Wolbachia, doxycycline and macrocyclic lactones: New prospects in the treatment of canine heartworm disease.

Melarsomine dihydrochloride (Immiticide®, Merial) is the only approved adulticidal drug for the treatment of canine heartworm disease (HWD). However, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period, which targets the bacterial endosymbiont Wolbachia, might be considered. There are published reports on the efficacy of ivermectin and doxycycline in both experimentally and naturally infected dogs, but no data on the use of other macrocyclic lactones (MLs) with a similar treatment regime. Preliminary results of studies in dogs show that a topical formulation of moxidectin, the only ML currently registered as a microfilaricide, is also adulticidal when combined with doxycycline. It is not yet known if the efficacy of these combination therapies is due to pharmacokinetic synergism. A recent study showed that serum levels of doxycycline in dogs treated with the combination protocol were not statistically different compared to dogs treated with doxycycline alone. However, lungs from dogs treated with the combination therapy showed a marked reduction in T regulatory cells, indicating that treatment efficacy may be due to a heightened immune response against the parasite. Further studies are necessary to evaluate the long-term clinical outcome of combination protocols and to establish the most efficient treatment for HWD in dogs.

Osteogenic response and osteoprotective effects in vivo of a nanostructured titanium surface with antibacterial properties.

In implantology, as an alternative approach to the use of antibiotics, direct surface modifications of the implant addressed to inhibit bacterial adhesion and to limit bacterial proliferation are a promising tactic. The present study evaluates in an in vivo normal model the osteogenic response and the osteointegration of an anodic spark deposition nanostructured titanium surface doped with gallium (ASD + Ga) in comparison with two other surface treatments of titanium: an anodic spark deposition treatment without gallium (ASD) and an acid etching treatment (CTR). Moreover the study assesses the osteoprotective potential and the antibacterial effect of the previously mentioned surface treatments in an experimentally-induced peri-implantitis model. The obtained data points out a more rapid primary fixation in ASD and ASD + Ga implants, compared with CTR surface. Regarding the antibacterial properties, the ASD + Ga surface shows osteoprotective action on bone peri-implant tissue in vivo as well as an antibacterial effect within the first considered time point.

Use of contrast-enhanced ultrasonography in chronic pathologic canine testes.

Contrast-enhanced ultrasound with sulphur hexafluoride microbubbles was performed in seven healthy dogs without a history of reproductive pathology and with histologically confirmed normal testes and in 42 dogs with chronic scrotal anomalies. All dogs underwent orchiectomy and histological examination. Enhancement patterns and perfusion parameters (peak intensity and regional blood flow) of testes of healthy dogs and testes with chronic lesions were compared. Fourteen non-pathologic and 60 pathologic testes were considered. Forty testes were neoplastic (24 interstitial cell tumours, 9 seminomas, 7 Sertoli cell tumours), 20 were non-neoplastic (16 testicular degenerations, 2 chronic orchitis, 1 testicular atrophy, 1 interstitial cell hyperplasia). In healthy dogs, the contrast medium flow had a rapid homogeneous wash-in and wash-out, with a short peak phase. With contrast ultrasound, testes that were inhomogeneous with a hyperenhancing pattern were associated with neoplasia (sensitivity: 87.5%, specificity: 100%). Lesions with persistent inner vessels and a hypo-to-isoechoic background were significantly associated with seminomas (sensitivity: 77.8%, specificity: 100%). Testes with non-neoplastic lesions were characterized by a scant/moderate homogeneous enhancement. Perfusion parameters were higher in neoplastic lesions. Contrast ultrasound was a feasible diagnostic tool in the assessment of testicular lesions, with hyperenhancement being an important feature in the diagnosis of malignancy.

Effect of pelvic inclination and torsional deformity on canine acetabular morphology with computed tomography. A phantom study.

OBJECTIVES: To evaluate how the inclination and torsional deformity of the hemipelvis using extra-rotation as a model affect acetabular angle (AA) and dorsal acetabular rim angle (DARA) assessment with computed tomography (CT). METHODS: A normal canine hemipelvis positioned in dorsal recumbency was scanned with a 16-slice multidetector CT scanner, with different degrees of torsional deformity, using extra-rotation around the long axis (0-5-10-15°) of the hemipelvis. Each degree of extra-rotation was acquired at 0°, +20° and -20° of gantry tilt, to mimic different pelvic inclinations on its transverse axis. Cranial and central individual acetabular angles (IAA) and central DARA were calculated and correlated with inclination and torsional deformity. RESULTS: A very strong negative correlation was found between cranial and central IAA, pelvic inclination, and torsional deformity. A very strong positive correlation was found between DARA, pelvic inclination, and torsional deformity. CLINICAL SIGNIFICANCE: Pelvic inclination and torsional deformity affect acetabular angles assessment with CT. The greater the inclination (ilia far from the tabletop in dorsal recumbency) and torsional deformity of the pelvis, the worse the acetabulum appeared. A standardized scanning protocol for acetabular morphology assessment is needed and it should consider pelvic inclination. The actual relevance of pelvic torsional deformity is not well known and it should be investigated more thoroughly.

Allogeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse.

Overstrain tendonitis are common pathologies in the sport horses. Therapeutic approaches to tendon healing do not always result in a satisfactory anatomical and functional repair, and healed tendon is often characterized by functional impairment and high risk of reinjury. Recently, mesenchymal stem cells (MSCs) and platelet rich plasma (PRP) have been proposed as novel therapeutic treatments to improve the tendon repair process. MSCs are multipotent, easy to culture and being originated from adult donors do not pose ethical issues. To date, autologous MSCs have been investigated mainly in the treatment of large bone defects, cardiovascular diseases, osteogenesis imperfecta and orthopaedic injuries both in human and veterinary medicine. The clinical applications in which autologous MSCs can be used are limited because patient-specific tissue collection and cell expansion require time. For clinical applications in which MSCs should be used right away, it would be more practical to use cells collected from a donor, expanded in vitro and banked to be readily available when needed. However, there are concerns over the safety and the efficacy of allogeneic MSCs. The safety and efficacy of a therapy based on the use of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) associated to platelet rich plasma (PRP) were evaluated in 19 horses affected by acute or subacute overstrain superficial digital flexor tendonitis (SDFT). The application of allogeneic ASCs neither raised clinical sign of acute or chronic adverse tissue reactions, nor the formation of abnormal tissue in the long-term. After a follow-up of 24 months, 89.5% horses returned to their previous level of competition, while the reinjury rate was 10.5%, comparable to those recently reported for SDFT treated with autologous bone marrow derived MSCs. This study suggests that the association between allogeneic ASCs and PRP can be considered a safe and effective strategy for the treatment of SDF tendonitis in the horse.

Sensitivity analysis of an energetic muscle model applied at whole body level in recumbent pedalling.

Musculoskeletal models are used in order to describe and analyse the mechanics of human movement. In order to get a complete evaluation of the human movement, energetic muscle models were developed and were shown to be promising. The aim of this work is to determine the sensitivity of muscle mechanical and energetic model estimates to changes in parameters during recumbent pedalling. Inputs of the model were electromyography and joint angles, collected experimentally on one participant. The sensitivity analysis was performed on muscle-specific tension, physiological cross-sectional area, muscle maximal force, tendon rest length and percentage of fast-twitch fibres using an integrated sensitivity ratio. Soleus, gastrocnemius, vasti, gluteus and medial hamstrings were selected for the analyses. The energetic model was found to be always less sensitive to parameter changes than the mechanical model. Tendon slack length was found to be the most critical parameter for both energetic and mechanical models even if the effect on the energetic output was smaller than on muscle force and joint moments.

A combination of doxycycline and ivermectin is adulticidal in dogs with naturally acquired heartworm disease (Dirofilaria immitis).

Canine heartworm disease is caused by infection with Dirofilaria immitis, a filarial nematode that resides in the pulmonary arteries and occasionally in the right heart chambers of infected dogs. Here the authors evaluated the effect of a combination of doxycycline (10 mg/kg/sid for 30 days) and ivermectin­pyrantel(6µg/kg [DOSAGE ERROR CORRECTED] of ivermectin+5mg/kg of pyrantel every 15 days for 180 days) on microfilariemia, antigenemia and parasite load at echocardiography in naturally infected dogs from an endemic region of Italy. Dogs were examined monthly for 6 months and followed-up 4 months later. One hundred percent of dogs became negative for circulating microfilariae by day 90, while 8/11 (72.7%) of dogs became antigen-negative by day 300. Of the 7 dogs that were positive for visualization of parasites at echocardiography, 6 (85.7%) became negative by day 300. Treatment was well-tolerated by all dogs. These results suggest that a combination of doxycycline and ivermectin is adulticide in dogs with D. immitis.

Radiographic features of pelvis and hip joint development of English Bulldogs.

OBJECTIVES: To evaluate distinctive features of pelvis and hip joint development of English Bulldogs throughout the first year of life. METHODS: The pelves of 20 English Bulldogs were radiographed at three different ages (<4, 6-8, and 12-14 months). At each time point, the dogs were clinically evaluated and the abnormal hip joints were classified as mild, moderate, or severely deformed. The pelves were compared to a phantom study in which external rotation of a normal hemipelvis around its long axis was artificially created at different degrees, with different pelvic inclinations, and classified as either normal and without deformity, or as mild, moderate, or severely deformed. Hip joints and pelvic scores were statistically compared. RESULTS: Although none of the dogs were considered lame at the end of the study, none of the hips showed normal development; 77.5% were moderately to severely deformed at 12-14 months of age. At this age, 75% of the hemipelves had moderate to severe torsional deformity (>5.2 degrees of external rotation), with retroversion of the acetabulum confirmed by the presence of the crossover sign. An external rotation of the hemipelvis on its long axis >5 degrees was likely associated with a moderate to severely altered hip joint conformation. CLINICAL SIGNIFICANCE: Abnormal hip conformation was common in this series of English Bulldogs. Torsional deformity of the pelves with acetabular retroversion was a common and distinctive feature, which has not yet been thoroughly studied in dogs. These findings need further evaluation in English Bulldogs as well as in other breeds.

Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo.

Equine mesenchymal stem cells (MSC) are of particular interest both for basic research and for the therapeutic approach to musculoskeletal diseases in the horse. Their multilineage differentiation potential gives them the capability to contribute to the repair of tendon, ligament and bone damage. MSCs are also considered a promising therapeutic aid in allogeneic cell transplantation, since they show low immunogenicity and immunomodulating functions.Adipose tissue-derived adult equine stem cells (AdMSC) can be isolated, expanded in vitro and then inoculated into the damaged tissue, eventually in the presence of a biological scaffold. Here we report our preliminary experience with adipose-derived mesenchymal stem cells in allogeneic cell-therapy of tendonitis in the horse. MSCs, derived from visceral adipose tissue, were grown in the presence of autologous platelet lysate and characterized for their differentiation and growth potential. Expanded AdMSC were inoculated into the damaged tendon after their dispersion in activated platelet-rich plasma (PRP), a biological scaffold that plays an important role in maintaining cells in defect sites and contributes to tissue healing. Fourteen out of sixteen treated horses showed a functional recovery and were able to return to their normal activity.

Incomplete humeral condylar fracture in two English Pointer dogs.

Incomplete humeral condylar fracture was diagnosed by means of radiology, CT, scintigraphy, arthroscopy and bone biopsy in two English Pointer dogs. In both cases an acute thoracic limb lameness, unrelated to a known episode of major trauma, was observed. Incomplete humeral condylar fracture, mainly described in the Spaniel breeds, has been recently diagnosed in Labrador retrievers, Rottweiler, German Wachtel and other breeds. The pathogenesis of the condition is still unknown, but incomplete ossification of the humeral condyle and mechanical stress, alone or associated, have to be considered. However, our clinical and histopathological data lead us to believe that in Pointers, high performance dogs, the mechanical stress can assume a critical ethiopathogenetic role.

Detection of expiratory flow limitation during mechanical ventilation: a simulation study.

Expiratory flow limitation (EFL) is frequent in mechanically ventilated patients with obstructive pulmonary disease and its prompt detection is important to optimize respiratory assistance. The present study aims to compare by simulation two methods for the detection of flow limitation in intensive care unit: the negative expiratory pressure (NEP) method and the external resistance (DeltaR) method. To this purpose, a non linear dynamic morphometric model of breathing mechanics, derived from the Weibel symmetrical description of lungs, was used to simulate a normal and an obstructive respiratory condition during artificial ventilation. Both methods revealed the presence of EFL in the pathological case. The NEP method seems to promote the collapse of the upper and intermediate airways, so producing an overestimation of the pathology result. On the contrary, during the DeltaR maneuver the same airways increase their radius and, therefore, EFL appears underestimated. The DeltaR method appears less practical with respect to the NEP method, because of the procedure required to select the appropriate resistance degree. Moreover the flow limited portion of expiration estimated by the DeltaR technique sounds rather dependent on the choice of the external resistance level.

Role of the mechanical properties of tracheobronchial airways in determining the respiratory resistance time course.

A physiologically based simulation model of breathing mechanics was considered in an attempt to interpret and explain the time course of input respiratory resistance during the breathing cycle, observed in recent studies on ventilated patients. The model assumes a flow-dependent Rohrer resistance for the upper extrathoracic airways and volume-dependent resistance and elastance for the intermediate airways. A volume-dependent resistance describes the dissipative pressure loss in the lower airways, and two constant elastances represent lung and chest wall elasticity. Simulated mouth flow and pressure signals obtained in a variety of well-controlled conditions were used to analyze total respiratory resistance and elastance estimated by an on-line algorithm based on a time-varying parameter model. These estimates were compared with those provided by classical estimation algorithms based on time-invariant models with two, three, and four parameters. The results show that the four-parameter model is difficult to identify, while the three-parameter one offers no substantial advantage for estimating input resistance with respect to the more simple two-parameter model. In contrast, the time-varying approach provides good on-line estimates of the simulated end-expiration and end-inspiration resistances. These values provide further information of potential clinical utility, with respect to time-invariant models. For example, the results show that the difference between the end-expiration and end-inspiration resistance increases when obstructions shift from the upper to the lower airways. The similarity of the results obtained with measured and simulated data indicates that, in spite of its simplicity, the simulation model describes important physiological mechanisms underlying changes in respiratory input resistance, specifically the mechanical properties of intermediate airways.

Unusual hyperparathyroidism in a cat.

A 5 month-old, male, domestic short hair cat was presented with inappetence and vomiting. it was depressed and reluctant to move. The cat had difficulties in keeping the standing position and grossly deformed thighs. Lytic changes and disruption of normal architecture of the bone were observed, involving mainly the femoral diaphyses. An inverse Ca/P ratio and kidney failure were diagnosed. The possibility of whether the bone changes could have been related to primary or secondary renal hyperparathyroidism is discussed.

Echographic examination of the stifle joint affected by cranial cruciate ligament rupture in the dog.

Ultrasound is a useful technique for the study of normal and pathologic stifle joints, in particular for soft tissue examination. The aim of this study was to evaluate sonography for examination of stifle joints affected by cranial cruciate ligament rupture. Forty-two medium to giant breed dogs were studied. Tibial compression radiography was performed. A 7.5 MHz transducer with an incorporated 2 cm thick standoff was employed. Sagittal and midsagittal images were collected. The stifle was positioned in maximum flexion during sonography. Sonographic findings were compared with pathologic findings at surgery. Ultrasound was useful in evaluating the presence of fibrous tissue within the joint due to repair processes. It was observed in 70% of stifles with radiographic evidence of chronic osteoarthritis. In 19.6% of the joints it was possible to identify the ruptured cranial cruciate ligament. Ultrasound was not an accurate test for cruciate rupture evaluation, but was specific for the soft tissue pathologic changes which were observed consequent to joint instability.

Effect of compliant intermediate airways on total respiratory resistance and elastance in mechanical ventilation.

Total respiratory resistance and elastance were estimated off-line in a sample of 60 patients undergoing mechanical ventilation by means of two regression models in order to analyse and understand a possible physiological mechanism determining differences in inspiration and expiration. The first model considered a single value for resistance and elastance over a whole breathing cycle, whereas the second model considered separate values for inspiratory and expiratory resistance and a single value for elastance. Inspiratory resistance was found to be lower than expiratory resistance, and intermediate values were obtained for resistance estimated over the whole breathing cycle. Student's t-test showed a highly significant difference between these resistance estimates, and principal components analysis demonstrated a significant increase in information when both inspiratory and expiratory resistances were used. Minor differences were found between values of elastance calculated with the two approaches. In an attempt to interpret these experimental results, a lung model incorporating the non-linear viscoelastic properties of the intermediate airways was considered. This model suggested that changes in intermediate airway volume play a significant role in breathing mechanics during artificial ventilation and indicated that inspiratory and expiratory resistance could be useful parameters for locating airway obstruction.

Analysis by mathematical model of haemodynamic data in the failing Fontan circulation.

Several late complications jeopardize the clinical performance of recipients of the Fontan operation. The underlying causes have been referred to disturbed flow dynamics in the cavopulmonary connections. Presumably, the large pressure drops occurring in the inferior and superior connections play a pivotal role in the pressure level of the entire circulation, especially in the venous. To address this issue, we retrospectively reviewed catheterization data of six patients with failing Fontan circulation and compared them with those of six patients with functioning Fontan circulation. The impact on the systemic and pulmonary pressure of the increase in the cavopulmonary connection resistances was studied through a steady-state mathematical model of the univentricular closed-loop circulation. In the patients with failing Fontan, pressure in the venae cavae was found to be significantly higher, especially at the inferior cava (19.3 +/- 2.2 versus 12.5 +/- 2.3 mmHg) with the pressure drop at the inferior cavopulmonary connection significantly increased (4.7 +/- 3.1 versus 0.33 +/- 0.82 mmHg). The proposed mathematical model permits us to clearly relate the pressure increase in the venae cavae to an increased resistance in the cavopulmonary connections. Therefore, the present analysis confirms that, to avoid possible congestion of venous circulation, the definitive palliation of univentricular heart should not cause pressure drops at the cavopulmonary connections.

Nodular fat necrosis in the feline and canine abdomen.

The radiographic appearance of nodular fat necrosis is described in ten cats and one dog. The most common radiographic sign was the presence of a focal mineralized circular to oval soft tissue mass in the abdominal fat as present in 9 cats. These masses had a distinct eggshell-like rim encapsulating the lesion. In one cat and one dog multiple masses were present, without radiographic signs of mineralization. Abdominal ultrasound was performed in three cats and one dog, findings included the presence of hyperechoic masses with associated acoustic shadowing, some with a hypoechoic centre. Almost all animals were old and obese. In three cats and one dog, changes were confirmed with biopsy or post mortem examination. Lesions having the appearance of those in this paper are most likely incidental findings and should not be confused with abdominal masses of neoplastic origin. Ultrasound can be helpful in identifying such lesions.

The teeth of the horse: evolution and anatomo-morphological and radiographic study of their development in the foetus.

The aim of this work was to study the ontogenetic process in teeth from their early appearance in the ossifying matrix of the mandible and maxilla, in different foetuses of scalar ages. Radiographic examinations of the skull and mandible hemisections were performed and the latero-medial (LM) and dorsoventral (DV) projections for the skull and mandible were analysed. A high-definition film-screen combination was used for this study. The exposure values ranged from 35 kV/6 mAs to 58 kV/10 mAs, according to the size of the skulls and their degree of ossification. The first dental germ observed was the P3, at 138-140 days of pregnancy. At 146 days, P2 and P4 dental germs were visible. At 160-168 days, the dental germ of the first deciduous incisor tooth (I1) appeared; at 180-188 days of pregnancy the germ of the second (I2), and at 224 days the germ of the third (I3), were detectable. At 275 days the dental germ of the mandibular first molar tooth (M1) appeared, while the maxillary M1, which was not visible radiographically, was represented by a jelly-like amorphous body within its alveolar cavity.

Anatomo-radiographic study on the osteogenesis of carpal and tarsal bones in horse fetus.

The aim of this study is to point out the time of appearance of the carpal and tarsal bones in the fetal horse, considering an estimated fetal age, to follow their morphological development through to birth, and to characterize possible abnormal shape and/or delay of their ossification. The right carpal and tarsal region of 140 equine fetuses of both sexes (71 males, 69 females) and different ages (from 70 to 340 days of gestation) were examined radiographically in order to identify the sites of ossification from their earliest appearance. The times of appearance of the sites of ossification of the carpal bones are chronologically stated for each bone.