective strategy to prepare injectable macroporous CPCs through syringe-foaming using a hydrophilic viscous polymeric solution (silanized-hydroxypropyl methylcellulose, Si-HPMC) as a foaming agent, that simultaneously meets all the aforementioned aims. Evidence from our in vivo studies shows the existence of newly formed bone within the implantation site, indicating the feasibility and effectiveness of this foaming strategy, which could be used in various CPC systems using other hydrophilic viscous polymeric solutions.
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http://dx.doi.org/10.1016/j.actbio.2015.11.055DOI Listing
February 2016

Complications of appendicular fracture repair in cats and small dogs using locking compression plates.

Vet Comp Orthop Traumatol 2016 29;29(1):46-52. Epub 2015 Oct 29.

Rosario Vallefuoco, DVM, Centre Hospitalier Veterinaire Fregis, 43 avenue Aristide Briand, 94110, Arcueil, France, E-mail:

Objective: Our objectives were: 1) to review the complications associated with stabilization of appendicular fractures in cats and small dogs using locking compression plates (LCP), and 2) to identify factors that could influence fixation construct stability.

Study Design: Retrospective clinical study.

Materials And Methods: Medical and radiographic records of cats and small dogs with appendicular fractures treated with LCP were reviewed. Only cases with adequate follow-up to document clinical union and cases for which complications appeared before the clinical union were included. Complications were classified as implant-related complications or other complications. Cases with implant-related complications were compared to cases with non-implant-related complications for differences in signalment (species, age, body weight, multiple fractures), fracture location and type (fractured bone, fracture localization, closed or open fracture), reduction method (open reduction and internal fixation [ORIF] or minimally invasive plate osteosynthesis [MIPO]) and fixation evaluations (implant size, plate-bridging ratio, plate span ratio, working length, plate screw density, number of screws and cortices engaged per plate and per main fragment, ratio between screw and bone diameter at the narrowest aspect of the bone, and presence of ancillary fixation).

Results: Seventy-five fractures from 63 cats (64 fractures) and 10 dogs (11 fractures) met the inclusion criteria. Eight humeral, 13 radio-ulnar, 26 femoral, and 28 tibio-fibular fractures were treated. Primary repair of the fracture was performed using 2.0 mm and 2.4 mm LCP in 22 and 53 fractures, respectively. Overall and implant-related complications were encountered in 13 and seven of 75 fractures, respectively. Fixation failure was not significantly associated with any aforementioned factor considered in this study, and in particular, there was no significant difference in the occurrence of fixation failure between fractures stabilized with two, or more than two, bicortical locking screws per main fragment.

Clinical Significance: 2.0 mm and 2.4 mm LCP were used to manage appendicular fractures in cats and small dogs. The overall complication and fixation failure rate were comparable to those reported in previous studies in which various locking plate systems were used.
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http://dx.doi.org/10.3415/VCOT-14-09-0146DOI Listing
October 2016

Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs.

PLoS One 2015 14;10(9):e0136934. Epub 2015 Sep 14.

INRA, UMR 1280, Physiologie des Adaptations Nutritionnelles, F-44093 Nantes, France; CRNH, West Human Nutrition Research Center of Nantes, CHU, Nantes, F-44093, France.

Aim: Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides.

Methods: HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured.

Results: NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification.

Conclusion: NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136934PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569091PMC
June 2016