Publications by authors named "Thomas Lilin"

23 Publications

  • Page 1 of 1

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model.

BMC Cancer 2021 Apr 26;21(1):461. Epub 2021 Apr 26.

Université Paris-Saclay, UVSQ, INRAE, BREED, 78350, Jouy-en-Josas, France.

Background: Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model.

Methods: Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure ("group 12") and N = 3 with 20 mmHg ("group 20"). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei.

Results: DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20.

Conclusions: This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.
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http://dx.doi.org/10.1186/s12885-021-07955-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073905PMC
April 2021

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine.

Eur Surg Res 2020 13;61(2-3):62-71. Epub 2020 Oct 13.

Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France.

Introduction: Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superiority to induce liver hypertrophy over absorbable material has been demonstrated. Nevertheless, the use of an absorbable material generates a reversible PVE (RPVE) capable of inducing significant liver hypertrophy. In small animal models, the possibility to proceed to a repeated RPVE (RRPVE) has shown to boost liver hypertrophy further. The aim of this preliminary study was to assess the feasibility and the tolerance of RRPVE in a large animal model, in comparison with permanent PVE (PPVE) and single RPVE.

Methods: Six swine (2 per group) were assigned either to single RPVE group (using powdered gelatin sponge), RRPVE group (2 RPVEs separated by 14 days) or PPVE group (using N-butyl-cyanoacrylate). The feasibility and tolerance of the procedures were evaluated using portography, liver function tests and histological analysis. Evolution of liver volumes was assessed with volumetric imaging by computed tomography.

Results: Embolization of portal branches corresponding to 75% of total liver volume was performed successfully in all animals. Procedures were well tolerated, inducing moderate changes in portal pressure and transient aminotransferase increase. None of the animals developed portal vein thrombosis. After RPVE, complete recanalization occurred at day 11. RRPVE showed a trend for higher hypertrophy, the non-embolized liver to total liver ratio reaching 5.2 ± 1.0% in the RPVE group, 6.8 ± 0.1% in the RRPVE group and 5.0 ± 0.3% in the PPVE group.

Discussion/conclusion: In this preliminary comparative study, RRPVE was as feasible and as well tolerated as the other procedures, and resulted in higher liver hypertrophy.
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http://dx.doi.org/10.1159/000509713DOI Listing
October 2020

Experimental infection of calves with seven serotypes of Epizootic Hemorrhagic Disease virus: production and characterization of reference sera.

Vet Ital 2019 Dec 31;55(4):339-346. Epub 2019 Dec 31.

UMR Virologie, INRA, Ecole Nationale Vétérinaire d'Alfort, laboratoire de santé animale d'Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France.

The aim of this study was to produce reference sera against the seven serotypes of Epizootic hemorrhagic disease virus (EHDV‑1, EHDV‑2, EHDV‑4, EHDV‑5, EHDV‑6, EHDV‑7, and EHDV‑8). In a high containment unit, seven Prim 'Holstein calves were inoculated at day 0 (D0) with the selected strains (1 EHDV serotype per calf ). Blood samples (EDTA and whole blood) were periodically taken from D0 until the end of the experiment (D31). Sera were tested with two commercially available EHDV competitive ELISAs (c‑ELISA). Viral genome was detected from EDTA blood samples using in‑house real‑time RT‑PCR. Sera taken on D31 post infection (pi) were tested and characterized by serum neutralization test (SNT) and virus neutralization test (VNT) (for calibration of reference sera). Viral RNA was first detected at D2 pi in five calves. All infected animals were RT‑PCR positive at D7 pi. Seroconversion was observed between D10 and D23 pi depending on the EHDV serotype. SNT and VNT have allowed to determine the neutralizing antibody titers of each serum and the potential cross‑reactions between serotypes. The two c‑ELISA used in this study showed similar results. The calibrated sera are now available for the serological identification of an EHDV isolated on tissue culture or to be used as positive control in seroneutralization assay.
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http://dx.doi.org/10.12834/VetIt.2104.11179.1DOI Listing
December 2019

Vertical Bone Augmentation Using Ring Technique with Three Different Materials in the Sheep Mandible Bone.

Int J Oral Maxillofac Implants 2018 Sep/Oct;33(5):1057-1063

Purpose: The purpose of this study was to examine the volumetric alterations and osseointegration properties in the augmented area of the ring technique using different types of bone graft material in sheep mandible bone.

Materials And Methods: Three different materials (columnar forms, 7-mm diameter, 3-mm height) were stabilized using dental implants with a turned surface in the mandible bone of Finnish Dorset cross-bred sheep: group A, autogenous bone; group B, bovine bone; group C, biphasic bone substitute. Animals were euthanized after 5 weeks (N = 6). Three-dimensional image data by digital oral scanner were taken at the surgery and sacrifice, and the volume alteration of the material was calculated. The bone samples were fixed in formalin and dehydrated in ethanol. Resin-embedded samples were subjected to non-decalcified ground sectioning, and histologic and histomorphometric analysis (bone and material area alteration, bone-to-implant contact [BIC]) were done.

Results: In three-dimensional (3D) image analysis, group A showed a statistically higher percentage of remaining materials compared with groups B and C. The histologic observation showed no new bone formations around the implants in all groups, especially at the maxillary site of the implant in the augmented area. In histomorphometric analysis, group A showed a statistically higher percentage of bone area (BA) compared with groups B and C; however, in all groups, bone-to-implant contact (BIC) showed low values, and there were no statistical differences between groups.

Conclusion: The results of this study suggested that the autogenous bone maintained bone volume around the dental implant using the ring technique, and the impact of surface properties was of some importance; osseointegration with the turned surface in the augmented area showed low BIC values in all groups.
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http://dx.doi.org/10.11607/jomi.6278DOI Listing
November 2018

Efficacy and Pharmacokinetics Evaluation of a Single Oral Dose of Afoxolaner against Sarcoptes scabiei in the Porcine Scabies Model for Human Infestation.

Antimicrob Agents Chemother 2018 09 27;62(9). Epub 2018 Aug 27.

Research Group Dynamyc, EA7380, Université Paris-Est Créteil, Créteil, France.

Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and either treated with 2.5 mg/kg single dose oral AFX ( = 4) or 0.2 mg/kg, two doses 8 days apart, oral ivermectin ([IVM] = 4) or not treated for scabies ( = 4). The response to treatment was assessed by the reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetics profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 posttreatment and remained unchanged until the study end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at the study end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1 ± 2.4 and 1.1 ± 0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2 ± 16.9 and 2.7 ± 0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed remarkably long MRTs in plasma and, notably, in the skin.
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http://dx.doi.org/10.1128/AAC.02334-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125498PMC
September 2018

Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.

Vaccine 2017 07 29;35(33):4262-4269. Epub 2017 Jun 29.

Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom. Electronic address:

African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV.
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http://dx.doi.org/10.1016/j.vaccine.2017.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518735PMC
July 2017

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

PLoS Negl Trop Dis 2016 Oct 12;10(10):e0005030. Epub 2016 Oct 12.

APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France.

Background: Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative.

Methodology/principal Findings: Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy.

Conclusions/significance: Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.
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http://dx.doi.org/10.1371/journal.pntd.0005030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061321PMC
October 2016

The Effect of Laser-Etched Surface Design on Soft Tissue Healing of Two Different Implant Abutment Systems: An Experimental Study in Dogs.

Int J Periodontics Restorative Dent 2016 Sep-Oct;36(5):673-9

This study describes the early soft tissue morphology around two different implant systems that received either smooth or laser-etched abutments in a beagle dog model. Implants were placed in the healed mandibular molar region of eight beagle dogs and allowed to heal for 7 weeks. When the most apical aspect of the junctional epithelium (JE) was above or within the upper half of the laser-etched region, fibers were oriented perpendicular to the abutment surface. In contrast, JE positioned within the lower half of the laser-etched region or within or below the implant-abutment gap level presented fibers oriented parallel to the abutment surface.
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http://dx.doi.org/10.11607/prd.2940DOI Listing
October 2017

Guidelines for Clinical Management of Laser-Etched (Laser-Lok) Abutments in Two Different Clinical Scenarios: A Preclinical Laboratory Soft Tissue Assessment Study.

Int J Periodontics Restorative Dent 2016 May-Jun;36(3):339-45

One-stage implants were placed in the mandibles of eight beagle dogs with laser-etched (LL) and machined abutments. After 4 weeks, half of the LL abutments were disconnected and reconnected after 10 minutes of saline storage, and the other half were replaced with a new LL abutment (impression simulation) with or without sulcus de-epithelialization. After abutment change, systems remained in vivo for 3 weeks. Results showed that LL abutments can be reconnected and that sulcus scoring prior to LL placement of one-stage implants receiving machined abutments may be beneficial.
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http://dx.doi.org/10.11607/prd.2773DOI Listing
September 2017

Microrobotized blasting improves the bone-to-textured implant response. A preclinical in vivo biomechanical study.

J Mech Behav Biomed Mater 2016 Mar 24;56:175-182. Epub 2015 Nov 24.

Department of Prosthodontics, University of Sao Paulo - Bauru College of Dentistry, Alameda Otávio Pinheiro Brisola 9-75, Bauru, SP 17.012-901, Brazil. Electronic address:

This study evaluated the effect of microrobotized blasting of titanium endosteal implants relative to their manually blasted counterparts. Two different implant systems were utilized presenting two different implant surfaces. Control surfaces (Manual) were fabricated by manually grit blasting the implant surfaces while experimental surfaces (Microblasted) were fabricated through a microrobotized system that provided a one pass grit blasting routine. Both surfaces were created with the same ~50µm average particle size alumina powder at ~310KPa. Surfaces were then etched with 37% HCl for 20min, washed, and packaged through standard industry procedures. The surfaces were characterized through scanning electron microscopy (SEM) and optical interferometry, and were then placed in a beagle dog radius model remaining in vivo for 3 and 6 weeks. The implant removal torque was recorded and statistical analysis evaluated implant system and surface type torque levels as a function of time in vivo. Histologic sections were qualitatively evaluated for tissue response. Electron microscopy depicted textured surfaces for both manual and microblasted surfaces. Optical interferometry showed significantly higher Sa, Sq, values for the microblasted surface and no significant difference for Sds and Sdr values between surfaces. In vivo results depicted that statistically significant gains in biomechanical fixation were obtained for both implant systems tested at 6 weeks in vivo, while only one system presented significant biomechanical gain at 3 weeks. Histologic sections showed qualitative higher amounts of new bone forming around microblasted implants relative to the manually blasted group. Microrobotized blasting resulted in higher biomechanical fixation of endosteal dental implants and should be considered as an alternative for impant surface manufacturing.
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http://dx.doi.org/10.1016/j.jmbbm.2015.11.002DOI Listing
March 2016

Infection of Siberian chipmunks (Tamias sibiricus barberi) with Borrelia sp. reveals a low reservoir competence under experimental conditions.

Ticks Tick Borne Dis 2015 Apr 21;6(3):393-400. Epub 2015 Mar 21.

Unité Epidémiologie Animale (UR INRA 346), Centre de recherche INRA de Clermont-Ferrand/Theix, 63122 Saint Genès Champanelle, France. Electronic address:

Reservoir competence is a key parameter in understanding the role of host species in the epidemiology of multi-host-especially vector-borne-pathogens. With this aim in view, we studied the reservoir competence of the Siberian chipmunk (Tamias sibiricus barberi) recently introduced into Europe, for the multi-host tick-borne bacteria, Borrelia burgdorferi sl, the agent of Lyme borreliosis. T. sibiricus were experimentally exposed to bites from Ixodes ricinus ticks infected with Borrelia burgdorferi sensu stricto and Borrelia afzelii, with subsequent assessment of bacteremia and antibody responses. Borrelia was detected in chipmunk blood samples, ear biopsies and organ necropsies, and in nymphs used for xenodiagnosis (at one and six months after the initial chipmunk infection) via both serological and molecular methods. In total, eight out of twelve chipmunks showed evidence of infection by Borrelia sp., either by ELISA or PCR. Five chipmunks developed an immune response against the bacteria one month after infection. Borrelia infection in at least one organ was observed in seven animals at 14, 38, 93 or 178 days post-infection. Xenodiagnosis was positive for one chipmunk at 38 days, but no longer at 178 days post-infection. Four chipmunks remained uninfected, despite similar infection pressures to those observed in the field. Taken together, these results suggest that chipmunks can be infected through Borrelia-infected tick bites, and can transmit Borrelia to nymphs, but do not remain persistently infected.
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http://dx.doi.org/10.1016/j.ttbdis.2015.03.008DOI Listing
April 2015

Evaluation of adaptive immune responses and heterologous protection induced by inactivated bluetongue virus vaccines.

Vaccine 2015 Jan 11;33(4):512-8. Epub 2014 Dec 11.

ANSES, UMR 1161 Virologie ANSES-INRA-ENVA, 23 avenue du Général de Gaulle, 94704 Maisons-Alfort, France.

Eradication of bluetongue virus is possible, as has been shown in several European countries. New serotypes have emerged, however, for which there are no specific commercial vaccines. This study addressed whether heterologous vaccines would help protect against 2 serotypes. Thirty-seven sheep were randomly allocated to 7 groups of 5 or 6 animals. Four groups were vaccinated with commercial vaccines against BTV strains 2, 4, and 9. A fifth positive control group was given a vaccine against BTV-8. The other 2 groups were unvaccinated controls. Sheep were then challenged by subcutaneous injection of either BTV-16 (2 groups) or BTV-8 (5 groups). Taken together, 24/25 sheep from the 4 experimental groups developed detectable antibodies against the vaccinated viruses. Furthermore, sheep that received heterologous vaccines showed significantly reduced viraemia and clinical scores for BTV-16 when compared to unvaccinated controls. Reductions in clinical signs and viraemia among heterologously vaccinated sheep were not as common after challenge with BTV-8. This study shows that heterologous protection can occur, but that it is difficult to predict if partial or complete protection will be achieved following inactivated-BTV vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2014.11.053DOI Listing
January 2015

α-Hemolysin, not Panton-Valentine leukocidin, impacts rabbit mortality from severe sepsis with methicillin-resistant Staphylococcus aureus osteomyelitis.

J Infect Dis 2014 Jun 26;209(11):1773-80. Epub 2013 Dec 26.

Département de Médecine Aigüe Spécialisée, Hôpital Universitaire Raymond-Poincaré, Assistance Publique-Hôpitaux de Paris, Garches.

Background: Severe sepsis, combining acute osteomyelitis and lung involvement, has been described increasingly in healthy children with the spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).

Methods: Outcomes (mortality, hematogenous spread, lung and bone involvements) of rabbit osteomyelitis caused by CA-MRSA LAC(WT) USA300 and its Panton-Valentine leukocidin (PVL)- and α-hemolysin (Hla)-negative isogenic derivatives (LACΔpvl and LACΔhla, respectively) were compared.

Results: Three days after inoculation (D3), all LAC(WT)- and LACΔpvl-, and 72% of LACΔhla-infected rabbits had no hematogenous spread and similar lung and bone bacterial densities. LACΔpvl and LACΔhla caused less severe histological lung lesions than LAC(WT) (P ≤ .01). Between D3 and D9, 10 (53%) LAC(WT)-, 11 (55%) LACΔpvl-, but no LACΔhla-infected rabbits (P < .005) died of severe sepsis with disseminated infection. Unlike deceased animals, most LAC(WT), LACΔpvl, and LACΔhla D14 survivors had no hematogenous spread (P < .001). LAC(WT) (88%) caused more bone abscesses than LACΔpvl (0, P = .001) or LACΔhla (30%, P = .01).

Conclusion: In this model, both PVL and Hla seemed to be required for early lung involvement via hematogenous spread. Hla, but not PVL, significantly impacted severe sepsis-related mortality. PVL was the predominant factor determining late-stage bone abscesses.
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http://dx.doi.org/10.1093/infdis/jit840DOI Listing
June 2014

Comparison of the neuropathology induced by two West Nile virus strains.

PLoS One 2013 18;8(12):e84473. Epub 2013 Dec 18.

Virology (UMR1161), French National Institute for Agricultural Research (INRA), Maisons-Alfort, France ; Virology (UMR1161), French Agency for Food, Environmental and Occupational Health and Safety (ANSES), Maisons-Alfort, France ; Virology (UMR1161), Paris-Est University, National Veterinary School of Alfort, Maisons-Alfort, France.

Some strains of West Nile virus (WNV) are neuroinvasive and may induce fatal encephalitis/meningitis in a variety of animal species including humans. Whether, however, there is a strain-specific signature in the brain is as yet unknown. Here we investigated the neuropathogenesis induced by two phylogenetically distant WNV strains of lineage 1, WNV(IS98) and WNV(KUN35 911). While four-week old C57Bl/6J mice were susceptible to both strains and succumbed rapidly after intraperitoneal inoculation, differences were observed in virulence and clinical disease. WNV(KUN35 911), the less virulent strain as judged by determination of LD50, induced typical signs of encephalitis. Such signs were not observed in WNV(IS98)-infected mice, although they died more rapidly. Histological examination of brain sections also revealed differences, as the level of apoptosis and inflammation was higher in WNV(KUN35 911)- than WNV(IS98)-infected mice. Moreover, staining for cleaved caspase 3 showed that the two WNV strains induced apoptotic death through different molecular mechanisms in one particular brain area. Finally, the two strains showed similar tropism in cortex, striatum, brainstem, and cerebellum but a different one in hippocampus. In summary, our data show that, upon peripheral administration, WNV(IS98) and WNV(KUN35 911) strains induce partially distinct lesions and tissue tropism in the brain. They suggest that the virulence of a WNV strain is not necessarily correlated with the severity of apoptotic and inflammatory lesions in the brain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084473PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867487PMC
October 2014

The "Skull Flap" a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion.

J Neurosci Rural Pract 2013 Oct;4(4):421-6

Department of Neurosurgery, Strasbourg University Hospital, Strasbourg, Paris, France.

Background: Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The "Skull Flap" (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device.

Materials And Methods: This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed.

Results: SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group.

Conclusion: The SF device has proved to be very easy to place, well-adaptable to a different type of flaps and ultimately very effective in maintaining satisfactory brain decompression and later on, making easy bone flap repositioning after brain swelling has subsided.
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http://dx.doi.org/10.4103/0976-3147.120244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858761PMC
October 2013

Simplified drilling technique does not decrease dental implant osseointegration: a preliminary report.

J Periodontol 2013 Nov 5;84(11):1599-605. Epub 2012 Dec 5.

Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.

Background: To date, some experimental studies have addressed the effect of bone drilling technique and sequence on dental implant osseointegration. In the present study, the authors hypothesize that there would be no differences in osseointegration when reducing the number of drills for osteotomy compared to the conventional drilling protocols.

Methods: Seventy-two implants (diameters 3.75 mm and 4.2 mm; n = 36 for each diameter) were bilaterally placed in the tibia of 18 beagles for 1, 3, and 5 weeks. Half of the implants of each diameter were placed using a simplified drilling procedure (pilot and final drill), and the other half were placed using a conventional drilling procedure (all drills in sequence). The retrieved samples were subjected to histologic and histomorphometric evaluation.

Results: Histology showed that new bone formed around the implant, and inflammation or bone resorption was not evident for both groups. Histomorphometrically, the simplified group presented significantly higher bone-to-implant contact and bone area fraction occupancy compared to the conventional group after 1 week; however, no differences were detected at 3 and 5 weeks.

Conclusion: Bone responses to the implant with the simplified protocol can be comparable to the conventional protocol.
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http://dx.doi.org/10.1902/jop.2012.120565DOI Listing
November 2013

Evaluation of collagen-based membranes for guided bone regeneration, by three-dimensional computerized microtomography.

Oral Surg Oral Med Oral Pathol Oral Radiol 2012 Oct 21;114(4):437-43. Epub 2012 Jul 21.

Department of Biomaterials and Biomimetics, New York University, New York, NY, USA.

Objective: The aim of this study was to evaluate the use of a collagen-based membrane compared with no treatment on guided bone regeneration by 3-dimensional computerized microtomography (μCT).

Study Design: Defects were created between the mesial and distal premolar roots of the second and third premolars (beagle dogs; n = 8). A collagen-based membrane (Vitala; Osteogenics Biomedical Inc., TX, USA) was placed in one of the defects (membrane group; n = 16), and the other was left untreated (no-membrane group; n = 16). Left and right sides provided healing samples for 2 and 16 weeks. Three-dimensional bone architecture was acquired by μCT and categorized as fully regenerated (F, bone height and width) or nonregenerated (N).

Results: Chi-square tests (95% level of significance) showed that tooth did not have an effect on outcome (P = .5). Significantly higher F outcomes were observed at 16 weeks than 2 weeks (P = .008) and in membrane group than in no-membrane group (P = .008).

Conclusions: The collagen-based membrane influenced bone regeneration at the furcation.
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http://dx.doi.org/10.1016/j.oooo.2011.11.032DOI Listing
October 2012

Assessment of a chair-side argon-based non-thermal plasma treatment on the surface characteristics and integration of dental implants with textured surfaces.

J Mech Behav Biomed Mater 2012 May 31;9:45-9. Epub 2012 Jan 31.

Department of Biomaterials and Biomimetics, New York University, New York, NY 10010, USA.

The biomechanical effects of a non-thermal plasma (NTP) treatment, suitable for use in a dental office, on the surface character and integration of a textured dental implant surface in a beagle dog model were evaluated. The experiment compared a control treatment, which presented an alumina-blasted/acid-etched (AB/AE) surface, to two experimental treatments, in which the same AB/AE surface also received NTP treatment for a period of 20 or 60 s per implant quadrant (PLASMA 20' and PLASMA 60' groups, respectively). The surface of each specimen was characterized by electron microscopy and optical interferometry, and surface energy and surface chemistry were determined prior to and after plasma treatment. Two implants of each type were then placed at six bilateral locations in 6 dogs, and allowed to heal for 2 or 4 weeks. Following sacrifice, removal torque was evaluated as a function of animal, implant surface and time in vivo in a mixed model ANOVA. Compared to the CONTROL group, PLASMA 20' and 60' groups presented substantially higher surface energy levels, lower amounts of adsorbed C species and significantly higher torque levels (p=.001). Result indicated that the NTP treatment increased the surface energy and the biomechanical fixation of textured-surface dental implants at early times in vivo.
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http://dx.doi.org/10.1016/j.jmbbm.2012.01.012DOI Listing
May 2012

Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis.

PLoS One 2009 Sep 25;4(9):e7204. Epub 2009 Sep 25.

Département de médecine aigüe, Hôpital Universitaire Raymond Poincaré, Assistance Publique-Hôpitaux de Paris, Garches, France.

Background: Extensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection.

Methodology/principal Findings: We compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACDeltapvl), using a low and a high inoculum (8x10(5) and 4x10(8) CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDeltapvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACDeltapvl but not with LAC. Respectively 67% and 60% of LAC-infected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACDeltapvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC.

Conclusions/significance: PVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007204PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744873PMC
September 2009

Transmission of Bartonella henselae by Ixodes ricinus.

Emerg Infect Dis 2008 Jul;14(7):1074-80

Institut National de la Recherche Agronomique, Maisons-Alfort, France.

Bartonella spp. are facultative intracellular bacteria associated with several emerging diseases in humans and animals. B. henselae causes cat-scratch disease and is increasingly associated with several other syndromes, particularly ocular infections and endocarditis. Cats are the main reservoir for B. henselae and the bacteria are transmitted to cats by cat fleas. However, new potential vectors are suspected of transmitting B. henselae, in particular, Ixodes ricinus, the most abundant ixodid tick that bites humans in western Europe. We used a membrane-feeding technique to infect I. ricinus with B. henselae and demonstrate transmission of B. henselae within I. ricinus across developmental stages, migration or multiplication of B. henselae in salivary glands after a second meal, and transmission of viable and infective B. henselae from ticks to blood. These results provide evidence that I. ricinus is a competent vector for B. henselae.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600320PMC
http://dx.doi.org/10.3201/eid1407.071110DOI Listing
July 2008

Bax deletion does not protect neurons from BSE-induced death.

Neurobiol Dis 2006 Sep 18;23(3):603-11. Epub 2006 Jul 18.

UMR Virologie 1161 INRA-AFSSA-ENVA, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France.

Neurodegeneration is a common neuropathological feature of prion diseases. Although evidence of apoptosis was found in natural and experimental prion diseases, the precise mechanisms by which neurons die are poorly understood. The pro-apoptotic BAX protein, a key factor of the mitochondrial pathway, plays a central role in the regulation of neuronal apoptosis. Recently, BAX was implicated in neuronal death in a transgenic model of inherited prion disease. Nevertheless, whether neurodegeneration occurs by similar mechanisms in other prion diseases remains unknown. Here, using mice knocked out for the Bax gene, we investigated BAX implication in neuronal death induced by a prion disease of infectious origin. A mouse-adapted prion strain of bovine spongiform encephalopathy (BSE) was inoculated intracerebrally into Bax-/- mice and their wild-type littermates. We found that Bax inactivation did not alter the development of the disease. Clinical illness was not prevented. PrP(res) deposition and astrogliosis occurred to the usual extent. Neuronal integrity was not maintained, and neurons in hippocampus and thalamus were not protected. These results demonstrated that BAX is not necessary for neuron death induced by the BSE strain. They suggest the existence of multiple molecular death pathways in prion diseases.
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http://dx.doi.org/10.1016/j.nbd.2006.05.013DOI Listing
September 2006

Establishment and characterization of continuous hematopoietic progenitors-derived pig normal mast cell lines.

Life Sci 2005 Jul;77(7):808-23

UMR-BIPAR, INRA-ENVA-AFSSA-Paris XII, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons Alfort cedex, France.

Mast cells (MCs) are tissue resident, hematopoietic stem cells-derived elements, distributed throughout the body. They are the pivotal mediating cells of allergic reactions. In addition, in mice, MCs play a critical role in the defense against several pathogens, such as bacteria, parasites and viruses. Whereas the biology of rodent and human MCs has been extensively studied using in vitro derived populations, the role of MCs in pigs has not yet been evaluated, given the very low availability of pure porcine MCs populations. In the present report, we describe an original method to obtain continuous factor-dependent normal pig MCs (PMC) lines from fetal hematopoietic progenitors. These Stem Cell Factor (SCF) and Interleukin-3- (IL-3)-dependent PMC lines retain their capacity to growth after conventional freezing methods and exhibit most of the morphological and biochemical properties of normal, although immature, MCs, including metachromatic granules containing sulfated polysaccharides, the expression of c-kit and high-affinity IgE receptors (FcepsilonRI), and the ability to store histamine that is released upon cross-linking of FcepsilonRI. In vitro derived PMC lines might thus be valuable tools to further investigate the reactivity of these elements towards several parasites frequently encountered in pig, such as, but not limited to, Ascaris suum, Trichinella spiralis or Trichuris suis, or towards antigens derived from these pathogens.
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http://dx.doi.org/10.1016/j.lfs.2005.01.017DOI Listing
July 2005