The pig as a model system for investigating the recruitment and contribution of myofibroblasts in skin healing.

In the skin-healing field, porcine models are regarded as a useful analogue for human skin due to their numerous anatomical and physiological similarities. Despite the widespread use of porcine models in skin healing studies, the initial origin, recruitment and transition of fibroblasts to matrix-secreting contractile myofibroblasts are not well defined for this model. In this review, we discuss the merit of the pig as an animal for studying myofibroblast origin, as well as the challenges associated with assessing their contributions to skin healing. Although a variety of wound types (incisional, partial thickness, full thickness, burns) have been investigated in pigs in attempts to mimic diverse injuries in humans, direct comparison of human healing profiles with regards to myofibroblasts shows evident differences. Following injury in porcine models, which often employ juvenile animals, myofibroblasts are described in the developing granulation tissue at 4 days, peaking at Days 7-14, and persisting at 60 days post-wounding, although variations are evident depending on the specific pig breed. In human wounds, the presence of myofibroblasts is variable and does not correlate with the age of the wound or clinical contraction. Our comparison of porcine myofibroblast-mediated healing processes with those in humans suggests that further validation of the pig model is essential. Moreover, we identify several limitations evident in experimental design that need to be better controlled, and standardisation of methodologies would be beneficial for the comparison and interpretation of results. In particular, we discuss anatomical location of the wounds, their size and depth, as well as the healing microenvironment (wet vs. moist vs. dry) in pigs and how this could influence myofibroblast recruitment. In summary, although a widespread model used in the skin healing field, further research is required to validate pigs as a useful analogue for human healing with regards to myofibroblasts.

Image-based design and 3D-metal printing of a rat hip implant for use in a clinically representative model of joint replacement.

The aim of this study was to obtain micro-computed tomography derived measurements of the rat proximal femur, to create parameterized rat hip implants that could be surgically installed in a clinically representative small animal model of joint replacement. The proximal femoral anatomy of N = 25 rats (male, Sprague-Dawley, 390-605 g) was quantified. Key measurements were used to parameterize computer-aided design models of monoblock rat femoral implants. Linear regression analysis was used to determine if rat hip dimensions could be predicted from animal weight. A correlation analysis was used to determine how implants could be scaled to create a range of sizes. Additive manufacturing (3D printing) was used to create implants in medical-grade metal alloys. Linear regressions comparing rat weight to femoral head diameter and neck-head axis length revealed a significant nonzero slope (P < .05). Pearson's correlation analysis revealed five significant correlations between key measurements in the rat femur (P < .05). Implants were installed into both cadaveric and live animals; iterative design modifications were made to prototypes based on these surgical findings. Animals were able to tolerate the installation of implants and were observed ambulating on their affected limbs postoperatively. Clinical significance: We have developed a preclinical rat hip hemiarthroplasty model using image-based and iterative design techniques to create 3D-metal printed implants in medical-grade metal alloys. Our findings support further development of this model for use as a low-cost translational test platform for preclinical orthopaedic research into areas such as osseointegration, metal-on-cartilage wear, and periprosthetic joint infection.

Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.

Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (Macaca fascicularis). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4+ and CD8+ T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).

In-vivo characterization of left-ventricle pressure-volume telemetry system in swine model.

We present in-vivo study related to the use of our implantable RF telemetry system for pressure-volume (PV) cardiac monitoring in a animal subject. We implant a commercial MEMS PV sensor into the subject's heart left-ventricle (LV), while the telemetry system is implanted outside of the heart and connected to the sensor with a 7-microwires tether. The RF telemetry system is suitable for commercial application in medium sized subjects, its total volume of 2.475cm(3) and a weight of 4.0g. Our designed system is 58 % smaller in volume, 44 % in weight and has a 55 % reduction in sampling power over the last reported research in PV telemetry. In-vivo data was captured in both an acute and a freely moving setting over a 24 hour period. We experimentally demonstrated viability of the methodology that includes the surgical procedure and real-time monitoring of the in-vivo data in a freely moving subject. Further improvements in catheter design will improve the data quality and safety of the subject. This real-time implantable technology allows for researchers to quantify cardiac pathologies by extracting real-time pressure-volume loops, wirelessly from within freely moving subjects.

Bridging Plate Development for Treatment of Segmental Bone Defects of the Canine Mandible: Mechanical Tests and Finite Element Method.

With regard to the canine mandible, a mistaken concept of application is to assume that systemic plate-bone resistance is provided by the implant so that biomechanical position could be ignored. Because the alveolar border of the mandible is a tensile zone, the plate would ideally be positioned near this area while avoiding important structures. The aim of this study was to develop 2 bridging plates for the treatment of a segmental bone defect of the canine mandible using monocortical screws to avoid damage to the tooth roots and remaining neurovascular structures. Computed tomography images of the heads of 4 dogs (rottweiler, Doberman, boxer, and miniature poodle breeds) were used as models to develop the project. The images were reconstructed in 3-dimensional (3D) format. For each dog breed, 6 mandible prototypes were produced, each with a segmental bone defect in the right mandible. The mandibular reconstruction was performed with pure titanium bridging plate and locking screws. One plate model was developed for medium- and large-breed dogs and another for small-breed dogs. Mechanical testing showed the platemandible system resists the bite forces in all dog breeds. All safety factors were greater than I in the platemandible system for medium- and large-breed dogs and greater than 10 in the plate-mandible system for small-breed dogs. Thus, bridging plates designed with differentiated geometry and monocortical locking screws showed mechanical resistance to support simulated induced bone model defects and were able to support at least 5 times the value of bite force for each evaluated dog.

Comparative study of 2 surgical techniques for castration of guinea pigs (Cavia porcellus).

The objective of this study was to compare 2 surgical approaches (scrotal or abdominal) for castration of guinea pigs and to investigate post-operative infection rates with either technique. Forty-eight guinea pigs were castrated by scrotal or abdominal technique after being randomly assigned to 1 of 2 groups (n = 24). Individuals were either castrated by an experienced exotic animal surgeon (n = 12) or by an experienced small animal surgeon (n = 12). Surgical wounds were evaluated daily before euthanasia for histological evaluation 2 wks after surgery. Post-operative infection rate was significantly higher in the scrotal group than in the abdominal group, with a higher rate for the experienced small animal surgeon. Castration of guinea pigs with the abdominal technique is significantly faster and has a significantly lower post-operative infection rate than the scrotal technique.

Cette étude avait pour objectif de comparer 2 approches chirurgicales (scrotale vs abdominale) pour la castration du cobaye (Cavia porcellus). Quarante-huit cobayes ont été castrés avec la technique scrotale ou abdominale après avoir été assignés de façon aléatoire à l'un des deux groupes (n = 24). La moitié des individus ont été castrés par un chirurgien d'expérience en pratique des animaux exotiques (n = 12) et l'autre moitié par un chirurgien d'expérience en pratique des animaux de compagnie (n = 12). Les plaies de chirurgie ont été évaluées quotidiennement avant que les cobayes ne soient euthanasiés pour examen histopathologique des plaies 2 semaines post-chirurgie. La prévalence d'infection post-opératoire était significativement plus élevée avec la technique scrotale comparativement à la technique abdominale, et le taux d'infection était plus élevé pour le chirurgien d'expérience en pratique des animaux de compagnie. La castration de cobaye avec la technique abdominale est de plus courte durée et est associée à un taux d'infection post-opératoire moins élevé comparativement à la technique scrotale.(Traduit par les auteurs).

Anti-inflammatory response of dietary vitamin E and its effects on pain and joint structures during early stages of surgically induced osteoarthritis in dogs.

There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1ß) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.

La vitamine E (VE) est connue par ses propriétés anti-inflammatoires et analgésiques dans le traitement de l'ostéoarthrose (OA) chez l'humain. Dans notre étude pilote nous avons utilisé un ensemble de paramètres cliniques et de laboratoire afin de déterminer si ces effets bénéfiques de la VE pourront être détectés chez le chien arthrosique, dans un modèle expérimental d'OA. Les chiens utilisés ont été divisés en 2 groupes: témoin (n = 8), qui a reçu un placebo et un groupe supplémenté (n = 7), qui a reçu 400 UI de VE/animal/jour pendant 55 jours, la supplémentation orale a commencé un jour après la section du ligament croisé crânial. Avant la chirurgie (J0), J28 et J55 après chirurgie, la boiterie et la douleur ont été évaluées à l'aide d'une échelle visuelle analogique (EVA), d'une échelle d'évaluation numérique (NRS), et par la mesure de l'activité électrodermique (EDA). Les lésions au niveau du cartilage et l'inflammation synoviale ont été évalués. Une seule comparaison statistique a été réalisée avec un seuil alpha à 10 %. Au jour 56, les chiens ont été euthanasiés et les concentrations de prostaglandine E2 (PGE2), d'oxyde d'azote (NOx) et d'interleukine-1 bêta (IL-1ß) ont été mesurées dans le liquide synovial. Les concentrations synoviales de NOx et de PGE2 étaient plus faibles dans le groupe traité (P < 0,0001 et P = 0,03, respectivement). Les valeurs de l'EVA, de NRS et de l'EDA ont montré une tendance constante à être plus faible dans le groupe traité par comparaison au groupe témoin, avec un effet significatif de la VE qui a été observé pour VAS au jour 55 et EDA au jour 28 (P ajustée = 0,07 dans les deux cas). Les analyses histologiques du cartilage ont montré une réduction significative des scores lésionnels chez le groupe traité. Cette étude est la première à démontrer qu'une supplémentation orale avec une dose élevée de VE chez des chiens arthrosiques permet de réduire la libération des marqueurs inflammatoires et les lésions histologiques au niveau du cartilage, ainsi qu'une tendance à améliorer les signes de douleur.(Traduit par Docteur Serge Messier).

Effects of sterilization with hydrogen peroxide gas plasma, ethylene oxide, and steam on bioadhesive properties of nylon and polyethylene lines used for stabilization of canine stifle joints.

OBJECTIVE: To compare effects of sterilization with hydrogen peroxide gas plasma (HPGP), ethylene oxide, and steam on bioadhesive properties of nylon and polyethylene lines used for stabilization of canine stifle joints. SAMPLE: Samples of a 36.3-kg test nylon leader line, 57.8-kg test nylon fishing line, and 2-mm ultrahigh-molecular weight polyethylene (UHMWPE) were used. PROCEDURES: In this in vitro study, samples of nylon leader line, fishing line, and UHMWPE sterilized by use of HPGP, ethylene oxide, and steam or unsterilized samples were used. Bacterial adherence on unsterilized and sterilized samples was tested with Staphylococcus epidermidis and Escherichia coli. Five samples were examined for each line type and sterilization condition, and final colony counts were obtained. RESULTS: Bacterial adherence was significantly affected by method of sterilization for all 3 line types. For most of the samples, bacterial adherence was similar or lower when HPGP sterilization was used, compared with results for sterilization via ethylene oxide and steam, respectively. Bacterial adherence was significantly higher for UHMWPE, compared with adherence for the nylon line, regardless of the sterilization method used. Bacterial adherence was higher for nylon fishing line than for nylon leader line for S epidermidis after ethylene oxide sterilization and for E coli after HPGP and ethylene oxide sterilization. CONCLUSIONS AND CLINICAL RELEVANCE: Effects of HPGP sterilization on bioadhesive properties of nylon and polyethylene lines compared favorably with those for ethylene oxide and steam sterilization. Also, nylon line may be a more suitable material than UHMWPE for suture prostheses on the basis of bacterial adherence properties.

Gait analysis in clinically healthy sheep from three different age groups using a pressure-sensitive walkway.

BACKGROUND: Understanding normal gait requires allowing for variations in normal patterns by the sex, age, and species in question. Therefore, the aim of this study was to evaluate kinetic and temporospatial parameters in clinically healthy sheep from three different age groups with a pressure-sensing walkway. The sheep were judged to be healthy based on the results of complete physical and orthopaedic examinations and had no history of lameness. Twenty-one clinically healthy female Santa Ines sheep were divided into three groups: G1 - seven animals, aged from 8 to 12 months and weighing 19.5-33 kg; G2 - seven individuals, aged from 2 to 4 years and weighing 26.5-42 kg; and G3 - seven sheep, aged more than 5 years and weighing 37.3-45 kg. The animals were examined from two directions: first on the left side and then on the right side of the handler. The data from the first five valid trials in each direction were collected for each sheep and analysed using the designated software. A trial was considered valid if the sheep walked within the correct velocity (1.1-1.3 m/s) and acceleration (from -0.15 to 0.15 m/s2) ranges. The peak vertical force (PVF), vertical impulse (VI), gait cycle time, stance time, swing time, stride length, and the percentage body weight distribution among the four limbs were determined. RESULTS: No significant differences were observed, in either the forelimbs or the hind limbs, between the left and right sides or between the two directions for any of the variables. No significant temporospatial differences were found among the groups. Significant PVF (%BW) differences were observed in the forelimbs (G1>G3) and hind limbs (G1>G3), and significant VI differences were observed in the forelimbs (G1>G3). CONCLUSIONS: Young healthy sheep differ from older sheep in the vertical forces they create when walking at the same velocity on a pressure-sensing walkway.

Measurement of vitamin A, vitamin E, selenium, and L-lactate in dogs with and without osteoarthritis secondary to ruptured cranial cruciate ligament.

This study compared vitamin A, vitamin E, selenium (Se), and L-lactate in blood and synovial fluid in 2 groups of 6 dogs; a control group (without OA) and an osteoarthritic group with spontaneous cranial cruciate ligament rupture and OA. Concentrations of vitamin E were significantly higher in serum than in synovial fluid in both OA (P = 0.006) and control (P = 0.0008) groups. Vitamin E concentration in synovial fluid was significantly higher in the OA group than in the control group (P = 0.009). Concentrations of Se were significantly higher in serum than in synovial fluid in both OA (P = 0.003) and control (P = 0.0006) groups. There were no significant differences in levels of Se, vitamin A, and L-lactate between the 2 groups. This is the first study to show an increased concentration of vitamin E in the synovial fluid of dogs with OA compared with dogs that did not have OA.

Mesure de la vitamine A, de la vitamine E, du sélénium et de L-lactate chez les chiens avec ou sans ostéo-arthrite causée par la rupture d'un ligament croisé crânial. Cette étude a comparé lesmesures de vitamine A, de vitamine E, de sélénium (Se) et de L-lactate dans le sang et le liquide synovial chez 2 groupes de 6 chiens; un groupe témoin (sans ostéo-arthrite) et un groupe atteint d'ostéo-arthrite présentant une rupture spontanée du ligament croisé crânial et de l'ostéo-arthrite. Les concentrations de vitamine E étaient significativement plus élevées dans le sérum que dans le liquide synovial du groupe atteint d'ostéo-arthrite OA (P = 0,006) et du groupe témoin (P = 0,0008). La concentration de vitamine E dans le liquide synovial était significativement supérieure dans le groupe atteint d'ostéo-arthrite que dans le groupe témoin (P = 0,009). Les concentrations de Se étaient significativement plus élevées dans le sérum que dans le liquide synovial du groupe atteint d'ostéo-arthrite (P = 0,003) et du groupe témoin (P = 0,0006). Il n'y avait pas de différences significatives dans les niveaux de Se, de vitamine A et de L-lactate entre les deux groupes. Il s'agit de la première étude pour démontrer une concentration accrue de vitamine E dans le liquide synovial des chiens atteints d'ostéo-arthrite comparativement à des chiens qui n'avaient pas l'ostéo-arthrite.(Traduit par Isabelle Vallières).

Clinical investigation of local implantation of gentamicin-impregnated collagen sponges in dogs.

The purpose of this study was to evaluate the effects on health and kidney function of local implantation of commercial gentamicin-impregnated collagen sponges. Four healthy dogs were submitted to local surgical implantation of collagen impregnated sponges. Follow-up with serial physical examinations and measurements of serum creatinine, urea nitrogen, and gentamicin were performed for 7 d. There were no adverse reactions, or changes in measurements of kidney function.

Atypical caudal duplication with phenotypic sex reversal in a dog.

A male German Shepherd Dog mix was presented for chronic non-weight-bearing lameness of the left hind limb. At clinical examination, the dog's left hind limb had severe joint contractures, with the presence of what appeared to be a second paw. The dog also had 2 sets of external genitalia of opposite phenotypic sex; a complete male reproductive tract with a left retained testicle and a right descended testicle, as well as rudimentary female external genitalia including a hypoplastic vulva with a blind-end vagina and a hypertrophied clitoris. The female genitalia were located on the proximal posterior third of the deformed limb. Following amputation of the hind limb, gross pathologic analysis revealed a duplication of the fibula, tarsal, and metatarsal bones, digits, and appendices. The supernumerary structures and female genitalia were concluded to represent a parasitic twin. As conjoined or parasitic twinning of non-identical twins is thought to be impossible, the presence of genitalia of opposite phenotypic sex appeared paradoxical. Polymerase chain reaction analyses were therefore performed to determine the genotypic sex of both animals, which revealed the presence of the Y chromosome in all tissues, including the female genitalia. The non-masculinization of the external genitalia in the parasitic twin was presumed to be the result of an embryonic developmental defect. On this basis, a diagnosis of atypical caudal duplication (parasitic twinning) with phenotypic sex reversal was made.

Finite element modeling for development and optimization of a bone plate for mandibular fracture in dogs.

This study aimed to develop a plate to treat fractures of the mandibular body in dogs and to validate the project using finite elements and biomechanical essays. Mandible prototypes were produced with 10 oblique ventrorostral fractures (favorable) and 10 oblique ventrocaudal fractures (unfavorable). Three groups were established for each fracture type. Osteosynthesis with a pure titanium plate of double-arch geometry and blocked monocortical screws of free angulation were used. The mechanical resistance of the prototype with unfavorable fracture was lower than that of the favorable fracture. In both fractures, the deflection increased and the relative stiffness decreased proportionally to the diminishing screw number The finite element analysis validated this plate study, since the maximum tension concentration observed on the plate was lower than the resistance limit tension admitted by the titanium. In conclusion, the double-arch geometry plate fixed with blocked monocortical screws has sufficient resistance to stabilize oblique fractures, without compromising mandibular dental or neurovascular structures.

Locked jaw syndrome in dogs and cats: 37 cases (1998-2005).

A consecutive series of cases of dogs and cats with locked jaw syndrome (inability to open or close the mouth) are reported in this study. Dogs were significantly overrepresented (84.0%) and adult dogs were more frequently affected (81.0%). Temporomandibular joint ankylosis due to fracture was the most common cause (54.0%) of locked jaw syndrome. Additional potential causes of locked jaw syndrome are masticatory muscle myositis, neoplasia, trigeminal nerve paralysis and central neurological lesions, temporomandibular joint luxation and dysplasia, osteoarthritis, retrobulbar abscess, tetanus, and severe ear disease. Treatment of locked jaw is directed towards the primary cause. It is important to treat the tonic spasm in order to minimize periarticular fibrosis. Surgical intervention is recommended for temporomandibular joint ankylosis. Masticatory muscle myositis treatment is initiated by gradually opening the mouth, with medical treatment based on immunosuppressive therapy. Fracture and masticatory muscle myositis are associated with a relatively good prognosis in regard to short-term outcome as compared to animals with central neurologic lesions or osteosarcoma which have a poor prognosis.

An animal model for interface tissue formation in cemented hip replacements.

OBJECTIVE: To create a model in sheep for investigation of early changes related to the formation of an interface membrane in hip prosthesis. STUDY DESIGN: Experimental study. ANIMALS: Twenty-four female adult Swiss Alpine sheep. METHODS: Sheep were divided into 2 groups of 12 for unilateral cemented total hip arthroplasty. In Group I, the prosthesis was fixed with retrograde cement gun injection to achieve a complete cement mantle, whereas in Group II a primary cement mantle defect was produced. Groups I and II were further divided into 2 sub-groups with study end points of 2 and 8.5 months after surgery. Radiographs were evaluated postoperatively and at euthanasia for migration of the femoral component and bone resorption. Histologic sections were evaluated semiquantitatively for changes in cell types and numbers, and bone reactions; and quantitatively for size of interface membrane and new bone formation. RESULTS: Radiographically, there tended to be an increase in bone resorption and periosteal bone formation throughout the femoral shaft in Group II compared with Group I, but this was only statistically significant at the region of the femoral neck (R5) at both time periods (P<.05). Semiquantitative histologic evaluation revealed significant increases (P<.05) in cellularity, numbers of fibroblasts, giant cells, macrophages, and mononuclear cells, in Group II primarily at 2 months after surgery. This was also true for interface membrane formation and bone remodeling. Quantitative data showed an increased in the size of the interface membrane and area of bone formation at 8.5 months in Group II. CONCLUSIONS: The cement defect model offered controlled and repeatable production of an interface membrane. The results suggest that a primary cement mantle defect could be a possible trigger for implant instability, eliciting a cascade of biomechanical and molecular events in bone tissue leading to aseptic loosening. CLINICAL RELEVANCE: The results show the effect of defects in the cement mantle in promoting interface membrane formation. Long-term and biochemical studies are required to evaluate the relevance of this interface membrane formation.

An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane.

BACKGROUND: Aseptic loosening of hip prosthesis as it occurs in clinical cases in human patients was attributed to wear particles of the implants, the response of the tissue dominated by macrophages and the production of inflammatory mediators and matrix degrading enzymes; however, the cascade of events initiating the process and their interaction regarding the time course is still open and discussed controversially. Therefore, the goal of this study was to establish an experimental animal model in sheep allowing to follow the cascade of early mechanical and biochemical events within the interface membrane and study the sequence of how they contribute to the pathological bone resorption necessary for aseptic loosening of the implant. METHODS: A cemented modular system (Biomedtrix) was used as a hip replacement in 24 adult Swiss Alpine sheep, with one group receiving a complete cement mantle as controls (n = 12), and the other group a cement mantle with a standardized, lateral, primary defect in the cement mantle (n = 12). Animals were followed over time for 2 and 8.5 months (n = 6 each). After sacrifice, samples from the interface membranes were harvested from five different regions of the femur and joint capsule. Explant cell cultures were performed and supernatant of cultures were tested and assayed for nitric oxide, prostaglandin E2, caseinolytic and collagenolytic activity. RNA extraction and quantification were performed for inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1, and interleukin 6. Overall differences between groups and time periods and interactions thereof were calculated using a factorial analysis of variance (ANOVA). RESULTS: The development of an interface membrane was noticed in both groups at both time points. However, in the controls the interface membrane regressed in thickness and biological activity, while both variables increased in the experimental group with the primary cement mantle defect over time. Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations. The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001). CONCLUSION: In this study, a primary cement mantle defect of the femoral shaft elicited biomechanical instability and biochemical changes over time in an experimental animal study in sheep, that resembled the changes described at the bone cement-interface in aseptic loosening of total hip prosthesis in humans. The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases. This animal model may aid in future studies aiming at prevention of aseptic loosening of hip prosthesis and reflect some aspects of the pathogenesis involved.

Tratamento homeopático da hepatotoxicose aguda induzida por tetracloreto de carbono em coelhos / Homeopatic treatment of acute carbon tetrachloride induced hepatotoxicity in rabbits

Quinze (15) coelhos (Oryctolagus cuniculus) foram submetidos à intoxicaçäo pelo tetracloreto de carbono na dosagem de 0,5 ml/kg de peso corporal, dose única, administrado por sonda gástrica. Foram realizadas as dosagens de alanina amino tranferase (ALT), aspartato amino transferase (AST), fosfatase alcalina (FA) e gama glutamil tranferase (GGT) antes e durante o experimento. Vinte e quatro (24) horas após a intoxicaçäo, os coelhos foram divididos aleatoriamente em três grupos de 5 animais. Cada grupo recebeu um tratamento diferente durante 13 dias. O grupo I foi tratado com tetracloreto de carbono diluído na 30ª centesimal hahnemanniana (30 CH), uma vez ao dia. O grupo II recebeu Phosphorus 30 CH, também uma vez ao dia. O grupo III desempenhou o papel de controle, recebendo diariamente uma dose de placebo, pelo mesmo período de tempo que os grupos anteriores. Os resultados das concentraçöes séricas de ALT, AST, GGT e FA foram submetidos à análise estatística. A variaçäo da concentraçäo de todas as enzimas foi significativa entre os dias, mas nem todas variaram significativamente entre os grupos considerados. O tetracloreto de carbono 30 CH foi capaz de acelerar a recuperaçäo do quadro de hepatite tóxica aguda determinada pela reduçäo dos níveis de ALT. O tratamento com Phosphorus 30 CH mostrou-se incapaz seja de reverter o quadro de hepatite tóxica, seja de acelerar a regeneraçäo hepática.

Osteossíntese diafisiária de tíbia em cäes mediante inserçäo intramedular de pinos de Steinmann pela crista tibial / Canine tibial osteosynthesis by the use of intramedullary Steinmann pins through the tibial crest insertion

As fraturas diafisárias de tíbia possuem alta prevalência na espécie canina. Este estudo visa avaliar o uso de pinos intramedulares de Steinmann na reduçäo destas fraturas. Dez cäes de idade, sexo e peso variados, portadores de fratura de tíbia foram submetidos à osteossíntese mediante inserçäo de dois pinos intramedulares de Steinmann pela crista tibial e em seguida, avaliados clinicamente e radiograficamente durante o período de cicatrizaçäo óssea. Diante dos resultados, demonstrou-se a versatilidade e eficiência do método.