Comparison of intradermal and serum testing for environmental allergen-specific immunoglobulin E determination in a laboratory colony of cats with naturally acquired atopic syndrome.

BACKGROUND: Allergen testing is used to select antigens included in the desensitisation vaccine. Intradermal skin test (IDT) is the gold standard in cats, yet allergen-specific immunoglobulin (Ig)E serological testing (ASIS) is often used. Feline data are lacking regarding the agreement between IDT and ASIS results. HYPOTHESIS/OBJECTIVES: The first objective of the study was to establish a colony of cats with naturally acquired feline atopic syndrome (FAS). Further objectives were to define their hypersensitivity disorder to detail the allergen tests results, and to assess similarity between the allergen tests. ANIMALS: Thirty-five cats with FAS and 10 control cats. MATERIALS AND METHODS: Enrolled cats went through a five phase-screening and quarantine process before joining the colony. An elimination diet trial was performed on all FAS cats. ASIS and IDT were consecutively performed on all cats under sedation. RESULTS: Reactions to 34 allergens were compiled for the 45 cats. Global sensitivity and specificity of ASIS were 34.7% and 78.9%, respectively. Only flea (ICC = 0.26, p = 0.040) and Dermatophagoides pteronyssinus (ICC = 0.48, p < 0.001) allergens had a significant intraclass correlation (weak agreement). Two FAS cats had negative tests including one cat with a concomitant food allergy. CONCLUSIONS AND CLINICAL RELEVANCE: This study depicts the first reported colony of cats with naturally acquired FAS. This is the first feline study to compare and show the poor agreement between allergen tests with a panel of 34 allergens. This colony also harbours two cats with FAS with negative allergen tests. These may represent the first described cats with an intrinsic form of atopic syndrome.

A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis.

With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.

Development of Two Innovative Performance-Based Objective Measures in Feline Osteoarthritis: Their Reliability and Responsiveness to Firocoxib Analgesic Treatment.

The metrological properties of two performance-based outcome measures of feline osteoarthritis (OA), namely Effort Path (Path) and Stairs Assay Compliance (Stairs), were tested. Cats naturally affected by OA (n = 32) were randomly distributed into four groups (A: 0.40, B: 0.25, C: 0.15, or D: 0.00 mg firocoxib/kg bodyweight) and assessed during baseline, treatment, and recovery periods. For Path, from an elevated walking platform, the cats landed on a pressure-sensitive mattress and jumped up onto a second elevated platform. Analysis included velocity, time to completion, peak vertical force (PVF), and vertical impulse. For Stairs, the number of steps and time to completion were recorded for 16 steps up and down in a 4 min period. Reliability was moderate to very good for Path and poor to good for Stairs. Different normalization methods are described in the manuscript. The placebo group remained stable within-time in Path, whereas treated cats trotted faster on the ramp (p < 0.0001), improved their PVF (p < 0.018) and completed the task quicker (p = 0.003). The percentage of cats completing the Stairs finish line was higher under treatment (p < 0.036), with huge effect size, the placebo group results being stable within-time. Both are promising performance-based outcome measures to better diagnose and manage feline OA pain.

Sensitivity of functional targeted neuropeptide evaluation in testing pregabalin analgesic efficacy in a rat model of osteoarthritis pain.

The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behaviour (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non-affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components.

Therapeutic response analysis in dogs with naturally occurring osteoarthritis.

OBJECTIVE: Reporting the rate of positive (+) and negative (-) responders based on an objective outcome measure of pain-related functional disability/lameness in dogs with naturally occurring osteoarthritis (OA), and the relationship between initial lameness severity and the odds of being a (+) responder. STUDY DESIGN: Retrospective analysis of published peer-reviewed clinical trials in dogs with naturally occurring OA. ANIMALS: Dogs (n = 213) with hip and/or stifle afflicted-joints. METHODS: A responder analysis was undertaken using a previously determined cut-off value of ±2.0% of body weight using the peak of vertical force (PVF). Among the selected trials, PVF was acquired under similar conditions. Therapeutic approaches were therapeutic diets, natural health products and nonsteroidal anti-inflammatory drugs. RESULTS: Among dogs receiving a therapeutic approach as described above (n = 121), 62.8% [95% confidence interval, 53.9-70.9] were defined as (+) responders, whereas 11.6% [7.0-18.5] were (-) responders, accounting for a net (+) response rate by 51.2% [42.0-60.4]. In dogs receiving a negative control (n = 92), the net (+) response rate was 1.1% [0.0-5.9]. The number needed to treat was 4, and the effect size 0.7 [0.4-1.0]. The odds ratio of being a (+) responder under the therapeutic approaches was 2.85 [1.57-5.17] (p < 0.001). For every less severe lameness manifested with an increment in PVF by 1% body weight, the chance of being a (+) responder following treatment decreased by 9% (odds ratio 0.91 [0.86-0.97], p = 0.006). CONCLUSION AND CLINICAL RELEVANCE: The rate of (+) responder optimizes decision making for the management of pain-related clinical signs of OA. Evidence-based medicine was further supported by clinical metrics based on an objective outcome measure of pain-related functional disability/lameness. This study also revealed that dogs with a mild lameness are less prone to be improved, emphasizing the need to carefully manage OA dogs in spite of a more subtle affliction.

Comparison of lidocaine and lidocaine-epinephrine for the paravertebral brachial plexus block in dogs.

OBJECTIVE: To compare the motor and sensory block efficacy and duration of a modified paravertebral brachial plexus block (PBPB) after administration of lidocaine alone (LI) or combined with epinephrine (LE). STUDY DESIGN: Prospective, randomized, blinded, crossover study. ANIMALS: A total of eight healthy female Beagle dogs. METHODS: Under general anesthesia, modified PBPB was performed on the left thoracic limb using neurostimulation and/or ultrasound guidance to administer lidocaine (2 mg kg-1; 0.2 mL kg-1) either alone (treatment LI, n = 10) or with epinephrine (1:100,000; treatment LE, n = 9). Sensory block was evaluated through reaction to a painful mechanical stimulus applied at five sites on the limb. Motor block effect was evaluated according to visual gait assessments and thoracic limb vertical force measurements under dynamic and static conditions. Data were analyzed using repeated-measures generalized estimating equations. All statistical tests were performed two-sided at the α = 0.05 significance threshold. RESULTS: The duration of sensory block did not differ significantly between treatments. Visible gait impairment was more persistent in LE than in LI (118 ± 63 minutes for LI and 163 ± 23 minutes for LE; mean ± standard deviation) (p = 0.027). At nadir value, dynamic peak vertical force was lower in LE than in LI (p = 0.007). For both dynamic and static evaluations, the nadir and the return to baseline force were delayed in LE (return to normal at 180-200 minutes) when compared with LI (130-140 minutes) (p < 0.005). CONCLUSIONS AND CLINICAL RELEVANCE: The addition of epinephrine to lidocaine prolonged the duration and increased the intensity of the regional block, as verified by visual gait assessment and kinetic analysis. No significant difference was noted between treatments regarding sensory blockade. Kinetic analysis could be useful to evaluate regional anesthetic effect in dogs.

Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). STUDY DESIGN: Randomized, blinded study. ANIMALS: Fifteen geriatric cats weighing 4.5 ± 1.0 kg. METHODS: Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. RESULTS: Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Kinetic measurements of gait for osteoarthritis research in dogs and cats.

Over the past 2 decades the measurement of ground reaction forces (GRF) has been extensively used in dogs and cats to gain insights on normal locomotion, discrepancies under pathologic conditions, and biomechanical changes following surgical procedures. Ground reaction forces have become a well-established outcome measure of pain-related functional impairment in animals affected by experimental and naturally occurring osteoarthritis. This paper comprehensively reviews the nature of GRF and presents arguments regarding its measurement in osteoarthritis research.

Mesure cinétique de la démarche du chien et du chat en contexte de recherche sur l'arthrose. Au cours des deux dernières décennies, la mesure des forces de réaction au sol (FRS) a été largement utilisée chez les chiens et les chats afin de mieux comprendre la locomotion normale, les anomalies en conditions pathologiques et les changements biomécaniques suivant une procédure chirurgicale. Les FRS au sol sont devenues un critère d'évaluation bien connu de la limitation fonctionnelle liée à la douleur chez l'animal atteint d'arthrose expérimentale et naturelle. Le présent manuscrit dresse un aperçu de la nature des FRS et présente les arguments qui supportent son usage dans un contexte de recherche sur l'arthrose.(Traduit par les auteurs).

Concurrent Validation of MI-CAT(V), a Clinical Metrology Instrument for Veterinarians Assessing Osteoarthritis Pain in Cats, through Testing for Firocoxib Analgesic Efficacy in a Prospective, Randomized, Controlled, and Blinded Study.

Veterinarians face the lack of a rapid, reliable, inexpensive, and treatment-sensitive metrological instrument reflecting feline osteoarthritis (OA) pain. The Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians (MI-CAT(V)) has been refined in 4 sub-sections, and we proposed its concurrent validation. Cats naturally affected by OA (n = 32) were randomly distributed into 4 groups of firocoxib analgesic (Gr. A: 0.40; B: 0.25; C: 0.15, and P: 0.00 mg/kg bodyweight). They were assessed during Baseline, Treatment, and Recovery periods using MI-CAT(V) and objective outcomes (effort path, stairs assay compliance, and actimetry). The MI-CAT(V) total score correlated to the effort path and actimetry (RhoS = -0.501 to -0.453; p < 0.001), also being sensitive to treatment responsiveness. The pooled treatment group improved its total, gait, and body posture scores during Treatment compared to the Baseline, Recovery, and placebo group (p < 0.05). The MI-CAT(V) suggested a dose-(especially for Gr. B) and cluster-response. Cats in the moderate and severe MI-CAT(V) clusters responded to firocoxib with a remaining analgesic effect, while the mild cluster seemed less responsive and experienced a negative rebound effect. The MI-CAT(V) was validated for its OA pain severity discriminatory abilities and sensitivity to firocoxib treatment, providing a new perspective for individualized care.

Surveillance of Ancylostoma caninum in naturally infected dogs in Quebec, Canada, and assessment of benzimidazole anthelmintics reveal a variable efficacy with the presence of a resistant isolate in imported dogs.

Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A. caninum within the United States of America in recent years, which has led us to investigate the potential of this scenario in Canada. The study objectives were to assess the prevalence of A. caninum in two different groups, including a colony of rescued dogs in Canada and three imported Greyhound dogs from USA, and to evaluate the efficacy of two benzimidazole (BZ) anthelmintics against A. caninum, complemented with a molecular genetic analysis adapted to low prevalence. Fecal samples were collected at pre- and post-treatment with fenbendazole for the native shelters-origin group, and a combination of anthelmintic formulations, including the pro-BZ febantel for the USA-origin group. The coprology analyses found several genera of internal parasites. Canine ancylostomiasis was the most prevalent parasitosis with 30.77% in the native group and 100% in the USA group, but with overall low average of A. caninum eggs per gram. Through the fecal egg count reduction test (FECRT), applying a cut-off at 90% as baseline of egg reduction for successful efficacy, BZ showed variable efficacy. Furthermore, molecular analysis confirmed the presence of A. caninum in both groups of dogs and found differences in the genetics linked to BZ resistance on the A. caninum ß-tubulin isotype 1 gene. In the isolate from the native group, both codons 167 and 200 were homozygous without the presence of single nucleotide polymorphism (SNP). In contrast, the selected isolate from the USA group, showed a homozygous allele at position 200 and a heterozygous SNP at position 167. The latter was congruent with the low efficacy in FECRT and agrees with the recent findings of USA A. caninum isolate resistant phenotype to the BZ anthelmintics. The limitations of the study include an overall low eggs-per-gram in both canine groups, and the shortage of additional fecal samples from the USA group, restraining the molecular analysis only to one out of the three Greyhounds. This study provided some insights on the efficacy of BZs against A. caninum and revealed the presence of BZ resistant isolates in imported dogs in Quebec, Canada. All this information should be considered, for choosing the best strategy in the control of A. caninum using anthelmintic drugs.

Does a placebo effect really occur in dogs afflicted by hip osteoarthritis as measured by force platform gait analysis?

A recent study investigated the therapeutic response of dogs afflicted by hip osteoarthritis when evaluating therapeutic modalities compared to a negative (placebo) control group. Authors suggested a placebo effect based on peak vertical force measurement. In addition, small effect size for each of the tested therapeutics as well as the extremely large sample size needed (>450) to discern therapeutic efficacy using force platform gait analysis were reported. We wish to express our concerns regarding the eligibility criteria used to select the studied cohort, the small effect size, and the placebo effect reported in force platform gait analysis.

Clinical validity of outcome pain measures in naturally occurring canine osteoarthritis.

BACKGROUND: The conceptual validity of kinetic gait analysis and disability outcome assessment methods has guided their use in the assessment of pain caused by osteoarthritis (OA). No consensus on the best clinical methods for pain evaluation in canine OA exists, particularly, when evaluating treatments where a smaller treatment effect is anticipated than with pharmacological pain killers. This study thus aimed at determining the technical validity of some clinical endpoints on OA pain in dogs using the green-lipped mussel (GLM)-enriched diet.Twenty-three adult dogs with clinical OA completed the prospective controlled study. All the dogs were fed a balanced diet over a 30-day control period followed by a GLM-enriched diet over a 60-day period. The kinetic gait analysis parameter (PVF(BW), peak vertical force adjusted for body weight change), electrodermal activity (EDA), and a standardized multifactorial pain questionnaire (MFQ) were performed on day (D) 0 (inclusion), D30 (start) and D90 (end). The owners completed a client-specific outcome measures (CSOM) instrument twice a week. Motor activity (MA) was continuously recorded in seven dogs using telemetered accelerometric counts. We hypothesized that these methods would produce convergent results related to diet changes. A Type I error of 0.05 was adjusted to correct for the multiplicity of the primary clinical endpoints. RESULTS: Neither the EDA nor the MFQ were found reliable or could be validated. Changes in the PVFBW (P(adj) = 0.0004), the CSOM (P(adj) = 0.006) and the MA intensity (P(adj) = 0.02) from D0 to D90 suggested an effect of diet(s). Only the PVFBW clearly increased after the GLM-diet (P(adj) = 0.003). The CSOM exhibited a negative relationship with the PVF(BW) (P = 0.02) and MA duration (P = 0.02). CONCLUSIONS: The PVF(BW) exhibited the best technical validity for the characterization of the beneficial effect of a GLM-enriched diet. The CSOM and MA appeared less responsive following a GLM-diet, but these measures appeared complementary to gait analysis. Apparently, the CSOM provides the capacity to rely on pain OA assessment influenced by both lameness quantification (PVF(BW)) and physical functioning (MA).

Brachystemma calycinum D. Don Effectively Reduces the Locomotor Disability in Dogs with Naturally Occurring Osteoarthritis: A Randomized Placebo-Controlled Trial.

Objective. The aim of this randomized placebo-controlled trial was to evaluate the beneficial effect of a whole plant extract of Brachystemma calycinum D. Don (BCD) in naturally occurring osteoarthritis (OA) in dogs. Methods. Dogs had stifle/hip OA and poor limb loading based on the peak of the vertically oriented ground reaction force (PVF) measured using a force platform. At baseline, PVF and case-specific outcome measure of disability (CSOM) were recorded. Dogs (16 per group) were then assigned to receive BCD (200 mg/kg/day) or a placebo. The PVF was measured at week (W) 3 and W6. Locomotor activity was recorded throughout the study duration using collar-mounted accelerometer, and CSOM was assessed biweekly by the owner. Results. BCD-treated dogs had higher PVF at W3 and W6 when compared to Baseline (P < 0.001) and at W6 when compared to placebo-treated dogs (P = 0.040). Higher daily duration (P = 0.024) and intensity (P = 0.012) of locomotor activity were observed in BCD-treated dogs compared to baseline. No significant change was observed in either group for CSOM. Conclusions. Treatment with BCD improved the limb impairment and enhanced the locomotor activity in dogs afflicted by naturally-occurring OA. Those preclinical findings provide interesting and new information about the potential of BCD as an OA therapeutic.

Evaluation of osteoarthritis in cats: novel information from a pilot study.

OBJECTIVE: To describe structural changes associated with osteoarthritis (OA) in cats and to quantify OA-associated disability using functional evaluations. STUDY DESIGN: Cross-sectional pilot study with longitudinal data. ANIMALS: Normal cats (n = 2) and coxofemoral joint OA cats (n = 4) were evaluated by physical examination, radiography, and magnetic resonance imaging (MRI). METHODS: Structural changes related to OA were scored using computed radiographs (CR) and MRI. Functional evaluation consisted of podobarometric gait analyses performed using a pressure-sensitive mattress and motor activity assessments using collar-attached, accelerometer-based activity sensors. RESULTS: Structural scores for the coxofemoral joint OA-related lesions were lower in normal cats than OA cats for MRI (P = .07). Use of MRI allowed for whole-organ assessment of the coxofemoral joint. Pelvic limb peak vertical ground reaction force (PVF) was higher in normal cats than OA cats (P = .10). During the night, motor activity was greater in normal cats than OA cats (P = .04). PVF was positively correlated with mean motor activity (Spearman coefficient [Rho] = 0.83, P = .04) and negatively correlated with age and MRI structural score (Rho = -0.93 and -0.79, P < .01 and .06, respectively). CONCLUSIONS: This study provides the first description of OA-related lesions in cats using MRI. Gait analysis and accelerometry should be considered as objective tools to characterize OA-associated disability, although these assessments were weakly correlated with structural changes.

Comparative short-term efficacy of Oridermyl(®) auricular ointment and Revolution(®) selamectin spot-on against feline Otodectes cynotis and its associated secondary otitis externa.

The efficacy of Oridermyl(®) (acaricidal/antibiotic/antifungal/anti-inflammatory ointment) and Revolution(®) (selamectin spot-on) was compared in a blinded randomized study on 24 adult cats with otoacariasis. Twelve cats were treated once daily for 10 d with Oridermyl(®) and 12 cats were treated on Day 0 with Revolution(®). Otitis was assessed with cytological counts of mean number of bacteria and yeast on Days 0 and 10, and scored clinically every other day. All auricular secretions were removed for mite count on Day 10. On Day 0, cytological examination confirmed the presence of secondary bacterial (24/24) and fungal (21/24) infections. No live mites were observed otoscopically after Day 4 and in auricular secretions at Day 10 in both groups. On Day 10, secondary infections were resolved for all cats treated with Oridermyl(®) but were present in all cats treated with Revolution(®). Improvement in clinical signs of otitis over time was superior in the Oridermyl(®) group (P < 0.001).

Estrogenic impregnation alters pain expression: analysis through functional neuropeptidomics in a surgical rat model of osteoarthritis.

PURPOSE: Several observational studies suggest that estrogens could bias pain perception. To evaluate the influence of estrogenic impregnation on pain expression, a prospective, randomized, controlled, blinded study was conducted in a Sprague-Dawley rat model of surgically induced osteoarthritis (OA). METHODS: Female rats were ovariectomized and pre-emptive 17ß-estradiol (0.025 mg, 90-day release time) or placebo pellets were installed subcutaneously during the OVX procedures. Thirty-five days after, OA was surgically induced on both 17ß-estradiol (OA-E) and placebo (OA-P) groups. Mechanical hypersensitivity was assessed by static weight-bearing (SWB) and paw withdrawal threshold (PWT) tests. Mass spectrometry coupled with high-performance liquid chromatography (HPLC-MS) was performed to quantify the spinal pronociceptive neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), somatostatin (SST), and dynorphin-A (Dyn-A). RESULTS: Compared to control, ovariectomized rats presented higher SP (P = 0.009) and CGRP (P = 0.017) concentrations. OA induction increased the spinal level of SP (+ 33%, P < 0.020) and decreased the release of BK (- 20%, (P < 0.037)). The OA-E rats at functional assessment put more % body weight on the affected hind limb than OA-P rats at D7 (P = 0.027) and D56 (P = 0.033), and showed higher PWT at D56 (P = 0.009), suggesting an analgesic and anti-allodynic effect of 17ß-estradiol. Interestingly, the 17ß-estradiol treatment counteracted the increase of spinal concentration of Dyn-A (P < 0.016) and CGRP (P < 0.018). CONCLUSION: These results clearly indicate that 17ß-estradiol interfers with the development of central sensitization and confirm that gender dimorphism should be considered when looking at pain evaluation.

Measurements of canine aqueous humor inflammatory mediators and the effect of carprofen following anterior chamber paracentesis.

OBJECTIVES: Phase I: To evaluate levels of prostaglandin E(2) (PGE(2) ), nitrites and nitrates (NO(x) ), tumor necrosis factor-alpha (TNF-α) and expression of inducible cyclo-oxygenase (COX-2), nitric oxide synthase (NOS-2), and matrix metalloproteinases (MMP-3 and -9) in canine aqueous humor following repeated anterior chamber paracenteses (ACP). Phase II: to evaluate the effect of carprofen on PGE(2) , NO(x) , and TNF-α in canine aqueous humor following ACP. ANIMALS STUDIED: Four beagles in phase I and 8 beagles in phase II. PROCEDURES: Phase I: ACP was performed at time (T) 0, 4 and 8 h. Phase II: A randomized, placebo-controlled cross-over design with four dogs per group where carprofen was given 4.4 mg/kg/day on day (D) 1, 2 and 3. ACP was performed at T0 and T1.5 on D3. Statistical analysis was performed with repeated measures anova and post hoc Tukey-Kramer multiple-comparison procedure. In phase II, TNF-α level was analyzed with a Wilcoxon signed-rank test. RESULTS: Phase I: PGE(2) significantly increased (P < 0.0001) to plateau at T4. NO(X) was decreased at T4 (P < 0.06), but increased at T8 (P < 0.0001). COX-2 showed detectable expression only at T8. TNF-α, NOS-2, MMP-3 and -9 were undetectable at all time points. Phase II: At T1.5, PGE(2) was significantly elevated in both groups but was lower in the carprofen group (P = 0.037). NO(x) and TNF-α did not statistically increase in either group. CONCLUSIONS: Following ACP, significant increases in PGE(2) levels confirmed inflammation characterized by a rise of COX-2. The NO(x) pathway took longer to induce as compared with PGE(2) . Carprofen decreased PGE(2) levels and could help control intraocular inflammation.

Treatment of feline otitis externa due to Otodectes cynotis and complicated by secondary bacterial and fungal infections with Oridermyl auricular ointment.

A blinded randomized study was conducted on 24 cats to confirm the presence of bacterial and/or fungal secondary infections associated with otoacariasis and to verify the efficacy of Oridermyl, an acaricidal/antibiotic/antifungal/anti-inflammatory ointment, for treatment of the primary infestation and secondary infections. Sixteen cats were treated once daily for 10 d; 4 cats were not treated and 4 were treated with a placebo ointment. On Days 0 and 10, ears were swabbed for counts of bacteria and yeasts, for bacterial culture and sensitivity, and examined for determination of the degree of clinical otitis. Auricular secretions were removed for mite counts on Day 10, except for 8 treated cats that were done on Day 30. There was a high number of bacteria and yeasts in most cats and Oridermyl treatment significantly decreased those numbers. Staphylococci were the most frequently isolated bacteria. No live ear mites were found in cats treated with Oridermyl or the placebo ointment.

Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in experimental dog osteoarthritis: inhibition of protease-activated receptor 2.

OBJECTIVE: The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the experimental dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. METHODS: Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred dogs. There were two experimental groups (n=6-7 dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of dogs was performed. RESULTS: Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p<0.02) of osteoarthritis cartilage lesions. BCD treatment also significantly reduced the osteoarthritis chondrocyte level of key inflammatory and catabolic factors (iNOS, p=0.009 and MMP-13, p=0.003) as well as the level of PAR-2 (p=0.03). Dogs treated with BCD showed a significant improvement in peak vertical force measured at 8 weeks (p<0.05). CONCLUSIONS: Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.

Respiratory safety pharmacology: concurrent validation of volume, rate, time, flow and ratio variables in conscious male Sprague-Dawley rats.

This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow- and ratio-derived parameters obtained using head-out plethysmography in rats following administration of reference drugs (isotonic saline, 2.0 mL/kg, IV; albuterol, 400 µg/kg, inhalation; methacholine, 136 µg/kg, IV; and remifentanil, 14 µg/kg, IV) to identify respiratory variables with superior sensitivity. Paired t-tests by block-period, and analysis of covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise comparisons using Dunnett's test were used. Variations in respiratory parameters observed over time justify the use of a control group in any respiratory safety pharmacology study for inter-groups comparison. Handling-, and slumbering-, induced perturbations were minimal. The system was sensitive and specific to detect changes in respiratory variables related to pharmacologically-induced bronchodilation, bronchoconstriction and central respiratory depression. The standard variables (respiratory rate, tidal and minute volumes) confirmed to be the cornerstone of respiratory safety pharmacology to detect pharmacological changes. Flow-derived parameters appeared as highly valuable complement for interpretation of respiratory response, whereas time- and ratio-derived parameters presented limited added value during interpretation.