Evaluation of S-adenosyl l-methionine in a double-blinded, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog

Objective: To evaluate the efficacy of S‐adenosyl l ‐methionine (SAMe) in the treatment of clinically inferred canine osteoarthritis (OA). Study Design: Six weeks, double‐blinded, placebo‐controlled, clinical trial. Animals: Dogs (n=33) with clinical signs, history, and orthopedic exams consistent with OA. Methods: Dogs were block randomized by body condition score (<6/9, or ≥6/9) into either the placebo or SAMe group. Outcome was assessed using pressure platform gait analysis, examination score, goniometry, and the Canine Brief Pain Inventory (CBPI) at the time of study entrance and at 3 and 6 weeks after entry. Groups were compared using parametric and nonparametric paired tests as appropriate, and numbers needed to treat (NNT) were calculated for the CBPI and peak vertical force (PVF). Results: Both groups (n=15 placebo, n=18 SAMe) had a reduction in mean PVF (P=.02) and vertical impulse (VI; P=.06) from the 1st to 3rd visit. There was no significant difference between the placebo group and SAMe group for PVF, VI, or either part of the CBPI (Severity or Impact). The NNT at 6 weeks for the Severity score was 3, Impact score was 25, and PVF was 45. Conclusions: These data do not support the use of SAMe as an effective stand alone treatment for reducing clinical signs of OA, as measured by PVF, VI, goniometry, CBPI (both Severity and Impact), and examination score within 6 weeks of treatment.     

Efficacy and safety of maropitant,a selective neurokinin1 receptor antagonist,in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs

Maropitant (Cerenia^TM), a selective neurokinin₁ receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One‐hundred eighty‐nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two‐period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10–14‐day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel.     

Efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs

Background: Vomiting, nausea, inappetence, and diarrhea are common delayed adverse effects of doxorubicin. Maropitant, a neurokinin‐1 receptor antagonist, is known to prevent acute vomiting in dogs receiving cisplatin. Objective: To evaluate the efficacy of maropitant in preventing delayed vomiting after administration of doxorubicin to dogs. Animals: Fifty‐nine dogs with cancer. Methods: This randomized, double‐blind, placebo‐controlled study used a cross‐over design. Dogs were randomized into 1 of 2 treatment groups. Group A received maropitant after the 1st doxorubicin, and placebo after the 2nd. Group B received placebo first, and maropitant second. Maropitant (2 mg/kg) or placebo tablets were administered PO for 5 days after doxorubicin treatment. Owners completed visual analog scales based on Veterinary Cooperative Oncology Group‐Common Terminology Criteria for Adverse Events to grade their pet's clinical signs during the week after administration of doxorubicin. Statistical differences in gastrointestinal toxicosis and myelosuppression between maropitant and placebo treatments were evaluated. Results: Significantly fewer dogs had vomiting (P= .001) or diarrhea (P= .041), and the severity of vomiting (P < .001) and diarrhea (P= .024) was less the week after doxorubicin when receiving maropitant compared with placebo. No differences were found between maropitant and placebo for other gastrointestinal and bone marrow toxicoses. Conclusions and Clinical Importance: Maropitant is effective in preventing delayed vomiting induced by doxorubicin. Its prophylactic use might improve quality of life and decrease the need for dose reductions in certain dogs.     

Prevalence of behavioral changes associated with age-related cognitive impairment in dogs

OBJECTIVE: To determine the prevalence of age-related behavioral changes, namely impairment, in a randomly chosen population of dogs. DESIGN: Age-stratified cohort study. ANIMALS: 97 spayed female and 83 castrated male dogs that were 11 to 16 years old. PROCEDURE: Data on possible impairment in 4 behavioral categories (ie, orientation in the home and yard, social interaction, house training, and sleep-wake cycle) linked to cognitive dysfunction were obtained from dog owners, using a structured telephone interview. Hospital records of dogs had been screened to exclude dogs with dysfunction in organ systems that may cause behavioral changes. Dogs with behavioral impairment were those with > or = 2 signs of dysfunction within a category. Dogs with impairment in 1 category were considered mildly impaired and those with impairment in > or =2 categories were considered severely impaired. RESULTS: Age by sex interactions for dogs with impairment in any category were not significant, and, therefore, data on castrated males and spayed females were pooled for analyses across ages. The prevalence of age-related progressive impairment was significant in all categories. The percentage of 11- to 12-year-old dogs with impairment in > or = 1 category was 28% (22/80), of which 10% (8/80) had impairment in > or = 2 behavioral categories. Of 15- to 16-year-old dogs, 68% (23/34) had impairment in > or =1 category, of which 35% (12/34) had impairments in > or = 2 categories. There were no significant effects of body weight on the prevalence of signs of dysfunction in the behavioral categories. CONCLUSIONS AND CLINICAL RELEVANCE: Data collected provide estimates of the prevalence of various degrees of age-related behavioral changes associated with cognitive dysfunction in dogs. Age-related behavioral changes may be useful indicators for medical intervention for dogs with signs of cognitive impairment.     

Safety and efficacy of injectable and oral maropitant,a selective neurokinin1 receptor antagonist,in a randomized clinical trial for treatment of vomiting in dogs

Maropitant (Cerenia?), a selective neurokinin₁ receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two‐hundred seventy‐eight dogs were enrolled from 29 veterinary hospitals. Two‐hundred fifty‐two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant‐ and one placebo‐treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24‐h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly (P ≤ 0.0012) reduced in maropitant‐treated dogs as 50% (32/64) of placebo‐treated dogs continued to vomit compared to only 21.8% (41/188) of maropitant‐treated dogs. Post‐treatment clinical signs were consistent with clinical diagnoses and judged not to be treatment related. In this clinical trial, maropitant was safe and effective in reducing emesis due to various etiologies in dogs.     

The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats

S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione (GSH) donor, has been studied mechanistically in vitro, in humans with clinical liver disease, and in experimental animal models of liver disease. Collective findings encourage its therapeutic use in necroinflammatory and cholestatic liver disorders. A chronic longitudinal study (pre- and posttreatment parameters compared) was undertaken with 15 clinically healthy cats given a stable 1,4-butanedisulfonate (S'S isomer) SAMe salt (enteric coated tablets providing 180 mg SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine physical and clinicopathologic assessments, red blood cell (RBC) osmotic fragility, liver function and histology, hepatic concentrations of reduced GSH (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe concentrations were evaluated. SAMe administered PO significantly increased plasma SAMe concentrations, and peak concentrations usually occurred 2-4 hours after dosing. Chronic SAMe administration did not change peak or cumulative plasma SAMe concentrations and did not [corrected] cause overt signs of toxicity. A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P < .002], liver GSH increased 35% [P < .002], liver RGSH: GSSG ratio increased 69% [P < .03]) and improved RBC resilience to osmotic challenge (P < .03) were observed. Results prove that this SAMe PO product is enterically available and suggest that it imparts biologic effects that might be useful for attenuating systemic or hepatic oxidant challenge.     

Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0-112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8-14.0% compared with 3.0-3.9% for placebo (P = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.     

Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0–112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8–14.0% compared with 3.0–3.9% for placebo ( P  = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.     

Management of canine atopic dermatitis using the plant extract PYM00217: a randomized, double-blind, placebo-controlled clinical study

This study evaluated PYM00217, a proprietary blend of plant extracts, in the management of canine atopic dermatitis (AD). One hundred and twenty dogs were diagnosed with perennial AD on the basis of history, clinical signs, a positive test for perennial allergens and elimination of other dermatoses. Exclusion criteria included antimicrobials within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or ciclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days. Flea control, shampoos and ear cleaners were permitted. Dogs with a minimum canine atopic dermatitis extent and severity index (CADESI) of 25 were randomly allocated to receive PYM00217 (100, 200 or 400 mg kg-1 day-1) or placebo for 12 weeks. The mean reductions in CADESI (intention-to-treat population) were 3.9% (placebo; n=29), 4.4% (100 mg kg-1 day-1; n=30), 23.4% (200 mg kg-1 day-1; n=29) and 8.5% (400 mg kg-1 day-1; n=29). The reduction in the 200 mg kg-1 day-1 group was significant (P<0.01). For dogs with a baseline CADESI>or=50, the mean changes were +10.6% (placebo; n=12), +0.6% (100 mg kg-1 day-1; n=14), -29.3% (200 mg kg-1 day-1; n=14) and -3.4% (400 mg kg-1 day-1; n=15). The 200 mg kg-1 day-1 dose was significantly more effective than placebo (P=0.038). No serious adverse effects were reported. Minor adverse effects seen in 10% (placebo and 100 mg kg-1 day-1), 24% (200 mg kg-1 day-1) and 42% (400 mg kg-1 day-1) of cases were mainly minor gastrointestinal disorders and only five cases required cessation of dosing. Two dogs (one in each of the 100 mg kg-1 day-1 and 200 mg kg-1 day-1 groups) refused to eat the medicated food. In conclusion, PYM00217 at 200 mg kg-1 appears to be an effective, palatable and well-tolerated treatment for canine AD.     

Controlled Clinical Evaluation of Enalapril in Dogs With Heart Failure: Results of the Cooperative Veterinary Enalapril Study Group The COVE Study Group

The clinical efficacy and safety of enalapril were evaluated in dogs with moderate or severe heart failure. This study was conducted at 19 centers and included 211 clientowned dogs with heart failure caused by mitral regurgitation (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of various breeds, ages, and weights were included in the study. Replicates of 2 dogs each were formed, using separate allocation schedules for dogs with MR or DCM. One dog within each replicate received placebo tablets (vehicle tablets without enalapril) PO sid or bid, and the other dog received enalapril tablets at approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the experimental drug, all dogs, except 1 in the placebo group, received furosemide; 73.3% of the dogs in the placebo group and 78.3% of those in the enala pril group received digoxin. Doses of enalapril or placebo were administered for approximately 28 days. In the placebo group, 68.6% of the dogs completed the study compared with 84.9% in the enalapril group; the difference between groups was significant ( P = .01). Significantly ( P = .01) more dogs in the placebo group compared with the enalapril group died or were removed from the study because of progression of heart failure. On day 28, all 14 clinical variables measured improved significantly ( P = .01) in the enalapril group compared with the placebo group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to be removed from the study as a result of azotemia.     

Effect of N‐Acetylcysteine Supplementation on Intracellular Glutathione,Urine Isoprostanes,Clinical Score,and Survival in Hospitalized Ill Dogs

Background

Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes.

Hypothesis/Objectives

Supplementing dogs with N‐acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness.

Animals

Sixty systemically ill hospitalized client‐owned dogs and 14 healthy control dogs.

Methods

Randomized investigator‐blinded, placebo‐controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8‐isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high‐performance liquid chromatography. Atomic absorption spectroscopy and enzyme‐linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively.

Results

Ill dogs had significantly lower vitamin E concentrations (27 versus 55 μg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 μM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation.

Conclusions

Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.     

Reduction of behavioural disturbances in elderly dogs supplemented with a standardised Ginkgo leaf extract

In this open clinical trial conducted in 10 veterinary practices, Ginkgo leaf extract was administered as a dietary supplement to 42 elderly dogs (mean age 11.4 years) at a daily dose of 40 mg/ 10 kg body weight for 8 weeks. The "severity of the geriatric condition" in dogs with a history of geriatric behavioural disturbances (mean duration 12 months), was significantly reduced after 8 weeks of treatment (P = 0.0002). The positive effect was already apparent after 4 weeks. Thirty-six % of the dogs were completely free of clinical signs at study end. Overall efficacy of treatment as judged by the investigator was good or very good in 79% of the dogs. Five of six clinical sign scores (disorientation, sleep/activity changes, behavioural changes, general behaviour and general physical condition/vitality) also showed a significant decrease over the treatment period. In conclusion, these findings provide promising results that could increase the quality of life in the elderly dog and, as a consequence, that of the pet owner. The Ginkgo leaf extract appears to be an efficacious agent that provides a safe dietary supplement for the elderly dog with age-related behavioural disturbances.     

Effect of gonadectomy on subsequent development of age-related cognitive impairment in dogs.

OBJECTIVE: To determine whether gonadectomy predisposes dogs to development of age-related behavioral changes linked to cognitive impairment. DESIGN: Cohort study. ANIMALS: 29 sexually intact male dogs, 63 spayed female dogs, and 47 castrated male dogs 11 to 14 years old. PROCEDURE: Information on possible impairments in 4 behavioral categories linked to cognitive impairment (orientation in the home and yard, social interactions, house training, and sleep-wake cycle) was obtained from owners of the dogs by use of a structured telephone interview format. A second interview was performed 12 to 18 months after the initial interview, and differences in responses were evaluated. RESULTS: Sexually intact male dogs were significantly less likely than neutered dogs to progress from mild impairment (i.e., impairment in 1 category) to severe impairment (i.e., impairment in > or = 2 categories) during the time between the first and second interviews. This difference was not attributable to differences in ages of the dogs, duration of follow-up, or the owners' perceptions of the dogs' overall health. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the presence of circulating testosterone in aging sexually intact male dogs may slow the progression of cognitive impairment, at least among dogs that already have signs of mild impairment. Estrogens would be expected to have a similar protective role in sexually intact female dogs; unfortunately, too few sexually intact female dogs were available for inclusion in the study to test this hypothesis. There may be a need to evaluate possible methods for counteracting the effects of loss of sex hormones in gonadectomized dogs.     

Neurological Manifestations of Hypothyroidism: A Retrospective Study of 29 Dogs

Neuromuscular signs in association with hypothyroidism are described in 29 dogs. Eleven dogs had lower motor neuron signs, 9 had peripheral vestibular deficits, 4 had megaesophagus, and 5 had laryngeal paralysis. Primarily older (mean = 9.5 years), large-breed dogs were affected, and there was no sex or breed predisposition. Duration of clinical signs before presentation ranged from 2 to 8 weeks (mean = 5 weeks). The diagnosis was based on (1) results of neurological examination (29 dogs); (2) electromyographic abnormalities (18 dogs), including fibrillation potentials (n = 18), positive sharp waves (n = 15), and complex repetitive discharges (n = 4); (3) high serum cholesterol concentration (10 dogs; mean = 335 mg/dL); (4) low response to thyroid-stimulating hormone (29 dogs; mean T₄ prestimulation concentration = 0.8 μg/dL; mean T₄ poststimulation = 1.2 μg/dL); and (5) good response to thyroxine supplementation (26 dogs). Dogs with vestibular deficits had abnormal brainstem auditory-evoked responses (BAER), including increased latencies of P₁-P₆ and decreased amplitude of P_4,5-N₅. Seven other dogs had similar BAER abnormalities without manifesting clinical signs of vestibular involvement. Three dogs with vestibular signs had fibrillation potentials and positive sharp waves without exhibiting lower motor neuron signs. All dogs were supplemented with levothyroxine (0.02 mg/kg P0 bid). The follow-up period ranged between 6 and 30 months (mean, 14 months). Serum T₄ concentrations were measured at least 3 times for each dog every 2 months (mean T₄ concentration = 2.6 μg/dL). All but 1 dog with lower motor neuron signs and 1 dog with vestibular signs recovered after 2 months (mean, 57 days). Signs of megaesophagus became progressively less severe over 4 months. Dogs with laryngeal paralysis improved partially after 5 months. We suggest that either vestibular or lower motor neuron signs, megaesophagus, or laryngeal paralysis may be the only clinical signs of an underlying, more generalized polyneuropathy associated with hypothyroidism. Electro-diagnostic abnormalities may be detected before clinical disease develops.     

Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled challenge trial

Canine parvoviral enteritis continues to cause significant morbidity and mortality in dogs worldwide, and efficacious antiviral therapies are lacking. The present trial was aimed at evaluating the therapeutic efficacy of a recombinant feline interferon (type omega) preparation in the treatment of parvoviral enteritis in dogs. A double-blind, placebo-controlled challenge trial was performed in beagle pups (8-9 weeks); clinical signs, body weight, hematologic parameters, and mortality were monitored for a period of 14 days after challenge. Fourteen animals were inoculated with virulent canine parvovirus; 10 animals that developed clinical signs thereby meeting the inclusion criteria were admitted to the treatment phase in two randomly selected groups (placebo and IFN) of equal size. The IFN group received daily intravenous injections of rFeIFN-omega (2.5 MU/kg) for three consecutive days. The placebo group received daily injections of saline without IFN. Both groups of animals received individual supportive treatment consisting of adjusted diet and electrolyte solution.All five dogs in the placebo group developed fulminating enteritis with typical clinical signs and died within 10 days post-inoculation (or 6 days post-treatment). In the IFN-treated group, one animal died on day 2 after the treatment was started, whereas the other four dogs survived the challenge and gradually recovered. Our data confirm that the rFeIFN-omega can exert a significant therapeutic effect on dogs with parvoviral enteritis by improving clinical signs and reducing mortality.     

Evaluation of the influence of S-adenosylmethionine on systemic and hepatic effects of prednisolone in dogs

OBJECTIVE: To evaluate the influence of a 1,4-butanedisulfonate stable salt of S-adenosylmethionine (SAMe) administered orally on clinicopathologic and hepatic effects induced by long-term administration of prednisolone in dogs. ANIMALS: 12 healthy dogs. PROCEDURE: Following a pilot study (4 dogs), 2 groups of 4 dogs received prednisolone (2.2 mg/kg) orally once daily (84-day trial). One group received SAMe (20 mg/kg/d divided in 2 doses) for 42 days and then a placebo for 42 days; the other group received treatments in the reverse order. Before and during the trial, numerous variables were monitored, including serum total alkaline phosphatase (ALP) and glucocorticoid-induced ALP (G-ALP) activities, serum haptoglobin concentration, and total and oxidized glutathione (TGSH and GSSG) and thiobarbiturate-reacting substances (TBARS) concentrations in erythrocytes and liver tissue (days 0, 42, and 84). Hepatic specimens also were examined microscopically. RESULTS: The stable salt of SAMe was biologically available; plasma concentrations of SAMe or prednisolone were not affected by coadministration. Compared with baseline values, serum ALP and G-ALP activities and haptoglobin concentrations increased and erythrocyte GSSG and TBARS concentrations decreased with both treatments. Erythrocyte TGSH concentration decreased with the prednisolone-placebo treatment. Administration of SAMe appeared to conserve erythrocyte TGSH values and did not inhibit hepatocyte glycogen vacuolation but increased hepatic TGSH concentration and improved the hepatic tissue GSSG:TGSH ratio. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, administration of 20 mg of SAMe/kg/d may mitigate the apparent pro-oxidant influences of prednisolone but did not block development of classic clinicopathologic or histologic features of vacuolar hepatopathy.     

The effect of thyroid replacement in dogs with suboptimal thyroid function on owner-directed aggression: A randomized,double-blind,placebo-controlled clinical trial

The efficacy of thyroid hormone replacement therapy (THRT) as treatment for owner-directed aggression in client-owned dogs with borderline low thyroid hormone levels was evaluated by means of a 6-week-long, parallel design, double-blind placebo-controlled study. The designation of “borderline hypothyroid” was made if the dog's free normal thyroxine (T4) value was frankly low or in the bottom 20th percentile of the normal range and either total T4, total triiodothyronine (T3), or free T3 was frankly low or in the bottom 30th percentile of the normal range. The presence of thyroid autoantibodies also qualified a dog for enrollment. Owners recorded the number of aggressive episodes directed toward family members on a daily basis for 8 weeks (2-week baseline phase and 6-week study phase). Twenty-nine dogs completed the study; 14 in a treatment group and 15 in a placebo group. The median number of aggressive episodes per day decreased significantly from baseline in both treated and placebo group dogs in weeks 1-2, 3-4, 5-6, and week 6 (treatment, χ² = 24.8, P < 0.001; placebo, χ² = 20.2, P < 0.001), however the median frequency of aggression was significantly lower in the treatment group (1.21 episodes/day) than in the placebo group (1.71 episodes/day) during week 6 of the study (χ² = 4.047, P = 0.044). Three thyroxine-treated dogs had borderline-low thyroid levels on the final day of the study (day 42). When aggression frequency was compared between the treatment and placebo groups after the removal of 3 thyroxine-treated dogs, the treatment group did not have a significantly lower aggression frequency than the placebo group during week 6 (Kruskal–Wallis statistic: χ² = 3.035, n = 26, P = 0.08). The authors discuss the role of thyroid hormones in the regulation of aggression and other cognitive issues and provide rationale for using THRT in dogs exhibiting owner-directed aggression that also have low normal or baseline thyroid hormone levels.     

Measurement of peptidase activity and evaluation of effectiveness of administration of minocycline for treatment of dogs with periodontitis

OBJECTIVE: To determine clinical, enzymatic, and microbiologic effects of controlled-release localized administration of minocycline on dogs with periodontitis. ANIMALS: Five adult Beagles with periodontitis. PROCEDURE: After tooth scaling and root planing, 2 treatment, 1 placebo, and 1 control site were selected for each dog. Treatment sites (n = 10) received a periodontal formulation of minocycline hydrochloride, placebo sites (5) received ointment without minocycline, and control sites (5) did not receive ointment. Treatments were administered 4 times at weekly intervals. Peptidase activity and clinical and microbiologic effects were evaluated and compared among sites for 17 weeks. RESULTS: Bleeding of the gums on probing (BOP) and pocket depth (PD) improved at the treatment site and were maintained for 13 weeks after treatment. However, BOP and PD in placebo and control sites increased from weeks 9 to 17 Peptidase activity in the periodontal pocket decreased noticeably from week 1 to 17, compared with baseline values for the treatment site. However, peptidase activity for placebo and control sites increased and were above baseline values on week 9 and week 13, respectively. Total bacterial counts decreased by 90% for treatment sites and remained at that value for 13 weeks. However, for placebo and control sites, bacterial counts increased and reached the baseline value on week 17. CONCLUSIONS AND CLINICAL RELEVANCE: Increased peptidase activity is correlated with the progression of periodontitis in dogs. Treatment with minocycline, using a localized delivery system, was effective in dogs for at least 13 weeks after cessation of drug administration.     

Clinical Efficacy of Sildenafil in Treatment of Pulmonary Arterial Hypertension in Dogs

Background: Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. Hypothesis/Objectives: Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. Animals: Thirteen dogs with echocardiographic evidence of PAH. Methods: Prospective short‐term, randomized, placebo controlled, double‐blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. Results: Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34–83 mmHg) than at baseline (median, 72 mmHg; range, 61–86 mmHg; P= .018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49–197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101 ± 47 versus 74 ± 32; P= .05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. Conclusions and Clinical Importance: Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.     

Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease

The usual treatment of dogs with inflammatory bowel disease (IBD) consists of administration of immunosuppressive doses of steroids. However, some dogs are refractory to steroid treatment and pose a significant challenge to the veterinarian. Because cyclosporine A (cyA) has been shown to be effective in steroid-resistant IBD in humans, the purpose of this study was to investigate the pharmacokinetics and clinical efficacy of PO cyA treatment in dogs with steroid-refractory IBD (n = 14). All dogs were treated with cyA 5 mg/kg PO q24h for a period of 10 weeks. A clinical activity score was assigned to assess severity of clinical signs before and after treatment. The total number of infiltrating lymphocytes and T cells in duodenal biopsies were assessed before and after treatment in 9 dogs. In addition, serum concentration of cyA was measured in 8 dogs over a 24-hour period. Pharmacokinetic profiles in dogs with IBD were similar to those of healthy dogs. Improvement of clinical signs was observed in 12 of 14 dogs with IBD. Median clinical activity score after treatment with cyA was significantly reduced from a median score of 9 to a median score of 5 (P = 0.001). T cell numbers in duodenal biopsies were significantly decreased after treatment from a median +/- 95% range in the villous region of 28 (19-30) cells/10,000 microm2 before versus 7 (0-10)/10,000 microm2 after treatment, P = 0.01; and from a median +/- 95% range number in the crypt region of 15 (6-23) cells/10,000 microm2 before versus 4 (0-9)/10,000 microm2 after treatment, P = 0.02, implying T cell lysis as a possible mechanism of action. In conclusion, based on this small study, cyA appears to be an effective alternative drug in dogs with IBD that are refractory to immunosuppressive doses of steroids.