Treatment of canine generalized demodicosis associated with hyperadrenocorticism with spot-on moxidectin and imidacloprid

Background

Canine generalized demodicosis associated with hyperadrenocorticism is often problematic and might be intractable. The aim of this study was to report the efficacy of a weekly application of spot-on moxidectin/imidacloprid in dogs with hyperadrenocorticism and secondary generalized demodicosis.

Methods

Dogs with hyperadrenocorticism and secondary generalized demodicosis were included. The condition of hyperadrenocorticism was treated and stabilized with trilostane before and throughout the study period in all dogs.

Results

Average total live adult mite counts before treatment and after four, eight and 12 weeks of spot-on moxidectin/imidacloprid (2.5/10 mg/kg) applications were 20.1 ± 6.3 (range, 13–33), 0.5 ± 0.7 (range, 0–2; 6/11 were negative), 0.2 ± 0.4 (range, 0–1; 9/11 were negative), 0.2 ± 0.4 (range, 0–1; 9/11 were negative) and 0.1 ± 0.3 (range, 0–1; 10/11 were negative) respectively; this difference was significant (P < 0.001). Ten of 11 dogs (90.1%) achieved clinical remission, as demonstrated by the absence of demodectic mites at any life stage at monthly scrapings for eight consecutive weeks, and maintained remission throughout the 12-month follow-up period.

Conclusion

The weekly application of spot-on moxidectin/imidacloprid appeared to be effective and safe against generalized adult onset canine demodicosis associated with hyperadrenocorticism.     

Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves

Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.     

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

Background

Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.

Methods

Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (F_rel) was determined for S and R –ketoprofen.

Results

S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.

Conclusions

Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.     

Speckle tracking echocardiography in mature Irish Wolfhound dogs: technical feasibility,measurement error and reference intervals

Background

Two-dimensional strain measurements obtained by speckle tracking echocardiography (STE) have been reported in both humans and dogs. Incorporation of this technique into canine clinical practice requires the availability of measurements from clinically normal dogs, ideally of the same breed, taken under normal clinical conditions.The aims of this prospective study were to assess if it is possible to obtain STE data during a routine echocardiographic examination in Irish Wolfhound dogs and that these data will provide reference values and an estimation of measurement error.

Methods

Fifty- four healthy mature Irish Wolfhounds were used. These were scanned under normal clinical conditions to obtain in one session both standard echocardiographic parameters and STE data. Measurement error was determined separately in 5 healthy mature Irish Wolfhounds.

Results

Eight dogs were rejected by the software algorithm for reasons of image quality, resulting in a total of 46 dogs (85.2%) being included in the statistical analysis. In 46 dogs it was possible to obtain STE data from three scanning planes, as well as to measure the rotation of the left ventricle at two levels and thus calculate the torsion of the heart. The mean peak radial strain at the cardiac apex (RS-apex) was 45.1 ± 10.4% (n = 44), and the mean peak radial strain at the base (RS-base) was 36.9 ± 14.7% (n = 46). The mean peak circumferential strain at the apex (CS-apex) was -24.8 ± 6.2% (n = 44), and the mean peak circumferential strain at the heart base (CS-base) was -15.9 ± 3.2% (n = 44). The mean peak longitudinal strain (LS) was -16.2 ± 3.0% (n = 46). The calculated mean peak torsion of the heart was 11.6 ± 5.1 degrees (n = 45).The measurement error was 24.8%, 26.4%, 11.5%, 6.7%, 9.0% and 10 degrees, for RS-apex, RS-base, CS-apex, CS-base, LS and torsion, respectively.

Conclusions

It is concluded that this technique can be included in a normal echocardiographic examination in large breed dogs under clinical conditions. The usefulness of the reference values reported here, given their wide normal range, will ultimately be determined by the values that are obtained from a large numbers of diseased dogs.     

The relative plasma availabilities of ivermectin in reindeer (Rangifer tarandus tarandus) following subcutaneous and two different oral formulation applications

Background

Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection.

Results

The peak plasma concentration (C_max) was reached by 2 days after each treatment. The C_max and Area Under Curve (AUC) differed significantly between the groups: C_max was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC_∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation).

Conclusions

The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.     

Fluctuations of serum cortisol,insulin and non-esterified fatty acid concentrations in growing ewes over the year

Background

The physiological levels of endocrine and metabolic parameters in Slovene autochthonous breeds of sheep are not yet well known, nor are the mechanisms of their adaptability and responses to climate and environmental factors.Therefore, the aim of this study was to evaluate fluctuations of cortisol, insulin and non-esterified fatty acids (NEFA) in growing ewes over an one-year period. Blood samples were collected monthly from 10 yearling Jezersko-Solchava, 10 Bovec and 10 Istrian ewes. Serum cortisol, insulin and NEFA were measured with commercial kits.

Results

Mean monthly cortisol values fluctuated with low levels in summer and high levels in autumn. Significant peaked cortisol values of 25.69 ± 6.89, 14.67 ± 2.43 and 21.11 ± 7.25 μg/L in Jezersko-Solchava, Bovec and Istrian breed, respectively, were found in September (Bovec breed) and October (Jezersko-Solchava and Istrian breed). Mean monthly insulin values increased during the observation period. The highest levels of 14.60 ± 3.15, 16.03 ± 5.35 and 12.56 ± 2.52 μIU/mL in Jezersko-Solchava, Bovec and Istrian breed, respectively, were observed in the last sample collection in May. NEFA concentrations were found to be low except in some autumn and spring months. The peak values were observed in March for Jezersko-Solchava and Istrian breed (0.60 ± 0.05 and 0.66 ± 0.10 mmol/L), and in April for Bovec breed (0.71 ± 0.11 mmol/L).

Conclusions

Monthly fluctuations of cortisol, insulin and NEFA were measured in all observed sheep breeds, but between-breed differences in monthly values of examined parameters were insignificant. Significantly increased serum cortisol levels were found in autumn for all breeds and were probably associated with the onset of puberty and low environmental temperature. A gradual increase of insulin level in the examined ewes was in parallel with their growth. Significantly higher NEFA values in spring suggest qualitatively insufficient feed supply during that period.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.     

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Background

An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.

Objectives

To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).

Animals

Thirty healthy dogs and 15 client‐owned dogs with PDH.

Methods

Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.

Results

The serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.

Conclusions and Clinical Importance

Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.     

Relation of Vitamin D Status to Congestive Heart Failure and Cardiovascular Events in Dogs

Background

Vitamin D plays a pivotal role in cardiac function, and there is increasing evidence that vitamin D deficiency is associated with the development of congestive heart failure (CHF) in people.

Hypothesis

Serum vitamin D concentration is lower in dogs with CHF compared with unaffected controls and serum vitamin D concentration is associated with clinical outcome in dogs with CHF.

Animals

Eighty‐two client‐owned dogs.

Methods

In this cross‐sectional study, we examined the association between circulating 25‐hydroxyvitamin D [25(OH)D], a measure of vitamin D status, and CHF in dogs. In the prospective cohort study, we examined whether 25(OH)D serum concentration was associated with clinical outcome in dogs with CHF.

Results

Mean 25(OH)D concentration (100 ± 44 nmol/L) in 31 dogs with CHF was significantly lower than that of 51 unaffected dogs (123 ± 42 nmol/L; P = .023). The mean calculated vitamin D intake per kg of metabolic body weight in dogs with CHF was no different from that of unaffected dogs (1.37 ± 0.90 μg/kg metabolic body weight versus 0.98 ± 0.59 μg/kg body weight, respectively, P = .097). There was a significant association of serum 25(OH)D concentration on time to clinical manifestation of CHF or sudden death (P = .02).

Conclusion and Clinical Relevance

These findings suggest that low concentrations of 25(OH)D may be a risk factor for CHF in dogs. Low serum 25(OH)D concentration was associated with poor outcome in dogs with CHF. Strategies to improve vitamin D status in some dogs with CHF may prove beneficial without causing toxicity.     

Blood-to-saliva glucose time lag in sedated healthy dogs

The management of diabetes mellitus mandates measurement of blood glucose. Saliva offers an alternative to blood sampling, but measurement of the salivary glucose concentration is difficult, and the blood-to-saliva glucose time lag is uncertain. We aimed to determine the serum–saliva glucose time lag in the saliva of healthy dogs. The combined duct of the mandibular and sublingual salivary glands of 6 dogs was cannulated to collect saliva and prevent glucose degradation by oral bacteria. Following a 0.25 g/kg IV bolus of dextrose, paired serum–saliva samples were collected at baseline and in twelve 5-min blocks over 60 min. Serum and salivary glucose levels were analyzed with a linear mixed model for repeated measures with a compound symmetry error structure. Mean (±SD) saliva production was 10.3 ± 2.9 µL/kg/min, and the area under the curve (AUC_glucose)_saliva/serum ratio was 0.006, which highlights the magnitude of the large difference in glucose concentration between the 2 compartments. The serum–saliva glucose time lag was 30–40 min.     

Pharmacokinetics and plasma concentrations of acetylsalicylic acid after intravenous, rectal, and intragastric administration to horses

Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (± the standard error of the mean) was 1.32 ± 0.09 h⁻l, the mean elimination half-life was 0.53 ± 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 ± 98 μg · min/mL, the plasma clearance was 472 ± 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 ± 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 ± 0.80 μg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 ± 5.46 μg/mL at 2 h, then decreased to 1.92 ± 0.25 μg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 ± 94.55 μg · min/mL and the bioavailability was 0.17 ± 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 ± 0.10 μg/mL at 0.67 h, then declined to 0.37 ± 0.37 μg/mL by 36 h; the plasma concentration of SA peaked at 23.90 ± 4.94 μg/mL at 4 h and decreased to 0.85 ± 0.31 μg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 ± 24.90 μg · min/mL and the bioavailability was 0.059 ± 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate.     

Evaluation of the oral 13C-bicarbonate technique for measurements of energy expenditure in dogs before and after body weight reduction

Background

Overweight and obesity are the most common nutritional disorders in dogs and may lead to various secondary diseases and decreased lifespan. In obesity research, measurement of energy expenditure (EE) and determination of the energy requirements are essential. The objective with this study was to validate and evaluate the suitability of the oral ¹³C-bicarbonate technique (o¹³CBT) for measuring EE in dog obesity studies. A further objective was to investigate the impact of body weight (BW) reduction and changes in body composition on the EE when measured under conditions corresponding to the basal metabolic rate (BMR).

Results

The EE in five privately owned, overweight dogs was measured simultaneously with the o¹³CBT and indirect calorimetry (IC) for comparison of the results. Two measurements per dog were performed under the same standardised conditions (i.e. fasted and resting state) at the start, and after completing a 12-week BW reduction program. Additionally, measurements of body composition by Dual-energy X-ray absorptiometry (DEXA) were conducted at the beginning and at the end of the BW reduction program. There were no differences in EE results obtained by the o¹³CBT and IC. Overweight and the BW reduction did not affect the estimates for the respiratory quotient (RQ) or the recovery factor for the ¹³C-tracer (RF), both needed when using the o¹³CBT. The dogs lost 16% (SD ± 2.0) of their initial BW in reduced fat mass (P < 0.001), whereas fat free mass (FFM) remained unchanged. There was no effect of the BW reduction on the determined EE expressed in kJ/kg BW/d, or in kJ/kg BW^0.75/d. However, EE was lower (P < 0.001) after the BW reduction program when expressed in relation to FFM (kJ/kg FFM/d).

Conclusions

Results from the present study show that the o¹³CBT can be a used in obesity research to determine EE in fasted dogs and under resting conditions. Furthermore, the results suggest that the BMR does not change with reduced BW in overweight dogs as long as the FFM remains unchanged. This indicates that the BMR to maintain one gram of fat is equal to maintaining one gram of FFM in overweight dogs.     

Specific humoral and cellular immunity induced by Trypanosoma cruzi DNA immunization in a canine model

Chagas disease has a high incidence in Mexico and other Latin American countries. Because one of the most important known methods of prevention is vector control, which has been effective only in certain areas of South America, the development of a vaccine to protect people at risk has been proposed. In this study, we assessed the cellular and humoral immune response generated following immunization with pBCSP and pBCSSP4 plasmids containing the genes encoding a trans-sialidase protein (present in all three forms of T. cruzi) and an amastigote specific glycoprotein, respectively, in a canine model. Thirty-five beagle dogs were divided randomly into 5 groups (n = 7) and were immunized twice intramuscularly with 500 μg of pBCSSP4, pBCSP, pBk-CMV (empty plasmid) or saline solution. Fifteen days after the last immunization the 4 groups were infected intraperitoneally with 500 000 metacyclic trypomastigotes. The fifth group was unimmunized/infected. The parasitaemia in the immunized/infected dogs was for a shorter period (14 vs. 29 days) and the parasite load was lower. The concentration of IgG1 (0.612 ± 0.019 O.D.) and IgG2 (1.167 ± 0.097 O.D.) subclasses was measured (absorbance) 15 days after the last immunization with both recombinant plasmids, the majority of which were IgG2. The treatment of parasites using the serum from dogs immunized with pBCSP and pBCSSP4 plasmids produced 54% (± 11.8) and 68% (± 21.4) complement-mediated lysis, respectively. At 12 h post immunization, an increase in cytokines was not observed; however, vaccination with pBCSSP4 significantly increased the levels of IFN-γ and IL-10 at 9 months post-infection. The recombinant plasmid immunization stimulated the spleen cell proliferation showing a positive stimulatory index above 2.0. In conclusion, immunization using both genes effectively induces a humoral and cellular immune response.     

Simultaneous quantification of vitamin E and vitamin E metabolites in equine plasma and serum using LC-MS/MS

Vitamin E deficiencies can impact normal growth and development in humans and animals, and assessment of circulating levels of vitamin E and its metabolites may be an important endpoint for evaluation. Development of a sensitive method to detect and quantify low concentrations of vitamin E and metabolites in biological specimens allows for a proper diagnosis for patients and animals that are deficient. We developed a method to simultaneously extract, detect, and quantify the vitamin E compounds alpha-tocopherol (α-TP), gamma-tocopherol (γ-TP), alpha-tocotrienol (α-TT), and gamma-tocotrienol (γ-TT), and the corresponding metabolites formed after β-oxidation of α-TP and γ-TP, alpha-carboxymethylbutyl hydroxychroman (α-CMBHC) and alpha- or gamma-carboxyethyl hydroxychroman (α- or γ-CEHC), respectively, from equine plasma and serum. Quantification was achieved through liquid chromatography–tandem mass spectrometry. We applied a 96-well high-throughput format using a Phenomenex Phree plate to analyze plasma and serum. Compounds were separated by using a Waters ACQUITY UPLC BEH C18 column with a reverse-phase gradient. The limits of detection for the metabolites and vitamin E compounds were 8–330 pg/mL. To validate the method, intra-day and inter-day accuracy and precision were evaluated along with limits of detection and quantification. The method was then applied to determine concentrations of these analytes in plasma and serum of horses. Alpha-TP levels were 3–6 µg/mL of matrix; the metabolites were found at much lower levels, 0.2–1.0 ng/mL of matrix.     

Expression of hypoxia-inducible factor-1α and vascular density in mammary adenomas and adenocarcinomas in bitches

Background

The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed.

Results

A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P < 0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r = 0.59, P < 0.05), Ki-67 antigen expression (r = 0.43; P < 0.0005), TUNEL-positive cells (r = 0.62, P < 0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r = 0.57, P < 0.05).

Conclusion

Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans.     

Restricted nutrient intake does not alter serum-mediated measures of implant response in cell culture

Background

During nutritional stress, reduced intake may reduce the efficacy of anabolic implants. This study was conducted to evaluate basic cellular responses to a growth promotant implant at two intake levels.

Methods

Sixteen crossbred steers (293 ± 19.3 kg) were used to evaluate the impact of anabolic implants in either an adequate or a restricted nutritional state. Steers were trained to individual Calan gates, and then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of: presence or absence of an anabolic growth implant (Revalor-XS, 200 mg TBA and 40 mg estradiol; IMPLANT or CONTROL) and a moderate energy, pelleted, starting cattle diet fed at either 2.0 × or 1.0 × maintenance energy (NE_M) requirements (HIGH or LOW). Serum (d 0, 14, and 28) was used for application to bovine muscle satellite cells. After treatment with the serum (20% of total media) from the trial cattle, the satellite cells were incubated for 72 h. Protein abundance of myosin heavy chain (MHC), phosphorylated extracellular signal-related kinase (phospho-ERK), and phosphorylated mammalian target of rapamycin (phospho-mTOR) were analyzed to determine the effects of implant, intake, and their interaction (applied via the serum).

Results

Intake had no effect on MHC (P = 0.85) but IMPLANT increased (P < 0.01) MHC abundance vs. CONTROL. Implant status, intake status, and the interaction had no effect on the abundance of phospho-ERK (P ≥ 0.23). Implanting increased phospho-mTOR (P < 0.01) but there was no effect (P ≥ 0.51) of intake or intake × implant.

Conclusions

The nearly complete lack of interaction between implant and nutritional status indicates that the signaling molecules measured herein respond to implants and nutritional status independently. Furthermore, results suggest that the muscle hypertrophic effects of anabolic implants may not be mediated by circulating IGF-1.     

Evaluation of total oxidant and antioxidant status in dogs under different CO2 pneumoperitoneum conditions

Background

The induction of the pneumoperitoneum increases intraabdominal pressure (IAP), causing splanchnic ischemia, whereas its deflation normalizes IAP and splanchnic blood flow. We investigated the oxidant-antioxidant status of dogs who underwent low pressure (7 mm Hg), standard pressure (12 mm Hg), and high pressure (15 mm Hg) pneumoperitoneum.

Results

Twenty-four beagle dogs (12 males and 12 females), 4–6 years old, weighing 8–11 kg were used. The animals were assigned to one of four groups (n = 6 dogs). Group 1 served as a control; these animals received only anaesthesia for 90 min. In groups 2, 3 and 4, intra-abdominal pressure was increased to 7, 12 and 15 mmHg, respectively, and maintained for 60 min. Total oxidant status (TOS) and total antioxidant status (TAS) were determined in venous blood samples. The percentage ratio of TOS to TAS provided an oxidative stress index (OSI).No significant difference in TOS levels was found among the groups. A significant decrease in TAS levels and an increase in OSI levels were observed at 90 min and 24 h of pneumoperitoneum deflation within group 4. No differences were found among the groups.

Conclusions

A high pressure pneumoperitoneum induced significant changes in TAS and OSI. In addition, TOS and TAS levels are useful markers for evaluating changes in the oxidative status caused by a pneumoperitoneum during laparoscopy. Furthermore, a low-pressure pneumoperitoneum could attenuate oxidative stress induced by CO₂ insufflation in dogs.     

Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

Serum Concentrations of Gastrin after Famotidine and Omeprazole Administration to Dogs

Background

The duration of antacid‐induced hypergastrinemia after cessation of administration of omeprazole and famotidine apparently has not been determined in dogs.

Hypothesis

That serum gastrin will return to basal concentrations by 7 days after cessation of famotidine or omeprazole administration.

Animals

Nine healthy, adult, male, research colony dogs.

Methods

Randomized, cross‐over design. Serum gastrin was determined daily for 7 days to establish baseline concentrations. Famotidine (1.0 mg/kg q24h) or omeprazole (1.0 mg/kg q24h) was administered PO for 7 days followed by a 14‐day washout. Serum concentrations of gastrin were determined daily during 7 days of administration and daily for 7 days after cessation of administration. Each drug was evaluated in 8 of the 9 dogs.

Results

Omeprazole caused a significant increase in serum gastrin concentration (37.2 ± 7.3 to 71.3 ± 19.0 ng/L; P = .006). Famotidine induced a transient increase in serum gastrin (37.2 ± 7.3 to 65.5 ± 38.5 ng/L; P = .02) that peaked at administration day 3 and declined thereafter. By day 7 after cessation of both drugs, there was no difference in serum gastrin concentrations compared to those before administration (famotidine P = .99; omeprazole P = .99). During or after administration, gastrin concentrations above 3 times the upper reference range were rare (12 of 224 samples).

Conclusions and Clinical Importance

A 7‐day withdrawal from short‐term administration of famotidine or omeprazole is sufficient for serum gastrin to return to baseline concentrations. Withholding famotidine or omeprazole for longer before investigating pathologic causes of hypergastrinemia is unnecessary.