Combination In Dogs Research Articles

Epidural anaesthesia with temperature-responsive hydrogel and bupivacaine combination in dogs: a comprehensive study

Epidural anaesthesia with temperature-responsive hydrogel and bupivacaine combination in dogs: a comprehensive study

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20mg/kg of rabeprazole sodium only, and 800mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Evaluation of β-tricalcium Phosphate (β-TCP) and Platelet Rich Plasma (PRP) Combination for Fracture Healing in Dogs Stabilized with Intramedullary Pinning

Background: The use of synthetic bone substitute,b-tricalcium phosphate (β-TCP) as an osteo-conductive material and platelet-rich plasma (PRP) as an osteo-inductive material is the alternate strategies for replenishing bone loss. Thus, the present study was conducted to evaluate the bone healing efficacy of β-TCP and PRP combination in dogs with long bone fracture repaired with threaded intramedullary pinning. Methods: Fifteen dogs were selected, which were allotted to two groups irrespective of age, breed and sex. In six dogs of Group I intramedullary pinning was performed, while in nine dogs of Group II β-TCP and PRP was applied at fracture site after stabilising with intramedullary pin. Clinical and radiographic examinations were conducted preoperatively and postoperatively on 15th, 30th and 60th day. Result: The mean weight bearing and radiographic union scores were better in group II animals as compared to group I at different time intervals. The present findings suggest that β-TCP and PRP effectively enhances the bone healing in dogs with long bone fracture.

Preclinical/clinical trials of thrice-weekly administration of a combination of tegafur/gimeracil/oteracil (TS-1) and toceranib phosphate in dogs with intranasal tumors.

Intranasal tumors in dogs are malignant solid tumors that are primarily treated with radiotherapy and often recur post-treatment. Combination therapy is pivotal in cancer therapy. Effective drugs include fluoropyrimidine 5-fluorouracil (5-FU) and toceranib phosphate. TS-1, an oral formulation containing the 5-FU prodrug tegafur and enzyme modulators gimeracil and oteracil, is proven to be safe in dogs with solid tumors. While the oral drug toceranib phosphate (Palladia®) is safely administered, the combined toxicity with TS-1 is unknown. We aimed to determine the dosage of this combination in dogs. In the preclinical/clinical trials conducted here, we used a standard 3+3 cohort design with fixed doses of toceranib phosphate (2.4 mg/kg) administered thrice weekly. TS-1 administration was initiated at a dose of 0.5 mg/kg (upper limit 2.0 mg/kg) thrice weekly. Four cohorts were included to confirm the safety of TS-1 and toceranib phosphate. Each cohort was followed up for 1 month. The intranasal tumor types included in the clinical trial (n=13) were adenocarcinoma (n=7), squamous cell carcinoma (n=1), non-epithelial malignancy (n=2), undifferentiated carcinoma (n=1), and transitional carcinoma (n=2). The TS-1 dosage could be increased up to its dose limit in the preclinical/clinical trials. The TS-1 dose to combine with toceranib phosphate thrice weekly was 2.0 mg/kg. This regimen was well-tolerated in dogs. Thus, combined TS-1 and toceranib phosphate therapy is safe for dogs with intranasal tumors.

Ketamine-Propofol Coadministration for Induction and Infusion Maintenance in Anesthetized Dogs: Effects on Electroencephalography and Antinociception.

The effects of concurrent ketamine and propofol (ketofol) constant rate infusion (CRI) were examined in six dogs. The K:P ratio was 1:2, with an initial CRI of 0.25/0.5 mg/kg/min over ten minutes, followed by a 0.5 mg/kg ketamine bolus for induction. During induction, a comprehensive EEG frequency spectrum from delta to gamma was observed, accompanied by subanesthetic-dose ketofol-induced behavioral excitation, including nystagmus, tongue flicking, salivation and active muscle activity. The dogs were maintained on three 15 min decremental doses of ketofol CRI (0.8/1.6, 0.4/0.8 and 0.2/0.4 mg/kg/min). This phase featured a significant decrease in the Patient State Index, electromyographic activity and a shift to low beta waves (SEF95: 13-18 Hz). Additionally, profound antinociception to electric stimulation and a stable heart rate and blood pressure (MBP 81.5-110 mmHg) were observed, as well as a merging of ketamine and propofol EEG characteristics during maintenance. In the recovery phase, a return to beta and gamma EEG patterns and excitement behavior occurred, accompanied by a significant reduction in antinociception, highlighting features of low doses of ketofol. This study reveals biphasic EEG dynamic changes, associated behaviors and robust antinociception and cardiovascular function, suggesting the utility of ketofol as a total intravenous anesthetic combination in dogs.

Evaluation of Anaesthetic Indices and Physiological Variables Following Total Intravenous Anaesthesia with Acepromazine-Butorphanol-Propofol Combination in Dogs

The study determined the anaesthetic and physiological effects of Acepromazine-Butorphanol-Propofol (ABP-combination) and propofol alone (PRO alone) in dogs. Ten clinically healthy dogs were randomly assigned to two groups to evaluate the anaesthetic and physiological effects following ABP-combination and PRO-alone anaesthesia administered intravenously (iv). Acepromazine at 0.02mg/kg and Butorphanol at 0.05mg/kg iv were used to premedicate the dogs and Propofol at 4mg/kg for induction five minutes after premedication in ABP-combination group while Propofol alone at 6mg/kg for total intravenous anaesthesia (TIVA) induction without premedication. Onset of anaesthesia, duration of anaesthesia time to standing, onset and duration of analgesia and duration of intubation were measured, whereas temperature, heart rate and respiratory rates were measured before induction of anaesthesia and at five minutes interval during anaesthesia. All the anaesthetic indices were significantly (p<0.05) different between groups while onset and duration of analgesia was recorded in ABP group only. Significantly (p<0.05) longer duration of anaesthesia was produced by ABP-combination compared with PRO-alone. Time to standing were significantly different (p<0.05) between the two treatments. The onset and duration of analgesia was 5.0±2.0 and 33.6±3.2 min. following ABP-combination but no analgesia recorded with PRO-alone. There was significant decrease (p<0.05) in rectal temperature and respiratory rate from the baseline in ABP-combination group but not significant in PRO-alone group. There was significant (p<0.05) difference in heart rates between groups. ABP-combination TIVA provided longer duration of anaesthesia and analgesia with minimal effects on vital parameters. The dogs recovered from the anaesthesia uneventfully. The ABP-combination can be evaluated for clinical procedures in dog.

Application of neuromuscular blockade using Rocuronium for performing different surgeries and its reversal by Neostigmine-Glycopyrrolate combination in dogs

This study was executed in the clinical setup to investigate the effects of Rocuronium and its reversal by Neostigmine and Glycopyrrolate (Myopyrolate) combination in Propofol-Isoflurane anaesthetized dogs. Rocuronium-induced neuromuscular blockade was applied to 21 clinical cases. Out of which, 19 cases were of orthopaedic surgeries and 2 cases of ovariohysterectomy. After the animal had stabilized on the mixture of isoflurane and oxygen, the relaxation of muscle was induced using Rocuronium @ 0.5 mg/kg b.wt. Immediately IPPV was provided in volume control mode. Neuromuscular blockade was reversed using a single syringe combination drug having both Neostigmine and Glycopyrrolate (Myopyrolate) @ 0.05 mg/kg b.wt and @ 0.01 mg/kg b.wt, respectively. Rocuronium caused the centering of the ocular globe gradually in less than 30 sec. During orthopaedic surgeries, the reduction of fractured ends became easy without much tissue trauma. In ovariohysterectomy surgeries, the appropriate level of abdominal muscle relaxation further helped in the easy exteriorization of the ovarian stump. The onset time for Rocuronium was 17.64±1.10 sec and its duration of action was 27.82±0.72 min. The use of Rocuronium along with IPPV caused minimal alteration of the physiological parameters with no clinical consequences and thus can be considered a complication-free anaesthetic protocol for interventions demanding muscle relaxation.

Biological Pulp Response of Pulpine, Polyamidoamine Dendrimer and Their Combination in Dogs and their Remineralizing Effect on Carious Affected Human Dentin: A Randomized Clinical Trial

Biological Pulp Response of Pulpine, Polyamidoamine Dendrimer and Their Combination in Dogs and their Remineralizing Effect on Carious Affected Human Dentin: A Randomized Clinical Trial

Dissociative anaesthesia in dogs and cats with use of tiletamine and zolazepam combination. What we already know about it.

This article is an attempt to gather available literature regarding the use of tiletamine and zolazepam combination in anaesthesia in dogs and cats. Although tiletamine and zolazepam mixture has been known in veterinary practice for a long time, the increased interest in these drugs has been observed only recently. Tiletamine, similarly to ketamine, is a drug which belongs to the phencyclidine group. Ketamine has considerable popularity in veterinary practice what suggests that other dissociative anaesthetic drugs, such as tiletamine, could also prove effective in cats' and dogs' anaesthetic care. Zolazepam is a widely used benzodiazepine known for its muscle relaxant and anticonvulsant properties. While conducting an electronic search for articles regarding the use of tiletamine-zolazepam combination in dogs and cats, it has been discovered that the literature on the subject (tiletamine-zolazepam combination in dogs and cats) is quite scarce. Very few articles were published after 2010. Databases used were: Google Scholar, Scopus, PubMed. Most of the adverse effects, including those affecting the cardiovascular, nervous, and respiratory systems, were strictly dose-dependent. Tiletamine-zolazepam combination can be safely used as a premedication agent, induction for inhalation anaesthesia, or an independent anaesthetic for short procedures. Contraindications using tiletamine-zolazepam mixture include central nervous system (CNS) diseases such as epilepsy and seizures, head trauma, penetrative eye trauma, cardiovascular abnormalities (hypertrophy cardiomyopathy in cats, arrythmias or conditions where increase of heart rate is inadvisable), hyperthyroidism, pancreatic deficiencies or kidney failure.

Clinical and Laboratory Findings in Dogs Undergoing Adjuvant Chemotherapy with Gemcitabine/Carboplatin Combination for Mammary Neoplasia

Adjuvant chemotherapy might be indicated in some canine mammary cancer cases due to metastatic potential. In this regard, studies to determine adverse events following chemotherapy protocols are valuable. The purpose of this prospective clinical trial was to evaluate the safety and tolerability of gemcitabine and carboplatin combination in dogs with malignant mammary tumors. For this prospective clinical trial, 21 female dogs mastectomized due to malignant mammary neoplasia underwent adjuvant chemotherapy with gemcitabine (3 mg/kg, 60-minute IV infusion) and carboplatin (10 mg/kg, 20-minute IV infusion) based protocol every 21 days for three cycles. They were monitored periodically for treatment-related adverse events by clinical and laboratory evaluations. A total of 17 (80.9%) dogs developed leukopenia, 10 (47.6%) neutropenia, and 15 (71.4%) thrombocytopenia at least once along with the three chemotherapy cycles. All these hematologic toxicities were grade 1, 2, or 3. Two (9.5%) animals had evidence of gastrointestinal toxicity; however, clinical signs were mild to moderate (grades 1 and 2). No dog had life-threatening adverse events (grade 4) or even died (grade 5) of treatment-related complications. The adjuvant chemotherapy protocol with gemcitabine and carboplatin was well-tolerated and safe in female dogs for mammary cancer treatment with self-limiting hematological and gastrointestinal adverse events.

Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST).

BackgroundThe renin‐angiotensin‐aldosterone system (RAAS), when chronically activated, is harmful and RAAS‐suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people.Hypothesis/ObjectivesTo determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE‐I), benazepril, and spironolactone, would be superior to benazepril alone.AnimalsFive hundred and sixty‐nine client‐owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10‐days' duration.MethodsAfter initial stabilization, dogs were randomized into a positive‐controlled, double‐blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d.ResultsA significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32‐0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59‐0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups.Conclusion and Clinical ImportanceThe combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.

Oral Transmucosal or Intramuscular Administration of Dexmedetomidine-Methadone Combination in Dogs: Sedative and Physiological Effects.

Simple SummaryDuring the last decade, new alternative non-invasive administration routes for drug delivery have gained interest in veterinary medicine. The administration of drugs via the oral transmucosal route is non-invasive, painless, easy to perform, and generally well tolerated. Furthermore, it avoids gastric acid degradation typical of oral administration. All these characteristics contribute to make this administration route very attractive, especially for veterinary patients who are difficult to inject, fearful, or anxious. In contrast, intramuscular injection is associated with pain and requires more invasive restraint, potentially incrementing patients’ discomfort. The aim of this study was to assess and compare the sedative and clinical effects of a dexmedetomidine–methadone combination following either oral transmucosal and intramuscular administration in healthy dogs and to record any possible adverse effects following each administration route. The present study suggests that oral transmucosal administration of dexmedetomidine and methadone combination provided a satisfactory level of sedation, allowing safe handling of the patients with less pronounced cardiorespiratory effects. Indeed, thanks to the lesser impact on the cardiac function, it could be considered as a useful option for those patients difficult to restrain in which cardiovascular stability should be preserved.The aim of this study was to compare the sedative and physiological effects following either oral transmucosal (OTM) or intramuscular administration of dexmedetomidine–methadone combination in healthy dogs. Thirty dogs were randomly assigned to receive a dexmedetomidine–methadone combination either by the OTM (n = 15) or intramuscular (n = 15) route. Sedation was scored 10, 20, and 30 min after drugs administration. Heart rate (HR), non-invasive blood pressure (NIBP), respiratory rate (fR), and body rectal temperature were recorded before drugs administration and then every 10 min for 30 min. Propofol dose required for orotracheal intubation was recorded. Sedation scores increased over time within both groups with higher values in intramuscular group (p < 0.05). Within each group, HR decreased significantly compared with baseline (p < 0.001) and was significantly lower in intramuscular group compared with the OTM group (p < 0.001). In both groups, NIBP increased significantly compared with baseline (p < 0.05). In the intramuscular group, fR was lower compared with the OTM group at all the observational time points (p < 0.001). Propofol dose was lower in the intramuscular group (p < 0.05). Compared to intramuscular dexmedetomidine–methadone, OTM combination produced lower but effective sedation in healthy dogs.

Evaluation of lumbo-sacral epidural anaesthesia or analgesia with lidocaine-acepromazine combination in dogs undergoing cystotomy

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Epidural anaesthesia is one of the most frequently used regional anesthetic techniques recommended for surgical procedures caudal to the umbilicus in dogs. However, the use of lignocaine alone for epidural regional analgesia has been discovered to have shorter duration of analgesia and prolong onset of action, hence there is need to explore combinations of agents that will overcome this challenge. This study aimed to evaluate the anaesthetic/analgesic effect of cranial epidural anaesthesia in dogs undergoing cystotomy using Lignocaine in combination with acepromazine at the dose rates of 7 mg/kg and 0.05 mg/kg respectively.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Eight apparently healthy matured, male and female dogs were used for the experiment. The onset and duration of analgesia was determined. The pulse rates, respiratory rates, mean arterial blood pressure, rectal temperature, complete blood count and the oxygen saturation level were determined at baseline, intra operative and post-operative. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were no significant differences in all the parameters measured before and after the epidural administration of the agents. The onset of anaesthesia was rapid and the duration of anaesthesia was sufficient enough for the procedure to be carried out. However, there was significant difference in PCV, Hb and total RBC count between the baseline and other timing intervals. There were no significant differences in leucocytic and cardiopulmonary parameters between the baseline and other timing intervals.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The epidural administration of lignocaine and acepromazine combination at the doses indicated can produced sufficient epidural anaesthesia with rapid onset for the purpose of cystotomy in dogs without major systemic influence on hemodynamic and cardiopulmonary changes.&lt;/p&gt;

Phase-I trial of survivin inhibition with EZN-3042 in dogs with spontaneous lymphoma

BackgroundLymphoma is a common cancer in dogs. While most dogs receiving chemotherapy experience remission, very few are cured, and median survival times are generally in the 12-month range. Novel approaches to treatment are unquestionably needed. The Inhibitor of Apoptosis Protein (IAP) family member survivin, which is one of the most commonly overexpressed proteins in human cancer, plays a key role in apoptosis resistance, a major cause of drug-resistant treatment failure. Survivin targeting therapies have shown promise preclinically; however, none have been evaluated in dogs to date. The goal of the current study was to determine the safety and pharmacodynamic effects of systemic administration of the anti-survivin locked nucleic acid antisense oligonucleotide EZN-3042 in dogs with lymphoma.ResultsWe performed a prospective phase-I clinical trial in dogs with biopsy-accessible peripheral nodal lymphoma. Eighteen dogs were treated with EZN-3042 as a 2-h IV infusion at 5 dose levels, from 3.25 to 8.25 mg/kg twice weekly for 3 treatments. No dose-limiting toxicities were encountered. Reduction in tumor survivin mRNA and protein were observed in 3 of 5 evaluable dogs at the 8.25 mg/kg dose cohort.ConclusionsIn conclusion, reduced survivin expression was demonstrated in lymphoma tissues in the majority of dogs treated with EZN-3042 at 8.25 mg/kg twice weekly, which was associated with minimal adverse effects. This dose may be used in future studies of EZN-3042/chemotherapy combinations in dogs with spontaneous lymphoma and other cancers.

Comparison of Lidocaine, and Lidocaine-Neostigmine for Epidural Analgesia in Dogs

ABSTRACT Objectives: Evaluate and compare the analgesic effect of epidural lidocaine and lidocaine- neostigmine combination in dogs. Methods: Six healthy dogs of mixed breed weighing 12–15 kg were selected for this study. All dogs received all treatments in a cross-over design with at least a one-week interval. Dogs were premeditated with Xylazine (0.5 mg/kg) and general anesthesia was induced with thiopental sodium (12.5 mg/kg) to perform the lumbosacral puncture. Epidural analgesia was done using either 6 mg/kg of lidocaine 2% or a combination of 6 mg/kg of Lidocaine 2%, with 10 µg/kg neostigmine. The degree of analgesia was evaluated using a numerical rating scale. Analgesia was defined as lack of response to pinprick test and pressure from hemostat clamp and was performed after one hour of epidural injection, and thereafter every 10 min until complete recovery. Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were recorded before (baseline, 0) and at every 10 min until a complete recovery was observed. Results: HR, RR and RT did not differ between treatments at any time point. The lidocaine–neostigmine combination produced a significant (P < 0.05) longer duration of analgesia than lidocaine alone. The addition of neostigmine resulted in a significantly longer duration of analgesia. Co-administration of epidural neostigmine and lignocaine appears to be a useful technique for postoperative analgesia as it increases the duration of analgesia Conclusion: Adding neostigmine to epidural administered lidocaine in dogs increases the analgesic effect on both hind limbs and perineal region. Short running title: Lidocaine-neostigmine epidural in the dog.

Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I–V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Comparison the effects of ketamine alone and ketamine-diazepam combination in dogs of local breed in Mekelle, Ethiopia

Comparison the effects of ketamine alone and ketamine-diazepam combination in dogs of local breed in Mekelle, Ethiopia

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma.

Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8+ and CD4+ T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.Electronic supplementary materialThe online version of this article (10.1007/s00262-018-2201-5) contains supplementary material, which is available to authorized users.

Sedative, analgesic, and behavioral effects of nalbuphine-xylazine and nalbuphine-midazolam combinations in dogs

Abstract The purpose of the present study was to evaluate the sedative, analgesic, and behavioral effects of nalbuphine-xylazine (NX) and nalbuphine-midazolam (NM) combinations for neuroleptanalgesia in dogs. A prospective randomized crossover study was done on six adult mongrel dogs. Dogs were randomly allocated into NX and NM groups with a washout period 2 weeks. Nalbuphine was given at dose of 0.5 mg/kg IV approximately 20 minutes before administration of the tranquilizer. Dogs were randomly allocated into one of the two groups: NX group received xylazine at a dose of 1 mg/kg IV; and NM group received midazolam at a dose of 0.5 mg/kg IV. Sedative, analgesic, and behavioral evaluations were done before administration of nalbuphine (baseline), before administration of tranquilizer (0 time), and each 10 minutes till 60 minutes, vital parameters were also recorded. Most of the sedation scores showed significant increase in NX 10 and 20 minutes in NM group. Significant change in sedation was still recorded in both groups till 60 minutes. The degree of analgesia was at its peak 10–30 minutes in NX group and started to decrease at 40 and 50 minutes. In NM group, the peak analgesic scoring was at 20 minutes and started to decline until 60 minutes. Most of the behavioral parameters were significantly decreased at 10 minutes in NX group and 20 minutes following injection in NM group. The combination of NX provided greater sedation and analgesia compared with NM combination.

In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma cells.

OBJECTIVE To assess the in vitro effects of doxorubicin and tetrathiomolybdate (TM) on cells from a canine hemangiosarcoma cell line. SAMPLE Cultured cells from the canine hemangiosarcoma-derived cell line DEN-HSA. PROCEDURES Cells were treated with TM (0 to 1.5μM), doxorubicin (0 to 5μM), or both with or without 24 hours of pretreatment with ascorbic acid (750μM). Degree of cellular cytotoxicity was measured with a colorimetric assay. Long-term growth inhibition was assessed with a 10-day colony-formation assay. Induction of apoptosis was quantitated by fluorometric assessment of caspase-3 and -7 activation. Formation of reactive oxygen species (ROS) was also detected fluorometrically. RESULTS Exposure of cells to the combination of TM and doxorubicin resulted in a greater decrease in proliferation and clonogenic survival rates than exposure to each drug alone. This treatment combination increased ROS formation and apoptosis to a greater extent than did doxorubicin or TM alone. Ascorbic acid inhibited both TM-induced ROS formation and apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the enhancement in cytotoxic effects observed with DEN-HSA cell exposure to the combination of doxorubicin and TM was achieved through an increase in ROS production. These findings provide a rationale for a clinical trial of this treatment combination in dogs with hemangiosarcoma.